Apparatus, systems and methods for assessing internal organs

Abstract

To determine data indicative of blood oxygen levels of internal organs.SOLUTION: The disclosed apparatus comprises: a body comprising a contact surface for engaging with a subject in a vicinity of an internal organ of the subject, the body defining a first recess and a second recess, the first and second recesses extending from the contact surface into the body, the second recess being separate from the first recess; a light source comprising a light emitting region located within the first recess and configured to emit light of at least two discreet wavelengths from the first recess of the body; and a photo-detector comprising a light sensitive region located within the second recess and configured to detect light received at the second recess, the detected light comprising the emitted light reflected from a region of a subject in proximity to an internal organ. The light emitting region and the light sensitive region are set back from the contact surface by about 1 mm to about 20 mm and nearest points of the light emitting region and the light sensitive region are separated from one another by about 4 mm to about 20 mm, such that the detected light is indicative of blood oxygen levels in blood vessels of an outermost surface of the internal organ.SELECTED DRAWING: Figure 1

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] 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]

[0002] The present disclosure relates generally to devices, systems and methods for assessing the health of internal organs of a subject. In particular, but not exclusively, the present disclosure relates to devices, systems and methods for determining blood oxygen saturation in the internal organs of a subject. [Background technology]

[0003] Pulse oximetry is used to noninvasively measure the absolute arterial circulating oxygen level (blood oxygen saturation) of blood in a subject's skin, thereby providing an indicator of the subject's health status. Absolute arterial oxygen level can be determined by analyzing the ratio of red and near-infrared light intensities. Arterial oxygen level can be obtained, for example, by transmitting light through the subject's finger or by reflecting light off the subject's skin, for example, on the subject's forehead, and measuring the light captured by a detector. The light is typically generated by a light-emitting diode (LED) placed directly on the subject's skin to maximize the light delivered to the subject. The signal is generated by blood flow within the skin.

[0004] The inventors have determined that it is possible to accurately determine blood oxygen levels in the microvasculature of a visceral organ and assess organ health by utilizing a device placed near the subject's internal organs, where the light detector of the device is recessed from the surface of the device that is in contact with the subject (e.g., located on the subject's skin), and the light source and light detector are positioned a defined distance from their respective centers, such as about 5 mm to about 20 mm. Summary of the Invention

[0005] Some embodiments relate to an apparatus for determining data indicative of blood oxygen levels in an internal organ, the apparatus comprising: a body including a contact surface for contacting a subject near an internal organ of the subject, the body defining a first recess and a second recess, the first recess and the second recess extending into the body from the contact surface, the second recess being separate 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 discreet wavelengths from the first recess of the body; and a light detector including a light-sensitive region located within the second recess and configured to detect light received at the second recess, the detected light comprising emitted light reflected from a region near the internal organ of the subject; wherein the light-emitting region and the light-sensitive region are recessed from the contact surface by about 1 mm to about 20 mm, and the nearest points of the light-emitting region and the light-sensitive region are separated by about 4 mm to about 20 mm, and the detected light is indicative of blood oxygen levels in blood vessels at the outermost surface of the internal organ.

[0006] The spacing between the closest points of the light emitting and photosensitive regions can range from about 5 mm to about 15 mm, hi some embodiments, the spacing ranges from about 6 mm to about 8 mm.

[0007] In some embodiments, the body may further comprise an outer frame defining a contact surface and a cavity, and an inner frame shaped to fit within the cavity and defining first and second recesses.

[0008] The light source can be configured to emit and sense light including light having wavelengths in at least a first wavelength range of 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 photodetector can be configured to emit and sense light including light having discrete wavelengths of at least about 660 nm, about 805 nm, about 895 nm, and / or about 940 nm.

[0009] Some embodiments of the present invention relate to a system for determining blood oxygen levels of an internal organ. The system includes the device described above and a processor. The device and processor are connected to enable transmission of data indicative of the blood oxygen levels of the internal organ from the device to the processor. The processor may include a memory, a display, and a user interface, all of which are coupled to the processor. Some embodiments relate to a method for obtaining data indicative of the blood oxygen levels of an internal organ of a subject. The method includes: placing the device described above on an external surface of the subject proximate to the internal organ; illuminating the internal organ through the external surface of the subject with light from a light source, the light comprising two or more discrete wavelengths; receiving the light with a photodetector of the device, the received light being reflected from the internal organ at the two or more discrete wavelengths; and generating a first signal indicative of the intensity of the light at the first wavelength and a second signal indicative of the intensity of the light at the second wavelength.

[0010] In some embodiments, the method includes placing a device on the scalp of the subject, wherein the internal organ comprises the brain. In some embodiments, the method includes placing a device adjacent to a region of the skull beneath the scalp, wherein the region of the skull is relatively thin. The region of the skull may be adjacent to the Sylvian fissure. In some embodiments, the method includes placing a device in the ear canal of the subject, wherein the internal organ comprises the brain. In some embodiments, the method includes placing a device in the suprasternal fossa, supraclavicular space, or between the ribs of the subject, wherein the internal organ comprises the lungs. In some embodiments, the method includes placing a device in the right upper quadrant or under the ribs of the upper abdomen of the subject, wherein the internal organ comprises the liver. In some embodiments, the method includes placing a device in either the abdomen or lower quadrant of the subject, wherein the internal organ comprises the intestines. In some embodiments, the method includes placing a device on the back of the subject, wherein the internal organ comprises the kidneys. In some embodiments, the method includes placing a device on the sternum or along the left border of the sternum where it meets the ribs, wherein the internal organ comprises the heart. In some embodiments, the method comprises placing a device on a skeletal muscle of the subject, and the viscera comprises skeletal muscle.

[0011] In some embodiments, the method may further include, in response to receiving an indication that the device is incorrectly positioned relative to the internal organ, repositioning the device relative to the internal organ based on the indication.

[0012] Some embodiments relate to a computer-implemented method for assessing the health of a subject, the method including receiving one or more signals obtained from measured light reflected from an area of ​​the subject proximate to an internal organ 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 information characteristic of a health state to assess the health of the subject.

[0013] In some embodiments, determining that the at least one waveform represents a signal primarily associated with an internal organ comprises determining that the at least one waveform corresponds substantially to a venous waveform.

[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 includes A-wave, X-wave, and Y-wave components corresponding to the A-wave, X-wave, and Y-wave of a venous signal. For example, the internal organ may be one of the brain, lungs, liver, intestines, and fetal organs.

[0015] In some embodiments, determining that the at least one waveform represents a signal primarily associated with an internal organ comprises determining that the at least one waveform does not represent an arterial signal originating from an area of ​​the subject's skin.

[0016] In some embodiments, determining that at least one waveform represents a signal primarily associated with an internal organ comprises receiving a further signal obtained from the subject substantially simultaneously with the one or more signals, wherein the further signal is obtained from measurement light reflected from the subject's skin at a further wavelength; and determining that the signal peaks of the at least one waveform are temporally offset from the signal peaks of each of the further waveforms of the further signal.

[0017] The at least one waveform may include at least one window corresponding to a systolic and a diastolic portion of a cardiac cycle, hi some embodiments, the method further includes determining timing of the systolic and diastolic portions of a cardiac cycle associated with the at least one waveform based on the additional signal.

[0018] In some embodiments, the method further includes determining an estimate of the diastolic blood oxygen level of the splanchnic organ based on the time offset between the signal peaks of the further waveform and the respective signal peaks and the known systolic blood oxygen level. For example, the further waveform of the further signal may be indicative of an arterial pulse of the subject. The further waveform of the further signal may be indicative of a venous signal obtained from the subject's jugular vein. The further signal may be derived from light measured at a wavelength in the range of about 780 nm to about 820 nm, which is sensitive to blood but insensitive to changes in blood oxygen level.

[0019] In some embodiments, determining that the at least one waveform represents a signal primarily associated with a viscera comprises determining that the at least one waveform substantially matches a template waveform characteristic of a viscera.

[0020] In some embodiments, the method further includes, in response to determining that the at least one waveform represents an arterial signal originating from an area of ​​the subject's skin, determining that the at least one waveform does not represent a signal primarily associated with an internal organ.

[0021] In some embodiments, the one or more signals may include a first signal derived from light of a first wavelength and a second signal derived from light of a second wavelength. The at least one waveform may include a first waveform of the first signal and a second waveform of the second signal. Determining that the at least one waveform represents a signal primarily associated with a viscera includes determining a plurality of modified ratio values ​​of multiple ratios throughout a window of the at least one waveform corresponding to a cardiac cycle, wherein the modified ratio values ​​of the multiple ratios are indicative of blood oxygen levels of the viscera; and determining that the determined modified ratio values ​​of the multiple ratios substantially correspond to modified ratio values ​​of multiple ratios characteristic of the viscera.

[0022] In some embodiments, the internal organ includes the brain, and determining that the one or more signals are primarily associated with the brain includes determining that a waveform of at least one of the one or more signals includes a first component having a generally increasing signal level at a first rate, followed by a second component having a generally decreasing signal level at a second rate that is less than the first rate.

[0023] In some embodiments, determining that 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 derived from the skin.

[0024] In some embodiments, where the internal organ includes a lung, a first signal of the one or more signals is derived from light having a wavelength of approximately 660 nm, and determining that the first signal is primarily associated with the lung includes determining that a first waveform of the first signal corresponds to an inverse pulmonary artery pressure waveform.

[0025] In some embodiments in which the internal organ includes a lung, determining that the one or more signals are primarily associated with the lung includes determining that a waveform of at least one of the one or more signals includes components corresponding to a systolic pulse, a diastolic pulse, and a dicrotic notch.

[0026] In some embodiments, the internal organ includes a liver, and determining that the one or more signals are primarily associated with the liver includes determining that a waveform of at least one of the one or more signals includes at least one of an X-wave component and a P-wave component.

[0027] In some embodiments, determining that one or more signals are primarily associated with the liver further comprises determining that a pulse start of at least one waveform is delayed relative to a corresponding pulse start of an arterial signal derived from the skin.

[0028] In some embodiments where the internal organ includes the intestine, determining that the one or more signals are primarily associated with the intestine includes determining that a waveform of at least one of the one or more signals includes one or more venous wave components, the 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 subject's skin.

[0029] In some embodiments, the internal organ includes a kidney, and a first signal of the one or more signals is derived from light having a wavelength of about 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.

[0030] In some embodiments in which the viscera include skeletal muscle, determining that the first signal is primarily associated with skeletal muscle includes determining that at least one waveform of the one or more signals corresponds to an arterial waveform having a relatively low pulse amplitude.

[0031] The method may further include assessing the subject's health based on the comparison and outputting the assessment of the subject's health. For example, comparing the data obtained from the at least one waveform to information characteristic of a health condition may include comparing one or more components of the at least one waveform to one or more corresponding components of one or more template waveforms, each of the one or more template waveforms being characteristic of a health condition. In some embodiments, comparing the data obtained from the at least one waveform to information characteristic of a health condition may include comparing a first shape of the at least one waveform to a second shape of the one or more template waveforms.

[0032] In some embodiments, the method determines that the subject is likely to have heart failure in response to determining that the wave V component of at least one waveform has a greater amplitude than the corresponding wave V component of a corresponding visceral template waveform.

[0033] In some embodiments, in response to determining that a first component of at least one waveform indicates an increase in signal level at a first rate, a second component following the first component indicates a decrease in signal level at a second rate, and the first rate is less than the second rate, determining that the subject is likely to have relatively high intracranial pressure and / or a cerebral hematoma.

[0034] In some embodiments where the internal organ includes the brain, in response to determining that at least one waveform does not depict a V wave or a Y wave component, it is determined that the subject is likely to have relatively high intracranial pressure.

[0035] In some embodiments where the internal organ includes the brain, in response to determining that the AC signal level value of at least one waveform exceeds a threshold, the method determines that the subject is likely to have elevated intracranial pressure.

[0036] In some embodiments, where the internal organ includes the brain, in response to determining that the DC signal level value of at least one waveform of the one or more signals is below a threshold, it is determined that the subject is likely experiencing increased intracranial pressure.

[0037] In some embodiments, in response to determining that at least one waveform includes vibrations of approximately 7 Hz, it is determined that the subject is likely to have relatively very high intracranial pressure and / or cerebral hematoma.

[0038] In some embodiments, where the one or more signals include a first signal associated with a respective first waveform and a second signal associated with a respective second waveform, the first wavelength being longer than the second wavelength, and the first and second waveforms represent signals primarily associated with the lungs, in response to determining that the first waveform includes a venous waveform characteristic and the second waveform includes a venous waveform characteristic, determining that the health condition includes hypoventilated lungs.

[0039] In some embodiments, where the one or more signals include a first signal associated with a respective first waveform and a second signal associated with a respective second waveform, the first wavelength is longer than the second wavelength, and the viscera include lungs, in response to determining that the first waveform includes a prominent V wave component and the second waveform does not include a prominent V wave component, determining that the health condition includes hypoventilated lungs.

[0040] In some embodiments, where the viscera includes a liver, the health state is determined to include high portal vein blood flow in response to determining that at least one waveform of the one or more signals includes a prominent P-wave component.

[0041] In some embodiments in which the internal organ includes a liver, 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, the health condition is determined to include one or more of hepatitis, cirrhosis, and right heart failure.

[0042] In some embodiments where the internal organ includes a heart, the method further includes determining that the heart is damaged due to myocardial infarction or heart failure in response to determining that the at least one waveform substantially matches a template waveform characteristic of abnormal cardiac motion.

[0043] In some embodiments, where the internal organ comprises a heart, the method further comprises analyzing the one or more signals to determine cardiac cycle timing of contraction and relaxation of the heart chambers.

[0044] In some embodiments, where the one or more signals include a first signal derived from light of a first wavelength and a second signal derived 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 modified ratio values ​​of a plurality of ratios across a window of the at least one waveform. The window corresponds to a systolic and diastolic phase of a cardiac cycle. The modified ratio values ​​of the plurality of ratios are indicative of splanchnic blood oxygen levels. Determining the modified ratio values ​​of the plurality of ratios across a window of the at least one waveform corresponding to the cardiac cycle may include sampling the oxygen level at a relatively high rate across the window.

[0045] In some embodiments, comparing data obtained from the at least one waveform with information characteristic of the health state includes determining that the organ is potentially unhealthy in response to determining that corrected ratio values ​​of the determined plurality of multi-ratios deviate from corrected ratio values ​​of a multi-ratio characteristic of the organ.

[0046] In some embodiments, the method further includes substantially simultaneously receiving third and fourth signals obtained from the subject as the one or more signals, the third and fourth signals being obtained from measurement light reflected from the subject's skin at different third and fourth wavelengths, respectively; and determining a plurality of modified ratio values ​​of the multiple ratios over windows of the third and fourth waveforms associated with the respective third and fourth signals, where the windows correspond to systolic and diastolic phases of a cardiac cycle. The modified ratio values ​​of the multiple ratios are indicative of blood oxygen levels at the skin. In some embodiments, the method includes comparing the modified ratio values ​​of the multiple ratios derived from the subject's skin with the modified ratio values ​​of the multiple ratios derived from the subject's internal organs, and determining that the first and second signals represent signals primarily related to the internal organs in response to determining that the modified ratio values ​​of the multiple ratios are different over the windows corresponding to the cardiac cycle.

[0047] For example, the modified ratio for a multi-ratio can be calculated as follows:

[0048]

number

[0049] where the first wavelength is shorter than the second wavelength. AC1(t) is the change in signal level of the first signal from I1 at time t. AC2(t) is the change in signal value of the second signal from I2 at time t. I1(t0) is the signal value of the first signal at time t used as a first normalization factor. I2(t0) is the signal value of the second signal at time t used as a second normalization factor, acquired at time t for the longer wavelength. 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 t. The time t0 at which the normalization factors are determined may be a time after time t. In some embodiments, the normalization factor (I1) and the normalization factor (I2) of the multiple-ratio modified ratio R may be calculated using respiratory oscillations to account for changes in signal values ​​as a result of the subject's respiratory cycle. where time t0 is defined by the time of the peak signal value at the start of each respiratory oscillation for each wavelength. In some embodiments, the method further comprises averaging the determined multi-ratio correction ratio values ​​over the phases of the respiratory cycle in which they occur using the cardiac oscillations to determine an average level of the multi-ratio correction ratio for one or more of the inspiration, inspiration pause, expiration and expiration pause phases of the respiratory cycle.

[0050] In some embodiments, the method further includes determining a splanchnic tissue oxygen level value based on a maximum value of the modified ratios of the multiple ratios over the systolic and diastolic phases of the cardiac cycle. For example, the method may include determining a time point of the end of diastole and a maximum R value based on determining the A-wave components of the first and second waveforms. The method may include determining a splanchnic tissue oxygen level value based on a rate of change of the modified ratio values ​​of the multiple ratios over the systolic and diastolic phases of the cardiac cycle.

[0051] The method includes comparing the blood oxygen level to a threshold level, and determining that the subject is suffering from an adverse health condition in response to determining that the blood oxygen level is below the threshold level.

[0052] In some embodiments, the method can include comparing the blood oxygen level to a threshold level, and in response to determining that the blood oxygen level is above or below the threshold level determining that the subject has elevated intracranial pressure, where the internal organ includes the brain.

[0053] In some embodiments, the method may include analyzing the drop in blood oxygen levels during the diastolic cardiac phase to determine clinical information.

[0054] In some embodiments, the method may include determining oscillations in minimum blood oxygen levels of a body organ over multiple respiratory cycles to assess pulmonary oxygen exchange.

[0055] In some embodiments where the internal organ includes a lung, the method may include determining blood oxygen levels throughout the first and second waveforms; and determining an indication of systemic arterial blood oxygen level based on the peak blood oxygen level during the diastolic cardiac phase.

[0056] In some embodiments, where the internal organ includes a lung, the method further includes determining a maximum blood oxygen level to provide an indication of lung function.

[0057] In some embodiments where the internal organ includes a lung, the method further includes determining a minimum blood oxygen level to estimate a mixed venous oxygen value of blood entering the lung.

[0058] In some embodiments, determining that at least one waveform of the one or more signals represents a signal primarily associated with an internal organ comprises determining that the blood oxygen level waveform significantly matches a template blood oxygen waveform characteristic of an internal organ.

[0059] In some embodiments, the method may include receiving at least one additional signal, the additional signal being obtained from received light reflected from an additional region of the subject proximate another internal organ at each distinct wavelength; 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 information characteristic of a health condition to diagnose a systemic or localized disorder in the subject.

[0060] In some embodiments, the method may include receiving at least one additional signal, the additional signal being obtained from received light reflected from the subject's skin at each distinct wavelength; 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 characteristic of a health condition to diagnose a systemic or localized disorder in the subject.

[0061] In some embodiments, assessing health includes monitoring splanchnic blood flow based on comparing the shape and / or amplitude of at least one waveform to one or more template waveforms, wherein at least one or more waveforms may be associated with a first signal at a wavelength of 805 nm.

[0062] In some embodiments, the method may include determining that the subject's arterial blood pressure is significantly higher than the central venous pressure and that blood flow is high in response to at least one waveform substantially resembling an arterial blood pressure waveform.

[0063] In embodiments where the targeted organ is the liver, the method may include determining that there is excessively high portal vein blood flow and / or hypoxic liver in response to determining that at least one waveform includes a P-wave component having a relatively high amplitude.

