Performance of transabdominal fetal oximetry using optical tomography

Abstract

To provide systems, methods and devices for determining fetal hemoglobin oxygen saturation levels and / or fetal tissue oxygenation levels.SOLUTION: Fetal tissue oxygenation may be performed transabdominally by, for example, receiving a plurality of detected electronic signals that correspond to light emitted from a pregnant mammal's abdomen and a fetus contained therein, detected by the detector and converted into the detected electronic signal. An indication of a depth of the fetus within the pregnant mammal's abdomen is received, and a portion of the detected electronic signals that corresponds to light incident on the fetus is isolated responsively to the indication of the depth of the fetus by using, for example, time of flight of photons that correspond to the detected electronic signals. Then, a fetal tissue oxygen saturation level is determined using the isolated portion of the detected electronic signals that corresponds to light incident on the fetus.SELECTED DRAWING: Figure 18

Description

[Technical Field]

[0001] (Related Applications) This application is a non-provisional patent application of U.S. Provisional Patent Application No. 62 / 694,122, filed July 5, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR PERFORMING TRANS-ABDOMINAL FETAL OXIMETRY AND / OR TRANS-ABDOMINAL FETAL PULSE OXIMETRY USING MATERNAL AND / OR FETAL HEART RATE," and this application is a non-provisional patent application of U.S. Provisional Patent Application No. 62 / 694,122, filed July 5, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR PERFORMING TRANS-ABDOMINAL FETAL OXIMETRY AND / OR TRANS-ABDOMINAL FETAL PULSE OXIMETRY USING MATERNAL AND / OR FETAL HEART RATE." This application is a non-provisional patent application of U.S. Provisional Patent Application No. 62 / 694,130, filed July 5, 2018, entitled "Oximetry Using Short Separation Measurements," which ... TomographyNo. 62 / 694,135, filed July 5, 2019, entitled "SYSTEMS, DEVICES, AND METHODS FOR PERFORMING TRANS-ABDOMINAL FETAL OXIMETRY AND / OR TRANS-ABDOMINAL FETAL PULSE OXIMETRY USING DIFFUSE OPTICAL TOMOGRAPHY," which is a non-provisional patent application of U.S. Provisional Patent Application No. 62 / 694,135, filed July 5, 2019, entitled "SYSTEMS, DEVICES, AND METHODS FOR DETERMINING AN INDIVIDUALIZED RATIO OF RATIOS FOR A PULSE OXIMETER IN THE CONTEXT OF TRANS-ABDOMINAL FETAL OXIMETRY AND / OR TRANS-ABDOMINAL FETAL PULSE OXIMETRY USING DIFFUSE OPTICAL TOMOGRAPHY." This application is a non-provisional patent application of U.S. Provisional Patent Application No. 62 / 694,146, filed July 5, 2018, entitled "TRANS-ABDOMINAL FETAL PULSE OXIMETRY," which is a non-provisional patent application of U.S. Provisional Patent Application No. 62 / 694,170, filed July 5, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR PERFORMING TRANS-ABDOMINAL FETAL OXIMETRY AND / OR TRANS-ABDOMINAL FETAL PULSE OXIMETRY USING A BROAD SPECTRUM LIGHT SOURCE," which is a non-provisional patent application of U.S. Provisional Patent Application No. 62 / 694,170, filed July 5, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR PERFORMING TRANS-ABDOMINAL FETAL OXIMETRY AND / OR TRANS-ABDOMINAL FETAL PULSE OXIMETRY USING A BROAD SPECTRUM LIGHT SOURCE," which is a non-provisional patent application of U.S. Provisional Patent Application No.No. 62 / 694,184, filed July 5, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR PERFORMING TRANS-ABDOMINAL FETAL OXIMETRY AND / OR TRANS-ABDOMINAL FETAL PULSE OXIMETRY USING FREQUENCY-DOMAIN SPECTROSCOPY," which is a non-provisional patent application of U.S. Provisional Patent Application No. 62 / 694,184, filed July 5, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR PERFORMING TRANS-ABDOMINAL FETAL OXIMETRY AND / OR TRANS-ABDOMINAL FETAL PULSE OXIMETRY USING TIME-DOMAIN DIFFUSE CORRELATION SPECTROSCOPY." This application is a non-provisional adaptation of U.S. Provisional Patent Application No. 62 / 694,199, filed July 5, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR PERFORMING TRANS-ABDOMINAL MECONIUM DETECTION," and this application is a non-provisional adaptation of U.S. Provisional Patent Application No. 62 / 694,261, filed July 5, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR PERFORMING TRANS-ABDOMINAL MECONIUM DETECTION," all of which are each incorporated herein by reference in their entirety.

[0002] The present invention is in the field of medical devices, and more specifically in the field of transabdominal fetal oximetry, transabdominal fetal pulse oximetry, diffuse optical tomography, and fetal tissue oxygenation. [Background technology]

[0003] Oximetry is a method for determining the oxygen saturation of hemoglobin in mammalian blood. Typically, in adult humans, 90% (or more) of hemoglobin is saturated with oxygen (i.e., bound to oxygen), whereas fetal blood is only 30%-60% saturated with oxygen. Pulse oximetry is a form of oximetry that uses changes in blood volume throughout the cardiac cycle to internally calibrate hemoglobin oxygen saturation measurements in arterial blood.

[0004] Current methods of monitoring fetal health, such as monitoring fetal heart rate, are ineffective in determining the level of fetal distress and often produce false positive results suggesting fetal distress, which can lead to unnecessary cesarean section deliveries. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] U.S. Provisional Patent Application No. 62 / 694,122 [Patent Document 2] U.S. Provisional Patent Application No. 62 / 694,130 [Patent Document 3] U.S. Provisional Patent Application No. 62 / 694,135 [Patent Document 4] U.S. Provisional Patent Application No. 62 / 694,146 [Patent Document 5] U.S. Provisional Patent Application No. 62 / 694,170 [Patent Document 6] U.S. Provisional Patent Application No. 62 / 694,184 [Patent Document 7] U.S. Provisional Patent Application No. 62 / 694,199 [Patent Document 8] U.S. Provisional Patent Application No. 62 / 694,261 Summary of the Invention [Problem to be solved by the invention]

[0006] Described herein are systems, methods, and devices for determining fetal hemoglobin oxygen saturation levels and / or fetal tissue oxygenation levels using, for example, transabdominal fetal oximetry, transabdominal fetal pulse oximetry, and / or diffuse optical tomography (DOT). [Means for solving the problem]

[0007] In one embodiment, a processor receives a plurality of detected electronic signals from one or more detectors communicatively coupled to the processor. The detectors may be arranged in an array with one or more light sources. The detected electronic signals correspond to light of two or more wavelengths projected onto and emitted (e.g., via backscattering and / or transmission) from the abdomen of the pregnant mammal and / or the fetus contained therein, and such light is detected by the detector(s) and converted into one or more digital signals to form the plurality of detected electronic signals. The emitted and detected light represents a portion of the light projected onto the abdomen of the pregnant mammal and the fetus contained therein by the one or more light sources. In some embodiments, the received plurality of detected electronic signals are synchronized in the time domain so that each of the signals corresponds to one another in time (e.g., have the same start time, the same end time, etc.). This synchronization may be achieved through alignment or correlation of timestamps present in the plurality of detected electronic signals. The detected signals may be time-stamped by a time-stamping device (e.g., a source of electrical ground) that simultaneously or nearly simultaneously interrupts each of the detected electronic signals so that each of these individual signals has a common start time.

[0008] Optionally, an indication of fetal depth within the abdomen of the pregnant mammal may be received. Fetal depth may correspond, for example, to the distance between the epidermis of the pregnant mammal and the epidermis of the fetus or the distance between the epidermis of the pregnant mammal and the brain of the fetus at a particular location. Fetal depth may be received, for example, from an ultrasound device, a Doppler device, and / or an image (e.g., MRI) of the abdomen of the pregnant mammal.

[0009] Depending on the depth of the fetus, a portion (or portions) of the detected electronic signal corresponding to light incident on the fetus will be isolated from the detected electronic signal (sometimes referred to herein as an "isolated fetal signal" or "fetal signal"). This isolation may be accomplished using, for example, the time of flight for photons expected to have incident on the fetus and / or the location, direction, and / or position associated with the detected photon or series of photons.

[0010] In some embodiments, determining the portion of the detected electronic signals corresponding to light incident on the fetus may include receiving a secondary signal and analyzing the received plurality of detected electronic signals using the secondary signal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus.

[0011] Additionally or alternatively, determining the portion of the detected electronic signals corresponding to light incident on the fetus may include receiving a heart rate signal for the pregnant mammal, for example from an ECG machine and / or a pulse oximeter, and the received plurality of detected electronic signals are then analyzed and / or processed using the heart rate signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus.

[0012] Additionally or alternatively, determining the portion of the detected electronic signals corresponding to light incident on the fetus may include receiving a respiratory signal for the pregnant mammal, and analyzing / processing the received plurality of detected electronic signals using the respiratory signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus.

[0013] Additionally or alternatively, determining the portion of the detected electronic signals corresponding to light incident on the fetus may include receiving a heart rate signal for the fetus, and analyzing the received plurality of detected electronic signals using the heart rate signal for the fetus to isolate the portion of the received plurality of detected electronic signals corresponding to light incident on the fetus.

[0014] Additionally or alternatively, determining the portion of the detected electronic signal corresponding to light incident on the fetus may include receiving one or more short separation signals that may correspond to light that incident only on the abdomen of the pregnant mammal (i.e., that is not expected to have incident on the fetus), and analyzing the received plurality of detected electronic signals using the short separation signals to remove the portion of the detected electronic signal corresponding to the signal at the short separation interval(s).

[0015] The isolated portion of the detected electronic signal corresponding to the light incident on the fetus may then be used to determine the fetal tissue oxygen saturation level, which may then be facilitated for provision to a user, for example, by providing the fetal tissue oxygen saturation level to a monitor or other display device.

[0016] In some embodiments, the detected electronic signal and / or the isolated fetal signal may also be used to generate an image of the fetus or a portion of the fetus using the portion of the detected electronic signal corresponding to light incident on the fetus. The image may, for example, show local variations in detected light intensity and / or tissue oxygen saturation levels for the fetus and / or pregnant mammal.

[0017] In another embodiment, a processor receives a plurality of detected electronic signals from one or more detectors communicatively coupled to the processor. The detectors may be arranged in an array with one or more light sources. The detected electronic signals correspond to light of two or more wavelengths projected onto and emitted (e.g., via backscattering and / or transmission) from the abdomen of the pregnant mammal and / or the fetus contained therein, and such light is detected by the detector(s) and converted into one or more digital signals, resulting in the plurality of detected electronic signals. The emitted and detected light represents a portion of the light projected onto the abdomen of the pregnant mammal and the fetus contained therein by the one or more light sources. In some embodiments, the received plurality of detected electronic signals are synchronized in the time domain so that each of the signals corresponds to one another in time (e.g., has the same start time, the same end time, etc.).

[0018] A signal at a short distance interval corresponding to light incident only on the abdomen of the pregnant mammal is received, and in response to the signal at the short distance interval, a portion or portions of the detected electronic signal corresponding to light incident on the fetus are isolated from the detected electronic signal (sometimes referred to herein as an "isolated fetal signal" or "fetal signal").

[0019] In some embodiments, determining the portion of the detected electronic signals corresponding to light incident on the fetus may further include receiving a secondary signal and analyzing the received plurality of detected electronic signals using the secondary signal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus.

[0020] Additionally or alternatively, determining the portion of the detected electronic signals corresponding to light incident on the fetus may include receiving a heart rate signal for the pregnant mammal, for example from an ECG machine and / or a pulse oximeter, and the received plurality of detected electronic signals are then analyzed and / or processed using the heart rate signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus.

[0021] Additionally or alternatively, determining the portion of the detected electronic signals corresponding to light incident on the fetus may include receiving a respiratory signal for the pregnant mammal, and analyzing / processing the received plurality of detected electronic signals using the respiratory signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus.

[0022] Additionally or alternatively, determining the portion of the detected electronic signals corresponding to light incident on the fetus may include receiving a heart rate signal for the fetus, and analyzing the received plurality of detected electronic signals using the heart rate signal for the fetus to isolate the portion of the received plurality of detected electronic signals corresponding to light incident on the fetus.

[0023] The isolated portion of the detected electronic signal corresponding to the light incident on the fetus may then be used to determine the fetal tissue oxygen saturation level, which may then be facilitated for provision to a user, for example, by providing the fetal tissue oxygen saturation level to a monitor or other display device.

[0024] In some embodiments, the detected electronic signal and / or the isolated fetal signal may also be used to generate an image of the fetus or a portion of the fetus using the portion of the detected electronic signal corresponding to light incident on the fetus. The image may be indicative of, for example, fetal tissue oxygen saturation levels and / or local variations in the pregnant mammal. [Brief explanation of the drawings]

[0025] [Figure 1A] FIG. 1 is a block diagram illustrating an exemplary system for determining the level of oxygen saturation for fetal hemoglobin and / or whether meconium is present in the amniotic fluid of a pregnant mammal, consistent with certain embodiments of the present invention. [Figure 1B] 1 is a block diagram illustrating an exemplary fetal probe consistent with certain embodiments of the present invention. [Figure 1C] 1 is a block diagram illustrating an exemplary fetal probe consistent with certain embodiments of the present invention. [Figure 2A] 1 provides an illustration of exemplary dimensions for tissue layers within a maternal abdomen containing a fetus, consistent with certain embodiments of the present invention. [Figure 2B] 1 provides an illustration of exemplary dimensions for layers of tissue within different maternal abdomens containing a fetus, consistent with certain embodiments of the present invention. [Figure 3] 1 provides a midsagittal plan view of the abdomen of a pregnant mammal with a fetal probe positioned thereon, consistent with certain embodiments of the present invention. [Figure 4] 1 is a flowchart illustrating a process for determining the level of oxygen saturation for fetal hemoglobin according to some embodiments of the present invention. [Figure 5] 1 is a flowchart illustrating an example process for generating a fetal signal, according to some embodiments of the present invention. [Figure 6] 1 is a flowchart illustrating an example process for generating a fetal signal, according to some embodiments of the present invention. [Figure 7] 1 is a flowchart illustrating an example process for generating a fetal signal, according to some embodiments of the present invention. [Figure 8]1 is a flowchart illustrating an exemplary process for generating a fetal signal and / or determining whether meconium is present in the amniotic fluid of a pregnant mammal, according to some embodiments of the present invention. [Figure 9] FIG. 1 is a block diagram of an exemplary processor-based system that stores data and / or executes instructions for the processes disclosed herein, consistent with some embodiments of the present invention. [Figure 10] 1 is a flowchart illustrating an example process for determining fetal hemoglobin oxygen saturation levels, consistent with certain embodiments of the present invention. [Figure 11] 1 is a flowchart illustrating an example process for determining fetal hemoglobin oxygen saturation levels, consistent with certain embodiments of the present invention. [Figure 12] 1 is a flowchart illustrating a process for determining an individualized ratio (R) value of multiple ratios for a pulse oximeter, consistent with some embodiments of the present invention. [Figure 13] 1 is a flowchart illustrating a process for determining the level of oxygen saturation for fetal hemoglobin, consistent with certain embodiments of the present invention. [Figure 14A] 1 depicts an exemplary fetal probe configured to detect signals at short and long range intervals upon contact with the abdomen of a pregnant mammal, consistent with some embodiments of the present invention, with the maternal abdominal layers depicted as a single layer. [Figure 14B] 1 illustrates an exemplary fetal probe configured to detect signals at short and long range intervals upon contact with the abdomen of a pregnant mammal, consistent with some embodiments of the present invention, showing different layers of maternal tissue. [Figure 15A]1 depicts an exemplary fetal probe configured to detect signals at two short distance intervals and one long distance interval upon contact with the abdomen of a pregnant mammal, consistent with some embodiments of the present invention, with the layers of the maternal abdomen depicted as a single layer. [Figure 15B] 1 illustrates an exemplary fetal probe configured to detect signals at two short distance intervals and one long distance interval upon contact with the abdomen of a pregnant mammal, consistent with some embodiments of the present invention, showing each of the layers of the maternal abdomen. [Figure 16] 1 is a flowchart illustrating an example process for using a set of signals at short distance intervals to generate a fetal signal that can be used to determine fetal hemoglobin oxygen saturation level, consistent with some embodiments of the present invention. [Figure 17] 1 is a flowchart illustrating an example process for using measurements at two short distance intervals to generate a fetal signal that can be used to determine fetal hemoglobin oxygen saturation level, consistent with some embodiments of the present invention. [Figure 18] 1 is a flowchart illustrating one exemplary process for generating images of a pregnant mammal's abdomen and / or a fetus contained therein using diffuse optical tomography (DOT) and determining fetal tissue oxygen saturation levels therefrom, consistent with certain embodiments of the present invention. [Figure 19] 1 is a flowchart illustrating an example process for generating images of a pregnant mammal's abdomen and / or a fetus contained therein using DOT and determining fetal tissue oxygen saturation levels from the images, consistent with certain embodiments of the present invention. [Figure 20] 1 is a flowchart illustrating a process for non-invasively determining fetal hemoglobin oxygen saturation levels using a multi-source frequency domain spectrometer according to some embodiments of the present invention. [Figure 21]1 is a flowchart illustrating an example process for processing received time-domain diffuse imaging correlation spectroscopy (TD-DCS) signals to generate fetal signals, consistent with some embodiments of the present invention. [Figure 22] 1 is a flowchart illustrating one example process for determining fetal blood flow indication and / or fetal hemoglobin oxygen saturation level, consistent with certain embodiments of the present invention. [Figure 23] 23 is an example of an image 2300 generated through execution of step 1815 in FIG. 8. DETAILED DESCRIPTION OF THE INVENTION

[0026] Described herein are systems, devices, and methods for performing transabdominal fetal oximetry (oxygen saturation measurement), fetal pulse oximetry, and diffuse optical tomography (DOT). The output of fetal oximetry and / or fetal pulse oximetry is the level of oxygen saturation in the fetal blood (also referred to herein as "fetal hemoglobin oxygen saturation level" and "oxygen saturation level"), which may also be understood as the percentage of hemoglobin present in the fetal blood that is bound to oxygen. The output of DOT is the level of oxygen saturation in the fetal tissues (e.g., brain, skin, muscle, etc.). The fetal blood oxygen saturation level and / or fetal tissue oxygenation level may be used (e.g., by trained medical professionals) to assess fetal health and may also be used to assess the level of oxygen-deprivation stress that may be experienced during, for example, the labor and delivery process, intrauterine fetal procedures, and / or procedures or treatments administered to a pregnant mammal. Typically, oxygen saturation values ​​for fetal blood fall within the range of 30% to 60%, with values ​​below 30% indicating fetal asphyxia. Sometimes, the oxygen saturation level may be determined using a predetermined ratio ("R") of multiple ratios that provides an indication of how light passes through maternal and / or fetal tissue.

[0027] Traditionally, pulse oximetry is performed by using two different beams of light, each of a different wavelength or wavelength range. Often, a beam of light in the red spectrum and a beam of light in the near-infrared (NIR) spectrum are used, or two beams in the NIR spectrum are used. These two wavelengths have different path lengths (i.e., penetration depth into tissue) when passing through tissue, which must be taken into account with a calibration factor related to the path length (l or l). Traditionally, standard calibration factors are provided by device manufacturers for pulse oximetry devices. While the use of such standard calibration factors works well in situations where light passes through relatively homogeneous tissue (e.g., thickness, composition, etc.), such as in the case of a finger or earlobe, when the tissue is heterogeneous (e.g., in the case of the abdomen of a pregnant mammal), the robustness of calculations made using these standard calibration factors decreases, and confidence in the accuracy of the generated values ​​may fall below an acceptable level.

[0028] However, because the wavelength of the light beam determines the path length of the light through tissue, if the wavelengths of the two light beams are sufficiently close, the path lengths for each individual beam will be similar enough that the effect of path length on the oximetry calculations will be reduced to zero or nearly zero, which will make the oximetry calculations that contribute to the determination of fetal hemoglobin oxygen saturation described herein more accurate and easier to perform.

