Integral detection scheme for fast blood flow measurements

Abstract

Various embodiments of an integration detection scheme for rapid blood flow measurements are disclosed. A first control signal can be sent to a switch to cause an integrator to integrate current from a photodiode. An integrated current can be received from the integrator, and a data signal based at least in part on the integrated current can be sent to a computing device. A second control signal can be sent to the switch to cause the integrator to stop integrating current from the photodiode.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefit and priority of co-pending U.S. Provisional Patent Application No. 62 / 960,870, filed January 14, 2020, entitled “INTEGRATED DETECTION SCHEME FOR FAST BLOOD FLOW MEASUREMENT”, the contents of which are incorporated herein by reference in their entirety. Background Technology

[0003] Blood flow is a crucial indicator of tissue health because it directly informs the state of oxygen and nutrient supply to the tissue. Therefore, bedside blood flow monitoring is of great significance in the treatment of a variety of diseases, including stroke, traumatic brain injury, cancer, and peripheral vascular disease. Diffuse Correlation Spectroscopy (DCS) measures tissue blood flow based on the temporal intensity fluctuations of highly coherent light that has diffused through the tissue. A major limitation of traditional methods for estimating tissue dynamics using DCS is the need for expensive, bulky, and highly sensitive photon counting detectors and electronics that cannot be directly embedded in low-cost probes. Summary of the Invention

[0004] Various embodiments of this disclosure include a system comprising: a photodiode configured to output a photodiode current based at least in part on a plurality of photons received by the photodiode; an integrator configured to output an integrated current based at least in part on the photodiode current; a first computing device including a processor and a memory; and machine-readable instructions stored in the memory, which, when executed by the processor, cause the first computing device to perform at least the following operations: in response to receiving a first command from a second computing device, sending a first control signal to a switch, the first control signal causing the integrator to begin outputting the integrated current; receiving the integrated current from the integrator; reading an input corresponding to the integrated current; and in response to receiving a second command from the second computing device, sending a second control signal to the switch, the second control signal causing the integrator to stop outputting the integrated current. In one or more embodiments, the machine-readable instructions, when executed by the processor, also cause the first computing device to send a data signal to the second computing device, the data signal being based at least in part on the integrated current. In one or more embodiments, the system further includes a voltage-controlled current source, and the machine-readable instructions, when executed by the processor, also cause the first computing device to send at least a drain control signal to the voltage-controlled current source, the drain control signal specifying the value of the input voltage of the voltage-controlled current source. In one or more embodiments, the voltage-controlled current source includes an operational amplifier buffer and a metal-oxide-semiconductor field-effect transistor. In one or more embodiments, the integrating current is a function of integration time. In one or more embodiments, the integrator includes an operational amplifier. In one or more embodiments, the integrator includes a resistor-capacitor circuit.

[0005] Various embodiments of this disclosure include a method comprising: sending an activation integration control signal to a switch by a computing device; receiving an integration current from an integrator by the computing device, the integration current being at least partially based on a photodiode current generated by a photodiode; reading an input corresponding to the integration current by the computing device; and sending a reset integration control signal to the switch by the computing device. In one or more embodiments, sending the integration control signal to the switch further comprises: sending a first integration control signal to a first switch by the computing device, wherein the first integration control signal causes the first switch to close; and sending a second integration control signal to a second switch by the computing device, wherein the second integration control signal causes the second switch to open. In one or more embodiments, sending the integration control signal to the switch causes the integrator to integrate a signal from the photodiode. In one or more embodiments, the method may further comprise sending a drain control signal to a voltage-controlled current source by the computing device. In one or more embodiments, the drain control signal causes the voltage-controlled current source to generate an input voltage.

[0006] Various embodiments of this disclosure include a non-transitory computer-readable medium comprising an application executable in at least one computing device, the application, when executed, causing the at least one computing device to perform at least the following operations: sending a drain control signal to a voltage-controlled current source, the drain control signal causing the voltage-controlled current source to generate an input voltage; sending an integral control signal to a switch, the integral control signal causing the switch to close; reading an input corresponding to an integral current; and sending a reset control signal to the switch, the reset control signal causing the switch to open. In one or more embodiments, the application, when executed, also causes the at least one computing device to perform at least the following operations: receiving a dark current, wherein the dark current includes a leakage current flowing through a photodiode; and reading an input corresponding to the dark current. In one or more embodiments, the application, when executed, also causes the at least one computing device to determine a correction current at least partially based on the integral current and the dark current. In one or more embodiments, in response to receiving a first command from another computing device, the drain control signal is sent to the voltage-controlled current source, the first command including a plurality of volts; in response to receiving a second command from the other computing device, the integration control signal is sent to the switch, the second command including an instruction to cause the integrator to begin integration; and in response to receiving a third command from the other computing device, the reset control signal is sent to the switch, the third command including an instruction to cause the integrator to stop integration. Attached Figure Description

[0007] To gain a more complete understanding of the embodiments and their advantages, reference will now be made to the following description in conjunction with the accompanying drawings, which are briefly described below:

[0008] Figure 1 This is an example of an overall layout for implementing integrated diffuse correlation spectroscopy according to various embodiments of this disclosure.

