Near-infrared spectroscopic sensor

Abstract

A system for performing near-infrared spectroscopy (NIRS) to monitor tissue oxygenation and / or hemodynamics includes a sensor coupled to a controller and / or processing unit, the sensor including a light source operable to emit light at a variety of different wavelengths and a detector operable to collect corresponding backscattered light.

Description

[Technical field]

[0001] SYSTEMS AND METHODS FOR PERFORMING NEAR-INFRARED SPECTROSCOPY (NIRS) FIELD OF THEINVENTION The present invention has exemplary applications in medical monitoring, for example in optical monitoring of spinal oxygenation and hemodynamics. [Background technology]

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Application No. 62 / 897182, filed Sep. 6, 2019, and entitled "METHOD AND APPARATUS FOR NEAR-INFRARED SPECTROSCOPY," which is incorporated herein by reference for all purposes. For U.S. purposes, this application claims the benefit under 35 U.S.C. § 119 of U.S. Application No. 62 / 897182, filed Sep. 6, 2019, and entitled "METHOD AND APPARATUS FOR NEAR-INFRARED SPECTROSCOPY."

[0003] Near-infrared spectroscopy (NIRS) is an optical technique that uses near-infrared light, which has wavelengths ranging from about 600 nm to about 1000 nm. NIRS involves directing light with wavelengths in or around the near-infrared region at a material and detecting the resulting scattered light.

[0004] NIRS has a wide range of medical applications. It provides a non-invasive technique for monitoring tissue oxygenation. NIRS can be used to measure local changes in tissue concentrations of oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), and total hemoglobin (THb).

[0005] One problem with conventional NIRS systems is that multiple light sources and / or multiple detectors may be required to provide an accurate NIRS measurement, and some NIRS sensors are too large or complex for some applications.

[0006] A related problem is that conventional NIRS systems are not compatible for use in some parts of the body.

[0007] Another problem is that some existing NIRS systems are not optically efficient: they direct light to the tissue through a lossy optical path and / or collect backscattered light. Summary of the Invention [Problem to be solved by the invention]

[0008] There remains a need for a compact system that provides accurate NIRS measurements. There remains a need for a system that is well adapted to measure oxygenation and hemodynamics in specific regions of the body. There is a particular need for such a system that is suitable for NIRS monitoring of spinal cord tissue in a clinical setting. [Means for solving the problem]

[0009] The present invention has many aspects. These include: Method and system for performing near-infrared spectroscopy Methods and systems for monitoring spinal cord oxygenation and / or hemodynamics Including, but not limited to:

[0010] One aspect of the invention described herein provides a near infrared spectroscopy (NIRS) sensor. The NIRS sensor can include a body having a dorsal side, a ventral side, and a proximal end and a distal end. The body can support a light source and a light detector in a spaced apart relationship. The light source can be operable to emit light from the ventral side of the body. The light detector can be operable to detect light incident on the ventral side of the body and generate an output signal. The sensor can also include a flexible flap extending laterally from the body along opposing first and second sides of the body.

[0011] In some embodiments, the flap extends between the first side and the second side around the distal end of the body, hi some embodiments, the portion of the flap that extends around the distal end of the body follows an arc.

[0012] In some embodiments, the flap has a thickness that is less than the thickness of the body, hi some embodiments, the flap has a thickness in the range of 0.2 mm to 0.4 mm.

[0013] In some embodiments, the flap is made from a silicone rubber material.

[0014] In some embodiments, the flap of material extends continuously across the dorsal side of the body, enclosing the light source and the light detector.

[0015] In some embodiments, the flap comprises a flexible mesh.

[0016] In some embodiments, the flap is curved such that the ventral surface of the flap is concave, hi some embodiments, the ventral surface of the flap has a cylindrical shape.

[0017] In some embodiments, the flaps are wider at the distal end of the body and taper in width along the body towards the proximal end of the body.

[0018] In some embodiments, the perimeter of the flap is teardrop shaped.

[0019] In some embodiments, the periphery of the flap has a convex portion adjacent the distal end of the body that merges into concave tapered portions on either side of the body.

[0020] In some embodiments, the NIRS sensor includes a line of weakness in the flap that runs along both sides of the body.

[0021] In some embodiments, the flap has shallow grooves formed in the dorsal surface of the flap that run along both sides of the body.

[0022] In some embodiments, a portion of the body between the light source and the photodetector is opaque to the light emitted by the light source, preventing direct transmission of light from the light source to the photodetector.

[0023] In some embodiments, the light source is operative to emit light having a wavelength in the range of 600 nm to 1000 nm.

[0024] In some embodiments, the light source comprises multiple light emitters.

[0025] In some embodiments, multiple light emitters are provided in a single package.

[0026] In some embodiments, the package has a diameter of 2 mm or less.

[0027] In some embodiments, the multiple light emitters are spaced apart from one another by a distance of 2 mm or less.

[0028] In some embodiments, each of the multiple light emitters emits a different wavelength of the multiple wavelengths of light.

[0029] In some embodiments, the multiple wavelengths of light are distributed about an isosbestic point.

[0030] In some embodiments, the isosbestic point is at a wavelength of 810 nm.

[0031] In some embodiments, the multiple wavelengths include one or more wavelengths above the isosbestic point and one or more wavelengths below the isosbestic point.

[0032] In some embodiments, the plurality of wavelengths includes isosbestic wavelengths.

[0033] In some embodiments, the plurality of wavelengths includes at least five wavelengths.

[0034] In some embodiments, the plurality of wavelengths comprises two or more wavelengths selected from 660±10 nm, 730±10 nm, 810±10 nm, 850±10 nm, and 940±10 nm.

[0035] In some embodiments, the multiple wavelengths include wavelengths of approximately 660±10 nm, 730±10 nm, 810±10 nm, 850±10 nm, and 940±10 nm.

[0036] In some embodiments, the light source is spaced from the light detector by a distance in the range of 5 mm to 20 mm.

[0037] In some embodiments, the light detector is a first light detector and the NIRS sensor includes a second light detector spaced apart from the light source, the second light detector operable to detect light incident on the ventral surface of the body.

[0038] In some embodiments, the first photodetector is spaced a first distance from the light source and the second photodetector is spaced a second distance from the light source that is different from the first distance.

[0039] In some embodiments, the second distance is in the range of 1.5 to 2 times the first distance.

[0040] In some embodiments, the rear side of the body defines a plurality of recesses, hi some embodiments, the recesses comprise a row of shallow depressions.

[0041] In some embodiments, the NIRS sensor includes a cable connected to a proximal end of the body, hi some embodiments, the cable includes a first conductor connected to drive the light source and a second conductor connected to carry an output signal from the light detector.

[0042] In some embodiments, the cable includes a sheath that surrounds the first and second conductors. The first conductor can run within a first conductive shield within the sheath. The second conductor can run within a second conductive shield within the sheath.

[0043] In some embodiments, the first conductor includes a plurality of conductors, each connected to carry electrical current to a corresponding one of the plurality of light emitters of the light source.

[0044] In some embodiments, the NIRS sensor includes a transformer amplifier within the body connected to convert the current signal output by the photodetector into a voltage signal.

[0045] In some embodiments, the light source, photodetector and transformer amplifier are all mounted on a printed circuit board embedded in the body.

[0046] In some embodiments, the circuit board is a flexible circuit board.

[0047] In some embodiments, the material of the flap encapsulates a transformer amplifier.

[0048] In some embodiments, the transformer amplifier is between the light source and the photodetector.

[0049] In some embodiments, the transformer amplifier is a high sensitivity transformer amplifier.In some embodiments, the transformer amplifier is a high speed transformer amplifier.

[0050] In some embodiments, the body comprises a molded biocompatible silicone rubber material.

[0051] In some embodiments, the NIRS sensors described herein are combined with a NIRS controller, which can include electronic circuitry connected to control the light source to emit different wavelengths of light at different times.

[0052] In some embodiments, the NIRS controller is configured to control multiple light emitters of the light source to be illuminated in a time-multiplexed pattern such that the light source emits light at one wavelength at a time.

[0053] In some embodiments, the NIRS controller is configured to control the light source to sequentially emit light at each of five different wavelengths, λ1 through λ5, and to sample the output signal of the photodetector in coordination with operation of the light source to obtain a series of light intensity measurements, each of the light intensity measurements corresponding to one of the wavelengths.

[0054] In some embodiments, the NIRS controller is configured to continuously sample the output signal of the photodetector and identify portions of the sampled output signal that correspond to different wavelengths emitted by the light source.

[0055] In some embodiments, the NIRS controller is configured to generate a data frame divided into a number of time slots corresponding to a number of light emitters of the light source and to control one of the light emitters to emit light in a corresponding one of the time slots, hi some embodiments, the data frame includes at least one time slot during which all of the light emitters of the light source are turned off.

[0056] In some embodiments, the NIRS controller is configured to drive each of the multiple light emitters of the light source with a corresponding programmable drive waveform.

[0057] In some embodiments, the NIRS controller is configured to drive multiple light emitters of the light source with corresponding drive signals, in some embodiments, the corresponding drive signals for different ones of the light emitters differ in one or more of waveform, duty cycle, amplitude, and frequency.

[0058] In some embodiments, the NIRS controller includes a data store that stores data representing waveforms for driving each of the multiple light emitters of the light source.

[0059] In some embodiments, the NIRS sensor described herein processes the output signal of the photodetector according to an algorithm to: Changes in oxygenation (O2Hb) chromophore concentration, -Changes in deoxygenated (HHb) chromophore concentration, Total hemoglobin (THb), Hemoglobin difference (Hbdiff), Tissue Oxygenation Index (TOI), and ·Changes in the redox state of cytochrome c oxidase (CCO) and a processing unit configured to calculate one or more NIRS parameters selected from the group consisting of:

[0060] In some embodiments, the algorithm includes a modified Beer-Lambert law.

[0061] In some embodiments, the processing unit includes a trained artificial neural network.

[0062] Another aspect of the invention described herein provides a method for monitoring one or more properties of tissue by near-infrared spectroscopy (NIRS). The method can include controlling a light source to sequentially illuminate the tissue with a plurality of different wavelengths of light and detecting with a photodetector a portion of the light backscattered from the tissue for each of the wavelengths. The method can also include processing an output signal of the photodetector to generate a measurement of one or more NIRS parameters.

[0063] In some embodiments, the multiple wavelengths of light are distributed about an isosbestic point.

[0064] In some embodiments, the isosbestic point is at a wavelength of 810 nm.

[0065] In some embodiments, the multiple wavelengths include one or more wavelengths above the isosbestic point and one or more wavelengths below the isosbestic point.