[0064] In some embodiments, the method may include determining that the venous pressure is high and organ blood flow is low in response to determining that at least one waveform includes an exaggerated venous waveform. For example, the exaggerated venous waveform may include a high amplitude V-wave component and optionally a high amplitude A-wave component, and the subject may be determined to have one or more of an elevated central venous pressure level, fluid overload, and heart failure.

[0065] In some embodiments, the method includes receiving information indicative of a targeted internal organ. For example, determining that at least one waveform of the one or more signals primarily represents a signal related to an internal organ can be based at least in part on the received information indicative of the targeted internal organ. The information characteristic of the health condition can be based at least in part on the received information indicative of the targeted internal organ.

[0066] Some embodiments relate to a computer-implemented method for assessing the respiration of a subject. The method includes receiving one or more signals resulting from measurement light reflected from an area of ​​the subject proximate an internal organ at each distinct wavelength; calculating a statistical measure of the intensities of the one or more signals; and determining that the statistical measure changes over time and relating the change to the subject's breathing pattern. The method may further include outputting control commands for controlling a ventilator based on the determined breathing pattern. The internal organ may be or include any of the brain, liver, lungs, intestines, heart, and fetus.

[0067] Some embodiments relate to a system for assessing the health of a subject, the system comprising one or more processors and a memory containing computer-executable instructions, the memory coupled to the one or more processors, wherein the one or more processors are configured to execute the computer-executable instructions to cause the system to perform any one of the described methods.

[0068] Some embodiments relate to a computer program comprising instructions that, when executed by one or more processors, cause the one or more processors to perform any one of the described methods.

[0069] Some embodiments relate to a system for assessing the health status of a subject. The system comprises at least one of the described devices for determining blood oxygen levels, a memory containing computer-executable instructions, and a processor coupled to the memory and configured to execute the computer-executable instructions to perform any one of the described methods. In some embodiments, the system includes a second device for determining blood oxygen levels, the second device configured to receive a further signal indicative of the subject's cutaneous arterial pulse and comprising a second light source and a second photodetector configured to provide the further signal to the processor. In some embodiments, the system includes one or more second devices for determining blood oxygen levels of an internal organ, the one or more second devices configured to receive a further signal indicative of the signal from the internal organ and comprising a second light source and a second photodetector configured to provide the further signal to the processor. In some embodiments, the system includes one or more second devices for determining blood oxygen levels of one or more second internal organs, the one or more second devices configured to receive a further signal indicative of the signal from the second internal organ and comprising a second light source and a second photodetector configured to provide the further signal to the processor.

[0070] In some embodiments, the device may be coupled to a catheter that is placed inside the subject's body.

[0071] Some embodiments relate to a method of obtaining data indicative of intracranial pressure in a subject, the method including: positioning a light source of any one of the described devices remotely relative to the subject's skull near a sulcus in the subject's brain; shining light from the light source through the subject's skull and into the sulcus, the light comprising light of one or more discrete wavelengths; receiving the light with a photodetector of the device, the received light reflected from cerebrospinal fluid in the sulcus at the one or more discrete wavelengths; generating one or more signals indicative of the intensity of the light at the one or more discrete wavelengths; and providing the one or more signals to the described system to enable determining elevated intracranial pressure in the subject based on a waveform of at least one of the one or more signals.

[0072] The method may include determining an increase in intracranial pressure in the subject based on at least one waveform of the one or more signals, and in response to determining that the pulse waveform includes one or more oscillations, determining the increase in intracranial pressure based on one or more of the pattern, amplitude, and frequency of the one or more oscillations.

[0073] In some embodiments, determining an increase in intracranial pressure may include determining that the pulse waveform includes oscillations similar to the waveform of the intracranial pressure trace, with the onset of the pulse preceding a corresponding wave component of an arterial signal obtained from the skin of the forehead.

[0074] Some embodiments relate to a method for assessing the health of a fetus in a subject, the method including: receiving one or more signals, the one or more signals obtained from received light reflected from a region of the fetus proximate to an internal organ at respective discrete wavelengths; receiving at least one additional signal, the at least one additional signal obtained from received light reflected from a region of the subject at additional discrete wavelengths; determining that at least one waveform of the at least one signal represents a signal primarily related to the internal organ based on a waveform comparison, the waveform comparison including 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 waveform with information characteristic of the health to assess the health of the fetus.

[0075] The method includes placing any one of the described devices (first device) on an external surface of the subject adjacent to fetal internal organs to detect a first signal; and placing any one of the described devices (second device) on any one of the subject's forehead, finger, ear, and nose to detect a second signal. Comparing the waveforms may include determining a time offset between peak signal levels. The method may include placing the first device on the subject's abdomen. The method may include placing the first device intravaginally in the subject. [Brief explanation of the drawings]

[0076] Embodiments will now be described in more detail, by way of example, with reference to the accompanying drawings, which are briefly described below, in which like reference labels indicate like features and in which:

[0077] [Figure 1] 1 is an isometric view of an apparatus for acquiring data related to blood oxygen levels of internal organs of a subject, according to some embodiments. [Figure 2] (a) is a side view of the device in Figure 1, (b) is a top view of the device in Figure 1 [Figure 3] Cross-section of the device taken along line AA in Figure 1 [Figure 4] Exploded isometric view of the device in Figure 1 [Figure 5] 1 is a schematic diagram of a system for obtaining data related to blood oxygen levels from an internal organ of a subject, according to some embodiments. [Figure 6] 1 is a flowchart of a method for obtaining data indicative of visceral blood oxygen levels of a subject, according to some embodiments. [Figure 7] (a) Plot of the first and second signals obtained from the detected light reflected from the brain of a healthy subject, and (b) Plot of the corrected ratio of the multiple ratios calculated from the first and second signals in Figure 7(a). [Figure 8] (a) is a plot of the third and fourth signals obtained from the detected light reflected from the skin of the forehead of a healthy subject; (b) is a plot of the fifth and sixth signals obtained from the detected light reflected from the internal jugular vein of a healthy subject, acquired approximately simultaneously with the detected light in the plot of FIG. 8(a); and (c) is a plot of the first and second signals obtained from the detected light reflected from the brain of a healthy subject, acquired simultaneously with the detected light in the plot of FIG. 8(a). [Figure 9] 1 is a flowchart of a method for assessing the health of a subject according to some embodiments. [Figure 10] (a) Plot of first and second signals obtained from detected light reflected from well-ventilated lungs of a healthy subject. (b) Plot of corrected ratios of multiple ratios calculated from the first and second signals of FIG. 10(a). [Figure 11] Plot of the first and second signals resulting from the detected light reflected from the liver of the subject. [Figure 12] 12(a) is a plot of the third and fourth signals obtained from the detected light reflected from the nasal skin of a sheep subject with relatively high intracranial pressure; and (b) is a plot of the first and second signals obtained from the detected light reflected from the brain of the sheep subject, obtained simultaneously with the light reflected from the nasal skin of the plot in FIG. 12(a). [Figure 13]13(a) is a plot of the third and fourth signals obtained from the detected light reflected from the skin of the nose of a sheep subject with relatively high intracranial pressure, and FIG. 13(b) is a plot of the first and second signals obtained from the detected light reflected from the brain of the sheep subject, acquired simultaneously with the detected light of the plot in FIG. 13(a). [Figure 14] (a) Plot of the third and fourth signals obtained from the detected light reflected from the skin of the nose of a sheep subject with relatively extremely high intracranial pressure; and (b) plot of the first and second signals obtained from the detected light reflected from the brain of the sheep subject, acquired simultaneously with the detected light in the plot of FIG. 14(a). [Figure 15] 15(a) is a plot of the third and fourth signals obtained from the detected light reflected from the skin of the forehead of a healthy subject in a supine position; (b) is a plot of the first and second signals obtained from the detected light reflected from the hypoventilated lungs of a healthy subject, acquired simultaneously with the detected light of the plot in FIG. 15(a); and (c) is a plot of the corrected ratio of the multiple ratios calculated from the first and second signals of FIG. 15(b). [Figure 16] Plot of the first and second signals obtained from detected light reflected from the intestine of a healthy subject [Figure 17] Plot of the corrected ratio of the calculated multiple ratios of the first and second signals obtained from the detected light reflected from the brain of three subjects under different levels of systemic hypoxia against the corresponding blood oxygen levels determined by drawing blood from the internal jugular vein. [Figure 18] Plot of corrected ratios of calculated multiple ratios of first and second signals obtained from detected light reflected from the brain of a sheep subject under various levels of cerebral hypoxia due to reduced blood flow to the brain, against the corresponding blood oxygen levels determined by drawing blood from the sagittal sinus vein. [Figure 19] 10 is a plot of the calculated multiple ratio correction ratios averaged over each pulse from the waveforms of the first and second signals obtained from the detected light reflected from the brain of a sheep subject after injecting blood into the brain to increase intracranial pressure and disrupt cerebral blood flow. [Figure 20]20(a) is a plot of the third and fourth signals obtained from detected light from the internal jugular vein of a healthy subject over a period long enough to include several respiratory cycles; (b) is a plot of the first and second signals obtained from detected light reflected from the subject's brain acquired simultaneously with the detected light in the plot of FIG. 20(a); and (c) is a plot of the corrected ratio of the multiple ratios calculated from the first and second signals in FIG. 20(b). [Figure 21] Plot of the first and second signals obtained from the detected light reflected from the lungs of a human subject while breathing and holding their breath. [Figure 22] Plot of two signals from light of the first and second wavelengths reflected from the subject's brain with sensors placed in the subject's ear canal. [Figure 23] (a) Plot of the success rate of brain pulse detection using a device with the light source and photodetector centers separated laterally by distances of 10 mm, 15 mm, 20 mm, and 40 mm, where the distance between the light source and photodetector and the device contact surface is zero (i.e., the light source and photodetector are positioned on the subject's skin, similar to the placement of a conventional optical oximeter device). (b) Bar graph of the success rate of brain pulse detection using a device with the light source and photodetector centers separated by distances of 10 mm, 15 mm, and 20 mm, where the light source and photodetector and device contact surface are kept constant at 10 mm (i.e., the light source and photodetector are 10 mm away from the subject's skin). (c) Bar graph of the percentage of successful brain pulse detection using a device with a 15 mm lateral separation between the centers of the light source and photodetector, and the contact surface between the light source, photodetector, and device varied between 0 mm, 5 mm, 10 mm, 15 mm, and 20 mm (i.e., the distance of the light source and photodetector from the subject's skin varied between 0, 5, 10, 15, and 20). [Figure 24] Bar graph of the percentage of successful brain pulse detection using a device in which the centers of the light source and photodetector are separated laterally by 10 mm and the distance between the photodetector and the contact surface of the device is fixed, where the distance between the photodetector 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 offset from the light source, respectively). DETAILED DESCRIPTION OF THE INVENTION

[0078] Throughout this specification and the claims that follow, unless the context requires otherwise, the word "comprise" and variations such as "comprises" and "comprising" will be understood to mean the inclusion of a stated integer or step or group of integers or steps, but not the exclusion of other integers or steps or groups of integers or steps.

[0079] The reference to prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that that prior art forms part of the general knowledge in Australia.

[0080] Any reference herein to any prior patent or technical publication is intended to constitute the incorporation by reference of the entire subject matter of such prior publication into this specification.

[0081] The described embodiments generally relate to devices, systems and methods for assessing the visceral health of a subject.

[0082] Monitoring internal organs such as the brain after acute brain injury often relies on invasive techniques such as intracranial pressure monitoring, intraparenchymal oxygen sensors, jugular bulb venous catheters, etc. These approaches are risky, technically challenging, expensive, and can detect deterioration late (Barone DG, Czosnyka M., ScientificWorldJournal. 2014, 2014:795762, the disclosure of which is incorporated herein by reference in its entirety).

[0083] Noninvasive monitors of cerebral oxygen levels, such as cerebral oximeters that analyze near-infrared light scattering, exist to study the brain. However, cerebral oximetry has not found a significant role in clinical applications, with studies showing 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). Oxygen saturation measurements can also take 10-15 seconds, limiting the amount of information provided. Furthermore, these monitors do not provide information about pulse shape, which represents blood flow within organs.

[0084] In our previously published International Patent Publication No. WO 2008 / 134813 (the disclosure of which is incorporated herein by reference in its entirety), we described a noninvasive method for directly measuring blood oxygen saturation (e.g., central and mixed veins) by placing an optical oximeter device on the skin over deep vasculature. As noted above, pulse oximetry using red and infrared light sources is an established technique for measuring hemoglobin oxygen saturation in cutaneous blood vessels. Deoxyhemoglobin (Hb) absorbs more in the red band, while oxyhemoglobin absorbs more in the infrared band. The previous International Patent Publication disclosed preferred wavelengths of red light between about 620 nm and about 750 nm and infrared light between about 750 nm and about 1000 nm. In pulse oximetry, light is first transmitted through tissue, and the intensity of the transmitted or reflected light is then measured by a photodetector. The pulse oximeter determines the AC (pulsatile) component of absorbance at each wavelength, determining the amount of red and infrared AC components. It indicates the concentration of oxyhemoglobin and deoxyhemoglobin molecules in the blood. The ratio of oxygenated hemoglobin to total hemoglobin indicates the oxygen saturation of the blood.

[0085] In WO 2008 / 134813, the inventors demonstrated that by utilizing the pulsatile nature of deep vasculature to generate plethysmographic tracings, it is possible to precisely locate emitter and receiver elements to optimize the detected signal, thereby eliminating the need for simultaneous ultrasound examinations and measurements from multiple locations. The specificity of plethysmography in the described technique was used to identify signals originating from the vasculature of interest and to filter out signals originating from other interfering chromophores, such as small blood vessels and surrounding tissue.

[0086] In WO 2008 / 134813, the inventors demonstrated that by utilizing the pulsatile nature of deep vasculature to generate plethysmographic tracings, it is possible to precisely locate emitter and receiver elements to optimize the detected signal, thereby eliminating the need for simultaneous ultrasound examinations and measurements from multiple locations. The specificity of plethysmography in the described technique was used to identify signals originating from the vasculature of interest and to filter out signals originating from other interfering chromophores, such as small blood vessels and surrounding tissue.

[0087] In International Patent Publication No. WO 2012 / 003550 (the disclosure of which is incorporated herein by reference in its entirety), the inventors determined that improvements in the accuracy and reliability of oximeter blood oxygen saturation determinations from deep vasculature can be made by employing one or more of: (a) selecting optimal wavelengths for determining light absorption by hemoglobin in the blood (e.g., about 1045 nm to about 1055 nm and about 1085 nm to about 1095 nm); (b) positioning the emitter and receiver elements of the oximeter within the patient's ear canal; (c) increasing the distance between the emitter and receiver elements to a threshold level of about 60 mm; and (d) angling the emitter element at an angle of about 45° relative to the angle of the receiver element.

[0088] Monitoring microvascular blood oxygen levels and blood flow in patients' internal organs is of clinical value because failure can lead to organ failure and death. Early warning of impending organ failure may allow for early intervention, thereby reducing patient morbidity and mortality.

[0089] The tissue oxygen level of the viscera may indicate the health of the viscera. Therefore, monitoring the tissue oxygen level for low tissue oxygen levels may provide an early indication of pending organ failure. Analysis of reflected light from areas of the viscera, such as the brain, liver, lungs, kidneys, intestines, and heart of a subject, may provide an indication of oxygen transfer to the viscera, the tissue oxygen level of the viscera, and therefore the microvascular blood oxygen level in the blood vessels associated with the viscera, which may provide valuable clinical information regarding the health of the subject.

[0090] Some embodiments relate to devices, systems, and methods for assessing the health of a subject based on at least one signal derived from received light reflected from an area of ​​the subject proximate to an internal organ. The inventors have recognized that to ensure an accurate assessment of the subject's health, it is important to ensure that the at least one signal being considered actually represents light reflected from the internal organ, and not the overlying skin. Accordingly, described embodiments include determining that the waveform of the at least one signal actually represents a signal associated with the internal organ. Described embodiments may include determining that the waveform of the at least one signal is dominated by, or primarily associated with, received light reflected from the internal organ.

[0091] Some embodiments relate to devices, systems, and methods for determining a more appropriate or optimal placement of a sensor with respect to an internal organ to obtain a signal primarily related to received light reflected from the internal organ. For example, in response to determining that the received signal is not primarily related to received light reflected from the internal organ, the processor of the system may be configured to output instructions for repositioning or positioning the device including the sensor with respect to the targeted internal organ. The instructions may be effective to cause automatic repositioning of the device or may instruct an operator to reposition the device. In some embodiments, the instructions may include an indicated distance or coordinates that can be used to reposition the device with respect to the targeted internal organ.

[0092] Some embodiments relate to devices, systems and methods for determining, by a processor of the system, that a received signal may not result from or be primarily associated with received light reflected from an internal organ of interest, or is a contaminated signal that results from or is primarily associated with the skin.

[0093] For example, a waveform may be compared to one or more template waveforms characteristic of typical or healthy organs to determine whether the waveform is sufficiently similar to the template waveform to be determined to be associated with a signal dominated by light reflected from an internal organ. Because some internal organs are expected to have a pulse with venous characteristics in their signals, the waveform may be compared to a typical or measured venous waveform to confirm that the signal is primarily associated with an internal organ. In some cases, a skin signal or other arterial signal acquired from the subject simultaneously with the signal is expected to produce a waveform that is faster than the waveform of the signal primarily associated with an internal organ, which is used to confirm that the signal is primarily associated with an internal organ. In some embodiments, a multi-ratio correction ratio calculation is performed over a window of the waveform corresponding to the cardiac cycle or pulse, and the result is compared to a characteristic value of a typical or healthy internal organ to make a determination. In this case, performing a multi-ratio correction ratio calculation requires at least two signals obtained from received light reflected from an area of ​​the subject at two different wavelengths.

[0094] Once it has been determined that at least one signal primarily represents a signal related to a viscera, the data obtained from the waveforms can be used to assess the health of the viscera, and therefore the health of the subject. For example, the data obtained from the waveforms can be compared to information characteristic of health conditions to assess the health of the subject. For example, such health conditions can include elevated intracranial pressure, respiratory disorders, liver failure, heart failure (such as leaking heart valves), cerebral hematoma, intestinal ischemia and / or hypoventilated lungs, and / or health conditions related to visceral movement.

[0095] In some embodiments, a multi-ratio correction ratio calculation is performed on data obtained from at least two waveforms obtained from the internal organs to perform a health assessment.

[0096] Some embodiments relate to devices, systems, and methods for assessing the health of a subject based on a signal derived from received light reflected from an area of ​​the subject proximate to an internal organ, where the pulse shape and amplitude of the signal primarily indicate temporal blood flow changes over the duration of a blood pulse in the organ's microcirculation. This can be achieved, for example, by exposing the internal organ to light at wavelengths of approximately 780 nm and 820 nm, preferably 805 nm, since light at these wavelengths is absorbed to similar extents regardless of oxygen saturation level. Data obtained from waveforms corresponding to signals primarily indicative of visceral blood flow can be used to perform health assessments based on the nature of blood flow in the organ and circulatory system.

