Devices, systems and methods for evaluating internal organs

Abstract

An apparatus for determining data indicative of blood oxygen level of an internal organ is disclosed. The apparatus includes: a body including a contact surface for engaging with a subject near the subject's internal organ; 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 spaced apart from the first recess; a light source including 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 including a photosensitive region located 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 to 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 about 1 mm to about 20 mm, and the closest points of the light emitting region and the photosensitive region are separated from each other by about 4 mm to about 20 mm, such that the detected light indicates blood oxygen level in a blood vessel at an outermost surface of the internal organ. Also disclosed are systems comprising the device and methods of using the device to assess the health of a subject's internal organs, particularly but not exclusively for determining blood oxygen saturation of a subject's internal organs.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to Australian Provisional Patent Application No. 2019902373 filed on July 4, 2019, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0003] 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

[0004] Pulse oximetry is used to non-invasively measure the absolute arterial circulating oxygen level (oxygen saturation) of the blood of the subject's skin, thereby providing an indication of the subject's health. The absolute arterial oxygen level can be determined by analyzing the ratio of the intensities of red light and near-infrared light. The arterial oxygen level can be obtained, for example, by transmitting light through the subject's fingers 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 to the subject. The signal originates from the blood flow in the skin.

[0005] The inventors have now determined that by utilizing a device located proximate an internal organ of interest on a subject, blood oxygen concentration in the microvasculature of the internal organ can be accurately determined and organ health assessed, wherein a light source and a light detector of the device are disposed rearwardly from a surface of the device that contacts the subject (e.g., located 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

[0006] 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 subject's internal organ; 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 located 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 located within the second recess and configured to detect light received at the second recess, wherein the detected light comprises emitted light reflected from a region of the subject adjacent to 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 the closest points of the light emitting region and the photosensitive region are separated from each other by approximately 4 mm to approximately 20 mm, such that the detected light indicates blood oxygen level in blood vessels at an outermost surface of the internal organ.

[0007] The spacing between the closest points of the light emitting area and the light sensitive area 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.

[0008] 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.

[0009] 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.

[0010] 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 the processor are connected so that data indicating 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 connected to the processor. Some embodiments relate to a method for obtaining data indicating the blood oxygen level of an internal organ of a subject, comprising: positioning the above-mentioned device on an outer surface of the subject adjacent to the internal organ; projecting light from a light source through the outer surface of the subject to the internal organ, wherein the light includes two or more discrete wavelengths of light; receiving light at a light detector of the device, the received light being reflected from the internal organ at two or more discrete wavelengths respectively; and generating a first signal indicating the intensity of the light of the first wavelength and a second signal indicating the intensity of the light of the second wavelength.

[0011] In some embodiments, the method includes positioning the device on the scalp of the subject, wherein the internal organ includes the brain. In some embodiments, the method includes positioning the device near an area of ​​the skull under the scalp where the skull area is relatively thin. An area of ​​the skull may be adjacent to the Sylvian fissure. In some embodiments, the method includes positioning the device in the ear canal of the subject, wherein the internal organ includes the brain. In some embodiments, the method includes positioning the device on the sternal notch, on 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 intestine. In some embodiments, the method includes positioning the device on the back of the subject, 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 with the ribs, wherein the internal organ includes the heart. In some embodiments, the method includes positioning the device on the skeletal muscle of the subject, wherein the internal organ includes the skeletal muscle.

[0012] 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.

[0013] Some embodiments relate to a computer-implemented method for assessing the health of a subject, the method comprising: receiving one or more signals obtained from measured light reflected from an area adjacent to an internal organ of the subject at respective different wavelengths; determining that at least one waveform of the one or more signals represents a signal primarily associated with the internal organ; and comparing data obtained from the at least one waveform with informational features of a health condition to assess the health of the subject.

[0014] 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.

[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 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 a brain, a lung, a liver, an intestine, and a fetal organ.

[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 is not indicative of an arterial signal obtained from a skin region of the subject.

[0017] In some embodiments, determining that at least one waveform represents a signal primarily associated with an internal organ includes: receiving an additional signal obtained from the subject substantially simultaneously 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.

[0018] 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 further signal.

[0019] In some embodiments, the method further includes determining an estimate of the diastolic blood oxygen level of the internal organ based on the time offset between the signal peak and the corresponding signal peak of the additional waveform and the known systolic blood oxygen level. For example, the additional waveform of the additional signal can be indicative of an arterial pulse of the subject. The additional waveform of the additional signal can be indicative of a venous signal obtained from a jugular vein of the subject. The additional signal can 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 levels.

[0020] 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.

[0021] 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 area of ​​the subject, determining that the at least one waveform does not represent a signal primarily associated with an internal organ.

[0022] 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 at least one waveform may include a first waveform of the first signal and a second waveform of the second signal, and determining that at least one waveform represents a signal primarily related to an internal organ may include: determining ratio values ​​of a plurality of corrected ratios on a window corresponding to at least one waveform of a cardiac cycle, wherein the ratio values ​​of the corrected ratios indicate a blood oxygen level of the internal organ; and determining that the determined ratio values ​​of the plurality of corrected ratios substantially correspond to characteristics of the ratio values ​​of the corrected ratios of the internal organ.

[0023] 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.

[0024] 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.

[0025] 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.

[0026] 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 systolic pulses, diastolic pulses, and dicrotic notches.

[0027] 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.

[0028] 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.

[0029] In some embodiments, wherein the internal organ comprises intestines, and determining that the one or more signals are primarily associated with the intestines comprises determining that at least one waveform of the one or more signals comprises 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.

[0030] 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.

[0031] In some embodiments, wherein the internal organ comprises skeletal muscle, and determining that the first signal is primarily associated with the skeletal muscle comprises determining that at least one waveform of the one or more signals corresponds to an arterial waveform having a relatively low pulse amplitude.

[0032] The method may further include assessing the health of the subject based on the comparison and outputting an assessment of the health of the subject. 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.

[0033] 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 be suffering from heart failure.

[0034] 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 cerebral hematoma.

[0035] In some embodiments, wherein the internal organ comprises 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.

[0036] 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.

[0037] In some embodiments, wherein the internal organ comprises 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.

[0038] 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.

[0039] 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 feature and the second waveform includes a venous waveform feature, it is determined that the health condition includes pulmonary malventilation.

[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, 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 malventilation.

[0041] In some embodiments, wherein the internal organ comprises a liver, and in response 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.

[0042] In some embodiments, wherein the internal organ comprises 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 comprises any one or more of hepatitis, cirrhosis, and right heart failure.

[0043] 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.

[0044] In some embodiments, wherein the internal organ comprises a heart, and the method further comprises analyzing the one or more signals to determine the timing of cardiac chamber contraction and relaxation in the cardiac cycle.

[0045] 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 the at least one waveform includes a first waveform of the first signal and a second waveform of the second signal, the method further includes: 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 at least one waveform corresponding to the cardiac cycle may include sampling the oxygen level at a relatively high rate over the window.

[0046] In some embodiments, comparing the 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 the determined ratio values ​​of the plurality of modified ratios deviate from ratio values ​​characteristic of the internal organ.

[0047] In some embodiments, the method further includes: receiving a third and a fourth signal obtained from the subject as one or more signals substantially simultaneously, wherein the third and the fourth signals are obtained 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 a cardiac cycle, and wherein the ratio value of the modified ratio values ​​indicates a blood oxygen level of the skin. In some embodiments, the method includes comparing the ratio values ​​of the plurality of modified ratio values ​​obtained from the subject's skin with the ratio values ​​of the plurality of modified ratio values ​​obtained from an internal organ of the subject, and in response to determining that the ratio values ​​of the modified ratio values ​​are different over a window corresponding to the cardiac cycle, determining that the first and second signals represent signals primarily associated with the internal organs.

[0048] For example, the ratio of ratios of modified ratios can be calculated as follows:

[0049]

[0050] Wherein the first wavelength is shorter than the second wavelength, AC1(t) is the change in the signal level of the first signal I1 at time t, AC2(t) is the change in the signal value of the second signal I2 at time t, I1(t0) is the signal value of the first signal used as a first normalization factor at time t0, and I2(t0) is the signal value of the second signal used as a second normalization factor for a longer wavelength at time t0, 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 ratio R of the modified ratio 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 breathing cycle to determine an averaged ratio level of the modified ratio for one or more of the inspiration, inspiration pause, expiration, and expiration pause phases of the breathing cycle.

[0051] In some embodiments, the method further includes determining a tissue oxygen level value of the internal organ based on a ratio value of the maximum modified ratio values ​​over the systolic and diastolic phases of the cardiac cycle. For example, the method may include determining a time point of diastole termination and a maximum R value based on a determination of the A wave component of the first and second waveforms. The method may include determining a tissue oxygen level value of the internal organ based on a rate of change of the ratio value of the modified ratio over the systolic and diastolic phases of the cardiac cycle.

[0052] 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.

[0053] In some embodiments, the method may include comparing the blood oxygen level to a threshold level; and in response 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.

[0054] In some embodiments, the method may include analyzing a drop in blood oxygen levels during the diastolic phase to determine clinical information.

[0055] In some embodiments, the method may include determining minimal oscillations in blood oxygen levels in a body organ over a plurality of breathing cycles to assess oxygen exchange in the lungs.

[0056] In some embodiments, wherein the internal organ includes lungs, 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.

[0057] In some embodiments, wherein the internal organ comprises lungs; and the method further comprises: determining a maximum blood oxygen level to provide an indication of lung function.

[0058] 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.

[0059] 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 a blood oxygen level is significantly consistent with a template blood oxygen waveform characteristic of an internal organ.

[0060] In some embodiments, the method may include receiving at least one additional signal originating from received light reflected at respective different wavelengths from additional regions 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.

[0061] 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 features of a health condition to diagnose a systemic or regional disease in the subject.

[0062] In some embodiments, assessing health includes monitoring blood flow in an internal organ based on a comparison of the 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.

[0063] 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 central venous pressure and that blood flow is high.

[0064] In some embodiments, wherein when the target organ is the liver, the method may include determining that very high portal blood flow and / or liver hypoxia is present in response to determining that at least one waveform includes a P wave component having a relatively high amplitude.

[0065] 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 an optional 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.

[0066] In some embodiments, the method includes receiving information indicative of an internal organ determined to be 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.

[0067] 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 different 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.

[0068] 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 so that the system performs any of the methods described.

[0069] 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.

[0070] Some embodiments relate to a system for assessing the health of a subject, comprising: any of the devices for determining blood oxygen levels; a memory comprising computer executable instructions; 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 comprises a second device for determining blood oxygen levels, the second device comprising a second light source and a second light detector, the second light detector being configured to receive an additional signal indicating an arterial pulse in the subject's skin, and being configured to provide the additional signal to the processor. In some embodiments, the system comprises one or more second devices for determining blood oxygen levels of internal organs, the one or more second devices comprising a second light source and a second light detector, the second light detector being configured to receive an additional signal indicating a signal from the internal organ, and being configured to provide the additional signal to the processor. In some embodiments, the system comprises one or more second devices for determining blood oxygen levels 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 being configured to receive an additional signal indicating a signal from the second internal organ, and being configured to provide the additional signal to the processor.

[0071] In some embodiments, the device may be coupled to a catheter placed within the body of a subject.