[0066] In some embodiments, the plurality of wavelengths includes isosbestic wavelengths.

[0067] In some embodiments, the plurality of wavelengths includes three or four wavelengths.

[0068] In some embodiments, the plurality of wavelengths includes at least five wavelengths.

[0069] In some embodiments, the multiple wavelengths include wavelengths of approximately 660±10 nm, 730±10 nm, 810±10 nm, 850±10 nm, and 940±10 nm.

[0070] In some embodiments, the plurality of wavelengths comprises two or more wavelengths selected from 660±10 nm, 730±10 nm, 810±10 nm, 850±10 nm, and 940±10 nm.

[0071] In some embodiments, the light source includes a plurality of semiconductor light emitters, and the method includes controlling the light emitters of the light source to emit light in a repeating sequence and sampling an output signal of the photodetector in coordination with operation of the light emitters to obtain a sequence of light intensity measurements, each of which can correspond to one of a plurality of wavelengths.

[0072] In some embodiments, the repeating sequence includes a plurality of time slots, and at least one of the time slots in the repeating sequence is a free time slot in which all of the plurality of light emitters are controlled to be turned off.

[0073] In some embodiments, the method includes measuring a baseline intensity of light detected in an empty time slot.

[0074] In some embodiments, each of the lights corresponds to one of the time slots, and the method includes illuminating each of the lights in the corresponding time slot.

[0075] In some embodiments, the method includes utilizing separately controlled signal gains and / or filtering on the output signals for different ones of the time slots.

[0076] In some embodiments, the method includes continuously sampling the output signal at a sampling rate and processing the sampled output signal to identify light intensity peaks corresponding to detected light at each of the multiple wavelengths.

[0077] In some embodiments, the method includes sampling the output signal at a frequency of at least 100 Hz and down-sampling the sampled signal.

[0078] In some embodiments, the sampling of the output signal is asynchronous with the illumination of the tissue with light of multiple different wavelengths.

[0079] In some embodiments, the method comprises: Comparing the intensity of the light intensity peak with the minimum peak value; determining the distance of a previous one of the light intensity peaks; Identifying the distance to the next light intensity peak among the light intensity peaks testing each of the light intensity peaks for one or more of:

[0080] In some embodiments, the method includes providing a separate drive signal to a light source for each of the multiple wavelengths.

[0081] In some embodiments, each individual drive signal includes a corresponding programmable drive waveform.

[0082] In some embodiments, the corresponding programmable waveform is: ·Waveform, Duty cycle, amplitude, and ·frequency One or more of the following are different:

[0083] In some embodiments, providing the individual drive signals includes retrieving digitized waveform data from a data store that represents a waveform for driving each of the light emitters.

[0084] In some embodiments, the method includes providing the digitized waveform data to a digital-to-analog converter, modulating current sources with the output of the digital-to-analog converter, and connecting the current sources to corresponding light emitters by a network of electronically controlled switches.

[0085] In some embodiments, the method includes setting drive signal levels for a number of different wavelengths such that corresponding levels of the photodetector output signals are all within a desired range.

[0086] In some embodiments, processing the output signal comprises:

number

[0087] In some embodiments, the method includes normalizing the output signal of the photodetector for each of the plurality of wavelengths, hi some embodiments, the normalizing includes utilizing a factor V-V0, where V is a voltage of a drive signal for a light emitter of the light source and V0 is a turn-on voltage of the light emitter.

[0088] In some embodiments, the method includes measuring V0 for each of a plurality of light emitters of the light source.

[0089] In some embodiments, the method includes determining the one or more NIRS parameters by an artificial neural network.

[0090] In some embodiments, the method includes providing the adjusted normalized intensities of the detected light for the multiple wavelengths as input to an artificial neural network.

[0091] In some embodiments, the method further comprises:

number

[0092] In some embodiments, the method includes processing the output signal to identify a contact quality measure and providing an indication of the contact quality measure.

[0093] In some embodiments, the one or more NIRS parameters are: Changes in oxygenation (O2Hb) chromophore concentration, -Changes in deoxygenated (HHb) chromophore concentration, Total hemoglobin (THb), Hemoglobin difference (Hbdiff), Tissue Oxygenation Index (TOI), and ·Changes in the redox state of cytochrome c oxidase (CCO) The NIRS parameters are selected from the group consisting of:

[0094] In some embodiments, the method includes acquiring one or more NIRS parameters for multiple pairs of light sources and light detectors to provide a data set determining the one or more NIRS parameters as a function of depth.

[0095] In some embodiments, each of the plurality of pairs of light source and light detector includes a light source of the plurality of light sources and a corresponding light detector of the plurality of light detectors.

[0096] In some embodiments, the tissue is a human spinal cord.

[0097] In some embodiments, the light source emits light from the ventral surface of the sensor and the light detector receives the light through the ventral surface of the sensor.

[0098] In some embodiments, the method includes placing a ventral surface of the sensor on the dura mater of the spinal cord of the person.

[0099] Further aspects and features of exemplary embodiments of the present invention are illustrated in the accompanying drawings and / or described in the following description.

[0100] It is emphasized that the invention relates to all combinations of the above described features, even if they are recited in different claims. [Brief description of the drawings]

[0101] The accompanying drawings illustrate non-limiting exemplary embodiments of the present invention.

[0102] [Figure 1] FIG. 1 is a schematic diagram of a NIRS monitoring system in accordance with an exemplary embodiment of the present invention.

[0103] [Diagram 2] FIG. 1 is a schematic diagram of a NIRS sensor according to an exemplary embodiment of the present invention. [Figure 2A] 3 is a schematic cross-sectional view of the NIRS sensor of FIG. 2 taken along the plane indicated by line AA shown in FIG. 2. [Figure 2B] 3 is a schematic cross-sectional view of the NIRS sensor of FIG. 2 taken along the plane indicated by line BB shown in FIG. 2. [Figure 2C] FIG. 2 is a schematic diagram illustrating an exemplary light source including multiple light emitters.

[0104] [Figure 2D] FIG. 1 is a cross-sectional view of an exemplary cable that can be used to connect a NIRS sensor described herein to a NIRS controller that includes electronics for driving the NIRS sensor and / or processing signals from the NIRS sensor. [Figure 2E]FIG. 1 is a schematic diagram of an exemplary connector that may be provided to connect a NIRS sensor to a NIRS controller.

[0105] [Diagram 3] FIG. 1 is a schematic diagram of a NIRS controller in accordance with an exemplary embodiment of the present invention. [Figure 3A] FIG. 4 is a block diagram of an example analog module in the NIRS controller shown in FIG. [Figure 3B] FIG. 2 is a schematic diagram of a data frame. [Figure 3C] 4 illustrates an exemplary frame of data sampled from a photodetector.

[0106] [Figure 3D] FIG. 1 is a top view of a NIRS sensor in accordance with an exemplary embodiment of the present technology. [Figure 3E] FIG. 1 is a bottom view of a NIRS sensor in accordance with an exemplary embodiment of the present technology. [Figure 3F] FIG. 1 is a side elevation view of a NIRS sensor in accordance with an exemplary embodiment of the present technology. [Figure 3G] FIG. 1 is a cross-sectional view of a NIRS sensor in accordance with an exemplary embodiment of the present technology; [Figure 3H] FIG. 1 is a longitudinal cross-sectional view of a NIRS sensor in accordance with an exemplary embodiment of the present technology;

[0107] [Figure 4] FIG. 1 is a schematic diagram illustrating an example artificial neural network (ANN) architecture that may be used to estimate NIRS parameters based on normalized intensity values ​​detected by a NIRS sensor.

[0108] [Diagram 5] 1 is a flow chart illustrating an exemplary method for monitoring spinal cord oxygenation and hemodynamics using a NIRS monitoring system.

[0109] [Figure 6]6A and 6B show a NIRS sensor utilized to monitor the tissue of a patient's spinal cord. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0110] Throughout the following description, specific details are set forth to provide a more thorough understanding to those skilled in the art. However, well-known elements may not be shown or described in detail to avoid unnecessarily obscuring the disclosure. The following description of examples of technology is not intended to be exhaustive or to limit the system to the precise form of any example embodiment. Therefore, the specification and drawings should be viewed in an illustrative rather than a restrictive sense.

[0111] FIGURE 1 is a schematic diagram of a NIRS monitoring system 10 in accordance with an exemplary embodiment of the present invention. The NIRS monitoring system 10 includes a NIRS sensor 100 that includes a light source 120 and a light detector 140 spaced apart from one another on a flexible support. FIGURE 1 shows light 101 emitted from the light source 120. The NIRS sensor 100 measures the corresponding backscattered light at the light detector 140.

[0112] The NIRS monitoring system 10 can be used for medical applications. The NIRS monitoring system 10 can advantageously monitor changes in hemodynamics and tissue oxygenation in real time. As described below, the system 10 can include adaptabilities that make the system 10 particularly well suited for monitoring tissue of the spinal cord. Use of the system 10 can be particularly beneficial for patients suffering from spinal cord injury (SCI), as maintaining adequate oxygenation of spinal cord tissue is critical to promoting recovery from SCI. The system 10 can provide real-time measurements of tissue oxygenation and / or hemodynamics in the spinal cord of patients suffering from SCI.

[0113] Signals are transmitted between the NIRS sensor 100 and the control system 400 by the cable 200. The cable 200 can carry signals from the control system 400 to the NIRS sensor 100 that control the light 101 emitted by the light source 120. The cable 200 can carry signals from the NIRS sensor 100 to the control system 400 that are indicative of the intensity of the backscattered light detected by the light detector 140.

[0114] In the illustrated embodiment, signals are conveyed between the NIRS sensor 100 and the control system 400 in the form of electrical signals in conductors in the cable 200. The NIRS controller 400 can optionally send signals received from the NIRS sensor 100 to a processing unit 800 for further processing. The NIRS controller 400 can optionally receive instructions from the processing unit 800.

[0115] The cable 200 may include a jacket, catheter or tube sheath made of a suitably flexible medical grade material. The conductors may extend along a lumen within the sheath. The sheath material is preferably electrically insulating.

[0116] In some embodiments, the cable 200 includes a multi-branch shielded twisted pair cable. For example, the cable 200 can include one or more inner twisted signal wires surrounded by a first plurality of conductive wires forming an inner shield that electrically isolates the inner twisted signal wires. The shielded inner twisted signal wires can be twisted together with an additional one or more outer twisted signal wires and covered by a second plurality of outer conductive wires forming an outer shield that electrically isolates the outer twisted signal wires (including the shielded inner twisted signal wires). This structure helps reduce electrical noise and artifacts.

