Devices, systems, and methods for evaluating internal organs

Abstract

A device for determining data indicative of a blood oxygen level of an internal organ is disclosed. The device comprises: a body comprising a contact surface for engaging with a subject near an internal organ of the subject; a body defining a first groove and a second groove, the first and second grooves extending into the body from the contact surface, the second groove being spaced apart from the first groove; a light source comprising a light emitting region located within the first recess and configured to emit light of at least two discrete wavelengths from the first recess of the body onto the internal organ; and a light detector comprising a photosensitive region located within the second recess and configured to detect light received at the second recess, where the detected light comprises emitted light reflected from a region of the subject adjacent to the internal organ. Also disclosed are systems including the device and methods of assessing the health of an internal organ of a subject using the device, particularly, but not exclusively, for determining the blood oxygen saturation of an internal organ of a subject.

Description

[0001] This application is a divisional application, the original application of which is a PCT application with application number PCT / AU2020 / 050695 and application date July 3, 2020, and a Chinese application that entered the Chinese national phase on January 4, 2022. The Chinese application number is 202080048950.5, and the name is “Device, system and method for evaluating internal organs”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to Australian Provisional Patent Application No. 2019902373 filed on 4 July 2019, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0004] The present disclosure generally relates to devices, systems and methods for assessing the health of a subject's internal organs. In particular, but not exclusively, the present disclosure relates to devices, systems and methods for determining blood oxygen saturation in a subject's internal organs. Background Art

[0005] Pulse oximetry is used to non-invasively measure the absolute arterial circulating oxygen level (oxygen saturation) of the blood of a subject's skin, thereby providing an indication of the subject's health. Absolute arterial oxygen level can be determined by analyzing the ratio of the intensities of red light and near-infrared light. Arterial oxygen level can be obtained, for example, by transmitting light through the subject's finger or by reflecting light from the subject's forehead skin and measuring the light captured by a detector. The light is typically generated by a light emitting diode (LED), which is placed directly against the subject's skin to maximize the light projected onto the subject. The signal originates from the blood flow in the skin.

[0006] The inventors have now determined that by utilizing a device positioned proximate an internal organ of interest on a subject, it is possible to accurately determine blood oxygen concentration in the microvasculature of the internal organ and assess organ health, wherein a light source and a light detector of the device are positioned back from a surface of the device that contacts the subject (e.g., positioned on the subject's skin), and wherein the light source and the light detector are spaced apart by a defined range, e.g., approximately 5 mm to approximately 20 mm from a center of each of the light source and the light detector. Summary of the Invention

[0007] Some embodiments relate to an apparatus for determining data indicative of blood oxygen level of an internal organ, the apparatus comprising: a body comprising a contact surface for engaging a subject near the internal organ of the subject; the body defining a first recess and a second recess, the first and second recesses extending from the contact surface into the body, the second recess being separate from the first recess; a light source comprising a light emitting region positioned within the first recess and configured to emit light of at least two discrete wavelengths from the first recess of the body toward the internal organ; and a light detector comprising a photosensitive region positioned within the second recess and configured to detect light received at the second recess, wherein the detected light includes emitted light reflected from an area of the subject adjacent the internal organ; wherein the apparatus is configured such that the light emitting region and the photosensitive region are retracted from the contact surface by approximately 1 mm to approximately 20 mm, and their nearest points are separated by approximately 4 mm to approximately 20 mm, such that the detected light is indicative of blood oxygen level in a blood vessel at an outermost surface of the internal organ.

[0008] The spacing between the closest points of the light emitting region and the light sensitive region can be in the range of about 5 mm to about 15 mm. In some embodiments, the spacing is in the range of about 6 mm to about 8 mm.

[0009] In some embodiments, the body may further include an outer frame defining the contact surface and the cavity; and an inner frame shaped to fit within the cavity, wherein the inner frame defines the first groove and the second groove.

[0010] The light source can be configured to emit and sense light including light having a wavelength within a first wavelength range of at least about 600 nm to about 750 nm, a second wavelength range of about 855 nm to about 945 nm, and a third wavelength range of about 780 nm to about 820 nm. The light detector can be configured to emit and sense light including discrete wavelengths of at least about 660 nm, about 805 nm, about 895 nm, and / or about 940 nm.

[0011] Some embodiments of the present invention relate to a system for determining the blood oxygen level of an internal organ, the system comprising the above-mentioned device and a processor, wherein the device and processor are connected so that data indicative of the blood oxygen level of the internal organ can be transmitted from the device to the processor. The processor may include a memory, a display, and a user interface, all of which are coupled to the processor. Some embodiments relate to a method of obtaining data indicative of the blood oxygen level of an internal organ of a subject, comprising: positioning the above-mentioned device on an external surface of the subject adjacent to the internal organ; projecting light from a light source through the external surface of the subject toward the internal organ, wherein the light comprises light of two or more discrete wavelengths; receiving light at a light detector of the device, the received light being reflected from the internal organ at the two or more discrete wavelengths respectively; and generating a first signal indicative of the intensity of the light of the first wavelength and a second signal indicative of the intensity of the light of the second wavelength.

[0012] In some embodiments, the method includes positioning the device on the subject's scalp, wherein the internal organ includes the brain. In some embodiments, the method includes positioning the device near an area of the skull beneath the scalp where the skull is relatively thin. This area of the skull may be adjacent to the Sylvian fissure. In some embodiments, the method includes positioning the device in the subject's ear canal, wherein the internal organ includes the brain. In some embodiments, the method includes positioning the device above the sternal notch, above the supraclavicular space, or between the ribs of the subject, wherein the internal organ includes the lungs. In some embodiments, the method includes positioning the device below the ribs in the right upper abdomen or upper abdomen of the subject, wherein the internal organ includes the liver. In some embodiments, the method includes positioning the device in the abdomen or either lower abdomen of the subject, wherein the internal organ includes the intestines. In some embodiments, the method includes positioning the device on the subject's back, wherein the internal organ includes the kidneys. In some embodiments, the method includes positioning the device on the sternum of the chest or along the left border of the sternum where it intersects the ribs, wherein the internal organ includes the heart. In some embodiments, the method includes positioning the device on skeletal muscle of the subject, wherein the internal organ includes skeletal muscle.

[0013] In some embodiments, the method may further include, in response to receiving an instruction indicating that the device is inaccurately positioned relative to the internal organ, repositioning the device relative to the internal organ based on the instruction.

[0014] Some embodiments relate to a computer-implemented method of assessing the health of a subject, the method comprising: receiving one or more signals derived from measured light reflected at respective different wavelengths from an area adjacent to an internal organ of the subject; determining that at least one waveform of the one or more signals represents a signal primarily associated with the internal organ; and comparing data derived from the at least one waveform to informational features of a health condition to assess the health of the subject.

[0015] In some embodiments, determining that the at least one waveform represents a signal primarily associated with an internal organ includes determining that the at least one waveform substantially corresponds to a venous waveform.

[0016] In some embodiments, determining that the at least one waveform represents a signal primarily associated with an internal organ includes determining that the at least one waveform includes an A-wave component, an X-wave component, and a Y-wave component corresponding to an A-wave, an X-wave, and a Y-wave of a venous signal. For example, the internal organ may be one of the brain, lungs, liver, intestines, and a fetal organ.

[0017] In some embodiments, determining that the at least one waveform represents a signal primarily associated with an internal organ includes determining that the at least one waveform is not indicative of an arterial signal obtained from a skin region of the subject.

[0018] In some embodiments, determining that at least one waveform represents a signal primarily associated with an internal organ comprises: receiving an additional signal obtained from the subject substantially concurrently with the one or more signals, wherein the additional signal is obtained from measured light reflected from the subject's skin at an additional wavelength; and determining that a signal peak of the at least one waveform is temporally offset from a corresponding signal peak of an additional waveform of the additional signal.

[0019] The at least one waveform may include at least one window corresponding to the systolic and diastolic phases of the cardiac cycle.In some embodiments, the method further includes determining the times of the systolic and diastolic phases of the cardiac cycle associated with the at least one waveform based on the additional signal.

[0020] In some embodiments, the method further includes determining an estimate of the diastolic blood oxygen level of the internal organ based on a time offset between a signal peak and a corresponding signal peak of the additional waveform and a known systolic blood oxygen level. For example, the additional waveform of the additional signal may indicate an arterial pulse of the subject. The additional waveform of the additional signal may indicate a venous signal obtained from the jugular vein of the subject. The additional signal may be obtained from measured light having a wavelength in the range of about 780 nm to about 820 nm, which is sensitive to blood but not to changes in blood oxygen level.

[0021] In some embodiments, determining that the at least one waveform represents a signal primarily associated with an internal organ includes determining that the at least one waveform is substantially consistent with a template waveform characteristic of the internal organ.

[0022] In some embodiments, the method further includes, in response to determining that the at least one waveform is indicative of an arterial signal obtained from a skin region of the subject, determining that the at least one waveform does not represent a signal primarily associated with an internal organ.

[0023] In some embodiments, the one or more signals may include a first signal obtained from light of a first wavelength and a second signal obtained from light of a second wavelength, and the at least one waveform may include a first waveform of the first signal and a second waveform of the second signal, and determining that the at least one waveform represents a signal primarily associated with an internal organ may include: determining ratio values of a plurality of modified ratios over a window corresponding to the at least one waveform of a cardiac cycle, wherein the ratio values of the modified ratios indicate a blood oxygen level of the internal organ; and determining that the determined ratio values of the plurality of modified ratios substantially correspond to characteristics of the ratio values of the modified ratios of the internal organ.

[0024] In some embodiments, the internal organ includes a brain, and determining that the one or more signals are primarily associated with the brain includes determining that at least one waveform of the one or more signals includes a first component in which the signal level generally increases at a first rate, followed by a second component in which the signal level generally decreases at a second rate, the second rate having a smaller amplitude than the first rate.

[0025] In some embodiments, determining that the one or more signals are primarily brain related further comprises determining that a pulse onset of at least one waveform is delayed relative to a corresponding pulse onset of an arterial signal obtained from the skin.

[0026] In some embodiments, wherein the internal organ includes lungs, a first signal of the one or more signals is obtained from light having a wavelength of approximately 660 nm, and determining that the first signal is primarily associated with the lungs includes determining that a first waveform of the first signal corresponds to an inverted pulmonary artery pressure waveform.

[0027] In some embodiments, wherein the internal organ includes lungs, determining that the one or more signals are primarily associated with the lungs includes determining that at least one waveform of the one or more signals includes components corresponding to a systolic pulse, a diastolic pulse, and a dicrotic notch.

[0028] In some embodiments, wherein the internal organ comprises a liver, and determining that the one or more signals are primarily associated with the liver comprises determining that at least one waveform of the one or more signals comprises at least one of an X-wave component and a P-wave component.

[0029] In some embodiments, wherein determining that the one or more signals are primarily liver related further comprises determining that a pulse onset of at least one waveform is delayed relative to a corresponding pulse onset of an arterial signal obtained from the skin.

[0030] In some embodiments, wherein the internal organ includes intestines, and determining that the one or more signals are primarily associated with the intestines includes determining that at least one waveform of the one or more signals includes one or more venous wave components, a pulse onset of the one or more venous wave components being delayed relative to a corresponding wave component of an arterial signal obtained from the skin of the subject.

[0031] In some embodiments, wherein the internal organ includes a kidney, a first signal of the one or more signals is obtained from light having a wavelength of approximately 895 nm, and determining that the first signal is primarily associated with the kidney includes determining that a first waveform of the first signal corresponds to an arterial waveform.

[0032] In some embodiments, wherein the internal organ includes skeletal muscle, and determining that the first signal is primarily associated with the skeletal muscle includes determining that at least one waveform of the one or more signals corresponds to an arterial waveform having a relatively low pulse amplitude.

[0033] The method may further include assessing the health of the subject based on the comparison and outputting an assessment of the subject's health. For example, comparing the data acquired from the at least one waveform with informational features of the health condition may include comparing one or more components of the at least one waveform with one or more corresponding components of one or more template waveforms, each of the one or more template waveforms being characteristic of the health condition. In some embodiments, comparing the data acquired from the at least one waveform with informational features of the health condition may include comparing a first shape of the at least one waveform with a second shape of the one or more template waveforms.

[0034] In some embodiments, in response to determining that the V wave component of the at least one waveform has a greater amplitude than a corresponding V wave component of a corresponding template waveform of the internal organ, it is determined that the subject may have heart failure.

[0035] In some embodiments, in response to determining that a first component of the at least one waveform indicates a signal level increasing at a first rate, a second component following the first component indicates a signal level decreasing at a second rate, and the amplitude of the first rate is less than the second rate, it is determined that the subject may have relatively high intracranial pressure and / or a cerebral hematoma.

[0036] In some embodiments, wherein the internal organ includes the brain, and in response to determining that the at least one waveform does not depict a V-wave or Y-wave component, it is determined that the subject may have relatively high intracranial pressure.

[0037] In some embodiments, wherein the internal organ comprises a brain, and in response to determining that the AC signal level value of the at least one waveform exceeds a threshold, it is determined that the subject may have increased intracranial pressure.

[0038] In some embodiments, wherein the internal organ includes a brain, and in response to determining that a DC signal level value of at least one waveform of the one or more signals is less than a threshold, it is determined that the subject may have increased intracranial pressure.

[0039] In some embodiments, in response to determining that the at least one waveform includes oscillations at approximately 7 Hz, it is determined that the subject may have relatively very high intracranial pressure and / or a cerebral hematoma.

[0040] In some embodiments, wherein the one or more signals include a first signal associated with a corresponding first waveform and a second signal associated with a corresponding second waveform, and wherein the first wavelength is longer than the second wavelength, and the first and second waveforms represent signals primarily associated with the lungs, in response to determining that the first waveform includes a venous waveform characteristic and the second waveform includes a venous waveform characteristic, it is determined that the health condition includes pulmonary hypoventilation.

[0041] In some embodiments, wherein the one or more signals include a first signal associated with a corresponding first waveform and a second signal associated with a corresponding second waveform, wherein the first wavelength is longer than the second wavelength, and the internal organ includes a lung, in response to determining that the first waveform includes a significant V wave component and the second waveform does not include a significant V wave component, it is determined that the health condition includes pulmonary hypoventilation.

[0042] In some embodiments, wherein the internal organ comprises a liver, and responsive to determining that at least one waveform of the one or more signals comprises a significant P-wave component, determining that the health condition comprises high portal blood flow.

[0043] In some embodiments, wherein the internal organ includes a liver, and in response to determining that at least one waveform of the one or more signals differs by a threshold amount from a template waveform representative of a healthy liver, determining that the health condition includes any one or more of hepatitis, cirrhosis, and right heart failure.

[0044] In some embodiments, wherein the internal organ comprises a heart, and the method further comprises, in response to determining that the at least one waveform is substantially consistent with a template waveform characteristic of abnormal motion of the heart, determining that the heart is damaged due to myocardial infarction or heart failure.

[0045] In some embodiments, wherein the internal organ comprises a heart, the method further comprises analyzing the one or more signals to determine the timing of cardiac chamber contraction and relaxation in the cardiac cycle.

[0046] In some embodiments, wherein the one or more signals include a first signal obtained from light of a first wavelength and a second signal obtained from light of a second wavelength, and wherein the at least one waveform includes a first waveform of the first signal and a second waveform of the second signal, the method further comprises: determining a ratio value of a plurality of modified ratio values over a window of the at least one waveform, wherein the window corresponds to systolic and diastolic phases of a cardiac cycle, and wherein the ratio value of the modified ratio values indicates a blood oxygen level of an internal organ. Determining the ratio value of the plurality of modified ratio values over the window of the at least one waveform corresponding to the cardiac cycle may include sampling the oxygen level at a relatively high rate over the window.

[0047] In some embodiments, comparing data acquired from the at least one waveform to information characteristic of a health condition includes determining that the internal organ is potentially unhealthy in response to determining that a ratio value of the determined plurality of modified ratios deviates from a ratio value characteristic of the internal organ.

[0048] In some embodiments, the method further comprises: receiving, substantially simultaneously, third and fourth signals acquired from the subject as one or more signals, wherein the third and fourth signals are derived from measured light reflected from the subject's skin at respective third and fourth different wavelengths; and determining a ratio value of a plurality of modified ratio values over a window of third and fourth waveforms associated with the respective third and fourth signals, wherein the window corresponds to systolic and diastolic phases of the cardiac cycle, and wherein the ratio value of the modified ratio values is indicative of skin blood oxygenation level. In some embodiments, the method comprises comparing the ratio values of the plurality of modified ratio values acquired from the subject's skin with the ratio values of the plurality of modified ratio values acquired from the subject's internal organs, and in response to determining that the ratio values of the modified ratio values differ over the window corresponding to the cardiac cycle, determining that the first and second signals represent signals primarily associated with the internal organs.

[0049] For example, the ratio of ratios can be calculated as follows:

[0050]

[0051] Wherein, the first wavelength is shorter than the second wavelength, AC1(t) is the change in signal level of the first signal I1 at time t, AC2(t) is the change in signal value of the second signal I2 at time t, I1(t0) is the signal value of the first signal at time t0 used as a first normalization factor, and I2(t0) is the signal value of the second signal at time t0 used as a second normalization factor for a longer wavelength, also taken at time t0. Time t0 may be the time of the peak light intensity signal value (I1) of the first signal, and the normalization factor (I2) of the second signal may be the light intensity signal value of the second signal also at time t0. The time t0 for determining the normalization factor may be a time after time t. In some embodiments, the normalization factor (I1) and the normalization factor (I2) of the modified ratio R may be calculated using respiratory oscillations to account for changes in signal values as a result of the subject's respiratory cycle, wherein t0 is defined by the time point of the peak signal value at the beginning of each respiratory oscillation for each wavelength. In some embodiments, the method further includes averaging the determined ratio values of the modified ratio using cardiac oscillations occurring over phases of the respiratory cycle to determine an averaged modified ratio level for one or more of the inspiration, inspiration pause, expiration, and expiration pause phases of the respiratory cycle.

[0052] In some embodiments, the method further includes determining a tissue oxygen level value for the internal organ based on a maximum modified ratio value ratio value during the systolic and diastolic phases of the cardiac cycle. For example, the method may include determining a time point of end of diastole and a maximum R value based on determining the A wave component of the first and second waveforms. The method may include determining a tissue oxygen level value for the internal organ based on a rate of change of the modified ratio value ratio during the systolic and diastolic phases of the cardiac cycle.

[0053] The method may include comparing the blood oxygen level to a threshold level; and in response to determining that the blood oxygen level is below the threshold level, determining that the subject is suffering from an adverse health condition.

[0054] In some embodiments, the method may include comparing the blood oxygen level to a threshold level; and responsive to determining that the blood oxygen level is greater than or less than the threshold level, determining that the subject has increased intracranial pressure, wherein the internal organ includes the brain.

[0055] In some embodiments, the method may include analyzing a drop in blood oxygen levels during the diastolic phase to determine clinical information.

[0056] In some embodiments, the method may include determining minimal oscillations in blood oxygen levels in a body organ over multiple respiratory cycles to assess oxygen exchange in the lungs.

[0057] In some embodiments, wherein the internal organ includes a lung, the method may include determining blood oxygen levels throughout the first and second waveforms; and determining an indication of systemic arterial blood oxygen level based on the peak blood oxygen level during the diastolic phase.

[0058] In some embodiments, wherein the internal organ comprises a lung; and the method further comprises: determining a maximum blood oxygen level to provide an indication of lung function.

[0059] In some embodiments, wherein the internal organ comprises a lung; and the method further comprises: determining a minimum blood oxygen level to estimate a mixed venous oxygen value of blood entering the lung.

[0060] In some embodiments, determining that at least one waveform of the one or more signals represents a signal primarily associated with an internal organ includes determining that a waveform of the blood oxygen level is significantly consistent with a template blood oxygen waveform characteristic of an internal organ.

[0061] In some embodiments, the method may include receiving at least one additional signal resulting from received light reflected at a respective different wavelength from an additional region of the subject adjacent to another internal organ; determining that at least one additional waveform of the at least one additional signal represents an additional signal primarily associated with the additional internal organ; and comparing data obtained from the at least one additional waveform with informational features of a health condition to diagnose a systemic or regional disease in the subject.

[0062] In some embodiments, the method may include: receiving at least one additional signal obtained from received light reflected from the subject's skin at respective different wavelengths; determining that at least one additional waveform of the at least one additional signal represents an additional signal primarily associated with the subject's skin; and comparing data obtained from the at least one additional waveform with information characteristics of a health condition to diagnose a systemic or regional disease in the subject.

[0063] In some embodiments, assessing health includes monitoring blood flow in an internal organ based on a comparison of a shape and / or amplitude of at least one waveform to one or more template waveforms.The at least one or more waveforms may be associated with a first signal having a wavelength of 805 nm.

[0064] In some embodiments, the method may include, in response to determining that the at least one waveform is substantially similar to an arterial blood pressure waveform, determining that the subject's arterial blood pressure is much greater than the central venous pressure and that blood flow is high.

[0065] In some embodiments, wherein when the target organ is the liver, the method may include determining that very high portal blood flow and / or hepatic hypoxia is present responsive to determining that at least one waveform includes a P wave component having a relatively high amplitude.

[0066] In some embodiments, the method may include determining that venous pressure is high and organ blood flow is low in response to determining that at least one waveform includes an exaggerated venous waveform. For example, the exaggerated venous waveform may include a high-amplitude V-wave component and optionally a high-amplitude A-wave component, and, for example, may determine that the subject has one or more of an elevated central venous pressure level, fluid overload, and heart failure.

