# US 12,213,770 B2 · Portable device for quantitative measurement of tissue autoregulation and neurovascular coupling using EEG, metabolism, and blood flow diagnostics

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- Number: US 12,213,770 B2
- Document ID: US12213770B2
- Status: Granted
- Kind: B2
- Application number: 17/377,123
- Filed: 2021-07-15
- Published: 2021-11-04
- Granted: 2025-02-04
- Earliest claimed: 2019-04-01
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Yama Akbari; Robert H. Wilson; Christian Crouzet; Thomas Milner; Bernard Choi
- Web page: https://patentgrep.com/patent/US12213770B2

## CPC

- A61B 5/02028: {Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction}
- A61B 5/0261: {using optical means, e.g. infrared light}
- A61B 5/0075: {by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy (A61B5/0071 takes precedence)}
- A61B 5/0205: Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
- A61B 5/14546: {for measuring analytes not otherwise provided for, e.g. ions, cytochromes}
- A61B 5/14553: {specially adapted for cerebral tissue}
- A61B 5/369: Electroencephalography [EEG]
- A61B 5/37: Intracranial electroencephalography [IC-EEG], e.g. electrocorticography [ECoG]
- A61B 5/4836: {Diagnosis combined with treatment in closed-loop systems or methods (A61B5/0036 takes precedence)}
- A61B 5/4866: {Evaluating metabolism (using breath test A61B5/083)}
- A61B 5/4875: {Hydration status, fluid retention of the body}
- A61B 5/6801: {specially adapted to be attached to or worn on the body surface}
- A61B 5/6814: {Head}
- A61B 5/6841: {by using templates}
- A61N 1/0456: {Specially adapted for transcutaneous electrical nerve stimulation [TENS]}
- A61N 1/0472: {Structure-related aspects}
- A61N 1/36025: {for treating a mental or cerebral condition}
- A61N 2/006: {for magnetic stimulation of nerve tissue}
- A61N 5/0622: {Optical stimulation for exciting neural tissue}
- A61N 2005/0626: {Monitoring, verifying, controlling systems and methods}
- A61N 2005/0644: {Handheld applicators}
- 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

A portable device for quantitative measurement of tissue autoregulation and neurovascular coupling via portable measurement of blood flow, oxygenation, metabolism, and/or EEG signals and methods for using said device. The device may comprise a body and a plurality of legs pivotably attached to the body. The plurality of legs may comprise at least one reference electrode leg and at least one measurement electrode leg for electrical measurement, and an optical detection fiber leg and at least one optical source fiber leg for optical blood flow, oxygenation, and metabolism measurement. The present invention is additionally directed to a portable device for blood flow measurement and therapeutic photobiomodulation. The device may comprise a body and a plurality of legs. The plurality of legs may comprise at least one optical detection fiber leg and at least one optical source fiber leg, and at least one leg for therapeutic photobiomodulation.

## Claims

### Claim 1

A non-invasive method of determining a depth-calibrated absolute value of cerebral metabolic rate of oxygen (CMRO2) using optical measurement of tissue perfusion, absorption, and scattering, the method comprising:
a. positioning one or more light sources and two or more detectors in proximity to a cerebral tissue of a subject;
b. emitting a coherent light signal from one or more of the light sources into the head, such that that one or more backscattered light signals are generated;
c. detecting one or more of the backscattered light signals via the two or more detectors;
d. determining a dynamic perfusion metric, a tissue absorption coefficient, and a tissue scattering coefficient from the detected signals;
e. determining a mean penetration depth of the detected signals, using the tissue absorption coefficient and tissue scattering coefficient; and
f. determining an absolute value of CMRO2 using the mean penetration depth, the dynamic perfusion metric, the tissue absorption coefficient, and the tissue scattering coefficient;
wherein absolute value of CMRO2 is depth-calibrated using the mean penetration depth, and
wherein the dynamic perfusion metric, the tissue absorption coefficient, and the tissue scattering coefficient provide all the information necessary to calculate the depth-calibrated absolute value of CMRO2.

### Claim 2 (depends on 1)

The method of claim 1, additionally comprising modifying the light emission or detection to change the mean penetration depth, and calculating a depth-calibrated absolute value of CMRO2 at each mean penetration depth.

### Claim 3 (depends on 2)

The method of claim 2, wherein the mean penetration depth is changed by adjusting one or more source-detector separation distances, a modulation frequency or wavelength of the coherent light signal, or a combination thereof.

### Claim 4 (depends on 1)

The method of claim 1, additionally comprising determining one or more fluid metrics from the detected signals.

### Claim 5 (depends on 4)

The method of claim 4, wherein the fluid metrics are indicative of a degree of swelling or edema of the tissue.

### Claim 6 (depends on 4)

The method of claim 4, wherein the fluid metrics comprise a parameter of cellular components of the tissue.

### Claim 7 (depends on 6)

The method of claim 6, wherein the parameter of cellular components of the tissue comprises a shape, a size, or a refractive index of the cellular components.

### Claim 8 (depends on 1)

The method of claim 1, wherein separate values of CMRO2 are calculated using a diffuse flow calibrated perfusion metric and a directed flow calibrated perfusion metric.

### Claim 9 (depends on 1)

The method of claim 1, wherein the absolute value of CMRO2 is corrected to account for an effect of a geometry or arrangement of the light sources and detectors.

### Claim 10 (depends on 1)

The method of claim 1, additionally comprising dividing the absolute value of CMRO2 by the calibrated perfusion metric to determine a depth-calibrated value of cerebral autoregulation.