[0029] Fetal hemoglobin oxygen saturation may be determined in a variety of ways, including using the various example inputs and equations disclosed herein. These examples are provided by way of illustration and not limitation. In some embodiments, two or more methods of determining fetal hemoglobin oxygen saturation may be combined, for example, to achieve a more accurate fetal hemoglobin oxygen saturation value and / or to achieve a fetal hemoglobin oxygen saturation value with a higher level of confidence and / or statistical robustness. In some instances, fetal hemoglobin oxygen saturation may be determined via oximetry, and in other instances, fetal hemoglobin oxygen saturation may be determined using pulse oximetry.

[0030] In some embodiments, diffuse optical tomography ( Tomography Diffuse Optical Tomography (DOT) may also be used. DOT is a tissue imaging technique that can be used to measure spatial and temporal variations in tissue light absorption and scattering properties and local variations in oxygen concentration. Based on these measurements, a spatial map of tissue properties, such as total oxygen concentration and how the tissue or cells scatter incident light, can be obtained using, for example, a model-based reconstruction algorithm. In the embodiments disclosed herein, the tissues imaged are maternal abdominal tissue and fetal tissue, including, but not limited to, fetal skin, muscle, and / or brain tissue.

[0031] DOT may be performed by projecting low-energy electromagnetic radiation (typically NIR light) onto one or more locations on the surface of the body and measuring the intensity (e.g., number of photons) of the transmitted and / or back-reflected light detected by one or more photoelectric detectors. DOT systems typically include multiple lasers (e.g., synchronous picosecond pulsed diode lasers) or optical fibers coupled to one or more lasers, multiple highly sensitive photoelectric detectors (e.g., single-photon sensitive detectors), and a processor configured to process the output of the photoelectric detectors. The multiple lasers or optical fibers and photoelectric detectors may be arranged in an array configured to cover and conform to a portion of the abdomen of a pregnant mammal so as to image a fetus within the abdomen.

[0032] As incident laser light or pulses enter the abdomen, they are spread and attenuated by maternal and fetal tissue layers, and the reflection of the incident light from and / or light passing through these tissues will be detected by a photodetector. The characteristics of the detected light / photons (e.g., shape, time of flight, location of detection, power, intensity, etc.) are then analyzed to generate an image of the tissue under consideration (e.g., fetal tissue). The analysis may include the application of a physical model (e.g., a model of tissue layers for the maternal abdomen, which may be general or specific to the pregnant mammal under consideration). In many cases, the propagation of light through tissue depends on the scattering and absorption properties of the tissue, or on the specific layer of tissue (when imaging multiple layers). This scattering effect may be understood, for example, through the use of a model that employs scattering coefficients, absorption coefficients, and other properties for the detected light / photons, which may be specific to a particular type of tissue (e.g., fat, skin, muscle, etc.). In some cases, the scattering and / or absorption coefficients may be specific to the particular pregnant mammal and / or fetus under consideration.

[0033] In some embodiments, DOT may be used to image the maternal abdomen to examine oxygen levels in portions of the image representing the fetus to determine fetal tissue oxygen saturation, which may be interpreted as an indicator of fetal health and / or potential fetal acidosis. In some cases where the location of the fetus is known (e.g., through ultrasound), only portions of the DOT image corresponding to the fetal location may be considered to determine the level of fetal tissue oxygen saturation. In some embodiments, portions of the DOT image and / or other information gathered via DOT corresponding to maternal tissue may be ignored. In other embodiments, portions of the DOT image and / or other information gathered via DOT corresponding to maternal tissue may be used to separate portions of the DOT image and / or other information gathered via DOT corresponding to fetal tissue from portions of the DOT image and / or other information gathered via DOT corresponding to the mother.

[0034] Additionally or alternatively, diffuse imaging correlation spectroscopy (DCS) may be used to determine fetal hemoglobin oxygen saturation. DCS is an imaging technique in which light is projected onto an object and the light emerging from the object (e.g., via transmission and / or backscattering) is detected by a photodetector. Analysis of the emitted light / photons (e.g., quantification of temporal variations in the light field emerging from tissue, which may be caused by moving blood cells) may allow for determination of, for example, the blood flow and / or hemoglobin oxygenation of the object. Often, tissues (e.g., skin, muscle, fat, etc.) overlying the region of interest may confound the signal. In the context of the present invention, the region of interest is the fetus within the maternal abdomen, and the confounding effects of layers of maternal tissue located between the DCS system and the fetus are undesirable. One way to mitigate the confounding effects of maternal tissue is to use a time-domain (TD) DCS system (TD-DCS).

[0035] When a TD system is used, DCS may be accomplished by using short (e.g., 10 ps-50 ps) optical pulses, sinusoidally modulated at frequencies between, for example, 100 MHz and 1000 MHz, and projecting them into the abdomen of a pregnant mammal at a repetition rate of, for example, 1 MHz-50 MHz. These pulses will generate photon density waves within the tissue being imaged. From these, the amplitude difference and phase shift between the incident and detected light can be determined as a function of time. The emitted photons (e.g., backscattered or transmitted) are then collected by an optical fiber and guided to a detector (e.g., a photomultiplier tube) or detected directly by a microchannel plate photomultiplier tube (MCP-PMT). The MCP-PMT signal may then be amplified and / or attenuated and input to a constant fraction discriminator (CFD), the output of which is provided to a time-to-amplitude converter (TAC). The output of the TAC is counted as individual events by a pulse-height analyzer (PHA) and accumulated until a peak count is reached (e.g., 100,000 counts, 1,000,000 counts, etc.) This information can be used to generate a time-response curve that is used to generate an image of the abdomen of a pregnant mammal and / or to determine fetal hemoglobin oxygen saturation.

[0036] The DCS instrumentation consists of three main components: a long coherence length (>5 m) laser operating in the NIR to deliver light to the tissue, a single-photon counting avalanche photodiode (APD) detector that outputs an electronic pulse for each photon received, and a photon correlator that tracks the arrival time of all photons detected by the APD and derives an intensity correlation function from the time separation of all photon pairs. The correlator may be hardware and / or software computation of the temporal correlation function.

[0037] The systems, devices, and methods disclosed herein can be used to monitor fetal health during pregnancy and / or the labor and delivery process. Additionally or alternatively, the systems, devices, and methods disclosed herein can be used to monitor fetal health while the pregnant mammal is undergoing stress and / or medical procedures, whether or not related to the pregnancy. Additionally or alternatively, the systems, devices, and methods disclosed herein can be used to monitor fetal health during intrauterine fetal procedures (e.g., amniocentesis or surgery).

[0038] 1A provides an example system 100 for detecting and / or determining fetal hemoglobin oxygen saturation levels. The components of system 100 may be coupled together via wired and / or wireless communication links. In some cases, wireless communication of one or more components of system 100 may be enabled using short-range wireless communication protocols designed to communicate over relatively short distances (e.g., BLUETOOTH®, Near Field Communication (NFC), Radio Frequency Identification (RFID), and Wi-Fi), as described below, with, for example, a computer or personal electronic device (e.g., a tablet computer or smartphone).

[0039] System 100 includes a light source 105 and a detector 160, which may be contained in a single housing, sometimes referred to as fetal probe 115. Light source 105 may include a single light source or multiple light sources, and detector 160 may include a single detector or multiple detectors.

[0040] Light source 105 transmits light at one or more wavelengths, including NIR, to the abdomen of the pregnant mammal. Typically, the light emitted by light source 105 will be focused or emitted as a narrow beam to reduce light spread upon entry into the abdomen of the pregnant mammal. Light source 105 may be, for example, an LED and / or a laser coupled to a fiber optic cable, a tunable light bulb, and / or a tunable LED. In some cases, the light source may be one or more fiber optic cables arranged in an array and optically coupled to a laser. In some cases, light source 105 is tunable or user-configurable, while in other cases, one or more of the light sources may be configurable to emit light within a predefined wavelength range. Additionally or alternatively, one or more filters (not shown) and / or polarizers may filter / polarize the light emitted by light source 105 to one or more suitable wavelengths. These filters / polarizers may also be tunable or user-configurable.

[0041] Certain exemplary light sources 105 have a relatively small form factor and are adapted to operate with high efficiency, which may help conserve space and / or limit heat generated by the light source 105. In one embodiment, the light source 105 is configured to emit light in the range of 770 nm to 850 nm. Exemplary flux ratios for the light source include, but are not limited to, luminous / radiant flux of 175 mW to 260 mW, total radiant flux of 300 mW to 550 mW, and power ratings of 0.6 W to 3.5 W.

[0042] Detector 160 can be configured to detect optical signals emitted from the pregnant mammal and / or fetus, for example, via transmission and / or backscattering. Detector 160 converts the optical signals into electronic signals that are transmitted to a computer or processor and / or to an on-board transceiver that can transmit the signals to a computer / processor. This emitted light can then be processed to determine how much light of various wavelengths has passed through the fetus and / or how much light of various wavelengths has been reflected and / or absorbed by fetal oxygenated and / or deoxygenated hemoglobin, so that fetal hemoglobin oxygen saturation levels can be determined. This processing is discussed in more detail below. In some embodiments, detector 160 can be configured to detect / count single photons.

[0043] Exemplary detectors include, but are not limited to, cameras, conventional photomultiplier tubes (PMTs), silicon PMTs, avalanche photodiodes, and silicon photodiodes. In some embodiments, the detector may have relatively low cost (e.g., less than $50), low voltage requirements (e.g., less than 100 volts), and a non-glass (e.g., plastic) form factor. In other embodiments (e.g., non-contact pulse oximetry), a highly sensitive camera may be deployed to receive light emitted by the abdomen of the pregnant mammal. For example, detector 160 may be a highly sensitive camera adapted to capture subtle changes in fetal skin tone caused by changes in cardiovascular pressure associated with fetal myocardial contractions. In these embodiments, detector 160 and / or fetal probe 115 may or may not be in contact with the abdomen of the pregnant mammal; non-contact embodiments may be used to perform so-called non-contact pulse oximetry. In these embodiments, light source 105 may be adapted to provide light (e.g., light in the visible spectrum, near infrared, etc.) directed toward the abdomen of the pregnant mammal such that detector 160 can receive / detect light emitted by the abdomen of the pregnant mammal and the fetus. The emitted light captured by detector 160 can be transmitted to computer 150 for processing, for example, to convert the image into a measure of fetal hemoglobin oxygen saturation according to one or more of the processes described herein.

[0044] The fetal probe 115, light source 105, and / or detector 160 may be any suitable size and, in some circumstances, may be sized using any suitable sizing system (e.g., waist size and / or small, medium, large, etc.) to accommodate the size of the pregnant mammal. Exemplary lengths of the fetal probe 115 include lengths of 4 cm to 40 cm and widths of 2 cm to 10 cm. In some circumstances, the size and / or configuration of the fetal probe 115 or its components may be dependent on the skin pigmentation of the pregnant mammal and / or fetus. In some cases, the fetal probe 115 may be adapted to be applied to the skin of the pregnant mammal via a tape or strap cooperating with a mechanism (e.g., a snap, loop, etc.) (not shown). In some cases, the fetal probe 115 may function to preprocess or filter the detected signal.

[0045] System 100 may include multiple optional independent sensors / probes designed to monitor various aspects of maternal and / or fetal health and may be in contact with the pregnant mammal. These probes / sensors are a NIRS adult hemoglobin probe 125, a pulse oximetry probe 130, a Doppler and / or ultrasound probe 135, and a uterine contraction measurement device 140. Not all embodiments of system 100 include all of these components. In some embodiments, system 100 may further include an electrocardiogram (ECG) machine (not shown) that can be used to determine the heart rate of the pregnant mammal and / or the fetus, and / or an intrauterine pulse oximetry probe (not shown) that can be used to determine the fetal heart rate. Doppler and / or ultrasound probe 135 is configured to be placed on the abdomen of the pregnant mammal and is sized and shaped approximately like a silver U.S. dollar coin, and can provide information regarding the position, orientation, and / or heart rate of the fetus. The pulse oximetry probe 130 may be a conventional pulse oximetry probe placed on the hand and / or fingers of the pregnant mammal to measure the hemoglobin oxygen saturation of the pregnant mammal. The NIRS adult hemoglobin probe 125 may be placed, for example, on the second finger of the pregnant mammal and configured to use near-infrared spectroscopy to calculate, for example, the ratio of adult oxygenated hemoglobin to adult deoxygenated hemoglobin. The NIRS adult hemoglobin probe 125 may also be used to determine the heart rate of the pregnant mammal.

[0046] Optionally, system 100 may include a uterine contraction measuring device 140 configured to measure the strength and / or timing of uterine contractions of the pregnant mammal. In some embodiments, uterine contractions may be measured by uterine contraction measuring device 140 as a function of pressure (e.g., measured in mmHg) over time. In some cases, uterine contraction measuring device 140 is and / or includes a tocotransducer, an instrument that includes a pressure-sensitive area that detects changes in abdominal contour to measure uterine activity, and in this way monitors the frequency and duration of contractions.

[0047] In another embodiment, the uterine contraction measuring device 140 may be configured to pass an electric current through the pregnant mammal and measure the change in electric current with each uterine contraction. Additionally or alternatively, uterine contractions may also be measured via near-infrared spectroscopy, for example, using light received / detected by detector 160, since uterine contractions, being muscle contractions, are oscillations of the uterine muscle between contraction and relaxation states. During both of these phases, the oxygen consumption of the uterine muscle differs, and these differences may be detectable using NIRS.

[0048] Measurements and / or signals from NIRS adult hemoglobin probe 125, pulse oximetry probe 130, Doppler and / or ultrasound probe 135, and / or uterine contraction measurement device 140 may be transmitted to receiver 145 for transmission to computer 150 and display on display device 155, and may in some cases be considered secondary signals. As discussed below, measurements provided by NIRS adult hemoglobin probe 125, pulse oximetry probe 130, Doppler and / or ultrasound probe 135, and uterine contraction measurement device 140 may be used in conjunction with fetal probe 115 to isolate a fetal pulse signal and / or fetal heart rate from a maternal pulse signal and / or maternal heart rate. Receiver 145 may be configured to receive signals and / or data from one or more components of system 100, including, but not limited to, fetal probe 115, NIRS adult hemoglobin probe 125, pulse oximetry probe 130, Doppler and / or ultrasound probe 135, and / or uterine contraction measurement device 140. Communication between receiver 145 and other components of the system may occur using wired or wireless communication.

[0049] In some instances, one or more of the NIRS adult hemoglobin probe 125, pulse oximetry probe 130, Doppler and / or ultrasound probe 135, and uterine contraction measurement device 140 may include a dedicated display to provide measurements, for example, to a user or to a medical care provider. It is important to note that not all of these probes may be used in all instances. For example, if a pregnant mammal were to use the fetal probe 115 in an environment other than a hospital or treatment facility (e.g., at home or at work), some of the probes (e.g., the NIRS adult hemoglobin probe 125, pulse oximetry probe 130, Doppler and / or ultrasound probe 135, and uterine contraction measurement device 140) may not be used.

[0050] In some cases, receiver 145 may be configured to pre-process the received signal, for example, to make the signal compatible with computer 150 (e.g., convert an optical signal to an electrical signal), improve the signal-to-noise ratio (SNR), amplify the received signal, etc. In some cases, receiver 145 may reside within a component of computer 150. In some embodiments, computer 150 may amplify or otherwise condition the received detected signal, for example, to improve the signal-to-noise ratio.

[0051] Receiver 145 may be adapted to transmit the received, preprocessed, and / or processed signals to computer 150. Computer 150 may function to process the received signals and facilitate providing results to display device 155, as discussed in more detail below. Exemplary computers 150 include desktop and laptop computers, servers, tablet computers, personal electronic devices, mobile devices (e.g., smartphones), and the like. Exemplary display devices 155 are computer monitors, tablet computing devices, and displays provided by one or more of the components of system 100. In some cases, display device 155 may reside on receiver 145 and / or computer 150. Computer 150 may be communicatively coupled to database 170, which may be configured to store information related to physiological characteristics and / or combinations of physiological characteristics of a pregnant mammal and / or its fetus, the effects of physiological characteristics on light behavior, calculation of hemoglobin oxygen saturation levels, calibration coefficients, and the like.

[0052] In some embodiments, the pregnant mammal may be electrically isolated from one or more components of the system 100, for example, by an electrical isolator 120. Exemplary electrical isolators 120 include circuit breakers, ground fault switches, and fuses.

[0053] In some embodiments, system 100 may include an electrocardiogram (ECG) machine 175 configured to determine and / or measure the heart rate and / or pulse characteristics of the pregnant mammal. These characteristics may be used, for example, as a secondary signal and / or maternal heart rate signal as disclosed herein.

[0054] In some embodiments, system 100 may include a ventilation / respiratory signal source 180 that may be configured to monitor the respiration rate of the pregnant mammal and provide a respiratory signal indicative of the respiration rate of the pregnant mammal, e.g., to computer 150. Additionally or alternatively, ventilation / respiratory signal source 180 may be a source of a ventilation signal obtained, e.g., through cooperation with a ventilation machine. Exemplary ventilation / respiratory signal source 180 include, but are not limited to, a carbon dioxide measuring device, a stethoscope and / or an electroacoustic stethoscope, a device that measures chest excursion for the pregnant mammal, and a pulse oximeter. A signal from a pulse oximeter may be analyzed to determine a variability in a PPG signal corresponding to respiration for the pregnant mammal. Additionally or alternatively, ventilation / respiratory signal source 180 may provide a respiratory signal corresponding to the frequency at which gas (e.g., air, anesthetic, etc.) is provided to the pregnant mammal, e.g., during a surgical procedure. This respiratory signal may be used, e.g., to determine the respiratory rate for the pregnant mammal.

[0055] In some embodiments, system 100 may include a time stamping device 185. Time stamping device 185 may be configured to stamp signals provided by, for example, fetal probe 115, Doppler / ultrasound probe 135, pulse oximetry probe 130, NIRS adult hemoglobin probe, uterine contraction measurement device 140, ECG 175, and / or ventilation / respiratory signal source 180 with time stamps representing, for example, events (e.g., time or t, = 0, 10, 20, etc.) and / or chronological times (e.g., date and time). The time stamping device 185 may be adapted to time stamp the signals, e.g., via introducing a ground signal into the system 100, to simultaneously or nearly simultaneously interrupt or otherwise introduce a stamp or other indicia into the signals generated by one or more of the fetal probe 115, the Doppler / ultrasound probe 135, the pulse oximetry probe 130, the NIRS adult hemoglobin probe, the uterine contraction measuring device 140, the ECG 175, and / or the ventilation / respiration signal source 180. Additionally or alternatively, the time stamping device 185 may be adapted to time stamp the signals, e.g., via introducing an optical signal into the system 100, to simultaneously or nearly simultaneously interrupt or otherwise introduce a stamp or other indicia into the signals generated by one or more of the fetal probe 115, the pulse oximetry probe 130, the NIRS adult hemoglobin probe, the uterine contraction measuring device 140. Additionally or alternatively, the time stamping device 185 may be adapted to stamp signals, for example via introducing an acoustic signal into the system 100, and may be adapted to simultaneously or nearly simultaneously interrupt or otherwise introduce a stamp or other indicator into signals generated by one or more of the fetal probe 115, the Doppler / ultrasound probe 135, and / or the ventilation / respiration signal source 180.

[0056] The timestamps generated by the time stamping device 185 can serve as a simultaneous or near-simultaneous starting point or benchmark for processing, measuring, synchronizing, correlating, and / or analyzing signals from, for example, the fetal probe 115, the Doppler / ultrasound probe 135, the pulse oximetry probe 130, the NIRS adult hemoglobin probe, the uterine contraction measuring device 140, the ECG 175, and / or the ventilation / respiration signal source 180. In some instances, the timestamps can be used to correlate and / or synchronize two or more signals generated by, for example, the fetal probe 115, the Doppler / ultrasound probe 135, the pulse oximetry probe 130, the NIRS adult hemoglobin probe, the uterine contraction measuring device 140, the ECG 175, and / or the ventilation / respiration signal source 180 so that the signals are aligned, for example, in the time domain.

[0057] 1B is a block diagram illustrating an example fetal probe 115A having a housing 111 containing an example array of light sources and multiple detectors. Housing 111 may be any housing configured for a light source and multiple detectors and, in some cases, may include a power source 121 (e.g., a battery), a communication device (e.g., an antenna), a processor 151, a power port 141, and / or a communication port 131. Example fetal probe 115A includes light source 105 substantially aligned with four detectors 160A-160D along the X-axis. In some embodiments, the gain or sensitivity of detectors 160A-160D may vary with their respective positions relative to light source 105, such that detectors located farther away from light source 105 have greater gain / sensitivity.