[0097] Some embodiments relate to devices, systems, and methods for acquiring data related to any one or more of microvascular blood oxygen levels, microvascular blood pulse shape and amplitude, and visceral movement of a subject. Some described embodiments advantageously enable non-invasive acquisition or extraction of such data from optical signals reflected by the subject's viscera while minimizing contributions from light reflected by the subject's skin. Thus, the described embodiments may enable visceral, i.e., subject, health assessments to be performed, including determining absolute microvascular blood oxygen saturation, microvascular blood pulse shape and amplitude, and visceral movement of the subject.

[0098] 1, 2(a), 2(b), 3, and 4, there is shown an apparatus 100 for determining data indicative of blood oxygen levels of an internal organ. The apparatus 100 comprises a body 110 having a contact surface 111 for contacting a subject 520 (see FIG. 5) near a targeted internal organ (e.g., brain 521) of the subject 520.

[0099] The body 110 of the device 100 defines a first recess 112 and a second recess 113. The first and second recesses 112, 113 extend into the body 110 from the contact surface 112, and the second recess 113 is separated from the first recess 112.

[0100] The device 100 is configured to house 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 toward the internal organ. The device 100 is configured to house a photodetector 130 in a second recess 113. The photodetector 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 somewhat altered relative to the wavelength and / or intensity of the emitted light, for example, as a result of light absorption and / or scattering by body tissue / organs. It should be understood that throughout this specification and the accompanying claims, references to light reflection or reflected light do not infer that the emitted light and reflected light are of the same wavelength and / or intensity. The device 100 is configured such that the light source 120 and the light detector 130 are recessed from the contact surface 111 (e.g., about 1 mm to about 20 mm, about 5 mm to about 15 mm, about 6 mm to about 12 mm, about 7 mm to about 10 mm, or about 7 mm, 8.5 mm, or 10 mm, etc.) and are separated from each other by a relatively small amount (e.g., a distance S) so that the received or detected light is indicative of blood oxygen levels in the blood vessels of an internal organ (e.g., veins of the surface 524 or the microvasculature of the brain 521).

[0101] Device 100 differs from standard cerebral oximeter monitors in that (contrary to existing teachings in the art) light source 120 and photodetector 130 are not in contact with the skin and have a small separation distance from each other. The inventors have determined that these modifications reduce light scattering through the skin and maximize the light that reaches photodetector 130 after passing through at least a portion of the organ. Thus, it overcomes a major limitation of existing cerebral oximeters, which obtain much of their signal from the skin rather than the underlying organ. Furthermore, by knowing the expected pulse waveform and oxygen level of the organ (which is significantly different from skin), it is possible to confirm that the signal is originating from the organ of interest. Standard cerebral oximeters cannot confirm the source of the signal.

[0102] Existing cerebral oximeters have a light source and photodetector separation of at least 40 mm, as wide separation is considered important to enable detection of light reflected from deep within the brain. However, the inventors have discovered that a much shorter separation reduces the skin signal and provides an improved signal originating from the organ.

[0103] The light source 120 may include a light-emitting region (shown as 432 in FIG. 4 ), and the photodetector 130 may include a light-sensitive region (shown as 433 in FIG. 4 ). In the embodiment shown in FIG. 4 , the light source 120 and the photodetector 130 each have a body located below the light-emitting region 433 and the light-sensitive region, respectively. In some embodiments, such as that shown in FIG. 1 , all or substantially all of the light source 120 facing the contact surface 111 is a light-emitting region (not shown), and all or substantially all of the photodetector 130 facing the contact surface 111 is a light-sensitive region (not shown). Thus, from the perspective shown in FIG. 1 , the light source 120 and the light-emitting region (not shown) are indistinguishable, as are the photodetector 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 a 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 can be, for example, about 7 mm.

[0104] The center of the light source 120 may be separated from the center of the photodetector 130 by a distance X of about 20 mm or about 15 mm. In the embodiment shown in FIG. 1, the center of the light source 120 is also the center of the light-emitting region, and the center of the photodetector 130 is also the center of the light-sensitive region, while in other embodiments, the body of the light source 120 surrounds the light-emitting region, and the body of the photodetector 130 surrounds the light-sensitive region. For example, in one aspect, the center points of the light source 120 (or light-emitting region) and the photodetector 130 (or light-sensitive region) are separated by about 10 mm to about 20 mm, e.g., about 15 mm. The spacing S between the nearest peripheries of the light source 120 and the photodetector 130 is about 4 mm to about 20 mm, e.g., about 6 mm to about 8 mm, or about 7 mm. In some embodiments, the diameter of the light source 120 and the photodetector 130 is about 8 mm in each case.

[0105] The light emitting region of the light source 120 may be set back from the contact surface 111 by a distance Y. Thus, the body 110 of the device may help space the light emitting region from the subject 520 when the contact surface 111 contacts the subject 520.

[0106] In some embodiments, the photodetector 130 may include a photosensitive region (not shown) that is set back from the contact surface 111 by a distance Y. Thus, the body 110 of the device 100 may help space the photosensitive region from the subject 520 when the contact surface 111 contacts the subject 520.

[0107] The spacing Y can range from about 1 mm to about 20 mm. In some embodiments, the spacing Y can range from about 7 mm to about 10 mm. The spacing Y can be, for example, about 8.5 mm. In a preferred embodiment of the present invention, the light source 120 (specifically, the light-emitting region of the light source 120) and the photodetector 130 (specifically, the light-sensitive region of the photodetector 130) are recessed from the contact surface 111 by about 7 mm to about 10 mm, for example, about 8.5 mm. The center points of the light source 120 and the photodetector 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 region) and the photodetector 130 (or light-sensitive region) are each about 8 mm. Experimental demonstration of the optimal spacing between the light-emitting region and the light-sensitive region, and the optimal distances of the light-emitting region and the light-sensitive region from the contact surface 111, are provided in Example 1 and FIGS. 23(a)-(c).

[0108] In another embodiment of the present invention, the light source 120 is spaced from the contact surface 111 by up to 5 mm greater than the distance of the light detector 130 from the contact surface 111. The effectiveness of this embodiment is illustrated in Example 1 and FIG.

[0109] The first and second recesses 112, 113 may have a depth D extending from the base 115 to the plane defined by the contact surface 112. The depth D may range from about 1 mm to about 10 mm. The depth D may be, for example, about 8.5 mm. If the light source 120 and the light detector 130 protrude into the recesses 112 and 113, respectively, the depth D may be slightly less than the spacing Y (also referred to as the "set back").

[0110] In some embodiments, the body 110 further comprises a wall 114 separating the first recess 112 from the second recess 113. The wall 114 may extend from the base 115 of the body 110 toward the contact surface 111 to a wall height WH. The wall 114 serves to limit light emitted from the light source 120 from being reflected or scattered toward the photodetector 130 without first interacting with the internal organs. The wall height WH may be at least about 2 mm. In some embodiments, the wall height is about 4 mm. The wall height WH may be less than or equal to the depth D. The wall 114 may have a wall thickness WT in the range of about 1 mm to 2 mm. The wall thickness WT may be, for example, about 1.8 mm.

[0111] 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 around 895 nm, or about 940 nm, or about 945 nm (the longer or first wavelength). The second discrete wavelength may be centered around 660 nm (the shorter or second wavelength). The emitted light may include light having wavelengths within at least two discrete narrow wavelength bands.

[0112] In some embodiments, the shorter wavelength light may include light having a wavelength in the range of about 600 nm to about 750 nm. For example, the shorter wavelength may be centered at about 660 nm and include a wavelength in the range of about 640 nm to about 680 nm. The longer wavelength light may include light having a wavelength in the range of about 850 nm to about 1000 nm. For example, the longer wavelength may be centered at about 895 nm and include a wavelength in the range of about 855 nm to about 945 nm. In some embodiments, the longer wavelength is about 940 nm. Shorter wavelength light is absorbed more by blood with low oxygen saturation (or low blood oxygen levels) than longer wavelength light. Longer wavelength light is absorbed more by blood with high oxygen saturation (or high blood oxygen levels) than shorter wavelength light. As a result, different intensities in each wavelength band are reflected by the internal organs and received and detected by the photodetector 130. This principle is utilized to determine blood oxygen levels, as described in more detail below.

[0113] Light in the range of about 640 nm to about 680 nm is relatively sensitive to changes in blood oxygen levels and is absorbed more 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 received light intensity can be used (in combination with light of longer wavelengths) to determine blood oxygen levels.

[0114] Light in the range of about 850 nm to about 1000 nm is relatively sensitive to changes in blood oxygen levels and is absorbed more by oxygenated blood than by 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 received light intensity can be used (in combination with light of shorter wavelengths) to determine blood oxygen levels.

[0115] 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 oxygen saturation level, so light reflected from internal organs at this wavelength may therefore provide a more reliable signal for determining the stage of the cardiac cycle and / or for health assessment based on pulsatile changes in blood flow.

[0116] In some embodiments, light source 120 is configured to emit light having a wavelength in a narrow mid-band, ranging from about 780 nm to about 820 nm. Light source 120 may be configured to emit light with a wavelength centered at about 805 nm. The amount of light in the mid-band is absorbed by blood but is not affected by blood oxygen saturation. For example, light source 120 may include a third LED adapted to emit light in a narrow mid-band.

[0117] The light source 120 may include one or more semiconductor diodes, such as light emitting diodes. The photodetector 130 may also include one or more semiconductor diodes. The light source 120 and the photodetector 130 may generally be short cylindrical in shape, such as a pill shape. The light source 120 and the photodetector 130 may have a diameter Z of approximately 8 mm.

[0118] Light source 120 may have a light output of up to about 20 milliwatts (mW). In some embodiments, light source 120 may include two LEDs. The total light output from both LEDs may be up to about 20 mW, e.g., 50 microwatts (μW) to about 20 mW, about 100 μW to about 10 mW, about 200 μW to about 5 mW, etc. In some embodiments, light source 120 may include two LEDs, and the total light output from both LEDs may be about 100 μW, 200 μW, 500 μW, 10 mW, 15 mW, 20 mW, or greater than 20 mW.

[0119] Photodetector 130 may be configured to detect a wide range of wavelengths. Light source 120 may be configured to generate pulsed light at successively different frequencies, so that at any given time, only light over a narrow bandwidth is emitted. The wavelength of the light can then be associated with the light detected by photodetector 130 based on the timing of the detection.

[0120] In some embodiments, photodetector 130 is configured to detect discrete narrowband ranges of wavelengths corresponding to the wavelength of the emitted light. Photodetector 130 may output multiple signals indicative of the intensity of light detected in each discrete narrowband range of wavelengths. In some embodiments, photodetector 130 may output a multiplexed signal of the multiple signals.

[0121] The photodetector 130 may be configured to generate one or more signals indicative of the intensity of light detected by the photodetector 130. The device 100 may be further configured to transmit the signals to a processor 562 (FIG. 5). The device 100 may include a conductive cable 140 (or wiring) for transmitting the signals to the processor 562, or may transmit the signals wirelessly to the processor 562. The signals are indicative of the blood oxygen level of the internal organs.

[0122] The photodetector 130 may be similar to the PIN photodetector used in, for example, the Nellcor™ Maxfast forehead sensor by Medtronic.

[0123] In some embodiments, device 100 includes at least two optical waveguides (e.g., optical fibers). Thus, the light-emitting region of light source 120 may include an end of a first optical waveguide (not shown) disposed in first recess 112. Photodetector 130 may include a second optical waveguide (not shown) having one end disposed in second recess 113, and the light-sensitive region may be located outside body 110 of device 100.

[0124] 3 and 4, the body 110 of the device 100 may be formed from multiple components, including a base 115 and a spacer 116.

[0125] The base 115 may be formed from a rigid material, for example, a polymer such as ABS. The base 115 may define a recess 418 for accommodating at least a portion of the light source 120 and the light detector 130. The base 115 may have a base thickness BT of about 3 mm (see FIG. 2(a)).

[0126] The spacer 116 may be formed from a soft foam. The spacer 116 may have a spacer thickness ST of about 9 mm (see FIG. 2(a)). Therefore, the main body 110 may have an overall height H of about 22 mm. The spacer 116 may be used to define a distance Y from the subject 520 to the light-emitting region when the contact surface 112 contacts the subject 520. Therefore, the spacer thickness ST may be equal to or greater than the distance Y. The spacer thickness ST may be in the range of about 8 mm to about 11 mm. The spacer 116 and the main body 110 may have a length L of about 47 mm and a width W of about 32 mm.

[0127] In some embodiments, the body 110 further includes a frame 450 configured to reside within 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.

[0128] The frame 450 may define a first recess 112, a second recess 113, and may include a wall 114. The frame 450 may have a frame height FH extending from the base 115 toward the contact surface 111. The frame height FH may be less than the spacer thickness ST, such that when the frame 450 is positioned within the cavity 419, the upper rim 451 of the frame 450 may not reach the plane defined by the contact surface 111. The frame height FH may be less than approximately 21 mm. In some embodiments, the frame height FH may be less than approximately 11 mm. The frame height FH is approximately 8.5 mm. The frame 450 may have a frame length FL of approximately 30 mm and a frame width of approximately 13 mm. The frame 450 may be formed from a rigid material, for example, a polymer such as ABS.

[0129] The frame 450 may define a first opening 452 that allows light from the light source 120 to emit from the first recess 112 and a second opening 453 that allows light from the second recess 113 to be received by the photodetector 130. In some embodiments, the first opening 452 and the second opening 453 allow the tops (light-emitting regions) 432 and (light-sensitive regions) 433 of the light source 120 and the photodetector 130, respectively, to protrude into the respective first and second recesses 112, 113.

[0130] 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 house the support 440.

[0131] Referring to FIG. 6, a process flow diagram of a method 600 for acquiring data indicative of visceral blood oxygen levels of a subject 520 is shown.

[0132] The method 600 includes, at 602, positioning the device 100, 550 from an exterior surface (eg, skin) of the subject 520 near or adjacent to an internal organ such that the light source 120 of the device 100, 550 is spaced from the exterior surface.

[0133] At 604, the device illuminates the organ through the exterior surface with light from the light source 120. The light includes light of at least a first and a second wavelength.

[0134] The photodetector 130 of the device 100 receives light at the first and second wavelengths after the illuminated light interacts with the internal organs, for example, the received light may have been partially absorbed and reflected by the internal organs.

[0135] At 608, apparatus 100 generates a first signal indicative of the intensity of light at a first wavelength and a second signal indicative of the intensity of light at a second wavelength. For example, the first wavelength can be about 660 nm and the second wavelength can be about 895 nm. In some embodiments, apparatus 100 also generates a third signal indicative of the intensity of light at a third wavelength. For example, the third wavelength can be in the range of about 780 nm to about 820 nm, or about 805 nm.

[0136] In some embodiments, the first device 100 is placed on a subject near an internal organ to target the subject's internal organ. This allows light generated by the light source 120 of the device 100 to be projected through the external surface of the subject onto the region of the internal organ. The generated light may interact with, for example, the microvasculature and veins of a body organ. The microvasculature of a body organ may include, for example, any one or more of arterioles, capillaries, and venules. Thus, the light received by the photodetector 130 may represent the blood oxygen level in the microvasculature or veins of the organ. The low oxygen level achieved in the venules and veins is in equilibrium with the extravascular tissue oxygen level and can be used to assess the tissue oxygen level of the organ.

[0137] However, the emitted light may also interact with the subject's skin, including blood vessels. This may affect the light received by the device 100 and, therefore, the generated signal. The inventors have discovered that by spacing the light source 120 away from the external surface (e.g., skin) of the subject 520, so that the light source 120 and photodetector 130 do not contact the skin, the light received by the photodetector 130 is dominated by light indicative of internal organ blood oxygen levels. The received light has minimal contribution from light indicative of blood oxygen levels originating from the subject's skin. The intensity of the light source 120 may be optimized to minimize contribution from light reflected from the skin.

[0138] Brain-targeting device placement

[0139] In some embodiments where the organ being evaluated is the brain, device 100 may be placed on the scalp in a location where the skull is relatively thin compared to other locations on the skull. For example, suitable locations may include the temples, occipital, orbital, parietal, and frontal regions of the skull.

[0140] The device's novel design, with a relatively short separation distance between the photodetector and the LED, allows the device (or sensor head) to be modified, miniaturized, and otherwise configured for placement in either the right or left ear canal. Placement in the ear canal allows for assessment of the health of the temporal lobe and cerebellum of the brain, both of which are adjacent to the ear canal. Device 100 can also be inserted into the ear canal.

[0141] In some embodiments, the device 100 is positioned over a cerebral sulcus in the brain 521 of the subject 520, such as the lateral sulcus (sylvian fissure). When the device 100 is positioned over or above the lateral sulcus or other cortical sulcus, the emitted light may interact with the cerebrospinal fluid (CSF) that covers the brain. In such a situation, each arterial pressure pulse of blood into the skull causes pulsatile changes in intracranial pressure levels, and the signal obtained from the detected light may be dominated by the effects of CSF movement in response to pulsatile changes in intracranial pressure. As described in more detail below, signals obtained from the device when positioned over or above the lateral sulcus or other cortical sulcus of a subject can be used to determine and / or monitor changes in intracranial pressure in the brain.

[0142] Lung-targeting device placement

[0143] In some embodiments, the device 100 may be configured to be placed over the suprasternal fossa, over the supraclavicular space, or between the ribs of the subject 520 so that the device 100 is near the lungs of the subject 520 to obtain data indicative of blood oxygen levels in the lungs.

[0144] Liver-targeting device placement

[0145] The device 100 may be configured to be placed in the right upper quadrant or under the ribs of the subject's upper abdomen so that the device 100 is near the subject's 520 liver to obtain data indicative of liver blood oxygen levels.

[0146] Placement of a bowel-targeting device

[0147] The device 100 may be configured to be placed in either the abdominal or lower quadrant of the subject so that the device 100 is near the intestines of the subject 520 to obtain data indicative of intestinal blood oxygen levels.

[0148] Kidney-targeted device placement

[0149] The device 100 may be configured to be placed on the back of the subject such that the device 100 is near the kidneys of the subject 520 to obtain data indicative of renal blood oxygen levels.

[0150] Placement of a device to target skeletal muscle

[0151] The device 100 may be configured to be placed over a muscle of a subject, such as a leg muscle, to target a skeletal muscle, such as the gastrocnemius (or calf muscle), to obtain data indicative of the blood oxygen level of the skeletal muscle.

[0152] Placement of a device to target the right ventricle of the heart

[0153] The device 100 may be placed on the chest, above the sternum, for example, to target the right ventricle of the heart, or It may be configured to be placed along the left edge of the sternum where it meets the ribs.

[0154] Fetal targeting device placement

[0155] The device 100 can be configured to be placed on the abdomen of the subject 520 such that the device 100 (transabdominal sensor) is proximate to the uterus (womb) of the subject 520 to obtain data indicative of blood oxygen levels in the fetal internal organs within the uterus. The fetus has a different heart rate, rhythm, and pulse shape compared to the mother. The fetus also has a different blood oxygen level compared to the mother.

[0156] In some embodiments, device 100 may comprise a light source adapted to be placed intravaginally within the mother and to illuminate the fetal brain to enable measurement of cerebral oxygen levels during delivery of the fetus.