[0072] Some embodiments relate to a method of obtaining data indicative of intracranial pressure of a subject, the method comprising: positioning a light source of any one of the devices proximate 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 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 of the subject based on the waveform of at least one of the one or more signals.

[0073] The method may include determining elevated intracranial pressure of 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, amplitude, and frequency of the one or more oscillations.

[0074] 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.

[0075] Some embodiments relate to a method for assessing the health of a fetus in a subject, the method comprising: receiving one or more signals obtained from received light reflected from a fetal region 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 with information features of the health status to assess the health of the fetus.

[0076] The method may include positioning any 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 of the devices (second device) on any of a forehead, a finger, an ear, and a nose of the subject, to detect a second signal. Comparison of the waveforms may include determining a time 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

[0077] The following embodiments are described in further detail, by way of example, with reference to the accompanying drawings briefly described below. Like reference numerals in the drawings represent like features.

[0078] Figure 1 is a perspective view of an apparatus for obtaining data related to blood oxygen levels of an internal organ of a subject according to some embodiments;

[0079] Figure 2(a) is Figure 1 Side view of the device;

[0080] Figure 2(b) is Figure 1 A top view of the equipment;

[0081] Figure 3 yes Figure 1 A cross-sectional view of the equipment along line AA;

[0082] Figure 4 yes Figure 1 An exploded perspective view of the device;

[0083] Figure 5 is a schematic diagram of a system for obtaining data related to blood oxygen levels of an internal organ of a subject according to some embodiments;

[0084] 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;

[0085] Figure 7 (a) is a graph of first and second signals derived from detected light reflected from the brain of a healthy human subject;

[0086] Figure 7 (b) is based on Figure 7 (a) a graph of a modified ratio of the calculated ratio of the first and second signals;

[0087] 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;

[0088] 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 is substantially the same as Figure 8 (a) A graph of the detected light obtained simultaneously;

[0089] Figure 8 (c) is a graph of first and second signals derived from detected light reflected from the brain of a healthy subject, and Figure 8 (a) A graph of the detected light obtained simultaneously;

[0090] Fig. 9 is a flow chart of a method of assessing the health of a subject according to some embodiments;

[0091] Fig.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;

[0092] Fig.10 (b) is based on Fig.10 (a) a graph of a modified ratio of the calculated ratio of the first and second signals;

[0093] Fig.11 is a graph of first and second signals derived from detected light reflected from a liver of a human subject;

[0094] Fig.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;

[0095] Fig.12 (b) is a graph of first and second signals derived from detected light reflected from the brain of a sheep subject, and Fig.12 (a) A graph of the light reflected from the nose skin obtained simultaneously;

[0096] Fig.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;

[0097] Fig.13 (b) is a graph of first and second signals derived from detected light reflected from the brain of a sheep subject, and Fig.13 (a) A graph of the detected light obtained simultaneously;

[0098] Fig.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;

[0099] Fig.14 (b) is a graph of first and second signals derived from detected light reflected from the brain of a sheep subject, and Fig.14 (a) A graph of the detected light obtained simultaneously;

[0100] Fig.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;

[0101] Fig.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 Fig.15 (a) A graph of the detected light obtained simultaneously;

[0102] Fig.15 (c) is based on Fig.15 (b) a graph of a modified ratio of the calculated ratio of the first and second signals;

[0103] Fig.16 are graphs of first and second signals derived from detected light reflected from the intestine of a healthy human subject;

[0104] Fig.17 is a graph of a modified ratio of calculated ratios of first and second signals derived from detected light reflected from the brains of three human subjects at different levels of systemic hypoxia relative to corresponding blood oxygen levels determined by sampling blood from the internal jugular vein;

[0105] Fig.18is a plot of a modified ratio of a calculated ratio of first and second signals derived from light reflected from a detected 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;

[0106] Fig.19 is a graph of a modified ratio of calculated 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;

[0107] Fig. 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 a number of respiratory cycles;

[0108] Fig. 20 (b) is a graph of first and second signals derived from detected light reflected from the subject's brain, and Fig. 20 (a) A graph of the detected light obtained simultaneously;

[0109] Fig. 20 (c) is based on Fig. 20 (b) a graph of a modified ratio of the calculated ratio of the first and second signals;

[0110] Fig.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 his breath;

[0111] Fig. 22 is a graph of two signals from light at first and second wavelengths reflected from a brain of a human subject, wherein the sensor is placed in the ear canal of the subject; and

[0112] 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 the light detector when the distance between the light source and the light detector and the contact surface of the device is zero (i.e., the light source and the light detector are located in the subject's skin, as is the case with a conventional optical oximeter device).

[0113] Figure 23(b) shows a bar graph of the percentage of successful brain pulse detection using a device with lateral spacing between the center of the light source and the light detector of 10 mm, 15 mm and 20 mm, when the distance between the light source and the light detector and the contact surface of the device is constant at 10 mm (that is, there is a spacing of 10 mm between the light source and the light detector and the subject's skin).

[0114] 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 center of the light source and the light detector, while the distance between the light source and the light detector and the contact surface of the device varied between 0 mm, 5 mm, 10 mm, 15 mm and 20 mm (i.e., the spacing between the light source and the light detector and the subject's skin varied between 0, 5, 10, 15 and 20 mm).

[0115] Fig.24 A bar graph showing the percentage of successful brain pulse detection using a device with a light source and light detector having a center lateral spacing of 10 mm, wherein 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, respectively, offset from the light source). DETAILED DESCRIPTION

[0116] Throughout the specification and the claims that follow, unless the context requires otherwise, the word "comprise" and variations such as "comprising" and "having", will be understood to mean the inclusion of stated integers or steps or combinations of integers or steps but not the exclusion of any other integers or steps or combinations of integers or steps.

[0117] 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.

[0118] 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 way of reference.

[0119] The described embodiments relate generally to devices, systems, and methods for assessing the health of a subject's internal organs.

[0120] Monitoring of internal organs, such as the brain after acute brain injury, typically relies on invasive techniques such as intracranial pressure monitoring, intra-parenchymal 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).

[0121] Non-invasive monitors of brain oxygen levels (e.g., cerebral oximeters that analyze near-infrared light scattering) have been proposed to study the brain. However, cerebral oximetry has not been found to have a significant role in clinical applications, and studies have shown inconsistent results. See, for example, 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 shape of the pulse that represents blood flow within the organ.

[0122] 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 of 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 of blood vessels in the skin. Deoxyhemoglobin (Hb) absorbs more in the red band, while oxygenated hemoglobin 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 light detector. The pulse oximeter determines the AC (pulsatile) component of the absorbance at each wavelength and determines the amount of the red component and the infrared AC component, which indicates the concentration of oxygenated and deoxygenated hemoglobin molecules in the blood. The ratio of oxygenated hemoglobin to total hemoglobin indicates the oxygen saturation of the blood.

[0123] In WO2008 / 134813, the inventors demonstrated that by exploiting the pulsatile properties of deep vascular structures to generate plethysmographic traces, the transmitter and receiver elements can be precisely positioned 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 the technique is used to identify the signal as coming from the vascular structure of interest and filter out signals from other interfering chromophores (e.g., small vessels and surrounding tissue).

[0124] In WO2008 / 134813, the inventors demonstrated that by exploiting the pulsatile properties of deep vascular structures to generate plethysmographic traces, the transmitter and receiver elements can be precisely positioned 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 the technique is used to identify the signal as coming from the vascular structure of interest and filter out signals from other interfering chromophores (e.g., small vessels and surrounding tissue).

[0125] In International Patent Publication No. WO2012 / 003550 (the disclosure of which is incorporated herein by reference in its entirety), the inventors determined that the accuracy and reliability of blood oxygen saturation determined by blood oximetry from deep vascular structures can be improved by adopting 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 an angle of about 45°.

[0126] Monitoring microvascular oxygen levels and blood flow to a patient's internal organs has clinical value because disease may lead to organ failure and cause the patient's death. Early warning of impending organ failure could enable earlier intervention, thereby reducing patient morbidity and mortality.

[0127] 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 reflected light 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, tissue oxygen levels of the internal organs, and corresponding subject health.

[0128] 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 by an area of ​​the subject proximate an internal organ. The inventors have recognized that in order to ensure an accurate assessment of the health of the subject, it is important to ensure that at least one of the signals under consideration actually indicates light reflected from the internal organ rather than the overlying skin. Accordingly, the described embodiments relate to determining that the waveform of at least one signal represents a signal that is 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.

[0129] 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 associated primarily with received light reflected from the internal organ. For example, in response to determining that the received signal is not associated primarily with received light reflected from the internal organ, a processor of the system can be configured to output an instruction for relocating or positioning 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.

[0130] 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.

[0131] For example, the waveform can be compared to one or more template waveforms (characteristics of typical or healthy internal organs) to determine whether the waveform is similar enough to the template waveform 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 in the signal are expected, and therefore, 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 an earlier waveform 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 calculation of a corrected ratio of the ratio is performed on 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 a determination. In this case, at least two signals are required to perform the calculation of the corrected ratio of the ratio, and the at least two signals are derived from the received light reflected from the area of ​​the subject at two different wavelengths.

[0132] Once it has been determined that the at least one signal represents a signal primarily associated with an internal organ, the 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 information features of a health condition to assess the health of the subject. For example, such health conditions can include increased intracranial pressure, respiratory disorders, liver failure, heart failure (e.g., heart valve leakage), cerebral hematoma, intestinal ischemia and / or pulmonary hypoventilation, and / or health conditions associated with internal organ movement.

[0133] In some embodiments, calculation of a modified ratio of a ratio is performed on data acquired from at least two waveforms acquired from an internal organ to perform a health assessment.

[0134] Some embodiments relate to apparatus, systems, and methods for assessing the health of a subject 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 are primarily indicative of instantaneous blood flow changes within the pulse duration of blood in the organ's microcirculation. This can be accomplished, 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 levels. Data derived from the waveform corresponding to the signal primarily indicative of blood flow in the internal organ can be used to make health assessments based on the properties of blood flow in the organ and circulatory system.

[0135] Some embodiments relate to apparatus, systems, and methods for obtaining data related to any one or more of: microvascular blood oxygenation levels, 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 corresponding subjects, including determining absolute microvascular blood oxygen saturation, microvascular blood pulse shape and amplitude, and motion of a subject's internal organs.

[0136] 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 level of an internal organ. The apparatus 100 includes a body 110 including a contact surface 111 for contacting a subject 520 (see FIG. 5 ) near a target internal organ (e.g., a brain 521) of the subject 520. Figure 5 ) join.

[0137] 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 separated from the first groove 112.

[0138] 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 tissues / 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., spacing S) such that the received or detected light indicates the blood oxygen level in the blood vessels of the internal organ (e.g., veins on the surface 524 or the microvessels of the brain 521).

[0139] The device 100 differs from a standard cerebral oximeter because the light source 120 and the light detector 130 are not in contact with the skin and have a small separation distance from each other (unlike what is taught in the prior art). The inventors have determined that these changes reduce light scattering through the skin and maximize the light that reaches the light detector 130 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 the skin. In addition, through our knowledge of the expected pulse waveform and oxygen level 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.