[0067] In some embodiments, the method includes receiving information indicative of an internal organ identified as a target. For example, determining that at least one waveform of the one or more signals represents a signal primarily associated with an internal organ can be based at least in part on the received information indicative of the target internal organ. The information characteristic of the health condition can be based at least in part on the received information indicative of the target internal organ.

[0068] Some embodiments relate to a computer-implemented method of assessing breathing of a subject, the method comprising: receiving one or more signals obtained from measured light reflected at respective wavelengths from an area near an internal organ of the subject; calculating a statistical measure of the intensity of the one or more signals; and determining changes in the statistical measure over time and correlating the changes with a breathing pattern of the subject. The method may further comprise outputting control instructions to control a mechanical ventilator based on the determined breathing pattern. The internal organ may be or include any of the following: brain, liver, lungs, intestines, heart, fetus.

[0069] Some embodiments relate to a system for assessing the health of a subject, the system comprising: one or more processors; and a memory comprising computer-executable instructions, the memory being coupled to the one or more processors; wherein the one or more processors are configured to execute the computer-executable instructions to cause the system to perform any of the methods described.

[0070] Some embodiments relate to a computer program comprising instructions which, when executed by one or more processors, cause the one or more processors to perform any of the described methods.

[0071] Some embodiments relate to a system for assessing a subject's health, comprising: any of the devices described for determining blood oxygen level; a memory comprising computer-executable instructions; and a processor coupled to the memory and configured to execute the computer-executable instructions to perform any of the methods described. In some embodiments, the system includes a second device for determining blood oxygen level, the second device comprising a second light source and a second light detector, the second light detector configured to receive an additional signal indicative of an arterial pulse in the subject's skin and to provide the additional signal to the processor. In some embodiments, the system includes one or more second devices for determining blood oxygen level of an internal organ, the one or more second devices comprising a second light source and a second light detector, the second light detector configured to receive an additional signal indicative of a signal from the internal organ and to provide the additional signal to the processor. In some embodiments, the system includes one or more second devices for determining blood oxygen level of one or more second internal organs, the one or more second devices comprising a second light source and a second light detector, the second light detector configured to receive an additional signal indicative of a signal from the second internal organ and to provide the additional signal to the processor.

[0072] In some embodiments, the device may be coupled to a catheter placed within the body of a subject.

[0073] Some embodiments relate to a method of obtaining data indicative of intracranial pressure in a subject, the method comprising: positioning a light source of any one of the devices near an intergyral sulcus of the subject's brain in a manner spaced relative to the subject's skull; projecting light from the light source through the subject's skull into the intergyral sulcus, wherein the light comprises light of one or more discrete wavelengths; receiving the light at a light detector of the device, the received light reflected from cerebrospinal fluid in the intergyral sulcus at the one or more discrete wavelengths; generating one or more signals indicative of the intensity of the one or more discrete wavelengths of light; and providing the one or more signals to the system to allow determination of elevated intracranial pressure in the subject based on the waveform of at least one of the one or more signals.

[0074] The method may include determining elevated intracranial pressure in the subject based on a waveform of at least one of the one or more signals, and in response to determining that the pulse waveform includes one or more oscillations, determining the elevated intracranial pressure based on one or more of a mode, an amplitude, and a frequency of the one or more oscillations.

[0075] In some embodiments, determining elevated intracranial pressure may include determining that the pulse waveform includes oscillations similar to a waveform of the intracranial pressure trace, and that the pulse begins before a corresponding wave component of an arterial signal obtained from forehead skin.

[0076] Some embodiments relate to a method for assessing the health of a fetus within a subject, the method comprising: receiving one or more signals obtained from received light reflected from a region of the fetus adjacent to an internal organ at respective discrete wavelengths; receiving at least one additional signal obtained from received light reflected from a region of the subject at additional discrete wavelengths; determining based on a comparison of the waveforms that at least one waveform of the at least one signal represents a signal primarily associated with the internal organ, comprising comparing the at least one waveform with at least one additional waveform of the at least one additional signal; and comparing data obtained from at least one of the at least one waveforms to informational features of the health status to assess the health of the fetus.

[0077] The method may include positioning any one of the devices (first device) on an external surface of a subject, adjacent to an internal organ of a fetus, to detect a first signal; and positioning any one of the devices (second device) on any one of a forehead, a finger, an ear, and a nose of the subject to detect a second signal. Comparing the waveforms may include determining a temporal offset between peak signal levels. The method may include positioning the first device on the abdomen of the subject. The method may include positioning the first device intravaginally within the subject. BRIEF DESCRIPTION OF THE DRAWINGS

[0078] The following embodiments are described in further detail, by way of example, with reference to the accompanying drawings, which are briefly described below. In the drawings, like reference numerals represent like features.

[0079] Figure 1 is a perspective view of an apparatus for obtaining data related to blood oxygen levels of internal organs of a subject, according to some embodiments;

[0080] Figure 2(a) is Figure 1 Side view of the device;

[0081] Figure 2(b) is Figure 1 A top view of the equipment;

[0082] Figure 3 yes Figure 1 A cross-sectional view of the equipment along line AA;

[0083] Figure 4 yes Figure 1 An exploded perspective view of the equipment;

[0084] Figure 5 is a schematic diagram of a system for obtaining data related to blood oxygen levels of internal organs of a subject, according to some embodiments;

[0085] Figure 6 is a flow chart of a method of obtaining data indicative of blood oxygen levels of an internal organ of a subject, according to some embodiments;

[0086] Figure 7 (a) is a graph of first and second signals derived from detected light reflected from the brain of a healthy human subject;

[0087] Figure 7 (b) is based on Figure 7 (a) a graph of the ratio of the corrected ratio values calculated for the first and second signals;

[0088] Figure 8 (a) is a graph of third and fourth signals derived from detected light reflected from the forehead skin of a healthy human subject;

[0089] Figure 8 (b) is a graph of fifth and sixth signals derived from detected light reflected from the internal jugular vein of a healthy subject, which are substantially the same as Figure 8 (a) Graph of the detected light obtained simultaneously;

[0090] Figure 8 (c) is a graph of first and second signals derived from detected light reflected from the brain of a healthy subject, which are plotted against Figure 8 (a) Graph of the detected light obtained simultaneously;

[0091] Figure 9 is a flow chart of a method of assessing the health of a subject according to some embodiments;

[0092] Figure 10 (a) is a graph of first and second signals derived from detected light reflected from a well-ventilated lung of a healthy human subject;

[0093] Figure 10 (b) is based on Figure 10 (a) a graph of the ratio of the corrected ratio values calculated for the first and second signals;

[0094] Figure 11 is a graph of first and second signals derived from detected light reflected from a liver of a human subject;

[0095] Figure 12 (a) is a graph of third and fourth signals derived from detected light reflected from the skin of the nose of a sheep subject having relatively high intracranial pressure;

[0096] Figure 12 (b) is a graph of first and second signals derived from detected light reflected from the brain of a sheep subject, which are plotted against Figure 12 (a) Graph of light reflected from the nose skin obtained simultaneously;

[0097] Figure 13 (a) is a graph of third and fourth signals derived from detected light reflected from the skin of the nose of a sheep subject having relatively very high intracranial pressure;

[0098] Figure 13 (b) is a graph of first and second signals derived from detected light reflected from the brain of a sheep subject, which are plotted against Figure 13 (a) Graph of the detected light obtained simultaneously;

[0099] Figure 14 (a) is a graph of third and fourth signals derived from detected light reflected from the skin of the nose of a sheep subject having relatively extremely high intracranial pressure;

[0100] Figure 14 (b) is a graph of first and second signals derived from detected light reflected from the brain of a sheep subject, which are plotted against Figure 14 (a) Graph of the detected light obtained simultaneously;

[0101] Figure 15 (a) is a graph of third and fourth signals derived from detected light reflected from the forehead skin of a supine healthy human subject;

[0102] Figure 15 (b) is a graph of first and second signals derived from detected light reflected from the hypoventilated lung of an otherwise healthy human subject, compared to Figure 15 (a) Graph of the detected light obtained simultaneously;

[0103] Figure 15 (c) is based on Figure 15 (b) a graph of the ratio of the corrected ratio values calculated for the first and second signals;

[0104] Figure 16 is a graph of first and second signals derived from detected light reflected from the intestine of a healthy human subject;

[0105] Figure 17 is a graph of the calculated ratio of corrected ratios of first and second signals derived from detected light reflected from the brains of three human subjects subjected to varying levels of systemic hypoxia, relative to corresponding blood oxygen levels determined by sampling blood from the internal jugular vein;

[0106] Figure 18is a graph of the calculated ratio of corrected ratios of first and second signals derived from light reflected from the brain of a sheep subject at varying degrees of cerebral hypoxia due to reduced blood flow to the brain, relative to corresponding blood oxygen levels determined by sampling blood from the sagittal sinus vein;

[0107] Figure 19 is a graph of a ratio of calculated corrected ratios averaged over each pulse, each pulse being derived from the waveforms of corresponding first and second signals, the first and second signals being derived from detected light reflected from the brain of a sheep subject after blood was injected into the brain to elevate intracranial pressure and disrupt cerebral blood flow;

[0108] Figure 20 (a) is a graph of third and fourth signals derived from light detected from the internal jugular vein of a healthy human subject over a sufficiently long time period to include several respiratory cycles;

[0109] Figure 20 (b) is a graph of first and second signals derived from detected light reflected from the subject's brain, which are plotted against Figure 20 (a) Graph of the detected light obtained simultaneously;

[0110] Figure 20 (c) is based on Figure 20 (b) a graph of the ratio of the corrected ratio values calculated for the first and second signals;

[0111] Figure 21 is a graph of first and second signals derived from detected light reflected from the lungs of a human subject, the human subject breathing and then holding their breath;

[0112] Figure 22 is a graph of two signals from light at first and second wavelengths reflected from a brain of a human subject, wherein a sensor is placed in an ear canal of the subject; and

[0113] Figure 23(a) shows a graph of the percentage of successful brain pulse detection using a device with lateral spacing of 10 mm, 15 mm, 20 mm, and 40 mm between the center of the light source and light detector when the distance between the light source and light detector and the contact surface of the device is zero (i.e., the light source and light detector are located in the subject's skin, as is the case with a conventional optical oximeter device).

[0114] Figure 23(b) shows a bar graph of the percentage of successful brain pulse detection using a device with lateral spacing of 10 mm, 15 mm, and 20 mm between the center of the light source and light detector, when the distance between the light source and light detector and the contact surface of the device is constant at 10 mm (that is, there is a 10 mm spacing between the light source and light detector and the subject's skin).

[0115] Figure 23(c) shows a bar graph of the percentage of successful brain pulse detection using a device with a constant lateral spacing of 15 mm between the centers of the light source and light detector, while the distance between the light source and light detector and the contact surface of the device was varied between 0 mm, 5 mm, 10 mm, 15 mm and 20 mm (i.e., the spacing between the light source and light detector and the subject's skin was varied between 0, 5, 10, 15 and 20 mm).

[0116] Figure 24 A bar graph showing the percentage of successful brain pulse detection using a device with a center-to-center lateral spacing of 10 mm between the light source and light detector, where the distance between the light detector and the contact surface of the device is fixed at 10 mm and the distance between the light source and the contact surface of the device is varied between 15 mm and 20 mm (i.e., 5 mm and 10 mm away from the light source, respectively). DETAILED DESCRIPTION

[0117] Throughout the specification and claims that follow, unless the context requires otherwise, the word "comprise" and variations such as "comprising" and "including" and "having", will be understood to imply the inclusion of a stated integer or step or combination of integers or steps but not the exclusion of any other integer or step or combination of integers or steps.

[0118] The reference to any prior art in this specification is not, and should not be taken as, an acknowledgement or any form of suggestion that that prior art forms part of the common general knowledge in Australia.

[0119] References in this specification to prior patent documents or technical publications are intended to fully incorporate the subject matter of these prior publications into this specification by reference.

[0120] The described embodiments generally relate to devices, systems, and methods for assessing the health of a subject's internal organs.

[0121] Monitoring of internal organs, such as the brain after acute brain injury, typically relies on invasive techniques such as intracranial pressure monitoring, intraparenchymal oxygen sensors and jugular bulb venous catheters. These methods are risky, technically challenging, costly, and can degenerate at a late stage (Barone DG, Czosnyka M., Scientific World Journal. 2014, 2014: 795762, the disclosure of which is incorporated herein by reference in its entirety).

[0122] Non-invasive monitors of brain oxygen levels (e.g., brain oximeters that analyze near-infrared light scattering) have been proposed to study the brain. However, brain oximetry has not been found to have a significant role in clinical applications, and studies have shown inconsistent results. For example, see Schneider A et al., Acta Paediatr, 2014, 103(9): 934-938; Steppan J, Hogue CW, Jr., Best Pract Res Clin Anaesthesiol, 2014, 28(4): 429-439; and Lund A, Secher NH, Hirasawa A et al., Scand J Clin Lab Invest, 2016, 76(1): 82-87 (the disclosures of each of which are incorporated herein by reference in their entirety). Measurement of oxygen saturation may also take 10 to 15 seconds, which limits the amount of information provided. In addition, these monitors do not provide information on the pulse shape that represents blood flow within the organ.

[0123] In an earlier published International Patent Publication No. WO2008 / 134813 (the disclosure of which is incorporated herein by reference in its entirety), the present inventors described a non-invasive method for directly measuring blood oxygen saturation (e.g., central venous and mixed venous oxygen saturation) by placing an optical oximeter device on the skin over deep vascular structures. As described above, pulse oximetry using red and infrared light sources is an established technique for measuring hemoglobin oxygen saturation in blood vessels in the skin. Deoxyhemoglobin (Hb) absorbs more in the red band, while oxyhemoglobin absorbs more in the infrared band. In the earlier International Patent Publication, preferred wavelengths of red light from about 620 nm to about 750 nm and infrared light from about 750 nm to about 1000 nm are disclosed. In pulse oximetry, light is first transmitted through the tissue and then the intensity of the transmitted or reflected light is measured by a photodetector. A pulse oximeter measures the AC (pulsatile) component of absorbance at each wavelength and determines the amount of red and infrared AC components, which indicate the concentration of oxyhemoglobin and deoxyhemoglobin molecules in the blood. The ratio of oxyhemoglobin to total hemoglobin indicates the oxygen saturation of the blood.

[0124] In WO2008 / 134813, the present inventors demonstrated that by exploiting the pulsatile properties of deep vascular structures to generate plethysmographic traces, it is possible to precisely position the transmitter and receiver elements to optimize the detected signal, thereby eliminating the need for simultaneous ultrasound examination and measurement from more than one location. The unique nature of plethysmography in this technique is used to identify the signal as originating from the vascular structure of interest and to filter out signals from other interfering chromophores (e.g., small vessels and surrounding tissue).

[0125] In WO2008 / 134813, the present inventors demonstrated that by exploiting the pulsatile properties of deep vascular structures to generate plethysmographic traces, it is possible to precisely position the transmitter and receiver elements to optimize the detected signal, thereby eliminating the need for simultaneous ultrasound examination and measurement from more than one location. The unique nature of plethysmography in this technique is used to identify the signal as originating from the vascular structure of interest and to filter out signals from other interfering chromophores (e.g., small vessels and surrounding tissue).

[0126] In International Patent Publication No. WO 2012 / 003550 (the disclosure of which is incorporated herein by reference in its entirety), the present inventors determined that the accuracy and reliability of blood oxygen saturation determined by oximetry from deep vascular structures can be improved by employing one or more of the following methods: (a) selecting optimal wavelengths for determining light absorption by hemoglobin in blood (e.g., from about 1045 nm to about 1055 nm and from about 1085 nm to about 1095 nm); (b) positioning the oximeter transmitter and receiver elements within the patient's external auditory canal; (c) increasing the distance between the transmitter and receiver elements to a threshold level of about 60 mm; and (d) angling the transmitter element relative to the receiver element at about 45°.

[0127] Monitoring microvascular oxygen levels and blood flow in a patient's internal organs is of clinical value because disease can lead to organ failure and death. Early warning of impending organ failure could enable earlier intervention, thereby reducing patient morbidity and mortality.

[0128] Tissue oxygen levels of internal organs can be indicative of internal organ health. Therefore, monitoring tissue oxygen levels for low tissue oxygen levels can provide an early indication of impending organ failure. Analysis of light reflected from regions of a subject's internal organs (e.g., the brain, liver, lungs, kidneys, intestines, and heart) can provide an indication of microvascular blood oxygen levels in blood vessels associated with the internal organs, which can provide valuable clinical information about oxygen transfer to the internal organs, the tissue oxygen levels of the internal organs, and corresponding subject health.

[0129] Some embodiments relate to apparatus, systems, and methods for assessing the health of a subject based on at least one signal derived from received light reflected from an area of the subject proximate an internal organ. The inventors have recognized that in order to ensure an accurate assessment of the subject's health, it is important to ensure that at least one signal under consideration actually indicates light reflected from the internal organ and not from overlying skin. Accordingly, the described embodiments relate to determining that the waveform of at least one signal represents a signal actually associated with the internal organ. The described embodiments may relate to determining that the waveform of at least one signal is dominated by or primarily associated with received light reflected from the internal organ.

[0130] Some embodiments relate to devices, systems, and methods for determining a more appropriate or optimal placement of a sensor relative to an internal organ to obtain a signal primarily associated with received light reflected from the internal organ. For example, in response to determining that the received signal is not primarily associated with received light reflected from the internal organ, a processor of the system can be configured to output an instruction for relocating or repositioning a device including a sensor relative to the directed internal organ. The instruction can be effective to cause automatic repositioning of the device, or can instruct an operator to reposition the device. In some embodiments, the instruction can include an indicated distance or coordinate that can be used to reposition the device relative to the directed internal organ.

[0131] Some embodiments relate to devices, systems, and methods for determining, by a processor of the system, that a received signal may not be from or is not primarily associated with received light reflected from an internal organ of interest, but is instead a contamination signal from or primarily associated with the skin.

[0132] For example, a waveform can be compared to one or more template waveforms (characteristic of typical or healthy internal organs) to determine whether the waveform is sufficiently similar to the template waveforms to be determined to be associated with a signal dominated by light reflected from the internal organ. For some internal organs, pulses with venous characteristics are expected in the signal, so the waveform can be compared to a typical or measured venous waveform to determine that the signal is primarily associated with the internal organ. In some cases, it is expected that a skin signal or other arterial signal acquired from the subject at the same time as the signal will produce a waveform that is earlier than the waveform of the signal primarily associated with the internal organ, which can also be used to determine that the signal is primarily associated with the internal organ. In some embodiments, a ratio of the modified ratios is calculated over a window of the waveform corresponding to the cardiac cycle or pulse, and the result is compared to a characteristic value of a typical or healthy internal organ to make this determination. In this case, at least two signals are required to perform the calculation of the ratio of the modified ratios, the at least two signals being derived from light received at two different wavelengths reflected from an area of the subject.

[0133] Once it has been determined that the at least one signal represents a signal primarily associated with an internal organ, data derived from the waveform can be used to assess the health of the internal organ, and therefore the health of the subject. For example, the data derived from the waveform can be compared with informational features of a health condition to assess the health of the subject. For example, such health conditions can include increased intracranial pressure, respiratory impairment, liver failure, heart failure (e.g., a leaky heart valve), cerebral hematoma, intestinal ischemia, and / or pulmonary hypoventilation, and / or health conditions associated with internal organ motion.

[0134] In some embodiments, calculation of a ratio of modified ratios is performed on data acquired from at least two waveforms acquired from an internal organ to perform a health assessment.

[0135] Some embodiments relate to devices, systems, and methods for assessing a subject's health based on a signal derived from received light reflected from an area adjacent to an internal organ of the subject, wherein the pulse shape and amplitude of the signal primarily indicate instantaneous blood flow changes within the pulse duration of blood in the organ's microcirculation. This can be achieved, for example, by subjecting the internal organ to light having wavelengths of approximately 780 nm and 820 nm, preferably 805 nm, which are absorbed to the same extent regardless of oxygen saturation level. Data derived from the waveform corresponding to the signal primarily indicating blood flow in the internal organ can be used to perform a health assessment based on properties of blood flow in the organ and circulatory system.

[0136] Some embodiments relate to devices, systems, and methods for obtaining data related to any one or more of: microvascular blood oxygenation level, microvascular blood pulse shape and amplitude, and motion of a subject's internal organs. Some described embodiments advantageously enable non-invasive acquisition or extraction of such data from light signals reflected by internal organs, while minimizing the contribution of light reflected from the subject's skin. Thus, the described embodiments enable health assessments of internal organs and, accordingly, subjects, including determination of absolute microvascular blood oxygenation saturation, microvascular blood pulse shape and amplitude, and motion of a subject's internal organs.

[0137] refer to Figure 1 , Figure 2(a), Figure 2(b), Figure 3 and Figure 4 , shows an apparatus 100 for determining data indicating blood oxygen levels of an internal organ. The apparatus 100 includes a body 110 including a contact surface 111 for contacting a subject 520 (see FIG. 1 ) near a target internal organ (e.g., brain 521) of the subject 520. Figure 5 ) join.

[0138] The body 110 of the device 100 defines a first groove 112 and a second groove 113. The first and second grooves 112, 113 extend from the contact surface 111 into the body 110, and the second groove 113 is separate from the first groove 112.