[0157] In some embodiments, multiple devices 100, 550 may be used to acquire data from the same organ simultaneously or substantially simultaneously. For example, this may be used to determine differences between different regions of the organ, or to acquire additional data to enable more accurate results to be obtained that are more representative of the organ as a whole. In some embodiments, two devices 100 are placed on the scalp, one on each side of the head, to acquire data from the arterial pulse of the skin, or even from each hemisphere 521 of the brain.

[0158] Device 100 can be configured to simultaneously determine data from multiple organs or regions of the body, even the skin. This can be useful in detecting systemic and localized disorders of the body by monitoring abnormal combinations of blood oxygen levels, pulse shape, pulse amplitude, and / or organ movement patterns. This can determine whether changes in blood flow or oxygen levels are systemic (occurring in multiple regions) or localized (occurring in only one region).

[0159] Referring to FIG. 5, a system 500 for assessing the health of a subject 520 is shown, according to some embodiments. The system 500 includes a processor 562 and a memory 568 coupled to the processor 562. The system 500 may further include an apparatus, such as the apparatus 100, for determining data indicative of splanchnic blood oxygen levels. The system 500 may include a computing device 560 including the processor 562, a display 564, and a user interface 566. The processor 562 may be configured to execute instructions (computer-readable instructions or code) stored in the memory 568 to perform the described methods, e.g., assessing the health of the subject based on one or more signals indicative of splanchnic blood oxygen levels received from the apparatus 100. For example, the apparatus 100 may be connected to the processor 562 via the conductive cable 140 or wirelessly.

[0160] In some embodiments, the system 500 may also include a second device 550 for determining data indicative of blood oxygen levels. The second device 550 comprises a second light source and a second light detector configured to generate an additional signal. For example, the additional signal may be indicative of the timing 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 a 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.

[0161] The second light source can be adapted to generate light in the narrow mid-wavelength band discussed above, and the second photodetector can be adapted to receive and detect light in the narrow mid-wavelength band accordingly.

[0162] In some embodiments, second device 550 may be a component of a conventional skin pulse oximeter. Second device 550 may be configured to receive reflected light from subject 520. Alternatively, second device 550 may be placed on a portion of the subject, such as the forehead, nose, ear, or finger, and configured to receive light transmitted through a portion of subject 520.

[0163] The second device 550 may be placed on or near an exterior surface (e.g., skin) of the subject 520 at a location separate from the location of the first device 100 such that the third signal indicates supplemental information including pulse shape, pulse amplitude, relative timing of the pulses, and blood oxygen level relative to another location, as described in more detail below.

[0164] 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 Texas Instruments "Integrated Analog Front End for Pulse Oximeters" model AFE4490. The analog interface may also provide power to device 100, 550.

[0165] In some embodiments, system 500 further includes sensors attached to catheters 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, bowel), a cerebrospinal fluid ventricular drain (to assess the brain), a routine abdominal post-operative drain (to assess the liver, bowel), and / or a thoracic tube (to assess the heart and lungs). Processor 562 may be configured to receive signals from the sensors and process the received signals to assist in determining a health status for the subject.

[0166] To accurately assess the subject's health status based on the received signals, the received signal(s) preferably are primarily (or predominantly) indicative of the blood oxygen level of the targeted organ. For example, it is understood that poor placement of the device relative to the 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 targeted organ.

[0167] By determining that the waveform associated with the signal primarily represents a signal associated with the target organ 521 before assessing the subject's health based on the signal, the described embodiments provide a more accurate assessment of the subject's health.

[0168] Since signals characteristic of venous circulation are expected for some viscera, the waveform can be compared with a waveform of a central venous blood pressure trace or a typical venous signal having characteristics of a measured venous waveform to determine that the signal is primarily associated with a viscera. This is further explained with reference to Figures 7 and 8, in which waveforms associated with first and second signals originating from the viscera are analyzed. However, it will be appreciated that an assessment of the health of a viscera can also be determined based on waveforms associated with a single signal.

[0169] Referring to FIG. 7(a), an example is shown of a first waveform of a first signal 701 obtained from measurement light reflected from an internal organ at a first wavelength, and a second waveform of a second signal 702 obtained from measurement light reflected from an internal organ at a relatively shorter second wavelength. In this example, the first wavelength is approximately 895 nm, and the second wavelength is approximately 660 nm. These first and second signals 701, 702 were obtained from device 100 positioned near a human brain 521 in a subject 520. The amplitude or level of the signal represents the intensity of light detected by photodetector 130 and was plotted as a function of time.

[0170] Blood oxygen levels in the microcirculation of all regions of the body except the lungs typically increase during the systole phase of the cardiac cycle and decrease during the diastole phase as oxygen moves from the blood to the tissues. This leads to respective changes in the detected signal levels. The first and second waveforms of the respective first and second signals 701 and 702 exhibit multiple peaks and valleys representing intensity levels over time, indicative of the subject's pulse. Signals 701 and 702 can be described as pulsatile and / or plethysmographic signals.

[0171] In some embodiments, the second conventional device 550 may be placed at a location separate from the first device 100 to generate third and fourth signals indicative of the blood oxygen level at the skin. The separate location may be, for example, any one of the forehead, finger, ear, and nose of the subject 520. The third and / or fourth signals may be indicative of pulse shape, relative timing of the pulses, and arterial blood oxygen level from the separate location.

[0172] FIG. 8(a) shows an example of a third waveform of a third signal 803 obtained from measurement light reflected from the skin at a third wavelength and a fourth waveform of a fourth signal 804 obtained from measurement light reflected from the skin at a shorter fourth wavelength generated by the second device 550. In this example, the third wavelength is approximately 895 nm and the fourth wavelength is approximately 660 nm. The third and fourth waveforms of the third and fourth signals 803 and 804, respectively, exhibit multiple peaks and valleys representing intensity levels over time. The third and fourth signals 803 and 804 were obtained from the forehead of the human subject 520 and represent a pulsatile arterial signal of the skin. That is, the third and fourth waveforms are characteristic of the pressure waveform of an arterial circulation signal of the skin.

[0173] FIG. 8(b) shows an example of a fifth waveform of a fifth signal 805 obtained from measurement light reflected from the internal jugular vein at a fifth wavelength and a sixth waveform of a sixth signal 806 obtained from measurement light reflected from the internal jugular vein at a sixth, relatively short wavelength generated by the second device 550. In this example, the fifth wavelength is approximately 895 nm, and the sixth wavelength is approximately 660 nm. The fifth and sixth waveforms of the fifth and sixth signals 805, 806, respectively, exhibit multiple peaks and valleys representing intensity levels over time. The fifth and sixth signals 805, 806, obtained when the second device 550 is placed on the internal jugular vein of the subject 520, therefore represent pulsatile venous circulation signals. The illustrated fifth and sixth signals 805, 806 represent the shape of venous pressure changes typically observed in the vena cava when pressure levels are monitored. In other words, the fifth and sixth waveforms are characteristic of venous circulation pressure signals.

[0174] Similar to the plot of FIG. 7(a), FIG. 8(c) shows a first waveform of a first signal 801 obtained from measurement light reflected from an internal organ at a first wavelength and a second waveform of a second signal 802 obtained from measurement light reflected from an internal organ at a second, relatively shorter wavelength. These first and second signals 801, 802 were obtained from a sensor of the device 100 placed on the subject 520 near the brain 521 at the same time as the light detected for the plot of FIG. 8(a). The amplitude or level of the signals 801, 802 represents the intensity of the light detected by the photodetector 130 and was plotted as a function of time. From FIG. 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 more closely match the waveform shapes of the venous signal (shown in FIG. 8(b)) than the arterial signal (shown in FIG. 8(a)). Therefore, it can be inferred that the first and second signals 801, 802 likely originate from received light interacting primarily with the surface of the internal organs, in this case the brain 524 where most of the blood resides in the venules and veins. Therefore, the brain signal differs from the skin signal waveform and can be used to determine that the signal originates from the brain and not the skin.

[0175] 8(b) and 8(c), the waveform components may correspond to features typically found in venous blood pressure waveforms from veins, 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 that correspond to the A, C, X, V, and Y waves typically observed in pressure signals from veins (venous signals).

[0176] The A-wave component may be seen as a large trough in the waveform's signal value. The A-wave typically occurs at the end of the diastole of the cardiac cycle due to atrial contraction. The C-wave component may be seen as a small trough superimposed on the waveform's signal value after the A-wave minimum. This typically occurs at the beginning of the systole of the cardiac cycle due to tricuspid valve bulging. The X-wave component may be seen as an increase in signal value after the A-wave minimum. The X-wave typically begins at the end of the diastole of the cardiac cycle as blood is ejected from the heart, and therefore occurs during systole. The V-wave component may be seen as a trough superimposed on the waveform's signal value after the X-wave and the peak signal value. The V-wave typically occurs during the late systole of the cardiac cycle due to the atria filling. The Y-wave component may be seen as an increase in signal value after the V-wave maximum. The Y-wave typically occurs during the early diastole of the cardiac cycle as the ventricles begin to fill.

[0177] In some embodiments, determining that the waveform represents a signal primarily associated with the target viscera comprises 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.

[0178] As shown in later figures, signals representing light reflected from internal organs such as the brain, lungs, liver, intestines, and even fetal organs tend to exhibit the characteristics of a venous signal at at least one wavelength. For skeletal muscle and cardiac signals, typical venous signatures may not be present.

[0179] Using this knowledge, one or more signals from device 100 can be analyzed to determine or confirm that at least one of the signal waveforms represents a signal associated with an internal organ of subject 520. For example, in some embodiments, determining that the waveforms of one or more signals received from device 100 represent a signal waveform associated with an internal organ of subject 520 can include determining whether the waveform represents a venous signal waveform.

[0180] In some embodiments, an additional waveform from a further signal indicative of the subject's pulse, e.g., signal 803 shown in FIG. 8(a), can be compared to one or more waveforms to confirm that at least one of the signal waveforms represents a signal related to the subject's internal organs. For example, the waveform is expected to represent a signal component that is delayed in time compared to a corresponding component of the skin pulse, such as the onset (maximum signal intensity) of the cerebral pulse. This reflects the time it takes for blood to travel through the microcirculation and reach the cerebral venules. In some embodiments, a further or third signal can be obtained from reflected light having a wavelength in the range of about 780 nm to about 820 nm. In some embodiments, the signal is derived from light reflected from the subject's skin at any one of wavelengths of about 660 nm, about 805 nm, about 895 nm, or about 940 nm.

[0181] One or more signals originating from or primarily associated with different viscera may each have a characteristic waveform. The characteristic waveform may differ for each viscera, as shown in FIGS. 7, 8, 10-16, and 20, and will be described in more detail below. A waveform from at least one of the one or more signals may be compared to one or more characteristic waveforms to determine whether the waveform is sufficiently similar to any one of the characteristic waveforms. The comparison may be used to determine whether one or more signals represent a signal associated with a viscera and / or to determine the health status of the subject 520, as discussed in more detail below. In any event, in some embodiments, when the comparison is used to determine whether one or more signals represent a signal associated with a viscera and to determine the health status of the subject 520, different tolerances or thresholds for similarity may be applied. For example, a lower threshold of similarity may be applied when assessing whether one or more signals represent a signal associated with a viscera, and a relatively higher threshold of similarity may be applied when determining the health status of the subject 520.

[0182] In some embodiments, a modified multi-ratio ratio may be calculated from the signal levels of two or more signals across their respective waveforms. The modified multi-ratio ratio may be indicative of blood oxygen level, may be used to determine whether two or more signals represent signals related to internal organs, or may be used to determine the health status of the subject 520, as described in more detail below.

[0183] To compare two or more waveforms, such as those associated with signals from internal organs and those characteristic of signals from internal organs, it is preferable to compare the same portion or window of the pulsatile signal. Referring to FIG. 7 for illustrative purposes only, in some embodiments, the start of the waveform window may be determined at a peak signal level 707 of the second signal 702, and the end of the waveform window may be determined at a minimum signal level 708 of the second signal 702. In some embodiments, the end of the waveform window may be determined at a subsequent peak signal level 709 of the second signal 702. The waveform window may include a time-limited section of the signals 701, 702, 801, 802, 803, and 804. For example, the waveform window may include the section from a first extreme signal level to (or just before) a second extreme signal level in the signals 701, 702, 801, 802, 803, and 804. The window may include, for example, the interval from the first peak level to the second peak level (or just before the second peak level) in signals 701, 702, 801, 802, 803, and 804. Thus, the window may begin at the leading edge of wave A and end at the end of wave X. In some embodiments, the window of a waveform may include, for example, the interval from the first minimum signal level to the second minimum signal level (or just before the second minimum signal level) in signals 701, 702, 801, 802, 803, and 804. Thus, the window waveform may begin at wave X and end at the trough of wave A.

[0184] In some embodiments, the start and end of the window for comparing the waveforms of the signals may be determined using the waveform (or signal level) of an additional signal, such as the arterial signals 803, 804 or the jugular vein signals 805, 806. The waveform window may be determined to start at the peak signal level of the additional signal and end at the minimum signal level of the additional signal, for example. The additional signal may be derived from light having a wavelength in the range of about 780 nm to about 820 nm.

[0185] In some embodiments, analysis of waveforms from additional signals may also be used to determine the timing of systole and diastole in the cardiac cycle. This may be useful when it is not particularly easy to determine the phase of the cardiac cycle from the waveforms of one or more signals. For example, it may not be easy to determine the A-wave and X-wave components from the waveforms of one or more signals to determine when systole and diastole occur.

[0186] The waveforms may include discrete portions of the respective signals over a particular time period. In some embodiments, the waveforms may include a portion of a wavelength of a signal representing only a portion of a pulse of the subject, may include a wavelength of a signal representing a single pulse of the subject, or may include multiple wavelengths of a signal representing multiple pulses. Once the window or waveforms are 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 signals to derive the respective first and second waveforms. For example, the window function may include a rectangular, triangular, smoothed, and / or bell-shaped curve function.

[0187] In some embodiments, the waveform of one or more signals is selected based on the waveform (or signal level) of an additional signal obtained from light at a third wavelength in the range of about 780 nm to about 820 nm. The waveform can begin, for example, at a point between the peak signal level of the third signal and the minimum signal level of the additional signal. Light having a wavelength in the third wavelength range is sensitive to blood but insensitive to changes in blood oxygen levels, and therefore may provide a more reliable signal for determining the phase of the cardiac cycle and the shape of the waveform resulting from pulsatile blood flow. This is particularly useful for determining the waveform of complex signals, such as those obtained from the lungs and possibly the brain. For example, an additional signal based on light at a wavelength of about 805 nm can be used to recognize impairments in microvascular blood flow to an organ based on the waveform (or pulse shape and amplitude) of the additional signal. The additional signal can also be used for templates, discussed elsewhere, to define a characteristic waveform of an organ to determine whether a signal is representative of a given organ.

[0188] Although Figures 7, 8, 10-16 and 20 are shown in the time domain, it will be understood that waveforms can be analyzed in the time domain or the frequency domain.

[0189] 9, there is shown a process flow diagram of a computer-implemented method 900 for assessing the health status of a subject 520, according to some embodiments. The method 900 may be performed by a processor 562 executing instructions stored in a memory 568.

[0190] At 902, processor 562 receives one or more signals. The one or more signals are derived from received light reflected from a region 522 proximate to internal organ 521 in subject 520 at first and second wavelengths, respectively. For example, the received light may include emitted light that has interacted with internal organ 521.

[0191] At 904, the processor 562 determines that at least one of the one or more respective waveforms of the one or more signals represents a signal primarily associated with the internal organs 521. Determining whether one or more waveforms represent a signal associated with the internal organs is described in more detail below.

[0192] In some embodiments, in response to processor 562 not determining that at least one of the respective waveforms of one or more of the one or more signals represents a signal associated with an internal organ, 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 device to reposition light source 120 of device 100 relative to the exterior surface of subject 520. In some embodiments, the device may be configured to automatically reposition light source 120. In some embodiments, the system may be configured to instruct an operator to reposition the device relative to the targeted internal organ. Upon repositioning, updated one or more signals may be provided to processor 562 for processing.

[0193] At 906, processor 562 compares data obtained from at least one of the one or more waveforms with information characteristic of the health state to assess the health of subject 520. Processor 562 can analyze at least one of the one or more waveforms to derive data, which can include, for example, deconvoluted components or calculated slopes (or rates of change) of the waveforms.

[0194] In some embodiments, the processor 562 can assess the health status of the subject 520 and output an assessment of the health status of the subject 520. For example, the assessment can be output to the display 564 or any other user interface device, such as a speaker or a third-party device. In response to determining that the subject 520 is likely to have a health status, the processor 562 can send a signal such that information based on the assessment is output via the display 564 and / or speaker and / or alarm, such that it is displayed on the display 564 and / or an audible alarm is sounded. In some embodiments, a control signal can be sent to monitoring or control equipment coupled to the subject to adjust settings of the equipment. Determining whether the subject 520 is likely to have a health status is discussed in more detail below.

[0195] In some embodiments, the processor 562 may be configured to display one or more of the oxygen levels throughout the systolic and diastolic phases of each cardiac cycle, estimated tissue oxygen levels of organs (based on the trough level reached during diastole), respiratory inspiratory and expiratory oscillations of oxygen levels, skin and organ plethysmographic signals used to derive oxygen levels and organ and skin plethysmographic signals originating from 805 nm that may be used to recognize obstructions to microvascular blood flow within organs, organ movement (brain, liver, lungs and heart) related to the respiratory and cardiac cycles, asymmetry between signals from the left and right hemispheres of the brain, or other combinations of sensors across multiple organs of the body.

[0196] As previously mentioned, the inventors have recognized that waveforms associated with signals primarily arising from or related to internal organs exhibit particular characteristics and are generally significantly different from waveforms associated with signals primarily arising from or related to the skin. In some embodiments, processor 562 is configured to create or generate one or more templates for a particular internal organ based on one or more signals received from device 100 when device 100 is positioned to target the particular internal organ. In some cases, an operator can position device 100 relative to a particular internal organ and analyze waveforms resulting from the received signals to confirm that the signals are representative of the organ. A template for a particular internal organ can be created based on a characteristic waveform determined for the particular internal organ using multiple signals obtained from one or more subjects. Thus, one or more templates stored in memory 568 can be based on a library or database of characteristic waveforms previously obtained from a particular internal organ. The database can include multiple characteristic waveforms, each characteristic waveform associated with a particular internal organ. For example, the database can include characteristic waveforms for any one or more of the brain, fetal brain, lungs, liver, kidneys, intestines, skeletal muscle, heart, and fetal heart. Each characteristic waveform can be based on a waveform from one or more signals previously received from the organ with which the characteristic waveform is associated. For example, one or more characteristic waveforms can include an average or sum of multiple signals previously received from the same type of organ from different subjects. In some embodiments, one or more characteristic waveforms can be based on a theoretically expected (or idealized) waveform for the organ. In some embodiments, one or more templates can include non-organ-specific waveforms, such as waveforms associated with signals primarily arising from or related to the skin.