[0117] In an exemplary embodiment, 32 AWG enameled copper wire is used to carry the detector 140 signal and drive the light source 120. Two strands carrying the signal from the detector 140 are arranged in an arrangement of 12 wires (38 AWG) forming the "inner shield". Another five wires (32 AWG) for powering the light source 120 are twisted together with the shielded photodetector wire. The resulting wire assembly is arranged in an arrangement of eight wires (38 AWG) forming the "outer shield".

[0118] The NIRS sensor 100 can be sealed to the distal end of the cable 200. The exterior surfaces of the NIRS sensor 100 and the cable 200 can be sterilizable. This allows for the use of the NIRS sensor 100 in invasive applications. The cable 200 can be small in diameter (e.g., less than about 2 mm in diameter) and can be flexible and / or pliable.

[0119] In some embodiments, cable 200 has cable structure 200-1 as shown in FIG. 2D. Cable structure 200-1 includes an outer sheath or jacket 201 surrounding first and second conductor bundles 202A and 202B. Sheath 201 may be made of or coated on the outside with a suitable biocompatible material, such as medical grade implantable silicone rubber. Sheath 201 may have a suitably small outer diameter (e.g., a diameter of less than 4 mm, e.g., a diameter in the range of 3 mm to 4 mm).

[0120] Conductor bundle 202A can carry a high power drive signal for driving light source 120. Conductor bundle 202B can carry a lower power signal detected by one or more detectors 140.

[0121] Each of the conductor bundles 202A, 202B includes a conductive shield layer 203 surrounding a plurality of conductive wires 204. In FIG. 2D, each of the conductor bundles 202A, 202B includes six conductive wires 204. The wires 204 can be highly conductive wires, such as copper, silver, or silver-coated copper. Each of the wires 204 is insulated. For example, the wires 204 can be covered with an enamel insulating layer. In some embodiments, the wires 204 include polyurethane enameled wire. In some embodiments, the wires 204 are reinforced with nylon, silk, steel, and / or fiberglass threads.

[0122] The shielding layer 203 may be driven by a shielding driver circuit. The shielding layer 203 may reduce interference from external sources, such as power line noise or other electromagnetic noise.

[0123] Providing separate conductor bundles for driving the light source 120 and carrying the signals from the detector 140 helps to reduce interference and crosstalk between the light source drive signals and the detection signals.

[0124] Preferably, the cable 200 is strong enough to pull the NIRS sensor 100 to remove it from the patient. For example, in some embodiments, the cable 200 is configured to withstand a pulling force of at least 6 kgf, or at least 8 kgf, or at least 10 kgf, or at least 15 kgf.

[0125] The cable 200 may terminate in a connector that allows the cable 200 to be connected or disconnected from a NIRS controller. Any suitable type of connector may be provided. Figure 2E illustrates an exemplary connector 210 that may be provided in a miniature form factor.

[0126] Connector 210 includes a tubular pin 211 of an electrically insulating medical grade material (e.g., plastic, molded silicone, epoxy, combinations thereof, etc.) having contact rings 212 spaced therealong. Each of rings 212 may be connected to one conductor or shield layer of cable 200 (e.g., as described above). Contact rings 212 may be made, for example, of stainless steel or other durable conductive material.

[0127] The pin 211 may be inserted into a tubular socket. The inner surface of the tubular socket has contact rings spaced therealong. The contact rings 212 and the tubular socket contact rings are positioned such that when the pin 211 is fully inserted into the tubular socket, each of the contact rings 212 is aligned with and in electrical contact with a corresponding one of the contact rings on the tubular socket. The contact rings on the tubular socket may be electrically connected to conductors that connect to a NIRS controller.

[0128] The connector 210 may include any suitable number of pairs of contact rings and tubular sockets with corresponding contact rings 212. For example, the connector 210 may include between 5 and 15 pairs of contact rings.

[0129] In some embodiments, the connector 210 has a maximum OD (outer diameter) of no more than 4 mm. For example, the OD can be 3.5 mm or less. The configuration of the connector 210 and its ability to be made with very small diameters facilitates surgical insertion of the NIRS sensor 100.

[0130] The NIRS sensor 100 may be placed adjacent to tissue of the patient 20 to monitor changes in hemodynamics, oxygenation, and the like. For example, the NIRS sensor 100 may be placed on the spinal cord 25 of the patient 20 to monitor changes in tissue hemodynamics and oxygenation within the spinal cord 25. Because NIRS does not penetrate deeply into most tissues, it is useful to place the NIRS sensor 100 under the skin and other superficial tissue layers to directly monitor oxygenation of the spinal cord tissue. In some embodiments, the NIRS sensor 100 is placed on the membrane 26 (i.e., the dura mater) that encases the spinal cord 25 and surrounds the cerebrospinal fluid. This advantageously eliminates the need to insert a probe through the dura mater 26, thereby reducing the risk of damaging the spinal cord 25 and / or causing a leak of cerebrospinal fluid. The NIRS sensor 100 may conform to the outer contour of the spinal column or other part of the anatomy in which the NIRS sensor 100 is placed.

[0131] The NIRS sensor 100 can illuminate the spinal cord 25 with near-infrared light 101 and provide a measurement of blood delivery to the spinal cord 25 and / or oxygen consumption of the spinal cord 25 based on the amount of near-infrared light 101 that reaches the photodetector 140. NIRS Sensor

[0132] 2 is a schematic diagram of a NIRS sensor 100 according to an exemplary embodiment of the present invention. Figures 2A and 2B are schematic cross-sectional views of the NIRS sensor 100. The NIRS sensor 100 includes a light source 120 operative to emit near-infrared light (e.g., light in a wavelength range of about 600 nm to about 1000 nm) and a light detector 140.

[0133] In some embodiments, the NIRS sensor 100 has dimensions in the range of 14×4×2 mm or less, which advantageously allows the NIRS sensor 100 to be precisely positioned adjacent tissue of the patient 20 (e.g., adjacent the spinal cord 25).

[0134] The light source 120 and the light detector 140 are spaced apart from one another by a suitable inter-optode distance, typically in the range of 8 mm to 20 mm. In the illustrated embodiment, the light source 120 and the light detector 140 are spaced apart from one another by a fixed distance within the NIRS sensor 100. In such an embodiment, the inter-optode distance between the light source 120 and the detector 140 is constant and is independent of the placement and / or orientation of the NIRS sensor 100.

[0135] The light source 120 preferably includes an active light emitter disposed on the NIRS sensor 100. This configuration avoids transmission losses (such as may occur if light were transmitted to the light source 120 through an optical fiber extending along the cable 200, which is another possibility). The light source 120 may include multiple light emitters 121 within a single package. In some embodiments, the light emitters 121 are spaced apart from one another by a distance of 2 mm or less (e.g., 1 mm). For example, the package of the light source 120 may have a diameter of 2 mm or less.

[0136] Each light emitter 121 can emit light at a different wavelength. The light emitters 121 can be selected to emit light at a set of wavelengths in an appropriate wavelength band. The wavelengths emitted by the light emitters typically range from about 650 nm to about 1000 nm. The various wavelengths of light can include wavelengths distributed around an isosbestic point (e.g., 810 nm). The isosbestic point can be selected, for example, as a wavelength at which the light absorption of the target tissue does not change with changes in the relative concentrations of oxygenated and deoxygenated hemoglobin.

[0137] For example, the set of wavelengths provided by the light emitters 121 may include wavelengths above, below, and / or at the isosbestic point. Examples of possible wavelengths of light emitted by the light emitters 121 of the light source 120 include, but are not limited to, 660 nm, 730 nm, 810 nm, 850 nm, and 940 nm. In some embodiments, the light source 120 includes five light emitters 121 that emit light at wavelengths of about 660 nm, 730 nm, 810 nm, 850 nm, and 940 nm, respectively. In some embodiments, the set of wavelengths includes two or more wavelengths above the isosbestic point, two or more wavelengths below the isosbestic point, and at least one wavelength at or near the isosbestic point.

[0138] Providing multiple light emitters in a single package can advantageously minimize variations in optode distances between the various light emitters and the detector 140 .

[0139] The light emitters are configured to emit different wavelengths. The light emitters can be individually controlled. For example, the light source 120 can include separate electrical connections for energizing the light source 120 to emit light at each of the multiple wavelengths. The electrical connections can be connected to separate wires 129 of the wiring 160.

[0140] The light emitters may include, for example, light emitting semiconductor junctions, such as light emitting diodes (LEDs). Each LED may be independently controlled.

[0141] In some embodiments, the NIRS sensor 100 includes a suitable lens (not shown) configured to direct the various wavelengths of light emitted by the light source 120 to be incident on the target tissue at a particular angle (e.g., 90°). Such a lens may be incorporated into the packaging of the light source 120 and / or disposed between the target tissue and the light source 120.

[0142] 2C illustrates an exemplary light source 120 that includes a package 122 that includes light emitters 121-1, 121-2, 121-3, ..., 121-N (individually or collectively, light emitters 121) each configured to emit light at a different wavelength. Light source 120 optionally includes a light homogenizing element 123 that collects light from any of the light emitters 121 and directs the light from light source 120 as light 101. Light source 120 optionally includes a reflector 124 that redirects light that may be emitted backwards by light emitters 121 into beam 101. Light source 120 optionally includes one or more lenses 125 or other optical elements that increase the parallelism of beam 101.

[0143] In some embodiments, light source 120 includes five light emitters (eg, LEDs), each LED emitting light at a different wavelength.

[0144] The detector 140 is disposed on the NIRS sensor 100. The detector 140 is spaced from the light source 120 by a desired inter-optode distance to detect backscattered light. The detector 140 sends a signal corresponding to the detected light through wire 141 to the controller 400. The detector 140 may be sensitive to light in a wavelength range (e.g., 430 nm to 1100 nm) including the wavelength range (e.g., 650 nm to 1000 nm) that includes the light emitted by the light source 120. In some embodiments, the detector 140 has a peak sensitivity in the near infrared region of the electromagnetic spectrum (e.g., the 750 nm to 1000 nm region, e.g., 940 nm).

[0145] In some embodiments, detector 140 includes a semiconductor photodetector, such as a photodiode. For example, detector 140 may include a photodiode biased by an applied voltage such that the magnitude of the photocurrent is indicative of the intensity of light incident on photodetector 140. In some embodiments, detector 140 includes a silicon PIN photodiode (e.g., VBPW34S, Vishay Semiconductors). In some embodiments, detector 140 includes a 10 mm 2 Less than (e.g. 7.5 mm 2 ) area.