[0058] In one embodiment, fetal probe 115A may include light source 105 configured to emit light at multiple wavelengths, such as 735 nm, 760 nm, 810 nm, and 850 nm, and detectors 160A-160D may each be configured to detect light / photons at each of these wavelengths. An exemplary distance between light source 105 and detector 160A is 3 cm, an exemplary distance between light source 105 and detector 160B is 5 cm, an exemplary distance between light source 105 and detector 160C is 7 cm, and an exemplary distance between light source 105 and detector 160D is 10 cm.

[0059] 1C is a block diagram illustrating an example fetal probe 115A' having an example array of light sources and detectors. The example fetal probe 115A' includes a row of three light sources 105 substantially aligned with one another along the X-axis, nine detectors 160T-160Q and 160E-160I arranged in a 3-by-3 configuration above the light sources 105, and nine detectors 160J-160S arranged in a 3-by-3 configuration below the light sources 105. In some embodiments, the gain or sensitivity of detectors 160E-160S and 160T-160Q may vary with their respective positions relative to the light source 105, e.g., detectors located farther away from the light source 105 have greater gain / sensitivity.

[0060] 1B and 1C are provided by way of example only and are not intended to limit the array of light sources 105 and / or detectors 160. Any arrangement of light sources and detectors may be used to detect optical signals and convert them into the detected electronic signal(s) discussed herein.

[0061] 2A and 2B provide illustrations 201 and 202, respectively, of tissue layers present in two different maternal abdomens, each including a fetus. The information used to generate illustrations 201 and 202 may be received, for example, from an ultrasound imaging device (e.g., Doppler / ultrasound probe 135) and / or MRI images.

[0062] Diagrams 201 and 202 provide example dimensions for maternal tissue layers and fetuses located proximate the placement of fetal probe 115, including the depth of the fetus within the abdomen of each pregnant mammal. Fetal depth may be understood, for example, as the distance between the epidermis of the pregnant mammal and the epidermis of the fetus and / or the combined width of the maternal tissue layers and amniotic fluid. Diagram 201 shows maternal abdominal tissue for a fetus that has reached 29 weeks of gestation. The tissue layers shown in diagram 201 include subcutaneous fat layer 205A, abdominal (skeletal) muscle layer 210A, intra-abdominal fat layer 215A, uterine wall (smooth muscle) layer 220A, amniotic fluid layer 225A, and fetus 230A. Width measurements for each of these layers were taken proximate (e.g., directly beneath) fetal probe 115. The approximate locations of where the width measurements were taken are indicated by lines connecting the top and bottom surfaces of the layers of interest. For example, in Figure 2A, the width of subcutaneous fat layer 205A is represented by line 1, the width of abdominal muscle layer 210 is represented by line 2, the width of intra-abdominal fat layer 215A is represented by line 3, the width of uterine wall layer 220A is represented by line 4, and the width of amniotic fluid layer 225A is represented by line 5. Approximate dimensions for these layers of maternal tissue located proximate to (e.g., directly beneath) fetal probe 115 are as follows: Subcutaneous fat layer 205A: 10.2 mm (represented by line 1); abdominal muscle layer 210A: 7.1 mm (represented by line 2); Intraperitoneal fat layer 215A: 2.0 mm (represented by line 3); Uterine wall layer 220A: 3.1 mm (represented by line 4); Amniotic fluid layer 225A: 3.6 mm (represented by line 5); and Fetus 230A. In this example, the total distance from the maternal epidermis to the epidermis of fetus 230A (ie, fetal depth) is 28 mm.

[0063] The fetus shown in illustration 202 of FIG. 2B has reached 35 weeks of gestation. The tissue layers shown in illustration 202 include subcutaneous fat layer 205B, abdominal muscle (skeletal muscle) layer 210B, intra-abdominal fat layer 215B, uterine wall (smooth muscle) layer 220B, and fetus 230B. Width measurements for each of these layers were taken proximate (e.g., directly beneath) fetal probe 115. The approximate locations of where the width measurements were taken are represented by lines connecting the top and bottom surfaces of the layers of interest. For example, in FIG. 2B, the width of subcutaneous fat layer 205B is represented by line 1, the width of abdominal muscle layer 210B is represented by line 2, the width of intra-abdominal fat layer 215B is represented by line 3, and the width of uterine wall layer 220B is represented by line 4. The approximate dimensions for the maternal tissue layers located proximate (e.g., directly beneath) fetal probe 115 are as follows: Subcutaneous fat layer 205B: 11.3 mm (represented by line 1); abdominal muscle layer 210B: 3.1 mm (represented by line 2); Intraperitoneal fat layer 215B: 3.1 mm (represented by line 3); Uterine wall layer 220B: 2.3 mm (represented by line 4); and Fetus 230B.

[0064] In this example, the total distance from the maternal skin to the fetus (i.e., fetal depth) is 19.8 mm. Because the fetus is more developed and larger at 35 weeks gestation, the width of the amniotic fluid is negligible and is not included in this example. In addition, for illustrations 201 and 202, the width of the skin of a pregnant mammal is also negligible, approximately 1 mm to 1.5 mm.

[0065] In some embodiments, fetus 230A and / or fetal layer 230B may be divided into one or more additional layers (not shown). These layers may be associated with, for example, one or more of vernix caseosa, hair, skin, bone, etc. In some embodiments, information regarding one or more of these layers (e.g., the melanin content of the fetal skin and / or hair color) may be inferred from, for example, the parentage of the fetus, genetic testing of the fetus, and / or direct observation of the fetus, for example, via a scope and / or transvaginal examination.

[0066] FIG. 3 depicts a midsagittal plan view of a pregnant mammal's abdomen 305 with a fetal probe 115 positioned thereon. As shown in FIG. 3, the pregnant mammal's abdomen 305 includes an approximation of a fetus 310, a uterus 340, and maternal tissue (e.g., skin, muscle, etc.) 330. The fetal probe 115 can be positioned anywhere on the pregnant mammal's abdomen, and in some cases, more than one fetal probe 115 could be placed on the pregnant mammal's abdomen. FIG. 3 further illustrates that a first optical signal 315 is projected into the pregnant mammal's abdomen, with the penetration depth of the first optical signal 315 limited to the edge of the uterine wall 340, where the first optical signal 315 then backscatters or transmits to a detector, such as detector 160 of the fetal probe 115. FIG. 3 also illustrates that a second optical signal 320 is projected into the pregnant mammal's abdomen and penetrates the fetus 310 before being detected by detector 160. First optical signal 315 and / or second optical signal 320 may include light of a single wavelength or multiple wavelengths, which may be, for example, in the red, near-infrared, and / or broadband spectrum. An exemplary range for wavelengths included in first optical signal 315 and / or second optical signal 320 includes light from 700 nm to 900 nm. In some embodiments, first optical signal 315 and / or second optical signal 320 may include light of two or more different wavelengths or wavelength ranges, i.e., one red and one near-infrared. In some embodiments, the wavelength(s) of second optical signal 320 may be different from first optical signal 315. Additionally or alternatively, first optical signal 315 and second optical signal 320 may be projected onto the abdomen of the pregnant mammal at different times so that second optical signal 320 can be distinguished from first optical signal 315 during processing of the detected portions of each of first optical signal 315 and second optical signal 320. In some embodiments, the first optical signal 315 and the second optical signal 320 may include light of two different wavelengths or wavelength ranges, one red and one NIR, that are slightly different from each other. For example, the first optical signal 315 may include light with wavelengths in the red spectrum, and the second optical signal 320 may include light with wavelengths in the NIR spectrum.Additionally or alternatively, in some embodiments, the wavelengths of the first optical signal 315 and the second optical signal 320 may be selected so that the difference in their respective path lengths is small or negligible. In some embodiments, the two or more wavelengths included in the first optical signal 315 and the second optical signal 320 may also be input for pulse oximetry calculations that use differences in absorption and / or scattering of the optical signals using, for example, the Beer-Lambert equation or the modified Beer-Lambert equation, as discussed in some examples herein.

[0067] 4 is a flow chart illustrating a process 400 for non-invasively determining the level of oxygen saturation for fetal ATP. Process 400 may be performed, for example, by system 100 and / or its components.

[0068] Initially, a detected electronic signal corresponding to an optical signal emanating from the abdomen of the pregnant mammal and the fetus contained therein is received by a computer or processor, such as computer 150 (step 405). The optical signal may correspond to an optical signal of one or more wavelengths projected onto the abdomen of the pregnant mammal by one or more light sources, such as light source 105, and emanating via, for example, reflection, backscattering, and / or transmission (i.e., passing through the maternal abdomen). In some embodiments, the optical signal is a broadband optical signal (e.g., white light and / or a range of 10, 15, or 20 wavelengths), and the received detected signal may correspond to optical signals of multiple wavelengths. The optical signal emanating from the abdomen of the pregnant mammal may be detected by a detector, such as detector 160, configured to convert the optical signal (possibly a single photon) into an electronic signal, which is the detected electronic signal. Sometimes, the detected electronic signal may include a magnitude of intensity for different wavelengths of light corresponding to the optical signal. The detector can then directly and / or indirectly transmit the detected electronic signal to a processor housed in a computer, such as computer 150 .

[0069] The optical signal(s) corresponding to the detected electronic signal(s) may include one or more wavelengths of light generated by a light source, such as light source 105, which may be, for example, one or more monochromatic light sources, one or more broadband light sources. In some embodiments, the optical signal(s) may be filtered and / or polarized. An exemplary range of wavelengths for the optical signal(s) is between 600 nm and 1000 nm.

[0070] Optionally, at step 407, the detected electronic signals may be pre-processed, e.g., to remove noise from the signals and / or to remove confounding effects of anatomical or physiological signals of the pregnant mammal on the first and / or second detected electronic signals. Performing pre-processing includes, but is not limited to, applying filtering techniques to the detected electronic signals, applying amplification techniques to the detected electronic signals, utilizing a lock-in amplifier on the detected electronic signals, etc. When the pre-processing at step 407 includes applying a filter (e.g., bandpass or Kalman) to the detected electronic signals, the filtering may reduce noise or hum in the detected signals that may be caused, for example, by electronic noise generated by equipment generating and / or detecting the detected electronic signals and / or by environmental equipment coupled to the pregnant mammal in some cases. Optionally, the pre-processing step of step 407 may include analysis of the detected electronic signals with information about the tissues and / or tissue layers of the pregnant mammal, e.g., based on ultrasound images and / or MRI images, short separation analysis of the pregnant mammal, and / or dual short separation analysis of the pregnant mammal, to determine optical properties and / or oxygenation of maternal tissues and / or blood. Additionally or alternatively, the detected electronic signals may be generated using diffuse optical tomography, frequency domain spectroscopy, and / or time domain diffuse correlation spectroscopy, and the use of these techniques could assist in the pre-processing of step 407.

[0071] At step 410, a fetal heart rate signal is received, for example, from the Doppler / ultrasound probe 135. In some embodiments, the fetal heart rate signal may be derived from the received detected signal. At step 415, a maternal heart rate signal is received, for example, from the pulse oximetry probe 130, the NIRS adult hemoglobin probe 125, and / or a blood pressure sensing device. Optionally, at step 420, a secondary signal may be received. Exemplary secondary signals include, but are not limited to, a respiratory signal for the pregnant mammal, a ventilation signal for the pregnant mammal, an indication of whether meconium is detected in the amniotic fluid of the pregnant mammal, a signal indicative of uterine tone, a signal indicative of hemoglobin oxygen saturation level of the pregnant mammal, a pulse oximetry signal for the pregnant mammal, and combinations thereof. In some embodiments, the respiratory signal may be received from a ventilation device providing air, oxygen, and / or other gases to the pregnant mammal. Often, this delivery of air, oxygen, and / or other gases occurs at a periodic frequency (e.g., every 1 second, every 2 seconds, every 5 seconds), which may optionally be a secondary signal in conjunction with the time at which ventilation is delivered to the pregnant mammal (e.g., time = 0 seconds, 2 seconds, 4 seconds, etc.).

[0072] At step 425, it will be determined whether the fetal heart rate signal, maternal heart rate signal, and / or secondary signal (if received) should be correlated and / or synchronized. In some embodiments, two or more of the received detected electronic signal, fetal heart rate signal, maternal heart rate signal, and / or secondary signal may be time-stamped, for example, with a reference starting time (e.g., date, time, etc.) associated with absolute time (chronological time) and / or a coincident starting point (e.g., time=0) from which measurements are taken for each received detected electronic signal, maternal heart rate signal, fetal heart rate signal, and / or secondary signal. This time-stamping could aid in the synchronization of step 425. In some embodiments, the time-stamping may take the form of, for example, an electrical ground, an optical signal, and / or an acoustic signal introduced to two or more of the received detected electronic signal, fetal heart rate signal, maternal heart rate signal, and / or secondary signal. In one embodiment, an electrical ground or other interruption (e.g., intentionally introduced optical and / or acoustic noise and / or bursts of control signals) during operation of the devices measuring and / or providing the received detected electronic signal, fetal heart rate signal, maternal heart rate signal, and / or secondary signal can act as a synchronization timestamp. This timestamp would serve to provide a time synchronization point for signals recorded by different devices operating on different time scales. This synchronization can aid in the alignment of two or more signals; for example, the heartbeat provided by the maternal heart rate signal can be aligned with simultaneously occurring portions of the detected electronic signal so that, in an embodiment where the maternal heart rate is used to isolate the fetal signal from the detected electronic signal, the correct portion of the detected electronic signal is aligned with the appropriate maternal heart rate signal. The signals may be timestamped, for example, by timestamp marking device 185.

[0073] If so, a synchronization and / or correlation process will be performed (step 430). Optionally, performing step 430 may include synchronizing the signals in the time domain and / or correlating one or more scales of the measurements that record the signals.

[0074] Additionally or alternatively, in some embodiments, the detected electronic signal, the fetal heart rate signal, the maternal heart rate signal, and / or the secondary signal may be time-stamped with a chronological time (e.g., determined by clocks or other methods of synchronizing chronological time across multiple devices). Additionally or alternatively, in some embodiments, the detected electronic signal, the fetal heart rate signal, the maternal heart rate signal, and / or the secondary signal may be time-stamped with a relative time relative to a single event (e.g., the simultaneous start of measurements for each of the detected electronic signal, the fetal heart rate signal, the maternal heart rate signal, and / or the secondary signal). Additionally or alternatively, measurement time lags or other timing characteristics of the equipment used to generate and / or transmit the detected electronic signal, the fetal heart rate signal, the maternal heart rate signal, and / or the secondary signal may be used, for example, to synchronize start times and / or to correlate signals initially received / processed by different equipment over time.

[0075] If the signals do not need to be synchronized and / or correlated, and / or following the synchronization and / or correlation steps, process 400 may proceed to step 435. In step 435, a fetal signal is generated using two or more of the received signals, at least one of which may be a detected electronic signal. In some cases, performing step 435 involves using a respiratory signal for the pregnant mammal, a fetal heart rate signal, a maternal heart rate signal, and / or one or more secondary signals to isolate, amplify, and / or extract portions of the received detected electronic signal, such as the signal portion contributed by the fetus. If a respiratory signal of the pregnant mammal is used in step 435, it may be subtracted and / or regressed from the detected electronic signal, for example, through the use of one or more linear regression equations and / or models.

[0076] Further details regarding exemplary methods of step 435 are discussed herein and provided in FIGS. 3-6 . In some embodiments, performing step 430 and / or step 435 may include performing one or more procedures, for example, to reduce the signal-to-noise ratio or to amplify the portion of the detected electronic signal corresponding to light incident on the fetus. These processes include, but are not limited to, applying a filter, subtracting known noise components, multiplying the two signals, normalizing, and removing the maternal respiration signal. In some cases, performing step 435 may include processing the detected electronic signal using a lock-in amplifier to amplify a preferred portion of the detected signal and / or to reduce noise in the detected electronic signal. The preferred portion of the signal may, in some cases, correspond to a known quantity (e.g., wavelength or frequency) of light incident on the abdomen of the pregnant mammal.

[0077] In some embodiments, performing step 435 to generate a fetal signal may include filtering the detected electronic signal using, for example, the fetal heart rate signal, the maternal heart rate signal, and / or a secondary signal. In one example, the fetal heart rate signal is received in step 410 and correlated with the detected electronic signal in step 430. A filter (e.g., bandpass and / or Kalman) that captures a range of frequencies that correspond to or approximate (e.g., + / - 5%, + / - 10%, + / - 15%, or + / - 20%) the fetal heart rate may then be applied to the detected electronic signal, such that all frequencies contained in the detected electronic signal that do not correspond to (or approximate) the fetal heart rate are removed from the detected electronic signal. For example, if the fetal heart rate is 3 Hz, the filter may be set to filter out portions of the signal above 5 Hz and below 1 Hz. In another example, if the fetal heart rate is 3 Hz, the filter may be set to filter out portions of the signal above 4 Hz and below 2 Hz. In another example, if the fetal heart rate is 3 Hz, the filter may be set to filter out the portion of the signal above 3.8 Hz and below 2.2 Hz.

[0078] Additionally or alternatively, in another embodiment, a maternal heart rate signal is received in step 415 and correlated with the detected electronic signal in step 430. A filter that captures a range of frequencies that correspond to or approximate (e.g., + / - 10%, + / - 15%, or + / - 20%) the maternal heart rate frequency may then be applied to the detected electronic signal, such that all frequencies contained in the detected electronic signal that correspond to (or approximate) the maternal heart rate are removed from the detected electronic signal.

[0079] Additionally or alternatively, in another embodiment, a secondary signal in the form of a maternal respiration and / or ventilation signal is received in step 415 and correlated with the detected electronic signal in step 430. A filter may then be applied to the detected electronic signal that captures a range of frequencies that correspond to or approximate (e.g., + / - 5%, + / - 10%, + / - 15%, or + / - 20%) the maternal respiration and / or ventilation frequencies / signals, such that all frequencies contained in the detected electronic signal that correspond to maternal respiration and / or ventilation rates are removed from the detected electronic signal.

[0080] In some embodiments, the range of frequencies filtered out of the detected electronic signal may depend on how dynamic or irregular the fetal heart rate, maternal heart rate, and / or secondary signals are, such that, for example, a complete (or nearly complete) range of fetal signals is isolated and / or a complete (or nearly complete) range of maternal signals is removed. For example, if the fetal heart rate, maternal heart rate, and / or secondary signals change little over the course of a 60-second interval, then the frequency bands filtered may be relatively narrow for that 60-second interval. Alternatively, in another example, if the fetal heart rate, maternal heart rate, and / or secondary signals change little over the course of a 60-second interval, then the frequency bands filtered may be relatively narrow for that 60-second interval.

[0081] The fetal signal may then be analyzed to determine a fetal hemoglobin oxygen saturation level, for example, by applying the Beer-Lambert law to the fetal signal, by applying a modified Beer-Lambert law (see, e.g., equations provided herein) to the fetal signal, and / or by correlating components of the fetal signal (e.g., light intensity, wavelength, etc.) with known values ​​that, in some cases, correspond to experimentally determined fetal hemoglobin oxygen saturation level values ​​(step 440). Providing an indication of the fetal hemoglobin oxygen saturation level value to a user (e.g., a physician, nurse, or patient) may then be facilitated, for example, via providing the indication to a display device (e.g., display device 155) or to a computer display, for example, provided by computer 150, or to a screen of a device (e.g., fetal probe 115) (step 445).

[0082] 5 is a flow chart illustrating one example process 500 for generating a fetal signal. Process 500 may be performed, for example, by system 100 and / or its components.

[0083] After performing step 425 and / or step 430, the fetal heart rate signal may be normalized (step 505), and then the normalized fetal heart rate signal may be multiplied by the detected electronic signal to generate a fetal signal (step 510). In some embodiments, the fetal signal generated in step 510 may be referred to as a "multiplied signal." In some embodiments, normalizing in step 505 may include adjusting the values ​​of one or more measurements and / or one or more components of the detected electronic signal (e.g., magnitudes of intensity for different wavelengths of light) to a similar or common scale so that different values ​​can be more easily evaluated and / or analyzed.

[0084] 6 is a flow chart illustrating an example process 600 for generating a fetal signal that may be performed as part of process 500. Process 600 may be performed, for example, by system 100 and / or its components.

