# US 2021/0275091 A1 · Rapid assessment of microcirculation in patients to realize closed-loop systems > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0275091 A1 - Document ID: US20210275091A1 - Status: Published application - Kind: A1 - Application number: 17/196,306 - Filed: 2021-03-09 - Published: 2021-09-09 - Earliest claimed: 2020-03-09 - Assignees: Arizona Board of Regents on behalf of Arizona State University - Inventors: Jitendran Muthuswamy - Web page: https://patentgrep.com/patent/US20210275091A1 ## CPC - A61B 5/4836: {Diagnosis combined with treatment in closed-loop systems or methods (A61B5/0036 takes precedence)} - A61B 5/02007: {Evaluating blood vessel condition, e.g. elasticity, compliance} - A61B 5/0265: using electromagnetic means, e.g. electromagnetic flowmeter - A61B 5/0295: using plethysmography, i.e. measuring the variations in the volume of a body part as modified by the circulation of blood therethrough, e.g. impedance plethysmography - A61B 5/4064: {Evaluating the brain (for intracranial pressure A61B5/031; for cerebral blood gases A61B5/14553; using EEG A61B5/369)} - A61B 5/7257: {using Fourier transforms} - A61N 1/0534: {Electrodes for deep brain stimulation} - A61N 1/36067: {Movement disorders, e.g. tremor or Parkinson disease (stimulating motor muscle A61N1/36003)} - A61N 1/36135: {using physiological parameters} - A61N 1/36139: {with automatic adjustment} - A61B 5/4839: {combined with drug delivery} - A61B 2505/09: Rehabilitation or training - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) ## Abstract Rapid assessment of microcirculation in tissue to realize closed-loop systems is provided. Microcirculatory assessment systems according to embodiments described herein allow a user to assess changes in local blood flow in microvasculature in real-time using conventional electrical techniques. Some embodiments provide a closed-loop system that allows calibrated doses of electrical stimulation to be delivered in a deep brain stimulation (DBS) system depending on blood flow changes (in specific regions of the brain) being fed back to a controller. The approach described here is readily translatable with very minimal changes to existing hardware. Such closed-loop systems will improve the accuracy of electrode placement in DBS surgery and potentially reduce surgery time, optimize the delivery of electrical stimulation, increase battery life of implantable DBS systems, reduce post-surgical visits to medical practitioners and improve the quality of life of patients. ## Claims ### Claim 1 A method for providing a controlled therapeutic intervention, the method comprising: applying a therapeutic intervention to a patient; measuring a change in local blood flow in the patient in response to the therapeutic intervention; and adjusting the therapeutic intervention based on the change in local blood flow. ### Claim 2 (depends on 1) The method of claim 1, wherein measuring the change in local blood flow comprises measuring a change in an electrochemical impedance spectrogram (EIS) at a tissue of the patient. ### Claim 3 (depends on 2) The method of claim 2, wherein measuring the change in the EIS comprises: applying a multi-frequency excitation signal to the tissue; obtaining electrical parameter measurements in response to the multi-frequency excitation signal; and measuring the EIS as a function of the electrical parameter measurements and the multi-frequency excitation signal. ### Claim 4 (depends on 3) The method of claim 3, wherein the multi-frequency excitation signal comprises a triangular excitation signal having at least one of a ramp waveform or a sawtooth waveform. ### Claim 5 (depends on 3) The method of claim 3, wherein determining the EIS comprises determining a ratio of a fast Fourier transform (FFT) of the multi-frequency excitation signal and a FFT of the electrical parameter measurements. ### Claim 6 (depends on 2) The method of claim 2, wherein measuring the change in local blood flow comprises determining changes in blood flow as proportional to changes in the EIS. ### Claim 7 (depends on 1) The method of claim 1, wherein the therapeutic intervention comprises a neurological stimulation. ### Claim 8 (depends on 7) The method of claim 7, wherein: applying the therapeutic intervention comprises applying an electrical stimulation using a stimulation electrode at a first region of a first tissue of the patient; and measuring the change in local blood flow comprises monitoring blood flow at a second region in the first tissue or a second tissue of the patient in response to the electrical stimulation. ### Claim 9 (depends on 8) The method of claim 8, wherein adjusting the therapeutic intervention comprises adjusting placement of the stimulation electrode based on results of monitoring the blood flow in response to the electrical stimulation. ### Claim 10 (depends on 8) The method of claim 8, wherein adjusting the therapeutic intervention comprises providing feedback to a user based on results of monitoring the blood flow in response to the electrical stimulation. ### Claim 11 (depends on 8) The method of claim 8, wherein adjusting the therapeutic intervention comprises adjusting a dose of the electrical stimulation provided by the stimulation electrode based on results of monitoring the blood flow in response to the electrical stimulation. ### Claim 12 (depends on 11) The method of claim 11, wherein the dose of the electrical stimulation is adjusted using an automatic control. ### Claim 13 (depends on 12) The method of claim 12, wherein the automatic control is a proportional-integral-derivative (PID) control. ### Claim 14 (depends on 12) The method of claim 12, wherein the automatic control comprises an adaptive control scheme. ### Claim 15 (depends on 1) The method of claim 1, wherein the therapeutic intervention comprises one or more of chemical stimulation, a bioelectronic intervention, administration of a pharmaceutical, an electrical stimulation, an ultrasound stimulation, an optical stimulation, or a magnetic stimulation. ### Claim 16 A therapeutic intervention system, comprising: an intervention controller configured to provide a controlled therapeutic intervention to a patient; and a microcirculatory assessment system configured to measure a change in local blood flow in the patient in response to the controlled therapeutic intervention; wherein the intervention controller is further configured to adjust the controlled therapeutic intervention based on the change in local blood flow. ### Claim 17 (depends on 16) The therapeutic intervention system of claim 16, wherein the microcirculatory assessment system comprises: a counter electrode configured to measure an electrical response to a multi-frequency excitation signal applied to a tissue of the patient; and a processing device coupled to the counter electrode and configured to: determine an electrochemical impedance spectrogram (EIS) from the electrical response to the multi-frequency excitation signal; and measure blood flow of the tissue based on the EIS. ### Claim 18 (depends on 16) The therapeutic intervention system of claim 16, wherein: the intervention controller is configured to provide an electrical stimulation in a first tissue of the patient using a stimulation electrode; and the microcirculatory assessment system is further configured to monitor blood flow in the first tissue or a second tissue in response to the electrical stimulation in the first tissue. ### Claim 19 (depends on 18) The therapeutic intervention system of claim 18, wherein the intervention controller is further configured to adjust a dose of the electrical stimulation provided by the stimulation electrode in response to changes in the monitored blood flow of the first tissue or the second tissue. ### Claim 20 (depends on 18) The therapeutic intervention system of claim 18, wherein the therapeutic intervention system comprises a closed-loop deep brain stimulation (DBS) system.