[0146] In some embodiments, the NIRS sensor 100 includes a suitable lens or other optical element (not shown) positioned to help the detector 140 collect more backscattered light. Such a lens may be incorporated within the packaging of the light detector 140 and / or positioned between the target tissue and the detector 140.

[0147] Desirably, to the greatest extent possible, all light detected by photodetector 140 is light that is emitted forward from light source 120 and then backscattered from tissue to photodetector 140. NIRS sensor 100 may include mechanisms to reduce detection of ambient light by photodetector 140 and / or to reduce transmission of light from light source 120 to photodetector 140 by paths other than the backscattered paths described above.

[0148] The NIRS sensor 100 may include an optical isolation element 130. The optical isolation element 130 may be disposed between the light source 120 and the light detector 140 to prevent or reduce direct transmission of light from the light source 120 to the light detector 140. The optical isolation element 130 is made of a material that is substantially opaque to light of the wavelengths emitted by the light source 120. For example, the optical isolation element 130 may be made of a suitable black silicone rubber.

[0149] In the illustrated embodiment, the optical isolation element 130 is disposed between the light source 120 and the detector 140. The optical isolation element 130 is opaque to prevent or otherwise minimize light emitted by the light source 120 from directly impinging on the detector 140. In some embodiments, the isolation element 130 is made of opaque biocompatible silicone. In some embodiments, the optical isolation element 130 spans a width equal to the width of the light source 120 and / or the optical detector 140. In some embodiments, the optical isolation element 130 spans a width less than 5 mm.

[0150] In some embodiments, the NIRS sensor 100 includes a shield 145 that extends around the back and / or peripheral sides of the detector 140 to block or attenuate ambient light and / or light emitted by the light source 120 from reaching the shielded sides of the detector 140 directly. The shield 145 may also be made of a conductor that advantageously electrically shields the detector 140 to reduce the effects of electrical interference on the output signal of the detector 140. The shield 145 may be made of a suitable material or materials such as flexible thin aluminum, stainless steel, titanium, etc. The shield 145 may have the form of, for example, a sheet or pan or box attached to the structure of the detector 140.

[0151] In some embodiments, the NIRS sensor 100 includes a light shield 170 that covers the back surface of the light source 120 and / or the detector 140. The light shield 170 is optional but preferably forms a wall that extends around the perimeter of the light detector 140 and / or the light source 120.

[0152] In some embodiments, the light shield 170 is completely opaque to prevent ambient and / or light from the light source 120 from reaching the detector 140 except after the light is scattered back towards the light detector 140. In some embodiments, the material of the light shield 170 includes an additive that increases the opacity of the light shield 170.

[0153] In some embodiments, the light shield 170 absorbs and dissipates heat generated by the operation of the light source 120. This can reduce the operating temperature of the light emitters of the light source 120, which can reduce heating of the surface of the target tissue.

[0154] The NIRS sensor 100 may include a flexible flap 190 that extends laterally away from the area that includes the light source 120 and the detector 140. The flap 190 has the following uses. Place and hold the NIRS sensor 100 at a desired location (eg, a location for measuring tissue oxygenation or other NIRS parameters in the spinal cord or other body part). Blocks ambient light from reaching the light sensor 140. · Light from the light source 120 is blocked from reaching the photodetector 140 via a path internal to the NIRS sensor 100. Isolate the light source 120, light detector 140 and wiring 160 from blood and other fluids · Provides a surface for adhering the NIRS sensor 100 in place using a suitable biocompatible adhesive. The flap 190 is preferably integrated into the NIRS sensor 100 .

[0155] The flap 190 can be formed to extend outwardly as far as desired from the area in which the light source 120 and the light detector 140 are located. The size and shape of the flap 190 can be modified for a particular application. In some embodiments, the flap 190 is oversized so that the outer portion of the flap 190 can be trimmed (e.g., with surgical scissors) to fit the NIRS sensor 100 to a particular location. In some embodiments, the outer edge of the flap 190 can be shaped for a particular application.

[0156] The flap 190 can be very thin, for example, the flap 190 can have a thickness in the range of about 0.2 mm to 0.4 mm (e.g., 0.3 mm) in the portion that extends around the periphery of the NIRS sensor 100. The region of the NIRS sensor 100 that includes the light source 120 and the detector 140 can optionally be relatively thick. When the flap 190 is made of a silicone material as described herein, a thickness of 0.3 mm has been found to provide a good balance between being sufficiently robust and providing good flexibility.

[0157] In some embodiments, the flap 190 comprises a thin layer of flexible biocompatible material, such as a medical grade implantable silicone material. The material of the flap 190 optionally but preferably encapsulates the light detector 140 and the light source 120 such that the outer surface of the NIRS sensor 100 is provided by a continuous surface of the material of the flap 190. In such a case, the material of those portions of the flap 190 in front of the light source 120 and the light detector 140 is transparent or at least semi-transparent at the wavelengths emitted by the light source 120. Thus, the beam 101 is emitted by the light source 120 and can pass through the covering portion of the flap 190 into the adjacent tissue where it is backscattered. A portion of the backscattered light returns through the material of the flap 190 covering the light detector 140 where it is detected.

[0158] The layer of material in front of the light source 120 and the light detector 140 can be very thin (e.g., about 300 μm). In some embodiments, it is a medical grade silicone material (e.g., Nusil MED-6015).

[0159] The optical isolation element 130, shield 145 and / or light blocker 170 may optionally be enclosed and / or provided by the flap 190. In some embodiments, the optical isolation element 130 and / or light blocker 170 may be provided by a material that constitutes a part of the flap 190. For example, these components may be provided by a flexible, biocompatible material that is substantially opaque to light having wavelengths to which the detector 140 is sensitive.

[0160] For example, the flap 190 may include a first layer of opaque flexible biocompatible silicone material extending behind the light source 120 and the light detector 140 and a second layer of transparent or translucent biocompatible silicone material extending in front of the light source 120 and the light detector 140. The first layer may optionally extend around the periphery of the light detector 140 and the light source 120. A portion of the first layer may optionally extend into the area between the light source 120 and the light detector 140 to provide the light isolation element 130. The first layer may optionally encapsulate the shield 145.

[0161] The NIRS sensor 100 may optionally include a flexible mesh 150. The mesh 150 may be disposed behind the light source 120 and the detector 140. The mesh 150 advantageously provides improved mechanical support for the light source 120 and the detector 140. The mesh 150 may be made from a suitable material or materials, such as flexible polyurethane, medical grade nylon mesh, or the like. The mesh 150 may be encapsulated in the material of the flap 190.

[0162] In some embodiments, the shield 145 is deformable and retains the shape that it is formed into. This can be useful to facilitate forming the flap 190 of the NIRS sensor 100 to fit the spinal cord or other part of the body. For example, the shield 145 can include a deformable sheet of aluminum or other bendable material encapsulated within the material of the flap 190.

[0163] In some embodiments, the material providing the light shield 170 encapsulates the backside of the light source 120 and detector 140 , the wires 129 , 141 , the flexible mesh 150 , the shield 145 and a portion of the wiring 160 .

[0164] The flap 190 can include an adhesive outer layer to facilitate placement and fixation of the NIRS sensor 100 onto tissue (e.g., the dura 26). In some embodiments, the anterior surface of the flap 190 includes an outer layer of a biological adhesive (e.g., TISSEEL® Fibrin Sealant). The biological adhesive can be applied around the edges of the flap 190. The biological adhesive can help hold the NIRS sensor 100 in place on the target tissue (e.g., the dura 26). In some embodiments, one or more surfaces of the anterior surface of the flap 190 are prepared or prepared to receive a biocompatible adhesive.

[0165] The light source 120 and the edge of the flap 190 closest to the light source 120 are spaced apart by a suitable distance, typically in the range of 1 mm to 3 mm.

[0166] The configuration of the NIRS sensor 100, in which the detector 140 and light source 120 are encapsulated, for example, by the material that constitutes the flap 190, advantageously resists fluid penetration into the NIRS sensor 100 and electrically isolates the conductors within the NIRS sensor 100 from the patient.

[0167] The wiring 160 may include shielded twisted wires electrically connected to the controller 400. The wiring 160 includes a light source wire 129 and a detector wire 141. The light source 120 receives power from the controller 400 through the wire 129. The power causes the light source 120 to emit light. The wire 129 may include separate wires for controlling the light source 120 to emit different wavelengths of light.

[0168] In some embodiments, the detector wire 141 is twisted and surrounded by a first plurality of conductive wires or a first conductive layer to form an inner shield around the detector wire 141. In some embodiments, the shielded detector wire 141 is further twisted with the source wire 129 and surrounded by a second plurality of conductive wires or a second conductive layer to form an outer shield around the source wire 129 and the shielded detector wire 141. Such a configuration can advantageously keep the wiring 160 more compact to minimize the size of the cable 200.

[0169] The detector wire 141 may include wire having a suitable size, such as 32 AWG. The light source wire 129 may include wire having a suitable size, such as 32 AWG. The shield conductive wire may include wire having a suitable size, such as 38 AWG.

[0170] The detector 140 detects the light and sends a corresponding signal over a detector wire 141 to the controller 400 .

[0171] In some embodiments, the wire 160 is encapsulated in a biocompatible material, such as medical grade implantable silicone or biocompatible polyurethane. In some embodiments, the ends of the wire 160 are encapsulated in the material of the flap 190. The ends of the cable 200 may also be encapsulated within the NIRS sensor 100.

[0172] The NIRS sensor 100 may be manufactured using any suitable technique, such as injection molding, heat curing, etc. For example, the active elements of the NIRS sensor 100 (e.g., the light source 120, the detector 140, the wiring 160) may be disposed in a die and covered with a suitable flowable, curable elastomeric material that is cured to form the optical isolation element 130, the light blocker 170, and / or the flap 190. NIRS Controller

[0173] In use, the NIRS sensor 100 is connected to an electronic system that controls the light source 120 to emit light, monitors the output signal of the detector 140, and processes the output signal of the detector 140 to determine one or more NIRS parameters. It may be advantageous to separate the functions of controlling the NIRS sensor 100 and processing the signal from the detector 140 to generate the NIRS parameters.

[0174] 3 is a schematic diagram of an exemplary NIRS controller 400. The controller 400 is in signal communication with both the NIRS sensor 100 and the processing device 800. In other embodiments of the invention, the functions of the controller 400 and the processing device 800 can be combined or divided in various ways between multiple devices. For example, the controller 400 can collect and store data while not connected to the processing device 800. The stored data can then be uploaded to the processing device 800. In some embodiments, the controller 400 operates independently of the processing device 800.