[0140] Existing cerebral oximeters have a spacing of at least 40 mm between the light source and the light detector, as it is considered important to have a larger spacing to be able to detect light reflected from deep in the brain. However, the inventors have found that a shorter spacing provides an improved signal from the organ, reducing the skin signal.

[0141] The light source 120 may include a light emitting region (eg Figure 4 432 in FIG. 1 ), and the light detector 130 may include a photosensitive area (such as Figure 4 433 in FIG. 4). Figure 4 In the illustrated embodiment, 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 each other, 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.

[0142] 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 the light source 120 is also the center of the light emission area, and the center of the light detector 130 is also the center of the photosensitive area, but in other embodiments, the body of the light source 120 surrounds the light emission area, and the body of the light detector 130 surrounds the photosensitive area. For example, in one aspect, the center points of the light source 120 (or light emission area) and the light detector 130 (or photosensitive area) are spaced about 10 mm to about 20 mm, such as about 15 mm, and the spacing S between the nearest peripheries of the light source 120 and the light detector 130 is about 4 mm to about 20 mm, such as from about 6 mm to about 8 mm or about 7 mm. In some embodiments, the diameter of the light source 120 and the light detector 130 is about 8 mm in each case.

[0143] The light emission region of light source 120 may be set back from contact surface 111 by spacing Y. Thus, when contact surface 111 engages subject 520, body 110 of the device may help space the light emission region from subject 520.

[0144] In some embodiments, light detector 130 may include a photosensitive region (not shown) that is set back from contact surface 111 by spacing Y. Thus, when contact surface 111 engages subject 520, body 110 of device 100 may help space the photosensitive region from subject 520.

[0145] The spacing Y may be in the range of about 1 mm to about 20 mm. In some embodiments, the spacing Y may be in the range of about 7 mm to about 10 mm. The spacing Y may 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).

[0146] 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. Fig.24 The efficacy of this embodiment is demonstrated.

[0147] The first and second grooves 112, 113 may have a depth D extending from the base 115 to the plane defined by the contact surface 111. The depth D may be in the range of about 1 mm to about 10 mm. The depth D may 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 may be slightly less than the spacing Y (also referred to as "set back").

[0148] In some embodiments, the body 110 further includes a wall 114 separating the first groove 112 from the second groove 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 to be reflected or scattered to the light detector 130 without first interacting with the internal organs. The wall height WH of the wall can be at least about 2 mm. In some embodiments, the wall height is about 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 about 1 mm to 2 mm. The wall thickness WT can be, for example, about 1.8 mm.

[0149] The light source 120 may be configured to emit light including at least two discrete wavelengths. For example, the first discrete wavelength may be centered at about 895 nm or about 940 nm or about 945 nm (longer wavelength or first wavelength), and the second discrete wavelength may be centered at about 660 nm (shorter wavelength or second wavelength). The emitted light may include light having wavelengths in at least two discrete narrowband wavelengths.

[0150] In some embodiments, the shorter wavelength light may include light having a wavelength in the range of about 600nm to about 750nm. For example, the shorter wavelength may include a wavelength centered at about 660nm and ranging between about 640nm and about 680nm. The longer wavelength light may include light having a wavelength in the range of about 850nm to about 1000nm. For example, the longer wavelength may include a wavelength centered at about 895nm and ranging between about 855nm and about 945nm. In some embodiments, the longer wavelength is about 940nm. The shorter wavelength light is absorbed more by blood having low blood oxygen saturation (or low blood oxygen level) than the longer wavelength light. The longer wavelength light is absorbed more by blood having high blood oxygen saturation (or high blood oxygen level) than the shorter wavelength light. Therefore, the different intensities of each wavelength band are reflected by the internal organs to be received and detected by the light detector 130. This principle is used to determine the blood oxygen level and is explained in further detail below.

[0151] Light in the range of about 640 nm to about 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. Thus, light reflected from internal organs (or blood vessels associated with internal organs) at these wavelengths is affected by blood oxygen levels, and the intensity of the received light can (in combination with light of longer wavelengths) be used to determine blood oxygen levels.

[0152] 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 deoxygenated blood. Thus, light reflected from internal organs (or blood vessels associated with internal organs) at these wavelengths is affected by blood oxygen levels, and the intensity of the received light can be used (in combination with shorter wavelength light) to determine blood oxygen levels.

[0153] Light in the range of about 780 nm to about 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.

[0154] In some embodiments, the light source 120 is configured to emit light in a narrow intermediate wavelength band with a wavelength in the range of about 780 nm to about 820 nm. The light source 120 can be configured to emit light with a wavelength concentrated at about 805 nm. The amount of light in the intermediate wavelength band is absorbed by the blood but is not sensitive to the oxygen saturation of the blood. For example, the light source 120 may include a third LED adapted to emit light in the narrow intermediate wavelength band.

[0155] The light source 120 may include one or more semiconductor diodes, such as light emitting diodes. The light detector 130 may also include one or more semiconductor diodes. The light source 120 and the light detector 130 may generally be shaped as short cylinders, such as a pill shape. The light source 120 and the light detector 130 may have a diameter Z of about 8 mm.

[0156] The light source 120 can have an optical power output of up to about 20 milliwatts (mW). In some embodiments, the 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, the 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 more than 20 mW.

[0157] 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.

[0158] 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.

[0159] The light detector 130 may be configured to generate one or more signals indicating 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.

[0160] The optical detector 130 may be similar to the optical detector 130 provided by Medtronic in the Nellcor TM PIN photodetector used in the Maxfast forehead sensor.

[0161] In some embodiments, the device 100 includes at least two optical waveguides (e.g., optical fibers). Thus, the light emitting region of the light source 120 may include an end of a first optical waveguide (not shown) located in the first groove 112. The light detector 130 may include a second optical waveguide (not shown), one end of which is located in the second groove 113, and the photosensitive region may be located outside the body 110 of the device 100.

[0162] refer to Figure 3 and Figure 4 , the body 110 of the device 100 can be formed from multiple components, including a base 115 and a spacer 116.

[0163] 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 Figure 2a ).

[0164] 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 the 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.

[0165] 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.

[0166] 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 in 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 about 21 mm. In some embodiments, the frame height FH may be less than about 11 mm. The frame height FH may be about 8.5 mm. The frame 450 may have a frame length FL of about 30 mm and a frame width of about 13 mm. The frame 450 may be formed of a rigid material, for example, a polymer (e.g., ABS).

[0167] The frame 450 may define a first hole 452 that enables light from the light source 120 to be emitted from the first recess 112 and a second hole 453 that enables 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 upper portions (light emitting area) 432, (photosensitive area) 433 of the light source 120 and the light detector 130 to protrude into the corresponding first and second recesses 112, 113, respectively.

[0168] 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.

[0169] 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.

[0170] 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 apart from the external surface.

[0171] 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.

[0172] 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.

[0173] At 608, the device 100 generates a first signal indicating the intensity of the light of the first wavelength and a second signal indicating the intensity of the light of the second wavelength. For example, the first wavelength can be about 660nm and the second wavelength can be about 895nm. In some embodiments, the device 100 also generates a third signal indicating the intensity of the light of the third wavelength. For example, the third wavelength can be in the range of about 780nmd to about 820nm or about 805nm.

[0174] In some embodiments, the first device 100 is located near the internal organs of the subject, targeting the internal organs 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 organs. For example, the light generated 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.

[0175] 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 found that by separating the light source 120 from the outer surface (e.g., skin) of the subject 520 so 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.

[0176] Positioning the device to the target brain

[0177] In some embodiments, where the internal organ being evaluated is the brain, the device 100 may be located at a location on the scalp where the skull is relatively thin compared to other locations of the skull. For example, suitable locations may include the temples, occipital bones, orbits, parietal bones, and forehead regions of the skull.

[0178] 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 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.

[0179] In some embodiments, the device 100 is located at a position above the intergyral sulcus 521 of the brain of the 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, since each arterial pressure pulse of the 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 the 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 the subject, the signal from the device can be used to determine and / or monitor intracranial pressure changes in the brain.

[0180] Positioning the device to the target lung

[0181] In some embodiments, device 100 may be arranged to be located on the upper lateral bone, the supraclavicular space, or between the ribs of subject 520 so that device 100 is close to the lungs of subject 520 to obtain data indicative of blood oxygen levels in the lungs.

[0182] Positioning the device to the target liver

[0183] Device 100 may be positioned below the ribs in the right upper abdomen 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.

[0184] Positioning the device to the target intestine

[0185] Device 100 may be arranged to be located on the abdomen or any lower abdomen of the subject so that device 100 is proximate to the intestines of subject 520 to obtain data indicative of blood oxygen levels of the intestines.

[0186] Positioning the device to the target kidney

[0187] Device 100 may be arranged to be positioned on the back of the subject so that device 100 is proximate to the kidneys of subject 520 to obtain data indicative of the blood oxygen level of the kidneys.

[0188] 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.

[0189] Position the device in the right ventricle of the target heart

[0190] The device 100 may be arranged, for example, to be located on the sternum of the chest or along the left edge of the sternum where it intersects with the ribs, targeting the right ventricle of the heart.

[0191] Position the device to the target fetus

[0192] The device 100 can be arranged to be located on the abdomen of the subject 520 so that the device 100 (transabdominal sensor) is close to the uterus (uterus) of the subject 520 to obtain data indicating the blood oxygen level of the internal organs of the fetus in the uterus. The fetus has a different heart rate, rhythm, and pulse shape than the mother. The fetus also has a different blood oxygen level than the mother.

[0193] In some embodiments, the device 100 may include a light source adapted to be positioned within the vagina of the mother so that light can be projected onto the brain of the fetus, thereby enabling measurement of brain oxygen levels during labor of the fetus.

[0194] 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 so that more accurate results that are more representative of the entire organ can be obtained. 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 of the skin and from each hemisphere 521 of the brain.

[0195] The device 100 may be configured to simultaneously determine data from multiple organs or parts of the body as well as the skin. This may 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 motion. This allows for a determination of whether changes in blood flow or oxygen levels are systemic (occurring at multiple parts) or localized (occurring at only one part).

[0196] 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 device 100. The system 500 may include a computing device 560, the computing device 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 device 100. For example, the device 100 may be connected to the processor 562 via a conductive cable 140 or wirelessly.

[0197] In some embodiments, the system 500 may further include a second device 550 for determining data indicating blood oxygen level. The 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 time and characteristic waveform of the arterial pulse of the subject 520. The second light detector is configured to transmit data representing the additional signal to the processor 562. In some embodiments, the processor 562 may be configured to receive the first and second signals from the first device 100 and the third signal from the second device 550.

[0198] The second light source may be adapted to generate the above-mentioned 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.

[0199] 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 a forehead, nose, ear, or finger, and receive light transmitted through that portion of subject 520.

[0200] The second device 550 can be positioned on or near an external surface (e.g., skin) of the subject 520 at a location spaced apart from the location of the first device 100, so 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.

[0201] 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.

[0202] 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 health determinations about the subject.

[0203] 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) signals 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 light reflected by the subject's skin as well as light reflected by the target internal organ.

[0204] The described embodiments provide a more accurate assessment of the health of a subject 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.

[0205] For some internal organs, a signal with characteristics of a venous circulation is expected, so the waveform can be compared to a typical venous signal (which has the characteristics of the waveform of a central venous blood pressure trace or a measured venous waveform) to determine that the signal is primarily related to the internal organ. This will refer to Figure 7 and Figure 8 Further explained, 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 a waveform associated with a single signal.