[0009] Figure 2 Various embodiments according to this disclosure Figure 1 An example of a feasible implementation of the integrator shown.

[0010] Figure 3 This is an example of an overall layout for implementing an integral diffusion-related spectrum with adaptive DC current subtraction, according to various embodiments of the present disclosure.

[0011] Figure 4 According to various embodiments of the present invention Figure 3 The diagram shows an example of a feasible implementation scheme for the voltage-controlled current source.

[0012] Figure 5 Various embodiments according to this disclosure Figure 1 and Figure 3 Examples of schematic block diagrams of the first and second computing devices shown.

[0013] Figure 6 It is through various embodiments of this disclosure that... Figure 1 and Figure 3 The diagram shows an example flowchart of some functions implemented by a portion of the data acquisition application executed by the first computing device.

[0014] Figure 7 It is through various embodiments of this disclosure that... Figure 1 and Figure 3 An example flowchart of some functions implemented by a portion of the control application executed by the first computing device shown. Detailed Implementation

[0015] Various methods for measuring blood flow using integrated diffusion correlation spectroscopy are disclosed. The disclosed methods are based on measuring blood flow using diffuse speckle contraction (DCS) analysis. Traditional DCS relies on rapid sampling of instantaneous intensity i(t) fluctuations to estimate the blood flow index from the normalized autocorrelation of the detected intensity. On the other hand, the disclosed methods involve measuring the blood flow from the integrated photon intensity I sampled at measurement time t. tThe statistical data of (T) are used to estimate the organizational dynamics, where T is the integration time. The integrated photon intensity can be given by the following formula:

[0016]

[0017] The disclosed method achieves I by directly integrating the signal from the photodiode using a low-power circuit. t The method disclosed allows for the detection of diffuse light fluctuations using photodiodes and integrator circuits, enabling simple, low-cost, board-level detection of speckle intensity fluctuations. The disclosed method facilitates rapid, single-shot measurement of intensity dynamics over multiple integration times, inherently reducing measurement noise that is detected and compensated for in real time.

[0018] In the following discussion, a general description of the system and its components is provided, followed by a discussion of the operation of the system and its components.

[0019] Go to Figure 1 An example of the overall layout for achieving integrated diffusion-correlated spectroscopy is shown. A light source 103 can be used to irradiate tissue 106. The light source 103 will have a coherence length longer than the optical path length propagating in the tissue to facilitate measurement of geometry. The light source 103 can be any multimode or single-mode laser diode with associated collimating lenses / optics and / or temperature / wavelength stabilization circuitry to satisfy coherence conditions. Photons from the light source 103 can diffuse through tissue 106 and be received by photodiode 109.

[0020] The photodiode 109 can be any suitable semiconductor device that outputs a photodiode current 112 after receiving light. In some embodiments, a phototransistor or other photodetector can be used in place of or attached to the photodiode 109. The photodiode 109 can be unbiased and operate in photovoltaic mode, such that the photodiode current 112 flows from the anode to the cathode of the photodiode.

[0021] The photodiode current 112 can be proportional to the instantaneous speckle intensity fluctuation of the photons received by the photodiode 109. The photodiode 109 can also generate a dark current. The dark current can be the leakage current flowing through the photodiode 109 when no light is illuminating it. In some embodiments, a pinhole (not shown) can be placed between the photodiode 109 and the tissue 106 to improve the contrast of the photodiode 109.

[0022] Integrator 115 can receive the photodiode current 112 output by photodiode 109 and integrate the photodiode current 112 to generate an integrating current 121. Integrator 115 can be any circuit or other device capable of receiving an input signal and generating an output signal representing the integral of the input signal with respect to the integration time. Integrator 115 can be implemented using an operational amplifier, a resistor-capacitor circuit, or other integrating circuits. The integrating current 121 can be given by the following equation:

[0023]

[0024] Where T is the integration time, and C int It is the net capacitance in the feedback of integrator 115, and i in (t)∝I(t) is the instantaneous photodiode current 112.

[0025] The operation of integrator 115 depends on one or more integration control signals 118 received by integrator 115 from first computing device 124. For example, integrator 115 may receive an "activation" integration control signal 118 that causes integrator 115 to integrate the photodiode current 112 and output an integrated current 121. As another example, integrator 115 may receive a "reset" integration control signal 118 that resets integrator 115 and stops integrating the photodiode current 112.

[0026] The first computing device 124 can receive an input signal. The first computing device 124 can perform one or more read operations to read the input corresponding to the input signal. The first computing device 124 can record a photon intensity measurement of the input signal. Then, the first computing device 124 can output a data signal 130 including the photon intensity measurement of the input signal.

[0027] The input signal can be an integrating current 121, a dark current, or other input signals. For example, the first computing device 124 can receive the integrating current 121 from the integrator 115. Then, the first computing device 124 can read the input corresponding to the integrating current 121 and record the photon intensity measurement of the integrating current 121. In some embodiments, the first computing device 124 can correct for noise caused by the dark current in the integrating current 121 and record the corrected photon intensity measurement.