[0085] Following performance of step 510, the multiplied signal may be analyzed to determine a portion of the multiplied signal that corresponds to the heartbeat signal of the pregnant mammal (step 605). Sometimes, this analysis may include comparing the multiplied signal to the heartbeat signal of the pregnant mammal. The portion of the multiplied signal that corresponds to the heartbeat signal of the pregnant mammal is then subtracted from the portion of the multiplied signal, reversed, e.g., by a linear regression equation, or subtracted or removed from the multiplied signal (step 610), and the remaining portion of the multiplied signal is used to generate the fetal signal (step 615). In some embodiments, performance of step 605 may include synchronizing and / or otherwise correlating the maternal heart rate signal with the multiplied signal and / or the received detected electronic signal, e.g., so that a particular maternal pulse, as provided by the maternal heart rate signal, is correlated in time with the multiplied signal and / or the received detected signal such that the correct maternal pulse is subtracted from the multiplied signal and / or the received detected signal. In this manner, execution of process 600 does not rely on a periodic maternal heart rate signal, but instead can subtract the contribution of each maternal pulse to the multiplied signal and / or received detected signal in real time and / or on a pulse-by-pulse basis.

[0086] 7 is a flowchart illustrating a third exemplary process 700 for generating a fetal signal that may be performed as part of process 500. Process 700 may be performed, for example, by system 100 and / or its components.

[0087] Following performance of step 510, the multiplied signal may be analyzed to determine the portion of the multiplied signal that corresponds to the secondary signal (step 705). In some embodiments, performance of step 705 may include synchronizing and / or otherwise correlating the secondary signal with the multiplied signal and / or the received detected signal, for example, such that a portion of the secondary signal is time-correlated with the multiplied signal and / or the received detected signal so that the correct portion of the multiplied signal and / or the received detected signal (corresponding to the secondary signal) is subtracted from the multiplied signal and / or the received detected signal. In this manner, performance of process 700 does not rely on a periodic secondary signal, but instead, each variation of the secondary signal may be subtracted or reversed in real time from the multiplied signal and / or the received detected signal, for example, via a linear regression equation.

[0088] The portion of the multiplied signal that corresponds to the secondary signal will be subtracted or otherwise removed from the multiplied signal in step 710. If multiple secondary signals are being considered, steps 705 and 710 will be performed for each secondary signal, and the remaining portion of the multiplied signal will be used to generate the fetal signal (step 715).

[0089] 8 is a flowchart illustrating an example process 800 for generating a fetal signal and / or determining whether meconium is present in the amniotic fluid of a pregnant mammal. Process 800 may be performed, for example, by system 100 and / or its components.

[0090] Initially, the detected electronic signals of steps 405, 407, 510, 615, and / or 715 will be received. The detected electronic signals will then be analyzed to determine whether meconium is present in the amniotic fluid of the pregnant mammal (step 805). This analysis may include, but is not limited to, determining the wavelengths and / or frequencies of light incident on and / or reflected from the pregnant mammal and / or its amniotic fluid and / or the intensity of the emitted light. In some cases, the analysis may include comparatively analyzing the intensities of different wavelengths and / or different frequencies of light exiting the pregnant mammal and / or its amniotic fluid.

[0091] In some cases, the wavelength and / or wavelength range of light corresponding to the detected electronic signal of steps 405, 407, 510, 615, and / or 715 may have absorption and / or scattering characteristics indicative of the presence of meconium, and the second optical signal may be a reference wavelength and / or wavelength range. For example, light at 415 nm is known to be absorbed by meconium, and the detected electronic signal corresponds to a wavelength of light that includes only 415 nm or a wavelength range that includes 415 nm (e.g., 400 nm to 430 nm).

[0092] Following the analysis of step 805, a determination will be made as to whether meconium is present in the amniotic fluid (step 810). In some embodiments, this determination may be facilitated by comparing the results of the analysis to known values ​​for the intensity of wavelengths / frequencies of light when meconium is present and absent in the amniotic fluid. For example, meconium is known to absorb light at 415 nm, and the detected electronic signal may be analyzed to determine how much 415 nm light is absorbed and / or detected.

[0093] When meconium is not detected, providing an indication to a user that meconium was not detected may be facilitated (step 815), for example, via communicating the indication to a display device (e.g., display device 155). When meconium is detected, a secondary signal indicating that meconium was detected may be prepared and communicated, for example, to a processor executing process 400 (and optionally to a processor executing process 800), for receipt in step 440. Additionally or alternatively, when meconium is detected, providing an indication to a user that meconium was detected may be facilitated (step 825), for example, via communicating the indication to a display device (e.g., display device 155). Sometimes, the secondary signal of step 820 and / or the indication of step 825 may provide information regarding, for example, the amount of meconium detected and / or a characteristic (e.g., color) of the meconium. This secondary signal may be used, for example, as a filter for the detected electronic signal during fetal signal generation.

[0094] In some embodiments, two or more of the processes described herein may be performed together in any order to generate a fetal signal and / or determine the level of oxygen saturation for fetal hemoglobin.

[0095] 9 provides an example of a processor-based system 900 capable of storing and / or executing instructions for the processes described herein. Processor-based system 900 is representative of, for example, components of computing device 1450 and / or housing 125 and / or 605. It should be noted that not all of the various processor-based systems that may be employed in accordance with embodiments of the present invention have all of the features of system 900. For example, a particular processor-based system may not include a display because such functionality is provided by a client computer communicatively coupled to the processor-based system or because display functionality is not required. Such details are not important to the present invention.

[0096] System 900 includes a bus 902 or other communication mechanism for communicating information, and a processor 904 coupled with bus 902 for processing information. System 900 also includes a main memory 906, such as a random access memory (RAM) or other dynamic storage device, coupled to bus 902 for storing information and instructions to be executed by processor 904. Main memory 906 may also be used for storing temporary variables and / or other intermediate information during execution of instructions to be executed by processor 904. System 900 also includes a read-only memory (ROM) 908 or other static storage device, coupled to bus 902, for storing static information and instructions for processor 904. A storage device 910, which may be one or more of a floppy disk, a hard disk, a flash memory-based storage device, a magnetic tape or other magnetic storage medium, a compact disk (CD)-ROM, a digital versatile disk (DVD)-ROM, or other optical storage medium, or any other storage medium from which the processor 904 can read, is provided and coupled to bus 902 for storing information and instructions (e.g., an operating system, application programs, etc.).

[0097] The system 900 may be coupled via bus 902 to a display 912, such as a flat panel display, for displaying information to a user. An input device 914, such as a keyboard including alphanumeric and other keys, may be coupled to bus 902 for communicating information and command selections to the processor 904. Another type of user input device is a cursor control device 916, such as a mouse, trackball, or cursor direction keys, for communicating directional information and command selections to the processor 904 and for controlling cursor movement on the display 912. Although not shown in detail, other user interface devices, such as a microphone, speakers, etc., may be involved in receiving user input and / or providing output.

[0098] The processes referred to herein may be performed by processor 904 executing appropriate sequences of processor-readable instructions stored in main memory 906. Such instructions may be read into main memory 906 from another processor-readable medium, such as storage device 910, and execution of the sequences of instructions stored in main memory 906 causes processor 904 to perform the associated actions. In alternative embodiments, hardwired circuitry or firmware-controlled processing units (e.g., field programmable gate arrays) may be used in place of or in combination with processor 904 and its associated computer software to implement the invention. The processor-readable instructions may be rendered in any computer language.

[0099] System 900 may further include a communications interface 918 coupled to bus 902. Communications interface 918 may provide a bidirectional data communications channel with a computer network that provides connectivity to the plasma processing system discussed above. For example, communications interface 918 may be a LAN card that provides a data communications connection to a compatible local area network (LAN), which itself is communicatively coupled to other computer systems. The exact details of such communications paths are not important to the present invention. What is essential is that system 900 can send and receive messages and data through communications interface 918 and, in that manner, communicate with other controllers, etc.

[0100] For the embodiments described herein, the light directed toward the abdomen and fetus of the pregnant mammal may be at least two distinct wavelengths and / or frequencies (e.g., red, infrared, near infrared, etc.) of light, and the received detected electronic signals may correspond to these different wavelengths of light.

[0101] Thus, disclosed herein are systems, devices, and methods for determining fetal oxygen levels. In some embodiments, use of the systems, devices, and methods described herein may be particularly useful during labor and delivery of a fetus (e.g., during the first and / or second stage of labor) due to the difficulty of assessing fetal health during the labor and delivery process.

[0102] 10 provides a flowchart illustrating one example process 1000 for determining fetal hemoglobin oxygen saturation levels using broad-spectrum light. Process 1000 may be performed, for example, by system 100 and / or its components.

[0103] Initially, in step 1005, a detected electronic signal is received from a photodetector, such as detector 160. The detected electronic signal may correspond to optical signals of multiple wavelengths (e.g., a broad spectrum of wavelengths) incident on and exiting the abdomen of the pregnant mammal and its fetus, detected by the detector over a predetermined period of time. Detecting the optical signal may include counting photons of different wavelengths received by the detector and / or incident on an optical fiber coupled to the detector. Optionally, the received detected electronic signal may resemble the detected electronic signal received in step 405 of process 400, discussed above.

[0104] Optionally, in step 1007, the detected electronic signal may be preprocessed, for example to remove noise and / or to amplify desired portions of the detected signal(s). This preprocessing may be similar to the preprocessing performed in step 407 of process 400 and discussed above in connection with FIG. 4.

[0105] In step 1010, the portion of the detected electronic signal of step 1005 and / or the preprocessed view signal of step 1007 that was incident on the fetus is isolated from the detected electronic signal received in step 1005. This isolated portion of the received detected electronic signal is sometimes referred to herein as the fetal signal. Step 1010 may be performed using any suitable method of isolating the fetal signal from the detected electronic signal. Suitable methods include, but are not limited to, reducing noise in the signal, for example, through application of filtering or amplification techniques, determining the portion of the detected electronic signal contributed by the pregnant mammal and then subtracting or otherwise removing that portion of the detected electronic signal from the received detected electronic signal, and / or receiving information about the fetal heart rate and using that information to lock in (e.g., via a lock-in amplifier) ​​on the portion of the received detected electronic signal produced by the fetus. In some embodiments, the fetal signal may be generated, for example, through execution of processes 400, 500, 600, 700, and / or 800, individually discussed above with respect to FIGS.

[0106] The intensity of light for each wavelength of the optical signal contained in the fetal signal is then determined (step 1015). Sometimes, the intensity may be determined by counting each photon of each wavelength received over a predetermined period of time. In some embodiments, performing step 1015 may include processing the fetal signal using, for example, a continuous wave photon migration model.

[0107] In step 1020, a calibration factor and / or differential path length factor (DPF) is determined for each wavelength of light contained in the fetal signal. In some embodiments, the calibration factor may be empirically determined based on experimental data. In some cases, empirically determining the calibration factor may involve fitting intensity data for the detected electronic signal, for example, to a curve or other value to extract the DPF across wavelengths. In some cases, the DPF may be derived from an empirical model designed to compensate for differences in the diffuse path length factors of different wavelengths of light. In some embodiments, the empirical model may be derived by simulating how light travels (e.g., absorption and scattering) through maternal and / or fetal tissue layers. In some cases, the empirical model may be informed by structural models of the maternal abdomen, fetus, and / or tissue layers and may include one or more approximations (e.g., depth, density, etc.) and / or optical properties (e.g., absorption and / or scattering) derived using the structural models. In some cases (e.g., before performing step 1020), a range of values ​​for the empirical model may be simulated or tested to see what their individual impact is on determining the path length factor and / or correcting for the spectral dependency of the path length. These simulations and / or tests may be informed, for example, by ultrasound and / or MRI imaging of the subject pregnant mammal and / or group of pregnant mammals, using images such as those provided in Figures 2A and 2B and / or short separation analysis techniques such as those described herein with respect to processes 1100 and 1200.

[0108] The absorption coefficient for each wavelength of the fetal signal is then determined (step 1025) via calculation using, for example, a step that implements the modified Beer-Lambert law, shown below as Equation 1, for each wavelength.

number

number

[0109] Equation 1 can be solved by inputting the change in intensity as a function of wavelength λ for two or more wavelength pairs. From this, Equation 2, Δμ a to obtain a known extinction coefficient ε for a particular wavelength, which can be looked up, for example, in a look-up table stored, for example, in computer 150. HbO (λ) and ε Hb The change in absorption coefficient can be determined by inputting ΔC (λ). The wavelength pair used to perform the calculation of Equation 2 can be any wavelength pair within the spectrum of wavelengths of the optical signal incident on the abdomen of a pregnant mammal. In some embodiments, ΔC HbO and ΔC Hb Equation 2 is calculated many times (e.g., 10, 100, or 1000 times) at different combinations of wavelengths to arrive at multiple values ​​for ΔC HbO and ΔC Hb The calculated values ​​may be weighted and / or averaged according to one or more criteria to arrive at a robust (statistically valid and / or having an acceptable level of confidence and error rate) value as . Additionally or alternatively, the calculation of Equation 2 may be performed multiple times (e.g., 10, 100, or 1000 times) to fit multiple wavelengths to the equation simultaneously.

[0110] ΔC generated via Equation 2 HbO and ΔC Hb The value of is a relative, not absolute, value for the concentrations of oxygenated and deoxygenated hemoglobin in the fetal blood that is useful for monitoring the fetal hemoglobin oxygen saturation level of the fetus over time. In some embodiments, the determining of step 1030 may further include determining the overall oxygen saturation for the fetal hemoglobin by determining the ratio of the change in the concentration of oxygenated hemoglobin to the change in the concentration of total hemoglobin, which is the sum of oxygenated and deoxygenated hemoglobin.

[0111] 11 provides a flowchart illustrating an example process 1100 for determining fetal hemoglobin oxygen saturation levels using broad-spectrum light. In some embodiments, process 1100 is performed to generate two-dimensional and / or three-dimensional maps of hemoglobin saturation of a pregnant mammal, which may be generated using a broad spectrum of light. Process 1100 may be performed, for example, by system 100 and / or components thereof.

[0112] In step 1105, a detected electronic signal is received from a photodetector, such as detector 160. The detected electronic signal may correspond to optical signals of multiple wavelengths (e.g., 4, 8, 20 wavelengths, or a broad spectrum of multiple wavelengths) incident on and exiting the abdomen of the pregnant mammal and its fetus, detected by the detector over a predetermined period of time. Detecting the optical signal may include counting photons of different wavelengths received by the detector and / or incident on an optical fiber coupled to the detector, such as detector 160. Optionally, the received detected electronic signal may resemble the detected electronic signal received in step 405 of process 400, discussed above.

[0113] Optionally, in step 1107, the first and / or second detected electronic signals may be pre-processed, for example to remove noise and / or to amplify desired portions of the first and / or second detected electronic signals, respectively. This pre-processing may be similar to the pre-processing performed in step 407 of process 400 and discussed above in connection with FIG. 4.

[0114] The received detected electronic signal may include information regarding the location (e.g., x, y, z components) of where a portion of the signal is detected (e.g., where a particular photon is detected) on the abdomen of the pregnant mammal and / or the trajectory of the photon or beam of photons, and may optionally include a time measurement. Additionally or alternatively, the location information regarding the received detected electronic signal and / or portions thereof (e.g., photons of a particular wavelength or intensity) may be determined mathematically, for example, via geometric or probabilistic determinations. In some embodiments, the abdomen of the pregnant mammal and / or portions thereof (e.g., a cross-section or a region in which the fetus is located) may be represented and / or reconstructed as pixels in an image, for example, within a particular dimension (e.g., 2 mm). 2 , 5mm 2 , 10mm 2 , 2mm 3 , 5mm 3 , 10mm 3 Additionally or alternatively, the detected electronic signal may be detected by a photodetector via an area scanning motion (e.g., raster scanning) such that for each photon counted, the position and / or intensity of the detected signal at one or more wavelengths of light is detected, determined, and / or recorded.

[0115] Optionally, the intensity of light for the wavelengths of the detected electronic signal and / or the preprocessed detected electronic signal may be determined for each region of the maternal abdomen (step 1110). In some cases, the intensity may be determined by counting each photon of each wavelength associated with a particular region of the pregnant mammal's abdomen over a predetermined period of time. In some embodiments, performing step 1110 may include processing the fetal signal using, for example, a continuous wave photon transport model. Sometimes, performing step 1110 may include determining a location for a portion of the received detected electronic signal (e.g., a photon or group of photons of a given wavelength), for example, using information about where or when the portion of the detected electronic signal was received.

[0116] Additionally or alternatively, a time of flight for a detected photon included in the detected electronic signal may be received and / or determined (step 1115). In some cases, the time of flight for the detected photon will be specific to the wavelength (or range of wavelengths) of the detected photon.

[0117] Additionally or alternatively, for example, when process 1100 and / or portions thereof use frequency domain analysis, a phase delay of the detected electronic signal and / or an optical signal corresponding to the detected electronic signal may be received and / or determined (step 1120). In some cases, the phase delay will be specific to the wavelength (or wavelength range) of the detected photons.

[0118] Additionally or alternatively, autocorrelation information may be received and / or determined for a laser used to generate an optical signal delivered to the abdomen of the pregnant mammal that corresponds to the detected optical signal (step 1125).

[0119] In step 1130, a differential path length factor (DPF) will be determined for each wavelength of light contained in the detected electronic signal. Sometimes, step 1130 may be performed in a manner similar to that of performing step 1020. In some cases, this determination may be local (i.e., determined for each region and / or layer of the abdomen of the pregnant mammal), for example, using physiological and / or anatomical characteristics of the abdomen of the pregnant mammal.

[0120] An absorption coefficient for each wavelength of the fetal signal will then be determined for each abdomen of the pregnant mammal (step 1135). Sometimes, step 1135 is performed in a manner similar to the performance of step 1025, and Equation 1 may be used to determine the absorption coefficient for step 1135. In some embodiments, the performance of steps 1130 and / or 1135 may use intensity, time of flight, phase delay, and / or laser autocorrelation information received and / or determined in steps 1110 through 1125, respectively.

[0121] Next, an indication of the hemoglobin oxygen saturation level is determined for each region of the pregnant mammal's abdomen, step 1140. Step 1140 may be performed in a similar manner to step 1045, in which Equation 2 may be used to determine an indication of the hemoglobin oxygen saturation level for each region of the pregnant mammal's abdomen.

[0122] The fetal hemoglobin oxygen saturation reading may then be provided to the user (step 1145), for example, via a display on display device 155. In some cases, the fetal hemoglobin oxygen saturation reading may be provided / displayed as a two-dimensional and / or three-dimensional map of hemoglobin oxygen saturation levels determined for each region of the pregnant mammal's abdomen. The two-dimensional and / or three-dimensional map may, in some cases, be generated by mapping each hemoglobin oxygen saturation level with a distinct region of the pregnant mammal's abdomen, and different regions of hemoglobin oxygen saturation within the pregnant mammal's abdomen may be visually displayed, for example, via color coding and / or grayscale. When the user views the map, the user could determine the fetal hemoglobin oxygen saturation by viewing the region of the map that corresponds to the location of the fetus, known, for example, through ultrasound and / or MRI measurements.

[0123] 12 is a flow chart illustrating a process 1200 for determining an individualized ratio (R) value of multiple ratios for a pulse oximeter that can be used to perform transabdominal fetal pulse oximetry. Process 1200 may be performed, for example, by system 100 or components thereof.

[0124] Initially, a first detected electronic signal corresponding to an optical signal of a first wavelength or a first wavelength range emanating from the abdomen of the pregnant mammal and the fetus contained therein will be received (step 1205) by a computer or processor, such as computer 150. In step 1210, a second detected electronic signal corresponding to an optical signal of a second wavelength or a second wavelength range emanating from the abdomen of the pregnant mammal and the fetus contained therein will be received by a computer or processor, such as computer 150. The first and second detected electronic signals will be communicated to the computer directly or indirectly by / from a detector, such as detector 160, that received the optical signal and converted the optical signal to an electronic signal.

[0125] The first and second optical signals may be incident on and / or directed into the abdomen of the pregnant mammal by one or more light sources, such as light source 105. In many cases, the first and second optical signals have similar wavelengths and may be in the same band of the electromagnetic spectrum. For example, the first and second optical signals may both be in the red, near-infrared, or infrared bands of the electromagnetic spectrum. In many cases, the wavelengths of the first and second optical signals are selected so that the path lengths of the first and second optical signals are the same or are close enough to each other that they are mathematically meaningless. For example, the first optical signal may be 790 nm and the second optical signal may be 805 nm, or the first optical signal may be 780 nm and the second optical signal may be 800 nm. As another example, the first optical signal may be 810 nm and the second optical signal may be 825 nm, or the first optical signal may be 820 nm and the second optical signal may be 833 nm. In many cases, the light source used to generate the first and second optical signals may be a light source(s) capable of generating monochromatic light and / or light within a narrow band of wavelengths, such as a laser or LED. In some embodiments, the received detected electronic signal may resemble the detected electronic signal received in step 405 of process 400 discussed above. In some embodiments, process 1200 may be performed using many (e.g., 4, 5, 10, 15, 40, 400, or broadband, or white light, etc.) different optical signals and / or corresponding detected electronic signals.