[0175] The NIRS controller 400 controls the light source 120 to emit light at various wavelengths. In one example mode of operation, the NIRS controller 400 controls the light emitters of the light source 120 to be illuminated in a time-multiplexed pattern such that the light source 120 emits light at one wavelength at a time. For example, if the light source 120 is operable to emit light at five different wavelengths λ1 through λ5, the NIRS controller 400 can control the corresponding light emitters of the light source 120 to emit light in the following order: λ1, λ2, λ3, λ4, λ5, λ1, ... etc. The NIRS controller 400 can be configured to sample the output of the photodetector 140 in coordination with the operation of the light source to obtain a series of light intensity measurements, each corresponding to one of the wavelengths. In some embodiments, the NIRS controller 400 is configured to continuously sample the output of the photodetector 140 and identify portions of the signal that correspond to the different wavelengths emitted by the light source 120.

[0176] For example, the NIRS controller 400 may be configured to generate a data frame divided into a number of time slots corresponding to the number of light emitters 121 of the light source 120. The time slots may have equal duration, but this is not required. Each light emitter may be changed during one or more corresponding time slots. In some embodiments, all of the light emitters of the light source 120 are turned off for at least one of the time slots in the frame. This free time slot may serve as a marker to help the NIRS controller 400 identify the timing of the time slots and / or the sequence of wavelengths emitted by the various light emitters of the light source 120.

[0177] 3B shows an exemplary data frame 411 having time slots 412-1 through 412-5 corresponding to different wavelengths of light emitted by light source 120, and a free time slot 412-6. The free time slot 412-6 can be used to measure the baseline intensity of the detected light.

[0178] From an architectural standpoint, each frame in the example of Figure 3B is divided into six equal time slots. Each LED is illuminated for one time slot with a defined waveform. One time slot is left empty as a synchronization marker that helps identify the wavelength order.

[0179] In some embodiments, the output of the detector 140 is continuously sampled at a desired sampling rate. Peaks corresponding to detected light of distinct wavelengths can be identified by processing the sampled output signal from the light detector 140. For example, sampling can be performed at 100 Hz. The NIRS controller can provide a frame of data representing a full cycle of operation of the light source 120, which in this example can include 480 samples, each representing 10 ms. In some embodiments, the sampled signal is downsampled (e.g., to 10 Hz).

[0180] Each frame may be processed to find peaks that meet some specific criteria (including minimum peak value, distance from previous and next peaks, etc.) Free time slots (e.g., 412-6) may be used to identify which peaks correspond to which light emitters 121. Figure 3C shows an example frame of data sampled from the photodetector 140.

[0181] This scheme does not require that the sampling of the detector 140 output signal be coordinated with the driving of the emitter 121 .

[0182] The brightness of the light emitters in light source 120 may differ for different wavelengths, and the sensitivity of light detector 140 may differ for different wavelengths, and the percentage of light absorbed by tissue may vary with wavelength. To facilitate measurement of the intensity of the backscattered light with reasonable resolution and / or to reduce the effects of ambient light on the measurements, it may be desirable to separately control the signals applied to light source 120 to generate light at each of multiple wavelengths.

[0183] In some embodiments, the light emitters (e.g., LEDs) of light source 120 are driven individually in constant current mode during corresponding time slots. In some embodiments, the light emitters (e.g., LEDs) of light source 120 are driven with corresponding programmable drive waveforms. The drive waveforms for each of the light emitters can be selected to control bandwidth, match hardware and sensor parameters, etc.

[0184] For example, the NIRS controller 400 can be configured to drive each light emitter of the light source 120 with a corresponding selected drive signal. The drive signals for different ones of the light emitters can differ in waveform, duty cycle, amplitude, frequency and / or other characteristics. In some embodiments, the NIRS controller 400 can be configured to drive each light emitter of the light source 120 with a drive signal having an arbitrary waveform (e.g., instead of a square wave or other hardware-dependent waveform).

[0185] The NIRS controller 400 may include a data store that stores data representing a waveform for driving each of the light emitters 121. The data may include a digitized waveform. The NIRS controller 400 may include a digital-to-analog converter having an output connected to modulate a current source. The output of the current source may be connected to drive a corresponding light emitter 121 by a network of electronically controlled switches. At each time slot, the NIRS controller 400 may operate the switch to provide current from the current source to one of the corresponding light emitters 121 and utilize the corresponding waveform data to a DAC so that the corresponding light emitter is driven according to the appropriate stored waveform. In other embodiments, separate current sources may be connected to drive each of the light emitters 121. In such embodiments, a switching network may not be required.

[0186] The drive signal may be set in a calibration step in which the light source 120 is controlled to emit light into a phantom, as described elsewhere herein.

[0187] In the illustrated embodiment, the NIRS controller 400 includes an analog module 420, a digital module 440, and appropriate converters (e.g., an AD converter and / or a DA converter) to facilitate signal communication between the analog module 420 and the digital module 440.

[0188] The analog module 420 can provide power to and / or control the light source 120. In some embodiments, the analog module 420 receives the signal detected by the detector 140. In some embodiments, the analog module 420 performs initial signal conditioning and / or low-level processing on the signal received from the detector 140. For example, the analog module 420 can amplify and / or filter the signal before sampling it with an analog-to-digital converter. In some embodiments, different signal conditioning is performed for different time slots. For example, parameters such as signal gain and filtering can be individually adjustable for different time slots.

[0189] 3A is a block diagram of an example analog module 420 that receives the current signal 105 from the photodetector 140 of the NIRS sensor 100. The analog module 420 includes a TIA or "transamplifier" as known in the art 422 that converts the current signal 105 received from the NIRS sensor 100 to a voltage 106. In some embodiments, the voltage 106 is fed back to the TIA 422 through a baseline correction module 424. The current signal 105 is averaged and then subtracted from the background current to avoid saturation of the TIA 422. The baseline correction module 424 can advantageously reduce the sensitivity of the analog module 420 to changes in the level of ambient light detected by the photodetector 140.

[0190] In some embodiments, the analog module 420 includes a second amplifier stage 426 to further adjust the gain and offset of the preliminary signal conditioning provided by the analog module 420. In some embodiments, the second amplifier stage 426 includes a programmable gain amplifier (PGA).

[0191] In some embodiments, the analog module 420 is implemented as a separate plug-in board, which advantageously allows the analog module 420 to be changed or replaced without changing the remainder of the NIRS controller 400 design.

[0192] The digital module 440 is in signal communication with the NIRS processing unit 800. The digital module 440 operates to transmit and / or receive data.

[0193] In some embodiments, the digital module 440 implements a time division multiplexing scheme for presenting measurements of the intensity of light detected by the detector 140 for each of a plurality of wavelengths to the NIRS processing device 800. For example, frames each containing digital data representing the light intensity detected at the detector 140 for a full sequence of wavelengths may be transmitted sequentially to the NIRS processing device 800. Exemplary NIRS Sensors

[0194] 3D-3H show an exemplary NIRS sensor 500. The sensor 500 includes a body 502 that houses a light source 504 (e.g., a light emitting diode) and one or more photodetectors 506 (e.g., photodetectors 506A and 506B at different distances from the light source 504). In some embodiments, the sensor 500 includes multiple light sources 504 and a single photodetector 506. The light sources 504 can be at various distances from the photodetectors 506.

[0195] A soft, flexible flap 510 extends outwardly from the body 502. The flap 510 can provide one or more of the functions described elsewhere herein.

[0196] The flap 510 may be selectively weakened along a line proximal to the body 502 to facilitate bending of the flap 510 in a dorsal direction. The weakened portion may be provided, for example, by a shallow groove 510A extending along the dorsal aspect of the flap 510 proximal to the body 502. The flap 510 may bend in a dorsal direction as the sensor 500 is withdrawn from the patient. A feature such as the groove 510A facilitates such bending, thereby facilitating removal of the sensor 500.

[0197] In some cases, it may be desirable to withdraw the sensor 500 from the site where it was placed by pulling the sensor 500 in a proximal direction (e.g., by pulling the cable 200). This may avoid disturbing tissue overlying the site. Providing a flap 510 that tends to fold over in a dorsal direction as the sensor 500 is being pulled to withdraw it from the site where it was placed may help to avoid pushing or damaging target tissue (e.g., the patient's spinal cord) during withdrawal of the sensor 500.

[0198] In the illustrated embodiment, the flap 510 is 、 The flap 510 has a "teardrop" shape that is wider toward the distal end 502A of the body 502 and gradually narrows toward the proximal end 502B of the body 502. The teardrop shape of the flap 510 can facilitate removal of the sensor 500 by pulling the sensor 500 in a proximal direction. In the illustrated embodiment, the flap 510 is significantly narrower at the location of the light source 504 than at the location of the light detector 506.

[0199] The flap 510 can be rounded near the distal end 502A of the body 502. For example, FIG. 3D shows an embodiment in which the periphery 511 of the flap 510 has a convex portion 511A near the distal end 502A of the body 502, which joins concave tapered portions 511B on either side of the body 502. The convex portions 511A can be, for example, semicircular or approximately semicircular. The concave portions 511B can taper to join the edges of the body 502 near the proximal end 502B and / or near the longitudinal position of the light source 504.

[0200] In some embodiments (see, e.g., FIG. 3G), the flap 510 is formed to curve toward the longitudinal axis such that the rear surface of the flap 510 is concave. The rear surface of the flap 510 can have a cylindrical shape, for example. This curvature can help place the sensor 500 in a desired location (e.g., on the patient's spinal dura) and maintain the sensor 500 in the desired location.

[0201] As mentioned above, the sensor 500 may be configured to avoid direct transmission of light from the light source 504 to the light detector 506. In the sensor 500, this may be accomplished by forming a majority of the body 502 from a material that is opaque to the light detected by the light detector 506 and / or the light source 504. For example, the body 502 may be formed primarily from a dark colored medical grade silicone rubber material, such as a liquid silicone elastomer (e.g., MED-4800-7 NuSil, USA) pigmented with a medical grade color masterbatch.

[0202] To allow light to exit the light source 504 and be detected by the photodetector 506, a portion 514 of the material of the body 502 overlapping the light source 504 and one or more portions 515 of the material of the body 502 overlapping the photodetector 506 may be made of a material that is translucent to the wavelength of light detected by the photodetector 506 and / or emitted from the light source 504. For example, the body 502 may be overmolded with a translucent or ultra-translucent material in the portions 514 and 515 located over the light source 504 and the photodetector 506. In some embodiments, the material of the portions 514 and 515 is a medical grade implantable silicone material (e.g., MED-4840, NuSil, USA).