[0028] The first computing device 124 can act as a control mechanism for circuit control and data acquisition. The first computing device 124 can send one or more integration control signals 118 to the integrator 115 to control the operation of the integrator. For example, the first computing device 124 can send an integration control signal 118 to the integrator 115 to cause the integrator 115 to begin integrating the photodiode current 112. As another example, the first computing device 124 can send an integration control signal 118 to the integrator 115 to reset the integrator 115 and stop integrating the photodiode current 112.

[0029] The first computing device 124 can receive one or more commands 127 from the second computing device 133. One or more commands 127 can trigger a read operation on the first computing device 124. The first read operation can be performed simultaneously with the start of integration by the integrator 115. The first read operation can record the output of the integrator 115 at the "zero" integration time, thereby measuring the dark current. Subsequent timed read operations record the integrated current at the corresponding integration time. Multiple integration frames can be obtained by repeating this loop. Measuring the dark current in the first read operation provides a method for correcting dark noise in each integration frame.

[0030] I corrected (T)=I(T)-I dark (3)

[0031] The speckle visibility or intensity fluctuation variance at each integration time can be calculated by estimating the standard deviation and average intensity of the integration frames.

[0032] The second computing device 133 can send commands 127 to the first computing device 124. These commands 127 can cause the first computing device 124 to send one or more integration control signals 118 to the integrator 115 to control the operation of the integrator 115.

[0033] The second computing device 133 may receive data signal 130 from the first computing device 124. The second computing device 133 may read data from the integration frame from the data signal 130 to calculate speckle visibility and use diffuse speckle contrast analysis to estimate blood flow. In some embodiments, the functions performed by the second computing device 133 may be performed by an application executable by the first computing device 124.

[0034] Go to Figure 2 An example schematic diagram of a feasible embodiment of integrator 115 is shown. In this example, integrator 115 is a circuit that includes a start switch 203, a reset switch 206, a switching amplifier resistor 209, a feedback loop 212, and an operational amplifier 215. Figure 2Photodiode 109 is also shown, which feeds photodiode current 112 to integrator 115.

[0035] The start switch 203 and reset switch 206 can be bipolar transistors, metal-oxide-semiconductor field-effect transistors (MOSFETs), or any other suitable switching devices. The start switch 203 and reset switch 206 can control the operation of integrator 115. When the start switch 203 is closed and the reset switch 206 is open, integrator 115 integrates the photodiode current 112 and outputs an integrated current 121. When the start switch 203 is open and the reset switch 206 is closed, integrator 115 will not integrate the photodiode current 112 and integrator 115 can be reset. Each of the start switch 203 and reset switch 206 can be opened or closed based on an integration control signal 118 received from the first computing device 124.

[0036] The switching amplifier resistor 209 can be any suitable resistor or resistor layout. The switching amplifier resistor 209 can be connected between the start switch 203 and the operational amplifier 215.

[0037] Feedback loop 212 may include capacitor 218, feedback resistor 221, and reset switch 206. Capacitor 218 can be any suitable capacitor or capacitor arrangement. For example, capacitor 218 may be implemented as follows: Figure 2 The single capacitor shown is illustrated. As another example, capacitor 218 can be implemented as a series or parallel configuration of multiple capacitors. The net capacitance of feedback loop 212 can depend on the capacitance of capacitor 218, and the net capacitance of feedback loop 212 can determine the gain of integrator 115. When start switch 203 is closed and reset switch 206 is open, capacitor 218 can accumulate charge while integrator 115 integrates the photodiode current 112. When start switch 203 is open and reset switch 206 is closed, capacitor 218 can discharge through operational amplifier 215 and integrator 115 can be reset. Feedback resistor 221 can be any suitable resistor or resistor layout. For example, feedback resistor 221 can be implemented as shown... Figure 2 The single resistor is shown. As another example, the feedback resistor 221 can be implemented as a series or parallel configuration of multiple resistors.

[0038] Operational amplifier 215 can be any suitable operational amplifier including two inputs and one output. Operational amplifier 215 can receive photodiode current 112 as input via switching amplifier resistor 209. Operational amplifier can output integrating current 121, which is also the output of integrator 115.

[0039] Go to Figure 3 An example of the overall layout for achieving an integral diffusion-related spectrum with adaptive DC current subtraction is shown. In some examples, the photodiode 109 can have a detection area on the order of several square millimeters, which is much larger than the average size of a single speckle. Therefore, the photodiode current 112 represents the spatial average of several speckles, which results in a non-fluctuating DC offset. Thus, the photodiode current 112 can have two components in some cases: a non-fluctuating DC current 303 generated by dark noise and speckle averaging, and a fluctuating signal current 306 generated by speckle intensity fluctuations. In practice, the photodiode current 112 can be modeled as:

[0040] I = I dc +I sig (t) (4)

[0041] Where I is the photodiode current 112, I dc It can represent the spatially averaged non-fluctuating DC current 303, I of multiple speckles. sig (t) is a fluctuating signal current 306 that can represent the fluctuation of speckle intensity over time.

[0042] In some examples, integrator 115 can integrate both the non-fluctuating DC current 303 and the fluctuating signal current 306. However, the fluctuating signal current 306 may contain blood flow information. Furthermore, the non-fluctuating DC current 303 component of the photodiode current 112 may be significantly larger than the fluctuating signal current 306 component, which could result in poor signal contrast and signal-to-noise ratio.