[0206] 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 an internal organ at a second relatively shorter wavelength. In this example, the first wavelength is approximately 895nm and the second wavelength is approximately 660nm. 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 the light detected by the light detector 130 and is plotted as a function of time.

[0207] 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 show a plurality of peaks and troughs representing intensity levels over time and indicating the subject's pulse. The signals 701, 702 may be described as pulsatile signals and / or plethysmographic signals.

[0208] In some embodiments, the second conventional device 550 may be located at a location spaced apart from the 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, fingers, ears, and nose of the 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 locations.

[0209] 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, the fourth relatively shorter wavelength being 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 a plurality of peaks and troughs representing intensity levels varying over time. The third and fourth signals 803, 804 are 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.

[0210] Figure 8 (b) shows an example of a fifth waveform of a fifth signal 805 and a sixth waveform of a sixth signal 806, the fifth signal originating from measured light reflected from the internal jugular vein at a fifth wavelength, and the sixth signal originating from measured light reflected from the internal jugular vein at a sixth relatively shorter wavelength, the sixth relatively shorter wavelength being generated by the second device 550. In this example, the fifth wavelength is approximately 895nm and the sixth wavelength is approximately 660nm. The fifth and sixth waveforms of the corresponding fifth and sixth signals 805, 806 show multiple peaks and troughs representing intensity levels varying over time. The fifth and sixth signals 805, 806 represent pulsating venous circulation signals because the second device 550 is placed above the internal jugular vein of the subject 520. The fifth and sixth signals 805, 806 shown represent the shape of venous blood pressure changes typically observed in large veins when monitoring pressure levels. That is, the fifth and sixth waveforms are characteristic of venous circulation pressure signals.

[0211] 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 signals 801, 802 represents the intensity of 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 (such as Figure 8 (b)). Therefore, it can be inferred that the first and second signals 801, 802 are likely to 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 is different from the skin signal waveform and can be used to determine that the signal comes from the brain rather than the skin.

[0212] 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 of a vein (venous signal).

[0213] 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 diastolic phase of the cardiac cycle due to atria contraction. The C wave component can be observed as a small trough superimposed on the signal value of the waveform after the minimum signal value of the A wave. This typically occurs at the beginning of the systolic 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 diastolic phase of the cardiac cycle as blood empties from the heart, and therefore occurs during the systolic phase. The V wave component can be observed as a trough superimposed on the signal value of the waveform after the X wave and the peak signal value. The V wave typically occurs during the late systolic phase of the cardiac cycle due to filling of the atria of the heart. 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 diastolic phase of the cardiac cycle as the ventricles of the heart begin to fill.

[0214] 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.

[0215] As shown in the following figures, signals indicating light reflected from internal organs (e.g., 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 features may not be present.

[0216] 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.

[0217] In some embodiments, an additional signal (e.g., Figure 8 (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 a 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 light reflected from the subject's skin is any of the following wavelengths: about 660 nm, about 805 nm, about 895 nm, or about 940 nm.

[0218] One or more signals from or primarily associated with 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 Fig. 20Depicted, 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 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.

[0219] In some embodiments, a ratio of modified ratios may be calculated from the signal levels of two or more signals on corresponding waveforms. The ratio of modified ratios indicates the blood oxygen level and may 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.

[0220] To compare two or more waveforms, such as waveforms and signature waveforms associated with signals from internal organs, preferably the same portion or window of the pulsatile signal is compared. Figure 7 In some embodiments, the beginning of the waveform window may be determined as at a peak signal level 707 of the second signal 702, and the end of the waveform window may be determined as at a minimum signal level 708 of the second signal 702. In some embodiments, the end of the waveform window may be determined as at a subsequent peak signal level 709 of the second signal 702. The window of the waveform may include a time-limited segment of the signals 701, 702, 801, 802, 803, 804. For example, the window of the waveform may include a segment of the signals 701, 702, 801, 802, 803, 804 from a first extreme value of the signal level to a second extreme value of the signal level (or immediately before the second extreme value). The window may, for example, include a segment of the signals 701, 702, 801, 802, 803, 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 a segment of the 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 start at the X wave and end at the trough of the A wave.

[0221] In some embodiments, the determination of the start and end of the window for comparing the waveform of the signal can be determined using the waveform (or signal level) of another signal, such as the arterial signal 803, 804 or the jugular vein signal 805, 806. For example, the window of the waveform can be determined to start at the peak signal level of the individual signal and end at the minimum signal level of the individual signal. The individual signal can originate from light with a wavelength in the range of about 780nm to about 820nm.

[0222] In some embodiments, analysis of waveforms from additional signals may also be used to determine the timing of the systolic and diastolic phases of the cardiac cycle. This may be useful in situations where it is not particularly easy to determine the phase of the cardiac cycle based on the waveforms of one or more signals. 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 simple.

[0223] The waveform may include discrete portions of the corresponding signal within a specific time period. In some embodiments, the waveform may include a portion of the wavelength of the signal indicating only a portion of the pulses of the subject, may include the wavelength of the signal indicating a single pulse of the subject, or may include multiple wavelengths of the signal indicating multiple pulses. Once the window or waveform is determined, an average or summed waveform may be generated from the multiple waveforms to improve the signal-to-noise ratio. In some embodiments, a window function may be applied to the first and / or second signal to derive the corresponding first and second waveforms. For example, the window function may include a rectangular, triangular, smooth and / or bell curve function.

[0224] In some embodiments, the waveform of one or more signals is selected based on the waveform (or signal level) of another signal, the other signal originating from a third wavelength of light in the range of about 780nm to about 820nm. The waveform may start, for example, when the peak signal level of the third signal reaches the minimum signal level of the other signal. Light having a wavelength in the third wavelength range is sensitive to blood, but is not sensitive to changes in blood oxygen levels, and thus can provide a more reliable signal to determine the phase of the cardiac cycle and the shape of the waveform from the 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 with a wavelength of about 805nm 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 represents a given organ.

[0225] although Figure 7 , Figure 8 and Figures 10 to 16 and Fig. 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.

[0226] Reference now Fig. 9 , a process flow diagram of a computer-implemented method 900 of assessing the health of a subject 520 is shown, according to some embodiments. The method 900 may be implemented by the processor 562 executing instructions stored in the memory 568.

[0227] At 902, processor 562 receives one or more signals. The one or more signals originate from received light reflected from region 522 of subject 520 proximate internal organ 521 at first and second wavelengths, respectively. For example, the received light may include emitted light that has interacted with internal organ 521.

[0228] At 904, the 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 the internal organ 521. Determining whether one or more waveforms represent signals associated with an internal organ is discussed in more detail below.

[0229] 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 may output an error or control signal. For example, a control signal may 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 may be configured to automatically reposition the light source 120. In some embodiments, the system may be configured to instruct the operator to reposition the device relative to the target internal organ. Once repositioned, the updated one or more signals may be provided to the processor 562 for processing.

[0230] 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.

[0231] 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 an audible alarm is sounded. 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.

[0232] In some embodiments, processor 562 may be configured to display one or more of: oxygen levels throughout the systolic and diastolic phases of each cardiac cycle, estimated tissue oxygen levels of an organ (based on trough levels 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 may be used to identify diseases of microvascular blood flow in an organ, movement of organs (brain, liver, lungs, and heart) 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.

[0233] As previously mentioned, the inventors have recognized that waveforms associated with signals primarily from (or primarily associated with) internal organs exhibit specific characteristics and are generally significantly different from waveforms associated with signals primarily from (or primarily associated with) skin. In some embodiments, the processor 562 is configured to create or generate one or more templates of a specific internal organ based on one or more signals received from the device 100 when the device 100 is arranged to target a specific internal organ. In some cases, the operator can arrange the device 100 relative to a specific internal organ and analyze the waveform generated from the received signal to verify that the signal represents the internal organ. Based on the characteristic waveform of the specific internal organ determined, a template of a specific internal organ can be created using multiple signals originating from one or more subjects. Therefore, one or more templates stored in the memory 568 can be based on a library or database of characteristic waveforms previously obtained from a specific internal organ. The database may include multiple characteristic waveforms, each of which is associated with a specific internal organ. For example, the database may include characteristic waveforms of any one or more of the following: brain, fetal brain, lungs, liver, kidneys, intestines, skeletal muscle, heart, and fetal heart. Each characteristic waveform may 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 an 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.

[0234] In some embodiments, the processor 562 may receive information indicating an internal organ that is targeted by the device 100. The processor 562 may use the information indicating that the internal organ is targeted to help determine that one or more waveforms represent signals primarily associated with the targeted internal organ. The processor 562 may also use the information indicating that the internal organ is targeted to help determine a health condition. For example, the processor 562 may use information about the type of internal organ to select a template corresponding to the associated target internal organ, thereby reducing processing time. In some embodiments, the processor 562 may therefore only compare one or more waveforms to templates associated with a known target internal organ.

[0235] Determine if the waveform represents a signal primarily related to internal organs

[0236] In some embodiments, the memory 568 includes one or more templates, each template including information features of a specific internal organ, and in some embodiments, including features of a typical or healthy internal organ. For example, the template may depict a characteristic waveform of light intensity relative to time. The template may include a ratio of a modified ratio or a characteristic curve graph of blood oxygen level. The processor 562 may be configured to compare at least one or more waveforms with one or more template waveforms to determine whether it represents a signal primarily associated with the internal organ 521. The comparison may, for example, include calculating the difference between the waveform and the template waveform, and comparing the difference with a threshold to determine the possibility that the signal is primarily associated with the internal organ. The difference between multiple template waveforms may be calculated to determine the best fitting template waveform. The determination may include, for example, calculating the minimum sum of squared residual fit. If the sum of squared residuals is less than a threshold error value, the processor 562 may determine that the waveform represents (or is a good match) a signal primarily associated with the internal organ 521.

[0237] In some embodiments, 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 internal organs. For example, as described above, a venous waveform typically includes A, C, X, V, and / or Y wave components.

[0238] In some embodiments, an additional or third waveform may be derived from an additional signal obtained from the second device 550. The additional waveform may, for example, represent an arterial skin pulse obtained from a location away from or around an internal organ. The additional waveform may 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 is therefore not a signal associated with the internal organ 521, but is more likely to be from the skin.

[0239] 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 may 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 offset in time from a corresponding signal peak 808 of the additional waveform. For example, one or more waveforms may 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 indicates the beginning of the waveform).

[0240] In some embodiments, where 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, a ratio of the modified ratios may be used to determine whether the first and second signals represent signals associated with an internal organ, or to determine a health condition of the subject 520. This will be discussed in detail below.

[0241] Signal Waveform-Brain

[0242] If the internal organ 521 is the brain, then the one or more signals indicating light of a different wavelength and associated with the brain are expected to be similar to venous signals. Thus, in some embodiments, determining that at least one waveform represents a signal primarily associated with the internal organ includes determining that at least one waveform corresponds to a waveform of a venous pulse. In other embodiments, determining that at least one waveform represents a signal primarily associated with the internal organ includes determining that at least one waveform does not correspond to a waveform of an arterial pulse.