[0139] The device 100 is configured to receive a light source 120 in a first recess 112. The light source 120 is configured to emit light from the first recess 112 of the body 110 onto an internal organ. The device 100 is configured to receive a light detector 130 in a second recess 113. The light detector is configured to receive or detect light received at the second recess 113. The received light includes light emitted by the light source 120 that has interacted with the internal organ. For example, the received light may include at least a portion of the light emitted by the light source 120 that has been reflected and / or scattered by the internal organ. The wavelength and / or intensity of the received light may be changed relative to the wavelength and / or intensity of the emitted light, for example due to absorption and / or scattering of light by body tissue / organs. Throughout the specification and the appended claims, it should be understood that reference to light reflection or reflected light does not mean that the emitted light and the reflected light have the same wavelength and / or intensity. The device 100 is configured such that the light source 120 and the light detector 130 are retracted from the contact surface 111 (e.g., for example, from about 1 mm to about 20 mm, such as from about 5 mm to about 15 mm or about 6 mm to about 12 mm, about 7 mm to about 10 mm, or about 7 mm, 8.5 mm or 10 mm) and are spaced apart from each other by a relatively small amount (e.g., a spacing S) such that the received or detected light indicates the blood oxygen level in the blood vessels of the internal organ (e.g., the veins on the surface 524 or the microvessels of the brain 521).

[0140] Device 100 differs from a standard cerebral oximetry monitor in that light source 120 and light detector 130 are not in contact with the skin and have a small separation distance from each other (unlike the teachings of the prior art). The inventors have determined that these changes reduce light scattering through the skin and maximize the light that reaches light detector 130 after having traveled through at least a portion of the organ. This overcomes a major limitation of existing cerebral oximeters, which obtain most of their signals from the skin rather than the organ beneath it. Furthermore, by understanding the expected pulse waveform and oxygen levels of the organ (which is significantly different from the skin), we can also confirm that the signal is coming from the organ of interest. Standard cerebral oximeters cannot confirm the source of their signals.

[0141] Existing cerebral oximeters have a spacing of at least 40 mm between the light source and the light detector, as having a larger spacing is considered important to be able to detect light reflected from deep within the brain. However, the inventors have found that a shorter spacing provides an improved signal from the organ, reducing the skin signal.

[0142] The light source 120 may include a light emitting region (e.g. Figure 4 432 in FIG), and the light detector 130 may include a light-sensitive area (such as Figure 4 433 in FIG). Figure 4 In the embodiment shown, the light source 120 and the light detector 130 each have a body disposed below the light emitting region 433 and the light sensitive region, respectively. Figure 1 As depicted, all or substantially all of the light source 120 facing the contact surface 111 is a light emitting area (not shown), and all or substantially all of the light detector 130 facing the contact surface 111 is a light sensitive area (not shown). Figure 1 From the perspective depicted, the light source 120 and the light-emitting region (not shown) are indistinguishable from one another, as are the light detector 130 and the photosensitive region (not shown). The light-emitting region and the photosensitive region may be encapsulated by a protective structure. The spacing S between the closest points of the light-emitting region and the photosensitive region may be in the range of about 4 mm to about 20 mm. In some embodiments, the spacing S is in the range of about 4 mm to about 12 mm, about 5 mm to about 10 mm, or about 6 mm to about 8 mm. The spacing S may be, for example, about 7 mm.

[0143] The center of the light source 120 may be spaced apart from the center of the light detector 130 by a distance X of about 20 mm or about 15 mm. Figure 1 In the illustrated embodiment, the center of light source 120 is also the center of the light-emitting region, and the center of light detector 130 is also the center of the photosensitive region, but in other embodiments, the body of light source 120 surrounds the light-emitting region, and the body of light detector 130 surrounds the photosensitive region. For example, in one aspect, the center points of light source 120 (or light-emitting region) and light detector 130 (or photosensitive region) are separated by about 10 mm to about 20 mm, such as about 15 mm, and the spacing S between the closest perimeters of light source 120 and light detector 130 is about 4 mm to about 20 mm, such as about 6 mm to about 8 mm or about 7 mm. In some embodiments, the diameters of light source 120 and light detector 130 are each about 8 mm.

[0144] The light emission area of light source 120 may be set back from contact surface 111 by a spacing Y. Thus, when contact surface 111 engages subject 520, body 110 of the device may help to space the light emission area from subject 520.

[0145] In some embodiments, light detector 130 may include a photosensitive region (not shown) that is set back from contact surface 111 by a spacing Y. Thus, when contact surface 111 engages subject 520, body 110 of device 100 may help space the photosensitive region from subject 520.

[0146] The spacing Y can be in the range of about 1 mm to about 20 mm. In some embodiments, the spacing Y can be in the range of about 7 mm to about 10 mm. The spacing Y can be, for example, about 8.5 mm. In a preferred embodiment of the present invention, the light source 120 (particularly the light emitting area of the light source 120) and the light detector 130 (particularly the photosensitive area of the light detector 130) are retracted from the contact surface 111 by about 7 mm to about 10 mm, for example, about 8.5 mm, and the center points of the light source 120 and the light detector 130 are separated by about 10 mm to about 20 mm, for example, about 15 mm. In one aspect of this embodiment, the diameters of the light source 120 (or light emitting area) and the light detector 130 (or photosensitive area) are in each case about 8 mm. Experimental demonstration of the optimal spacing between the light emitting area and the photosensitive area and the optimal spacing between the light emitting area and the photosensitive area and the contact surface 11 is provided in Example 1 and Figures 23 (a) to (c).

[0147] In other embodiments of the present invention, the distance between the light source 120 and the contact surface 111 is 5 mm greater than the distance between the light detector 130 and the contact surface 111. Figure 24 The efficacy of this embodiment is demonstrated.

[0148] The first and second grooves 112, 113 can have a depth D extending from the base 115 to the plane defined by the contact surface 111. The depth D can be in the range of about 1 mm to about 10 mm. The depth D can be, for example, about 8.5 mm. In the case where the light source 120 and the light detector 130 protrude into the grooves 112 and 113, respectively, the depth D can be slightly less than the spacing Y (also referred to as "set back").

[0149] In some embodiments, the body 110 further includes a wall 114 separating the first recess 112 from the second recess 113. The wall 114 can extend from the base 115 of the body 110 toward the contact surface 111 by a wall height WH. The wall 114 helps limit the light emitted from the light source 120 from being reflected or scattered toward the light detector 130 without first interacting with internal organs. The wall height WH can be at least approximately 2 mm. In some embodiments, the wall height is approximately 4 mm. The wall height WH can be less than or equal to the depth D. The wall 114 can have a wall thickness WT in the range of approximately 1 mm to 2 mm. The wall thickness WT can be, for example, approximately 1.8 mm.

[0150] Light source 120 can be configured to emit light comprising at least two discrete wavelengths. For example, the first discrete wavelength can be centered around 895 nm, 940 nm, or 945 nm (the longer wavelength or first wavelength), and the second discrete wavelength can be centered around 660 nm (the shorter wavelength or second wavelength). The emitted light can include light having wavelengths in at least two discrete narrowband wavelengths.

[0151] In some embodiments, shorter wavelength light may include light with a wavelength in the range of approximately 600 nm to approximately 750 nm. For example, shorter wavelength light may include wavelengths centered at approximately 660 nm and ranging between approximately 640 nm and approximately 680 nm. Longer wavelength light may include light with a wavelength in the range of approximately 850 nm to approximately 1000 nm. For example, longer wavelength light may include wavelengths centered at approximately 895 nm and ranging between approximately 855 nm and approximately 945 nm. In some embodiments, the longer wavelength is approximately 940 nm. Shorter wavelength light is absorbed more by blood with low oxygen saturation (or low blood oxygen level) than longer wavelength light. Longer wavelength light is absorbed more by blood with high oxygen saturation (or high blood oxygen level) than shorter wavelength light. As a result, different intensities of each wavelength band are reflected by internal organs to be received and detected by light detector 130. This principle is used to determine blood oxygen level and is explained in further detail below.

[0152] Light in the range of approximately 640 nm to approximately 680 nm is relatively sensitive to changes in blood oxygen levels and is absorbed to a greater extent by deoxygenated blood than by oxygenated blood. Therefore, light reflected from internal organs (or blood vessels associated with internal organs) at these wavelengths is affected by blood oxygen levels, and the received light intensity can be used (in combination with longer wavelength light) to determine blood oxygen levels.

[0153] Light in the range of about 850 nm to about 1000 nm is relatively sensitive to changes in blood oxygen levels and is absorbed to a greater extent by oxygenated blood than by deoxygenated blood. Therefore, light reflected from internal organs (or blood vessels associated with internal organs) at these wavelengths is affected by blood oxygen levels, and the received light intensity can be used (in combination with shorter wavelength light) to determine blood oxygen levels.

[0154] Light in the range of approximately 780 nm to approximately 820 nm is relatively insensitive to changes in blood oxygen levels and is absorbed to the same extent regardless of blood oxygen saturation levels. Therefore, light reflected from internal organs at this wavelength can provide a more reliable signal from which to determine the phase of the cardiac cycle and / or perform health assessments based on pulsatile changes in blood flow.

[0155] In some embodiments, light source 120 is configured to emit light in a narrow intermediate wavelength band ranging from approximately 780 nm to approximately 820 nm. Light source 120 can also be configured to emit light with wavelengths centered around 805 nm. The amount of light in the intermediate wavelength band is absorbed by blood but is not sensitive to the oxygen saturation of the blood. For example, light source 120 may include a third LED adapted to emit light in the narrow intermediate wavelength band.

[0156] Light source 120 may include one or more semiconductor diodes, such as light emitting diodes. Light detector 130 may also include one or more semiconductor diodes. Light source 120 and light detector 130 may generally be shaped as short cylinders, such as a pill. Light source 120 and light detector 130 may have a diameter Z of approximately 8 mm.

[0157] Light source 120 can have an optical power output of up to about 20 milliwatts (mW). In some embodiments, light source 120 can include two LEDs with a total optical power output of up to about 20 mW, such as, for example, 50 microwatts (μW) to about 20 mW, about 100 μW to about 10 mW, or about 200 μW to about 5 mW. In some embodiments, light source 120 can include two LEDs with a total optical power output of about 100 μW, 200 μW, 500 μW, 10 mW, 15 mW, 20 mW, or greater than 20 mW.

[0158] The light detector 130 can be configured to detect a wide range of wavelengths. The light source 120 can be configured to generate pulsed light of sequentially different frequencies so that only light over a narrow bandwidth is emitted at any given time. The wavelength of the light can then be associated with the light detected by the light detector 130 based on the time of detection.

[0159] In some embodiments, the light detector 130 is configured to detect discrete narrowband wavelength ranges corresponding to the wavelength of the emitted light. The light detector 130 can output multiple signals indicating the intensity of the light detected within each discrete narrowband wavelength range. In some embodiments, the light detector 130 can output a multiplexed signal of the multiple signals.

[0160] The light detector 130 may be configured to generate one or more signals indicative of the intensity of light detected by the light detector 130. The device 100 may be further configured to transmit the signals to the processor 562 ( Figure 5 ). The device 100 may include a conductive cable 140 (or wire) to transmit the signal to the processor 562, or the signal may be transmitted wirelessly to the processor 562. The signal is indicative of the blood oxygen level of the internal organ.

[0161] The light detector 130 may be similar to the light detector 130 provided by Medtronic in its Nellcor TM The PIN photodetector used in the Maxfast forehead sensor.

[0162] In some embodiments, device 100 includes at least two optical waveguides (e.g., optical fibers). Thus, the light emitting region of light source 120 may include an end portion of a first optical waveguide (not shown) located in first groove 112. Light detector 130 may include a second optical waveguide (not shown), one end portion of which is located in second groove 113, and a photosensitive region may be located outside of body 110 of device 100.

[0163] refer to Figure 3 and Figure 4 , the body 110 of the device 100 may be formed from multiple components, including a base 115 and a spacer 116 .

[0164] The base 115 may be formed of a rigid material, for example, a polymer (such as ABS). The base 115 may define a recess 418 to accommodate at least a portion of the light source 120 and the light detector 130. The base 115 may have a base thickness BT of approximately 3 mm (see FIG. Figure 2a ).

[0165] The spacer 116 may be formed of soft foam. The spacer 116 may have a spacer thickness ST of approximately 9 mm (see Figure 2a ). Thus, the body 110 can have an overall height H of approximately 22 mm. When the contact surface 111 engages the subject 520, the spacer 116 can be used to define a spacing Y between the light emission area and the subject 520. Thus, the spacer thickness ST can be greater than or equal to the spacing Y. The spacer thickness ST can be in a range of approximately 8 mm to approximately 11 mm. The spacer 116 and the body 110 can have a length L of approximately 47 mm and a width W of approximately 32 mm.

[0166] In some embodiments, the body 110 further includes a frame 450 configured to be seated in the cavity 419 of the spacer 116. The cavity 419 extends from the contact surface 111 through the entire spacer thickness ST of the spacer 116.

[0167] The frame 450 may define a first groove 112, a second groove 113 and include a wall 114. The frame 450 may have a frame height FH extending from the base 115 toward the contact surface 111. When the frame 450 is located within the cavity 419, the frame height FH may be less than the spacer thickness ST, and the upper edge 451 of the frame 450 may not reach the plane defined by the contact surface 111. The frame height FH may be less than approximately 21 mm. In some embodiments, the frame height FH may be less than approximately 11 mm. The frame height FH may be approximately 8.5 mm. The frame 450 may have a frame length FL of approximately 30 mm and a frame width of approximately 13 mm. The frame 450 may be formed of a rigid material, for example, a polymer (e.g., ABS).

[0168] The frame 450 may define a first hole 452 and a second hole 453, the first hole enabling light from the light source 120 to be emitted from the first recess 112, and the second hole enabling light from the second recess 113 to be received by the light detector 130. In some embodiments, the first hole 452 and the second hole 453 are configured to allow the upper portions (light emitting region) 432 and (photosensitive region) 433 of the light source 120 and the light detector 130, respectively, to protrude into the corresponding first and second recesses 112 and 113.

[0169] In some embodiments, the light source 120 and the light detector 130 are generally housed on a support 440. The cavity 418 of the base 115 can be configured to receive the support 440.

[0170] refer to Figure 6 , a process flow diagram of a method 600 of obtaining data indicative of blood oxygen levels of internal organs of a subject 520 is shown.

[0171] The method 600 includes, at 602, positioning a device 100, 550 from an external surface (eg, skin) of a subject 520 near or adjacent to an internal organ such that a light source 120 of the device 100, 550 is spaced from the external surface.

[0172] At 604, the device projects light from the light source 120 through the outer surface to the internal organ. The light includes at least first and second wavelengths of light.

[0173] After the projected light interacts with the internal organ, the light of the first and second wavelengths is received by the light detector 130 of the device 100. For example, the received light may have been partially absorbed and reflected by the internal organ.

[0174] At 608, device 100 generates a first signal indicating the intensity of light at a first wavelength and a second signal indicating the intensity of light at a second wavelength. For example, the first wavelength may be approximately 660 nm and the second wavelength may be approximately 895 nm. In some embodiments, device 100 further generates a third signal indicating the intensity of light at a third wavelength. For example, the third wavelength may be in the range of approximately 780 nm to approximately 820 nm, or approximately 805 nm.

[0175] In some embodiments, the first device 100 is located near an internal organ of the subject, targeting the internal organ of the subject. This enables the light generated by the light source 120 of the device 100 to be projected through the outer surface of the subject to the area of the internal organ. For example, the generated light can interact with the microvessels and veins of the body organs. The microvessels of the body organs can, for example, include any one or more of the following: arterioles, capillaries, and venules. The light received by the light detector 130 can therefore represent the blood oxygen level of the microvessels or veins of the organ. This can be used to assess the tissue oxygen level of the organ because the low oxygen level reaching the venules and veins is balanced with the extravascular tissue oxygen level.

[0176] However, the projected light may also interact with the subject's skin, which also includes blood vessels. This may affect the light received by the device 100 and, therefore, the signal generated. The inventors have discovered that by separating the light source 120 from the outer surface (e.g., skin) of the subject 520, such that the light source 120 and the light detector 130 do not contact the skin, the light received by the light detector 130 is dominated by light indicating the blood oxygen level in the internal organs. In addition, the light indicating the blood oxygen level from the subject's skin contributes minimally to the received light. The intensity of the light source 120 can be optimized to minimize the contribution of light reflected from the skin.

[0177] Positioning the device in the target brain

[0178] In some embodiments, where the internal organ being evaluated is the brain, the device 100 may be positioned at a location on the scalp where the skull is relatively thin compared to other locations on the skull. For example, suitable locations may include the temples, occipital bones, orbits, parietal bones, and forehead regions of the skull.

[0179] Due to the novel design of the device, which has a relatively small separation distance between the light detector and the LED, the device (or sensor head) can be constructed (e.g., modified and miniaturized) to allow placement in either the right or left ear canal. Placement in the ear canal allows assessment of the health of the temporal lobe and cerebellum of the brain adjacent to the ear canal. The device 100 can also be inserted into the ear canal.

[0180] In some embodiments, the device 100 is positioned above an intergyral sulcus 521 of the brain of a subject 520, such as the lateral intergyral sulcus (Sylvian fissure). Placing the device 100 at or above the lateral intergyral sulcus or other cortical intergyral sulcus can cause the projected light to interact with the cerebrospinal fluid (CSF) covering the brain. In this case, because each arterial pressure pulse of blood entering the skull causes a pulsatile change in the intracranial pressure level, the signal from the detected light can be dominated by the influence of the movement of the CSF in response to the pulsatile changes in intracranial pressure. As discussed in more detail below, when the device is placed at or above the lateral intergyral sulcus or other cortical intergyral sulcus of a subject, the signal from the device can be used to determine and / or monitor intracranial pressure changes in the brain.

[0181] Positioning the device to the target lung

[0182] In some embodiments, device 100 may be positioned on the upper transverse bone, the supraclavicular space, or between the ribs of subject 520 so that device 100 is proximate to the lungs of subject 520 to obtain data indicative of blood oxygen levels in the lungs.

[0183] Positioning the device to the target liver

[0184] Device 100 may be positioned below the ribs in the right upper quadrant or epigastrium of the subject such that device 100 is proximate to the liver of subject 520 to obtain data indicative of liver blood oxygen levels.

[0185] Positioning the device in the target intestine

[0186] Device 100 may be arranged to be positioned on the abdomen or either lower abdomen of the subject such that device 100 is proximate to the intestines of subject 520 to obtain data indicative of the blood oxygen level of the intestines.

[0187] Positioning the device to the target kidney

[0188] Device 100 may be arranged to be positioned on the back of the subject such that device 100 is proximate to the kidneys of subject 520 to obtain data indicative of the blood oxygen level of the kidneys.

[0189] Positioning the Device to a Target Skeletal Muscle For example, the device 100 can be arranged to be positioned on a muscle (e.g., a leg muscle) of a subject, targeting a target skeletal muscle (e.g., a gastrocnemius muscle (or calf muscle)) to obtain data indicative of the blood oxygen level of the skeletal muscle.

[0190] Position the device in the right ventricle of the target heart

[0191] The device 100 may be positioned, for example, on the sternum of the chest or along the left edge of the sternum where it meets the ribs, targeting the right ventricle of the heart.

[0192] Positioning the device to the target fetus

[0193] Device 100 can be positioned on the abdomen of subject 520 such that device 100 (a transabdominal sensor) is proximal to the uterus (uterus) of subject 520 to obtain data indicating the blood oxygen levels of the internal organs of the fetus in utero. A fetus has a different heart rate, rhythm, and pulse shape than its mother. A fetus also has different blood oxygen levels than its mother.

[0194] In some embodiments, the device 100 may include a light source adapted to be positioned within the mother's vagina to enable light to be projected onto the fetus's brain, thereby enabling measurement of brain oxygen levels during labor.

[0195] In some embodiments, multiple devices 100, 550 can be used to obtain data from the same internal organ simultaneously or substantially simultaneously. This can be used, for example, to determine any differences between different regions of the internal organ or to obtain additional data, thereby enabling more accurate results that are more representative of the organ as a whole. In some embodiments, two devices 100 are placed on the scalp, one on each side of the head, to obtain data from the arterial pulses in the skin and from each hemisphere 521 of the brain.

[0196] The device 100 can be configured to simultaneously determine data from multiple organs or parts of the body, as well as the skin. This can be useful in detecting systemic and localized disease in the body by monitoring abnormal combinations of blood oxygen levels, pulse shapes, pulse amplitudes, and / or patterns of organ movement. This allows for determining whether changes in blood flow or oxygen levels are systemic (occurring at multiple sites) or localized (occurring at only one site).

[0197] refer to Figure 5 , according to some embodiments, a system 500 for assessing the health of a subject 520 is shown. The system 500 includes a processor 562, a memory 568 coupled to the processor 562. The system 500 may further include an apparatus for determining data indicative of blood oxygen levels of internal organs, such as the apparatus 100. The system 500 may include a computing device 560 including the processor 562, a display 564, and a user interface 566. The processor 562 may be configured to execute instructions (computer-readable instructions or code) stored in the memory 568 to perform the described methods, such as assessing the health of the subject based on one or more signals indicative of blood oxygen levels of internal organs received from the apparatus 100. For example, the apparatus 100 may be coupled to the processor 562 via a conductive cable 140 or wirelessly.

[0198] In some embodiments, system 500 may further include a second device 550 for determining data indicative of blood oxygen level. Second device 550 includes a second light source and a second light detector configured to generate an additional signal. For example, the additional signal may indicate the timing and characteristic waveform of an arterial pulse of subject 520. The second light detector is configured to transmit data representing the additional signal to processor 562. In some embodiments, processor 562 may be configured to receive the first and second signals from first device 100 and the third signal from second device 550.