[0043] One way to reduce the impact of the speckle spatial averaging that causes the non-fluctuating DC current 303 is to use a photodiode 109 with a smaller effective area, or by using a pinhole a as described in paragraph

[0019] . However, this proportionally reduces the fluctuating signal current 306 and decreases the detection threshold of the photodiode 109. A better alternative is to actively suppress the non-fluctuating DC current 303. In this way, the integrator 115 can integrate the fluctuating signal current 306.

[0044] Figure 3 The example illustrates a method for subtracting a non-fluctuating DC current 303 generated by dark noise and speckle averaging from the photodiode current 112 using a voltage-controlled current source 309. The voltage-controlled current source 309 can be used as a drain / sink for the non-fluctuating DC current 303. For example, the current consumption of the voltage-controlled current source 309 can absorb a programmable amount of non-fluctuating DC current 303 from the input of the integrator 115, which can improve the signal contrast and signal-to-noise ratio in the integrated current 121.

[0045] The voltage-controlled current source 309 can be any suitable current source whose strength is controlled by voltage elsewhere in the circuit. For example, a voltage-controlled current source may include an operational amplifier buffer and a MOSFET. As another example, a voltage-controlled current source may include a simple resistor and a controlled voltage source. The amount of current flowing through the voltage-controlled current source 309 can be controlled using a drain control signal 312. The drain control signal 312 can be received from the first computing device 124 or any other suitable computing device.

[0046] Absorbing DC current in this manner can result in a high signal-to-noise ratio due to fluctuations in the integrated speckle intensity. Since the non-fluctuating DC current 303 is removed from the photodiode current 112, the amplitude of the integrated current 121 output can be reduced. However, the variation in the integrated current 121 can be significantly increased.

[0047] Go to Figure 4 An example schematic of a feasible embodiment of the voltage-controlled current source 309 is shown. A current drain path 403 of an operational amplifier buffer 406, including a MOSFET 409 driving and controlling the amount of drain current 412, can be implemented. The voltage-controlled current source may also include a buffer-MOSFET resistor 415, a MOSFET-source resistor 418, and a DC voltage source 421.

[0048] Operational amplifier buffer 406 can be any suitable operational amplifier including two inputs and one output. The input of operational amplifier buffer 406 can be an input voltage 424 that can be controlled by the drain control signal 312 from the first computing device 124.

[0049] MOSFET 409 can be an n-channel enhancement-mode MOSFET. However, in some examples, various other MOSFETs or other electrical components suitable for controlling current flow can also be used. Both the buffer-MOSFET resistor 415 and the MOSFET-source resistor 418 can be any suitable resistor or resistor configuration. The buffer-MOSFET resistor 415 can be connected between the operational amplifier buffer 406 and the gate of MOSFET 409. The MOSFET source resistor 418 can be connected between the source terminal of MOSFET 409 and the DC voltage source 421. The DC voltage source 421 can be any suitable DC voltage source.

[0050] The drain current 412 can be a function of the input voltage 424 of the operational amplifier buffer 406. In some examples, the input voltage 424 of the operational amplifier buffer 406 can be controlled by a first computing device 124, a second computing device 133, or other computing devices. When the input voltage 424 is controlled in a manner that makes the drain current 412 equal to the non-fluctuating DC current 303, the signal contrast and signal-to-noise ratio are at their maximum values.

[0051] Go to Figure 5 The diagram illustrates one or more first computing devices 124 communicating with a second computing device 133. Each first computing device 124 includes a processor 503 and a memory 506, each electrically and communicatively coupled to a local interface 509. For this purpose, each first computing device 124 may represent a server computer, a client computing device (e.g., a personal computer, mobile device, smartphone, tablet, wearable computing device, etc.), a single-board computer (e.g., a microcontroller, system-on-a-chip (SoC), or similar device). The local interface 509 may include a data bus with an accompanying address / control bus or other bus structure.

[0052] The memory 506 stores data and several components executable by the processor 503. Specifically, the memory 506 stores and executes data acquisition application 512, control application 515, and potentially other applications. The memory 506 may also store measurement data 518 and other data. Additionally, the operating system may be stored in the memory 506 and executed by the processor 503.

[0053] It should be understood that other applications may exist, stored in memory 506 and executable by processor 503. In the case of implementing any of the components discussed herein in software form, any of a variety of programming languages ​​may be used, such as, for example, C, C++, C#, Objective C, etc. Perl, PHP, Visual Ruby or

[0054] Multiple software components are stored in memory 506 and are executable by processor 503. In this respect, the term "executable" refers to a program file that can ultimately be run by processor 503. Examples of executable programs may include a compiler that can be translated into machine code having a format that can be loaded into the random access portion of memory 506 and run by processor 503, or source code expressed in a suitable format, such as object code that can be loaded into the random access portion of memory 506 and executed by processor 503, or source code that can be interpreted by another executable program to generate instructions in the random access portion of memory 506 that will be executed by processor 503, and so on. Executable programs may be stored in any part or component of memory 506, including, for example, random access memory (RAM), read-only memory (ROM), hard disk drive, solid-state drive, universal serial bus (USB) flash drive, memory card, optical disc such as CD or DVD, floppy disk, magnetic tape, or other memory components.