[0243] In some embodiments, 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 660nm. When the target internal organ is the brain, the second signal 702, 802 from the light reflected by the brain at a second wavelength of approximately 660nm may more consistently represent the venous signal. Therefore, in some embodiments, the processor 562 uses the second signal 702, 802 to determine whether the waveform represents a signal primarily associated with the brain. In some embodiments, the first wavelength is approximately 805nm. The calculated change in oxygen level or the ratio of the corrected ratio may also be used as a template for this purpose, which will be discussed below.

[0244] 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).

[0245] 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.

[0246] In some embodiments, the processor 562 may analyze one or more waveforms to deconvolute components from the waveforms. The processor 562 may analyze the components to determine a gradient or rate of change and compare 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).

[0247] It is contemplated 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. Thus, in response to determining that a signal peak 807 of at least one of the corresponding waveforms of the one or more signals is temporally offset from a corresponding signal peak 808 of another waveform of another signal, processor 562 may determine that at least one of the corresponding one or more signals represents the brain.

[0248] Fig. 22 A first signal 4401 (approximately 895 nm) and a second signal 4402 (approximately 660 nm) obtained from the device 100 located in the ear canal of a human subject are shown. In this case, the processor 562 can be configured to determine that at least one waveform represents a signal primarily related to the brain by analyzing the second signal 4402.

[0249] Signal Waveform-Lungs

[0250] It has been found that the signal derived from the light reflected by 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. The blood flow may depend on the postural position of the person. Unlike other organs of the body, oxygen levels drop during systole and rise during diastole. In addition, the variation in oxygen levels during the pulse period is very large.

[0251] 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.

[0252] refer to Fig.10 (a) shows an example graph of a first signal 1001 from measured light reflected from an internal organ at a first wavelength (e.g., 895 nm) and a second signal 1002 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.

[0253] like Fig.10 As shown in (a), a first signal 1001 (895 nm) obtained from the ventilated lung represents a venous signal. The first signal 1001 includes A-wave, C-wave, X-wave, V-wave and Y-wave components.

[0254] Thus, in some embodiments, determining by the processor that the at least one waveform represents a signal primarily associated with an internal organ being the lungs may 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 may include comparing the first and / or second waveform to a typical or measured venous pulse waveform to determine a measure of consistency, or comparing the first and / or second waveform to a measured arterial pulse waveform of a subject to determine a measure of inconsistency.

[0255] Again, as described above, determining that at least one of the one or more signals represents a signal primarily associated with an internal organ may 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 may, for example, involve deconvolving the component from the waveform.

[0256] In some embodiments, the processor 562 can be configured to determine that the pulse shape of the waveform of the 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 representing 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 diastolic phase), the second rate having a smaller amplitude than the first rate.

[0257] 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.

[0258] In some embodiments, the processor 562 can be configured to determine that the pulse shape of the waveform of the signal from light of about 660 nm wavelength has a characteristic pulmonary pulse shape, wherein the light of about 660 nm wavelength is particularly sensitive to changes in deoxygenated blood levels. For example, the characteristic pulmonary pulse shape can include a waveform representing an 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.

[0259] Fig.21 Two signals 2601 are shown, including multiple pulses obtained when the subject breathes in region 2602, and then when the subject holds their breath in region 2603. It can be seen that the waveform (pulse) in region 2603 is more uniform in intensity range than the two signals 2601 in region 2602. In some embodiments, the 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.

[0260] Signal Waveform-Liver

[0261] refer to Fig.11 , shows an example graph of first and second signals 1101, 1102 received from a device 100 placed near the liver on 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).

[0262] As shown, A-wave, C-wave, and X-wave components may be observed in the first and second waveforms of the first and second signals 1101, 1102, respectively. In some embodiments, a V-wave component may also be observed. The waveforms of the first and second signals 1101, 1102 may also include additional small wave valleys (including the P-wave of the P1 wave and the P2 wave). The P1 wave may indicate a contribution to the first and second signals 1101, 1102, the first and second signals being derived from light reflected from a portal vein contraction pulse. The P2 wave may indicate a contribution to the first and second signals 1101, 1102, the first and second signals being derived from light reflected from a portal vein relaxation pulse. The presence of the P1 wave and / or the P2 wave appears to be unique to signals from the liver; it is not observed in other organs.

[0263] Thus, in some embodiments, determining by processor 562 that at least one waveform of the 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.

[0264] As described above, determining that at least one of the one or more signals represents a signal primarily associated with an internal organ such as the liver may include comparing components of the waveforms of the first and / or second signals to template waveform features of the liver, and may, for example, involve deconvolving the components from the waveforms.

[0265] In some embodiments, determining, by processor 562, that the at least one waveform represents a signal primarily associated with an internal organ being the liver may include determining that the at least one waveform includes at least one of an X-wave and a P-wave.

[0266] 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 representing 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 (X-wave component), followed by a second component having a signal level that generally decreases at a second rate (leading edge of diastolic phase), the second rate having a smaller amplitude than the first rate.

[0267] 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.

[0268] The P wave component of the liver trace may also result in characteristic components in the calculated corrected ratio of the ratio and the blood oxygen level, as discussed later. The processor 562 may determine that the signal represents a signal from the liver based on the presence of these characteristic components.

[0269] Signal waveform-intestinal

[0270] Fig.16 An example graph 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) is shown. The first and second signals 1601, 1602 are obtained from a device 100 placed on a subject 520 near the intestine.

[0271] The plethysmographic signal from light reflected by the intestine may resemble pressure changes 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 may be due to the fact that the venous pulsation must pass through the liver to reach the portal vein and then the microcirculation of the intestine. 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 significant. Therefore, the peak or maximum light intensity level of the pulse is very delayed and occurs in the late systolic period relative to the forehead skin pulse.

[0272] 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, Y waves, and these waves can be delayed relative to the corresponding waves in the skin and liver. In some embodiments, determining by the 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.

[0273] As with the brain and liver, the quality of gut-related signals may improve if subjects hold their breath.

[0274] In some embodiments, the processor 562 can determine the health of the intestine based on a comparison with a characteristic waveform similar to Fig.16 For example, the deviation from the characteristic waveform can be used to diagnose any one or more of the following diseases: ischemic hepatitis, liver cirrhosis, abdominal compartment syndrome, portal vein thrombosis, portal hypertension.

[0275] Signal Waveform-Kidney

[0276] Measured light reflected from the kidney at a first wavelength of about 895 nm and at a relatively shorter second wavelength of about 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.

[0277] The kidneys have very high arterial blood flow compared to other organs. Therefore, the pulse shape of the waveform of the first signal from light having a wavelength of approximately 895 nm is characteristically and unsurprisingly arterial, with a significant minimum level of contraction. In contrast, the waveform of the second signal from light having a wavelength of approximately 660 nm is relatively flat. However, the A, C, X, V, and Y wave components are discernible. The flat waveform may be due to the high oxygen level throughout the pulse.

[0278] 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 kidney includes determining that the waveform is characteristically arterialized, with 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 kidney 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 kidney includes determining that a pulse shape of the waveform substantially corresponds to a characteristic kidney pulse shape.

[0279] Signal Waveform-Fetus

[0280] The pulsatile signals emitted by the fetus differ from those emitted by 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, about 120-160 beats per minute compared to the mother's 70 beats per minute. The fetus has lower oxygen saturation levels. Arterial saturation in the fetal brain is low at about 90% (100% in the mother), and other organs are even lower at about 65% (100% in the mother). Thus, venous oxygen saturation levels are very low, between 25% and 40% (75% in the mother). Finally, the shape of the pulse waveform is different because the fetus has very low blood pressure and circulatory function is different from that of the mother. The fetal brain provides an ideal target because of the high blood flow relative to the blood flow in the mother's overlying tissues, including the skin, abdominal muscles, or cervix.

[0281] 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.

[0282] Signal Waveform-Muscle

[0283] Light reflected from the gastrocnemius muscle of a human subject at rest at a first wavelength of about 895 nm and a second relatively shorter wavelength of about 660 nm can be used to assess muscle health. A third signal from light having a wavelength of about 895 nm and a fourth signal from light having a wavelength of about 660 nm can be utilized, the third and fourth signals being from simultaneous recordings of the subject's forehead skin. At rest, muscle blood flow is low and is therefore characterized by a low pulse amplitude of the signal. The pulse shape is arterial in nature because skeletal muscle has relatively few venules relative to other organs.

[0284] 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 muscle includes determining that: the waveform determines 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 associated with muscle includes determining that the waveform depicts a signal having a relatively low pulse amplitude and which is substantially arterial in nature.

[0285] Assessing the health of the subject based on the waveform

[0286] As above reference Fig. 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 with information features of a health condition to assess the health of subject 520.

[0287] For example, in some embodiments, one or more waveforms of one or more received signals associated primarily with light reflected from a target internal organ may be compared to one or more characteristic pulse shapes of a corresponding healthy internal organ (e.g., which may be stored in a memory as a template). The processor may 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).

[0288] Further described embodiments involve evaluating one or more waveforms to determine the likelihood that a subject has various conditions, including organ disease associated with low microvascular oxygen levels or abnormal blood flow or abnormal motion. Examples include increased intracranial pressure (ICP), cerebral hemorrhage, stroke, ischemic hepatitis, pneumonia, intestinal ischemia, heart failure.

[0289] Pulsatile blood flow in the microcirculation of an organ may reflect differences in microvascular arteriolar pressure levels that facilitate blood flow and microvascular venous pressure levels that hinder blood flow during periods of the cardiac cycle. 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 from light reflected by the internal organ. A relative increase in systemic venous circulation pressure levels is associated with a plethysmographic signal that displays dominant or exaggerated features similar to 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 the organ.

[0290] Analyzing the waveform from 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 arterial and venous circulation diseases. Such systemic circulation diseases 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, arterial thrombosis, which may occur in a stroke.

[0291] Heart failure

[0292] The measured light reflected from the brain of a human subject at a first wavelength of about 895 nm and a second wavelength of about 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.

[0293] 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 by brain 521. Processor 562 can derive data from a waveform indicating a significant V wave component and compare the derived data to a template waveform feature of a signal representing a 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 features of the waveform will be significant.

[0294] 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.

[0295] Intracranial pressure (ICP)

[0296] refer to Fig.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 through an anterior burr hole to increase the intracranial pressure of the sheep to a range of about 50 mmHg to about 90 mmHg. Fig.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 about 895 nm and the fourth signal being from light having a wavelength of about 660 nm, both obtained from the skin of a sheep's nose, and Fig.12 The first and second signals of (a) are substantially simultaneous and represent arterial skin signals.

[0297] 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 (falling 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 features (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, as there is a significant lag in the start of the pulse compared to the skin signal, as shown in FIG. Fig.12 Indicated by the double-ended arrow in (b).

[0298] Therefore, it has been determined that this change in the waveform that has certain arterial characteristics in shape may indicate an increase in intracranial pressure. This is due to the increase in cerebral arterial pressure to maintain adequate blood flow, and the pulse waveform develops a more arterial shape because the arterial pressure is much greater than the central venous pressure. These two pressures affect the shape of the pulse waveform.

[0299] 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 one or more waveforms substantially represent the template waveform. This may include, for example, calculating a residual sum of squares. In response to determining that at least one waveform represents the template waveform, processor 562 may 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.