[0197] In some embodiments, processor 562 may receive information indicative of an organ being targeted by device 100. Processor 562 can use the information indicative of the targeted organ to assist in determining that one or more waveforms primarily represent signals associated with the target organ. Processor 562 can also use the information indicative of the targeted organ to assist in determining a health status. For example, processor 562 can use information regarding the type of organ to select a template that corresponds to the associated target organ, thereby reducing processing time. Thus, in some embodiments, processor 562 can compare one or more waveforms only to templates associated with known target organs.

[0198] Determine whether the waveform represents signals primarily related to internal organs

[0199] In some embodiments, memory 568 includes one or more templates, each template including information characteristic of a particular internal organ, and in some embodiments, information characteristic of a typical or healthy internal organ. For example, a template can depict a characteristic waveform of light intensity versus time. A template can include a modified ratio of multiple ratios or a characteristic plot of blood oxygen levels. Processor 562 can be configured to compare at least one or more waveforms to one or more template waveforms to determine whether it represents a signal primarily associated with internal organs 521. The comparison can include, for example, calculating the difference between the waveform and the template waveform and comparing it to a threshold to determine the likelihood that the signal is primarily associated with internal organs. The difference between multiple template waveforms can be calculated to determine an optimal template waveform. This determination can include, for example, calculating the minimum sum of squared residuals. If the sum of squared residuals is less than a threshold error value, processor 562 can determine that the waveform represents (or closely matches) a signal primarily associated with internal organs 521.

[0200] In some embodiments, the one or more waveforms can be compared to a typical venous waveform, and in response to the processor determining that at least one of the one or more signals substantially corresponds to a typical venous waveform, it can be determined that at least one of the one or more signals is dominated by signals originating from visceral organs. For example, and as noted above, a venous waveform typically includes A, C, X, V, and / or Y wave components.

[0201] In some embodiments, a further or third waveform may be derived from a further signal obtained from the second device 550. The further waveform may represent, for example, an arterial skin pulse obtained from a location away from or surrounding an internal organ. The further waveform may be compared with one or more waveforms with respect to shape, amplitude, and timing to determine whether at least one of the first and second waveforms represents an arterial pulse and is therefore not associated with an internal organ 521 and is more likely to originate from the skin.

[0202] In some embodiments, processor 562 may receive an arterial signal, such as signal 803 shown in FIG. 8(a), from a sensor of a device placed on the subject's skin to obtain an additional arterial waveform indicative of the subject's 520's cutaneous arterial pulse. Processor 562 may compare the additional waveform with one or more waveforms derived from the subject's 520's internal organs to determine whether at least one signal peak 807 of the one or more waveforms is offset in time from a respective signal peak 808 of the additional waveform. For example, one or more waveforms may depict a signal component, such as a peak signal level, that lags a corresponding component of the additional signal of the additional waveform (the peak signal level representing the onset of the waveform).

[0203] 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 modified ratio of the multiple ratios may be used to determine whether the first and second signals represent signals associated with an internal organ or to determine the health status of the subject 520, as described in more detail below.

[0204] Signal waveform - brain

[0205] If the internal organ 521 is the brain, it will exhibit light of a different wavelength, and one or more signals associated with the brain are expected to be similar to venous signals. Thus, in some embodiments, determining that at least one of the waveforms represents a signal primarily associated with a internal organ includes determining that at least one of the waveforms corresponds to a waveform of a venous pulse. In other embodiments, determining that at least one of the waveforms represents a signal primarily associated with a internal organ includes determining that at least one of the waveforms does not correspond to a waveform of an arterial pulse.

[0206] In some embodiments, the one or more signals include a first signal and a second signal. The first signal may be derived from a first wavelength of light that is shorter than the second wavelength of light that is derived from the second signal. For example, the second wavelength may be approximately 660 nm. If the targeted organ is the brain, the second signal 702, 802 derived from light reflected by the brain at a second wavelength of approximately 660 nm may more consistently represent a venous signal. Thus, 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 805 nm. A calculated change in oxygen level or a modified ratio of multiple ratios may also be used as a template for this purpose, as described below.

[0207] In some embodiments, processor 562 is configured to analyze one or more waveforms to determine one or more components that are compared to one or more corresponding components of one or more template waveforms. For example, processor 562 may 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 may be defined by a template waveform, such as a reference curve.

[0208] A characteristic brain pulse shape may include a first component having a generally increasing signal level at a first rate (corresponding to an X wave), followed by a second component having a generally decreasing signal level at a second rate (corresponding to the leading edge of an A wave) that is less in magnitude than the first rate of the X wave. Processor 562 may therefore determine the slope or rate of change of the first and second components.

[0209] In some embodiments, processor 562 can analyze one or more waveforms to deconvolute components from the waveforms. Processor 562 can analyze the components to determine slopes or rates of change and compare them to characteristic slopes or rates of change to determine whether at least one of the one or more signals represents a signal originating from the viscera (the same approach also applies to changes in oxygen levels over the pulse duration).

[0210] It is expected that the pulsating signal representing the internal organs may be offset in time from a third signal representing an arterial signal such as obtained from the skin (e.g., forehead, nose, ear) of the subject 520. Thus, in response to determining that at least one signal peak 807 of a respective waveform of the one or more signals is offset in time from a respective signal peak 808 of a further waveform of the further signals, the processor 562 may determine that at least one of the respective one or more signals represents the brain.

[0211] 22 shows a first signal 4401 (approximately 895 nm) and a second signal 4402 (approximately 660 nm) obtained from device 100 placed in the ear canal of a human subject, where processor 562 can be configured to determine that at least one of the waveforms represents a signal primarily related to the brain by analyzing second signal 4402.

[0212] Signal waveform - lungs

[0213] The signal derived from light reflected by the lungs has been found to be relatively complex and may depend on several additional factors. These factors may include whether the alveoli (air sacs) are ventilated and the blood flow (perfusion) to the air sacs. Blood flow may depend on the person's postural position. Unlike other organs in the body, oxygen levels decrease during systole and increase during diastole. Furthermore, the change in oxygen levels during the pulse period is quite large.

[0214] In some embodiments, to obtain one or more signals primarily related to the lungs, device 100 may be positioned near the upper region of the lungs (e.g., near the apex of the lungs) with the lungs above the heart and the subject oriented in a semi-upright body position.

[0215] 10(a), an exemplary plot of a first signal 1001 obtained from measurement light reflected from an internal organ at a first wavelength (e.g., 895 nm) and a second signal 1002 obtained from measurement light reflected from an internal organ at a second, shorter wavelength (e.g., 660 nm) is shown. These signals 1001, 1002 were obtained from an apparatus 100 positioned near well-ventilated and perfused lungs on a human subject 520.

[0216] As shown in Figure 10(a), a first signal 1001 (895 nm) obtained from a ventilated lung represents a venous signal. The first signal 1001 includes A-, C-, X-, V-, and Y-wave components.

[0217] Thus, in some embodiments, determining by the processor that at least one of the waveforms represents a signal primarily associated with the pulmonary viscera may include determining that at least one of the waveforms corresponds to a venous pulse waveform. As noted above, determining that at least one of the waveforms corresponds to a venous pulse waveform may include comparing the first and / or second waveforms to a typical or measured venous pulse waveform to determine a measure of suitability, or comparing the first and / or second waveforms to a measured arterial pulse waveform of the subject to determine a measure of incompatibility.

[0218] Again, and as noted above, determining that at least one of the one or more signals represents a signal primarily associated with the internal organs involves comparing components of the waveform(s) of the one or more signals to template waveform characteristics of the internal organs, in this case the lungs, and may involve, for example, deconvolving the components from the waveform(s).

[0219] In some embodiments, processor 562 can be configured to determine that the pulse shape of a waveform of a relatively long wavelength (e.g., approximately 895 nm) signal sensitive to oxygenated blood substantially corresponds to a characteristic pulmonary pulse shape. For example, the characteristic pulmonary pulse shape can include a waveform representative of a venous pulse signal and / or the characteristic pulmonary pulse shape can include a first component having a generally increasing signal level (X wave) at a first rate, followed by a second component having a generally decreasing signal level at a second rate that is less in magnitude than the first rate.

[0220] In some embodiments, the processor 562 may be configured to determine that the waveform of the signal represents a signal from the lungs when the first waveform is determined to include A waves, X waves, V waves, and Y waves.

[0221] In some embodiments, the processor 562 can be configured to determine that the pulse shape of a signal waveform from light of approximately 660 nm wavelength, which is particularly sensitive to changes in deoxygenated blood levels, has a characteristic pulmonary pulse shape. For example, the characteristic pulmonary pulse shape can include a waveform representative of an inverted pulmonary artery pressure waveform (e.g., 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 include, for example, a prominent systolic signal in the inverted pulmonary artery pressure waveform. The diastolic phase of the inverted pulmonary artery pressure waveform can include a dicrotic notch, similar in shape and timing to the waveform's V wave (which indicates the end of systole and the beginning of diastole). Furthermore, the onset of the systolic pulse typically precedes the onset of the cutaneous artery pulse, which may reflect an earlier contraction of the right ventricle compared to the left ventricle.

[0222] 21 shows two signals 2601 containing multiple pulses obtained while a subject is breathing in region 2602, and then while the subject is holding their breath in region 2603. It can be seen that the waveform (pulse) in region 2603 has a more uniform intensity range than the two signals 2601 in region 2602. In some embodiments, the subject may hold their breath while determining whether one or more signals represent signals from the lungs, which may simplify and / or improve the accuracy of the determination.

[0223] Signal waveform - Liver

[0224] 11, an exemplary plot of first and second signals 1101, 1102 received from device 100 positioned on a human subject 520 near the liver is shown. The first signal 1101 is obtained from measurement light reflected from the liver at a first wavelength (e.g., 895 nm), and the second signal 1102 is obtained from measurement light reflected from the liver at a second, shorter wavelength (e.g., 660 nm).

[0225] As shown, A-wave, C-wave, and X-wave components can be observed in the first and second waveforms of the first and second signals 1101, 1102, respectively. In some embodiments, a V-wave component can also be observed. The waveforms of the first and second signals 1101, 1102 can also include additional small valleys (P-waves, including P1 and P2 waves). The P1 wave can represent a contribution to light from the first and second signals 1101, 1102 reflected from a portal vein systolic pulse. The P2 wave can represent a contribution to light from the first and second signals 1101, 1102 reflected from a portal vein diastolic pulse. The presence of P1 and / or P2 waves is not observed in other organs and appears to be unique to signals from the liver.

[0226] Thus, in some embodiments, determining by processor 562 that at least one waveform of one or more signals derived from light reflected from 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.

[0227] As described above, determining that at least one of the one or more signals represents a signal associated with an internal organ, primarily the liver, may include comparing components of the waveform of the first and / or second signal with a template waveform characteristic of the liver, and may involve, for example, deconvolving the components from the waveform.

[0228] In some embodiments, determining by processor 562 that at least one of the waveforms represents a signal primarily associated with the liver may include determining that at least one of the waveforms includes at least one of an X wave and a P wave.

[0229] In some embodiments, processor 562 can be configured to determine that the pulse shape of at least one of the one or more waveforms substantially corresponds to a characteristic liver pulse shape. For example, the characteristic liver pulse shape can include a waveform representative of a venous pulse signal and / or the characteristic liver pulse shape can include a first component having a generally increasing signal level at a first rate (X-wave component), followed by a second component having a generally decreasing signal level (leading edge of diastole) at a second rate having a magnitude less than the first rate.

[0230] In some embodiments, the subject may hold their breath while determining whether one or more signals represent a signal from the liver, which may simplify and / or improve the accuracy of the determination.

[0231] The P-wave component of the liver tracing may also result in characteristic components in the calculated multi-ratio correction ratio and blood oxygen level, as described below. Based on the presence of these characteristic components, processor 562 can determine that the signal represents a signal from the liver.

[0232] Signal waveform - intestine

[0233] 16 shows an exemplary plot of a first signal 1601 obtained from measurement light reflected from the intestine at a first wavelength (e.g., 895 nm) and a second signal 1602 obtained from measurement light reflected from the intestine at a second, shorter wavelength (e.g., 660 nm). The first and second signals 1601, 1602 were obtained from device 100 positioned on subject 520 near the intestine.

[0234] Plethysmographic signals derived from light reflected from the intestine may resemble pressure changes in the central venous circulation due to A, C, V, X, and Y waves. These waves are temporally delayed compared to the skin and liver plethysmographic signals. This may be due to venous pulsation, which must pass through the liver to reach the portal vein and then the intestinal microcirculation. Thus, the delayed X wave may have a late convex component due to the simultaneous arrival of the arterial pulse of intestinal blood. The V wave may not be prominent. As a result, the peak or maximum light intensity level of the pulse is significantly delayed and occurs late in systole compared to the forehead skin pulse.

[0235] Thus, the signal waveform of the signal from the intestine may exhibit venous characteristics in any one or more of the A, C, X, V, and Y waves, which may be delayed relative to the corresponding waves of the skin and liver. In some embodiments, determining by processor 562 that at least one of the waveforms represents a signal primarily associated with the intestine may include determining that the peak signal time of one or more signals is offset from the peak signal time from additional signals, such as a cutaneous arterial signal. This offset (or lag) reflects the time it takes for these pressure pulsations in the venous circulation to pass along the portal vein, back through the liver, and reach the intestinal microcirculation.

[0236] As with the brain and liver, the quality of gut-related signals may improve if subjects hold their breath.

[0237] In some embodiments, the processor 562 can determine the health of the intestine based on a comparison to a characteristic waveform similar to that shown in Figure 16. Deviations from the characteristic waveform can be used to diagnose, for example, one or more of ischemic hepatitis, cirrhosis, abdominal compartment syndrome, portal vein thrombosis, and portal hypertension.

[0238] Signal waveform - kidney

[0239] Measurement light reflected from the kidney at a first wavelength of about 895 nm and a second, shorter wavelength of about 660 nm can be used to determine kidney health. The first and second signals can be obtained from device 100 positioned on subject 520 near the kidney.

[0240] The kidneys have a very high arterial blood flow compared to other organs. Therefore, the pulse shape of the first signal waveform from light with a wavelength of approximately 895 nm is unexpectedly not arterial, characterized by a prominent systolic minimum. The second signal waveform from light with a wavelength of approximately 660 nm is relatively flat in comparison, although A, C, X, V, and Y wave components are discernible. The flat waveform may be due to the high oxygen levels throughout the pulse.

[0241] Thus, in some embodiments, determining by processor 562 that at least one waveform of one or more received signals represents a primarily renal-related signal includes determining that the waveform is substantially arterial characterized by a prominent systolic minimum. In some embodiments, determining by processor 562 that at least one waveform of one or more received signals represents a primarily renal-related signal includes determining that the waveform is relatively flat but still includes A, C, X, V, and Y wave components. In some embodiments, determining by processor 562 that at least one waveform of one or more received signals represents a primarily renal-related signal includes determining that the pulse shape of the waveform substantially corresponds to a characteristic renal pulse shape.

[0242] Signal waveform - Fetus

[0243] The pulsatile signal originating from the fetus differs from that of the mother in many ways. These differences make it easy to confirm that the signal originates from the fetus. The heart rate is typically higher than that of the mother, approximately 120–160 beats per minute compared to 70. The fetus also has a lower oxygen saturation. The fetal brain has a low arterial saturation of approximately 90% (100% in the mother), and other organs are even lower, approximately 65% ​​(100% in the mother). As a result, the venous oxygen saturation is very low, at 25–40% (75% in the mother). Finally, the fetal blood pressure is very low, and the circulation is functionally different from the mother's circulation, resulting in a different pulse waveform shape. The fetal brain provides an ideal target because of its increased blood flow compared to that of overlying tissues, such as the skin, abdominal muscles, and cervix.

[0244] Because the fetal pulse is not synchronized with its mother (biological or surrogate), processor 562 may 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 derived from light from the fetus with the peak signal levels from further signals derived from light from the mother.

[0245] Signal waveform - Muscle

[0246] Muscle health can be assessed using measurement light reflected from the resting gastrocnemius muscle of a human subject at a first wavelength of approximately 895 nm and a second, shorter wavelength of approximately 660 nm. Simultaneous recordings from the subject's forehead skin provide a third signal derived from light at a wavelength of approximately 895 nm and a fourth signal derived from light at a wavelength of approximately 660 nm. Resting muscle blood flow is low, resulting in a signal characterized by a small pulse amplitude. Because skeletal muscle has relatively few venules compared to other organs, the pulse shape is essentially arterial.

[0247] Thus, in some embodiments, determining by processor 562 that at least one waveform of one or more received signals represents a primarily muscle-related signal includes determining a pulse shape of the waveform, determining that the waveform substantially corresponds to a characteristic muscle pulse shape. In some embodiments, determining by processor 562 that at least one waveform of one or more received signals represents a primarily muscle-related signal includes determining that the waveform has a relatively low pulse amplitude and is representative of a signal that is substantially arterial in nature.

[0248] Evaluating the health status of a subject based on waveforms

[0249] 9 above, once processor 562 determines that at least one of the one or more signals is primarily associated with light reflected from the target organ, one or more waveforms of the one or more signals may be analyzed to determine or assess the health of subject 520. For example, in some embodiments, at least one of the one or more waveforms may be compared to information characteristic of the health of subject 520 to assess the health of subject 520.

[0250] For example, in some embodiments, one or more waveforms of one or more received signals primarily related to light reflected from the target organ may be compared (e.g., stored in memory as templates) with one or more characteristic pulse shapes of each healthy organ, and the processor may be configured to determine a measure of similarity (or dissimilarity) between the waveforms and the characteristic pulse shapes, and determine or assess the health of the organ based on the measure of similarity (or dissimilarity).

[0251] Further described embodiments relate to the evaluation of one or more waveforms to determine the likelihood of a subject having various conditions involving organ damage related to low microvascular blood oxygen levels or abnormal blood flow or movement, such as elevated intracranial pressure (ICP), cerebral hemorrhage, stroke, ischemic hepatitis, pneumonia, ischemic bowel, heart failure, etc.

[0252] Pulsatile blood flow in the organ microcirculation may reflect differences over the cardiac cycle between microvascular arteriolar pressure, which promotes blood flow, and microvascular venous pressure, which resists blood flow. Differences in microvascular pressure levels vary over the systolic and diastolic phases of the cardiac cycle and may define the shape and amplitude of the signal waveform obtained from light reflected by the organ. Relative increases in systemic venous circulation pressure levels are associated with plethysmographic signals that exhibit predominantly or exaggerated features similar to central venous pressure waveforms. These features include the A, C, X, V, and Y waves, with peak signal levels during the diastolic phase of the cardiac cycle. This finding may indicate poor organ perfusion.

[0253] It can be useful to analyze waveforms derived from signals associated with wavelengths of light near 805 nm because they are not significantly affected by changes in blood oxygen concentration and are affected only by blood flow. The waveform shape resulting from signals associated with wavelengths around 805 nm can be used to detect abnormal patterns of blood flow resulting from disorders of arterial and venous circulation. Potential systemic circulatory disorders include heart failure and fluid overload, which increases pressure levels in the venous circulation. Furthermore, central venous pressure levels can also be estimated noninvasively. For example, similar characteristics may be seen in waveforms when arterial pressure levels are low and venous pressure levels are normal. Disorders associated with this condition include cerebral arterial vasospasm, which can occur in stroke, and arterial thrombosis.

[0254] heart failure

[0255] Measurement 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 has heart failure. In this example, the first and second signals represent a prominent early V-wave component.