[0055] Processor 503 may represent multiple processors 503 or multiple processor cores, and memory 506 may represent multiple memories 506 operating in parallel processing circuitry. In this case, local interface 509 may be a suitable network facilitating communication between any two of the multiple processors 503, between any processor 503 and any memory 506, or between any two memories 506. Local interface 509 may include additional systems designed to coordinate this communication, including, for example, performing load balancing. Processor 503 may be electrical or some other available structure.

[0056] Memory 506 is defined herein as including volatile and non-volatile memory as well as data storage components. Volatile components are those that do not retain data values ​​when power is lost. Non-volatile components are those that retain data when power is lost. Therefore, memory 506 may include, for example, random access memory (RAM), read-only memory (ROM), hard disk drives, solid-state drives, USB flash drives, memory cards accessed via memory card readers, floppy disks accessed via associated floppy disk drives, optical disks accessed via optical disk drives, magnetic tapes accessed via suitable magnetic tape drives, or other memory components, or any combination of two or more of these memory components. Furthermore, RAM may include, for example, static random access memory (SRAM), dynamic random access memory (DRAM), or magnetic random access memory (MRAM), and other such devices. ROM may include, for example, programmable read-only memory (PROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), or other similar memory devices.

[0057] Data acquisition application 512 represents an application that reads the input corresponding to the input signal received from integrator 115. Data acquisition application 512 can perform one or more read operations to read the input signal. The input signal may be, for example, an integration current 121 or a dark current. The data acquisition application can record the photon intensity measurement of the input signal in measurement data 518. The data acquisition application can transmit a data signal 130, including at least a portion of the measurement data 518, to a second computing device 133.

[0058] Control application 515 refers to an application that controls the operation of integrator 115 by sending one or more integration control signals 118 to integrator 115. For example, control application 515 may generate integration control signals 118 to "start" integration operation or "reset" integrator 115. Thus, control application 515 can control the timing of integration by generating integration control signals 118 to control the integration and reset of integrator 115. Control application 515 may send integration control signals 118 based on commands received from second computing device 133. In some examples, control application 515 may control the operation of voltage-controlled current source 309 by sending one or more drain control signals 312 to voltage-controlled current source 309. For example, control application 515 may generate drain control signals 312 to set the input voltage 424 of voltage-controlled current source 309.

[0059] Measurement data 518 represents a recorded measurement of the integrated photon intensity of the input signal received by the first computing device 124 at various integration times. For each read operation performed by the data acquisition application 512, the data acquisition application 512 may record the photon intensity measurement of the input signal in measurement data 518. Data signal 130, including at least a portion of measurement data 518, may be transmitted to the second computing device 133.

[0060] The second computing device 133 may include any system providing computing capabilities. The second computing device 133 may receive a data signal 130 including at least a portion of measurement data 518. The second computing device 133 may read integration frames from the data signal 130 to calculate speckle visibility and estimate blood flow using diffuse speckle contrast analysis. The second computing device 133 may send one or more commands 127 to a control application 515. These commands 127 may instruct the control application 515 to send one or more integration control signals 118 to the integrator 115. The integration control signals 118 may control the integration and reset of the integrator 115. The commands 127 may also specify how much photon intensity measurement to obtain before the integrator 115 is reset.

[0061] In some examples, command 127 may instruct control application 515 to send one or more drain control signals 312 to voltage-controlled current source 309. The drain control signals 312 may control the input voltage 424 of voltage-controlled current source 309. Command 127 may also specify the input voltage 424 of voltage-controlled current source 309. However, in some examples, the function performed by the second computing device 133 may be performed by an application executable by the first computing device 124.

[0062] Go to Figure 6 The diagram illustrates a flowchart of an example of the operation of a data acquisition application 512 provided according to various embodiments. It should be understood that... Figure 6 The flowcharts provided are merely examples of many different types of functional layouts that can be used to implement various embodiments of this disclosure. Alternatively, Figure 6 The flowchart can be viewed as an example depicting the elements of a method implemented according to one or more embodiments.

[0063] Starting at box 603, data acquisition application 512 performs a read operation to record the input corresponding to the dark current received at the first computing device 124. This read operation can be performed when control application 515 sends an integration control signal 118 that causes integrator 115 to begin integration. This allows the dark current to be measured before the integrated current 121 is received at the first computing device 124. The dark current can be any leakage current flowing from photodiode 109, and its generation is independent of the photons received by photodiode 109.

[0064] Then, at box 606, data acquisition application 512 performs a read operation to record the input corresponding to the integrating current 121 received at the first computing device 124. This read operation can be performed after control application 515 sends an integration control signal 118 that causes integrator 115 to begin integration. The photon intensity measurement of integrating current 121 can be recorded in measurement data 518.

[0065] Proceeding to box 609, data acquisition application 512 corrects for dark current noise in the integrated current 121 recorded at box 606. For example, the photon intensity measurement of the dark current recorded at box 603 can be subtracted from the photon intensity measurement of the integrated current 121. The corrected photon intensity measurement can then be recorded in measurement data 518.