[0126] Optionally, in step 1212, the first and / or second detected electronic signals may be preprocessed, for example, to remove noise and / or amplify desired portions of the first and / or second detected electronic signals. This preprocessing may be similar to the preprocessing performed in step 407 of process 400 and discussed above in connection with FIG. 4 . Additionally or alternatively, the preprocessing of step 1212 may include, for example, synchronizing the first and second detected electronic signals so that they are aligned in the time domain. In some cases, this synchronization may be similar to the correlation and / or synchronization of step 425. In some cases, the synchronization of the first and second detected electronic signals may be accomplished using timestamps present in the first and second detected electronic signals. These timestamps may be generated, for example, by timestamp marking device 185.

[0127] In step 1215, the first and second detected electronic signals and / or portions of the pre-processed first and second detected electronic signals that were incident on the fetus (referred to herein as the “first fetal signal” and “second fetal signal,” respectively) are isolated from the first and second detected electronic signals received in steps 1205 and 1210, respectively. Step 1215 may be performed using any suitable method of isolating the first and second fetal signals from the first and second detected electronic signals. Suitable methods include, but are not limited to, reducing noise in the signals through application of filtering or amplification techniques (such as those disclosed herein), determining the portions of the first and second detected electronic signals contributed by the pregnant mammal and then subtracting or otherwise removing those portions of the first and second detected electronic signals from the first and second detected electronic signals, and / or receiving information regarding the fetal heart rate and using that information to lock in (e.g., via a lock-in amplifier) ​​the portions of the first and second detected electronic signals generated by the fetus.

[0128] Next, in step 1220, the first and second fetal signals are analyzed and processed to determine a value of end-diastolic PPG pulse amplitude for each fetal signal, thereby determining the amplitude of the end-diastolic PPG pulse amplitude, as referred to herein. D1 and l D2 First and second PPG pulse amplitudes during end-diastole, referred to as end-diastole and end-diastole, respectively, are determined. In some instances, the end-diastolic PPG pulse amplitude may also be understood and / or referred to as an AC signal or AC value. Then, in step 1225, the first and second fetal signals are analyzed and processed to determine a value of the PPG pulse amplitude during systole for each fetal signal, thereby providing values ​​referred to herein as systole. S1 and l S2 The first and second PPG pulse amplitudes during systole, referred to as I and I, respectively, are then determined. In some instances, the PPG pulse amplitude during systole may also be understood and / or referred to as a DC signal or DC value. Since the path length of the first fetal signal and the path length of the second fetal signal are the same or mathematically equivalent, I D1 , I D2 , I S1 , and I S2 The value of can be found without factoring the path length.

[0129] A ratio (also referred to as "R") of the ratios will then be determined (step 1230). Step 1230 may be performed via performing the following calculation according to Equation 3:

number

[0130] In some embodiments, the R value determined via execution of process 1200 is determined on a case-by-case basis for each individual pregnant mammal and / or fetus, allowing for customized or individualized R values ​​for each situation, each pregnant mammal, and / or each fetus. This specificity of the individualized R value can be clinically important because it provides a more accurate R determination than if the R value were determined by the pulse oximeter manufacturer as an average across all situations. Typically, R values ​​are provided by pulse oximeter manufacturers based on evaluation of empirically determined results averaged across numerous situations / individuals. A problem with this approach is that it assumes that the conditions under which the pulse oximeter will be used are relatively uniform across patients and situations, such as the finger or earlobe being traditional locations on the body where pulse oximetry measurements are taken. However, such an assumption may not be appropriate for pregnant mammals because it may not be sufficiently accurate for all pregnant mammals / fetuses due to the wide variability between pregnant mammals and fetuses.

[0131] Sometimes, process 1200 may be performed multiple times during a monitoring session, e.g., on a periodic or on-demand basis, to tailor the R value specifically to a point in time or situation. For example, process 1200 may be performed every hour, every 30 minutes, or every minute during labor and delivery of the fetus, e.g., to adjust the R value when the fetus and / or the pregnant mammal or its uterus moves.

[0132] 13 is a flow chart illustrating a process 1300 for determining the level of oxygen saturation for fetal hemoglobin using a pulse oximeter. Process 1300 may be performed, for example, by system 100 or components thereof.

[0133] Initially, a first detected electronic signal corresponding to an optical signal of a first wavelength or in a first wavelength range emanating from the abdomen of the pregnant mammal and the fetus contained therein will be received by a computer or processor, such as computer 150 (step 1305). At step 1310, a second detected electronic signal corresponding to an optical signal of a second wavelength or in a second wavelength range emanating from the abdomen of the pregnant mammal and the fetus contained therein will be received by the computer or processor. The first and second detected electronic signals may be transmitted to the computer directly or indirectly by / from a detector, such as detector 160.

[0134] The first and second optical signals may be incident on and / or directed into the abdomen of the pregnant mammal by one or more light sources, such as light source 105. In many cases, the wavelengths of the first and second optical signals are selected so that the path lengths of the first and second optical signals are the same or are close enough to each other to be mathematically insignificant. For example, the first optical signal may be 790 nm and the second optical signal may be 810 nm, or the first optical signal may be 795 nm and the second optical signal may be 815 nm. In many cases, the light source(s) used to generate the first and second optical signals may be light source(s) capable of generating monochromatic light and / or light within a narrow band of wavelengths, such as a laser or LED. Optionally, in step 1312, the first detected electronic signal and / or the second detected electronic signal may be preprocessed, for example, to remove noise and / or amplify desired portions of the first and / or second detected electronic signals. This preprocessing may be similar to the preprocessing performed in step 407 of process 400 and discussed above in connection with FIG. 4. Additionally or alternatively, the preprocessing of step 1312 may include, for example, synchronizing the first and second detected electronic signals so that they are aligned in the time domain. In some cases, this synchronization may be similar to the correlation and / or synchronization of step 425. In some cases, the synchronization of the first and second detected electronic signals may be accomplished using timestamps present in the first and second detected electronic signals. These timestamps may have been generated, for example, by timestamp marking device 185.

[0135] In step 1315, the portions of the first and second detected electronic signals that were incident on the fetus (referred to herein as the “first fetal signal” and “second fetal signal,” respectively) are isolated from the first and second detected electronic signals received in steps 1305 and 1310, respectively, and / or preprocessed in step 1307. Step 1315 may be performed using any suitable method of isolating the first and second fetal signals from the first and second detected electronic signals. Suitable methods include, but are not limited to, reducing noise in the signals, for example through application of filtering or amplification techniques, determining the portions of the first and second detected electronic signals contributed by the pregnant mammal and then subtracting or otherwise removing those portions of the first and second detected electronic signals to isolate the first and second fetal signals from the first and second detected electronic signals, and / or receiving information regarding the fetal heart rate and using that information to lock in the portions of the first and second detected electronic signals generated by the fetus.

[0136] In step 1320, an R value for the fetus and / or the pulse oximetry device (e.g., fetal probe 115) is received. In some cases, the R value for the fetus may be the R value generated through execution of process 1200 and determined in step 1230. Additionally or alternatively, the R value may also be provided by the manufacturer of the pulse oximetry device or may be an otherwise known R value.

[0137] The first and second fetal signals are then analyzed and processed to determine fetal hemoglobin oxygen saturation levels in step 1325. In some instances, execution of step 1325 may involve determining oxygenated hemoglobin (ε) and deoxygenated hemoglobin (ε) for the first and second fetal signals. dThe extinction coefficient of hemoglobin may be understood to be the absorption constant of the sample divided by the hemoglobin concentration. Once the extinction coefficients are determined, they can be plugged into the following equation (Equation 4) to determine the hemoglobin oxygen saturation (SpO2) for the fetus:

number

number

[0138] Figure 14A depicts an example fetal probe 115B in contact with the abdomen of a pregnant mammal in a manner similar to that shown in Figure 3. In Figure 14A, the maternal tissue layers shown in, for example, Figures 2A and 2B are resolved or simplified into simplified layers of maternal tissue 1405 that approximate the properties of the multiple layers of tissue under consideration. In other embodiments, the maternal tissue layers may be resolved into two or more simplified layers (not shown). Fetal probe 115B is configured to enable short separation (SS) analysis of light emanating from the abdomen of a pregnant mammal and a fetus contained therein.

[0139] Fetal probe 115B includes first light source 105A emitting first light signal 315, second light source 105B emitting second light signal 320, and detector 160. First light beam 315 and / or second light beam 320 may include light of a single wavelength or multiple wavelengths, e.g., in the red, near-infrared, or infrared spectrum. In some circumstances, the characteristics of light signal 315 may differ from the wavelength of light signal 320 and / or may be projected onto the abdomen of the pregnant mammal at different times, so that the light projected from the two light sources can be distinguished when received by detector 160 and processed according to one or more of the processes described herein. In some embodiments, fetal probe 115B may include a filter (not shown) for detector 160 that can, for example, attenuate light from first light source 105A and second light source 105B so that detector 160 detects equal amounts of light from first light source 105A and second light source 105B.

[0140] In many instances, the depth of light propagation through the abdomen of the pregnant mammal depends on the distance between the light source and the detector. In some embodiments, the position of first light source 105A and / or second light source 105B can be adjusted (e.g., moved closer to or farther from detector 160) to, for example, adapt the depth of propagation for light emitted from the light source. The adjustment may be facilitated, for example, by a track or other positioning device (not shown) included in fetal probe 115B. In some instances, the positioning of first light source 105A and / or second light source 105B may be adjusted depending on the depth of fetus 310 within the abdomen of the pregnant mammal (i.e., a measurement of the width of maternal tissue 1405 located between fetal probe 115B and fetus 310). The measurement of the depth of fetus 310 within the abdomen of the pregnant mammal may be provided, for example, by an ultrasound or Doppler probe, such as Doppler / ultrasound probe 135, and / or an MRI image, such as illustrations 201 and 202.

[0141] In some embodiments, first light source 105A may be positioned relative to detector 160 such that light emitted from the first light source (i.e., optical signal 315) propagates only through maternal tissue 1405 and does not reach fetus 310. Second light source 105B may be positioned farther away from detector 160 (relative to first light source 105A) such that light projected by second light source 105B (i.e., optical signal 320) penetrates deeper into the abdomen of the pregnant mammal than optical signal 315, and backscattering therefrom and / or transmission therethrough is detected by detector 160. In other words, light source 105A may be positioned such that optical signal 315 only illuminates maternal tissue 1405, such that the portion of optical signal 315 detected by detector 160 is only backscattered from maternal tissue 1405 and not from fetus 310 and / or is transmitted only through maternal tissue 1405 and not through fetus 310, while light source 105B may be positioned such that optical signal 320 illuminates both maternal tissue 1405 and fetus 310, such that the portion of optical signal 320 detected by detector 160 is backscattered from and / or transmitted through maternal tissue 1405 and fetus 310. This positioning of first light source 105A facilitates measurements over a short range (SS), and the path of first optical signal 315 and / or the amount of first optical signal 315 detected by detector 160 may be referred to herein as the SS channel. This positioning of the second light source 105B facilitates measurements at long distances (LS), and the path of the second optical signal 320 and / or the amount of detection of the second optical signal 320 by the detector 160 may be referred to herein as the LS channel.

[0142] Figure 14B provides a similar setup to Figure 14A, except that the layers of tissue are not resolved into simplified layers of maternal tissue 1405, but instead approximations of the individual layers of maternal and fetal tissue are shown. More specifically, Figure 14B shows a first layer representing / approximating maternal skin layer 1415, a second layer representing / approximating maternal subcutaneous fat layer 1420, a third layer representing / approximating maternal abdominal (skeletal) muscle layer 1425, a fourth layer representing / approximating maternal intra-abdominal fat layer 1430, a fifth layer representing / approximating uterine wall (smooth muscle) layer 1435, a sixth layer representing / approximating amniotic fluid layer 1440, and a seventh layer representing / approximating fetus 310. In some embodiments, these representations and / or approximations of tissue layers may include the manner in which the layers may affect the behavior (e.g., scattering and / or absorption) of light and / or photons passing through each tissue layer. Sometimes, these approximations and / or representations may be made with the aid of computer modeling techniques, for example, via MATLAB® or other computer modeling software.

[0143] In some embodiments, the actual measurements and / or approximate dimensions of the maternal and / or fetal tissues used to develop the representations and / or approximations of the characteristics of the tissue layers may be based on, for example, ultrasound images, MRI images, illustrations such as illustrations 201 or 202, and / or other information about the pregnant mammal and / or fetus (e.g., melanin content, weight, body mass index, gestational age of the fetus, etc.).

[0144] 14B, the first light beam 1415 penetrates layers 1415-1440 and can therefore provide information about each of these layers separately and / or collectively. In some embodiments, the first light beam 1415 may be adjusted to penetrate only to the depth of the layer of maternal tissue under consideration (e.g., 1415, 1420, 1425, 1430, 1435), for example, to determine the characteristics and / or properties (e.g., light scattering, or light absorption, and / or hemoglobin saturation levels) of the tissue layer of interest.

[0145] Figure 15A depicts an exemplary fetal probe 115C in contact with the abdomen of a pregnant mammal in a manner similar to that shown in Figures 3, 14A, and 14B. The embodiment shown in Figure 15A utilizes a simplified layer of maternal tissue 1405, and the fetal probe 115C is configured to allow dual short-range (SS) analysis of light backscattered from and / or transmitted through the abdomen of the pregnant mammal and the fetus contained therein.

[0146] Fetal probe 115C includes first light source 105A emitting first light signal 315, compact detector 1510, second light source 105B emitting second light signal 320, and detector 160. A first portion of second light signal 320A may be detected by compact detector 1510, and a second portion of second light signal 320B may be detected by detector 160. First light beam 315 and / or second light beam 320 may include light of a single wavelength or multiple wavelengths, e.g., in the red, near-infrared, and / or broadband spectrum. In some circumstances, the wavelength of light signal 315 may be different from the wavelength of light signal 320 and / or may be projected onto the abdomen of the pregnant mammal at different times to enable differentiation between the light projected from the two light sources when received by detector 160 and processed according to one or more of the processes described herein. Miniature detector 1510 may be similar to detector 160, but may have, for example, a smaller size and / or lower sensitivity. In some cases, miniature detector 1510 may be a miniature fiber detector. In some embodiments, fetal probe 115C may include a filter (not shown) for detector 160 that can attenuate light so that detector 160 detects equal amounts of light from first light source 105A and second light source 105B.

[0147] In some embodiments, the position of first light source 105A and / or second light source 105B can be adjusted (e.g., moved closer to or farther from detector 160) to adapt the depth of light from the light sources detected by detector 160, for example. Adjustment may be facilitated, for example, by manual manipulation and / or placement of the detector and / or by moving the detector along a track or other positioning device contained within and / or associated with fetal probe 115C (not shown). In some cases, the positioning of first light source 105A and / or second light source 105B may be adjusted depending on the depth of fetus 310 within the abdomen of the pregnant mammal (i.e., a measurement of the width of maternal tissue 1405 located between fetal probe 115C and fetus 310). The measurement of the depth of fetus 310 within the abdomen of the pregnant mammal may be provided, for example, by an ultrasound or Doppler probe, such as Doppler / ultrasound probe 135, and / or images of the abdomen of the pregnant mammal, such as illustrations 201 and 202.

[0148] In some embodiments, first light source 105A may be positioned relative to detector 160 such that light emitted by the first light source (i.e., optical signal 315) propagates only through maternal tissue 305 and does not reach fetus 310. Second light source 105B may be positioned farther away from detector 160 (relative to first light source 105A) such that light projected by second light source 105B (i.e., optical signal 320) penetrates deeper into the abdomen of the pregnant mammal than optical signal 315, and light backscattered from and / or transmitted through the fetus is detected by detector 160. A compact detector 1510 may be positioned between first light source 105A and second light source 105B such that light (i.e., optical signal 320) propagates only through maternal tissue 1405 and does not reach fetus 310 before being detected by compact detector 1510. This positioning of first light source 105A facilitates collection of a first set of measurements over a short distance (SS), where the path of first optical signal 315 and / or the amount of detection of first optical signal 315 by detector 160 may be referred to herein as a first SS channel. This positioning of second light source 105B facilitates collection of measurements over a long distance (LS), where the path of second optical signal 320 and / or the amount of detection of second optical signal 320 by detector 160 may be referred to herein as an LS channel. This positioning of compact detector 1510 facilitates collection of a second set of measurements over a short distance (SS), where the path of first optical signal 315 and / or the amount of detection of first optical signal 315 by detector 160 may be referred to herein as a second SS channel. Thus, fetal probe 115C provides SS measurements of both first light source 105A and second light source 105B.

[0149] 16 is a flowchart illustrating an example process 1600 for using a set of signals at short intervals (SS) to generate a fetal signal that can be used to determine a fetal hemoglobin oxygen saturation level. Process 1600 may be performed, for example, by system 100 and / or its components. Specifically, process 1600 may be performed by receiving information from a fetal probe, such as fetal probes 115B and / or 115C depicted in FIGS. 14A and 14B and discussed above.

[0150] Initially, in step 1605, short-range detected electronic signals are received by a computer and / or processor, such as computer 150. The short-range detected electronic signals (also referred to herein as "short-range signals" or "SS signals") may correspond to one or more optical signals in short-range channels. The SS signals are derived from a set of optical signals projected from one or more light sources, such as light source 105, onto the abdomen of the pregnant mammal and emerging from the abdomen, and more specifically, from maternal tissue 1405, e.g., via transmission and / or backscattering. The SS signals may be similar to the portion of first optical signal 315 detected by a detector, such as detector 160 shown in FIG. 14A and / or FIG. 14B.

[0151] The SS signals may correspond to optical signals at two or more different wavelengths or wavelength ranges, e.g., in the red and / or near-infrared portions of the electromagnetic spectrum, that are detected by a detector, such as detector 160, and converted into electrical signals (i.e., SS signals) that are transmitted to a computer or processor. The light source for the optical signals that generate the SS signals may be sufficiently close to the detector such that, e.g., due to the distance between the light source and the detector, only light that is incident on the maternal tissue is detected by the detector.

[0152] In step 1610, a detected electronic signal at a long range interval is received, for example, by a computer and / or processor. The detected electronic signal at a long range interval (also referred to herein as a "signal at a long range interval" or "LS signal") may correspond to one or more optical signals in a long range channel. The LS signal may be derived from a second optical signal projected from a light source, such as light source 105B, onto the abdomen of the pregnant mammal, backscattered from and / or transmitted through the abdomen, more specifically through the maternal tissue and the fetus contained therein, detected by a detector, such as detector 160, and converted into an electrical signal (i.e., the LS signal) that is transmitted to a computer or processor. The LS signal corresponds to an optical signal, such as second optical signal 320, traveling along the LS channel. The LS signal may be at a second wavelength or a second wavelength range, for example, in the red and / or NIR spectrum, and may optionally be different from the wavelength or wavelength range of the SS signal. This difference could aid in differentiating the SS and / or LS optical signals and / or detected electronic signals, which may have some similarities to the detected electronic signals received in step 405 of process 400 discussed above in connection with FIG.

[0153] Optionally, in step 1612, the SS and / or LS signal(s) may be preprocessed, e.g., to remove noise and / or amplify desired portions of the first detected electronic signal(s) and / or second detected electronic signal(s), respectively. This preprocessing may be similar to the preprocessing performed in step 407 of process 400 and discussed above in connection with FIG. 4 . Additionally or alternatively, the preprocessing of step 1612 may include synchronizing and / or correlating the SS and LS signals so that they are aligned in the time domain. In some cases, this synchronization may be similar to the correlation and / or synchronization of step 425. Synchronization of the SS and LS signals may sometimes be accomplished using timestamps present in the SS and LS signals, e.g., timestamps that provide a simultaneous or near-simultaneous start of detection of the SS and LS signals. These timestamps may be generated, e.g., by timestamp marking device 185, in a manner similar to that discussed above.