[0256] To determine the likelihood that the subject has heart failure, such as a leaking heart valve leading to tricuspid regurgitation, processor 562 may analyze one or more waveforms of each signal derived from detected light reflected from brain 521. Processor 562 may derive data from waveforms that exhibit a prominent V-wave component and compare the derived data to a template waveform characteristic of signals representing subject 520 with heart failure to determine whether the derived data corresponds to the template waveform. In response to determining that the derived data corresponds substantially (e.g., by a threshold amount) to the template waveform, processor 562 determines that subject 520 is likely to have heart failure. This approach is applicable to a range of disorders that cause heart failure in which venous characteristics of the waveform become prominent.

[0257] In some embodiments, the processor 562 may derive data from the waveform indicative of the amplitude of the V wave component. The processor 562 may compare the derived amplitude to a threshold level to determine whether the subject is likely to suffer from heart failure.

[0258] Intracranial pressure (ICP)

[0259] Referring to FIG. 12(b), an exemplary plot is shown of a first signal 1201 obtained from measurement 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 obtained from light measured at a second, relatively shorter wavelength (e.g., 660 nm). The first and second signals 1201 and 1202 were obtained from sensors of the device 100 placed on the scalp of the animal subject after injecting 6 ml of blood into the anterior cranial fossa via the anterior cranial fossa to raise the sheep's intracranial pressure to a range of about 50 mmHg to about 90 mmHg. FIG. 12(a) shows an exemplary plot of a third signal 1203 derived from light at a wavelength of about 895 nm and a fourth signal 1204 derived from light at a wavelength of about 660 nm, representing arterial skin signals, obtained from the sheep's nose skin substantially simultaneously with the first and second signals of FIG. 12(a).

[0260] In a healthy subject, the waveform of one or more signals is expected to substantially correspond to a typical venous waveform. However, it can be seen that the first and second signals 1201, 1202 have waveforms with components that appear more characteristic of an arterial waveform than a venous waveform. Specifically, the initial magnitude of the pulse slope (or gradient) of the leading edge (falling optical intensity) 1211 of the pulse is greater than the initial magnitude of the gradient of the leading edge 811 of the characteristic signal representing the venous pulses 805, 806. In some cases, other venous features, such as the V-wave and / or Y-wave components, may be absent or reduced in the first and / or second waveforms or the third waveform (805 nm). It is clear that this still represents a brain signal, as there is a clear delay in the onset of the pulse compared to the skin signal, represented by the double-headed arrow in FIG. 12(b).

[0261] Therefore, it was determined that a change in the waveform, which has some arterial characteristics in shape, may indicate an increase in intracranial pressure. This is due to an increase in cerebral arterial pressure to maintain adequate blood flow. Because arterial pressure is much greater than central venous pressure, the pulse waveform becomes more arterial. These two pressures influence the shape of the pulse waveform.

[0262] Thus, in some embodiments, processor 562 may compare one or more waveforms of each one or more signals derived from detected light from brain 521 to a template waveform representative of subject 520 having relatively high intracranial pressure to determine whether one or more waveforms substantially represent the template waveform. This may include, for example, calculating a sum of squared residuals. In response to determining that at least one of the waveforms represents the template waveform, processor 562 may determine that subject 520 is likely to have relatively high intracranial pressure (e.g., if the intracranial pressure is less than about 90 mmHg), which may indicate, for example, the onset of cerebral edema or cerebral hemorrhage.

[0263] In some embodiments, processor 562 may analyze at least one of the first and second components of the waveform of each signal derived from detected light reflected from subject's brain 521 to determine the slope of the leading edge of the initial slope of each of the pulses (see, e.g., 1211 in FIG. 12 ). In response to determining that at least one of the slopes of the leading edges is greater than a threshold, processor 562 may determine that subject 520 is likely to have relatively high intracranial pressure.

[0264] In some embodiments, processor 562 may analyze at least one of the first and second components of the waveform of each signal derived from the detected light from brain 521 to determine whether a V-wave and / or Y-wave component is present. In response to determining that a V-wave and / or Y-wave component is not present, processor 562 may determine that subject 520 is likely to have relatively high intracranial pressure.

[0265] Disorders associated with relatively elevated pulmonary or systemic arterial pressure levels

[0266] Disorders associated with a relative increase in pulmonary arterial circulation pressure levels include pulmonary embolism, interstitial lung disease, chronic obstructive pulmonary disease, non-infectious pneumonia, acute lung injury, and / or acute respiratory distress syndrome. A relative increase in pulmonary arterial pressure levels compared to pulmonary venous pressure levels is associated with a pulmonary plethysmography pulse signal 1001 (e.g., from light having a wavelength of 895 nm or 805 nm), which exhibits several characteristics of the pulmonary arterial circulation pressure waveform. The A, C, V, and Y wave components become less prominent, replaced by components similar to those characteristic of the pulmonary arterial pressure waveform, including prominent systolic and diastolic pulses and dicrotic notches (which may coincide with the V and Y waves).

[0267] In some embodiments, the processor 562 may analyze the waveform shape of the signal derived from the detected light from the target organ to determine health conditions associated with a relative increase in venous pressure levels, such as systemic hypertension, and systemic arterial circulatory pressure levels compared to central venous pressure, such as acute brain injury, liver cirrhosis, and / or local organ dysfunction, such as compartment syndrome. For example, the processor may be configured to compare the waveform or data from the waveform to template waveforms or data characteristic of such health conditions to determine the likelihood that the subject exhibits a health condition.

[0268] Disorders associated with elevated arterial pressure levels, such as hypertension, in which the waveform develops a more arterial pulse shape, can also be detected. Other disorders include elevated intracranial pressure in the brain and compartment syndromes elsewhere in the body, such as compartment syndromes in the abdomen or calf. The same approach can be used with pulses or waveforms arising from the pulmonary microcirculation to detect abnormal waveforms that may result from disorders resulting in elevated pulmonary arterial pressure levels (interstitial lung injury, ARDS, pulmonary embolism) or elevated pulmonary venous pressure levels (left-sided heart failure).

[0269] Disorders associated with relatively elevated levels of systemic venous pressure

[0270] Relative increases in systemic venous circulation pressure levels may be associated with disorders including heart failure and fluid overload secondary to intravenous fluid administration. Monitoring waveform shape may be useful for monitoring systemic venous circulation pressure levels to detect heart failure, guide intravenous fluid resuscitation of the circulation, and avoid fluid overload.

[0271] Relative increases in systemic venous pressure levels are associated with waveforms at 660 nm or 805 nm, which indicate more prominent 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 increasing signal values.

[0272] The processor 562 may determine that a subject has such a disorder, for example, from determining that the magnitude or amplitude of any one or more of the A, V, X, and / or C wave components is greater than a threshold. The magnitude or amplitude of a component may be calculated as the range between the maximum and minimum values ​​of the component.

[0273] High intracranial pressure

[0274] Referring to FIG. 14(b), an exemplary plot of a first signal 1401 obtained from measurement light reflected from a subject's brain at a first wavelength (e.g., 895 nm) and a second signal 1402 obtained from measurement light reflected from the brain at a second, shorter wavelength (e.g., 660 nm) is shown. The first and second signals 1401, 1402 were obtained from the device 100 placed on the sheep's scalp after injecting 6 ml of blood into the anterior cranial fossa via the anterior cranial fossa, raising the sheep's intracranial pressure to above approximately 150 mmHg. FIG. 14(a) shows simultaneous third and fourth signals 1403, 1404 obtained from the skin of the subject's nose, which are shown for comparison.

[0275] As shown, first and second signals 1401, 1402 exhibit an increase in amplitude of an AC pulse signal that is characteristic of intracranial pressure in a subject.

[0276] If the pulse amplitude increases in the brain signal but remains unchanged in the skin signal, this indicates that the disorder is likely limited to the brain. One example is the independent increase in blood flow to the brain in response to an increase in intracranial pressure (ICP) levels. In this case, the pulse amplitude (signal level) increases in response to the brain signal, but there is no change in the skin pulse amplitude because the skin blood flow is unchanged. On the other hand, if the pulse amplitude increases in both locations (skin and brain), this indicates that the disorder is likely affecting all parts of the body. An example would be low oxygen levels throughout the body, which increases blood flow throughout the body to compensate. This changes the pulse waveform throughout the body. This approach can be applied to detect disorders in other organs of the body.

[0277] The processor 562 may analyze at least one waveform of each of the one or more signals derived from the detected light from the brain 521 to determine whether the waveform exhibits an increased amplitude of an AC component compared to a corresponding component of an arterial waveform of an additional signal acquired simultaneously with the one or more signals from the subject, such as a skin signal. In response to determining that the amplitude of the AC component has increased, the processor 562 may determine that the subject 520 is likely to have relatively high intracranial pressure or cerebral hemorrhage. Furthermore, a decrease followed by an increase in DC levels or cerebral microvascular blood oxygen levels may also indicate that the subject has high intracranial pressure levels or cerebral hemorrhage.

[0278] Hypoventilated lungs

[0279] In hypoventilated lungs, there is less blood flow in the pulmonary arteries, and therefore the pulmonary venous pressure level is relatively high compared to the pulmonary artery pressure experienced by this region of the lung, and the sensor waveform reflects this with a predominantly venous signal (Figure 15(b)).

[0280] To acquire one or more signals primarily related to the lungs, the device 100 may be placed on the back of the subject 520 while the subject is in a supine position with atelectatic (collapsed) alveolar air sacs.

[0281] Referring to Figure 15(b), an exemplary plot 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) is shown. The first and second signals 1501, 1502 were obtained from the device 100 placed on the subject 520 near the dependent, hypoventilated lungs. Figure 15(a) shows simultaneous third and fourth signals 1503, 1504 obtained from the skin on the forehead of the subject 520, shown for comparison.

[0282] As shown, first signal 1501 and second signal 1502 may include components consistent with pressure waveforms found in pulmonary veins. These features include A, C, X, V, and Y waves. The V wave is prominent in the waveform of second signal 1502 but less prominent in the waveform of first signal 1501. The minimum signal values ​​of first signal 1501 and second signal 1502 may occur during the V wave but not the A wave. The peak signal values ​​are synchronous for first signal 1501 and second signal 1502. Processor 562 may determine that a health condition includes hypoventilated lungs based on any one or more of these features.

[0283] For example, in some embodiments, processor 562 may be configured to compare the second waveform, i.e., a signal associated with a wavelength of approximately 660 nm, to a waveform characteristic of hypoventilated lungs exhibiting a prominent V-wave component. In response to determining that the waveform exhibits a characteristic waveform with a prominent V-wave, the processor may determine that the health condition includes hypoventilated lungs.

[0284] Note that oxygen levels remain relatively low and constant during systole and diastole because oxygen is not added to the blood to a significant extent when the air sacs collapse (see Figure 15(c)). The determination of oxygen levels is described in more detail below.

[0285] Hypoxia-Liver

[0286] Changes in portal vein blood flow are important for detecting various liver disorders such as hepatitis, liver cirrhosis, and right heart failure.

[0287] Under normal oxygenation, the P wave may be insignificant or may not be visible. However, with the development of systemic hypoxia, the P wave becomes very prominent due to the increased cardiac output associated with increased portal vein blood flow. Because the P wave is dominant, the X wave is not observed. Also, note that the pulse rate increases in hypoxic conditions.

[0288] Thus, in some embodiments, in response to determining that at least one waveform of one or more signals derived from light reflected by the liver differs from a template waveform representative of a healthy liver, processor 562 may determine that the subject is suffering from one or more of hepatitis, cirrhosis, and right heart failure. In some embodiments, in response to determining that at least one waveform of one or more signals derived from light reflected by the liver exhibits a predominant P-wave component, optionally no X-wave component, and optionally an increased pulse rate, processor 562 may determine that the subject has increased portal vein blood flow.

[0289] Intracranial Pressure - Sylvian Fissure

[0290] The first signal can be derived from light detected at a wavelength of approximately 660 nm reflected from the movement of cerebrospinal fluid in the Sylvian fissure of a human subject. In this context, a third signal derived from light at a wavelength of approximately 660 nm obtained from the skin of the subject's forehead represents an arterial pulse from the subject. The first waveform of the first signal has a shape similar to the waveform of the third signal, i.e., the arterial waveform. The first waveform of the first signal can also include specific oscillations indicative of a signal resulting from the movement of cerebrospinal fluid located in the Sylvian fissure.

[0291] The timing of the specific oscillations and the general shape of the first waveform of the first signal closely correlate with the observed waveform recorded for measuring intracranial pressure of cerebrospinal fluid, which results from pressure changes at the skull following each arterial pulse of blood to the brain (see Zweifel, C., Hutchinson, P., & Czosnyka, M., 2011; Intracranial pressure; in B. Matta, D. Menon, & M. Smith (Eds.), Core Topics in Neuroanaesthesia and Neurointensive Care, pp. 45-62, the disclosure of which is incorporated herein by reference in its entirety). Notably, the peak intensity level (which can be used as the onset of the waveform or pulse) occurs slightly before the forehead skin pulse. This is consistent with a pulse representing the effect of brain pressure changes on cerebrospinal fluid movement rather than from blood flow in the cerebral microcirculation. The pattern, amplitude, and frequency of the oscillations can be used to detect abnormally elevated intracranial pressure levels.

[0292] In some embodiments, the device 100 is positioned adjacent to a cerebral sulcus to enable noninvasive monitoring to detect elevated intracranial pressure levels. Light comprising at least one wavelength from the light source 120 may be emitted through the skull of the subject 520 into the cerebral sulcus. Light reflected from cerebrospinal fluid (CSF) within the sulcus may be received by the photodetector 130 of the device 100. The processor 562 may then generate at least one signal derived from the measured light reflected from the sulcus at each wavelength. One or more waveforms of the at least one signal may be analyzed to determine a measure of elevated intracranial pressure. For example, the one or more signals may include superimposed vibration signals. The frequency and amplitude of the vibration signals may increase with elevated intracranial pressure. In response to determining that the frequency or amplitude of the vibration signals exceeds a threshold level, the processor 562 may be configured to determine that the subject has elevated intracranial pressure.

[0293] When blood is present in the CSF, as occurs in subarachnoid hemorrhage, the signal level can be very strong compared to the signal from normal CSF, and therefore can be used to detect subarachnoid hemorrhage.

[0294] In some embodiments, device 100 generates and detects light at a wavelength of approximately 805 nm to generate the first signal and reduces the effect of blood oxygen level on the first signal, potentially resulting in a more accurate and reliable waveform shape that reflects ICP.

[0295] Organ Movement - Brain

[0296] Referring to FIG. 13(b), an exemplary plot of a first signal 1301 obtained from measured light reflected from a subject's brain at a first wavelength (e.g., 895 nm) and a second signal 1302 obtained from light measured at a second, shorter wavelength (e.g., 660 nm) is shown. The first and second signals 1301, 1302 were obtained from sensors in device 100 placed on the sheep's scalp after injecting 6 ml of blood through the anterior cranial fossa into the sheep's anterior cranial fossa to increase the sheep's intracranial pressure in the range of approximately 90 mmHg to approximately 150 mmHg. The first and second waveforms associated with signals 1201, 1202 are seen to contain high-amplitude oscillations at a particular frequency, in this case, approximately 7 Hz. Oscillations in the ICP pressure trace at this frequency have been previously recorded and represent cerebral "ringing" in response to systolic arterial pressure waves entering the brain. As ICP pressure levels increase, the amplitude of these oscillations increases, potentially resulting in changes in the waveforms detected by the monitor. The synchrony of the monitor pulsations with high-frequency oscillations is consistent with both being caused by a cardiac source. Previous clinical studies in the setting of brain injury have found that high-frequency and high-amplitude oscillations in ICP are associated with poor patient outcomes.

[0297] Figure 13(a) shows a simultaneous plot of the third and fourth signals 1303, 1304 obtained from the skin of a sheep's nose, representing an arterial waveform shown for comparison with the first and second signals 1301, 1302. This is useful for determining the timing of the systolic and diastolic phases of the cardiac cycle.

[0298] Processor 562 may analyze the waveform of at least one of each of the one or more signals derived from the detected light reflected from brain 521 to determine whether the waveform includes oscillations, for example, at about 7 Hz. In response to determining that the waveform includes oscillations, processor 562 may determine that subject 520 is likely to have relatively high intracranial pressure. High intracranial pressure may be caused by acute brain injury, for example, due to cerebral hemorrhage.

[0299] Organ Movement - Lungs

[0300] The lungs expand during inspiration and contract during expiration. Optical signals from the lungs reflect the extent of this movement associated with breathing. The optical signals can be used to detect abnormal breathing patterns and breathing stages. The optical signals detect the inspiratory and expiratory phases of breathing. This signal can be used to trigger a ventilator. Accordingly, the processor 562 can be configured to output control commands to control the ventilator based on the determined breathing pattern.

[0301] Organ Movement - Liver

[0302] The liver is located below the pulmonary diaphragm and moves during breathing. The first and second signals can be derived from light reflected by the liver of the subject 520 using the device 100 while the subject 520 breathes over several respiratory cycles. The signal levels of the first and second signals vary with the inspiration and expiration phases of breathing, and therefore the first and / or second signals derived from the liver can be used to detect abnormal breathing patterns and phases. Low-frequency respiratory vibrations have much larger amplitudes compared to high-frequency cardiac vibrations. Inspiration is associated with a sudden decrease in the signal level (transmitted light intensity) of the first and second signals, and expiration is associated with an increase in the signal level.

[0303] In some embodiments, detection of abnormal patterns and / or stages of breathing can be used to trigger a ventilator coupled to the subject and / or to detect liver damage such as cirrhosis.

[0304] For example, processor 562 may be configured to compare changes in the inhalation and / or exhalation phases of breathing indicated in a waveform of a signal derived from light reflected by the liver of subject 520 with corresponding changes in the inhalation and / or exhalation phases of breathing depicted in a template waveform characteristic of a relatively healthy liver. The waveform and template waveform may extend over at least one respiratory cycle. The respiratory cycle may span a time range greater than 1 second, for example, from about 1 second to about 10 seconds.

[0305] In some embodiments, the processor 562 may be configured to determine liver motion based on a statistical measure of at least one waveform. The statistical measure may be compared to information characteristics to determine motion. The statistical measure may include any one or more of a peak signal value, a minimum signal value, a median signal value, a root-mean-square signal value, and an average signal value of the first and second signal waveforms. The processor 562 may determine a signal level range, for example, from the difference between the peak signal value and the minimum signal value. The processor 562 may determine that the signal level range represents either a healthy or unhealthy condition. For example, the processor 562 may determine that the signal level range is outside a threshold range or exceeds a threshold.

[0306] Organ Movement - Heart

[0307] Cardiac motion can be used to detect the systolic and diastolic phases of the right and left ventricles, as well as atrial contraction, which can be used to detect abnormalities in cardiac function, including systolic and diastolic heart failure and electrical conduction disorders.

[0308] A first signal derived from measurement light reflected from the heart of a healthy human subject at a first wavelength (e.g., 895 nm) and a second signal derived from light measured at a second, relatively shorter wavelength (e.g., 660 nm) can be used to detect cardiac motion. The device 100 is positioned on the anterior chest adjacent to the right ventricle of the heart, a midline structure in direct contact with the chest wall beneath the sternum. A third signal can be obtained from light at a wavelength of approximately 895 nm, a fourth signal can be obtained from light at a wavelength of approximately 660 nm from the skin of the forehead, and a fifth signal can be obtained from the subject's right internal jugular vein.