[0199] The second light source may be adapted to generate the aforementioned narrow intermediate wavelength band of light.The second light detector may correspondingly be adapted to receive and detect the narrow intermediate wavelength band of light.

[0200] In some embodiments, second device 550 can be a component of a conventional skin pulse oximeter. Second device 550 can be configured to receive reflected light from subject 520. Alternatively, second device 550 can be configured to be placed on a portion of the subject, such as the forehead, nose, ear, or finger, and receive light transmitted through that portion of subject 520.

[0201] Second device 550 can be positioned on or near an external surface (e.g., skin) of subject 520 at a location spaced apart from the location of first device 100, such that the third signal indicates supplemental information, including pulse shape, pulse amplitude, relative timing of the pulses, and blood oxygen level relative to the spaced apart location. This will be discussed in further detail below.

[0202] In some embodiments, computing device 560 includes an analog interface (not shown) that connects device 100, 550 to processor 562. The analog interface may include, for example, a "Pulse Oximeter Integrated Analog Front End" model AFE4490 from Texas Instruments. The analog interface may also provide power to device 100, 550.

[0203] In some embodiments, the system 500 further includes sensors attached to a catheter and placed within the subject's body, such as an endotracheal tube (to assess the lungs, pulmonary artery), a nasogastric tube (to assess the lungs, heart, liver, esophagus, stomach, duodenum), a urinary catheter (to assess the bladder, intestines), a cerebrospinal fluid ventricular drain (to assess the brain), an abdominal conventional post-operative drain (to assess the liver, intestines), and / or a chest tube (to assess the heart and lungs). The processor 562 can be configured to receive and process signals received from the sensors to help make determinations about the subject's health.

[0204] In order to accurately assess the health of the subject based on the received signals, the received one or more signals will preferably be primarily (or dominated by) a signal indicative of the blood oxygen level of the target internal organ. For example, it will be appreciated that poor placement of the device relative to the internal organ may result in one or more signals that include contributions or information from both light reflected from the subject's skin and light reflected from the target internal organ.

[0205] By determining that a waveform associated with a signal represents a signal primarily associated with the target internal organ 521 before making an assessment of the subject's health based on the signal, the described embodiments provide a more accurate assessment of the subject's health.

[0206] For some internal organs, a signal characteristic of the venous circulation is expected, so the waveform can be compared to a typical venous signal (which has the characteristics of the waveform of the central venous blood pressure trace or the measured venous waveform) to determine that the signal is primarily related to the internal organ. This will refer to Figure 7 and Figure 8 To further explain, where waveforms associated with first and second signals from an internal organ are being analyzed, it should be understood, however, that an assessment of the health of the internal organ may also be determined based on waveforms associated with a single signal.

[0207] refer to Figure 7 (a) shows an example of a first waveform of a first signal 701 derived from measured light reflected from an internal organ at a first wavelength, and a second waveform of a second signal 702 derived from measured light reflected from the internal organ at a second, relatively shorter wavelength. In this example, the first wavelength is approximately 895 nm and the second wavelength is approximately 660 nm. These first and second signals 701, 702 are obtained from the device 100 placed on a subject 520 near a human brain 521. The amplitude or level of the signal represents the intensity of light detected by the light detector 130 and is plotted as a function of time.

[0208] Blood oxygen levels in the microcirculation of all regions of the body, except the lungs, typically increase during the systolic phase of the cardiac cycle and decrease during the diastolic phase as oxygen moves from the blood into the tissues. This results in corresponding changes in the detected signal levels. The first and second waveforms of the corresponding first and second signals 701, 702 display a plurality of peaks and troughs representing changes in intensity levels over time and indicating the subject's pulse. Signals 701, 702 can be described as pulsatile signals and / or plethysmographic signals.

[0209] In some embodiments, second conventional device 550 may be located at a location spaced apart from first device 100 to generate third and fourth signals indicative of blood oxygen levels in the skin. The spaced apart location may be, for example, any one of the forehead, finger, ear, and nose of subject 520. The third and / or fourth signals may indicate pulse shapes, relative timing of pulses, and arterial blood oxygen levels from the spaced apart location.

[0210] Figure 8 (a) shows an example of a third waveform of a third signal 803 derived from measured light reflected from the skin at a third wavelength, and a fourth waveform of a fourth signal 804 derived from measured light reflected from the skin at a fourth, relatively shorter wavelength, generated by the second device 550. In this example, the third wavelength is approximately 895 nm and the fourth wavelength is approximately 660 nm. The third and fourth waveforms of the respective third and fourth signals 803, 804 show multiple peaks and valleys representing intensity levels varying over time. The third and fourth signals 803, 804 were obtained from the forehead of a human subject 520 and represent skin pulsating arterial signals. That is, the third and fourth waveforms are characteristic of pressure waveforms of arterial circulation signals in the skin.

[0211] Figure 8 (b) shows an example of a simultaneous fifth waveform of a fifth signal 805 derived from measured light reflected from the internal jugular vein at a fifth wavelength, and a sixth waveform of a sixth signal 806 derived from measured light reflected from the internal jugular vein at a sixth, relatively shorter wavelength, generated by the second device 550. In this example, the fifth wavelength is approximately 895 nm, and the sixth wavelength is approximately 660 nm. The fifth and sixth waveforms of the corresponding fifth and sixth signals 805 and 806 show multiple peaks and valleys representing intensity levels varying over time. Because the second device 550 is placed over the internal jugular vein of the subject 520, the fifth and sixth signals 805 and 806 represent pulsatile venous circulation signals. The illustrated fifth and sixth signals 805 and 806 represent the shape of venous blood pressure variations typically observed in large veins when monitoring pressure levels. In other words, the fifth and sixth waveforms are characteristic of venous circulation pressure signals.

[0212] Similar to Figure 7 (a) is a graph of Figure 8(c) depicts a first waveform of a first signal 801 derived from measured light reflected from an internal organ at a first wavelength and a second waveform of a second signal 802 derived from measured light reflected from an internal organ at a second, relatively shorter wavelength. These first and second signals 801, 802 are obtained from sensors of the device 100 placed on the subject 520 near the brain 521, while Figure 8 (a) is a graph of detected light. The amplitude or level of the signals 801, 802 represents the intensity of the light detected by the light detector 130 and is plotted as a function of time. Figure 8 (c) It can be seen that the shapes of the first and second waveforms of the first and second signals 801, 802 obtained from the brain using the device 100 are similar to those of the arterial signal (e.g. Figure 8 (a)) to better match the venous signal (as shown in Figure 8 (b)). Therefore, it can be inferred that the first and second signals 801, 802 likely originate from received light interacting primarily with the surface of an internal organ (in this case, the brain 524), where most of the blood resides in venules and veins. Therefore, the brain signal waveform differs from the skin signal waveform and can be used to determine that the signal originates from the brain rather than the skin.

[0213] Reference again Figure 8 (b) and 8(c), the components of the waveforms may correspond to features typically found in a venous blood pressure waveform from a vein, such as A, C, X, V, and Y waves. For example, the first and / or second waveforms may include A, C, X, V, and / or Y wave components corresponding to the A, C, X, V, and Y waves typically observed in a pressure signal from a vein (venous signal).

[0214] In the signal values of the waveform, the A-wave component can be observed as a large trough. The A-wave typically occurs at the end of the diastole phase of the cardiac cycle due to atrial contraction. The C-wave component can be observed as a small trough superimposed on the waveform's signal values after the minimum signal value of the A-wave. This typically occurs at the beginning of the systole phase of the cardiac cycle due to tricuspid valve bulging. The X-wave component can be observed as an increase in signal value after the minimum point in the A-wave. The X-wave typically begins at the end of the diastole phase of the cardiac cycle as blood empties from the heart, thus occurring during the systole phase. The V-wave component can be observed as a trough superimposed on the waveform's signal values after the X-wave and the peak signal value. The V-wave typically occurs during the late systole phase of the cardiac cycle due to filling of the heart's atria. The Y-wave component can be observed as an increase in signal value after the local maximum of the V-wave. The Y-wave typically occurs during the early diastole phase of the cardiac cycle as the heart's ventricles begin to fill.

[0215] In some embodiments, determining that the waveform represents a signal primarily associated with the target internal organ includes determining that the waveform includes at least one of an X-wave component, an A-wave component, a C-wave component, a V-wave component, and a Y-wave component.

[0216] As shown in the following figures, signals indicating light reflected from internal organs (such as the brain, lungs, liver, intestines, and fetal organs) tend to exhibit the characteristics of a venous signal at at least one wavelength. For skeletal muscle and cardiac signals, typical venous characteristics may not be present.

[0217] This knowledge may be used to analyze one or more signals from device 100 to determine or confirm that at least one waveform of the signals represents a signal associated with an internal organ of subject 520. For example, in some embodiments, determining that the waveform of one or more signals received from device 100 represents a waveform of a signal associated with an internal organ of subject 520 may include determining whether the waveform represents a waveform of a venous signal.

[0218] In some embodiments, an additional signal (e.g., Figure 8 The additional waveform of the signal 803) depicted in (a) is compared to one or more waveforms to confirm that at least one waveform of the signal represents a signal associated with an internal organ of the subject 520. For example, it is expected that the waveform will depict a component of the signal, such as the onset of a brain pulse (maximum signal intensity) that is delayed in time compared to a corresponding component of the skin pulse. This reflects the time it takes for blood to move through the microcirculation to reach the cerebral venules. In some embodiments, the additional or third signal can originate from reflected light having a wavelength in the range of about 780 nm to about 820 nm. In some embodiments, the wavelength of the light originating from the subject's skin reflection is any of the following: about 660 nm, about 805 nm, about 895 nm, or about 940 nm.

[0219] The one or more signals from different internal organs or mainly related to different internal organs may each have a characteristic waveform. The characteristic waveforms of different internal organs may be different, such as Figure 7 、 Figure 8 、 Figures 10 to 16 and Figure 20As depicted, and discussed in detail below. A waveform from at least one of the one or more signals can be compared to one or more characteristic waveforms to determine whether the waveform is sufficiently similar to any of the characteristic waveforms. The comparison can be used to determine whether one or more signals represent signals associated with internal organs and / or to determine the health status of subject 520, which will be discussed in more detail below. In any case, in some embodiments, if the comparison is used to determine whether one or more signals represent signals associated with internal organs, and to determine the health status of subject 520, different similarity tolerances or thresholds can be applied. For example, when evaluating whether one or more signals represent signals associated with internal organs, a lower similarity threshold can be applied, while when determining the health status of subject 520, a relatively higher similarity threshold can be applied.

[0220] In some embodiments, a ratio of modified ratio values can be calculated from the signal levels of two or more signals on corresponding waveforms. The ratio of the modified ratio values indicates the blood oxygen level and can be used to determine whether the two or more signals represent signals related to internal organs, or to determine the health status of subject 520. This will be discussed in detail below.

[0221] For comparison of two or more waveforms, such as waveforms and signatures associated with signals from internal organs, preferably the same portion or window of the pulsatile signal is compared. Figure 7 In some embodiments, the start of the waveform window can be determined at a peak signal level 707 of the second signal 702, and the end of the waveform window can be determined at a minimum signal level 708 of the second signal 702. In some embodiments, the end of the waveform window can be determined at a subsequent peak signal level 709 of the second signal 702. The waveform window can include a time-limited segment of the signals 701, 702, 801, 802, 803, and 804. For example, the waveform window can include a segment of the signals 701, 702, 801, 802, 803, and 804 from a first extreme signal level to a second extreme signal level (or immediately before the second extreme signal level). The window can, for example, include a segment of the signals 701, 702, 801, 802, 803, and 804 from a first peak level to a second peak level (or immediately before the second peak level). Thus, the window may begin at the leading edge of the A wave and end at the end of the X wave. In some embodiments, the window of the waveform may, for example, include the segment of signals 701, 702, 801, 802, 803, 804 from a first minimum signal level to a second minimum signal level (or immediately before the second minimum signal level). Thus, the windowed waveform may begin at the X wave and end at the trough of the A wave.

[0222] In some embodiments, the start and end of the window for comparing the waveforms of the signals can be determined using the waveforms (or signal levels) of the other signals, such as the arterial signals 803, 804 or the jugular vein signals 805, 806. For example, the waveform window can be determined to begin at the peak signal level of the individual signals and end at the minimum signal level of the individual signals. The individual signals can originate from light with a wavelength in the range of approximately 780 nm to approximately 820 nm.

[0223] In some embodiments, analysis of waveforms from additional signals can also be used to determine the timing of the systolic and diastolic phases of the cardiac cycle. This can be useful in situations where determining the phase of the cardiac cycle based on the waveforms of one or more signals is not particularly easy. For example, determining the A-wave and X-wave components from the waveforms of one or more signals to determine when the systolic and diastolic phases occur may not be straightforward.

[0224] The waveform can include discrete portions of the corresponding signal within a specific time period. In some embodiments, the waveform can include a portion of the wavelength of the signal indicative of only a portion of the pulses of the subject, can include the wavelength of the signal indicative of a single pulse of the subject, or can include multiple wavelengths of the signal indicative of multiple pulses. Once the window or waveform is determined, an average or summed waveform can be generated from the multiple waveforms to improve the signal-to-noise ratio. In some embodiments, a window function can be applied to the first and / or second signal to derive the corresponding first and second waveforms. For example, the window function can include a rectangular, triangular, smooth, and / or bell-shaped curve function.

[0225] In some embodiments, the waveform of one or more signals is selected based on the waveform (or signal level) of an additional signal derived from light of a third wavelength in the range of about 780 nm to about 820 nm. The waveform may, for example, begin when the peak signal level of the third signal reaches the minimum signal level of the additional signal. Light having a wavelength in the third wavelength range is sensitive to blood but not to changes in blood oxygen levels and thus can provide a more reliable signal for determining the phase of the cardiac cycle and the shape of the waveform from pulsating blood flow. This is particularly useful for determining the waveform of complex signals, such as those obtained from the lungs and sometimes from the brain. For example, an additional signal based on light having a wavelength of about 805 nm can be used to identify diseases of the microvascular blood flow of an organ based on the waveform (or pulse shape and amplitude) of the additional signal. The additional signal can also be used in templates discussed elsewhere to define the characteristic waveform of an organ, thereby determining that the signal is representative of a given organ.

[0226] although Figure 7 、 Figure 8 and Figures 10 to 16 and Figure 20It is shown in the time domain, but it should be understood that the waveform can be analyzed in the time domain or the frequency domain.

[0227] Now refer to Figure 9 , a process flow diagram of a computer-implemented method 900 of assessing the health of a subject 520 according to some embodiments is shown. The method 900 may be implemented by the processor 562 executing instructions stored in the memory 568.

[0228] At 902, processor 562 receives one or more signals. The one or more signals originate from received light reflected at first and second wavelengths, respectively, from region 522 of subject 520 proximate to internal organ 521. For example, the received light may include emitted light that has interacted with internal organ 521.

[0229] At 904, processor 562 determines that at least one of the one or more corresponding waveforms of the one or more signals represents a signal primarily associated with internal organ 521. Determining whether one or more waveforms represent signals associated with internal organs is discussed in more detail below.

[0230] In some embodiments, in response to the processor 562 not determining that at least one of the one or more corresponding waveforms of the one or more signals represents a signal associated with an internal organ, the processor 562 can output an error or control signal. For example, a control signal can be provided to the device to cause or instruct the light source 120 of the device 100 to be repositioned relative to the outer surface of the subject 520. In some embodiments, the device can be configured to automatically reposition the light source 120. In some embodiments, the system can be configured to instruct the operator to reposition the device relative to the target internal organ. Once repositioned, the updated one or more signals can be provided to the processor 562 for processing.

[0231] At 906, processor 562 compares data from at least one of the one or more waveforms to informative features of a health condition to assess the health of subject 520. Processor 562 may analyze at least one of the one or more waveforms to derive data that may include, for example, a deconvolved component or a calculated gradient (or rate of change) of the waveform.

[0232] In some embodiments, processor 562 can assess the health of subject 520 and output a health assessment of subject 520. For example, the assessment can be output to display 564 or any other user interface device, such as a speaker or a third-party device. In response to determining that subject 520 may have a health condition, processor 562 can send a signal so that information based on the assessment is output via display 564 and / or speaker and / or alarm (to be displayed on display 564 and / or to sound an audible alarm). In some embodiments, a control signal can be transmitted to a monitoring or control device connected to the subject to adjust the settings of the equipment. Determining whether subject 520 may have a health condition will be discussed in more detail below.

[0233] In some embodiments, the processor 562 can be configured to display one or more of the following: oxygen levels throughout the entire systolic and diastolic phases of each cardiac cycle, estimated tissue oxygen levels of an organ (based on the trough level reached during the diastolic phase), respiratory inspiratory and expiratory oscillations in oxygen levels, skin and organ plethysmographic signals used to derive oxygen levels, and organ and skin plethysmographic signals generated from 805 nm, which can be used to identify diseases of microvascular blood flow in organs, organ (brain, liver, lungs, and heart) motion associated with the respiratory and cardiac cycles, any asymmetry between signals from the left and right hemispheres of the brain, or other combinations of sensors on multiple organs of the body.

[0234] As previously mentioned, the inventors have recognized that waveforms associated with signals primarily originating from (or associated with) internal organs exhibit specific characteristics and are generally significantly different from waveforms associated with signals primarily originating from (or associated with) the skin. In some embodiments, processor 562 is configured to create or generate one or more templates for a specific internal organ based on one or more signals received from device 100 when apparatus 100 is positioned to target the specific internal organ. In some cases, an operator can position apparatus 100 relative to the specific internal organ and analyze the waveforms generated from the received signals to verify that the signals represent the internal organ. Based on the determined characteristic waveforms for the specific internal organ, a template for the specific internal organ can be created using multiple signals originating from one or more subjects. Thus, one or more templates stored in memory 568 can be based on a library or database of characteristic waveforms previously obtained for specific internal organs. The database can include multiple characteristic waveforms, each associated with a specific internal organ. For example, the database can include characteristic waveforms for any one or more of the following: brain, fetal brain, lungs, liver, kidneys, intestines, skeletal muscle, heart, and fetal heart. Each characteristic waveform can be based on the waveform of one or more previously received signals from an internal organ that is associated with the characteristic waveform. For example, one or more characteristic waveforms may include the average or sum of multiple previously received signals of the same type of internal organ from different subjects. In some embodiments, one or more characteristic waveforms may be based on a theoretically expected (or ideal) waveform of an internal organ. In some embodiments, one or more templates may include waveforms that are not specific to an internal organ, such as waveforms associated with signals primarily from (or primarily associated with) the skin.

[0235] In some embodiments, processor 562 may receive information indicating an internal organ targeted by device 100. Processor 562 may use the information indicating the internal organ is targeted to help determine that one or more waveforms represent signals primarily associated with the targeted internal organ. Processor 562 may also use the information indicating the internal organ is targeted to help determine a health condition. For example, processor 562 may use information about the type of internal organ to select a template corresponding to the relevant target internal organ, thereby reducing processing time. In some embodiments, processor 562 may therefore only compare one or more waveforms to templates associated with known target internal organs.

[0236] Determine if the waveform represents a signal primarily associated with internal organs

[0237] In some embodiments, memory 568 includes one or more templates, each template including information characteristic of a specific internal organ, and in some embodiments, including characteristics of a typical or healthy internal organ. For example, a template may depict a characteristic waveform of light intensity versus time. A template may include a ratio of modified ratios or a characteristic graph of blood oxygen levels. Processor 562 may be configured to compare at least one or more waveforms with one or more template waveforms to determine whether they represent a signal primarily associated with internal organ 521. This comparison may, for example, include calculating a difference between the waveform and the template waveform and comparing the difference to a threshold to determine the likelihood that the signal is primarily associated with the internal organ. Differences between multiple template waveforms may be calculated to determine the best-fitting template waveform. This determination may include, for example, calculating a minimum sum of squared residual fit. If the sum of squared residuals is less than a threshold error value, processor 562 may determine that the waveform represents (or is a good match for) a signal primarily associated with internal organ 521.

[0238] In some embodiments, the one or more waveforms can be compared to a typical venous waveform, and in response to the processor determining that at least one of the one or more signals substantially corresponds to a typical venous waveform, it is determined that at least one of the one or more signals is dominated by signals originating from an internal organ. For example, as described above, a venous waveform typically includes A, C, X, V, and / or Y wave components.

[0239] In some embodiments, an additional or third waveform can be derived from an additional signal obtained from the second device 550. The additional waveform can, for example, represent an arterial skin pulse obtained from a location away from or around an internal organ. The additional waveform can be used to compare with one or more waveforms in terms of shape, amplitude, and timing to determine whether at least one of the first waveform and the second waveform represents an arterial pulse and, therefore, is not a signal associated with the internal organ 521, but is more likely to originate from the skin.

[0240] In some embodiments, processor 562 may receive an arterial signal from a sensor of a device placed on the subject's skin, e.g. Figure 8 (a) to obtain an additional arterial waveform indicative of a cutaneous artery pulse of subject 520. Processor 562 can compare the additional waveform to one or more waveforms from an internal organ of subject 520 to determine whether a signal peak 807 of at least one of the one or more waveforms is temporally offset from a corresponding signal peak 808 of the additional waveform. For example, one or more waveforms can depict a component of a signal, such as a peak signal level, that lags behind a corresponding component of the additional signal in the additional waveform (the peak signal level indicating the onset of the waveform).