[0154] In step 1615, the LS signal will be processed using the SS signal and / or the preprocessed SS signal and / or the preprocessed LS signal. The purpose of this processing may be to understand the characteristics of the signal backscattered from and / or transmitted solely through the tissue of the pregnant mammal, as represented by the SS signal. Further information regarding maternal tissue and exemplary dimensions of maternal tissue are shown in the illustrations 201 and 202 of FIGS. 2A and 2B, and are provided in FIGS. 14B and 15B and the associated discussion. The result of processing the SS signal will be the removal or subtraction of information similar to the SS signal that may be present in the LS signal. In this manner, the maternal contribution to the LS signal will be removed, which helps isolate the portion of the LS signal representing light incident on the fetus, i.e., the portion referred to herein as the fetal signal. Additionally or alternatively, the processing of step 1615 reduces contamination in the LS signal (e.g., maternal physiological signals such as light scattering caused by uterine contractions, light scattered from and / or transmitted through maternal blood, etc.) so that fetal signals present in the LS signal caused by backscattered light from the fetus can be more easily identified.

[0155] The processing of step 1615 can take many forms. Sometimes, when the SS and LS optical signals include multiple wavelengths of light, the processing of 1615 may include separating portions of the SS and LS optical signals into portions corresponding to each of the multiple wavelengths, so that each wavelength could be processed separately, for example.

[0156] In some cases, the processing of step 1615 may include using a back-reflection geometry. Additionally or alternatively, the processing of step 1615 may include subtracting the SS signal from the LS signal. Additionally or alternatively, the processing of step 1615 may include using the SS signal as a regressor during LS signal processing. Additionally or alternatively, the processing of step 1615 may include applying one or more amplifications (e.g., via a lock-in amplifier) ​​and / or filtering (e.g., via a band-pass filter or a Kalman filter) to the SS signal and / or the LS signal. In some cases, performing this filtering may be similar to performing step 435 discussed above in connection with FIG. 4.

[0157] In one embodiment, the SS signal(s) will be analyzed to determine how the light of the first optical signal interacts with maternal tissue. This information will be used to look for similar interactions of the LS signal with the pregnant mammal and fetus, which will then be known to be transmitted through and / or backscattered from the pregnant mammal. Portions of the LS signal associated with these similar interactions will be subtracted or otherwise removed from the LS signal. This can help remove contamination in the LS signal caused by the pregnant mammal and make it easier to identify, interpret, and / or analyze portions of the LS signal contributed by the fetus.

[0158] At step 1620, it will be determined whether a secondary signal (e.g., maternal heart rate signal, fetal heart rate signal, fetal depth within the abdomen of the pregnant mammal, maternal respiratory signal, uterine contraction information, light scattering information, information regarding noise in the signal, etc.) has been received. If a secondary signal has not been received, a fetal signal will be generated using the processed LS signal (step 1625). The fetal signal represents the portion of the LS signal contributed by light backscattered from and / or transmitted through the fetus.

[0159] If a secondary signal is received, the secondary signal is applied to the processed LS signal of step 1615 (step 1625), e.g., to further remove noise from the signal and / or to isolate the portion of the LS signal contributed by the fetus.

[0160] At step 1630, a fetal signal is generated using the processed LS signal of step 1615 or 1625 (step 1630). In some cases, the processed LS signal of step 1615 or 1625 may be the fetal signal without further processing or analysis being performed at step 1630. Additionally or alternatively, one or more additional processes (e.g., processes 400, 500, 600, 700, and / or 800) may be applied to the LS signal, e.g., to further refine the LS signal, to amplify the fetal contribution to the LS signal, and / or to clarify the fetal signal.

[0161] The fetal signal is then analyzed to determine a fetal hemoglobin oxygen saturation level (step 1635), e.g., using one or more processes described herein and / or performing calculations involving the Beer-Lambert law and / or modified Beer-Lambert law, and an indication of the fetal hemoglobin oxygen saturation level is facilitated to a user (e.g., a physician, a nurse, a pregnant mammal, etc.) via a display device, e.g., display device 155 (step 1640).

[0162] Initially, in step 1705, a first SS signal will be received by a computer and / or processor, such as computer 150. The first SS signal may originate from a first optical signal, such as first optical signal 315, projected from a light source, such as light source 105A (shown and discussed above with respect to FIGS. 15A and 15B), onto the abdomen of a pregnant mammal, backscattered from and / or transmitted through the abdomen, more specifically through maternal tissue (examples of which are provided in FIGS. 2A, 2B, 14A, 14B, 14A, and 15B and their associated discussion), and detected by a detector, such as detector 160. The first optical signal is detected by a detector, such as detector 160, and converted into an electrical signal (i.e., the first SS signal), which is communicated to the computer or processor and received in step 1705. The first optical SS signal may be at a first wavelength or in a first wavelength range, for example in the red and / or NIRS spectrum.

[0163] In step 1710, an LS signal is received, for example, by a computer and / or processor. The LS signal may originate from a second portion of a second optical signal, such as second portion of second optical signal 320B, projected from a light source, such as second light source 105B, onto the abdomen of the pregnant mammal and backscattered from and / or transmitted through the abdomen of the pregnant mammal and / or fetus (e.g., maternal tissue 1405 and / or fetus 310). The second portion of the second optical signal is detected by a detector, such as detector 160, and converted into an electrical signal (i.e., the LS signal), which is communicated to a computer or processor. The LS signal may be at a second wavelength or a second wavelength range within the NIRS spectrum that is different from the wavelength or wavelength range of the first optical signal and / or the SS signal.

[0164] In step 1715, a second SS signal is received, for example, by a computer and / or processor. The second SS signal may originate from a first portion of a second optical signal projected from a light source, such as second light source 105B, onto the abdomen of the pregnant mammal and backscattered from and / or transmitted through the abdomen, more specifically through maternal tissue 1405. The optical signal is detected by a detector, such as compact detector 1510, converted into an electrical signal (i.e., the second SS signal), and transmitted to a computer or processor. The second SS signal may correspond to an SS optical signal, such as first portion 320A of the second optical signal, detected by a detector, such as compact detector 1510. The second SS signal may be of the same wavelength and / or wavelength range as the LS signal.

[0165] Optionally, in step 1717, the first SS signal, the LS signal, and / or the second SS signal may be preprocessed, e.g., to remove noise and / or amplify desired portions of each of the first SS signal, the LS signal, and / or the second SS signal(s). This preprocessing may be the same as the preprocessing performed in step 407 of process 400 and discussed above with respect to FIG. 4. Additionally or alternatively, the processing of step 1717 may include synchronizing the SS signal, the LS signal, and / or the second SS signal, e.g., so that they are aligned in the time domain. In some cases, this synchronization may be similar to the correlation and / or synchronization of step 425. In some cases, synchronization of the SS signal, the LS signal, and / or the second SS signal(s) may be accomplished using timestamps present in the SS signal, the LS signal, and / or the second SS signal(s). These timestamps may be generated, for example, by timestamp marking device 185.

[0166] At step 1720, the LS signal is processed using both the first SS signal and the second SS signal. The purpose of the processing of step 1720 is to understand the characteristics of the signal backscattered from and / or transmitted through maternal tissue at two different locations on the abdomen of the pregnant mammal so that these characteristics can be removed from the LS signal to reveal the portion of the LS signal corresponding to light backscattered from and / or transmitted through the fetus. In some embodiments, the processing of step 1720 can reduce contamination of the fetal signal caused by light backscattered from and / or transmitted through the pregnant mammal and / or noise (e.g., maternal physiological signals such as scattering caused by uterine contractions or breathing, backscattering from and / or transmission through maternal blood, etc.). Receiving SS signals from two different locations can facilitate a better understanding of the spatially non-uniform response of the pregnant mammal's abdomen to incident light (e.g., the first and second light signals). For example, the thickness of the uterus of a pregnant mammal may be greater in one location than in another, and this difference may be taken into account with two different SS signals that may depend on the placement of the fetal probe containing the first and second detectors and / or the arrangement of the detectors and / or light sources within the probe.

[0167] The processing of step 1720 can take many forms. Sometimes, the processing may include back-reflection geometry. Additionally or alternatively, the processing of step 1720 may include subtracting both SS signals from the LS signal. Additionally or alternatively, the processing of step 1720 may include using the first and / or second SS signals as regressors when processing the LS signal. Additionally or alternatively, the processing of step 1720 may include applying one or more amplifications (e.g., via a lock-in amplifier) ​​and / or filtering (e.g., via a band-pass filter or a Kalman filter) to the detected electronic signal. In some cases, the two SS signals may be linearly combined and then used as a regressor input to a Kalman filtering algorithm for processing the LS signal.

[0168] At step 1725, it will be determined whether a secondary signal has been received. If a secondary signal has not been received, the processed LS signal will be used to generate a fetal signal (step 1735), which in some embodiments may be the same as the processed LS signal of step 1720. The fetal signal is representative of light backscattered from and / or transmitted through the fetus.

[0169] If a secondary signal has been received, the secondary signal is applied (step 1730) to the processed LS signal of step 1720 to generate a fetal signal (step 1735). Exemplary secondary signals include, but are not limited to, a maternal heart rate signal, a fetal heart rate signal, the depth of the fetus within the abdomen of the pregnant mammal, a maternal respiratory signal, uterine contraction information, light scattering information, information regarding noise in the signal, etc.

[0170] The fetal signal is then analyzed to determine a fetal hemoglobin oxygen saturation level (step 1740), e.g., using one or more processes described herein and / or performing calculations involving the Beer-Lambert law and / or a modified Beer-Lambert law. Step 1745 may facilitate providing an indication of the fetal hemoglobin oxygen saturation level to a user (e.g., a physician, clinician, nurse, pregnant mammal, etc.) via a display device, such as display device 155. In some embodiments, determining and / or providing an indication of the fetal hemoglobin oxygen saturation level may be similar to performing steps 1635 and / or 1640 discussed above and may include, among other things, determining a TWA for the fetal hemoglobin oxygen saturation level and / or simultaneously displaying the fetal hemoglobin oxygen saturation level with the fetal heart rate and / or the TWA of the fetal heart rate.

[0171] 18 provides a flowchart illustrating a process 1800 for generating images of a pregnant mammal's abdomen and / or a fetus contained therein using diffuse optical tomography (DOT) and determining fetal tissue oxygen saturation levels therefrom. Process 1800 may be performed, for example, by system 100 and / or its components. When DOT is performed, system 100 may include a plurality of light sources 105, which may be lasers (e.g., synchronous picosecond pulsed diode lasers) or optical fibers coupled to one or more lasers, a plurality of highly sensitive photodetectors (e.g., single-photon sensitive detectors), such as detector 160, and a processor configured to process the output of photodetector 16. In some embodiments, the plurality of lasers or optical fibers and the plurality of photodetectors may be arranged in an array configured to cover and conform to a portion of the abdomen of a pregnant mammal so as to image a fetus therein.

[0172] Initially, a plurality of detected electronic signals are received from a plurality of photodetectors (e.g., detector 160) by a processor and / or computer, such as computer 150 (step 1805). The detected electronic signals may be transmitted directly to the processor or computer by the photodetector, by a transceiver coupled to the detector, and / or by a fetal probe, such as fetal probe 115. The light entering and exiting the abdomen of the pregnant mammal can be generated by a plurality of light sources, such as light source 105, and may be of any acceptable frequency or wavelength (e.g., red and / or near-infrared (NIR)). Optionally, the received detected electronic signals may resemble the detected electronic signals received in step 405 of process 400 discussed above. In some embodiments, the received detected electronic signals may include and / or be associated with a detector identifier (e.g., an identification stamp) to allow the location of a particular detected electronic signal to be known. This localization may, in some cases, be used when the received detected electronic signals are processed and analyzed (step 1810) to determine various parameters of the detected light and / or imaged tissue.

[0173] At times, the processing and analysis of step 1810 may be performed using, for example, the number of photons detected by a particular detector that detected a particular photon, the location or position of the detector providing the particular detected electronic signal, the intensity of light detected by the particular detected electronic signal, light scatter, the angle of incident light, the angle of exit light, the path length of the photon, the time of flight of the photon, etc. Exemplary factors that may be determined through performance of step 1810 include, but are not limited to, light absorption, light scatter, tissue density, and tissue oxygen saturation. Further details regarding how detected electronic signals may be processed and analyzed are provided herein.

[0174] Optionally, performing step 1810 may include processing one or more of the received plurality of detected electronic signals, for example, to remove noise and / or amplify desired portions of each of the first and / or second detected electronic signals. This processing may be similar to the preprocessing performed in step 407 of process 400 and discussed above in connection with FIG. 4 . Additionally or alternatively, processing in step 1810 may include synchronizing the plurality of detected electronic signals so that they are aligned in the time domain. In some cases, this synchronization may be similar to the correlation and / or synchronization of step 425. Sometimes, synchronization of the plurality of detected S signals may be accomplished using timestamps present in the plurality of detected electronic signals. These timestamps may be generated, for example, by timestamp marking device 185.

[0175] In step 1815, an image of the pregnant mammal's abdomen or a portion thereof is generated using the results of the processing / analysis performed in step 1810. The image may, for example, show density and / or tissue oxygen saturation indications for various layers of tissue contained in the maternal abdomen and / or fetus (e.g., skin, fat, uterus, amniotic fluid, fetal skin, fetal brain, fetal muscle, etc.). In embodiments in which the image of the pregnant mammal's abdomen is generated using information about regional variations in tissue oxygen concentration, step 1815 may be performed, for example, by generating a color-coded image (e.g., through the use of grayscale or different colors indicating different levels of tissue oxygen saturation) to show tissue oxygen saturation for various layers of maternal tissue and / or fetal tissue and / or fetal tissue only, if step 1820 is performed prior to step 1815, for example, as described below. An example of an image 2300 generated via performance of step 1815 is provided in Figure 23, which shows a grayscale color-coded local variation in the intensity / quantity of detected photons measured in milliwatts, with lighter shading indicating higher intensity and darker shading indicating lower intensity according to scale 2310. In some embodiments, these intensity values ​​can be used to determine light absorption characteristics that are used to determine the level of tissue oxygenation within the image. Additionally or alternatively, the intensity values ​​may be used to directly determine the level of tissue oxygenation within the image.

[0176] In some embodiments, detected photons incident on the fetus can be differentiated from detected photons incident on the pregnant mammal using time of flight, i.e., the time it takes for an emitted photon to be detected by a photodetector for photon detection. This time of flight can be determined, for example, using the location, depth, and / or position of the fetus. Detected photons determined to have incident on the fetus can be used to generate an image, such as image 2300, from which tissue oxygenation of the fetus can be determined.

[0177] At step 1820, information regarding the location and / or position of the fetus is received. This information may be received, for example, via an ultrasound device or an MRI image. Sometimes, the location and / or depth of the fetus may be entered directly into the computer by a user and / or healthcare provider (e.g., a doctor and / or nurse), for example, following analysis of an ultrasound or MRI image by the user and / or healthcare provider.

[0178] In some embodiments, step 1820 may be performed prior to step 1815, such that information regarding the location and / or position of the fetus may be used to focus on the fetal tissue of interest and generate images of only the fetus and / or fetal tissue prior to generating images of the abdomen of the pregnant mammal. This may save considerable time and processing power compared to performing step 1815 before step 1820, e.g., because only the portion of the image corresponding to the fetus (as opposed to the entire maternal abdomen and / or portions thereof) is generated.

[0179] Optionally, in step 1825, a portion of the image corresponding to the location and / or position of the fetus may be examined or analyzed to determine a fetal tissue oxygen saturation level. Step 1825 may be performed, for example, by determining a numerical value for fetal tissue oxygen saturation based on the image generated in step 1815, intensity values ​​associated with the image, and / or the processed and analyzed signals of step 1810. An indication of the generated image and / or determined fetal tissue oxygen saturation level may then be provided to a user in step 1830 via communication of the image / fetal tissue oxygen saturation level to a display device, such as display device 155. If step 1825 is not performed, the fetal tissue oxygen saturation level may be determined by a user (e.g., a physician or technician) visually observing, for example, the image of the maternal abdomen and / or fetus provided via performance of step 1830.

[0180] 19 provides a flowchart illustrating a process 1900 for using DOT to generate images of a pregnant mammal's abdomen and / or a fetus contained therein and to determine fetal tissue oxygen saturation levels therefrom. Process 1900 may be performed, for example, by system 100 and / or its components. When DOT is performed, system 100 may include a plurality of light sources 105, which may be lasers (e.g., synchronous picosecond pulsed diode lasers) or optical fibers coupled to one or more lasers, a plurality of highly sensitive photodetectors (e.g., single-photon sensitive detectors), such as detector 160, and a processor configured to process the output of photodetector 16. In some embodiments, the plurality of lasers or optical fibers and the plurality of photodetectors may be arranged in an array configured to cover and conform to a portion of the abdomen of a pregnant mammal so as to image a fetus within the abdomen.

[0181] Initially, a plurality of detected electronic signals are received from a plurality of photodetectors (e.g., detector 160) by a processor and / or computer, such as computer 150 (step 1905). Examples of fetal probes that can be used to detect the plurality of electronic signals are provided in FIGS. 1B and 1C. The detected electronic signals may be transmitted directly to the processor or computer by the photodetectors, by a transceiver coupled to the detected electronic signals, and / or by a fetal probe, such as fetal probe 115. Light entering and exiting the abdomen of the pregnant mammal can be generated by a plurality of light sources, such as light source 105, and may be of any acceptable frequency or wavelength (e.g., red and / or near-infrared (NIR)). The received detected electronic signal may include and / or be associated with a detector identifier (e.g., modulation format; wavelength; detector location, orientation, and / or position, etc.) and / or the received detected electronic signal may be projected at a particular time such that the location of the particular detector detecting the electronic signal and / or the light source projecting the photons of the detected electronic signal are known.

[0182] One or more short-range interval signals may be received in step 1910, for example, via transmission of short-range interval signals(s) from, by way of example, fetal probes 115, 115B, and / or 115C. As noted above, the short-range interval signals may provide information regarding the contribution of the pregnant mammal's tissue to the plurality of detected electronic signals. In embodiments in which two or more short-range interval signals are received, the plurality of short-range interval signals may be used to determine information regarding the contribution of the pregnant mammal to the plurality of detected electronic signals and / or characteristics or properties of maternal tissue at different locations in the maternal abdomen.

[0183] In some embodiments, the signals at short range intervals may include information about one or more layers of maternal tissue and their properties (e.g., absorption, scattering, location, width, etc.). For example, signals at multiple short range intervals may be received, with each short range interval signal including information about a different layer (e.g., skin, abdominal muscle, fat, uterine wall, and / or amniotic fluid). In some embodiments, the signals at short range intervals may resemble the signals at short range intervals received in steps 1605, 1705, and / or 1715 of processes 1600 and / or 1700 discussed in connection with FIGS. 16 and 17 herein.

[0184] Then, either step 1915 or 1935 would be performed. If step 1915 is performed, the received detected electronic signals would be processed and analyzed using signals at one or more short distance intervals to, for example, determine which portions of the plurality of detected electronic signals are contributed by the pregnant mammal and / or are not reflected from or transmitted through the fetus. The portions of the plurality of detected electronic signals contributed by the pregnant mammal would then be removed from the detected electronic signals (step 1920), for example, via subtraction or application of a filter to the detected electronic signals that includes an indication or approximation of the portions of the plurality of detected electronic signals contributed by the pregnant mammal.

[0185] Optionally, at step 1925, an image of the fetus and / or fetal tissue, such as image 2300, may be generated using the remaining portion of the detected electronic signal. The image may, for example, show an indication of the density and / or tissue oxygen saturation of one or more layers of fetal tissue (e.g., skin, fat, brain, etc.). In embodiments in which the image of the pregnant mammal's abdomen is generated using information about regional variations in tissue oxygen concentration, step 1925 may be performed, for example, by generating a color-coded image (e.g., via the use of grayscale or different colors indicating different levels of tissue oxygen saturation) to indicate the tissue oxygen saturation for one or more layers of fetal tissue. If the image generated at step 1925 visually indicates the tissue oxygen saturation for one or more layers of fetal tissue, step 1930 is not performed and process 1900 may proceed to step 1960, whereby the generated image will be provided to a user via transmission of the image / fetal tissue oxygen saturation level to a display device, such as display device 155.

[0186] If step 1925 is performed, the image of the fetus and / or fetal tissue is analyzed to determine the tissue oxygen saturation level of the fetus and / or imaged fetal tissue (step 1930), and then in step 1960, an indication of the determined fetal tissue oxygen saturation level is provided to the user via transmission of the image / fetal oxygen saturation level indication to a display device, such as display device 155.