[0066] Then proceeding to box 612, the data acquisition application 512 determines whether to perform another read operation. Whether the data acquisition application 512 performs another read operation may depend on how many photon intensity measurements to record for a given integration frame. The data acquisition application 512 may perform subsequent read operations to obtain multiphoton intensity measurements for a given integration frame. If another read operation is to be performed, the execution of the data acquisition application 512 returns to box 606. If no other read operation is performed, the execution of the data acquisition application 512 proceeds to box 615.

[0067] In box 615, data acquisition application 512 sends data signal 130 to second computing device 133. Data signal 130 may be based on measurement data 518. For example, data signal 130 may include data about fluctuations in photon intensity measured during integration.

[0068] Go to Figure 7 The diagram illustrates a flowchart of an example of the operation of a control application 515 provided according to various embodiments. It should be understood that... Figure 7 The flowcharts provided are merely examples of many different types of functional layouts that can be used to implement various embodiments of this disclosure. Alternatively, Figure 7 The flowchart can be viewed as an example depicting the elements of a method implemented according to one or more embodiments.

[0069] Starting at box 703, control application 515 receives command 127 from the second computing device. Command 127 instructs the control application to cause integrator 115 to begin integrating photodiode current 112. Command 127 may also include instructions on how many photon intensity measurements the data acquisition application 512 should record before control application 515 causes integrator 115 to stop integrating photodiode current 112 and resets.

[0070] Next, at block 706, control application 515 sends at least one first integration control signal 118 to integrator 115. The first integration control signal 118 can cause integrator 115 to begin integration. For example, the first integration control signal 118 can cause multiple switches in integrator 115 to open or close, causing integrator 115 to begin integrating the photodiode current 112. The control signal can also be used to operate voltage-controlled current source 309.

[0071] At block 709, control application 515 sends at least one second integration control signal 118 to integrator 115. The second integration control signal 118 can reset the integrator and stop integrating the photodiode current 112. Once data acquisition application 512 has obtained multiple photon intensity measurements, control application 515 can send the second integration control signal 118.

[0072] Although the data acquisition application 512, the control application 515, and the various other systems described herein can be implemented by software or code executed by the general-purpose hardware described above, alternatively, the data acquisition application 512, the control application 515, and the various other systems described herein can also be implemented by dedicated hardware or a combination of software / general-purpose hardware and dedicated hardware. If implemented by dedicated hardware, each can be implemented as a circuit or state machine employing any one or a combination of various technologies. These technologies may include, but are not limited to, discrete logic circuits having logic gates that implement various logic functions when one or more data signals are applied, application-specific integrated circuits (ASICs) with appropriate logic gates, field-programmable gate arrays (FPGAs), or other components. These technologies are generally well known to those skilled in the art and therefore will not be described in detail herein.

[0073] Figure 4 and Figure 5 The flowchart illustrates the functionality and operation of a portion of the data acquisition application 512 or control application 515. If implemented in software, each block may represent a module, segment, or portion of code comprising program instructions for implementing a specified logical function. The program instructions may be implemented as source code comprising human-readable statements written in a programming language or as machine code comprising numeric instructions recognizable by a suitable execution system such as processor 503 in a computer system or other system. Machine code can be converted from source code through various processes. For example, machine code may be generated from source code using a compiler before the corresponding application is executed. As another example, machine code may be generated from source code while being executed by an interpreter. Other methods may also be used. If implemented in hardware, each block may represent circuitry or multiple interconnected circuits for implementing one or more specified logical functions.

[0074] although Figure 4 and Figure 5 The flowchart illustrates a specific execution order; however, it should be understood that the execution order may differ from that described. For example, the execution order of two or more blocks may be shuffled relative to the order shown. Furthermore, Figure 4 and Figure 5 Two or more consecutive blocks shown in the diagram can be executed simultaneously or partially simultaneously. Furthermore, in some embodiments, these blocks can be skipped or omitted. Figure 4 and Figure 5 One or more boxes are shown. Furthermore, any number of counters, status variables, warning signals, or messages may be added to the logic flow described herein for purposes such as enhancing usability, billing, performance measurement, or providing troubleshooting assistance. It should be understood that all such variations are within the scope of this disclosure.

[0075] Furthermore, any logic or application described herein, including data acquisition application 512 and control application 515 having software or code, can be implemented on any non-transitory computer-readable medium for use by or in conjunction with an instruction execution system, such as, for example, a processor 503 in a computer system or other system. In this sense, logic can include, for example, statements, which include instructions and statements that can be retrieved from a computer-readable medium and executed by an instruction execution system. In the context of this disclosure, "computer-readable medium" can be any medium capable of containing, storing, or maintaining the logic or application described herein for use by or in conjunction with an instruction execution system.

[0076] Computer-readable media can include any of a number of physical media, such as, for example, magnetic, optical, or semiconductor media. More specific examples of suitable computer-readable media include, but are not limited to, magnetic tape, floppy disk, magnetic hard disk drive, memory card, solid-state drive, USB flash drive, or optical disc. Furthermore, computer-readable media can be random access memory (RAM), including, for example, static random access memory (SRAM) and dynamic random access memory (DRAM), or magnetic random access memory (MRAM). Additionally, computer-readable media can be read-only memory (ROM), programmable read-only memory (PROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), or other types of memory devices.