[0241] In some embodiments, when the one or more signals include at least a first signal associated with a first waveform and a second signal associated with a second waveform, the ratio of the modified ratios can be used to determine whether the first and second signals represent signals associated with an internal organ, or to determine the health condition of the subject 520. This will be discussed in detail below.

[0242] Signal Waveform-Brain

[0243] If internal organ 521 is the brain, then one or more signals indicative of light of a different wavelength and associated with the brain are expected to resemble venous signals. Thus, in some embodiments, determining that at least one waveform represents a signal primarily associated with the internal organ includes determining that the at least one waveform corresponds to a waveform of a venous pulse. In other embodiments, determining that the at least one waveform represents a signal primarily associated with the internal organ includes determining that the at least one waveform does not correspond to a waveform of an arterial pulse.

[0244] In some embodiments, the one or more signals include a first signal and a second signal. The first wavelength of light originating from the first signal may be shorter than the second wavelength of light originating from the second signal. For example, the second wavelength may be approximately 660 nm. When the target internal organ is the brain, the second signals 702, 802, which are light reflected from the brain at a second wavelength of approximately 660 nm, may more consistently represent venous signals. Therefore, in some embodiments, the processor 562 uses the second signals 702, 802 to determine whether the waveform represents a signal primarily associated with the brain. In some embodiments, the first wavelength is approximately 805 nm. The calculated change in oxygen level or the ratio of the corrected ratio may also be used as a template for this purpose, as will be discussed below.

[0245] In some embodiments, the processor 562 is configured to analyze the one or more waveforms to determine one or more components to be compared with one or more corresponding components of one or more template waveforms. For example, the processor 562 can be configured to determine that the pulse shape of at least one of the one or more waveforms substantially corresponds to a characteristic brain pulse shape. The characteristic brain pulse shape can be defined by a template waveform (e.g., a reference curve).

[0246] The characteristic brain pulse shape may include a first component having a signal level that generally increases at a first rate (corresponding to the X wave), followed by a second component having a signal level that generally decreases at a second rate (corresponding to the leading edge of the A wave), the second rate having a smaller amplitude than the first rate of the X wave. Thus, the processor 562 may determine the gradient or rate of change of the first and second components.

[0247] In some embodiments, the processor 562 can analyze one or more waveforms to deconvolute components from the waveforms. The processor 562 can analyze these components to determine a gradient or rate of change and compare it to a characteristic gradient or rate of change to determine whether at least one of the one or more signals represents a signal originating from an internal organ (the same approach also applies to changes in oxygen levels over the duration of the pulse).

[0248] It is expected that a pulsatile signal representing an internal organ may be temporally offset from a third signal representing an arterial signal, such as a signal obtained from the skin (e.g., from the forehead, nose, ear) of subject 520. Therefore, in response to determining that a signal peak 807 of at least one of the respective waveforms of the one or more signals is temporally offset from a respective signal peak 808 of another waveform of another signal, processor 562 may determine that at least one of the respective one or more signals represents the brain.

[0249] Figure 22 A first signal 4401 (approximately 895 nm) and a second signal 4402 (approximately 660 nm) obtained from the device 100 positioned in the ear canal of a human subject are shown. In this case, the processor 562 can be configured to determine, by analyzing the second signal 4402, that at least one waveform represents a signal primarily associated with the brain.

[0250] Signal Waveform-Lungs

[0251] It has been found that the signal derived from light reflected from the lungs is relatively complex and may depend on many additional factors. These factors may include whether the alveoli (air sacs) are ventilated and the blood flow (perfusion) to the air sacs. Blood flow may depend on the person's postural position. Unlike other organs in the body, oxygen levels drop during systole and rise during diastole. Furthermore, oxygen levels vary greatly during the pulse period.

[0252] In some embodiments, to obtain one or more signals primarily associated with the lungs, device 100 can be positioned near an upper region of the lungs (e.g., near the apex of the lungs) where the lungs are above the heart, and the subject is oriented in a semi-upright body position.

[0253] refer to Figure 10 (a) shows an example graph of a first signal 1001 derived from measured light reflected from an internal organ at a first wavelength (e.g., 895 nm) and a second signal 1002 derived from measured light reflected from an internal organ at a second, relatively shorter wavelength (e.g., 660 nm). These signals 1001, 1002 are obtained from the device 100 placed on a human subject 520 near a well-ventilated and well-perfused lung.

[0254] like Figure 10 As shown in (a), a first signal 1001 (895 nm) obtained from a ventilated lung represents a venous signal. The first signal 1001 includes A-wave, C-wave, X-wave, V-wave, and Y-wave components.

[0255] Thus, in some embodiments, determining, by the processor, that the at least one waveform represents a signal primarily associated with an internal organ that is the lungs can include determining that the at least one waveform corresponds to a waveform of a venous pulse. As described above, determining that the at least one waveform corresponds to a waveform of a venous pulse can include comparing the first and / or second waveforms to a typical or measured venous pulse waveform to determine a measure of consistency, or comparing the first and / or second waveforms to a measured arterial pulse waveform of a subject to determine a measure of inconsistency.

[0256] Again, as described above, determining that at least one of the one or more signals represents a signal primarily associated with an internal organ can include comparing a component of the waveform of the one or more signals to a template waveform characteristic of an internal organ (in this case, the lungs) and can, for example, involve deconvolving the component from the waveform.

[0257] In some embodiments, the processor 562 can be configured to determine that the pulse shape of the waveform of a signal of a relatively long wavelength (e.g., approximately 895 nm) that is sensitive to oxygenated blood substantially corresponds to a characteristic pulmonary pulse shape. For example, the characteristic pulmonary pulse shape can include a waveform representative of a venous pulse signal, and / or the characteristic pulmonary pulse shape can include a first component having a signal level that generally increases at a first rate (X-wave), followed by a second component having a signal level that generally decreases at a second rate (leading edge of the diastolic phase), the second rate having a smaller amplitude than the first rate.

[0258] In some embodiments, the processor 562 may be configured to determine that the waveform of the signal represents a signal from the lungs when determining that the first waveform includes an A wave, an X wave, a V wave, and a Y wave.

[0259] In some embodiments, the processor 562 can be configured to determine that the pulse shape of the waveform of the signal from light of approximately 660 nm wavelength has a characteristic pulmonary pulse shape, wherein the light of approximately 660 nm wavelength is particularly sensitive to changes in deoxygenated blood levels. For example, the characteristic pulmonary pulse shape can include a waveform representative of the inverted pulmonary artery pressure waveform (e.g., see Singal et al., J. Med. Devices 9(2), 020906, 2015, the disclosure of which is incorporated herein by reference in its entirety). The waveform can, for example, include a significant systolic signal in the inverted pulmonary artery pressure waveform. The diastolic phase of the inverted pulmonary artery pressure waveform can also include a dicrotic notch, which is similar in shape and timing to the V wave in the waveform (marking the end of systole and the beginning of diastole). In addition, the onset of the systolic pulse generally precedes the onset of the cutaneous artery pulse. This may reflect that the right ventricle contracts earlier than the left ventricle.

[0260] Figure 21 Two signals 2601 are shown, including multiple pulses obtained when a subject breathes in region 2602, and then when the subject holds their breath in region 2603. As can be seen, the waveforms (pulses) in region 2603 are more uniform in intensity range than the two signals 2601 in region 2602. In some embodiments, a subject can hold their breath while determining whether one or more signals represent signals from the lungs. This can simplify and / or improve the accuracy of the determination.

[0261] Signal Waveform-Liver

[0262] refer to Figure 11 , shows example graphs of first and second signals 1101, 1102 received from a device 100 positioned near the liver of a human subject 520. The first signal 1101 is from measured light reflected from the liver at a first wavelength (e.g., 895 nm), and the second signal 1102 is from measured light reflected from the liver at a second, relatively shorter wavelength (e.g., 660 nm).

[0263] As shown, A-wave, C-wave, and X-wave components can be observed in the first and second waveforms of the first and second signals 1101 and 1102, respectively. In some embodiments, a V-wave component can also be observed. The waveforms of the first and second signals 1101 and 1102 can also include additional small troughs (including the P wave of the P1 wave and the P2 wave). The P1 wave can indicate the contribution to the first and second signals 1101 and 1102, which are derived from light reflected from the portal vein systolic pulse. The P2 wave can indicate the contribution to the first and second signals 1101 and 1102, which are derived from light reflected from the portal vein diastolic pulse. The presence of the P1 wave and / or the P2 wave appears to be unique to signals from the liver; they are not observed in other organs.

[0264] Thus, in some embodiments, determining by processor 562 that at least one waveform of one or more signals originating from light reflected by the liver represents a signal primarily associated with the liver may include determining that the at least one waveform corresponds to a waveform of a venous pulse.

[0265] As described above, determining that at least one of the one or more signals represents a signal primarily associated with an internal organ being the liver may include comparing components of the waveforms of the first and / or second signals to template waveform characteristics of the liver and may, for example, involve deconvolving the components from the waveforms.

[0266] In some embodiments, determining, by the processor 562, that the at least one waveform represents a signal primarily associated with an internal organ that is the liver may include determining that the at least one waveform includes at least one of an X-wave and a P-wave.

[0267] In some embodiments, the processor 562 can be configured to determine that the pulse shape of at least one of the one or more waveforms substantially corresponds to a characteristic liver pulse shape. For example, the characteristic liver pulse shape can include a waveform representative of a venous pulse signal, and / or the characteristic liver pulse shape can include a first component having a signal level that generally increases at a first rate (the X-wave component), followed by a second component having a signal level that generally decreases at a second rate (the leading edge of the diastolic phase), the second rate having a smaller amplitude than the first rate.

[0268] In some embodiments, the subject may hold their breath while determining whether one or more signals represent signals from the liver. This may simplify and / or improve the accuracy of the determination.

[0269] The P wave component of the liver trace may also result in characteristic components in the calculated corrected ratio of the ratio and blood oxygen level, as discussed later. The processor 562 can determine that the signal represents a signal from the liver based on the presence of these characteristic components.

[0270] Signal waveform-intestinal

[0271] Figure 16 An example graph is shown of a first signal 1601 from measured light reflected from the intestine at a first wavelength (e.g., 895 nm) and a second signal 1602 from measured light reflected from the intestine at a second, relatively shorter wavelength (e.g., 660 nm). The first and second signals 1601, 1602 are obtained from the device 100 placed on a subject 520 near the intestine.

[0272] The plethysmographic signal from light reflected from the intestine may resemble pressure variations in the central venous circulation, with A, C, V, X, and Y waves. These waves are delayed in time relative to the skin and liver plethysmographic signals. This is likely due to the fact that venous pulsations must pass through the liver to reach the portal vein and then the intestinal microcirculation. Therefore, the delayed X wave may have a late, convex component due to the simultaneous arrival of the arterial pulse of intestinal blood. The V wave may not be prominent. Consequently, the peak, or maximum light intensity level, of the pulse is significantly delayed and occurs in the late systolic period relative to the forehead skin pulse.

[0273] Thus, the signal waveform of the signal from the intestine can exhibit venous characteristics with any one or more of the A, C, X, V, and Y waves, and these waves can be delayed relative to the corresponding waves in the skin and liver. In some embodiments, determining by processor 562 that at least one waveform represents a signal primarily associated with the intestine can include determining that the peak signal time of one or more signals is offset from the peak signal time of another signal (e.g., a skin artery signal). This offset (or lag) reflects the time it takes for these pressure pulses in the venous circulation to travel backward through the liver along the portal vein to the microcirculation of the intestine.

[0274] As with the brain and liver, the quality of gut-related signals may improve if subjects hold their breath.

[0275] In some embodiments, the processor 562 can determine the health of the intestine based on comparison with a characteristic waveform similar to Figure 16 For example, the deviation from the characteristic waveform can be used to diagnose any one or more of the following diseases: ischemic hepatitis, cirrhosis, abdominal compartment syndrome, portal vein thrombosis, portal hypertension.

[0276] Signal Waveform-Kidney

[0277] Measured light reflected from the kidney at a first wavelength of approximately 895 nm and at a relatively shorter second wavelength of approximately 660 nm can be used to determine kidney health.The first and second signals can be obtained from the device 100 placed on the subject 520 near the kidney.

[0278] Compared to other organs, the kidneys have a very high arterial blood flow. Therefore, the pulse shape of the waveform of the first signal, derived from light with a wavelength of approximately 895 nm, is characteristically arterial, with a prominent minimum level of contraction, as expected. In contrast, the waveform of the second signal, derived from light with a wavelength of approximately 660 nm, is relatively flat. However, the A, C, X, V, and Y wave components are discernible. The flat waveform is likely due to the high oxygen levels throughout the pulse.

[0279] Thus, in some embodiments, determining by the processor 562 that at least one waveform of the one or more received signals represents a signal primarily associated with the kidneys includes determining that the waveform is characteristically arterialized, having a significant minimum level of contraction. In some embodiments, determining by the processor 562 that at least one waveform of the one or more received signals represents a signal primarily associated with the kidneys includes determining that the waveform is relatively flat but still includes A, C, X, V, and Y wave components. In some embodiments, determining by the processor 562 that at least one waveform of the one or more received signals represents a signal primarily associated with the kidneys includes determining that a pulse shape of the waveform substantially corresponds to a characteristic kidney pulse shape.

[0280] Signal waveform-fetus

[0281] The pulsatile signals emitted by the fetus differ from those of the mother in many ways. These differences make it straightforward to identify the signal as coming from the fetus. The heart rate is typically higher than the mother's, approximately 120-160 beats per minute compared to the mother's 70 beats per minute. The fetus also has lower oxygen saturation levels. Arterial saturation in the fetal brain is low, approximately 90% (compared to 100% in the mother), and even lower in other organs, approximately 65% (compared to 100% in the mother). Consequently, venous oxygen saturation levels are very low, ranging between 25% and 40% (compared to 75% in the mother). Finally, the shape of the pulse waveform is different because the fetus has very low blood pressure and circulatory function different from that of the mother. The fetal brain provides an ideal target because of its high blood flow relative to the blood flow in the mother's overlying tissues, including the skin, abdominal muscles, or cervix.

[0282] Because the fetus pulses out of sync with its mother, processor 562 can determine that one or more signals represent signals from the fetus based on a comparison of the peak signal levels of one or more signals of light from the fetus with the peak signal levels of other signals of light from the mother.

[0283] Signal Waveform-Muscle

[0284] Light reflected from the gastrocnemius muscle of a resting human subject at a first wavelength of approximately 895 nm and a second, shorter wavelength of approximately 660 nm can be measured to assess muscle health. A third signal derived from light having a wavelength of approximately 895 nm and a fourth signal derived from light having a wavelength of approximately 660 nm can be utilized, the third and fourth signals being simultaneously recorded from the subject's forehead skin. At rest, muscle blood flow is low and is therefore characterized by the signal's low pulse amplitude. The pulse shape is arterial in nature because skeletal muscle has relatively few venules compared to other organs.

[0285] Thus, in some embodiments, determining by the processor 562 that at least one waveform of the one or more received signals represents a signal primarily related to muscle includes determining that a pulse shape of the waveform substantially corresponds to a characteristic muscle pulse shape. In some embodiments, determining by the processor 562 that at least one waveform of the one or more received signals represents a signal primarily related to muscle includes determining that the waveform depicts a signal having a relatively low pulse amplitude and that is substantially arterial in nature.

[0286] Assessing the subject's health based on waveforms

[0287] As above reference Figure 9 As described above, once processor 562 determines that at least one of the one or more signals is primarily associated with light reflected from the target internal organ, one or more waveforms of the one or more signals may be analyzed to determine or assess the health of subject 520. For example, in some embodiments, at least one of the one or more waveforms may be compared to informational features of a health condition to assess the health of subject 520.

[0288] For example, in some embodiments, one or more waveforms of one or more received signals primarily associated with light reflected from a target internal organ can be compared to one or more characteristic pulse shapes of a corresponding healthy internal organ (e.g., which can be stored as a template in a memory). The processor can be configured to determine a measure of similarity (or dissimilarity) between the waveform and the characteristic pulse shape, and determine or assess the health of the internal organ based on the measure of similarity (or dissimilarity).

[0289] Further described embodiments involve evaluating one or more waveforms to determine the likelihood that a subject has various conditions, including organ diseases associated with low microvascular oxygen levels or abnormal blood flow or motion. Examples include increased intracranial pressure (ICP), cerebral hemorrhage, stroke, ischemic hepatitis, pneumonia, intestinal ischemia, and heart failure.

[0290] Pulsatile blood flow in an organ's microcirculation likely reflects differences in pressure levels between microvascular arterioles, which facilitate blood flow, and microvascular venules, which obstruct blood flow, during periods of the cardiac cycle. These differences in microvascular pressure levels vary during the systolic and diastolic phases of the cardiac cycle and can define the shape and amplitude of the waveform of the signal derived from light reflected from internal organs. A relative increase in systemic venous pressure levels is associated with a plethysmographic signal that displays dominant or exaggerated features similar to those of the central venous pressure waveform. These features include A, C, X, V, and Y waves with peak signal levels during the diastolic phase of the cardiac cycle. This finding may indicate low blood flow to that organ.

[0291] Analyzing the waveform of a signal associated with light having a wavelength of approximately 805 nm may be useful because light having a wavelength of approximately 805 nm is not significantly affected by changes in blood oxygen levels, but is only affected by blood flow. The waveform shape generated by a signal associated with a wavelength of approximately 805 nm can be used to detect abnormal blood flow patterns due to diseases of the arterial and venous circulation. Diseases of this type of systemic circulation that can be detected include heart failure and fluid overload, which increase pressure levels in the venous circulation. In addition, central venous pressure levels can also be estimated non-invasively. For example, if arterial blood pressure levels are low and venous blood pressure levels are normal, similar features can be seen in the waveform. Diseases in this case include cerebral artery spasm and arterial thrombosis, which may occur in a stroke.

[0292] heart failure

[0293] Measured light reflected from the brain of a human subject at a first wavelength of approximately 895 nm and a second wavelength of approximately 660 nm can be used to determine whether the human subject suffers from heart failure. In this case, the first and second signals depict a significant and early V-wave component.

[0294] To determine the likelihood that the subject has heart failure (e.g., a leaky heart valve causing tricuspid regurgitation), processor 562 can analyze one or more waveforms of a corresponding signal derived from detected light reflected from brain 521. Processor 562 can derive data from the waveform indicating a significant V wave component and compare the derived data to a template waveform characteristic of a signal representing subject 520 with heart failure to determine whether the derived data corresponds to the template waveform. In response to determining that it does substantially correspond (e.g., by a threshold amount) to the template waveform, processor 562 determines that subject 520 is likely to have heart failure. This method is applicable to a range of diseases that cause heart failure, in which case the venous characteristics of the waveform will be significant.

[0295] In some embodiments, processor 562 may derive data from the waveform indicating the amplitude of the wave component V. Processor 562 may compare the derived amplitude to a threshold level to determine whether the subject may be suffering from heart failure.

[0296] Intracranial pressure (ICP)

[0297] refer to Figure 12 (b) shows an example graph of a first signal 1201 from measured light reflected from the brain of a subject (in this case, a sheep) at a first wavelength (e.g., 895 nm) and a second signal 1202 from measured light at a second, relatively shorter wavelength (e.g., 660 nm). The first and second signals 1201, 1202 are obtained from sensors of the apparatus 100 placed on the scalp of an animal subject, followed by injection of 6 ml of blood into the anterior cranial fossa via an anterior burr hole to increase the sheep's intracranial pressure to a range of about 50 mmHg to about 90 mmHg. Figure 12 (a) shows an example graph of a third signal 1203 and a fourth signal 1204, the third signal being from light having a wavelength of approximately 895 nm and the fourth signal being from light having a wavelength of approximately 660 nm, both obtained from the skin of a sheep's nose, and the Figure 12 The first and second signals of (a) are substantially simultaneous and represent arterial skin signals.

[0298] For a healthy subject, it is expected that the waveform of one or more of the signals will substantially correspond to a typical venous waveform. However, it can be seen that the first and second signals 1201, 1202 have waveforms having components that appear to be more characteristic of an arterial waveform than a venous waveform. Specifically, the initial amplitude of the pulse slope (or gradient) of the leading edge (decreasing light intensity) 1211 of the pulse is greater than the initial amplitude of the slope of the leading edge 811 of the characteristic signal representing the venous pulse 805, 806. In some cases, other venous characteristics (e.g., V-wave and / or Y-wave components) may be absent or reduced in the first and / or second waveform or the third waveform (805nm). Clearly, this still represents a brain signal because there is a significant lag in the onset of the pulse compared to the skin signal, as shown in FIG. Figure 12 Indicated by the double-ended arrow in (b).

[0299] Therefore, it has been determined that this change in the waveform, which has certain arterial characteristics in shape, may indicate an increase in intracranial pressure. This is because the pressure in the cerebral arteries increases to maintain adequate blood flow, and the pulse waveform develops a more arterial shape because arterial pressure is much greater than central venous pressure. These two pressures influence the shape of the pulse waveform.

[0300] Thus, in some embodiments, processor 562 is configured to compare one or more waveforms of the corresponding one or more signals of detected light from brain 521 to a template waveform representing subject 520 experiencing relatively high intracranial pressure to determine whether the one or more waveforms substantially represent the template waveform. This can include, for example, calculating a sum of squared residuals. In response to determining that at least one waveform represents the template waveform, processor 562 can determine that subject 520 may have relatively high intracranial pressure (e.g., if the intracranial pressure is less than about 90 mmHg). For example, this may indicate the development of cerebral edema or cerebral hemorrhage.