[0203] The light source 504, the photodetector 506, and other electronics of the sensor 500 may be mounted on a flexible printed circuit board 520 embedded within the body 502. The sensor 500 may include electronics to process or modify the signal detected by the photodetector 506. For example, the sensor 500 may include a transformer amplifier (current-to-voltage amplifier) ​​that generates a voltage output signal based on the current signal from the photodetector 506. The transformer amplifier may include, for example, a transformer amplifier chip or a chip including a transformer amplifier microcircuit. Generating a voltage output signal in the sensor 500 may improve signal quality, reduce noise pickup, and / or simplify the configuration of the NIRS controller.

[0204] In the illustrated embodiment, the sensor 500 includes a high speed, high sensitivity transformer amplifier chip between the light source 504 and the photodetector 506. The effects of noise can be further reduced by using a low noise LED for the light source 504 and a highly responsivity, low noise photodetector (e.g., a photodiode) for the photodetector 506.

[0205] The dorsal surface of the body 502 includes features for holding the sensor 500 in place at a desired location, e.g., a location where the ventral surface of the body 502 is placed in contact with the patient's spinal cord. In the illustrated embodiment, these features include recesses 512. The recesses 512 can be in the form of, for example, shallow depressions. A retention device can engage one or more of the recesses 512. For example, the sensor 500 is often used to monitor a patient's spinal cord that is held in place by a fixation system. A lateral connector secured to a spinal fixator can be positioned to engage the recesses 512 to prevent the sensor 500 from lifting out of the tissue it is placed to monitor.

[0206] Sensor 500 may include any one or more of the features described above with respect to sensor 100. For example, The flap 510 can have any of the characteristics described above with respect to the flap 190. For example, in some embodiments, the flap 510 has a thickness of about 0.4 mm. · The body 502 and / or the flap 510 may be formed from a suitable biocompatible material, such as a suitable grade of biocompatible silicone. For example, the body 502 may be formed from MED-4840 liquid silicone rubber available from NuSil, USA, or a two-component platinum-catalyzed silicone elastomer, such as DowCorning® QP 1 from Nusil® Polymer Systems Technology Ltd. (Buckinghamshire, UK). The material of the body 502 may be made of one or more materials designed for medical parts intended for human implantation for up to 30 days, for example. The QP1 material is a pumpable thermosetting silicone elastomer, ideal for liquid injection molding or close tolerance parts. The light source 504 can emit light at multiple wavelengths (eg, five wavelengths). The inter-optode distance between the light source 504 and the photodetector 506 can be in the range of 8 mm to 20 mm. In an exemplary embodiment, the inter-optode distance between the light source 504 and the photodetector 506 is 10 mm. In another exemplary embodiment, the inter-optode distance between the light source 504 and the first photodetector 506A is 10 mm, and the inter-optode distance between the light source 504 and the second photodetector 506B is 16 mm. The sensor 500 can be connected to other devices via a cable 200. ·others.

[0207] Some embodiments provide two, three or more pairs of light sources and photodetectors separated by different distances. Such embodiments can include multiple light sources and / or multiple photodetectors. The distance between the various pairs of light sensors and photodetectors can range, for example, from 5 mm to 35 mm. Such a configuration is advantageous because the depth of tissue interrogated by the light source / photodetector pair increases with the distance the light source / photodetector pair is separated. Various pairs of light sources and photodetectors can be used as described herein to obtain any NIRS parameters for various depths within the tissue adjacent to the sensor 500 (e.g., the patient's spinal cord). Providing depth-resolved NIRS parameters can be useful in understanding the progress of healing, the effectiveness of a particular drug therapy, the general condition of the tissue and / or the like. Various pairs of light sources and photodetectors can also be spaced along the sensor 500 to provide spatially resolved NIRS parameters at the same or different depths.

[0208] When the sensor 500 is in operation, the light emitter 504 emits light at the ventral side of the body 502. The light interacts with tissue. A portion of the light is backscattered and detected by the photodetector 506. In an embodiment with two photodetectors 506A, 506B at different distances from the light source 504, the sensor 500 can be used as a two-channel SC-NIRS sensor that can measure optical density at both the superficial and deep layers of the spinal cord. The resulting output can be processed to quantify and monitor tissue hemodynamics and oxygenation in an extended volume of the spinal cord. Furthermore, by processing the data detected by the two photodetectors 506, more accurate measurements can be achieved.

[0209] The design features of the sensor 500 can facilitate insertion of the sensor, fixation of the sensor (e.g., in a position to monitor the patient's spinal cord), and safe removal of the sensor. The sensor 500 can be implemented to minimize the overall volume of the sensor 500. NIRS processing equipment

[0210] The NIRS processing unit 800 is in signal communication with the NIRS controller 400 to receive and / or transmit data. The NIRS processing unit 800 executes software that operates to process the light intensity data from the NIRS controller 400 to generate, collect, store, analyze and / or display various NIRS parameters.

[0211] The NIRS parameters may be, for example (but not limited to): - Stored in the data store. -Displayed in numerical form on the display. -The data is displayed on the screen in the form of a graph showing the change over time. Printed for the user. Monitored by a condition monitoring device, which for example activates an alarm if one or more NIRS parameters have values ​​outside the corresponding range. ·others.

[0212] The NIRS processing unit 800 executes one or more algorithms to process the data obtained by the light detector 140. For example, the NIRS processing unit 800 may calculate and / or monitor one or more NIRS parameters such as: · Changes in oxygenation (O2Hb) chromophore concentration. · Change in deoxygenated (HHb) chromophore concentration. Total hemoglobin (THb) – THb is a NIRS parameter of tissue hemodynamics defined as the sum of O2Hb and HHb. Hemoglobin difference (Hbdiff) – Hbdiff is a NIRS parameter of tissue oxygenation change defined by subtracting HHb from O2Hb. · Tissue Oxygenation Index (TOI)-TOI is an absolute measure of tissue oxygenation. · Changes in the redox state of cytochrome c oxidase (CCO) – CCO is an intracellular oxygenation parameter (the redox state of CCO reflects tissue oxygen supply and consumption at the mitochondrial level).

[0213] The algorithm may utilize a modified Beer-Lambert law (see Equation 1 below).

[0214] If the light source 120 of the NIRS sensor 100 includes an illuminant that can be controlled to emit light at different wavelengths (e.g., five different wavelengths) at different times, the NIRS processing unit 800 can execute a multi-wavelength (MW) NIRS algorithm to calculate the NIRS parameters.

[0215] TOI is a particularly useful NIRS parameter for monitoring patients suffering from SCI and other indications. TOI can be a nonlinear function of light attenuation. For a given wavelength, the attenuation is governed by a modified Beer-Lambert law:

number

[0216] By recording measurements of the intensity of the backscattered light at multiple wavelengths, the NIRS processing device 800 can advantageously employ a wavelength-dependent model that takes scattering into account. By performing attenuation calculations based on data corresponding to signals picked up from multiple wavelengths, greater accuracy may be advantageously obtained. An example of a wavelength-dependent algorithm for estimating changes in the concentration of CCO is described in Dizem Arifler et al., Optimal wavelength combinations for near-infrared spectroscopic monitoring of changes in brain tissue hemoglobin and cytochrome c oxidase concentrations, Biomed Opt Express, March 1, 2015;6(3):933-947, which is incorporated by reference herein as if fully set forth herein for all purposes.

[0217] In some embodiments, the NIRS system 10 adjusts the drive values ​​of the light emitters 121 depending on the individual situation. The drive values ​​can be adjusted so that the output signals from the photodetectors 140 are within a predetermined range. This can be beneficial, for example, when the output signals are digitized using an ADC. A higher resolution measurement can be obtained when the measured signals have an amplitude in the higher part of the ADC range (as long as the ADC does not saturate). In such an embodiment, each of the light emitters 121 can be initially operated with a predetermined drive signal level. Based on the corresponding output signals from the photodetectors 140, the drive signal levels of the various light emitters 121 can be individually adjusted to bring the corresponding output signals into the desired range. If the corresponding output signals are already within the desired range, the adjustment can be zero (no adjustment). In other cases, the adjustment can increase or decrease the drive signal within the allowable limits.

[0218] When such adjustments are made, it may be desirable to normalize the output signal from the photodetector 140 to take into account that the output of the corresponding light emitter 121 is not "standard." Normalization may facilitate the use of common algorithms to generate NIRS parameters and may help to avoid misinterpreting changes in detected intensity caused by absorption as changes in detected intensity caused by a light emitter 121 having a light output different from the standard light output.

[0219] Normalization can be performed by dividing the value of the detector's output signal by a factor that indicates how the actual optical output power at that wavelength corresponds to a "standard" or "reference" optical power for that wavelength. For example, if for a particular wavelength the selected power level is 1.2 times higher than the reference power level, then the normalized output signal can be obtained by dividing the detector 140 output signal by 1.2.

[0220] If the drive signal for light emitter 121 is a voltage signal and light emitter 121 includes a semiconductor junction, the normalization should take into account that the optical power output of light emitter 121 typically varies proportionally to V-V0, where V is the voltage of the signal driving light emitter 121 and V0 is the turn-on voltage of the light emitter.

[0221] For example, the NIRS system 10 may include set is the standard voltage of the light emitter, then V0 and V set The system 10 can use the normalization factor V set For example, the normalization can be based on the difference between V and V0.

number

[0222] Although V0 can be predicted theoretically, variations in the manufacturing process can cause V0 to vary between different light sources 120. In some cases, V0 is measured for each light emitter 121. One way to measure V0 is to use an optical phantom (i.e., a material that simulates the optical properties of biological tissue and mimics the light distribution of biological tissue). The NIRS sensor 100 can be placed in contact with the optical phantom to perform NIRS on the optical phantom. The optical phantom can provide known attenuation at various wavelengths. The NIRS controller 400 drives the light emitters 121 of the light source 120 to irradiate the optical phantom with light of various wavelengths. The intensity of the light detected by the photodetector 140 is measured in each case. In some embodiments, this process of irradiating the optical phantom with light is repeated for various intensity levels for each of the light emitters of the light source 120.

[0223] Since the power varies as V-V0, V0 can be estimated by measuring the power detected at two or more voltages and extrapolating to find the voltage for zero optical power. If power is detected at three or more voltages, a linear least squares fitting can be used to estimate V0. The system 10 can process the results of the phantom measurements to identify an offset voltage (V0) for each of the light emitters 121.