[0077] Furthermore, any logic or application described herein, including data acquisition application 512 and control application 515, can be implemented and constructed in various ways. For example, the one or more applications described herein can be implemented as modules or components of a single application. Additionally, the one or more applications described herein can execute in shared or separate computing devices or combinations thereof. For example, multiple applications described herein can execute in the same computing device, or in multiple computing devices within the same computing environment or computing cluster.

[0078] Unless otherwise specifically stated, delimited language such as the phrase "at least one of X, Y, or Z" is generally understood in the context of presentation to mean that items, terms, etc., can be X, Y, or Z or any combination thereof (e.g., X; Y; Z; X and / or Y; X and / or Z; Y and / or Z; X, Y, and / or Z, etc.). Therefore, such delimited language is generally not intended and should not imply that certain embodiments require at least one of X, at least one of Y, or at least one of Z to be present individually.

[0079] It should be emphasized that the above embodiments of this disclosure are merely feasible examples of implementation methods described to clearly understand the principles of this disclosure. Many variations and modifications can be made to the above embodiments without substantially departing from the spirit and principles of this disclosure. All such modifications and variations are intended to be included within the scope of this disclosure and protected by the appended claims.

[0080] Several exemplary implementations of this disclosure are set forth in the following clauses. As explained in the foregoing discussion, although these clauses illustrate various implementations and embodiments of this disclosure, they are not the only description of implementations or embodiments of this disclosure.

[0081] Clause 1 - A system comprising: a photodiode configured to output a photodiode current based at least in part on a plurality of photons received by the photodiode; an integrator configured to output an integrated current based at least in part on the photodiode current; a first computing device including a processor and a memory; and machine-readable instructions stored in the memory, the machine-readable instructions, when executed by the processor, causing the first computing device to perform at least the following operations: in response to receiving a first command from a second computing device, sending a first control signal to a switch, the first control signal causing the integrator to begin outputting the integrated current; receiving the integrated current from the integrator; reading an input corresponding to the integrated current; and in response to receiving a second command from the second computing device, sending a second control signal to the switch, the second control signal causing the integrator to stop outputting the integrated current.

[0082] The system of Clause 2-1, wherein the machine-readable instructions, when executed by the processor, also cause the first computing device to send at least a data signal to the second computing device, the data signal being at least partially based on the integral current.

[0083] The system of Clause 3-Clause 1 or 2 further includes a voltage-controlled current source, wherein the machine-readable instructions, when executed by the processor, also cause the first computing device to send at least a drain control signal to the voltage-controlled current source, the drain control signal specifying the value of the input voltage of the voltage-controlled current source.

[0084] A system of any one of Clauses 4-1-3, wherein the voltage-controlled current source comprises an operational amplifier buffer and a metal-oxide-semiconductor field-effect transistor.

[0085] A system of any one of Clauses 5-1-4, wherein the integral current is a function of the integral time.

[0086] A system of any one of Clauses 6-1-5, wherein: the plurality of photons diffuse through the tissue, the photodiode current is proportional to the speckle intensity fluctuation of the plurality of photons, and the photodiode operates in photovoltaic mode such that the photodiode current flows from the anode of the photodiode to the cathode of the photodiode.

[0087] A system of any one of Clauses 7-1-6, wherein the integrator includes an operational amplifier.

[0088] A system of any one of Clauses 8-1-6, wherein the integrator comprises a resistor-capacitor circuit.

[0089] Clause 9 - A method comprising: sending an activation integral control signal to a switch by a computing device; receiving an integral current from an integrator by the computing device, the integral current being at least partially based on a photodiode current generated by a photodiode; and sending a reset integral control signal to the switch by the computing device.

[0090] The method of Clauses 10-9, wherein sending the activation integration control signal to the switch causes the integrator to integrate the signal from the photodiode, and sending the activation integration control signal to the switch further comprises: sending a first activation integration control signal to a first switch by the computing device, wherein the first activation integration control signal causes the first switch to close; and sending a second activation integration control signal to a second switch by the computing device, wherein the second activation integration control signal causes the second switch to open.

[0091] The method of Clauses 11-9 or 10, wherein sending the reset integral control signal to the switch comprises: sending a first reset integral control signal to the first switch by the computing device, wherein the first reset integral control signal causes the first switch to open; and sending a second integral reset control signal to the second switch by the computing device, wherein the second integral reset control signal causes the second switch to close.

[0092] The method of any one of Clauses 12-9-11 further includes sending a drain control signal from the computing device to a voltage-controlled current source, wherein the drain control signal causes the voltage-controlled current source to generate an input voltage.

[0093] Clause 13 - A non-transitory computer-readable medium comprising an application executable in at least one computing device, the application, when executed, causing the at least one computing device to perform at least the following operations: sending a drain control signal to a voltage-controlled current source, the drain control signal causing the voltage-controlled current source to generate an input voltage; sending a first integral control signal to a switch, the first integral control signal causing the switch to close; reading an input corresponding to an integral current; and sending a second integral control signal to the switch, the second integral control signal causing the switch to open.

[0094] Non-transitory computer-readable media of Clauses 14-13, wherein the application, when executed, also causes the at least one computing device to perform at least the following operations: receive a dark current, wherein the dark current includes a leakage current flowing through a photodiode; read an input corresponding to the dark current; and determine a correction current based at least in part on the integral current and the dark current.