[0300] In some embodiments, processor 562 may 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 (see, for example, Fig.12 1211), the corresponding signal is from the 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 can determine that the subject 520 may have a relatively high intracranial pressure.

[0301] 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 the light detected from brain 521 to determine whether there is a V wave and / or a Y wave component. In response to determining that there is no V wave and / or a Y wave component, processor 562 may determine that subject 520 may have relatively high intracranial pressure.

[0302] Disorders associated with relatively elevated pressure levels in the pulmonary or systemic arterial circulation

[0303] 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 displays some features 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 the features from the pulmonary arterial pressure waveform, including prominent systolic pulses, diastolic pulses, and dicrotic notches (which may coincide with the V and Y waves).

[0304] In some embodiments, processor 562 can analyze the waveform shape of the signal of detected light originating from the target internal organ to determine health conditions associated with a relative increase in systemic arterial circulation pressure levels relative to central venous pressure levels, such as systemic hypertension and local organ diseases, 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 to a template waveform or data characteristic of such a health condition to determine the likelihood that the subject exhibits the health condition.

[0305] Diseases associated with increased arterial pressure levels can also be detected, such as hypertension, in which case the waveform develops into a more arterialized pulse shape. Other diseases include increased intracranial pressure in the brain and compartment syndromes in other parts of the body, such as in the abdomen or calves. 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 pressure levels in the pulmonary arteries (interstitial lung damage, ARDS, pulmonary embolism) or increased pressure levels in the pulmonary veins (left-sided heart failure).

[0306] Diseases associated with relatively elevated systemic venous pressure levels

[0307] 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.

[0308] A relative increase in systemic venous pressure levels is associated with a 660 nm or 805 nm waveform that shows more pronounced or exaggerated features of the central venous pressure waveform. These features include the A, C, and V wave components with minimal signal values, and the X and Y wave components with increased signal values.

[0309] 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.

[0310] High intracranial pressure

[0311] refer to Fig.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 through an anterior burr hole to increase the sheep's intracranial pressure to a range greater than about 150 mmHg. Fig.14 (a) shows simultaneous third and fourth signals 1403, 1404 obtained from the nose skin of the subject 520 and is shown for comparison.

[0312] As shown, the first and second signals 1401, 1402 show an increase in the amplitude of the AC pulse signal, which is characteristic of the intracranial pressure of the subject.

[0313] 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 since 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 affect 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.

[0314] Processor 562 may analyze at least one waveform of the corresponding one or more signals to determine whether the waveform shows an increase in AC component amplitude relative to a corresponding component of an arterial waveform of another signal, the one or more signals originating from the detected light of the brain 521, the other signal being obtained simultaneously with one or more signals from the subject, such as a skin signal. In response to determining that the AC component amplitude is increased, processor 562 may determine that subject 520 may have relatively high intracranial pressure or a cerebral hemorrhage. In addition, a decrease in DC level or cerebral microvascular blood oxygen level, followed by an increase, may also indicate that the subject suffers from a high intracranial pressure level or a cerebral hemorrhage.

[0315] Poor lung ventilation

[0316] 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 area of ​​the lung, and the sensor waveform reflects this, with the venous signal being dominant ( Fig.15 (b)).

[0317] 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).

[0318] refer to Fig.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 on the subject 520 near the dependent hypoventilated lung. Fig.15 (a) shows simultaneous third and fourth signals 1503, 1504 obtained from the forehead skin of subject 520, which are shown for comparison.

[0319] As shown, the first signal 1501 and the second signal 1502 may include components consistent with the pressure waveform found in the pulmonary veins. These features include A, C, X, V, and Y waves. The V wave is significant in the waveform of the second signal 1502, but less significant in the waveform of the first signal 1501. The minimum signal values ​​of the first signal 1501 and the second signal 1502 may occur during the V wave rather than the A wave. The peak signal values ​​are synchronous for the first signal 1501 and the second signal 1502. The processor 562 can determine that the health condition includes poor pulmonary ventilation based on any one or more of these features.

[0320] For example, in some embodiments, processor 562 may 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 with a significant V wave, the processor may determine that the health condition includes hypoventilation of the lungs.

[0321] 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 great extent as the balloon collapses (see Fig.15 (c)). Determining oxygen levels is discussed in further detail below.

[0322] Hypoxia-liver

[0323] Changes in portal blood flow are important in the detection of a range of liver diseases, including hepatitis, cirrhosis, and right heart failure.

[0324] Under normal oxygenation conditions, the P wave may not be prominent or visible in the signal. However, as systemic hypoxia develops, the P wave becomes very prominent due to increased cardiac output and increased portal blood flow. The dominance of the P wave causes the X wave to not be observed. Also note that under hypoxic conditions, the pulse rate is higher.

[0325] 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 is different 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 blood flow.

[0326] Intracranial Pressure - Sylvian Fissure

[0327] The first signal can 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 forehead skin of the subject represents an arterial pulse of the subject. The first waveform of the first signal has a shape similar to 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.

[0328] The timing of the specific oscillations of the first signal and the general shape of the first waveform are closely related to the observed waveform recorded for intracranial pressure measurement in the cerebrospinal fluid, which is caused by pressure changes in the skull after each pulse of arterial blood input 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). It is noteworthy that the peak intensity level (which can be used as the beginning 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.

[0329] In some embodiments, the device 100 is located near the intergyral sulcus to enable non-invasive monitoring to detect elevated intracranial pressure levels. Light including at least one wavelength from the light source 120 can be projected through the skull of the subject 520 to 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, the at least one signal being derived from the measured light reflected from the intergyral sulcus at a corresponding wavelength. The waveform of at least one signal can be analyzed to determine a measured value of elevated intracranial pressure. For example, one or more signals can include superimposed oscillating signals. The frequency and amplitude of the oscillating signal can increase with the increase of intracranial pressure. In response to determining that the frequency or amplitude of the oscillating signal is higher than a threshold level, the processor 562 can be configured to determine that the subject is experiencing elevated intracranial pressure.

[0330] If blood is present in the CSF, such as in the case of a subarachnoid hemorrhage, the signal level may become very strong compared to the signal of normal CSF. Therefore, the signal can be used to detect a subarachnoid hemorrhage.

[0331] In some embodiments, the apparatus 100 generates and detects light having a wavelength of approximately 805 nm to generate the first signal and reduce 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.

[0332] Organ Movement - Brain

[0333] refer to Fig.13(b) shows an example graph of a first signal 1301 derived from measured light reflected from a subject's brain at a first wavelength (e.g., 895 nm) and a second signal 1302 derived from measured light at a second relatively shorter wavelength (e.g., 660 nm). The first and second signals 1301, 1302 were obtained from sensors of the apparatus 100, which was placed on the scalp of a sheep, followed by injection of 6 ml of blood into the anterior cranial fossa through an anterior burr hole to increase the sheep's intracranial pressure to a range of about 90 mmHg to about 150 mmHg. It can be seen that the first and second waveforms associated with the signals 1201, 1202 include high amplitude oscillations of a particular frequency, in this case about 7 Hz. Oscillations of this frequency in the ICP pressure trace have been previously documented and represent "ringing" of the brain in response to systolic arterial pressure waves entering the brain. Increased ICP pressure levels may increase the amplitude of these oscillations, resulting in changes in the waveforms of the monitor that we detect. The synchronous nature of the monitor beats and high-frequency oscillations is consistent with the 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 recovery outcomes.

[0334] Fig.13 (a) shows a simultaneous graph of a third and fourth signal 1303, 1304 obtained from the nose skin of a sheep and depicts an arterial waveform shown for comparison with the first and second signals 1301, 1302. This may help determine the timing of the systolic and diastolic phases of the cardiac cycle.

[0335] Processor 562 can analyze at least one waveform of the corresponding one or more signals to determine whether the waveform includes oscillations, for example, at about 7 Hz, the corresponding one or more signals originating from detected light reflected by brain 521. In response to determining that the waveform includes oscillations, processor 562 can determine that subject 520 may have relatively very high intracranial pressure. For example, very high intracranial pressure may be caused by acute brain injury caused by a cerebral hemorrhage.

[0336] Organ Movement - Lungs

[0337] The lungs expand during inspiration and contract during expiration. The light signal from the lungs reflects the extent of this movement during breathing. The light signal can be used to detect abnormal breathing patterns and breathing phases. The light signal detects the inspiration and expiration phases of breathing. The signal can be used to trigger a mechanical ventilator. Therefore, the processor 562 can be configured to output control instructions to control the mechanical ventilator based on the determined breathing pattern.

[0338] 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 inhalation and exhalation 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.

[0339] 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.

[0340] For example, processor 562 can be configured to compare changes in the inspiratory and / or expiratory phases of breathing 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 breathing depicted in a template waveform characteristic of a relatively healthy liver. The waveform and template waveform can extend at least one respiratory cycle. A respiratory cycle can span a time range of more than 1 second, and can, for example, span a time range from about 1 second to about 10 seconds.

[0341] In some embodiments, the processor 562 can be configured to determine the movement of the liver based on statistical measurements of at least one waveform. The statistical measurements can be compared with the information features to determine the movement. The statistical measurements can include any one or more of the peak signal value, the minimum signal value, the median signal value, the root mean square signal value, and the average signal value of the waveforms of the first and second signals. The processor 562 can determine the 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 that 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.

[0342] Organ Movement-Heart

[0343] 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 diseases.

[0344] A first signal obtained from measured light of a first wavelength (e.g., 895 nm) reflected from the heart of a healthy human subject and a second signal obtained from measured light of 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 right internal jugular vein of the subject.

[0345] In some embodiments, the processor may 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 movement of the heart and / or the time in the cardiac cycle when the heart chamber contracts and relaxes. 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 time of contraction of each chamber in the cardiac cycle and the time of relaxation of the right ventricle and the left ventricle. Therefore, abnormal movement of the heart that may occur after heart damage caused by damage to the muscle due to 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 diseases of electrical signal conduction that coordinate the activation of myocardial contraction.

[0346] Analyze blood oxygen levels using the ratio calculation of the corrected ratio

[0347] In some embodiments, processor 562 is configured to determine the subject's blood oxygen level based on analysis of first and second waveforms of corresponding first and second signals derived from light reflected by a target internal organ of subject 520, which blood oxygen level may be indicative of the subject's health. The intensity of light reflected by blood within a blood vessel is affected by the blood oxygen level. The absorption may be based on the intensity of the first and second signals of the corresponding first and second wavelengths detected using known methods of calibrating the intensity of the light produced. 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.

[0348] 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 (related to 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:

[0349]

[0350] Wherein, I1 is the signal value (peak or maximum signal value) at the beginning of the pulse of signal 1, which originates from the light received at the shorter wavelength 1, AC1 is the change in the signal level from I1 at the peak of the contraction phase of signal 1 (the minimum signal value corresponding to the peak or maximum value of the blood pulse), which originates from the light received at wavelength 1, I2 is the signal value (peak or maximum signal value) at the beginning of the pulse of signal 2, which originates from the light received at the longer wavelength 2, and AC2 is the change in the signal level from I2 at the peak of the contraction phase of signal 2 (the minimum signal value corresponding to the peak or maximum value of the blood pulse), which originates from the light received at wavelength 2. Therefore, a single ratio R' of ratios is obtained for each waveform (or each pulse).

[0351] 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.