[0301] In some embodiments, the processor 562 can be configured to analyze at least one of the first component and the second component of the waveform of the corresponding signal to determine the gradient of the leading edge of the corresponding initial slope of the pulse (e.g., see Figure 12 1211), the corresponding signal being from detected light reflected by the subject's brain 521. In response to determining that at least one of the gradients of the leading edge is greater than a threshold, the processor 562 may determine that the subject 520 may have relatively high intracranial pressure.

[0302] In some embodiments, processor 562 is configured to analyze at least one of the first component and the second component of the waveform of the corresponding signal from light detected from brain 521 to determine whether a V-wave and / or a Y-wave component is present. In response to determining the absence of the V-wave and / or Y-wave components, processor 562 may determine that subject 520 may have relatively high intracranial pressure.

[0303] Disorders associated with relatively elevated pressure levels in the pulmonary or systemic arterial circulation

[0304] Diseases associated with a relative increase in pulmonary arterial circulation pressure levels include pulmonary embolism, interstitial lung disease, chronic obstructive pulmonary disease, pneumonia, acute lung injury, and / or acute respiratory distress syndrome. The relative increase in pulmonary arterial pressure levels compared to pulmonary venous pressure levels is associated with a pulmonary plethysmographic pulse signal 1001 (e.g., from light having a wavelength of 895 nm or 805 nm) that exhibits some characteristics of the pulmonary arterial circulation pressure waveform, such as the A, C, V, and Y wave components becoming less prominent and the development of components similar to those characteristic of the pulmonary arterial pressure waveform, including a prominent systolic pulse, a diastolic pulse, and a dicrotic notch (which may coincide with the V and Y waves).

[0305] In some embodiments, processor 562 can analyze the waveform shape of the signal of detected light originating from the target internal organ to determine a health condition associated with a relative increase in systemic arterial circulation pressure level relative to central venous pressure level, such as systemic hypertension and local organ disease, such as acute brain injury, liver cirrhosis, and / or compartment syndrome. For example, the processor can be configured to compare the waveform or data from the waveform with a template waveform or data characteristic of such a health condition to determine the likelihood that the subject exhibits the health condition.

[0306] Diseases associated with increased arterial pressure levels can also be detected, such as hypertension, in which case the waveform develops into a more arterial pulse shape. Other diseases include increased intracranial pressure in the brain and compartment syndromes in other parts of the body, such as the abdomen or lower legs. The same method can be used on pulses or waveforms from the microcirculation of the lungs to detect abnormal waveforms that may be caused by diseases that lead to increased pulmonary artery pressure levels (interstitial lung damage, ARDS, pulmonary embolism) or increased pulmonary venous pressure levels (left-sided heart failure).

[0307] Disorders associated with relatively elevated systemic venous pressure levels

[0308] Relative increases in systemic venous pressure levels may be associated with conditions including heart failure and fluid overload secondary to intravenous fluid administration. Monitoring waveform shape may be useful for monitoring systemic venous pressure levels to detect heart failure and guide resuscitation of circulating intravenous fluids to avoid fluid overload.

[0309] A relative increase in systemic venous pressure levels is associated with a 660 nm or 805 nm waveform that displays more pronounced or exaggerated features of the central venous pressure waveform. These features include the A, C, and V wave components, which have minimal signal values, and the X and Y wave components, which have increased signal values.

[0310] Processor 562 can determine that the subject has such a disease, for example, by determining that the magnitude or amplitude of any one or more of the A-wave, V-wave, X-wave, and / or C-wave components is greater than a threshold value. The magnitude or amplitude of a component can be calculated as the range between a maximum value and a minimum value of the component.

[0311] High intracranial pressure

[0312] refer to Figure 14(b) shows an example graph of a first signal 1401 derived from measured light reflected from a subject's brain at a first wavelength (e.g., 895 nm) and a second signal 1402 derived from measured light reflected from the brain at a second, relatively shorter wavelength (e.g., 660 nm). The first and second signals 1401, 1402 were obtained from the device 100 placed on the scalp of a sheep, followed by injection of 6 ml of blood into the anterior cranial fossa via an anterior burr hole to increase the sheep's intracranial pressure to a range greater than approximately 150 mmHg. Figure 14 (a) shows simultaneous third and fourth signals 1403, 1404 obtained from the nose skin of the subject 520 and is shown for comparison.

[0313] As shown, the first and second signals 1401, 1402 exhibit increases in the amplitude of the AC pulse signal, which is characteristic of intracranial pressure in the subject.

[0314] If the pulse amplitude increases in the brain signal, but there is no change in the skin signal, this indicates that the disease is likely confined to the brain. An example is an increase in blood flow to the brain alone in response to an increase in intracranial pressure (ICP) levels. In this case, the amplitude (signal level) of the pulse on the brain signal increases, but because there is no change in skin blood flow, there is no such change in the skin pulse amplitude. On the other hand, if the pulse amplitude increases in both sites (skin and brain), this indicates that the disease may be affecting all parts of the body. An example is low oxygen levels throughout the body, compensated by an increase in blood flow throughout the body, which would cause a change in the pulse waveform throughout the body. This method is suitable for detecting diseases in other organs of the body.

[0315] Processor 562 can analyze at least one waveform of the corresponding one or more signals, the one or more signals originating from detected light in brain 521, to determine whether the waveform exhibits an increase in AC component amplitude relative to a corresponding component of an arterial waveform of another signal acquired simultaneously with one or more signals from the subject, such as a skin signal. In response to determining an increase in AC component amplitude, processor 562 can determine that subject 520 may have relatively high intracranial pressure or a cerebral hemorrhage. Furthermore, a decrease followed by an increase in DC level or cerebral microvascular oxygenation may also indicate that the subject has high intracranial pressure or a cerebral hemorrhage.

[0316] Poor lung ventilation

[0317] In a poorly ventilated lung, pulmonary artery blood flow is low. Therefore, the pulmonary venous pressure level is relatively high compared to the pulmonary artery pressure experienced in this region of the lung, and the sensor waveform reflects this, with the venous signal being dominant ( Figure 15 (b)).

[0318] To obtain one or more signals primarily related to the lungs, device 100 may be positioned on the back of subject 520 while the subject is lying supine so that the alveolar air sacs are not expanded (collapsed).

[0319] refer to Figure 15 (b) shows an example graph of a first signal 1501 derived from light of a longer wavelength (e.g., 895 nm) and a second signal 1502 derived from light of a shorter wavelength (e.g., 660 nm). The first and second signals 1501, 1502 are obtained from the device 100 placed near the lungs of a subject 520 with dependent hypoventilation. Figure 15 (a) shows simultaneous third and fourth signals 1503, 1504 obtained from the forehead skin of the subject 520, which are shown for comparison.

[0320] As shown, first signal 1501 and second signal 1502 may include components consistent with pressure waveforms found in pulmonary veins. These features include A, C, X, V, and Y waves. The V wave is prominent in the waveform of second signal 1502 but less prominent in the waveform of first signal 1501. The minimum signal values of first signal 1501 and second signal 1502 may occur during the V wave rather than the A wave. The peak signal values for first signal 1501 and second signal 1502 are synchronized. Processor 562 may determine that the health condition includes pulmonary hypoventilation based on any one or more of these features.

[0321] For example, in some embodiments, the processor 562 can be configured to compare data derived from the second waveform (i.e., a signal associated with a wavelength of approximately 660 nm) to a characteristic waveform of hypoventilated lungs depicting a significant V-wave component. In response to determining that the waveform represents a characteristic waveform having a significant V-wave component, the processor can determine that the health condition includes hypoventilation of the lungs.

[0322] It is noteworthy that during systole and diastole, oxygen levels remain relatively low and constant because oxygen is not added to the blood to a significant extent as the balloon collapses (see Figure 15 (c)). Determining oxygen levels is discussed in further detail below.

[0323] Hypoxia-liver

[0324] Changes in portal blood flow are important for detecting a range of liver diseases, including hepatitis, cirrhosis, and right heart failure.

[0325] Under normal oxygenation conditions, the P wave may be subtle or invisible in the signal. However, as systemic hypoxia develops, the P wave becomes very prominent due to increased cardiac output and increased portal venous blood flow. The dominance of the P wave causes the X wave to be unobservable. Also note that under hypoxic conditions, the pulse rate is higher.

[0326] Thus, in some embodiments, in response to determining that at least one waveform of the one or more signals derived from light reflected by the liver differs from a template waveform representing a healthy liver, processor 562 can determine that the subject suffers from any one or more of hepatitis, cirrhosis, and right heart failure. In some embodiments, in response to determining that at least one waveform of the one or more signals derived from light reflected by the liver exhibits a dominant P-wave component, and optionally an absence of an X-wave component, and optionally an increased pulse rate, processor 562 can determine that the subject has increased portal venous blood flow.

[0327] Intracranial pressure - Sylvian fissure

[0328] The first signal may be derived from detected light having a wavelength of approximately 660 nm that is reflected from the movement of cerebrospinal fluid located in the Sylvian fissure of a human subject. In this context, a third signal derived from light having a wavelength of approximately 660 nm obtained from the subject's forehead skin represents an arterial pulse of the subject. The first waveform of the first signal has a shape similar to that of the waveform of the third signal, namely, an arterial waveform. The first waveform of the first signal may also include specific oscillations that indicate a signal generated by the movement of cerebrospinal fluid located in the Sylvian fissure.

[0329] The timing of the specific oscillations of the first signal and the general shape of the first waveform closely correlate with recorded observed waveforms for intracranial pressure measurements in the cerebrospinal fluid, which are caused by pressure changes in the skull following each pulse of arterial blood delivered to the brain. (See Zweifel, C., Hutchinson, P., & Czosnyka, M., 2011; Intracranial pressure; in B. Matta, D. Menon, & M. Smith (Eds.), Core Topics in Neuroanaesthesia and Neurointensive Care, pp. 45-62, the disclosure of which is incorporated herein by reference in its entirety.) Notably, the peak intensity level (which can be used as the start of the waveform or pulse) occurs slightly before the forehead skin pulse, which is consistent with a pulse representing the effect of pressure changes in the brain on cerebrospinal fluid movement, rather than from blood flow in the brain's microcirculation. The pattern, amplitude, and frequency of the oscillations can be used to detect abnormally elevated intracranial pressure levels.

[0330] In some embodiments, the device 100 is located near the intergyral sulcus to enable non-invasive monitoring to detect elevated intracranial pressure levels. Light comprising at least one wavelength from the light source 120 can be projected through the skull of the subject 520 into the intergyral sulcus. Light reflected from the cerebrospinal fluid (CSF) in the intergyral sulcus can be received at the light detector 130 of the device 100. The processor 562 can then generate at least one signal derived from the measured light reflected from the intergyral sulcus at the corresponding wavelength. The waveform of the at least one signal can be analyzed to determine a measurement of elevated intracranial pressure. For example, one or more signals can include a superimposed oscillating signal. The frequency and amplitude of the oscillating signal can increase as intracranial pressure increases. In response to determining that the frequency or amplitude of the oscillating signal is above a threshold level, the processor 562 can be configured to determine that the subject is experiencing elevated intracranial pressure.

[0331] If blood is present in the CSF, as occurs with a subarachnoid hemorrhage, the signal level may become significantly stronger compared to the signal from normal CSF. Therefore, the signal can be used to detect subarachnoid hemorrhage.

[0332] In some embodiments, device 100 generates and detects light having a wavelength of approximately 805 nm to generate the first signal and reduces the effect of blood oxygen level on the first signal. This may result in a more accurate and / or reliable waveform shape that reflects ICP.

[0333] Organ Movement-Brain

[0334] refer to Figure 13(b) shows an example graph of a first signal 1301 derived from light measured at a first wavelength (e.g., 895 nm) reflected from a subject's brain, and a second signal 1302 derived from light measured at a second, relatively shorter wavelength (e.g., 660 nm). The first and second signals 1301, 1302 were obtained from sensors of the device 100, which was placed on the scalp of a sheep. Six milliliters of blood was then injected into the anterior cranial fossa via an anterior burr hole to increase the sheep's intracranial pressure to a range of approximately 90 mmHg to approximately 150 mmHg. As can be seen, the first and second waveforms associated with signals 1201, 1202 include high-amplitude oscillations at a specific frequency, in this case approximately 7 Hz. Oscillations of this frequency in ICP pressure traces have been previously documented and represent "ringing" of the brain in response to systolic arterial pressure waves entering the brain. Increasing ICP pressure levels may increase the amplitude of these oscillations, resulting in changes in the waveforms detected by the monitor. The synchronous nature of the monitor's beats and high-frequency oscillations is consistent with beats and high-frequency oscillations being triggered by a cardiac source. Previous clinical studies, in the context of brain injury, have found that high frequency and amplitude oscillations in ICP are associated with poorer patient outcomes.

[0335] Figure 13 (a) shows a simultaneous graph of third and fourth signals 1303, 1304 obtained from the skin of a sheep's nose, and depicts an arterial waveform shown for comparison with the first and second signals 1301, 1302. This may be helpful in determining the timing of the systolic and diastolic phases of the cardiac cycle.

[0336] Processor 562 can analyze at least one waveform of the corresponding one or more signals, which originate from detected light reflected from brain 521, to determine whether the waveform includes oscillations, for example, at approximately 7 Hz. In response to determining that the waveform includes oscillations, processor 562 can determine that subject 520 may have relatively high intracranial pressure. For example, high intracranial pressure may be caused by acute brain injury due to a cerebral hemorrhage.

[0337] Organ Exercise-Lungs

[0338] The lungs expand during inspiration and contract during expiration. Light signals from the lungs reflect the extent of this movement during breathing. Light signals can be used to detect abnormal breathing patterns and breathing phases. Light signals detect the inspiration and expiration phases of breathing. This signal can be used to trigger a mechanical ventilator. Therefore, processor 562 can be configured to output control instructions to control the mechanical ventilator based on the determined breathing pattern.

[0339] Organ Motion - The liver is located below the diaphragm of the lungs and moves during breathing. As subject 520 breathes over several respiratory cycles, first and second signals can be obtained using device 100 from light reflected from the liver of subject 520. The signal levels of the first and second signals vary with the inspiration and expiration phases of breathing, and therefore, the first and / or second signals originating from the liver can be used to detect abnormal breathing patterns and breathing phases. Low-frequency respiratory oscillations are much larger in amplitude than high-frequency cardiac oscillations. Inhalation is associated with a rapid drop in the signal level (transmitted light intensity) of the first and second signals, and exhalation is associated with an increase in the signal level.

[0340] In some embodiments, detection of abnormal patterns and / or phases of breathing can be used to trigger a mechanical ventilator coupled to the subject and / or to detect liver disease, such as cirrhosis.

[0341] For example, processor 562 can be configured to compare changes in the inspiratory and / or expiratory phases of respiration depicted in the waveform of a signal derived from light reflected from the liver of subject 520 with corresponding changes in the inspiratory and / or expiratory phases of respiration depicted in a template waveform characteristic of a relatively healthy liver. The waveform and template waveform can extend over at least one respiratory cycle. A respiratory cycle can span a time range exceeding 1 second, and can, for example, span a time range from about 1 second to about 10 seconds.

[0342] In some embodiments, the processor 562 can be configured to determine liver motion based on statistical measurements of at least one waveform. The statistical measurements can be compared to the informational features to determine motion. The statistical measurements can include any one or more of a peak signal value, a minimum signal value, a median signal value, a root mean square signal value, and an average signal value of the waveforms of the first and second signals. The processor 562 can determine a range of signal levels, for example, based on the difference between the peak signal value and the minimum signal value. The processor 562 can determine whether the range of signal levels represents a healthy or unhealthy condition. For example, the processor 562 can determine that the range of signal levels is outside a threshold range or exceeds a threshold.

[0343] Organ Movement-Heart

[0344] The motion of the heart can be used to detect the systolic and diastolic phases of the right and left ventricles and atrial contraction, which can be used to detect abnormalities in cardiac function, including systolic and diastolic heart failure and electrical conduction disorders.

[0345] A first signal obtained from light measured at a first wavelength (e.g., 895 nm) reflected from the heart of a healthy human subject and a second signal obtained from light measured at a second, relatively shorter wavelength (e.g., 660 nm) can be used to detect cardiac motion. The device 100 is placed on the anterior chest, adjacent to the right ventricle of the heart. The right ventricle of the heart is a midline structure that is in direct contact with the chest wall below the sternum. A third signal can be obtained from light having a wavelength of approximately 895 nm, a fourth signal from light having a wavelength of approximately 660 nm from the forehead skin, and a fifth signal from the subject's right internal jugular vein.

[0346] In some embodiments, the processor can be configured to analyze the first waveform and the second waveform of the first signal 3101 and the second signal 3102, respectively, to determine abnormal motion of the heart and / or the timing of contraction and relaxation of the heart chambers in the cardiac cycle. The heart has four chambers, namely the left and right atria and the left and right ventricles. They contract in this order. The waveforms of the first and second signals show the timing of contraction of each chamber and the timing of relaxation of the right ventricle and the left ventricle in the cardiac cycle. Therefore, abnormal motion of the heart that may occur after damage to the heart due to damage to the muscle caused by myocardial infarction or other causes of heart failure (such as chronic hypertension) can be detected by analyzing the waveforms. The waveforms can also be analyzed to detect abnormal timing of contraction of the heart chambers, such as may occur in diseases of the electrical signal conduction that coordinates the activation of myocardial contraction.

[0347] Analyze blood oxygen levels using the ratio calculation of the corrected ratio

[0348] In some embodiments, processor 562 is configured to determine the subject's blood oxygen level based on analysis of the first and second waveforms of respective first and second signals derived from light reflected from a target internal organ of subject 520, which may indicate the subject's health. The intensity of light reflected from blood within blood vessels is affected by the blood oxygen level. The absorption can be based on the intensity of the first and second signals at the respective first and second wavelengths detected using known methods for calibrating the intensity of the generated light. The blood oxygen level is related to a ratio R based on the ratio of the intensities (or absorption) of the signals at the two wavelengths.

[0349] For conventional pulse oximetry based on optical signals from cutaneous arterial blood, the ratio R of the ratios is normalized based on the maximum signal value at the beginning of the pulse (correlated with the maximum intensity of the received light), also known as the DC level. The maximum intensity corresponds to the beginning of the systolic phase of the cardiac cycle. The signal for each wavelength is normalized based on the maximum intensity of the corresponding wavelength. The conventional ratio R of the ratios is given by:

[0350]

[0351] Here, I1 is the signal value (peak value or maximum signal value) at the beginning of the pulse of signal 1, which originates from light received at the shorter wavelength 1; AC1 is the change in signal level from I1 at the peak value (minimum signal value corresponding to the peak value or maximum value of the blood pulse) of the contraction phase of signal 1, which originates from light received at wavelength 1; I2 is the signal value (peak value or maximum signal value) at the beginning of the pulse of signal 2, which originates from light received at the longer wavelength 2; AC2 is the change in signal level from I2 at the peak value (minimum signal value corresponding to the peak value or maximum value of the blood pulse) of the contraction phase of signal 2, which originates from light received at wavelength 2. Thus, a single ratio R′ is obtained for each waveform (or each pulse).

[0352] In order to provide useful results for assessing the health of a subject's internal organs, the ratio of odds is modified.The modified ratio equation takes into account some characteristics of the microvascular blood in the internal organs that make it different from the arterial blood in the skin.

[0353] When calculating ratio values of ratios from signals originating from internal organs, the signal values may need to be normalized in a correct manner due to the unique characteristics of microvascular blood in internal organs, which is very different from the known methods used in skin pulse oximetry for calculating R' and measuring arterial blood oxygen levels.

[0354] In organs, microvascular blood oxygen levels vary greatly during the cardiac cycle due to oxygen exchange with the organ's tissues. Microvascular blood oxygen levels are higher during systole and decrease during diastole (the opposite is true in the lungs); therefore, the timing of the maximum transmitted light intensity values (the start of the pulse) may be out of sync for the two wavelengths. In skin pulse oximetry, oxygen levels generally remain more constant, and the timing of the maximum transmitted light intensity values (the start of the pulse) is always synchronized for the two wavelengths.

[0355] In organs, the minimum light intensity level occurs at the end of the pulse (waveform) during diastole, particularly for signals derived from light with a wavelength of 660 nm (or 895 nm in the lungs). This typically occurs during the A wave in the diastole phase of the cardiac cycle. In contrast, in skin pulse oximetry, the minimum light intensity level occurs during systole.

[0356] The minimum blood oxygen level measured during the diastole phase of the cardiac cycle is particularly important because the oxygen concentration in microvascular blood may have dropped to the point of equilibrium with the oxygen concentration in the extravascular tissues of the organ. Therefore, this level can provide an estimate of the oxygen level in the extravascular tissues of the organ. The exception is the lungs, where the minimum oxygen level occurs during systole and represents the oxygen level in the mixed venous blood returning to the lungs.

[0357] Peak oxygen levels measured during the systolic phase provide an estimate of the arterial oxygen level in the microvascular blood of an organ. The exception is the lungs, where peak oxygen levels occur during diastole and represent how well the lungs are oxygenating returning venous blood. This provides an estimate of systemic arterial oxygen levels.

[0358] To account for these differences and enable measurement of diastolic oxygen levels, a modified ratio of the blood oxygen levels is calculated throughout the cardiac cycle, allowing measurement of changes in oxygen levels throughout the cycle. The drop in oxygen levels during the diastolic phase of the cardiac cycle provides important clinical information. In contrast, with skin pulse oximetry, oxygen levels are only measured and reported during systole.