[0095] A non-transitory computer-readable medium of Clauses 15-13 or 14, wherein: in response to receiving a first command from another computing device, the drain control signal is sent to the voltage-controlled current source, the first command comprising a plurality of volts; in response to receiving a second command from the other computing device, the first integration control signal is sent to the switch, the second command comprising an instruction to cause the integrator to begin integration; and in response to receiving a third command from the other computing device, the second integration control signal is sent to the switch, the third command comprising an instruction to cause the integrator to stop integration.

Claims

1. A system comprising: A photodiode configured to output a photodiode current proportional to the speckle intensity fluctuation of a plurality of photons diffused through the tissue and received by the photodiode; An integrator configured to output an integrated current based at least in part on the photodiode current; A first computing device, the first computing device including a processor and a memory; as well as Machine-readable instructions stored in the memory, when executed by the processor, cause the first computing device to perform at least the following operations: In response to receiving a first command from a second computing device, a first control signal is sent to a switch, the first control signal causing the integrator to start outputting the integrated current; Receive integrated current from the integrator; Read the input corresponding to the integrated current; The photon intensity measurement is determined at least in part based on the input; as well as In response to receiving a second command from the second computing device, a second control signal is sent to the switch, the second control signal causing the integrator to stop outputting the integrated current.

2. The system according to claim 1, wherein, When executed by the processor, the machine-readable instructions also cause the first computing device to send at least a data signal to the second computing device, the data signal being at least partially based on the integral current.

3. The system of claim 1 or 2 further includes a voltage-controlled current source, wherein the machine-readable instructions, when executed by the processor, also cause the first computing device to send at least a drain control signal to the voltage-controlled current source, the drain control signal specifying the value of the input voltage of the voltage-controlled current source.

4. The system according to claim 3, wherein, The voltage-controlled current source includes an operational amplifier buffer and a metal-oxide-semiconductor field-effect transistor.

5. The system according to claim 1, wherein, The integral current is a function of the integral time.

6. The system according to claim 1, wherein: The photodiode operates in photovoltaic mode, causing the photodiode current to flow from the anode to the cathode.

7. The system according to claim 1, wherein, The integrator includes an operational amplifier.

8. The system according to claim 1, wherein, The integrator includes a resistor-capacitor circuit.

9. A method comprising: The computing device sends the activation integral control signal to the switch; The computing device receives an integrated current from an integrator, the integrated current being at least partially based on a photodiode current proportional to the speckle intensity fluctuations of multiple photons diffused through the tissue, the photodiode current being generated by a photodiode; The computing device reads the input corresponding to the integral current; The photon intensity measurement is determined at least in part based on the input; and The computing device sends a reset integral control signal to the switch.

10. The method according to claim 9, wherein, Sending the activation integration control signal to the switch to cause the integrator to integrate the signal from the photodiode, and sending the activation integration control signal to the switch further includes: The computing device sends a first activation integral control signal to a first switch, wherein the first activation integral control signal causes the first switch to close; and The computing device sends a second activation integral control signal to the second switch, wherein the second activation integral control signal causes the second switch to open.

11. The method according to claim 9, wherein, Sending the reset integral control signal to the switch includes: The computing device sends a first reset integral control signal to a first switch, wherein the first reset integral control signal causes the first switch to open; and The computing device sends a second integral reset control signal to the second switch, wherein the second integral reset control signal causes the second switch to close.

12. The method according to any one of claims 9-11, further comprising sending a drain control signal to a voltage-controlled current source by the computing device, wherein, The drain control signal causes the voltage-controlled current source to generate an input voltage.

13. A non-transitory computer-readable medium comprising an application executable in at least one computing device, the application, when executed, causing the at least one computing device to perform at least the following operations: A drain control signal is sent to a voltage-controlled current source, which causes the voltage-controlled current source to generate an input voltage to control the drain current through the switch. A first integral control signal is sent to the switch, the first integral control signal causing the switch to close and being generated at least in part based on a photodiode current that is proportional to the speckle intensity fluctuations of multiple photons diffused through the tissue; Read the input corresponding to the integral current; as well as The photon intensity measurement is determined at least in part based on the input; A second integral control signal is sent from the integrator to the switch, and the second integral control signal causes the switch to open in response to the drain current through the switch being equal to the non-fluctuating DC current from the photodiode.

14. The non-transitory computer-readable medium according to claim 13, wherein, When the application is executed, it also causes the at least one computing device to perform at least the following operations: Receive dark current, wherein the dark current includes leakage current flowing through the photodiode; Read the input corresponding to the dark current; and The correction current is determined at least in part based on the integral current and the dark current.

15. The non-transitory computer-readable medium according to claim 13 or 14, wherein: In response to receiving a first command from another computing device, the drain control signal is sent to the voltage-controlled current source, the first command comprising multiple volts. In response to receiving a second command from the other computing device, the first integration control signal is sent to the switch, the second command including an instruction to cause the integrator to begin integration, and In response to receiving a third command from the other computing device, the second integration control signal is sent to the switch, the third command including an instruction to stop the integrator from integrating.

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