[0352] When calculating ratio values ​​of ratios from signals originating from internal organs, it may be necessary to normalize the signal values ​​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.

[0353] In organs, microvascular blood oxygen levels vary greatly during the cardiac cycle due to oxygen exchange with the tissues of the organ. Levels in microvascular blood are higher during systole and decrease during diastole (the opposite is true in the lungs); therefore, the time points of the maximum transmitted light intensity values ​​(the beginning of the pulse) may not be synchronized for the two wavelengths. In skin pulse oximetry, the oxygen level usually remains more constant and the time points of the maximum transmitted light intensity values ​​(the beginning of the pulse) are always synchronized for the two wavelengths.

[0354] In organs, the minimum light intensity level occurs later in the pulse (waveform) during diastole, especially for signals derived from light with a wavelength of 660nm (or 895nm 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.

[0355] The minimum blood oxygen level measured during the diastolic phase of the cardiac cycle is particularly important because the oxygen concentration in the microvascular blood may have dropped to a point of equilibrium with the oxygen concentration of 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.

[0356] Peak oxygen levels measured during the systolic phase provide an estimate of arterial oxygen levels in the microvascular blood of the organ. The exception is the lungs, where peak oxygen levels occur during diastole and represent how well the lungs oxygenate the returning venous blood. It provides an estimate of systemic arterial oxygen levels.

[0357] To account for these differences and enable measurement of diastolic oxygen levels, a ratio of the corrected ratios is calculated throughout the cardiac cycle to allow 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, only oxygen levels during systole are measured and reported.

[0358] Monitoring of diastolic oxygen levels is particularly important because no accurate non-invasive methods have previously been available. The diastolic oxygen level reflects tissue oxygen levels, which are of fundamental importance because even short periods of low tissue oxygen can lead to tissue necrosis with the risk of organ failure and death. Therefore, monitoring of the diastolic oxygen level allows early detection and treatment of systemic diseases, including sepsis, heart failure and bleeding, and can also be used to optimize fluid resuscitation and anti-nutritional administration. In addition, monitoring of the diastolic oxygen level 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 syndrome and pneumonia.

[0359] In order to perform a ratio calculation (R) of a 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 a 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 the values. The maximum signal value (DC level) for each wavelength at the beginning of a pulse or waveform is particularly important in the calculation of R. It is used both for normalization of the signal and for evaluating changes in light intensity levels during the pulse (referred to as the AC level).

[0360] 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 may be calculated as follows:

[0361]

[0362] Wherein, AC1(t) is the change in signal level of the shorter wavelength signal of I1 at time t, AC2(t) is the change in signal value of the longer wavelength signal of I2 at time t, and I1(t0) is the signal value (peak or maximum signal value) at the beginning 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 for the second normalization factor for the longer wavelength signal. The determination of a suitable time t0 is described below.

[0363] Unlike conventional methods, the ratio R value of the modified ratio is calculated for all t values ​​in the window of the entire waveform corresponding to the cardiac cycle or pulse of the subject, thereby allowing the oxygen level to be monitored during the systolic and diastolic phases of the pulse. In some embodiments, the processor 562 can determine the ratio of the modified ratio multiple times in the window of one or more waveforms corresponding to the cardiac cycle. For example, the signal can be sampled at a sampling rate greater than the pulse rate (or heart rate) to provide multiple signal values ​​in the entire waveform. The signal can be sampled at a sampling rate greater than 5Hz. In some embodiments, the sampling rate can be in the range of 100Hz to 5000Hz. The sampling rate can be 500Hz. The sampling rate can be high enough to be considered substantially continuous. This provides a measurement of changes in oxygen levels in all stages of the cardiac cycle.

[0364] 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 not be synchronized, 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 not synchronized, a normalization factor may be determined at time t0 that corresponds to the peak light intensity signal value of the first or second signal.

[0365] 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 ratio R of the corrected ratios may not be accurate. 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 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 from the organ more rapidly 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 ratio R of the corrected ratio. This prevents the use of conventional methods in this case.

[0366] To address the limitations of the above-described method for calculating the ratio R of the modified ratio values, when the light intensity during the systolic or diastolic phase of the pulse exceeds the level at the beginning of the pulse (I) (e.g., due to breathing), 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 .

[0367] Another way to deal with the problem of signal values ​​increasing above earlier peak signal values ​​during a pulse is to use a forward normalization approach (i.e., still use the peak signal value at the start of the pulse t0), but provide a ratio R value of the modified ratio 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.

[0368] Another approach (particularly 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 this the breath normalization method.

[0369] It has been found that the temporal distance (or temporal offset) between the peak signals is proportional to the degree of difference between the 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 the signal, and determine the diastolic oxygen level of the internal organ based on the temporal distance and the associated arterial or systolic oxygen level, wherein the signal is primarily associated with the target internal organ. In the case of the lungs, the diastolic or arterial oxygen level is generally known, so the mixed venous oxygen level can be estimated.

[0370] The minimum microvascular oxygen saturation, which occurs during diastole, was found to also vary with the phase of the respiratory cycle, with levels falling further during the expiratory phase. The lower levels achieved during expiration reflect the 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 the microvascular blood of an organ in relation to the respiratory phase can be used to assess the extent of oxygen exchange through the lungs with 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.

[0371] Reference again Fig. 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 the DC offset, thereby generating an AC signal for further analysis. The ratio of the corrected 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).

[0372] In some embodiments, the 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 determined ratio of the modified ratios with a characteristic waveform or template. The characteristic waveform or template can, for example, include a ratio of the modified ratios determined based on the arterial skin signal. The ratio of the modified ratios of the arterial skin signal is not much different from a value of about 0.6 for most pulses (or systolic and diastolic cardiac cycle phases). Therefore, the processor 562 can determine that the ratio value of the modified ratios indicates that the first and second signals (the ratio of the modified ratios is calculated based on the signals) are primarily associated with the internal organ, and the ratio value of the modified ratios differs from the ratio by more than a threshold amount (e.g., 0.2). For example, if the average value of the ratio values ​​of the determined modified ratios is greater than about 0.7, the processor can be configured to determine that the first and second signals are primarily associated with the target internal organ. The specific example of an internal organ will be discussed below. Templates can also be used to represent characteristic temporal changes in the ratio of the modified ratios for the systolic and diastolic phases of a given internal organ.

[0373] In some embodiments, processor 562 may be configured to analyze changes in the determined blood oxygen values ​​to determine whether the blood oxygen values ​​indicate blood oxygen values ​​of internal organs. In some embodiments, in response to determining that the blood oxygen level is relatively high at the 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 the internal organs.

[0374] In some embodiments, processor 562 can assess the health of an internal organ based on a calculated value of a ratio of the determined modified ratios. For example, processor 562 can determine the subject's blood oxygen level using a ratio equation of the modified ratios, and can perform a health assessment based on the determined blood oxygen level and the target internal organ.

[0375] For example, the 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.

[0376] In some embodiments, processor 562 may 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 may 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 the organ. Processor 562 may determine blood oxygen levels of internal organs of subject 520 based on blood oxygen levels determined at specific times in the waveforms.

[0377] 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, the processor 562 can determine the equilibrium blood oxygen level value of the internal organ by determining the signal value of the first or second signal when the signal is at a minimum level. However, in some cases, the blood oxygen level may not be able to reach equilibrium with the tissue oxygen level. If the signal comes primarily from the capillary bed, or if there is very high blood flow or shunting, an unbalanced state may occur. The capillary bed signal is unique and different from the signal from the venules.

[0378] Fig.17 is an example graph of the ratio of oxygen saturation of the internal jugular vein of three human subjects during a whole body hypoxia experiment relative to a modified ratio value determined by obtaining signals from the brains of the three human subjects using the device 100. Blood was drawn 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 value. This shows that the ratio of the modified ratio value, calculated from the signal derived from light reflected by the human brain, can be easily mapped to the oxygen level in the venous blood discharged from the brain. It also provides evidence that the ratio value of the modified ratio can be used to determine blood oxygen levels associated with internal organs.

[0379] Fig.18is a graph of 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 change intracranial pressure and reduce blood flow and tissue oxygen levels. The sagittal sinus vein drains blood from the vein. Fig.18 The graph of FIG. 1 shows the ratio of the modified ratio values ​​determined by obtaining signals from the sheep's brain using the device 100. The blood oxygen level is inversely proportional to the ratio of the modified ratio values. This provides further evidence that the ratio value of the modified ratio can be used to determine the blood oxygen level associated with the brain and internal organs.

[0380] Corrected Ratio of Ratios - Brain

[0381] 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 originating 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. The 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 because this may represent tissue oxygen level. A decrease in the ratio of the determined modified ratio values ​​observed during the X wave and the Y wave indicates an increase in oxygen level during these phases of the cardiac cycle.

[0382] 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).

[0383] In some embodiments, the processor may calculate a statistical measure (e.g., a median, mean, or peak) of the ratio of the modified ratios and compare it to a threshold. The statistical measure may be based on a portion of the calculated ratio of the modified ratios of the waveform. For example, the statistical measure may be an average of the largest 30% of the calculated ratio values ​​of the modified ratios. The statistical measure may be associated with a variation or range of the determined ratio of the modified ratios. Since a variation in the determined ratio of the modified ratios is expected from a signal associated with the brain 521, the variation may be determined and compared to a threshold. For the processor 562, the value of the variation (or range) of the ratio values ​​of the determined ratios may be, for example, greater than 1 to determine that the signal is associated with the brain 521. The statistical measure may be calculated from the A wave front edge during the diastolic phase (away from the peak signal) of the cardiac cycle.

[0384] This is in contrast to typical modified ratio values ​​determined from arterial skin signals, where there is little variation during a pulse and where the threshold value may be about 0.7 or about 1.

[0385] In some embodiments, the processor 562 may be configured to assess the health of the brain by analyzing the ratio value of the modified ratio. For example, the processor 562 may compare the ratio value of the modified ratio with a characteristic waveform or template for health assessment. In some embodiments, the processor 562 may compare a statistical measure of the ratio value of the ratio with a threshold value for health assessment.

[0386] The minimum or equilibrium blood oxygen level of the brain can provide valuable clinical information about tissue oxygen levels. For example, low tissue oxygen levels in the brain may indicate that subject 520 suffers from 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) of the ratio 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 suffers from hypoxia. Brain hypoxia may occur due to stroke, vasospasm, and increased ICP.

[0387] For example, Fig.19 A graph of the ratio of the determined corrected ratios from the signal derived from the measured light reflected from the brain of a sheep using the device 100 is shown. As shown, the ratio of the determined corrected ratios from the signal derived from the light reflected from the brain using the device 100 was found to increase immediately after blood was injected into the sheep's brain, thereby increasing intracranial pressure. This may indicate a decrease in the brain's blood oxygen level (decreased cerebral perfusion) after the increase in intracranial pressure. Therefore, low blood oxygen levels in the brain may indicate a disease that causes reduced blood flow. After the initial increase in the ratio of the corrected ratios, 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.

[0388] 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 emergency treatment.