[0309] In some embodiments, the processor can be configured to analyze the first and second waveforms of the first and second signals 3101 and 3102, respectively, to determine abnormal cardiac behavior and / or the timing of ventricular contraction and relaxation during the cardiac cycle. The heart has four chambers: the right and left atria, and the right and left ventricles, which contract in that order. The waveforms of the first and second signals indicate the timing of each ventricle's contraction and the relaxation of the right and left ventricles during the cardiac cycle. Thus, abnormal cardiac behavior, which may occur following muscle damage from a myocardial infarction or damage to the heart due to 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 in the contractions of the heart chambers, such as may occur due to impaired conduction of the electrical signals that regulate activation of myocardial contractions.

[0310] Analysis of blood oxygen levels using ratio correction ratio calculations

[0311] In some embodiments, the processor 562 is configured to determine the subject's blood oxygen level based on an analysis of first and second waveforms of respective first and second signals derived from light reflected by a target organ of the subject 520, which may be indicative of the subject's health. The intensity of light reflected by blood in the blood vessels is affected by the blood oxygen concentration. The absorption can be based on the intensity of the detected first and second signals at the respective first and second wavelengths using known calibration methods for the intensity of the generated light. The blood oxygen level is correlated with a ratio of ratios R based on the intensity (or absorption) of the signals at the two wavelengths.

[0312] In conventional pulse oximetry, which is based on optical signals from cutaneous arterial blood, the multi-ratio ratio R is normalized based on the maximum signal value at the start of the pulse, also known as the DC level (related to the maximum intensity of the received light). The maximum intensity corresponds to the start of the systolic phase of the cardiac cycle. The signal at each wavelength is normalized based on the maximum intensity at its respective wavelength. The conventional multi-ratio ratio R is given by the following equation:

[0313]

number

[0314] I1 is the signal value at the start of the pulse (peak or maximum signal value) of signal 1 obtained from light received at short wavelength 1. AC1 is the change in signal level from I1 at the systolic peak (minimum signal value corresponding to the peak or maximum of the blood pulse) of signal 1 obtained from light received at wavelength 1. I2 is the signal value (peak or maximum signal value) at the start of the pulse of signal 2 obtained from light received at longer wavelength 2. AC2 is the change in signal level from I2 at the systolic peak (minimum signal value corresponding to the peak or maximum of the blood pulse) of signal 2 obtained from light received at wavelength 2. As a result, a single, multi-ratio ratio R' value is obtained for each waveform (or each pulse).

[0315] The ratios of the multiple ratios are corrected to provide useful results for assessing the splanchnic health of a subject. The corrected ratios of the ratio equations account for some of the characteristics of splanchnic microvascular blood that differ from cutaneous arterial blood.

[0316] When calculating the ratio values ​​of multiple ratios from signals originating from splanchnic organs, the unique characteristics of splanchnic microvascular blood make it necessary to correct and normalize the signal values, as this is quite different from the known method used in cutaneous pulse oximetry, which is used to calculate R' and measure the oxygen concentration of arterial blood.

[0317] In organs, oxygen exchange with organ tissues causes microvascular blood oxygen levels to vary significantly throughout the cardiac cycle. Levels are higher in microvascular blood during systole and decrease during diastole (and vice versa in the lungs). As a result, the time points of maximum transmitted light intensity (start of the pulse) may not be synchronized at both wavelengths. In skin pulse oximetry, oxygen levels typically remain more constant, and the time points of maximum transmitted light intensity (start of the pulse) are always synchronized at both wavelengths.

[0318] In organs, the minimum light intensity level occurs during the second half of the diastolic pulse, especially for signals derived from light with a wavelength of 660 nm (or 895 nm for the lungs). This usually occurs during the A wave of the diastolic phase of the cardiac cycle. In contrast, in skin pulse oximetry, the minimum light intensity level occurs during systole.

[0319] The minimum blood oxygen level measured during the diastole of the cardiac cycle is particularly important because the oxygen concentration in the blood of the microvasculature may have decreased to equilibrium with the oxygen concentration in the extravascular tissues of the organ. This level may therefore provide an estimate of the oxygen level in the extravascular tissues of the organ. The exception is the lung, where the minimum oxygen level occurs during systole and represents the oxygen level of the mixed venous blood returning to the lung.

[0320] Peak oxygen levels measured during systole provide an estimate of the arterial oxygen level in the organ's microvasculature. The exception is the lungs, where peak oxygen levels occur during diastole, representing the degree to which the lungs have oxygenated the returning venous blood. This provides an estimate of the systemic arterial oxygen level.

[0321] To address these differences and allow for measurement of diastolic oxygen levels, a multi-ratio correction ratio is calculated throughout the cardiac cycle, allowing for measurement of changes in oxygen levels throughout this period. The decrease in oxygen levels during the diastolic phase of the cardiac cycle provides important clinical information. In contrast, skin pulse oximetry measures and reports only systolic oxygen levels.

[0322] Monitoring diastolic oxygen levels is particularly important because accurate, noninvasive methods have not previously been available. Diastolic oxygen levels reflect tissue oxygen levels, and even brief periods of low tissue oxygen can lead to tissue necrosis, potentially resulting in organ failure and death. Therefore, monitoring diastolic oxygen levels allows for early detection and treatment of systemic disorders, including sepsis, heart failure, and hemorrhage, and can be used to optimize fluid resuscitation and inotropic drug therapy. Furthermore, monitoring diastolic oxygen levels can provide early detection and treatment of organ-specific disorders, such as elevated intracranial pressure, stroke, cerebral vasospasm, encephalitis, ischemic hepatitis, ischemic bowel, nephritis, hepatitis, colitis and inflammatory bowel disease, abdominal and muscular compartment syndrome, and pneumonia.

[0323] To perform the multi-ratio correction ratio calculation (R), first and second waveforms are required, each associated with a signal dominated by measurement light reflected from the internal organs at a different wavelength. For example, the first wavelength may be approximately 660 nm, and the second wavelength may be approximately 895 nm. Determining the multi-ratio correction ratio value for a waveform involves determining multiple signal level values ​​across a window of the waveform corresponding to the subject's cardiac cycle and normalizing those values. The maximum signal value at each wavelength at the beginning of the pulse or waveform (DC level) is particularly important in calculating R. This is used both to normalize the signal and to evaluate changes in light intensity level during the pulse (referred to as AC level).

[0324] The modified multi-ratio ratio R value indicates the splanchnic blood oxygen level value throughout the subject's cardiac cycle or pulse. In some embodiments, the modified multi-ratio ratio R at a given time t during systole and diastole of the waveform may be calculated as follows:

[0325]

number

[0326] AC1(t) is the change in signal level of the short wavelength signal from I1 at time t. AC2(t) is the change in signal value of the long wavelength signal from I2 at time t. I1(t0) is the signal value at the start of the pulse of signal 1 (peak or maximum signal value). I1(t0) is used as the first normalization factor for the short wavelength, and this point in time defines t0. I2(t0) is the signal value of the long wavelength signal at time t0, which is used for the second normalization factor for the longer wavelength signal. Determining the appropriate time t0 is described below.

[0327] The multi-ratio corrected ratio R value is calculated for all values ​​of t throughout a window of the waveform corresponding to the subject's cardiac cycle or pulse, thereby monitoring oxygen levels during both the systolic and diastolic phases of the pulse, unlike conventional approaches. In some embodiments, the processor 562 can determine the multi-ratio corrected ratio R multiple times throughout one or more windows of the waveform corresponding to the cardiac cycle. The signal can be sampled, for example, at a sampling rate greater than the pulse rate (or heart rate) to provide multiple signal values ​​throughout the waveform. The signal may be sampled at a sample rate greater than 5 Hz. In some embodiments, the sampling rate can range from 100 Hz to 5000 Hz. The sampling rate can be 500 Hz. The sampling rate may be high enough to be considered substantially continuous. This provides a measure of changes in oxygen levels throughout all phases of the cardiac cycle.

[0328] As previously mentioned, in an organ, the time location of the peak signal value (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 a second signal (a later occurring shorter wavelength, such as 660 nm). In embodiments where the waveforms (or pulses) of the two signals are not synchronized, the normalization factor may be determined at time t0 corresponding to the peak light intensity signal value of the first or second signal.

[0329] If there are signal value fluctuations such that the intensity I(t) during the pulse is equal to or greater than the normalization factor used, the calculated multiple-ratio correction ratio R may be inaccurate. Unlike skin, the presence of low-frequency respiratory oscillations in the plethysmography signal can prevent the calculation of multiple-ratio ratios using traditional approaches, especially for the diastolic pulse period. This can occur during the lower chest pressure phase of the respiratory cycle (as venous blood is more rapidly expelled from the organs during this phase), resulting in diastolic transmitted light intensity levels that may actually exceed the peak signal value (e.g., maximum light intensity) at the beginning of the pulse. This causes diastolic AC levels to become negative, making it impossible to calculate the multiple-ratio correction ratio R. This precludes the use of traditional approaches in this situation.

[0330] To address limitations of the above approach for calculating the corrected ratio of the multiple ratios R, if during the systole or diastole of a pulse the light intensity exceeds the level (I) at the start of the pulse (e.g., due to breathing), the maximum signal value of the next pulse 3208 is used in the calculation to derive the corrected ratio R of the multiple ratios of the previous pulse (backward normalization approach). Thus, in some embodiments, the time t0 at which the normalization coefficient is determined can represent the light intensity value at t0 of the next pulse for purposes of calculating the corrected ratio of the multiple ratios of the previous pulse. For purposes of this approach, we refer to this time point as t 0+1 Define it as:

[0331] Another approach to addressing the issue of signal values ​​during a pulse increasing beyond the previous peak signal value is to perform a forward normalization approach (i.e., still use the peak signal value at the beginning of pulse t), but provide a multi-ratio correction ratio R calculated separately for each phase of the respiratory cycle (inspiration, inspiratory pause, expiration, expiratory pause). These phases can be identified by low frequency oscillations in the plethysmographic signal occurring at the frequency of the respiratory rate.

[0332] Another approach is to evaluate the modified ratio R of multiple ratios calculated based on respiratory oscillations in the signal rather than cardiac oscillations, especially for the liver and lungs, where the influence of respiratory oscillation amplitude on the signal value during respiration is much greater than cardiac oscillations. 0R represents the peak signal value at the onset of respiratory oscillation for each wavelength. We refer to this time point as t for this approach. 0R We call this the respiration normalization approach.

[0333] It has been found that the temporal distance (or time offset) between the peak signals is proportional to the magnitude of the difference between the systolic and diastolic oxygen levels and can be used to estimate the diastolic oxygen level because the arterial or systolic oxygen level is typically known (by conventional methods). For example, in some embodiments, the processor may be configured to determine the temporal distance between peak values ​​of a first and second waveform associated with signals primarily related to the target viscera, and determine the diastolic oxygen level of the viscera based on the temporal distance and the associated arterial or systolic oxygen level. In the case of the lungs, the mixed venous oxygen level can be estimated because the diastolic or arterial oxygen level is typically known.

[0334] The minimum microvascular blood oxygen saturation level, which occurs during diastole, also varied with the respiratory cycle, with a further decrease in levels during the expiratory phase. The lower levels achieved during exhalation reflect a decrease in blood oxygenation during this phase of pulmonary ventilation due to potential air sac collapse during exhalation. This oscillation in the minimum oxygen level in organ microvascular blood associated with the respiratory phase can be used to assess the degree of oxygen exchange by the lungs with blood circulation. This knowledge can be used to detect pulmonary impairment and adjust mechanical ventilation parameters, such as the patient's positive end-expiratory pressure level, to improve pulmonary oxygen exchange.

[0335] Referring again to the method 900 for assessing the health status of a subject of FIG. 9, in some embodiments, the processor 562 processes one or more received signals to remove DC offsets and generate an AC signal for further analysis. A correction ratio of the multiple ratios may be determined from the AC signal. The signal may be an analog electrical signal that is digitally sampled (digitized) using an analog-to-digital converter (not shown).

[0336] In some embodiments, the processor 562 may be configured to determine that the first and second signals are associated with a viscera based on a comparison of the determined multi-ratio correction ratio with a characteristic waveform or template. The characteristic waveform or template may include, for example, a multi-ratio correction ratio determined from an arterial skin signal. The multi-ratio correction ratio from the arterial skin signal does not vary significantly from a value of approximately 0.6 for the majority of the pulse (or systolic and diastolic phases of the cardiac cycle). Thus, the processor 562 may determine that a multi-ratio correction ratio value that differs from this by more than a threshold amount, e.g., 0.2, indicates that the first and second signals (for which the multi-ratio correction ratio is calculated) are primarily associated with a viscera. For example, if the average of the determined multi-ratio correction ratio values ​​is greater than approximately 0.7, the processor may be configured to determine that the first and second signals are primarily associated with a target viscera. This is described with respect to a specific example of a viscera below. A template representing a characteristic temporal variation of the multi-ratio correction ratio over systole and diastole for a given viscera may also be used.

[0337] In some embodiments, processor 562 may be configured to analyze the variability in the determined blood oxygen value to determine whether the blood oxygen value is indicative of a splanchnic value. 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 signal levels of two or more of the waveforms decrease, processor 562 may determine that the blood oxygen level is indicative of a splanchnic blood oxygen concentration.

[0338] In some embodiments, processor 562 may assess the health of the internal organs based on calculation of the determined multi-ratio modified ratio. For example, processor 562 may determine the subject's blood oxygen level using a multi-ratio modified ratio equation and perform a health assessment based on the determined blood oxygen level and the target internal organs.

[0339] For example, processor 562 may determine the blood oxygen level from the determined multi-ratio corrected ratio by comparing the multi-ratio corrected ratio value to a lookup table or by applying an empirically determined equation. The lookup table data or data determined from the empirical equation may be based on simultaneous measurements using conventional oximeter technology.

[0340] In some embodiments, processor 562 may determine blood oxygen levels across two or more waveforms (e.g., for each of the determined multiple ratio modified ratio values, or at least a subset thereof). Additionally, blood oxygen levels may be determined across the systolic and diastolic phases of each cardiac cycle (or pulse), allowing monitoring of changes in microvascular blood oxygen levels due to oxygen exchange with organ tissues. Processor 562 may determine splanchnic blood oxygen levels of subject 520 based on the blood oxygen levels determined at particular times across the waveforms.

[0341] The minimum signal levels of the first and second signals may coincide when the blood oxygen level in the microcirculation reaches equilibrium with the tissue level in the splanchnic organs. Thus, in some embodiments, the processor 562 can determine the equilibrium blood oxygen level value in the splanchnic organs by determining the signal value of the first or second signal when the signal is at its minimum level. However, in some cases, the blood oxygen concentration may not reach equilibrium with the tissue oxygen concentration. A non-equilibrium condition may occur if the signal originates primarily from the capillary bed or if there is very high blood flow or shunting. The capillary bed signal is distinctive and distinct from the venular signal.

[0342] FIG. 17 shows an exemplary plot of the oxygen saturation of the internal jugular vein of three subjects during a systemic hypoxia test plotted against the modified multi-ratio ratio determined from applying the device 100 to obtain signals from the brains of the three subjects. Blood oxygen saturation was measured by drawing blood from a vein placed in a blood gas analyzer. The blood oxygen concentration in the vein was shown to be inversely proportional to the modified multi-ratio ratio. This demonstrates that the modified multi-ratio ratio calculated from signals obtained from light reflected by the human brain can be easily mapped to the oxygen level of venous blood draining from the brain. This may also provide evidence that the modified multi-ratio ratio value can be used to determine blood oxygen levels associated with internal organs.

[0343] FIG. 18 is a plot of oxygen saturation in the superior sagittal sinus vein of a single sheep during a brain injury test in which blood was infused directly into the skull to alter intracranial pressure and reduce blood flow and tissue oxygen levels. The superior sagittal sinus vein drains blood from the vein. The plot in FIG. 18 shows the corrected multi-ratio ratio determined from applying device 100 to obtain signals from the sheep's brain. Blood oxygen concentration is inversely proportional to the corrected multi-ratio ratio. This provides further evidence that the corrected multi-ratio value can be used to determine blood oxygen levels associated with the brain and internal organs.

[0344] Multiple Ratio Correction Ratio-Brain

[0345] Referring to FIG. 7(b), a plot of a modified multi-ratio ratio 703 determined from first and second signals 701, 702 obtained from measurement light reflected by the brain 521 of the subject 520 is shown. As shown, when the modified multi-ratio ratio plot 703 is at a minimum, the blood oxygen level is at a maximum. The modified multi-ratio ratio 704 at the time of the maximum signal value indicates a minimum blood oxygen level. A minimum signal value point 708 may also occur during the A-wave component (at the end of the diastole of the cardiac cycle), and the processor 562 may determine a blood oxygen level value at the minimum of the A-wave component, which may represent the tissue oxygen level. An observed decrease in the determined modified multi-ratio ratio between the X and Y waves indicates an increase in the oxygen level during these phases of the cardiac cycle.

[0346] The processor 562 may determine that the first and second signals 701, 702 are associated with the brain 521 based on a comparison of the determined multi-ratio correction ratios with a characteristic waveform or template of an expected multi-ratio correction ratio for the brain (rather than an expected multi-ratio correction ratio for the skin).

[0347] In some embodiments, the processor can calculate a statistical measure (e.g., median, mean, or peak value) of the multi-ratio correction ratio and compare it to a threshold. The statistical measure may be based on a portion of the calculated multi-ratio correction ratios across the waveform. For example, the statistical measure could be an average of up to 30% of the calculated multi-ratio correction ratios. The statistical measure may be related to the variability or range of the determined correction ratios. Since the variability of the determined multi-ratio correction ratios is expected from signals associated with the brain 521, the variability can be determined and compared to a threshold. The value of the variability (or range) of the determined multi-ratio correction ratio values ​​may be greater than 1, for example, for the processor 562 to determine that the signals are associated with the brain 521. The statistical measure can be calculated from the leading edge of the A-wave during the diastole of the cardiac cycle (away from the peak signal).

[0348] This contrasts with typical multi-ratio correction ratios determined from arterial skin signals, which change very little over the course of a pulse and have values ​​between about 0.5 and about 0.7, so the threshold would be about 0.7 or about 1.

[0349] In some embodiments, processor 562 may be configured to assess brain health by analyzing the modified ratio values ​​of the multiple ratios. For example, processor 562 may compare the modified ratio values ​​of the multiple ratios to a characteristic waveform or template to perform the health assessment. In some embodiments, processor 562 may compare a statistical measure of the modified ratio values ​​of the multiple ratios to a threshold to perform the health assessment.

[0350] The brain's minimum or equilibrium blood oxygen level may provide valuable clinical information regarding tissue oxygen levels. For example, low tissue oxygen levels in the brain may indicate that the subject 520 is suffering from an adverse health condition, such as elevated intracranial pressure, and is at risk for developing brain damage. Accordingly, the processor 562 may compare a statistical measure of the corrected ratio values ​​(or blood oxygen levels) of the multiple ratios to a threshold, and in response to determining that the statistical measure is below the threshold, the processor 562 may determine that the subject 520 is hypoxic. Cerebral hypoxia may occur due to stroke, vasospasm, and elevated intracranial pressure.