[0359] Monitoring of diastolic oxygen levels is particularly important because no accurate noninvasive method has previously been available. Diastolic oxygen levels reflect tissue oxygen levels, which are of fundamental importance because even brief periods of low tissue oxygen can lead to tissue necrosis and the risk of organ failure and death. Therefore, monitoring of diastolic oxygen levels allows for early detection and treatment of systemic diseases, including sepsis, heart failure, and bleeding, and can also be used to optimize fluid resuscitation and the administration of anti-nutritional agents. In addition, monitoring of diastolic oxygen levels can provide early detection and treatment of organ-specific diseases, such as increased intracranial pressure, stroke, cerebral vasospasm, encephalitis, ischemic hepatitis, intestinal ischemia, nephritis, hepatitis, colitis, and inflammatory bowel disease, as well as abdominal and muscle compartment syndromes and pneumonia.

[0360] In order to perform a ratio calculation (R) of the modified ratio, first and second waveforms are required that are associated with corresponding signals dominated by measured light reflected from an internal organ at different wavelengths. For example, the first wavelength can be approximately 660 nm and the second wavelength can be approximately 895 nm. Determining the ratio value for the modified ratio of the waveform includes determining a plurality of signal level values over a window of the waveform corresponding to the subject's cardiac cycle and normalizing these values. The maximum signal value (DC level) for each wavelength at the beginning of the pulse or waveform is particularly important in the calculation of R. It is used both for normalization of the signal and for evaluating the change in light intensity level during the pulse (referred to as the AC level).

[0361] The ratio R of the modified ratios indicates the blood oxygen level values of the internal organs throughout the subject's cardiac cycle or pulse. In some embodiments, the ratio R of the modified ratios at a given time point t during the systolic and diastolic phases of the waveform can be calculated as follows:

[0362]

[0363] Where AC1(t) is the change in signal level of the shorter wavelength signal I1 at time t, AC2(t) is the change in signal value of the longer wavelength signal I2 at time t, and I1(t0) is the signal value (peak or maximum signal value) at the start of the pulse of Signal 1. I1(t0) is used as the first normalization factor for the shorter wavelength, and this time point defines t0. I2(t0) is the signal value of the longer wavelength signal at t0, which is used as the second normalization factor for the longer wavelength signal. Determination of an appropriate time t0 is described below.

[0364] Unlike conventional methods, a ratio, R, of the modified ratio is calculated for all t values in a window of the entire waveform corresponding to the subject's cardiac cycle or pulse, thereby allowing oxygen levels to be monitored during the systolic and diastolic phases of the pulse. In some embodiments, the processor 562 may determine the ratio of the modified ratio multiple times in a window of one or more waveforms corresponding to the cardiac cycle. For example, the signal may be sampled at a sampling rate greater than the pulse rate (or heart rate) to provide multiple signal values throughout the waveform. The signal may be sampled at a sampling rate greater than 5 Hz. In some embodiments, the sampling rate may be in the range of 100 Hz to 5000 Hz. The sampling rate may be 500 Hz. The sampling rate may be high enough to be considered substantially continuous. This provides a measurement of changes in oxygen levels during all phases of the cardiac cycle.

[0365] As described above, in an organ, the temporal positions of the peak signal values (maximum transmitted light intensity, absolute signal level, or DC level) of two or more signals may be asynchronous, with the absolute signal level of the second signal (at a shorter wavelength, such as 660 nm) occurring later. In an embodiment, when the start of the waveforms (or pulses) of the two signals are asynchronous, a normalization factor corresponding to the peak light intensity signal value of the first or second signal may be determined at time t0.

[0366] If there are variations in the signal values such that the intensity I(t) during the pulse is greater than or equal to the normalization factor used, the calculated corrected ratio R of the ratios may be inaccurate. Unlike the skin, the presence of low-frequency respiratory oscillations in the plethysmographic signal may prevent the use of conventional methods to calculate the ratio of the ratios, particularly for time periods of the pulse during the diastolic phase. This can occur during the lower chest pressure phase of the respiratory cycle (due to venous blood being drained more rapidly from the organ during this phase), so the light intensity level transmitted during diastole may actually exceed the peak signal value (e.g., maximum light intensity) at the start of the pulse. This results in negative AC levels during diastole, making it impossible to calculate the corrected ratio R of the ratios. This prevents the use of conventional methods in this situation.

[0367] To address the limitations of the above-described method for calculating the ratio R of modified ratio values, when the light intensity during the systolic or diastolic phase of a pulse exceeds the level at the beginning of the pulse (I) (e.g., due to respiration), the maximum signal value of the next pulse 3208 is used in the calculation to derive the ratio of the modified ratio values of the previous pulse (backward normalization method). Therefore, in some embodiments, the time t0 at which the normalization factor is determined can represent the light intensity value of the next pulse at t0 to calculate the ratio of the modified ratio values of the previous pulse. For this method, we define this time point as t 0+1 .

[0368] Another approach to addressing the problem of signal values increasing above earlier peak signal values during a pulse is to employ a forward normalization approach (i.e., still using the peak signal value at t0 at the start of the pulse), but providing a modified ratio R value calculated separately for each phase of the respiratory cycle (inspiration, inspiratory pause, expiration, and expiratory pause). These phases can be identified by low-frequency oscillations in the plethysmographic signal that appear at the respiratory rate.

[0369] Another approach (especially for the liver and lungs, where the amplitude of respiratory oscillations during respiration has a much greater influence on the signal value than cardiac oscillations) is to evaluate the calculated modified ratio R based on the respiratory oscillations rather than the cardiac oscillations in the signal, where t 0R represents the peak signal value at the onset of respiratory oscillation for each wavelength. For this method, we define this time point as t 0R . We call it the breath normalization method.

[0370] It has been found that the temporal distance (or temporal offset) between peak signals is proportional to the degree of difference between systolic and diastolic oxygen levels and can be used to estimate the diastolic oxygen level, since the arterial or systolic oxygen level is generally known (via conventional methods). For example, in some embodiments, the processor can be configured to determine the temporal distance between the peaks of the first and second waveforms associated with a signal primarily associated with the target internal organ, and determine the diastolic oxygen level of the internal organ based on the temporal distance and the associated arterial or systolic oxygen level. In the case of the lungs, the diastolic or arterial oxygen level is generally known, so the mixed venous oxygen level can be estimated.

[0371] The researchers found that the minimum microvascular oxygen saturation, which occurs during diastole, also varies with the phase of the respiratory cycle, with levels falling further during the expiratory phase. The lower levels achieved during expiration reflect reduced oxygenation of the blood during this phase of lung ventilation, as the air sacs may collapse during expiration. This oscillation of the minimum oxygen level in an organ's microvascular blood, associated with the respiratory phase, can be used to assess the degree of oxygen exchange between the lungs and the blood circulation. This knowledge can be used to detect lung disease and adjust mechanical ventilation parameters, such as the patient's level of positive end-expiratory pressure, to improve oxygen exchange in the lungs.

[0372] Reference again Figure 9 In the method 900 for assessing the health of a subject, in some embodiments, the processor 562 processes one or more received signals to remove a DC offset, thereby generating an AC signal for further analysis. A modified ratio can be determined from the AC signal. The signal can be an analog electrical signal digitally sampled (digitized) using an analog-to-digital converter (not shown).

[0373] In some embodiments, processor 562 can be configured to determine that the first and second signals are associated with an internal organ based on a comparison of the ratio of the determined modified ratio values to a characteristic waveform or template. The characteristic waveform or template can, for example, include a ratio of the modified ratio values determined based on the arteriocutaneous signal. The ratio of the modified ratio values for the arteriocutaneous signal is not significantly different from a value of approximately 0.6 for most pulses (or systolic and diastolic phases of the cardiac cycle). Therefore, processor 562 can determine that the ratio value of the modified ratio values, from which the ratio of the modified ratio values is calculated, differs by more than a threshold amount (e.g., 0.2), indicating that the first and second signals are primarily associated with an internal organ. For example, if the average of the ratio values of the determined modified ratio values is greater than approximately 0.7, the processor can be configured to determine that the first and second signals are primarily associated with the target internal organ. Specific examples of internal organs are discussed below. Templates can also be used to represent characteristic temporal variations in the ratio of the modified ratio values for the systolic and diastolic phases of a given internal organ.

[0374] In some embodiments, processor 562 may be configured to analyze changes in the determined blood oxygen levels to determine whether the blood oxygen levels indicate blood oxygen levels of internal organs. In some embodiments, in response to determining that the blood oxygen level is relatively high at a peak of at least one of the two waveforms and decreases as the two or more signal levels decrease, processor 562 may determine that the blood oxygen level indicates the blood oxygen level of an internal organ.

[0375] In some embodiments, processor 562 may assess the health of an internal organ based on a calculated value of a ratio of the determined modified ratios. For example, processor 562 may determine the subject's blood oxygen level using a modified ratio equation and may perform a health assessment based on the determined blood oxygen level and a target internal organ.

[0376] For example, processor 562 may determine the blood oxygen level based on the determined ratio value of the corrected ratio by comparing the ratio value of the corrected ratio to a lookup table or applying an empirically determined equation. The data used for the lookup table or the data used to determine the empirical equation may be based on simultaneous measurements using conventional oximetry techniques.

[0377] In some embodiments, processor 562 can determine blood oxygen levels in two or more waveforms (e.g., a ratio value for each corresponding modified ratio value determined, or at least a subset thereof). In addition, blood oxygen levels can be determined throughout the systolic and diastolic periods of each cardiac cycle (or pulse), thereby enabling monitoring of changes in oxygen levels in microvascular blood due to oxygen exchange with tissues of organs. Processor 562 can determine the blood oxygen levels of internal organs of subject 520 based on the blood oxygen levels determined at specific times in the waveforms.

[0378] The minimum signal levels of the first and second signals can coincide with the time when the blood oxygen level in the microcirculation reaches equilibrium with the tissue level in the internal organ. Therefore, in some embodiments, processor 562 can determine the equilibrium blood oxygen level of the internal organ by determining the signal value of the first or second signal when the signal is at its minimum level. However, in some cases, the blood oxygen level may not reach equilibrium with the tissue oxygen level. If the signal originates primarily from the capillary bed, or if there is very high blood flow or shunting, an imbalanced state may occur. Capillary bed signals are unique and different from signals from venules.

[0379] Figure 17 The figure is an example graph showing the ratio of oxygen saturation in the internal jugular vein of three human subjects during a whole-body hypoxia experiment relative to a modified ratio value determined using signals obtained from the brains of the three human subjects using the device 100. Blood was aspirated from a vein placed in a blood gas machine to determine the oxygen saturation of the blood. The blood oxygen level in the vein is shown to be inversely proportional to the ratio of the modified ratio values. This demonstrates that the ratio of the modified ratio values, calculated from signals derived from light reflected from the human brain, can be easily mapped to the oxygen level in the venous blood draining from the brain. It also provides evidence that the ratio value of the modified ratio value can be used to determine blood oxygen levels relative to internal organs.

[0380] Figure 18This graph shows oxygen saturation in the sagittal sinus vein of a single sheep during a brain injury experiment, in which blood was injected directly into the skull to alter intracranial pressure and reduce blood flow and tissue oxygen levels. The sagittal sinus vein drains blood from the vein. Figure 18 The graph shows the ratio of the modified ratio values determined using signals obtained from the sheep's brain using device 100. The blood oxygen level is inversely proportional to the ratio of the modified ratio values. This provides further evidence that the ratio of the modified ratio values can be used to determine blood oxygen levels associated with the brain and internal organs.

[0381] Corrected Ratio of Ratios - Brain

[0382] refer to Figure 7 (b) shows a graph of a ratio 703 of modified ratio values determined based on first and second signals 701, 702, the first and second signals being derived from measured light reflected from the brain 521 of the subject 520. As shown, when the ratio curve 703 of the modified ratio values is at a minimum, the blood oxygen level is at a maximum. When the signal value is at a maximum, the ratio 704 of the modified ratio values indicates that the blood oxygen level is at a minimum. A minimum signal value point 708 may also occur during the A-wave component (at the end of the diastolic phase of the cardiac cycle), and the processor 562 may determine the blood oxygen level value at the minimum of the A-wave component, as this may represent tissue oxygen level. A decrease in the ratio of the determined modified ratio values observed during the X-wave and Y-wave indicates an increase in oxygen level during these phases of the cardiac cycle.

[0383] The processor 562 can determine that the first and second signals 701, 702 are related to the brain 521 based on comparing the ratio of the determined corrected ratios with a characteristic waveform of the brain or a template of the expected corrected ratio ratio (rather than the expected corrected ratio ratio of the skin).

[0384] In some embodiments, the processor can calculate a statistical measure (e.g., a median, mean, or peak) of the ratio of the modified ratios and compare it to a threshold value. The statistical measure can be based on a portion of the calculated ratio of the modified ratios of the waveform. For example, the statistical measure can be the average of the largest 30% of the calculated ratio values of the modified ratios. The statistical measure can be related to the variation or range of the ratio of the determined modified ratios. Since a variation in the ratio of the determined modified ratios is expected from a signal associated with the brain 521, the variation can be determined and compared to a threshold value. For the processor 562, the value of the variation (or range) of the ratio values of the determined ratios can be, for example, greater than 1 to determine that the signal is associated with the brain 521. The statistical measure can be calculated from the edge of the A wave front during the diastolic phase of the cardiac cycle (away from the peak signal).

[0385] This is in contrast to typical modified ratio values determined from arterial skin signals, which vary little over the course of a pulse and have values from about 0.5 to about 0.7. Thus, the threshold value may be about 0.7 or about 1.

[0386] In some embodiments, the processor 562 may be configured to assess brain health by analyzing the modified ratio values. For example, the processor 562 may compare the modified ratio values with a characteristic waveform or template to perform a health assessment. In some embodiments, the processor 562 may compare a statistical measure of the ratio values with a threshold value to perform a health assessment.

[0387] The minimum or equilibrium blood oxygen level of the brain can provide valuable clinical information about tissue oxygen levels. For example, a low tissue oxygen level in the brain may indicate that subject 520 has an adverse health condition, such as increased intracranial pressure, and is at risk of developing brain damage. Therefore, processor 562 can compare the statistical measurement of the ratio value (or blood oxygen level) with a threshold value, and in response to determining that the statistical measurement value is less than the threshold value, processor 562 can determine that subject 520 has hypoxia. Cerebral hypoxia may occur due to stroke, vasospasm, and increased ICP.

[0388] For example, Figure 19 A graph showing the ratio of the corrected ratio values derived from signals measured using device 100 from light reflected from the sheep's brain is shown. As shown, the ratio of the corrected ratio values derived from signals measured using device 100 from light reflected from the brain was found to increase immediately after blood was injected into the sheep's brain, thereby increasing intracranial pressure. This may indicate a decrease in blood oxygen levels in the brain (decreased cerebral perfusion) following the increase in intracranial pressure. Therefore, low blood oxygen levels in the brain may indicate a disease that causes reduced blood flow. After an initial increase in the ratio of the corrected ratio values, a decrease was observed that correlated with the increase in blood oxygen levels. This may be due to a subsequent increase in blood pressure to restore blood flow.

[0389] Thus, processor 562 may compare the determined minimum blood oxygen level to a threshold level. In response to determining that the minimum blood oxygen level is less than the threshold level, processor 562 may determine that subject 520 suffers from organ ischemia and requires urgent treatment.

[0390] Figure 20 (b) shows signals 2001, 2002 obtained from light reflected from the brain 521 of the human subject 520 using the apparatus 100. As shown in the figure, the light intensity (or signal value) of the first and second signals 2001, 2002 obtained from the brain 521 of the human subject 520 varies according to the breathing cycle of the subject 520. Figure 20(a) shows simultaneous third and fourth signals 2003, 2004 obtained from light reflected from the internal jugular vein of subject 520, which provide a method of indicating the phase of the respiratory cycle. "Expiratory (Exp)" indicates the respiratory phase of exhalation. "Inspiratory (Insp)" indicates the respiratory phase of inspiration. As shown, the intensity of the third and fourth signals 2003, 2004 also varies according to the respiratory cycle of subject 520, and generally decreases during the expiratory phase of the respiratory cycle (e.g., exhalation) and increases during the inspiratory phase of the cycle (e.g., inhalation). Figure 20 (c) shows the simultaneous change in the ratio of the corrected ratios during each cardiac cycle. Oxygen levels are shown to decrease during expiration (the ratio of the corrected ratios increases).

[0391] As described above, the ratio of the modified ratio (or blood oxygen level) varies with the phase of the respiratory cycle in the internal organs. During the inspiration period, the oxygen level may be higher. These changes reflect the degree of oxygenation of arterial blood by the lungs during the inspiration and expiration phases, and thus can monitor lung function. Its applications include detecting lung damage, adjusting mechanical ventilation to establish the optimal positive end-expiratory pressure (PEEP) level, and adjusting mechanical ventilation to reduce ventilator-associated lung damage by selecting the lowest ventilation pressure level that still provides adequate organ tissue oxygen levels.

[0392] Corrected Ratio of Ratios - Lung

[0393] The lungs have a unique microcirculation in that the surrounding tissue is composed of alveolar sacs that are filled with oxygen during inspiration. The pulmonary arteries carry mixed venous blood from the body to the microcirculation of the lungs, where oxygen is added to the blood from the alveolar sacs. Therefore, the oxygen level in the pulmonary microvascular blood is low during periods of high blood flow into the lungs, which occurs during the systolic and diastolic recoil of the pulmonary arteries (the peak in signal 1001 after the X-wave and Y-wave components). Peak oxygen levels are expected to occur during the A-wave component (during end-diastole). In the lungs, the minimum (trough) oxygen level during systole provides an estimate of the mixed venous blood oxygen level. The peak oxygen level during diastole provides a measure of the degree of oxygenation of the blood in the lungs.

[0394] Figure 10(b) shows the ratio of the corrected ratios calculated from the first and second signals 1001, 1002, which are associated with well-ventilated lungs. During the cardiac cycle, the ratio of the corrected ratios is observed to rise from 0 to a value exceeding 2. As shown, a minimum in the calculated ratio of the corrected ratios (which indicates a maximum blood oxygen value) is observed to occur during the A wave component of the first signal 1001 (during diastole), which coincides with the time of the additional peak 1005. The maximum blood oxygen value can provide an indication of lung function based on the degree of oxygenation of the blood. The maximum in the ratio of the corrected ratios (indicating a minimum blood oxygen value) occurs during the X wave component of the signal 1001 during the systolic phase of the cardiac cycle. The minimum blood oxygen value can provide an estimate of the mixed venous oxygen value of the blood entering the lungs.

[0395] Figure 15 (c) shows the ratio of the modified ratio values calculated from the first and second signals 1501, 1502, associated with a dependent and poorly ventilated and perfused lung. As shown, in contrast to the behavior observed in a well-ventilated lung, the ratio of the modified ratio values remains high (around a value of 1), and thus the blood oxygen level remains low during the diastolic A wave. In effect, blood is shunted through the lungs, and no oxygen is added to the blood.

[0396] The processor 562 may determine that the first and second signals 1001, 1002, 1501, 1502 are associated with the lungs based on the ratio of the determined modified ratios. This may be due to the positioning of the device 100 on the subject. The device 100 may be adjusted until the desired signal associated with the lungs is obtained. The lungs are characterized by oxygen levels being low during systole and high during diastole (see Figure 10 (b)). This is the reverse of the skin oxygen level. This feature can be used to determine that the signal is coming from the lungs.

[0397] In some embodiments, the processor 562 can determine that the first and second signals 1001, 1002, 1501, 1502 are associated with the lungs based on a ratio R of the modified ratios, where the ratio of the modified ratios is determined during the leading edge of the A wave before the X wave (indicating peak oxygen levels in the blood in the lungs) or during the X wave (during contraction when blood oxygen levels are low).

[0398] Processor 562 can assess lung health by analyzing the ratio of the modified ratios. For example, processor 562 can compare the ratio of the modified ratios to a characteristic waveform or template to perform a health assessment. In lung injury, the level of oxygen added to venous blood may be low. Therefore, if the ratio of the modified ratios is high, this may indicate lung injury.

[0399] In some embodiments, in response to determining that the ratio of the modified ratios is slowly decreasing to a moderate level (indicating that the blood oxygen level is slowly increasing to a low or moderate level), processor 562 determines that the subject has unhealthy and / or poorly ventilated lungs.

[0400] In some embodiments, processor 562 may compare the statistical measure of the ratio of the modified ratios to a threshold value to perform a health assessment. For example, in response to determining that the ratio of the modified ratios does not reach the arterial oxygen level during diastole (the ratio of the modified ratios is 0.5), processor 562 determines that the subject has unhealthy and / or poorly ventilated lungs.

[0401] In some embodiments, in response to determining that the mean or median of the ratio of the modified ratios is between about 1 and about 1.5, the processor may determine that the subject has unhealthy or poorly ventilated lungs.

[0402] Corrected Odds Ratio - Liver

[0403] The device 100 can be used to obtain first and second signals obtained from light reflected from a healthy liver of a subject 520, and a modified ratio of the first and second signals associated with the liver can be calculated. The modified ratio decreases during the X-wave (indicating an increase in oxygen levels) and then increases to maintain a relatively high and constant level during the diastole phase of the cardiac cycle until the next X-wave. This change in behavior, such as a decrease in oxygen levels in the blood, may indicate a condition in which blood flow to the liver is reduced, such as any one or more of ischemic hepatitis, abdominal compartment syndrome, and portal vein thrombosis.