[0389] Fig. 20 (b) shows signals 2001, 2002 obtained from light reflected from the brain 521 of the human subject 520 using the device 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. Fig. 20(a) shows the third and fourth signals 2003, 2004 simultaneously obtained from the light reflected from the internal jugular vein of the subject 520, which provides a method of indicating the phase of the respiratory cycle. "Expiratory (Exp)" represents the respiratory phase of exhalation. "Inspiratory (Insp)" represents 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 the subject 520, and generally decreases during the expiratory phase (e.g., exhalation) of the respiratory cycle, and increases during the inspiratory phase (e.g., inhalation) of the cycle. Fig. 20 (c) shows the simultaneous change in the ratio of the corrected ratios during each cardiac cycle. Oxygen levels are shown to decrease during exhalation (the ratio of the corrected ratios increases).

[0390] As described above, the ratio of the modified ratio (or blood oxygen level) varies with the stage 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-related lung damage by selecting the lowest ventilation pressure level that still provides adequate organ tissue oxygen levels.

[0391] Corrected Ratio Ratio - Lung

[0392] The lungs have a unique microcirculation in that the surrounding tissue is composed of alveolar sacs, which 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 (peaks 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.

[0393] Fig.10(b) shows the ratio of the corrected ratio values ​​calculated from the first and second signals 1001, 1002, the first and second signals being associated with well-ventilated lungs. During the cardiac cycle, the ratio of the corrected ratio values ​​is observed to rise from 0 to a value exceeding 2. As shown, a minimum in the calculated ratio of the corrected ratio values ​​(which indicates a maximum blood oxygen value) is observed to occur during the A wave component of the first signal 1001 (during diastole) coinciding 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 ratio values ​​(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.

[0394] Fig.15 (c) shows the ratio of the modified ratio values ​​calculated from the first and second signals 1501, 1502, which are 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 about 1) and therefore 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.

[0395] 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 ratio. 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 Fig.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.

[0396] In some embodiments, the processor 562 can determine that the first and second signals 1001, 1002, 1501, 1502 are related to the lungs based on a ratio R of the modified ratios, wherein 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).

[0397] The processor 562 can assess the health of the lungs by analyzing the ratio of the modified ratios. For example, the 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 degree of oxygen addition to the venous blood may be low. Therefore, if the ratio of the modified ratios is high, this may indicate lung injury.

[0398] 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.

[0399] 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.

[0400] 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.

[0401] Corrected Ratio Ratio - Liver

[0402] The device 100 can be used to obtain the first and second signals obtained from light reflected from the healthy liver of the subject 520, and a ratio of the modified ratios of the first and second signals associated with the liver can be calculated. The ratio of the modified ratios decreases during the X wave (indicating an increase in oxygen levels) and then increases to maintain a relatively high and constant level during the diastolic 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 disease 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.

[0403] The processor 562 can determine that the first and second signals 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 maximum 30% of the ratio of the modified ratios calculated on the waveform. For example, in response to determining that the statistical measure is greater than about 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 about 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 about 1, the processor 562 can determine that the first and second signals are associated with the liver.

[0404] A statistical measurement value 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 measurement value is equal to approximately 0.7, processor 562 determines that the first and second signals are associated with subject 520's skin.

[0405] 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 of particular interest because the blood oxygen level at this time (which can be calculated by the ratio of the modified ratio values) may be similar to or equal to the tissue oxygen level of the liver.

[0406] 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 the 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 about 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 about 2, the processor 562 can determine that the subject has an unhealthy liver (e.g., due to hypoxia or ischemic liver).

[0407] Modified Odds Ratio - Intestinal

[0408] The first and second signals acquired using the device 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 period (illustrated by a decrease in the ratio of the calculated modified ratio values). Thereafter, there is a rapid drop in 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 counterflow design provides free oxygen exchange between the arterial and venous sides of the microcirculation during all phases of the cardiac cycle.

[0409] 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 measurement value (e.g., a median or mean) of the ratio of the modified ratios can be compared to a threshold value. The statistical measurement value can be based on the maximum 30% of the ratio of the modified ratios calculated on the waveform. For example, in response to determining that the statistical measurement value 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 measurement value is greater than approximately 1, the processor 562 can determine that the first and second signals are associated with the intestine. A statistical measurement value equal to or less than 0.7 can indicate that the first and second signals are associated with the subject's skin.

[0410] In some embodiments, processor 562 may determine that the first and second signals are bowel related based on a ratio of modified ratios determined during an A-wave leading edge preceding an X-wave.

[0411] 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 waveform 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.

[0412] 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.

[0413] Corrected Ratio Ratio - Renal

[0414] A ratio value R of the corrected ratio of the signals obtained from the 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.

[0415] Modified Ratio Ratio - Muscle

[0416] A ratio R of the modified ratios of the signals obtained from the light reflected by the calf muscle at rest may 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.

[0417] The present invention will now be further described with reference to the following non-limiting examples:

[0418] Example - Evaluating improvements to brain sensor devices to improve detection of light pulses in the brain

[0419] method

[0420] Variations in the design of the brain sensor device were evaluated to improve the detection of brain impulses and provide a comparison with a prior art device. Evaluations were performed on 5 healthy volunteers. Two evaluations were performed on each volunteer, one on the left temple and one on the right temple, resulting in a total of 10 evaluations for each device modification. The outcome measure was the detection of a pulsating light signal consistent with the shape and characteristics of brain impulses, Figures 23(a), (b) and (c) and Fig.24The results shown in 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 Photodetectors and LEDs used in the Maxfast forehead sensor. The total optical power used (all LEDs) is approximately 200 μW.

[0421] In the first experiment, a variation in a conventional pulse oximetry device was tested, in which a light detector (PD) and a light emitting diode (LED) were separately in contact with the subject's skin. In this experiment, the spacing between the center points of the light source (LED) and the light detector (PD) was varied between 10mm, 15mm, 20mm, and 40mm.

[0422] The results in Figure 23(a) show that using a modification of the prior art pulse oximeter device with different spacings 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.

[0423] In the second experiment, the spacing of the PD and LED from 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.

[0424] 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.

[0425] In the third trial, the spacing between the center points of the light source (LED) and the light detector (PD) was fixed at 15 mm (the optimal spacing from the second trial), and the effect of varying the spacing between PD and LED and the skin between 0 mm, 5 mm, 10 mm, 15 mm, and 20 mm was tested.

[0426] The results in FIG. 23( c ) show that no brain pulses were detected at 0 mm and 20 mm spacings, and 25% of brain pulses were detected at 15 mm spacing and 50% of brain pulses were detected at 5 mm spacing. The best result of 100% brain pulse detection was obtained when the spacing between the PD and LED and the skin was 10 mm. In subsequent tests performed by the inventors (results not shown), the best brain pulse detection of 100% was also observed when the spacing between the PD and LED and the skin was 8.5 mm.

[0427] 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 varying the spacing of the LED from the skin between 15 mm and 20 mm (i.e., 5 mm and 10 mm recessed from the PD position, respectively) was tested.

[0428] Fig.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%.

[0429] Those skilled in the art will appreciate that, without departing from the broad overall scope of the present disclosure, various changes and / or modifications may be made to the above-described embodiments. Therefore, the present embodiments are considered in all aspects to be illustrative and not restrictive.

Claims

1. 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 proximate an internal organ of the subject; 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 including a light emitting region within the first recess and configured to emit light of at least two discrete wavelengths from the first recess of the body onto an internal organ; as well as a light detector comprising a photosensitive region within the second recess and configured to detect light received at the second recess, wherein the detected light comprises emitted light reflected from a region of the subject adjacent an internal organ; wherein the device is configured such that both the light emitting area and the photosensitive area are retracted by 5 mm to 15 mm from the contact surface, and the nearest points of the light emitting area and the photosensitive area are separated from each other by 4 mm to 20 mm, so that the detected light indicates the blood oxygen level in the blood vessels on the outermost surface of the internal organ.

2. The device according to claim 1, wherein: The spacing between the closest points of the light emitting area and the photosensitive area is in the range of 5 mm to 15 mm.

3. The device according to claim 2, wherein: The interval is in the range of 6 mm to 12 mm.

4. The device according to any one of claims 1 to 3, wherein: The light emitting area and the photosensitive area are recessed from the contact surface by 7 mm to 10 mm.

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

6. The device according to any one of claims 1 to 3, wherein: The body further comprises 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 an internal organ.

7. The device according to claim 6, wherein: The wall extends from a base of the body towards the contact surface for a wall height, and wherein the wall height is at least 2 mm.

8. The device according to claim 6, wherein: The wall has a thickness of 1 mm to 2 mm.

9. The device according to claim 7, 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 5 mm to 15 mm.

10. The device according to any one of claims 1 to 3, wherein: The light source is configured to emit light including light having a wavelength within a first wavelength range of 600 nm to 750 nm and light within a second wavelength range of 855 nm to 945 nm.

11. The device according to claim 10, wherein: The light source is configured to emit light, the light also including light having a wavelength within a third wavelength range of 780 nm to 820 nm.

12. The apparatus according to any one of claims 1 to 3, wherein: The light detector is configured to sense light including discrete wavelengths of 660 nm, 805 nm, 895 nm, and / or 940 nm.

13. The apparatus according to claim 7, wherein: The wall height is 4 mm.

14. The apparatus according to claim 8, wherein: The thickness of the wall is 1.8 mm.

15. The apparatus according to claim 9, wherein: The depth is 8.5 mm.

16. A system for determining blood oxygen levels of internal organs, the system comprising a device according to any one of claims 1 to 15 and a processor, wherein: The device and processor are connected to enable data indicative of blood oxygen levels of internal organs to be transmitted from the device to the processor.

17. The system of claim 16, wherein: The processor includes a memory, a display, and a user interface, all coupled to the processor.

18. A method of obtaining data indicative of blood oxygen level of an internal organ of a subject, comprising: positioning a device according to any one of claims 1 to 15 on an external surface of a subject adjacent to an internal organ; projecting light from a light source through an external surface of the subject to an 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 two or more discrete wavelengths; as well as A first signal indicative of the intensity of light at the first wavelength and a second signal indicative of the intensity of light at the second wavelength are generated.

19. The method according to claim 18, further comprising: In response to receiving an instruction indicating that the device is inaccurately positioned relative to the internal organ, the device is repositioned relative to the internal organ based on the instruction.

20. A method of determining the blood oxygen level of an internal organ of a subject, comprising: positioning a device of the system according to any one of claims 16 to 17 on an external surface of a subject adjacent to an internal organ; projecting light from a light source through an external surface of the subject to an 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 two or more discrete wavelengths respectively; and A first signal indicating the intensity of the light of the first wavelength and a second signal indicating the intensity of the light of the second wavelength are generated, wherein data related to the first signal and the second signal are transmitted to a processor and a blood oxygen level of an internal organ is determined.

21. The method according to claim 20, further comprising: In response to receiving an instruction indicating that the device is inaccurately positioned relative to the internal organ, the device is repositioned relative to the internal organ based on the instruction.

22. A computer-implemented method of assessing the health of a subject, the method comprising: positioning a device of the system according to any one of claims 16 to 17 on an external surface of a subject adjacent to an internal organ; projecting light from a light source through an external surface of the subject to an 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 two or more discrete wavelengths; wherein data related to the received light is transmitted to a processor, and one or more signals derived from the received light are generated, and at least one waveform of the one or more signals is determined to represent a signal primarily associated with an internal organ; and Data derived from the at least one waveform is compared to informative features of a health condition to assess the health of the subject.

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