[0187] If step 1925 is not performed, the remaining portions of the plurality of detected electronic signals are analyzed to determine an indication of the fetal tissue oxygen saturation level, and this determined indication of the fetal tissue oxygen saturation level is provided to the user via execution of step 1960.

[0188] At step 1935, the received detected electronic signals are processed and analyzed in a manner similar to that performed in step 1810. Then, at step 1940, an image of the pregnant mammal's abdomen, or a portion thereof, is generated using the results of the processing / analysis performed in step 1935 in a manner similar to that performed in step 1815. Image 2300, discussed above in connection with FIG. 23, is one exemplary image that may be generated in step 1940.

[0189] Optionally, performing steps 1935 and / or 1915 may include preprocessing the plurality of detected electronic signals, for example, to remove noise and / or amplify desired portions of each of the plurality of detected electronic signals. This preprocessing may be similar to the preprocessing performed in step 407 of process 400 and discussed above in connection with FIG. 4 . Additionally or alternatively, performing steps 1935 and / or 1915 may include synchronizing two or more of the plurality of detected electronic signals so that they are aligned in the time domain. In some cases, the synchronization may be similar to the correlation and / or synchronization of step 425. In some instances, the synchronization of the plurality of detected electronic signals may be accomplished using timestamps present in the plurality of detected electronic signals. These timestamps may be generated, for example, by timestamp marking device 185.

[0190] In step 1945, the generated image and / or received detected electronic signals are further processed and analyzed using the short range interval signals received in step 1910, for example to determine what portions of the image and / or detected electronic signals are contributed by the pregnant mammal. The portions of the image and / or received detected electronic signals contributed by the pregnant mammal are then removed from the image of step 1940 and / or from the received detected electronic signals of step 1905 (step 1950), and the remaining portions of the image and / or received detected electronic signals are analyzed to determine the level of fetal tissue oxygen saturation (step 1955). Step 1960 is then performed.

[0191] In some embodiments, determining and / or providing an indication of fetal tissue oxygen saturation (e.g., steps 1930, 1955, and 1960) may be similar to performing steps 1825 and / or 1830 discussed above, and may include, among other things, determining a time-weighted average (TWA) for the fetal tissue oxygen saturation level and / or simultaneously displaying the fetal tissue oxygen saturation level with the fetal heart rate and / or the TWA of the fetal heart rate, as discussed herein.

[0192] Sometimes the processing and analysis of steps 1915, 1930, 1935, 1945, and / or 1955 may be performed using information regarding, for example, the number of photons detected by a particular detector that detected a particular photon or group of photons, the location or position of the detector providing the particular detected electronic signal, the intensity of light (or number of photons) detected by a particular detector, the intensity of light (or number of photons) of a particular wavelength or range of wavelengths detected by a particular detector, the degree of light scattering, the angle of incident light, the angle of exiting light, the path length of the photons, the time of flight of the photons, etc. Further details regarding how the detected electronic signals are processed and analyzed are provided below.

[0193] The DOT imaging of processes 1800 and 1900 may be performed using, for example, a time-domain (TD) system, a frequency-domain (FD) system, and / or a steady-state domain (SSD) system. When a TD system is used, short (e.g., 10 ps-50 ps) light pulses, sinusoidally modulated at frequencies between, for example, 100 MHz and 1000 MHz, may be projected into the abdomen of a pregnant mammal at a repetition rate of, for example, 1 MHz-50 MHz. These pulses will cause photon density waves to appear within the tissue being imaged. From there, the amplitude difference and phase shift between the incident and detected light may be determined as a function of time. The emitted photons (e.g., backscattered or transmitted) are then collected by an optical fiber and guided to a detector (e.g., a photomultiplier tube) such as detector 160, or may be detected directly by a detector such as detector 160, which in some embodiments is a microchannel plate photomultiplier tube (MCP-PMT). The MCP-PMT signal may then be amplified and / or attenuated and input to a Constant Fraction Discriminator (CFD), the output of which is provided to a Time-to-Amplitude Converter (TAC). The output of the TAC is counted as individual events by a Pulse-Height Analyzer (PHA) and accumulated until a peak count (e.g., 100,000 counts, 1,000,000 counts, etc.) is reached. This information can be used to generate a time-response curve that can be used to generate images of the pregnant mammal's abdomen and / or to determine fetal tissue hemoglobin oxygen saturation.

[0194] If the DOT imaging of processes 1800 and / or 1900 is performed using an FD system, a sinusoidally amplitude-modulated light source may be used to project light onto the abdomen of the pregnant mammal. The modulation frequency may be, for example, between 100 MHz and 1000 MHz. Measured parameters of the FD system may include the phase shift (φ) and the demodulation of light transmitted through the tissue compared to the incident light. Demodulation (M) can be understood via Equation 6, reproduced below:

number

[0195] The phase shift (φ) and M may be measured for all frequencies, and in some cases, a Fourier transform may be performed on the collected data to estimate φ and M.

[0196] The TD system may include a light source (e.g., a laser) (e.g., light source 105), an intensity modulator, a light delivery system (e.g., fetal probe 115), a light collection / detection system (e.g., detector 160), and a processor (e.g., computer 150) to perform cross-correlation techniques that can be used to measure phase shifts and modulation.

[0197] If the DOT imaging of processes 1800 and / or 1900 is performed using an SSD system, a light source may continuously emit light, for example, at two different wavelengths (e.g., between 700 nm and 850 nm), to various points on the abdomen of the pregnant mammal, and the intensity of the light exiting the abdomen of the pregnant mammal may be measured via one or more detectors, such as detector 160. The output voltage of the detectors may be measured and then processed to generate an image of the abdomen of the pregnant mammal, which may, for example, show the local intensity of the detected light.

[0198] Sometimes, processing of data acquired by a DOT system involves determining whether the detected electronic signal is absorbed μ a and transport scattering μ' sThis may involve the application of a backprojection algorithm, where the optical properties of the detected photons are fitted to analytical equations based on diffusion theory to yield coefficients for the . Such processing can reveal a map of spatially dependent optical properties within the abdomen of a pregnant mammal. The spatially dependent optical properties indicate differences between tissue types (e.g., skin, muscle, fetus, etc.) through which light passes, which can be used to understand or determine fetal tissue oxygen saturation. Sometimes, these calculations may also take into account the probability that a detected photon passed through a particular location or layer of tissue. These probabilities could be used to assign different properties (e.g., weights) to different regions or layers of the abdominal tissue of a pregnant mammal.

[0199] Additionally or alternatively, processing of the data acquired by the DOT system may involve applying a model-based iterative image reconstruction (MO-BIIR) algorithm to the data. This process involves three stages: the first stage involves the application of μ-based iterative image reconstruction algorithms for different tissue layers, tissue types, tissue locations, fetal locations, etc. a and μ' s and application of a forward model that provides predictions of detected electronic signals and / or measurements based on approximations of system parameters such as (i) the detected electrical signals and / or measurements. In some embodiments, these predicted parameters may be informed by normative or average values ​​for a typical pregnant mammal and may be based on typical values ​​for the position, location, or optical properties of the pregnant mammal's abdomen or fetus. Additionally or alternatively, these predicted parameters may be customized to a particular situation using, for example, ultrasound and / or short range interval signal information indicative of certain pregnant mammal's abdominal characteristics (e.g., uterine thickness, skin thickness, fetal tissue type, fetal tissue thickness, fetal depth, etc.).

[0200] The second step is to compare the predicted data with the received data. This comparison will result in an error function, also called an objective function or norm. The third step is to update the system parameters of the first step (i.e., the forward model) to provide a new set of predicted data. This process may be repeated iteratively, for example, until the error function is at an acceptable value.

[0201] In some cases, the detected electronic signals received in processes 700 and / or 1900 may be the result of two different wavelengths of light projected onto the maternal abdomen. Exemplary values ​​for the first wavelength (λ1) range between 760 nm and 805 nm, and exemplary values ​​for the second wavelength (λ2) range between 808 nm and 830 nm. In many cases, the light at λ1 and λ2 will be monochromatic or within a narrow band of the electromagnetic spectrum. Light at both wavelengths will be incident on the pregnant mammal's abdomen, collected via an optical cable, transmitted to one or more detectors such as detector 160, and / or detected directly by detector 160. The data collected by the detectors may then be processed, for example, via the Beer-Lambert law, to determine the change in absorption coefficient and the change in oxygenated hemoglobin saturation (Δ[HbO]) and the change in deoxygenated hemoglobin saturation (Δ[Hb]) at each detector.

[0202] A reconstruction algorithm is applied to account for the path length differences between the various source and detector positions, resulting in a predicted difference in absorption coefficients at each detector, Δμ aEquations 8a and 8b can then be solved to determine the change in oxygenated hemoglobin saturation (Δ[HbO]) and the change in deoxygenated hemoglobin saturation (Δ[Hb]). These values ​​can then be used to generate two-dimensional or three-dimensional maps of the abdomen of a pregnant mammal showing the local variations in oxygenated hemoglobin saturation (Δ[HbO]) and the local changes in deoxygenated hemoglobin saturation (Δ[Hb]). The changes in oxygenated hemoglobin saturation (Δ[HbO]) and the changes in deoxygenated hemoglobin saturation (Δ[Hb]) may be shown using, for example, grayscale, color coding, and the images may be topographical, cross-sectional, and / or volumetric. This process does not provide an absolute value for fetal hemoglobin oxygen saturation, but does provide a relative value for fetal hemoglobin oxygen saturation that can be used to monitor fetal hemoglobin oxygen saturation over time to determine changes to fetal hemoglobin oxygen saturation that may indicate that the fetus is in a state of distress, such as in the case of a rapidly or slowly declining fetal hemoglobin oxygen saturation level.

[0203] 20 provides a flowchart of a process 2000 for noninvasively determining fetal hemoglobin oxygen saturation using a multi-source frequency domain spectrometer. Process 2000 may be performed, for example, by system 100 or any of its components or any combination of components.

[0204] Initially, multiple fetal signals, such as those generated by processes 400, 500, 600, 700, 1000, 1200, 1300, 1600, 1700, and 1900, are received (step 2005). The received fetal signals may be at two or more wavelengths and correspond to light projected from multiple light sources, such as light source 105, and detected by detectors, such as detector 160. The location of each light source within a probe, such as fetal probe 115, 115A, 115A', 115B, and / or 115C, and / or the distance (r) between each light source and detector may be known. The light used to generate the fetal signals (i.e., the light projected onto the abdomen of the pregnant mammal) may be sinusoidally modulated. Light is emitted from each of the light sources sequentially (i.e., one at a time) and, in some cases, may be regulated by a multiplexer circuit, for example, so that the light from each light source can be detected and analyzed separately. In some cases, each of the light sources may be set to emit light for a time that is a multiple of a desired frequency (e.g., 300 MHz, 400 MHz, or 500 MHz) for a desired number of periods, which may be coordinated by a multiplexer circuit.

[0205] Optionally, in step 2007, the plurality of fetal signals may be preprocessed, for example, to remove noise and / or amplify desired portions of the fetal signals. This preprocessing may be similar to the preprocessing performed in step 407 of process 400 and discussed above in connection with FIG. 4 . Additionally or alternatively, performing steps 1935 and / or 1915 may include synchronizing two or more of the fetal signals, for example, so that they are aligned in the time domain. In some cases, this synchronization may be similar to the correlation and / or synchronization of step 425. In some instances, synchronization of the plurality of fetal signals may be performed using timestamps present in the first and second detected electronic signals. These timestamps may have been generated, for example, by timestamp marking device 185.

[0206] The received and / or preprocessed fetal signal is processed (e.g., fast Fourier transformed) to provide values ​​for the phase lag (φ) between the light source and detector, DC intensity, and AC amplitude (step 2010).

[0207] These values ​​are plotted individually as a function of the distance r from the detector, and the slope of each graph is determined, thereby giving S ac , S dc , and S φ This will result in a value of (step 2015).

[0208] S ac , S dc , and S φ Using the values ​​of , the absorption coefficient μ a and the reduced scattering coefficient μ s is obtained (Step 2020). S ac , S dc , and S φ Using μ s and μ a One way to determine is through infinite geometry calculations using Equation 7, Equation 8, and / or Equation 9 provided below.

number

number

number

number

number

[0209] Determining the scattering coefficient in this manner allows for the determination of fetal hemoglobin oxygen saturation regardless of pathlength. This may be useful when performing transabdominal fetal oximetry, as pathlength varies substantially between pregnant mammals, and thus approximations based on standard pathlengths may not be accurate. Eliminating pathlength from the calculation of fetal hemoglobin oxygen saturation allows for the calculation of fetal hemoglobin oxygen saturation without the need to calibrate to account for pathlength. This removes a significant amount of complexity from these determinations, as well as a potential source of error from these determinations.

[0210] μ s and μ aOnce the solution for is found, the fetal hemoglobin oxygen saturation level may then be found (step 2025), for example, using Equations 12 and 13 below.

number

number

[0211] Once determined, the ratio of the Hb concentration to the HbO concentration is calculated to determine a hemoglobin oxygen saturation level for the fetus, and an indication of this determined fetal hemoglobin oxygen saturation level is then provided to a user via a step facilitating display of the fetal hemoglobin oxygen saturation level on a computer display device, such as display device 155 (step 2030).

[0212] In some embodiments, determining (step 2025) and / or providing an indication (step 2030) of fetal hemoglobin oxygen saturation is similar to performing step 240 and / or step 245 discussed above, and may include, among other things, determining a TWA for the fetal hemoglobin oxygen saturation level and / or simultaneously displaying the fetal hemoglobin oxygen saturation level with the fetal heart rate and / or the TWA of the fetal heart rate.

[0213] FIG. 21 is a flowchart illustrating a process 2100 for processing a received TD-DCS signal to generate a fetal signal. Process 2100 may be performed, for example, by system 100 and / or its components. When a TD system is used, system 100 may be configured to perform DCS by directing one or more light sources 105 to emit short (e.g., 10 ps to 50 ps) light pulses, which may be sinusoidally modulated at frequencies between 100 MHz and 1000 MHz, for example. These light pulses may be projected into the abdomen of a pregnant mammal at a repetition rate of, for example, 1 MHz to 50 MHz. These pulses will cause photon density waves to appear within the tissue being imaged. From there, the amplitude difference and phase shift between the incident and detected light can be determined as a function of time. The emitted photons (e.g., backscattered or transmitted) are then collected by an optical fiber and guided to a detector (e.g., a photomultiplier tube) or detected directly by a detector, such as a microchannel plate photomultiplier tube (MCP-PMT). The MCP-PMT signal may then be amplified and / or attenuated and input to a Constant Fraction Discriminator (CFD), the output of which is provided to a Time-to-Amplitude Converter (TAC). The output of the TAC is counted as individual events by a Pulse-Height Analyzer (PHA) and accumulated until a peak count (e.g., 100,000 counts, 1,000,000 counts, etc.) is reached. This information can be used to generate a time-response curve that can be used to generate an image of the abdomen of a pregnant mammal and / or to determine fetal hemoglobin oxygen saturation.

[0214] In some cases, system 100 includes light source 105, which is a long coherence length (>5 m) laser operating in the NIR to deliver light to tissue, and detector 160 can be a single-photon counting avalanche photodiode (SPAD) detector that outputs an electronic pulse for each photon received. The system can further include a photon correlator (which can be a stand-alone device and / or included in computer 150) that tracks the arrival time of all photons detected by the APD and derives an intensity correlation function from the time separation of all photon pairs (see FIG. 1 ). The correlator can be hardware and / or software configured to perform the computation of the temporal correlation function.

[0215] Initially, TD-DCS signals corresponding to optical signals entering and exiting the abdomen of a pregnant mammal and the fetus contained therein will be received by a computer or processor, such as computer 150 (step 2105). Detected electronic signals may be transmitted directly or indirectly by / from a detector, such as detector 160, to the computer.

[0216] At step 2110, a fetal heart rate signal will be received, for example, from Doppler / ultrasound probe 135. At step 2115, a maternal heart rate signal will be received, for example, from pulse oximetry probe 130, NIRS adult hemoglobin probe 125, and / or a blood pressure sensing device. Optionally, a secondary signal may be received at step 2120. Exemplary secondary signals include, but are not limited to, a respiratory signal for the pregnant mammal, an indication of whether meconium is detected in the amniotic fluid of the pregnant mammal, a signal indicative of uterine tone, a signal indicative of hemoglobin oxygen saturation level of the pregnant mammal, a pulse oximetry signal for the pregnant mammal, and combinations thereof.

[0217] In step 2125, it will be determined whether the fetal heart rate signal, the maternal heart rate signal, and / or the secondary signal should be correlated and / or synchronized. If so, a synchronization and / or correlation process will be performed (step 2130). Sometimes, performing step 2130 may include synchronizing the signals in the time domain and / or correlating one or more scales of measurement from which the signals are recorded. In some cases, this synchronization may be similar to the correlation and / or synchronization of step 425. In some cases, synchronization of multiple fetal signals may be performed using timestamps present in the first and second detected electronic signals. These timestamps may have been generated, for example, by timestamp marking device 185. If the signals do not need to be synchronized or correlated, process 2100 may proceed to step 2135.

[0218] In step 2135, a fetal signal is generated using two or more of the received signals, at least one of which may be the detected electronic signal. In many instances, performing step 2135 involves using a fetal heart rate signal, a maternal heart rate signal, and / or one or more secondary signals to isolate or otherwise extract signal portions, such as portions contributed by the fetus, of the received detected electronic signal. Performing step 2135 may be similar to the isolation of fetal signals described herein in connection with processes 400, 500, 600, 700, 1000, 1200, 1300, 1600, 1700, and 1900. In some embodiments, performing steps 2130 and / or 2135 may include performing one or more procedures, for example, to reduce the signal-to-noise ratio or amplify the signal; such procedures include, but are not limited to, applying a filter, subtracting known noise components, multiplying two signals, normalizing, etc. In some cases, performing step 2135 may include processing the detected electronic signal using a lock-in amplifier to amplify a preferred portion of the signal and / or to reduce noise in the signal. The preferred portion of the signal may in some cases correspond to a known quantity (e.g., wavelength or frequency) of light incident on the abdomen of the pregnant mammal.

[0219] 22 provides a flowchart of a process 2200 for determining an indication of fetal blood flow and / or fetal hemoglobin oxygen saturation using TD-DCS and / or fetal signals. Process 2200 can be performed, for example, by system 100 and / or its components.

[0220] In step 2205, a TD-DCS and / or fetal signal corresponding to light signals incident on and exiting the abdomen of the pregnant mammal and its fetus is received. The fetal signal is a TD-DCS signal and may have been generated through performance of one or more of processes 400, 500, 600, 700, 1000, 1200, 1300, 1600, 1700, 1900, and / or 2100. Sometimes, the TD-DCS signal received in step 2205 may be preprocessed, for example, to remove noise and / or to isolate the portion of the TD-DCS signal corresponding to light incident on the fetus, for example, by removing one or more confounding effects of the pregnant mammal from the TD-DCS signal.

[0221] In step 2210, a time of flight is determined for each counted photon of the TD-DCS / fetal signal. In some embodiments, the time of flight (TOF) may be measured as the difference between the time of emission and the time of detection. In other embodiments, the time of flight may be a relative determination (e.g., a relatively short or long time of flight). In some cases, absolute and / or relative time of flight may be determined through application of a time-gating strategy to the TD-DCS / fetal signal and / or through mathematical analysis of the TD-DCS / fetal signal, e.g., via the DCS autocorrelation function. The time of flight information may be used to differentiate between short and long photon paths through the tissue of the pregnant mammal and / or fetal tissue and used to determine, for example, blood flow indices and / or hemoglobin saturation levels for different depths and / or layers of the pregnant mammal / fetal tissue. The time of flight for the photons may be used.

[0222] In some embodiments, the TD-DCS / fetal signal is achieved via time-correlated single-photon counting (TCSPC), which can be used to time-tag each detected photon with two values: the TOF from the source to the detector to obtain the TPSF, and the absolute arrival time. The absolute arrival time can be used to calculate the temporal autocorrelation function for the DCS. In these embodiments, step 2210 may be performed by analyzing the correlation function over different times or gates of the temporal point-spread function (TPSF), which can allow differentiation between short and long times of flight for multiple photons. This can then be used to assess properties of different depths of tissue (e.g., blood flow velocity, hemoglobin saturation, etc.). In some cases, the TPSF information can also be used to determine the scattering and / or absorption coefficients for different layers of tissue in the abdomen of a pregnant mammal. In some cases, evaluation of properties at different depths and / or layers of tissue may incorporate information obtained using single-space analysis and / or dual-space analysis, as described above in connection with process 1100 of FIG. 11 and process 1200 of FIG. 12.