[0404] The processor 562 can determine that the first and second signals 2201, 2202 are associated with the liver based on the determined ratio of the modified ratios. A statistical measure (e.g., a median or mean) of the ratio of the modified ratios can be compared to a threshold. The statistical measure can be based on the largest 30% of the ratio of the modified ratios calculated over the waveforms. For example, in response to determining that the statistical measure is greater than approximately 0.7, the processor 562 can determine that the first and second signals 2201, 2202 are associated with the liver. In some embodiments, in response to determining that the statistical measure is approximately 1, the processor 562 can determine that the first and second signals 2201, 2202 are associated with the liver. In some embodiments, in response to determining that the statistical measure is greater than approximately 1, the processor 562 can determine that the first and second signals 2201, 2202 are associated with the liver.

[0405] A statistical measure equal to or less than 0.7 may indicate that the first and second signals are associated with the subject's skin. In some embodiments, in response to determining that the statistical measure is equal to approximately 0.7, processor 562 determines that the first and second signals are associated with subject 520's skin.

[0406] In some embodiments, processor 562 may determine that the first and second signals are associated with the liver based on a ratio of the modified ratio values determined during the leading edge of the A wave preceding the X wave. This is particularly interesting because the blood oxygen level at this time (which can be calculated from the ratio of the modified ratio values) may be similar to or equal to the tissue oxygen level of the liver.

[0407] The processor 562 can assess the health of the liver by analyzing the ratio of the modified ratios. For example, the processor 562 can compare the ratio of the modified ratios with a characteristic waveform or template to perform a health assessment. In some embodiments, the processor 562 can compare a statistical measurement of the ratio of the ratios with a threshold value to perform a health assessment. For example, in response to determining that the statistical measurement is between approximately 0.5 and 1.5, the processor 562 can determine that the subject has a healthy liver. In some embodiments, in response to determining that the statistical measurement is greater than approximately 2, the processor 562 can determine that the subject has an unhealthy liver (e.g., due to hypoxia or ischemia of the liver).

[0408] Corrected odds ratio - intestinal

[0409] The first and second signals acquired using the apparatus 100 from light reflected from the healthy intestine of the subject 520 can be used to calculate a ratio of the modified ratio values based on the first and second signals associated with the intestine. The oxygen level is similar during the systolic and diastolic phases, with only a brief increase during the X-wave and systolic phases (illustrated by a decrease in the ratio of the calculated modified ratio values). Thereafter, there is a rapid drop in the oxygen level, and then the oxygen level levels off during diastole - the relatively stable and low oxygen level throughout the pulse may reflect the unique blood flow through the microcirculation of the intestinal villi. The counter-flow design provides free oxygen exchange between the arterial and venous sides of the microcirculation during all phases of the cardiac cycle.

[0410] The processor 562 can determine that the first and second signals are associated with the intestine based on the determined ratio of the modified ratios. A statistical measure (e.g., a median or mean) of the ratio of the modified ratios can be compared to a threshold value. The statistical measure can be based on the largest 30% of the ratio of the modified ratios calculated on the waveforms. For example, in response to determining that the statistical measure is greater than approximately 0.7, the processor 562 can determine that the first and second signals are associated with the intestine. In some embodiments, in response to determining that the statistical measure is greater than approximately 1, the processor 562 can determine that the first and second signals are associated with the intestine. A statistical measure equal to or less than 0.7 can indicate that the first and second signals are associated with the subject's skin.

[0411] In some embodiments, the processor 562 may determine that the first and second signals are bowel related based on a ratio of the modified ratio values determined during the leading edge of the A wave preceding the X wave.

[0412] In some embodiments, the processor 562 can determine the health of the intestine based on a comparison of one or more waveforms of the first and second signals with a characteristic waveform. The difference in the ratio of the waveforms or the calculated modified ratio compared to the characteristic waveform can be used to diagnose intestinal diseases, such as intestinal ischemia, which will result in very low blood oxygen levels in the intestine.

[0413] The processor 562 can assess intestinal health by analyzing the ratio value of the modified ratio. For example, the processor 562 can compare the ratio value of the modified ratio with a characteristic waveform or template to perform a health assessment. In some embodiments, the processor 562 can compare a statistical measurement of the ratio of the ratio with a threshold value to perform a health assessment. For example, in response to determining that the statistical measurement value is greater than 2, the processor can determine that the subject has an unhealthy, ischemic intestine.

[0414] Corrected Odds Ratio - Kidney

[0415] A ratio value R of the corrected ratios of signals obtained from light reflected from the subject's kidneys may be calculated. Low values of the ratio R of the corrected ratios most of the time indicate that the blood oxygen level in the kidneys remains high.

[0416] Modified Ratio of Muscle

[0417] A ratio R of the modified ratios of the signals obtained from the light reflected from the calf muscle at rest can be calculated. Low values of the ratio R of the modified ratios most of the time indicate low blood flow to the muscle when the muscle is at rest.

[0418] The present invention will now be further described with reference to the following non-limiting examples:

[0419] Example - Evaluating improvements to brain sensor devices to improve detection of light pulses in the brain

[0420] method

[0421] Variations in the design of the brain sensor device were evaluated to improve detection of brain impulses and provide a comparison with a state-of-the-art device. Evaluations were conducted on five healthy volunteers. Two evaluations were performed on each volunteer, one at the left temple and one at the right temple, for a total of 10 evaluations for each device modification. The outcome measure was the detection of a pulsating light signal that was consistent with the shape and characteristics of brain impulses, Figures 23(a), (b), and (c) and Figure 24The results shown in the table are reported as the percentage of tests in which brain impulses were detected. In each test, the photodetector (PD) and light-emitting diode (LED) were circular and 8 mm in diameter. The photodetector and LED (emitting light at wavelengths of 660 nm and 895 nm) were equivalent to those manufactured by Medtronic (710 Medtronic Boulevard, Minneapolis, MN 55432-5604, USA). TM The photodetectors and LEDs used in the Maxfast forehead sensor. The total optical power used (all LEDs) is approximately 200 μW.

[0422] In the first experiment, a variation of a conventional pulse oximetry device was tested, in which a photodetector (PD) and a light-emitting diode (LED) were placed in contact with the subject's skin. In this experiment, the separation between the center points of the light source (LED) and the photodetector (PD) was varied between 10mm, 15mm, 20mm, and 40mm.

[0423] The results in Figure 23(a) show that using a modification of the prior art pulse oximeter device with different spacing between the PD and LED, it is impossible to detect brain pulse signals in the absence of spacing between the PD / LED and the subject's skin.

[0424] In the second experiment, the spacing between the PD and LED and the skin was kept constant at 10 mm, and the effect of varying the separation between the center points of the light source (LED) and the light detector (PD) between 10 mm, 15 mm, and 20 mm was tested.

[0425] The results in Figure 23(b) show that while brain pulses were detected in 50% of the tests when the PD and LED were laterally spaced 10 mm and 20 mm from their centers, a spacing of 15 mm between the PD and LED provided 100% brain pulse detection.

[0426] In the third trial, the separation between the center points of the light source (LED) and the light detector (PD) was fixed at 15 mm (the optimal separation from the second trial), and the effect of varying the distance between the PD and LED and the skin between 0 mm, 5 mm, 10 mm, 15 mm, and 20 mm was tested.

[0427] The results in FIG23( c ) show that no brain impulses were detected at spacings of 0 mm and 20 mm, while 25% of brain impulses were detected at a spacing of 15 mm and 50% of brain impulses were detected at a spacing of 5 mm. The best result of 100% brain impulse detection was achieved when the PD and LED were 10 mm apart from the skin. In subsequent tests conducted by the inventors (results not shown), the best result of 100% brain impulse detection was also observed when the PD and LED were 8.5 mm apart from the skin.

[0428] In the fourth experiment, the spacing between the center points of the light source (LED) and the light detector (PD) was fixed at 10 mm, the spacing of the PD from the skin was fixed at 10 mm, and the effect of changing the spacing between the LED and the skin between 15 mm and 20 mm (i.e., 5 mm and 10 mm recessed from the PD position, respectively) was tested.

[0429] Figure 24 The results in show that when the LED is positioned 10 mm farther from the skin surface than the PD, the brain signal detection result is relatively poor, but when the LED is positioned 5 mm farther from the skin surface than the PD, the brain signal detection is 100%.

[0430] It will be appreciated by those skilled in the art that various changes and / or modifications may be made to the above embodiments without departing from the broad overall scope of the present disclosure. Therefore, the present embodiments are to be considered in all aspects as illustrative and not restrictive.

Claims

1. An apparatus for determining data indicative of a subject's health, the apparatus comprising: a body comprising a contact surface for engaging the subject proximate the subject's brain; the body defining a first groove and a second groove extending from the contact surface into the body, the second groove being spaced apart from the first groove; a light source comprising a light emitting region within the first recess and configured to emit light of at least one discrete wavelength from the first recess of the body onto the brain; as well as a light detector comprising a light-sensitive region within the second recess and configured to detect light received at the second recess, wherein the detected light includes emitted light reflected from a region of the subject adjacent to the brain; wherein the device is configured such that both the light emitting area and the photosensitive area are retracted from the contact surface by approximately 1 mm to approximately 20 mm, and the nearest points of the light emitting area and the photosensitive area are separated from each other by approximately 4 mm to approximately 20 mm, so that the detected light indicates blood in the blood vessels on the outermost surface of the brain.

2. The device according to claim 1, wherein The spacing between the closest points of the light emitting region and the light sensitive region is about 5 mm to about 15 mm, optionally wherein the spacing is about 6 mm to about 12 mm.

3. The device according to claim 1 or 2, wherein: At least one of the light emitting region and the photosensitive region is set back from the contact surface by about 7 mm to about 10 mm.

4. The apparatus according to any one of claims 1 to 3, wherein The subject further comprises: an outer frame defining the contact surface and the cavity; and An inner frame is shaped to fit within the cavity, wherein the inner frame defines the first and second grooves.

5. The apparatus according to any one of claims 1 to 4, wherein The body further includes a wall separating the first recess from the second recess, wherein, in use, the wall helps to limit emitted light from the light source from being reflected or scattered to the light detector without first interacting with the brain, optionally wherein the wall extends a wall height from the base of the body toward the contact surface, and wherein the wall height is at least about 2 mm or about 4 mm, optionally wherein the wall has a wall thickness of about 1 mm to 2 mm or 1.8 mm.

6. The apparatus according to any one of claims 1 to 5, wherein: The first groove and the second groove have a depth extending from the base to a plane defined by the contact surface, wherein the depth is about 5 mm to about 15 mm or about 8.5 mm.

7. The apparatus according to any one of claims 1 to 6, wherein: The light source is configured to emit light, the light including light with a wavelength within a first wavelength range of at least about 600 nm to about 750 nm and a second wavelength range of about 855 nm to about 945 nm, optionally wherein the light source is configured to emit light, the light also including light with a wavelength within a third wavelength range of about 780 nm to about 820 nm.

8. The apparatus according to any one of claims 1 to 7, wherein The light detector is configured to sense light including light at discrete wavelengths of at least approximately 660 nm, approximately 805 nm, approximately 895 nm, and / or approximately 940 nm.

9. A system for determining the health of a subject, the system comprising the apparatus according to any one of claims 1 to 8 and a processor, wherein: The device and processor are connected to enable data indicative of blood in blood vessels at the outermost surface of the brain to be transmitted from the device to the processor, optionally wherein the processor includes a memory and the system includes a display and a user interface, the display and user interface being coupled to the processor.

10. A method of determining or obtaining data indicative of a subject's health using an apparatus according to any one of claims 1 to 8, the method comprising: generating at least one signal indicative of an intensity of at least one discrete wavelength of light reflected from an outermost surface of the subject's brain to an outer surface of the subject; as well as At least one waveform of the at least one signal is determined to represent a signal primarily associated with the brain to assess the health of the subject.

11. The method according to claim 10, further comprising: positioning the device on an external surface of the subject adjacent to the brain; projecting light from the device through an external surface of the subject into the brain, wherein the light comprises light of at least one discrete wavelength; receiving light at a light detector of the device, the received light reflected from the brain at at least one discrete wavelength; and In response to receiving an instruction indicating that the device is inaccurately positioned relative to the brain, the device is repositioned relative to the brain based on the instruction.

12. The method according to claim 10 or 11, further comprising: Data derived from the at least one waveform is compared to informative features of a health condition to assess the health of the subject.

13. The method according to any one of claims 10 to 12, wherein Determining that the at least one waveform represents a signal primarily associated with the brain includes determining that the at least one waveform substantially corresponds to a venous waveform.

14. The method according to any one of claims 10 to 13, wherein Determining that the at least one waveform represents a signal primarily associated with the brain includes determining that the at least one waveform includes at least one of an X-wave component, an A-wave component, a C-wave component, a V-wave component, and a Y-wave component corresponding to an X-wave, an A-wave, a C-wave, a V-wave, and a Y-wave of a venous signal.

15. The method according to any one of claims 10 to 14, wherein In response to determining that the V wave component of the at least one waveform has a greater amplitude than a corresponding V wave component of a corresponding template waveform of the brain, it is determined that the subject may have one or more of an elevated central venous pressure level, fluid overload, and heart failure.

16. The method according to any one of claims 10 to 15, further comprising: analyzing the at least one waveform to determine whether the at least one waveform includes a V-wave or a Y-wave component; as well as Responsive to determining that the at least one waveform does not depict a V-wave or Y-wave component, it is determined that the subject may have relatively high intracranial pressure.

17. The method according to any one of claims 10 to 16, further comprising: analyzing the at least one waveform to determine whether the at least one waveform includes oscillations at approximately 7 Hz; as well as In response to determining that the at least one waveform includes oscillations at approximately 7 Hz, it is determined that the subject may have relatively very high intracranial pressure and / or a cerebral hematoma.

18. The method according to any one of claims 10 to 17, in, the one or more discrete wavelengths including a first wavelength and a second wavelength, The at least one signal includes a first signal and a second signal, Wherein, the method further comprises: determining a blood oxygen level in a blood vessel of the brain based on the first signal and the second signal, comparing the blood oxygen level to a threshold level, and responsive to determining that the blood oxygen level is greater than or less than the threshold level, determining that the subject has increased intracranial pressure, Optionally, the first waveform and / or the second waveform includes an A-wave component, a C-wave component, an X-wave component, a V-wave component and / or a Y-wave component corresponding to an A-wave, a C-wave, an X-wave, a V-wave and a Y-wave, wherein the A-wave, C-wave, X-wave, V-wave and Y-wave are typically observed in a venous pressure signal (venous signal), Optionally, among the signal values of the waveform, the A-wave component is the large trough, the C-wave component is the small trough superimposed on the signal value of the waveform after the minimum signal value of the A-wave, the X-wave component is the increase in signal value after the minimum point in the A-wave, the V-wave component is the trough superimposed on the signal value of the waveform after the X-wave and peak signal value, and the Y-wave component is the increase in signal value after the local maximum of the V-wave.

19. The method of any one of claims 10 to 18, further comprising determining minimal oscillations of blood oxygen levels in the brain over a plurality of respiratory cycles to assess oxygen exchange in the lungs.

20. The method of any one of claims 10 to 19, further comprising monitoring blood flow in the brain based on a comparison of the shape and / or amplitude of the at least one waveform to one or more template waveforms, wherein At least one or more waveforms are associated with a first signal having a wavelength of 805 nm.

21. The method of any one of claims 10 to 20, further comprising, in response to determining that the at least one waveform is substantially similar to an arterial blood pressure waveform, determining that the subject's arterial blood pressure is much greater than central venous pressure and that blood flow is high.

22. The method of any one of claims 10 to 21, further comprising, in response to determining that the at least one waveform comprises an exaggerated venous waveform, determining that venous pressure is high and cerebral blood flow is low, wherein The exaggerated venous waveform includes a high-amplitude V-wave component and optionally a high-amplitude A-wave component, and wherein the subject is determined to have one or more of an elevated central venous pressure level, fluid overload, and heart failure, Optionally, determining that the at least one waveform comprises an exaggerated venous waveform comprises determining that the magnitude or amplitude of any one or more of the A-wave, V-wave component, X-wave component and / or C-wave component is greater than a threshold value.

23. The method according to any one of claims 10 to 22, further comprising: projecting light through the subject's skull into the intergyral sulcus, wherein the received light is reflected from cerebrospinal fluid in the intergyral sulcus at one or more discrete wavelengths; and The one or more signals are provided to allow determination of elevated intracranial pressure of the subject based on at least one waveform of the at least one signal.

24. The method according to any one of claims 10 to 23, further comprising: determining a pulse waveform of at least one of the one or more signals; as well as In response to determining that the pulse waveform includes one or more oscillations, determining elevated intracranial pressure based on one or more of a mode, an amplitude, and a frequency of the one or more oscillations, optionally wherein determining elevated intracranial pressure includes determining that the at least one waveform includes oscillations similar to a waveform of an intracranial pressure trace and that the pulse begins before a corresponding wave component of an arterial signal obtained from forehead skin.

25. The method of any one of claims 10 to 24, further comprising, in response to determining that the at least one waveform comprises an exaggerated venous waveform, determining that venous pressure is relatively high and cerebral blood flow is low, wherein The exaggerated venous waveform includes a high-amplitude V-wave component and an optional high-amplitude A-wave component, Optionally, wherein the subject is determined to have one or more of cerebral artery spasm and arterial thrombosis, elevated central venous pressure levels, fluid overload, heart failure, which may occur in stroke, Optionally, determining that the at least one waveform comprises an exaggerated venous waveform comprises determining that the magnitude or amplitude of any one or more of an A-wave component, a V-wave component, an X-wave component and / or a C-wave component is greater than a threshold value.

26. The method according to any one of claims 10 to 25, wherein A calculation of a ratio of the modified ratio values is performed over a window of the waveform corresponding to a cardiac cycle or pulse and the result is compared to a characteristic value of a typical or healthy brain to make a determination, wherein the calculation of the ratio of the modified ratio values is performed using at least two signals, the at least two signals resulting from received light reflected from a region of the subject at two different wavelengths.

27. The method according to any one of claims 10 to 26, wherein Assessing the health of the subject includes determining one or more health conditions including one or more of increased intracranial pressure (ICP), a cerebral hematoma, and / or a health condition related to brain movement.

28. The method according to any one of claims 10 to 27, wherein The outer surface of the subject is located at a location on the subject's scalp where the skull is relatively thin compared to other locations on the skull, including one or more of the following: the temple, occipital bone, orbital bone, parietal bone and frontal region of the skull, and adjacent to the sylvian fissure or intergyral sulcus.

29. The method according to any one of claims 10 to 28, wherein Assessing the subject's health includes determining the likelihood that the subject has a condition associated with low microvascular oxygen levels or abnormal blood flow or motion, including one or more of increased intracranial pressure (ICP), cerebral hemorrhage, and stroke.

30. The method according to any one of claims 10 to 29, wherein The waveforms are used to detect abnormal blood flow patterns due to arterial and venous circulation disorders, including one or more of cerebral artery spasm and arterial thrombosis, which may occur in stroke.

31. A method according to any one of claims 10 to 30, comprising determining an estimate of the diastolic blood oxygen level of the brain based on a time offset between a signal peak and a corresponding signal peak of a further waveform and a known systolic blood oxygen level, wherein The further waveform of the further signal is indicative of an arterial pulse of the subject.

32. The method of any one of claims 10 to 31 , comprising comparing the ratio value of the ratio or the statistical measure of blood oxygen level to a threshold value, and in response to determining that the statistical measure is less than the threshold value, determining that the subject suffers from hypoxia.

33. The method according to any one of claims 10 to 32, further comprising: obtaining simultaneous arterial signals from the subject; as well as The at least one waveform is compared to the simultaneous arterial signal to determine whether disease is likely localized to the brain.

34. The method of any one of claims 10 to 33, further comprising comparing the at least one waveform to a template waveform representative of a subject experiencing relatively high intracranial pressure to determine whether one or more of the waveforms is substantially representative of the template waveform, and thereby determining whether the subject is likely to have relatively high intracranial pressure, optionally wherein, Comparing the at least one waveform to a template waveform further includes calculating a sum of squared residuals.

35. The method of any one of claims 10 to 34, further comprising analysing at least one of the first and second components of the at least one waveform to determine a gradient of a leading edge of an initial slope of the or each waveform; and determining that the subject may have relatively high intracranial pressure in response to determining that at least one of the gradients of the leading edge is greater than a threshold value.

36. The method of any one of claims 10 to 35, further comprising analyzing at least one of the first and second components of the at least one waveform to determine whether a V wave component and / or a Y wave component is present; and in response to determining that a V wave and / or a Y wave component is absent, determining that the subject may have relatively high intracranial pressure.

37. The method according to any one of claims 10 to 36, further comprising: analyzing the at least one waveform to determine whether the at least one waveform exhibits an increase in AC component amplitude relative to a corresponding component of the arterial signal; as well as In response to determining that the AC component amplitude is increased, it is determined that the subject may have relatively high intracranial pressure or a cerebral hemorrhage.

38. The method according to any one of claims 10 to 37, further comprising: analyzing the at least one waveform to determine whether the at least one waveform exhibits a DC component that decreases in amplitude followed by an increase; as well as In response to determining that the DC component amplitude decreases and then increases, the subject is determined to have a high intracranial pressure level or a cerebral hemorrhage.

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