[0224] In some embodiments, the processing device 800 implements a machine learning approach to train an algorithm to generate accurate NIRS parameters. The machine learning approach can help derive the nonlinear dependence of TOI on optical attenuation. The approach involves estimating optical attenuation at various wavelengths and feeding the estimates (along with their higher moments) to a linear regression model or a multi-layer neural network. The linear regression model or multi-layer neural network can be trained on multiple subjects using reference TOI data that can be calculated from imaging of various optical phantoms.

[0225] A reference data set including a reference (or "expected") TOI and corresponding data obtained using the NIRS sensors described herein can be used to train a model and / or neural network for calculating the TOI.

[0226] Reference TOI data can be collected simultaneously with acquiring NIRS data by performing alternative TOI measurements. TOI can be measured, for example, by analyzing venous blood samples, using a clinical monitor for tissue oxygen saturation measurements, etc. Reference data can also be obtained by inducing occlusion or performing isometric and isotonic contractions and recording the TOI using the sensor and reference device simultaneously.

[0227] The reference data set preferably includes reference TOI data and corresponding NIRS data for multiple subjects. The reference data may be normalized (e.g., as described above) and used to train a model. The trained model is then used by software running on the NIRS processing device 800 to calculate the TOI and / or other NIRS parameters of tissues based on measurements of attenuation at various wavelengths.

[0228] 4 is a schematic diagram illustrating an exemplary artificial neural network (ANN) 600 architecture that may be configured to estimate TOI based on measurements of attenuation at various wavelengths. In the exemplary embodiment shown in FIG. 4, a single hidden layer is used. In other embodiments, multiple hidden layers may be used.

[0229] In the exemplary embodiment shown in Figure 4, the normalized intensity of the light detected by the NIRS sensor 100 is adjusted to take into account the background light level and then fed to the input layer of the ANN 600. The adjusted normalized intensities of the various wavelengths are:

number

[0230] Calculating the TOI from a set of various wavelength attenuations advantageously provides a highly reproducible measurement of the TOI that potentially accommodates the complexities of the attenuation / TOI relationship. This technique also advantageously allows its calibration to be refined for a particular subject (i.e., patient 20) as new reference data becomes available. Subject-to-subject variability is expected due to variability in tissue properties between subjects. The recalibration methods described above allow the NIRS system 10 to accommodate differences between subjects. signal quality control

[0231] In some embodiments, the NIRS monitoring system 10 measures a contact quality value to assess the quality of optical coupling between the tissue of the patient 20 (e.g., the spinal cord 25) and the NIRS sensor 100. Poor coupling between the NIRS sensor 100 and the tissue of the patient 20 may result in the detector 140 sending a low intensity signal to the NIRS controller 400. Receiving a low intensity signal at the NIRS controller 400 may result in inaccurate TOI calculations at the NIRS processor 800. By driving the light source 120 with a specific waveform and / or using pattern recognition techniques described below, the NIRS monitoring system 10 can quantify the quality of contact between the NIRS sensor 100 and the tissue in real time.

[0232] In some embodiments, the NIRS processing device 800 performs a base level check that includes detecting the presence of expected wavelengths within a single frame. Frames in which no signal can be detected from all wavelengths or where the signal from one or more wavelengths is saturated may be eliminated. The NIRS processing device 800 may optionally flag frames that contain all of the expected wavelengths and are not saturated at any wavelength.

[0233] In some embodiments, the NIRS processing device 800 calculates the signal-to-noise ratio by filtering the measured signal (y[n]) with the expected signal (s[n]) and dividing by the total signal energy. The ratio of the measured signal to the total signal power is given by

number

[0234] In some embodiments, the NIRS processing device 800 implements the calculation of the contact quality measurements in software to reduce the complexity, size and cost of the NIRS sensor 100. For example, the NIRS processing device 800 can reconstruct an "expected" data frame based on the detected amplitudes and then calculate the signal-to-noise ratio of the frame using a non-matched filter.

[0235] If too many frames are rejected or the signal-to-noise ratio falls below a threshold for more than a certain percentage of frames, the NIRS system 10 can generate a signal indicating that contact of the NIRS sensor 100 with the tissue it is monitoring is likely poor. Use of NIRS system for spinal cord injury (SCI)

[0236] The NIRS monitoring system 10 has an exemplary application for monitoring spinal cord oxygenation, hemodynamics and / or oxidative metabolism following spinal cord injury (SCI), a dangerous condition caused by trauma to the spine or disease that damages spinal cord tissue. SCI causes widespread permanent disabilities and multiple organ dysfunction that impair quality of life.

[0237] Monitoring oxygenation and hemodynamics of spinal cord tissue during acute treatment of SCI provides unique information that can be used to optimize hemodynamic management of SCI patients. Current techniques involve measuring the patient's mean arterial blood pressure (MAP) to estimate the desired blood flow in the spinal cord. These techniques lack accuracy because they cannot measure how changes in MAP actually alter oxygenation and blood flow within the injured spinal cord.

[0238] 5 is a flow chart illustrating a method 1000 of monitoring spinal cord oxygenation using the NIRS monitoring system 10. The method 1000 is non-invasive (e.g., the method 1000 does not require the direct insertion of a NIRS sensor into the spinal cord 25). The method 1000 can be performed in real time.

[0239] In block 1100, a NIRS sensor 100 is placed on the spinal cord 25 of the patient 20. The NIRS sensor 100 may be placed under the skin or other superficial tissue layer. The NIRS sensor 100 may be placed above the dura 26 to monitor the tissue of the spinal cord 25.

[0240] A soft "flap" 190 around the light source 120 and detector 140 facilitates placement and fixation of the NIRS sensor 100 above the dura and isolates the components of the NIRS sensor 100 from blood and other fluids in the epidural space. The flap is flexible, made of transparent implantable silicone rubber, and has a thickness of about 0.3 mm. The width of the flap around the sensor may be, for example, about 2 mm. A suitable biological adhesive (e.g., TISSEEL® fibrin sealant) may be applied around the edges of the flap 190 to fix the position of the NIRS sensor 100 above the dura.

[0241] In block 1200, the NIRS controller 400 sends power and / or control signals to the light source 120 over the wiring 160. The NIRS controller 400 can send independent control signals to each of the multiple light emitters of the light source 120. For example, the NIRS controller 400 can send a first control signal to a first light emitter of the light source 120, a second control signal to a second light emitter of the light source 120, .... In some embodiments, the NIRS controller 400 can send the control signals in sequence to sequentially control the emission timing of the light emitters of the light source 120. In some embodiments, the NIRS controller 400 can send a repeating sequence of such control signals. In some embodiments, the control signals can control the intensity of light emitted by the light emitters of the light source 120.

[0242] In block 1300, the detector 140 of the NIRS sensor 100 detects the backscattered light from the spinal cord 25. The NIRS controller 400 can apply a bias voltage to the detector 140 and can measure a photocurrent to determine the intensity of the light incident on the detector 140. The detector 140 sends a signal to the NIRS controller 400 corresponding to the detected light.

[0243] In block 1400, an analog module 420 of the NIRS controller 400 converts a current signal corresponding to the light detected by the detector 140 into a voltage. The analog module 420 can optionally amplify the voltage. The analog module 420 can optionally perform a baseline correction on the voltage. The analog module 420 can optionally further amplify the voltage with a PGA 426. The analog module 420 can optionally further amplify the voltage after baseline correction.

[0244] In block 1500, a voltage corresponding to the light detected by the detector 140 is sent through one or more analog-to-digital converters to the digital module 440. The digital module 440 can optionally implement a time division multiplexing scheme to send the data to the NIRS processing device 800. Data can be transferred between the digital module 440 and the NIRS processing device 800 through a USB cable.

[0245] In block 1600, the NIRS processing device 800 executes one or more algorithms to process data corresponding to signals of various wavelengths sensed by the detector 400. The NIRS processing device 800 may execute a multi-wavelength (MW) NIRS algorithm that includes comparing the intensity of light detected for various wavelengths to calculate an attenuation value. The NIRS processing device may calculate a TOI based on the attenuation value. The NIRS processing device 800 may implement machine learning techniques (e.g., ANN 600) to derive a relationship between attenuation and TOI.

[0246] 6A and 6B show a NIRS sensor (eg, sensor 500) attached to the spinal cord of a patient.

[0247] An advantage of the embodiments of the NIRS system described herein is that the system measures NIRS parameters such as TOI using a single light source (with five wavelengths) and one photodetector. This allows the sensor to be much smaller than some commercially available NIRS sensors. Thus, embodiments of the present technology can provide a sensor that can be attached directly to the top surface of the dura to measure NIRS parameters of the spinal cord. Such a small sensor can be removed without the need for additional surgery. Another advantage is that instead of using optical fibers, light attenuation and leakage are reduced by providing a light source and photodetector in a probe that can be placed directly on the tissue of interest (e.g., the spinal cord).

[0248] The scope of the present invention includes a wide variety of possible auxiliary designs for and / or alternative uses of NIRS monitoring system 10. These variations may be utilized with any of the embodiments described herein, as appropriate, and include, but are not limited to, the following: The NIRS sensor 100 or 500 can be implanted onto any internal organ of a subject, such as the liver, kidney, bladder, intestine or brain, to directly monitor their tissue oxygenation and hemodynamics. Various functions and features of the NIRS controller 400 and the NIRS processor 800 may be replaced and / or combined into an integrated module. The optical isolation element 130, the light shield 170 and / or the flap 190 can be made of a single common material (e.g., biocompatible silicone) that encapsulates the active elements of the NIRS sensor 100 or 500 (e.g., the light source 120, the detector 140, the wiring 160, etc.) while providing a transparent window through which the light source 120 emits light and through which the detector 140 collects light. Interpretation of terms

[0249] Unless the context clearly requires otherwise, throughout the specification and claims (if any): "Including" and the like words should be construed in their inclusive sense, i.e. "including but not limited to", and not in their exclusive or exhaustive sense. "Connected," "coupled," or variations thereof means a direct or indirect connection or coupling between two or more elements. The coupling or connection between the elements may be physical, logical, or a combination thereof. The words "herein," "above," "below," and words of similar import, when used to describe this specification, shall refer to this specification as a whole and not to specific portions of this specification. "Or", in relation to a list of two or more items, covers all of the following interpretations of the word: any of the items in the list, all the items in the list, and any combination of the items in the list. The singular forms "a", "an" and "the" include the appropriate plural references.

[0250] In this specification and the appended claims (if any), directional words such as "vertical," "lateral," "horizontal," "upward," "downward," "forward," "rearward," "inner," "outer," "left," "right," "front," "rear," "top," "bottom," "down," "above," "below," and the like, are dependent on the particular orientation of the device being described and illustrated. The subject matter described herein can assume a variety of alternative orientations. Thus, these directional terms are not precisely defined and should not be interpreted in a narrow sense.