[0351] For example, FIG. 19 shows a plot of the modified ratio of the multiple ratios determined from signals obtained using device 100 from measured light reflected by the brain of a sheep. As shown, the modified ratio of the multiple ratios determined from signals derived from light reflected by the brain using device 100 was found to increase immediately after infusing blood into the sheep's brain, thereby increasing intracranial pressure. This may indicate a decrease in cerebral blood oxygen levels (and decreased cerebral perfusion) following increased intracranial pressure. Thus, low blood oxygen levels in the brain may indicate an injury resulting in decreased blood flow. Following an initial increase in the modified ratio of the multiple ratios, a decrease associated with increased blood oxygen levels was observed. This may be due to a subsequent increase in blood pressure to restore blood flow.

[0352] Accordingly, processor 562 may compare the determined minimum blood oxygen level with a threshold level. In response to determining that the minimum blood oxygen level is lower than the threshold level, processor 562 may determine that subject 520 is suffering from organ ischemia and requires urgent treatment.

[0353] FIG. 20(b) shows signals 2001, 2002 derived from light reflected by the brain 521 of a human subject 520 using the apparatus 100. As shown, the light intensities (or signal values) of the first and second signals 2001, 2002 derived from the brain 521 of the human subject 520 vary in response to the subject's 520 respiratory cycle. FIG. 20(a) shows simultaneous third and fourth signals 2003, 2004 derived from light reflected by the subject's 520 internal jugular vein, which provides a method of indicating the phase of the respiratory cycle. "Exp" indicates the exhalation respiratory phase. "Insp" indicates the inspiration respiratory phase. As shown, the intensities of the third and fourth signals 2003, 2004 also vary in response to the subject's 520 respiratory cycle, generally decreasing during the exhalation phase of the respiratory cycle (e.g., exhaling) and increasing during the inspiration phase of the cycle (e.g., inhaling). The simultaneous change in the multi-ratio correction ratio is shown during each cardiac cycle and is shown in Figure 20(c). The oxygen level is shown to decrease during expiration (increase in the multi-ratio correction ratio).

[0354] As mentioned above, the corrected ratio (or blood oxygen level) of the multi-ratio varies depending on the phase of the splanchnic respiratory cycle. Higher oxygen levels are possible during inspiration. These changes reflect the degree of oxygenation of arterial blood by the lungs during inspiration and expiration, allowing for monitoring of pulmonary function. Applications include detecting lung injury, adjusting the ventilator to establish the highest positive end-expiratory pressure (PEEP) level, and reducing ventilator-associated lung injury by selecting the lowest ventilation pressure level that provides adequate organ tissue oxygen levels.

[0355] Multiple Ratio Correction Ratio - Lung

[0356] The lungs have a unique microcirculation in that the surrounding tissue consists of alveolar sacs that fill with oxygen during inspiration. The pulmonary arteries transport mixed venous blood from the body to the pulmonary microcirculation, where oxygen is added to the blood from the alveolar sacs. Therefore, the oxygen level in pulmonary microvascular blood is low during periods of high blood flow to the lungs, which occurs during systole (following the X- and Y-wave components and peaking at signal 1001) and diastolic recoil of the pulmonary arteries. Peak oxygen levels are expected to occur during the A-wave component (late 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.

[0357] FIG. 10(b) shows a modified multi-ratio ratio calculated from the first and second signals 1001, 1002 associated with highly ventilated lungs. The modified multi-ratio ratio is observed to rise from 0 to a value greater than 2 during the cardiac cycle. As shown, the minimum value of the calculated modified multi-ratio ratio (indicating the maximum blood oxygen value) is observed to occur during the A-wave component (during diastole) of the first signal 1001, which coincides with the timing of the additional peak 1005. This maximum blood oxygen value may provide an indication of lung function with respect to the degree of blood oxygenation. The maximum value of the modified multi-ratio ratio (indicating the 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 may provide an estimate of the mixed venous blood oxygen value of the blood entering the lungs.

[0358] Figure 15(c) shows the modified ratio of the multiple ratios calculated from the first and second signals 1501, 1502, which are dependent and associated with both hypoventilated and perfused lungs. As shown, the modified ratio of the multiple ratios remains high (at a value of approximately 1), and therefore, blood oxygen levels remain low during the diastolic A-wave, in contrast to the behavior observed in hyperventilated lungs (see Figure 10(c)). In effect, blood is being shuffled through the lungs without oxygen being added to the blood.

[0359] The processor 562 may determine that the first and second signals 1001, 1002, 1501, 1502 are associated with the lungs based on the determined modified ratio of the multiple ratios. This may be due to the positioning of the device 100 on the subject. The device 100 may be adjusted until the desired signals associated with the lungs are obtained. A characteristic of the lungs is that they have low oxygen levels during systole and elevated oxygen levels during diastole (see FIG. 10(b)), which is the opposite of the oxygen levels at the skin. This characteristic can be used to confirm that the signals originate from the lungs.

[0360] In some embodiments, the processor 562 may determine that the first and second signals 1001, 1002, 1501, 1502 are pulmonary related based on a modified ratio R of multiple ratios determined during the leading edge of the A wave (indicating the peak oxygen level in the pulmonary blood) before or during the X wave (during the systolic phase when blood oxygen levels are low).

[0361] The processor 562 may assess lung health by analyzing the modified ratio of the multiple ratios. For example, the processor 562 may compare the modified ratio of the multiple ratios to a characteristic waveform or template to perform the health assessment. In lung injury, the degree of oxygen added to venous blood may be low. Therefore, if the modified ratio of the multiple ratios is high, this may indicate lung injury.

[0362] In some embodiments, in response to determining that the corrected ratio of the multiple 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 hypoventilated lungs.

[0363] In some embodiments, processor 562 may compare a statistical measure of the modified ratio of the multiple ratios to a threshold value to perform a health assessment. For example, in response to determining that the modified ratio of the multiple ratios does not reach the arterial oxygen level during diastole (a modified ratio of the multiple ratios of 0.5), processor 562 determines that the subject has unhealthy and / or underventilated lungs.

[0364] In some embodiments, in response to determining that the mean or median corrected ratio of the multiple ratios is between about 1 and about 1.5, the processor may determine that the subject has unhealthy or underventilated lungs.

[0365] Corrected Multiple Ratios - Liver

[0366] The device 100 can be used to acquire first and second signals derived from light reflected by a healthy liver of the subject 520 and calculate a modified ratio of the multiple ratios from the first and second signals related to the liver. The modified ratio of the multiple ratios decreases during the X wave (indicating an increase in oxygen levels), then increases and remains at a relatively high and constant level throughout the diastolic phase of the cardiac cycle until the next X wave. This change in behavior, such as a decrease in blood oxygen levels, may be indicative of liver damage accompanied by one or more of reduced blood flow, such as ischemic hepatitis, abdominal compartment syndrome, portal vein thrombosis, etc.

[0367] The processor 562 may determine that the first and second signals are associated with the liver based on the determined multiple-ratio correction ratio. A statistical measure (e.g., median or mean) of the multiple-ratio correction ratio may be compared to a threshold. The statistical measure may be based on up to 30% of the calculated multiple-ratio correction ratios across the waveform. For example, in response to determining the statistical measure to be greater than approximately 0.7, the processor 562 may determine that the first and second signals 2202, 2202 are associated with the liver. In some embodiments, in response to determining the statistical measure to be greater than approximately 1, the processor 562 may determine that the first and second signals 2202, 2202 are associated with the liver. In some embodiments, in response to determining the statistical measure to be greater than approximately 1, the processor 562 may determine that the first and second signals 2202, 2202 are associated with the liver.

[0368] A statistical measure of 0.7 or less may indicate the first and second signals associated with the skin of the subject. In some embodiments, in response to determining that the statistical measure is equal to about 0.7, processor 562 determines that the first and second signals are associated with the skin of subject 520.

[0369] In some embodiments, processor 562 may determine that the first and second signals are associated with the liver based on a modified ratio of the multiple ratios determined during the leading edge of the A wave before the X wave. This is of particular interest because the blood oxygen level at this time (which may be calculated from the modified ratio of the multiple ratios) may be the same as or equal to the tissue oxygen level of the liver.

[0370] Processor 562 may assess liver health by analyzing a modified ratio of the multiple ratios. For example, processor 562 may compare a modified ratio of the multiple ratios to a characteristic waveform or template to perform the health assessment. In some embodiments, processor 562 may compare a statistical measure of the ratio of the multiple ratios to a threshold to perform the health assessment. For example, in response to determining the statistical measure to be between about 0.5 and 1.5, processor 562 may determine that the subject has a healthy liver. In some embodiments, in response to determining that the statistical measure is greater than about 2, processor 562 may determine that the subject has an unhealthy liver (e.g., due to hypoxia or ischemia).

[0371] Multiple Ratio Correction Ratio - Intestine

[0372] Using the device 100, first and second signals derived from light reflected by the healthy intestine of the subject 520 can be used to calculate a corrected ratio of multiple ratios from the first and second signals related to the intestine. Oxygen levels are similar during systole and diastole, with a slight increase (indicated by a decrease in the calculated corrected ratio) between the X-wave and systole. Oxygen levels then rapidly decrease and plateau during diastole. The relatively stable low oxygen levels 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.

[0373] The processor 562 may determine that the first and second signals are associated with the bowel based on the determined modified ratio of the multiple ratios. A statistical measure (e.g., median or mean) of the modified ratio of the multiple ratios may be compared to a threshold. The statistical measure may be based on up to 30% of the calculated modified ratios of the multiple ratios across the waveform. For example, in response to determining the statistical measure to be greater than about 0.7, the processor 562 may determine that the first and second signals are associated with the bowel. In some embodiments, in response to determining the statistical measure to be greater than about 1, the processor 562 may determine that the first and second signals are associated with the bowel. A statistical measure of 0.7 or less may indicate the first and second signals are associated with the subject's skin.

[0374] In some embodiments, the processor 562 may determine that the first and second signals are associated with the intestine based on a modified ratio of the ratios determined during the leading edge of the A wave before the X wave.

[0375] In some embodiments, the processor 562 may determine the health of the intestine based on a comparison of one or more waveforms of the first and second signals to the characteristic waveform. Differences in the waveforms, or a modified ratio of the ratios compared to the characteristic waveform, may be used to diagnose intestinal disorders such as intestinal infarction, which results in very low blood oxygen levels in the intestine.

[0376] The processor 562 may assess gut health by analyzing the modified ratio of the multiple ratios. For example, the processor 562 may compare the modified ratio of the multiple ratios to a characteristic waveform or template to perform the health assessment. In some embodiments, the processor 562 may compare a statistical measure of the modified ratio of the multiple ratios to a threshold to perform the health assessment. For example, in response to determining that the statistical measure is greater than 2, the processor may determine that the subject has an unhealthy ischemic gut.

[0377] Corrected Multiple Ratios - Kidney

[0378] A modified multi-ratio ratio R can be calculated from the signal obtained from the light reflected by the subject's kidneys. A low value of the modified multi-ratio ratio R most of the time indicates that the blood oxygen concentration in the kidneys remains very high.

[0379] Multiple ratio correction ratio - Muscle

[0380] A modified multi-ratio ratio, R, can be calculated from the signal obtained from light reflected by the calf muscle at rest. A low value for the modified multi-ratio ratio, R, most of the time indicates low blood flow to the muscle while it is at rest.

[0381] The invention will now be further described with reference to the following non-limiting examples.

[0382] Example - Evaluating modifications to a brain sensor device to improve the brain's detection of light pulses

[0383] method

[0384] Variations in the design of the brain sensor device were evaluated to improve brain pulse detection and provide a comparison with prior art configurations. Evaluations were conducted on five healthy volunteers. Two evaluations were performed on each volunteer, one on the left temple and one on the right temple, for a total of 10 evaluations per device modification. The outcome measure was the detection of a pulsating optical signal consistent with the shape and characteristics of a brain pulse. Results, shown in Figures 23(a), (b), (c), and 24, are reported as the percentage of tests in which a brain pulse was detected. In each test, the photodetector (PD) and light-emitting diode (LED) were circular and 8 mm in diameter. The photodetector and LED (emitting at wavelengths of 660 nm and 895 nm) were equivalent to the photodetector and LED used in the Nellcor™ Maxfast forehead sensor manufactured by Medtronic (710 Medtronic Parkway, Minneapolis, MN 55432-5604, USA). The total optical power used (both LEDs) was approximately 200 μW.

[0385] In the first study, variations on a conventional pulse oximetry device, in which a photodetector (PD) and a light-emitting diode (LED) are each in contact with the subject's skin, were tested by varying the distance between the center points of the light source (LED) and the photodetector (PD) between 10 mm, 15 mm, 20 mm, and 40 mm.

[0386] The results in Figure 23(a) show that using a modification of the prior art pulse oximetry device in which the spacing between the PD and the LED was varied, brain pulse signals could not be detected when there was no spacing between the subject's skin and the PD / LED.

[0387] In the second study, the distance between the PD and LED from the skin was kept constant at 10 mm, and the effect of varying the distance between the center points of the light source (LED) and the photodetector (PD) between 10 mm, 15 mm, and 20 mm was tested.

[0388] The results in Figure 23(b) show that when the PD and LED were separated laterally by 10 and 20 mm from the center, the brain pulse was detected in 50% of the tests, while a 15 mm separation between the PD and LED provided 100% brain pulse detection.

[0389] In the third study, the distance between the center points of the light source (LED) and photodetector (PD) was fixed at 15 mm (the optimal distance from the second study) and the effect of varying the distance between the PD and LED from the skin was tested among 0 mm, 5 mm, 10 mm, 15 mm, and 20 mm.

[0390] The results in Figure 23(c) show that no brain pulse was detected at 0 mm and 20 mm spacing, 25% at 15 mm spacing, and 50% at 5 mm spacing. Optimal results of 100% brain pulse detection were obtained with a 10 mm spacing between the PD and LED from the skin. In subsequent testing conducted by the inventors (results not shown), optimal 100% brain pulse detection was also observed with a 8.5 mm spacing between the PD and LED from the skin.

[0391] In the fourth study, the spacing between the center points of the light source (LED) and photodetector (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 by 15 mm and 20 mm (i.e., 5 mm and 10 mm, respectively, set back from the position of the PD) was tested.

[0392] The results in Figure 24 show that the brain signal detection results were relatively poor when the LED was located 10 mm farther from the skin surface than the PD, but there was 100% brain signal detection when the LED was located 5 mm farther from the skin surface than the PD.

[0393] It will be understood that those skilled in the art may make numerous variations and / or modifications to the above-described embodiments without departing from the broad general scope of the present disclosure, and the present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

1. 1. An apparatus for determining data indicative of splanchnic blood oxygen levels, comprising: a body including a contact surface for contacting a subject and adjacent an internal organ of the subject, the body defining a first recess and a second recess, the first recess and the second recess extending from the contact surface into the body, the second recess being separate 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 discreet wavelengths from the first recess of the body; a photodetector including a photosensitive region located within the second recess and configured to detect light received at the second recess, the detected light including emitted light reflected from a region adjacent an internal organ of the subject; Equipped with the light-emitting area and the light-sensitive area are recessed from the contact surface by about 1 mm to about 20 mm, and the nearest points of the light-emitting area and the light-sensitive area are separated by about 4 mm to about 20 mm; the detected light being indicative of blood oxygen levels in blood vessels at the outermost surface of the organ. It is configured as follows: Device.

2. the spacing between the closest points of the light-emitting region and the light-sensitive region is in the range of about 5 mm to about 15 mm; 10. The apparatus of claim 1.

3. The spacing is in the range of about 6 mm to about 12 mm.

3. The apparatus of claim 2.

4. the light-emitting area and the light-sensitive area are recessed from the contact surface by about 1 mm to about 20 mm; 4. The device according to claim 1.

5. the light-emitting area and the light-sensitive area are recessed from the contact surface by about 7 mm to about 10 mm; 5. The apparatus of claim 4.

6. The body includes: an outer frame defining the contact surface and the cavity; an inner frame shaped to fit within the cavity and defining the first recess and the second recess; Further comprising:

6. The device according to any one of claims 1 to 5.

7. the light source is configured to emit and sense light including light having wavelengths in at least a first wavelength range of about 600 nm to about 750 nm and a second wavelength range of about 855 nm to about 945 nm; An apparatus according to any one of claims 1 to 6.

8. the light source is configured to emit and sense light further comprising light having a wavelength within a third wavelength range of about 780 nm to about 820 nm; 8. The apparatus of claim 7.

9. the photodetector is configured to emit and sense light including light having at least about 660 nm, about 805 nm, about 895 nm, and / or about 940 nm distinct wavelengths; An apparatus according to any one of claims 1 to 6.

10. 1. A system for determining data indicative of splanchnic blood oxygen levels, comprising: A device according to any one of claims 1 to 9; a processor; Equipped with the device and the processor are connected to enable transmission of data indicative of blood oxygen levels from the device to the processor; system.

11. the processor includes a memory, a display, and a user interface; the memory, the display, and the user interface are all coupled to the processor; The system of claim 10.

12. 1. A method for obtaining data indicative of splanchnic blood oxygen levels in a subject, comprising: placing a device according to any one of claims 1 to 9 on the external surface of the subject close to the internal organ; irradiating light from said light source through said exterior surface of said subject onto said internal organ, wherein said light comprises light of two or more discrete wavelengths; receiving light at a photodetector of the device, wherein the received light is reflected from the internal organ at two or more discrete wavelengths; and generating a first signal indicative of the intensity of light at a first wavelength and a second signal indicative of the intensity of light at a second wavelength; Including, method.

13. 1. A method for determining splanchnic blood oxygen levels in a subject, comprising: placing the device of the system of any of claims 10 and 11 on an external surface of the subject near the internal organ; irradiating light from said light source through said exterior surface of said subject onto said internal organ, wherein said light comprises light of two or more discrete wavelengths; receiving light at a photodetector of the device, wherein the received light is reflected from the internal organ at two or more discrete wavelengths; and generating a first signal indicative of an intensity of light at a first wavelength and a second signal indicative of an intensity of light at a second wavelength, wherein data relating to the first and second signals is transmitted to the processor to determine the blood oxygen level in the internal organ; Including, method.

14. and, in response to receiving an indication that the device is incorrectly positioned relative to the organ, repositioning the device relative to the organ based on the indication.

14. The method of claim 12 or claim 13.

15. 1. A computer-implemented method for assessing the health of a subject, comprising: placing the device of the system of any of claims 10 and 11 on an external surface of the subject near the internal organ; irradiating light from said light source through said exterior surface of said subject onto said internal organ, wherein said light comprises light of two or more discrete wavelengths; receiving light at a photodetector of said device, wherein the received light is reflected from said internal organ at two or more discrete wavelengths; transmitting data related to the received light to the processor, generating one or more signals derived from the received light, and determining that a waveform of at least one of the one or more signals represents a signal primarily related to the internal organ; and comparing data obtained from said at least one waveform with information characteristic of a health state to assess said health of said subject; Including, A computer-implemented method.

Images