[0223] In step 2215, it will be determined whether the received TD-DCS / fetal signal should be filtered, for example, using a preferred TOF, a preferred TOF range, and / or TOF information (e.g., fastest TOF or slowest TOF) for the photons contained in the signal. If the received TD-DCS / fetal signal is not to be filtered, process 2200 can proceed to step 2225.

[0224] If the determination of step 2215 is positive, the received TD-DCS / fetal signal will be filtered using one or more TOF-based criteria. In some cases, the TOF-based filtering criteria used in step 2220 may be a minimum TOF threshold and / or a maximum TOF threshold, such that only photons having a TOF within a selected range are considered. In some cases, differentiation between short and long TOF may be facilitated by application of a time-gating strategy to the DCS autocorrelation function.

[0225] Generally, photons with a longer TOF penetrate deeper into the tissue. If the depth of the various layers of maternal tissue is known and / or can be approximated, i.e., via data regarding the anatomy of the pregnant mammal provided by ultrasound and / or MRI images such as image 201 of FIG. 2A and image 202 of FIG. 2B, via approximations of tissue location, density, or other optical properties as provided by the tissue layers of the pregnant mammal discussed above in connection with FIGS. 14A, 14B, 15A, and 15B, via analysis techniques at short distance intervals such as those described above with respect to processes 1600 and 1700, and / or via tissue or tissue layer modeling facilitated, for example, by a diffusion equation, the range of TOFs to be filtered may be set to a TOF corresponding to the depth of the fetus and / or set to exclude photons that have passed only through the tissue of the pregnant mammal. In this manner, the received TD-DCS / fetal signal may be filtered (step 2220), e.g., to remove photons having a TOF indicative of having passed only through a pregnant mammal. The remainder of the TD-DCS / fetal signal then carries information about photons that were incident on the fetus. The remainder of the TD-DCS / fetal signal may also be referred to as the filtered TD-DCS / fetal signal.

[0226] In some cases, the filtering of step 2220 can be based on the understanding that light passing through upper layers of tissue should have a shorter TOF than light passing through deeper layers of tissue. Differences in TOF can also be caused by the movement of red blood cells within the tissue, which can cause flow-dependent variations in the detected intensity (i.e., number of photons). This allows for the separation of photons from the overall TD-DCS and / or fetal signal that have a TOF consistent with having entered the fetus and traveled deep enough into the abdomen of the pregnant mammal to be affected by fetal blood flow.

[0227] At step 2225, it will be determined whether further processing of the TD-DCS / fetal signal and / or the improved TD-DCS / fetal signal is desired and / or necessary. This determination may be based on, for example, the signal-to-noise ratio, fetal signal clarity, and / or fetal signal strength or intensity. If further processing of the filtered TD-DCS / fetal signal and / or the TD-DCS / fetal signal is not desired and / or necessary, process 2200 may proceed to step 2235. Otherwise, at step 2230, the TD-DCS and / or fetal signal will be further processed to generate an improved fetal signal. Processing at step 2230 may include, but is not limited to, filtering, amplification, etc. Examples of the types of further processing on the received signal at step 2230 are provided above in connection with processes 400, 500, 600, 700, 1000, 1200, 1300, 1600, 1700, 1900, 2000, 2100, discussed herein with respect to Figures 4, 5, 6, 7, 10, 12, 13, 16, 17, 19, 20, and 21, respectively.

[0228] The TOF, TD-DCS / fetal signal, and / or improved TD-DCS / fetal signal are then analyzed to determine an indication of fetal blood flow and / or fetal hemoglobin oxygen saturation levels using any suitable method, including, but not limited to, the Beer-Lambert law (step 2235). In step 2240, providing the indication to a user (e.g., a clinician, doctor, nurse, etc.) may be facilitated via display, for example, as a GUI or other indicator on display device 155. In some embodiments, the received TD-DCS / fetal signal may include an indication of the speckle pattern and / or changes in the speckle pattern caused by red blood cells moving through the fetal tissue. Sometimes, execution of process 2200 includes quantifying speckle variability and measuring the temporal intensity autocorrelation curve of a single speckle. The decay of this autocorrelation curve over time can be input into a version of the diffusion equation adapted to process 2200, or a portion thereof, to yield a blood flow index (BFi).

[0229] In some embodiments, determining the fetal hemoglobin oxygen saturation level (i.e., performing steps 440, 1030, 1325, 1635, 1740, 1825, 1930, 1955, and / or 2235) and / or presenting the fetal hemoglobin oxygen saturation level to the user (i.e., performing steps 440, 1035, 1330, 1640, 1745, 1830, 1960, and / or 2240) may involve using a running average of fetal blood flow and / or fetal hemoglobin oxygen saturation level, and / or a running average of fetal blood flow and / or fetal hemoglobin oxygen saturation level. The method may include calculating a time-weighted average (TWA) of fetal blood flow and / or fetal hemoglobin oxygen saturation levels over one or more time periods (e.g., 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes, etc.), so that the clinician can observe the average values ​​of fetal blood flow and / or fetal hemoglobin oxygen saturation and determine how they may have changed over time and / or how long the fetus had a particular blood flow and / or hemoglobin oxygen saturation. In this manner, the clinician may be able to determine whether the fetus is at risk for significant metabolic acidosis. The TWA may be calculated via Equation 16.

number

[0230] One or more indicators of metabolic acidosis (e.g., mild, moderate, severe, etc.) and / or inflection point(s) may be provided to the clinician along with the fetal blood flow and / or hemoglobin oxygen saturation and / or average fetal blood flow and / or hemoglobin oxygen saturation levels. These indicators / inflection points may be based on information gathered, for example, during previously conducted fetal metabolism experiments and / or clinical studies. In some embodiments, the indicator(s) / inflection point(s) may be provided to the clinician, for example, via a graph of the fetal blood flow / hemoglobin oxygen saturation level and / or average fetal blood flow / hemoglobin oxygen saturation level showing one or more indicators or inflection points on the graph, or via a change in the manner (e.g., color, font, etc.) in which the fetal blood flow / hemoglobin oxygen saturation level and / or average fetal blood flow / hemoglobin oxygen saturation level are displayed to the clinician. Additionally or alternatively, an alarm or other indication may be provided to the clinician if fetal blood flow and / or hemoglobin oxygen saturation levels are determined to be below a critical threshold, or below a critical TWA for a critical duration, which may represent an inflection point for metabolic acidosis and / or indicate that significant metabolic acidosis is occurring.

[0231] Additionally or alternatively, performing steps 2235 and / or 2240 may include simultaneously providing the time-weighted average of the fetal heart rate and the fetal hemoglobin oxygen saturation level, for example, by plotting both values ​​on one or more graphs so that they are visually displayed simultaneously. Additionally or alternatively, the TWA of the fetal blood flow and / or hemoglobin oxygen saturation level may be combined with the TWA of the fetal heart rate, for example, by simultaneously providing them for display via a graph or table.

[0232] The embodiments of the present invention are, for example, as follows. [Embodiment 1] receiving, by a processor, a plurality of detected electronic signals from a detector communicatively coupled to the processor, the plurality of detected electronic signals corresponding to light emitted from an abdomen of a pregnant mammal and a fetus contained therein, the plurality of detected electronic signals being detected by the detector and converted into the detected electronic signals, the emitted light being a portion of light projected onto the abdomen of the pregnant mammal and a fetus contained therein by a light source; receiving, by the processor, an indication of the depth of the fetus within the abdomen of the pregnant mammal; isolating, by the processor, a portion of the detected electronic signal corresponding to light incident on the fetus in response to an indication of the fetus's depth; determining, by the processor, a fetal tissue oxygen saturation level using the isolated portion of the detected electronic signal corresponding to light incident on the fetus; facilitating, by the processor, providing the fetal tissue oxygen saturation level to a user; A method of providing [Embodiment 2] generating, by the processor, an image of the fetus or a portion thereof using the portion of the detected electronic signal corresponding to light incident on the fetus; 2. The method of claim 1, further comprising: [Embodiment 3] 3. The method of embodiment 2, wherein the image shows regional variations in fetal tissue oxygen saturation levels. [Embodiment 4] determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, a secondary signal; analyzing, by the processor, the received plurality of detected electronic signals using the secondary signal to isolate the processed portion of the received plurality of detected electronic signals corresponding to light incident on the fetus; 2. The method of embodiment 1, further comprising: [Embodiment 5] determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, a heart rate signal for said pregnant mammal; analyzing, by the processor, the received plurality of detected electronic signals using the heart rate signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus; 2. The method of embodiment 1, further comprising: [Embodiment 6] determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, a respiratory signal for said pregnant mammal; analyzing, by the processor, the received plurality of detected electronic signals using the respiratory signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus; 2. The method of embodiment 1, further comprising: [Embodiment 7] determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by the processor, a heart rate signal for the fetus; analyzing, by the processor, the received plurality of detected electronic signals using the heart rate signal for the fetus to isolate the portions of the plurality of detected electronic signals corresponding to light incident on the fetus; 2. The method of embodiment 1, further comprising: [Embodiment 8] determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, signals at short range intervals corresponding to light incident only on said abdomen of said pregnant mammal; analyzing, by the processor, the received plurality of detected electronic signals using signals at the short range interval to remove portions of the detected electronic signals corresponding to signals at the short range interval; 2. The method of embodiment 1, further comprising: [Embodiment 9] 2. The method of claim 1, wherein the depth of the fetus is received from at least one of an ultrasound device, a Doppler device, and an image of the abdomen of the pregnant mammal. [Embodiment 10] 2. The method of claim 1, wherein the plurality of detected electronic signals are received from a plurality of detectors. [Embodiment 11] 2. The method of claim 1, wherein the received detected electronic signals are synchronized in the time domain. [Embodiment 12] receiving, by a processor, a plurality of detected electronic signals from a detector communicatively coupled to the processor, the plurality of detected electronic signals corresponding to light emitted from an abdomen of a pregnant mammal and a fetus contained therein, the plurality of detected electronic signals being detected by the detector and converted into the detected electronic signals, the emitted light being a portion of light projected onto the abdomen of the pregnant mammal and a fetus contained therein by a light source; receiving, by said processor, signals at short range intervals corresponding to light incident only on said abdomen of said pregnant mammal; analyzing the plurality of detected electronic signals using signals at the short distance interval to isolate portions of the detected electronic signals corresponding to light incident on the fetus; determining, by the processor, a fetal tissue oxygen saturation level using the isolated portion of the detected electronic signal corresponding to light incident on the fetus; facilitating, by the processor, providing the fetal tissue oxygen saturation level to a user; A method of providing [Embodiment 13] generating, by the processor, an image of the fetus or a portion thereof using the portion of the detected electronic signal corresponding to light incident on the fetus; 13. The method of claim 12, further comprising: [Embodiment 14] 14. The method of claim 13, wherein the image shows regional variations in fetal tissue oxygen saturation levels. [Embodiment 15] determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, a secondary signal; analyzing, by the processor, the received plurality of detected electronic signals using the secondary signal to isolate the processed portion of the received plurality of detected electronic signals corresponding to light incident on the fetus; 13. The method of embodiment 12, further comprising: [Embodiment 16] determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, a heart rate signal for said pregnant mammal; analyzing, by the processor, the received plurality of detected electronic signals using the heart rate signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus; 13. The method of embodiment 12, further comprising: [Embodiment 17] determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, a respiratory signal for said pregnant mammal; analyzing, by the processor, the received plurality of detected electronic signals using the respiratory signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus; 13. The method of embodiment 12, further comprising: [Embodiment 18] determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by the processor, a heart rate signal for the fetus; analyzing, by the processor, the received plurality of detected electronic signals using the heart rate signal for the fetus to isolate the portions of the plurality of detected electronic signals corresponding to light incident on the fetus; 13. The method of embodiment 12, further comprising: [Embodiment 19] 13. The method of claim 12, wherein the depth of the fetus is received from at least one of an ultrasound device, a Doppler device, and an image of the abdomen of the pregnant mammal. [Embodiment 20] 13. The method of claim 12, wherein the plurality of detected electronic signals are received from a plurality of detectors. [Embodiment 21] 13. The method of claim 12, wherein the received detected electronic signals are synchronized in the time domain. [Embodiment 22] a detector configured to receive a plurality of optical signals, convert the plurality of optical signals into a plurality of individual detected electronic signals, and communicate the plurality of detected electronic signals to a processor, the plurality of optical signals corresponding to light emitted from an abdomen of a pregnant mammal and a fetus contained therein, the emitted light being a portion of light projected onto the abdomen of the pregnant mammal and a fetus contained therein by a light source; a processor communicatively coupled to the detector and a memory; The memory, when executed by the processor, causes the processor to: receiving an indication of the depth of the fetus within the abdomen of the pregnant mammal; determining a portion of the detected electronic signal corresponding to light incident on the fetus in response to the indication of the depth of the fetus; determining a fetal tissue oxygen saturation level using the portion of the detected electronic signal corresponding to light incident on the fetus; and the memory having stored thereon a set of instructions directed to facilitate providing the fetal tissue oxygen saturation level to a user; A system that includes: [Embodiment 23] The set of instructions further instructs the processor to: 23. The system of claim 22, wherein the portion of the detected electronic signal corresponding to light incident on the fetus is used to generate an image of the fetus or a portion thereof. [Embodiment 24] 24. The method of embodiment 23, wherein the image shows regional variations in fetal tissue oxygen saturation levels. [Embodiment 25] The set of instructions further directs the processor to determine the portion of the detected electronic signal corresponding to light incident on the fetus, causing the processor to: to receive the secondary signal; and The system of embodiment 22, further comprising analyzing the received plurality of detected electronic signals using the secondary signal to isolate the analyzed portion of the received plurality of detected electronic signals that corresponds to light incident on the fetus. [Embodiment 26] The set of instructions further directs the processor to determine the portion of the detected electronic signal corresponding to light incident on the fetus, causing the processor to: receiving a heart rate signal for said pregnant mammal; and 23. The system of claim 22, further comprising analyzing the received plurality of detected electronic signals using the heart rate signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus. [Embodiment 27] The set of instructions further directs the processor to determine the portion of the detected electronic signal corresponding to light incident on the fetus, causing the processor to: receiving a respiratory signal for said pregnant mammal; and 23. The system of claim 22, further comprising analyzing the received plurality of detected electronic signals using the respiratory signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus. [Embodiment 28] The set of instructions further directs the processor to determine the portion of the detected electronic signal corresponding to light incident on the fetus, by: receiving a heart rate signal for the fetus; and 23. The system of claim 22, further comprising analyzing the received plurality of detected electronic signals using the heart rate signal for the fetus to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus. [Embodiment 29] The set of instructions further directs the processor to determine the portion of the detected electronic signal corresponding to light incident on the fetus, by: receiving signals at short range intervals corresponding to light incident only on the abdomen of the pregnant mammal; and The system of embodiment 22, further comprising analyzing the received plurality of detected electronic signals using signals at the short distance intervals to remove portions of the detected electronic signals corresponding to signals at the short distance intervals. [Embodiment 30] The system of embodiment 22, wherein the depth of the fetus is received from at least one of an ultrasound device, a Doppler device, and an image of the abdomen of the pregnant mammal. [Embodiment 31] 23. The system of claim 22, wherein the plurality of detected electronic signals are received from a plurality of detectors. [Embodiment 32] 23. The system of claim 22, wherein the received detected electronic signals are synchronized in the time domain. The systems, methods, devices, and apparatus described herein can be used to assess fetal tissue and / or hemoglobin oxygenation during pregnancy for many different indications, including, but not limited to, monitoring fetal health during labor and delivery, monitoring fetal health before the onset of labor, monitoring fetal health during intrauterine fetal procedures, and / or monitoring fetal health during medical procedures (e.g., surgery, medication, etc.) in pregnant mammals. [Explanation of symbols]

[0233] 100 System for detecting and / or determining fetal hemoglobin oxygen saturation 105, 105A, 105B light source 111 Housing 115, 115A, 115', 115B, 115C fetal probes 120 Electrical isolator 121 Power supply 125 NIRS Adult Hemoglobin Probe 130 Pulse Oximetry Probe 131 communication port 135 Doppler and / or ultrasound probes 140 Uterine contraction measurement device 141 Power Port 145 Receiver 150 Computers 151 processors 155 Display Devices 160, 160A-160V detector 170 databases 175 Electrocardiogram (ECG) Machine 180 Ventilation / Respiration Signal Source 185 Time stamping device 201, 202 Diagram of layers of maternal tissue 205A, 205B Subcutaneous fat layer 210A, 210B abdominal muscle (skeletal muscle) layer 215A, 215B Intraperitoneal fat layer 220A, 220B Uterine wall (smooth muscle) layer 225A amniotic fluid layer 230A, 230B Fetus 305 Abdomen of pregnant mammal 310 Fetus 315 First Light Signal 320 Second Optical Signal 320A First portion of the second optical signal 320B second portion of the second optical signal 330 Maternal tissue 340 Uterus 900 processor-based systems 902 Bus 904 processor 906 Main Memory 908 Read-Only Memory (ROM) 910 Storage Devices 912 Display 914 Input Devices 916 Cursor Control Device 918 Communication Interface 1405 Maternal tissue 1415 Maternal skin layer 1420 Maternal subcutaneous fat layer 1425 Maternal abdominal muscle (skeletal muscle) layer 1430 Maternal intraperitoneal fat layer 1435 Uterine wall (smooth muscle) layer 1440 amniotic fluid layer 1450 Computing Devices 1510 Small Detector 2300 Example images 2310 scale

Claims

1. receiving, by a processor, a plurality of detected electronic signals from a detector communicatively coupled to the processor, the plurality of detected electronic signals corresponding to light emitted from an abdomen of a pregnant mammal and a fetus contained therein, the plurality of detected electronic signals being detected by the detector and converted into the detected electronic signals, the emitted light being a portion of light projected onto the abdomen of the pregnant mammal and a fetus contained therein by a light source; receiving, by said processor, signals at short range intervals corresponding to light incident only on said abdomen of said pregnant mammal; analyzing the plurality of detected electronic signals using signals at the short distance interval to isolate portions of the detected electronic signals corresponding to light incident on the fetus; determining, by the processor, a fetal tissue oxygen saturation level using the isolated portion of the detected electronic signal corresponding to light incident on the fetus; providing, by the processor, the fetal tissue oxygen saturation level on a display device; A method comprising: determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, a respiratory signal for said pregnant mammal; analyzing, by the processor, the received plurality of detected electronic signals using the respiratory signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus; The method further comprises:

2. generating, by the processor, an image of the fetus or a portion thereof using the portion of the detected electronic signal corresponding to light incident on the fetus; The method of claim 1 further comprising:

3. The method of claim 2 , wherein the image shows local variations in fetal tissue oxygen saturation levels.

4. determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, a secondary signal; analyzing, by the processor, the received plurality of detected electronic signals using the secondary signal to isolate the processed portion of the received plurality of detected electronic signals corresponding to light incident on the fetus; The method of claim 1 further comprising:

5. determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by said processor, a heart rate signal for said pregnant mammal; analyzing, by the processor, the received plurality of detected electronic signals using the heart rate signal for the pregnant mammal to isolate the portion of the plurality of detected electronic signals corresponding to light incident on the fetus; The method of claim 1 further comprising:

6. determining the portion of the detected electronic signal corresponding to light incident on the fetus, receiving, by the processor, a heart rate signal for the fetus; analyzing, by the processor, the received plurality of detected electronic signals using the heart rate signal for the fetus to isolate the portions of the plurality of detected electronic signals corresponding to light incident on the fetus; The method of claim 1 further comprising:

7. The method of claim 1, wherein the depth of the fetus within the abdomen of the pregnant mammal is received from at least one of an ultrasound device, a Doppler device, and an MRI image of the abdomen of the pregnant mammal; 10. The method of claim 1, further comprising isolating the portion of the plurality of detected electronic signals corresponding to light incident on the fetus according to a depth of the fetus.

8. The method of claim 1 , wherein the plurality of detected electronic signals are received from a plurality of detectors.

9. The method of claim 1 , wherein the received detected electronic signals are synchronized in the time domain.

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