[0251] Various features are described herein as being present in "some embodiments." Such features are not required and may not be present in all embodiments. An embodiment of the invention may include zero, any one, or any combination of two or more of such features. This is limited only to the extent that certain such features are incompatible with other such features, in the sense that one of ordinary skill in the art would not be able to construct a practical embodiment combining such incompatible features. As a result, a statement that "some embodiments" have feature A and "some embodiments" have feature B should be interpreted as an explicit indication that the inventors also contemplate embodiments combining feature A and feature B (unless otherwise stated in the specification or unless feature A and feature B are fundamentally incompatible).

[0252] Where a component (e.g., a circuit, module, assembly, device) is referred to above, unless otherwise indicated, the reference to that component (including the reference to "means") should be interpreted to include all components that perform the function of the described component (i.e., are functionally equivalent), including components that are not structurally equivalent to the disclosed structures that perform that function in the illustrated exemplary embodiments of the invention.

[0253] Specific examples of systems, methods, and devices have been described herein for illustrative purposes. These are examples only. The techniques provided herein can be utilized in systems other than the exemplary systems described above. Many changes, modifications, additions, omissions, and substitutions are possible within the scope of the practice of the invention. The invention includes variations of the described embodiments that would be apparent to one of ordinary skill in the art, including variations obtained by replacing features, elements, and / or acts with equivalent features, elements, and / or acts, mixing and matching features, elements, and / or acts from different embodiments, combining features, elements, and / or acts of the embodiments described herein with features, elements, and / or acts of other technologies, and / or omitting combinations of features, elements, and / or acts from the described embodiments.

[0254] It is therefore intended that the following appended claims and any claims hereafter introduced be interpreted to include all such modifications, permutations, additions, omissions, and subcombinations that can reasonably be inferred. The scope of the claims should not be limited by the preferred embodiments set forth in the examples, but should be accorded the broadest interpretation consistent with the description as a whole.

Claims

1. 1. A near infrared spectroscopy (NIRS) sensor, comprising: a body having a dorsal side, a ventral side, a proximal end and a distal end, the proximal end of the body being connectable to a cable, the body supporting a light source and a light detector in a spaced apart relationship, the light source operative to emit light from the ventral side of the body, the light detector operative to detect light incident on the ventral side of the body and to generate an output signal; a flexible flap extending laterally from the body along opposing first and second sides of the body; Including, the flap extends between the first side and the second side around a distal end of the body; a portion of the flap extending around the distal end of the body follows an arc; the flap has a thickness less than a thickness of the body; the flap has a thickness in the range of 0.2 mm to 0.4 mm; The NIRS sensor wherein the flap is wider at a distal end of the body and tapers in width along the body toward the proximal end of the body.

2. The NIRS sensor of claim 1 , wherein the flap is made of a silicone rubber material.

3. 3. The NIRS sensor of claim 1 or 2, wherein the flap of material extends continuously across the rear side of the body and encapsulates the light source and the light detector.

4. The NIRS sensor of claim 1 , wherein the flap comprises a flexible mesh.

5. The NIRS sensor of claim 1 , wherein the flap is formed with a curvature such that a ventral surface of the flap is concave.

6. The NIRS sensor of claim 4 , wherein the ventral surface of the flap has a cylindrical shape.

7. The NIRS sensor of claim 1 , wherein the flap has a peripheral contour that is teardrop shaped.

8. The NIRS sensor of claim 6 , wherein the periphery of the flap has a convex portion adjacent the distal end of the body that merges into concave tapered portions on either side of the body.

9. The NIRS sensor of claim 1 including a line of weakness in the flap that extends along either side of the body.

10. The NIRS sensor of claim 1 , wherein the flap has shallow grooves formed in a rear surface of the flap that extend along both sides of the body.

11. 11. The NIRS sensor of claim 1, wherein a portion of the body between the light source and the photodetector is opaque to light emitted by the light source and prevents direct transmission of light from the light source to the photodetector.

12. 12. The NIRS sensor of claim 1, wherein the light source is operative to emit light having a wavelength in the range of 600 nm to 1000 nm.

13. The NIRS sensor of claim 1 , wherein the light source comprises a plurality of light emitters.

14. The NIRS sensor of claim 13 , wherein the multiple light emitters are provided in a single package.

15. The NIRS sensor of claim 14 , wherein the package has a diameter of 2 mm or less.

16. 16. The NIRS sensor of claim 13, wherein the multiple light emitters are spaced apart from one another by a distance of 2 mm or less.

17. 17. The NIRS sensor of claim 13, wherein each of the plurality of light emitters emits a different one of a plurality of wavelengths of light.

18. 20. The NIRS sensor of claim 17, wherein the multiple wavelengths of light are distributed about an isosbestic point.

19. 20. The NIRS sensor of claim 18, wherein the isosbestic point is at a wavelength of 810 nm.

20. 19. The NIRS sensor of claim 17 or 18, wherein the plurality of wavelengths includes one or more wavelengths above the isosbestic point and one or more wavelengths below the isosbestic point.

21. 21. The NIRS sensor of claim 20, wherein the plurality of wavelengths includes the wavelength of the isosbestic point.

22. 22. The NIRS sensor of claim 17, wherein the plurality of wavelengths includes at least five wavelengths.

23. 23. The NIRS sensor of claim 17, wherein the plurality of wavelengths includes two or more wavelengths selected from 660±10 nm, 730±10 nm, 810±10 nm, 850±10 nm, and 940±10 nm.

24. 24. The NIRS sensor of claim 17, wherein the plurality of wavelengths includes wavelengths of approximately 660±10 nm, 730±10 nm, 810±10 nm, 850±10 nm, and 940±10 nm.

25. 25. The NIRS sensor of claim 1, wherein the light source is spaced from the light detector by a distance in the range of 5 mm to 20 mm.

26. 26. The NIRS sensor of claim 1 , wherein the light detector is a first light detector and the NIRS sensor includes a second light detector spaced apart from the light source, the second light detector operative to detect light incident on a ventral side of the body.

27. 27. The NIRS sensor of claim 26, wherein the first photodetector is spaced a first distance from the light source and the second photodetector is spaced a second distance from the light source that is different from the first distance.

28. 30. The NIRS sensor of claim 27, wherein the second distance is in the range of 1.5 to 2 times the first distance.

29. 29. The NIRS sensor of claim 1, wherein a rear side of the body has a plurality of recesses formed therein.

30. 30. The NIRS sensor of claim 29, wherein the recess comprises an array of shallow depressions.

31. A NIRS sensor as described in any one of claims 1 to 30, wherein the cable includes a first conductor connected to drive the light source and a second conductor connected to carry an output signal from the photodetector.

32. 32. The NIRS sensor of claim 31 , wherein the cable includes a sheath surrounding the first and second conductors, the first conductor passing within a first conductive shield within the sheath, and the second conductor passing within a second conductive shield within the sheath.

33. 33. The NIRS sensor of claim 31 or 32, wherein the first conductor comprises a plurality of conductors, each connected to carry current to a corresponding one of a plurality of light emitters of the light source.

34. 34. The NIRS sensor of claim 1, further comprising a transformer amplifier within the body connected to convert a current signal output by the photodetector to a voltage signal.

35. 35. The NIRS sensor of claim 34, wherein the light source, the photodetector, and the transformer amplifier are all mounted on a printed circuit board embedded in the body.

36. 36. The NIRS sensor of claim 35, wherein the circuit board is a flexible circuit board.

37. 37. The NIRS sensor of any one of claims 34 to 36, wherein the material of the flap encapsulates the transformer amplifier.

38. 38. The NIRS sensor of claim 34, wherein the transformer amplifier is between the light source and the light detector.

39. 39. The NIRS sensor of any one of claims 34 to 38, wherein the transformer amplifier is a high sensitivity transformer amplifier.

40. 40. The NIRS sensor of claim 34, wherein the transformer amplifier is a high speed transformer amplifier.

41. 41. The NIRS sensor of claim 1, wherein the body comprises a molded biocompatible silicone rubber material.

42. 42. The NIRS sensor of claim 1 in combination with a NIRS controller, the NIRS controller including electronic circuitry connected to control the light source to emit different wavelengths of light at different times.

43. 43. The NIRS sensor of claim 42, wherein the NIRS controller is configured to control multiple light emitters of the light source to be illuminated in a time-multiplexed pattern such that the light source emits light one wavelength at a time.

44. The NIRS controller controls five different wavelengths (λ 1 From λ 5 43. The NIRS sensor of claim 42, configured to control the light source to emit light at each of the wavelengths in sequence, and to sample the photodetector output signal in coordination with operation of the light source to obtain a series of light intensity measurements, each light intensity measurement corresponding to one of the wavelengths.

45. 45. The NIRS sensor of claim 42, wherein the NIRS controller is configured to continuously sample the output signal of the photodetector and identify portions of the sampled output signal that correspond to different wavelengths emitted by the light source.

46. 46. ​​The NIRS sensor of claim 42, wherein the NIRS controller is configured to generate a data frame divided into a number of time slots corresponding to a number of light emitters of the light source and to control one of the light emitters to emit light in a corresponding one of the time slots.

47. 47. The NIRS sensor of claim 46, wherein the data frame includes at least one time slot during which all of the light emitters of the light source are turned off.

48. 48. The NIRS sensor of claim 42, wherein the NIRS controller is configured to drive each of a plurality of light emitters of the light source with a corresponding programmable drive waveform.

49. 48. The NIRS sensor of claim 42, wherein the NIRS controller is configured to drive multiple light emitters of the light source with corresponding drive signals.

50. 50. The NIRS sensor of claim 49, wherein the corresponding drive signals for different ones of the light emitters differ in one or more of waveform, duty cycle, amplitude, and frequency.

51. 51. The NIRS sensor of claim 42, wherein the NIRS controller includes a data store that stores data representing waveforms for driving each of a plurality of light emitters of the light source.

52. Processing the output signal of the photodetector according to an algorithm; Oxygenation (O 2 Hb) change in chromophore concentration; - Change in deoxygenated (HHb) chromophore concentration, - Total hemoglobin (THb), Hemoglobin difference (Hbdiff), - Tissue Oxygenation Index (TOI), and -Changes in the redox state of cytochrome c oxidase (CCO) 52. The NIRS sensor of claim 1 in combination with a processing unit configured to calculate one or more NIRS parameters selected from the group consisting of:

53. 53. The NIRS sensor of claim 52, wherein the algorithm includes a modified Beer-Lambert law.

54. 53. The NIRS sensor of claim 52, wherein the processing unit includes a trained artificial neural network.

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