# US 12,599,332 B2 · Non-invasive assessment of glymphatic flow and neurodegeneration from a wearable device

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- Number: US 12,599,332 B2
- Document ID: US12599332B2
- Status: Granted
- Kind: B2
- Application number: 18/636,234
- Filed: 2024-04-15
- Published: 2024-08-15
- Granted: 2026-04-14
- Earliest claimed: 2021-09-14
- Assignees: Applied Cognition, Inc.
- Applicants: Applied Cognition, Inc.
- Inventors: Paul Dagum; Gregory T. A. Kovacs; Laurent B. Giovangrandi; Carl J. Weber; Joerg C. Student; Nathan Whipple; Jonathan I. Kaplan
- Web page: https://patentgrep.com/patent/US12599332B2

## CPC

- A61B 5/4064: {Evaluating the brain (for intracranial pressure A61B5/031; for cerebral blood gases A61B5/14553; using EEG A61B5/369)}
- A61B 5/4088: {Diagnosing of monitoring cognitive diseases, e.g. Alzheimer, prion diseases or dementia}
- A61B 5/0006: {ECG or EEG signals}
- A61B 5/0205: Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
- A61B 5/372: Analysis of electroencephalograms
- A61B 5/418: {lymph vessels, ducts or nodes}
- A61B 5/4806: {Sleep evaluation (A61B5/4821 takes precedence; devices for inducing sleep A61M21/02)}
- A61B 5/6817: {Ear canal}
- A61B 5/7275: {Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor}
- G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients
- G16H 40/63: for local operation
- G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems
- G16H 50/30: for calculating health indices; for individual health risk assessment
- A61B 2562/166: the sensor is mounted on a specially adapted printed circuit board
- G01R 33/5601: {involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent}
- G01R 33/56341: {Diffusion imaging}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)

## Abstract

A computer-implemented method and system includes accessing neurophysiological and neurovascular data recorded during sleep. A function mapping is executed from said neurophysiological and neurovascular data to a target that is one of a glymphatic flow marker, a molecular analysis marker of neurodegeneration, or a neuroimaging marker of neurodegeneration. A target prediction model is output based on the function mapping. The target prediction model can receive new neurophysiological and neurovascular data and output a predicted marker of neurodegeneration.

## Claims

### Claim 1

A brain monitoring system comprising:
left electrodes and right electrodes that collect neurovascular measurements from a patient's head during a sleep interval; and
a computing module that:
receives transcranial impedance data derived from the neurovascular measurements collected by the left electrodes and right electrodes,
applies the transcranial impedance data to a model to determine an indication of glymphatic flow, and
responsive to the indication of glymphatic flow, performs at least one of: a) displaying the indication of glymphatic flow on a display, and b) administering a therapeutic intervention.

### Claim 2 (depends on 1)

The brain monitoring system of claim 1, wherein the computing module further receives electroencephalogram data derived from neurophysiological measurements collected by the left electrodes and the right electrodes, and
wherein the model is derived from the electroencephalogram data.

### Claim 3 (depends on 1)

The brain monitoring system of claim 1, wherein the computing module performs the administering of the therapeutic intervention and wherein the therapeutic intervention is a neuromodulation intervention.

### Claim 4 (depends on 3)

The brain monitoring system of claim 3, wherein the computing module modifies an intensity of the neuromodulation intervention.

### Claim 5 (depends on 3)

The brain monitoring system of claim 3, wherein the computing module further determines and displays a measure of an effect of the neuromodulation intervention.

### Claim 6 (depends on 1)

The brain monitoring system of claim 1, further comprising an input device that receives instructions for the therapeutic intervention.

### Claim 7 (depends on 1)

The brain monitoring system of claim 1, further comprising a flexible band, wherein the left electrodes and the right electrodes are coupled to the flexible band.

### Claim 8 (depends on 1)

The brain monitoring system of claim 1, wherein the computing module further determines and displays an effect of a pharmaceutical intervention.

### Claim 9 (depends on 8)

The brain monitoring system of claim 8, wherein the pharmaceutical intervention comprises a dosage of dexmedetomidine.

### Claim 10 (depends on 1)

The brain monitoring system of claim 1, wherein an initial therapeutic intervention is administered to the patient while the neurovascular measurements are collected from the patient's head during the sleep interval.

### Claim 11

A brain monitoring system comprising:
left electrodes and right electrodes that collect neurovascular measurements from a patient's head during a sleep interval; and
a computing module that:
receives transcranial impedance data derived from the neurovascular measurements collected from the left electrodes and the right electrodes,
applies the transcranial impedance data to a model to determine an indication of fluid flow in intracranial perivascular pathways, and
responsive to the indication of fluid flow in the intracranial perivascular pathways, performs at least one of: a) displaying the indication of fluid flow in the intracranial perivascular pathways on a display, and b) administering a therapeutic intervention.

### Claim 12 (depends on 11)

The brain monitoring system of claim 11, wherein the computing module further receives electroencephalogram data derived from neurophysiological measurements collected by the left electrodes and the right electrodes, and
wherein the model is derived from the electroencephalogram data.

### Claim 13 (depends on 11)

The brain monitoring system of claim 11, wherein the computing module performs the administering of the therapeutic intervention and wherein the therapeutic intervention is a neuromodulation intervention.

### Claim 14 (depends on 13)

The brain monitoring system of claim 13, wherein the computing module modifies an intensity of the neuromodulation intervention.

### Claim 15 (depends on 13)

The brain monitoring system of claim 13, wherein the computing module further determines and displays a measure of an effect of the neuromodulation intervention.

### Claim 16 (depends on 11)

The brain monitoring system of claim 11, further comprising an input device that receives instructions for the therapeutic intervention.

### Claim 17 (depends on 11)

The brain monitoring system of claim 11, further comprising a flexible band, wherein the left electrodes and the right electrodes are coupled to the flexible band.

### Claim 18 (depends on 11)

The brain monitoring system of claim 11, wherein the computing module further determines and displays an effect of a pharmaceutical intervention.

### Claim 19 (depends on 18)

The brain monitoring system of claim 18, wherein the pharmaceutical intervention comprises a dosage of dexmedetomidine.

### Claim 20 (depends on 11)

The brain monitoring system of claim 11, wherein an initial therapeutic intervention is administered to the patient while the neurovascular measurements are collected from the patient's head during the sleep interval.

### Claim 21

A brain monitoring system comprising:
left electrodes and right electrodes that collect neurovascular measurements from a patient's head during a sleep interval; and
a computing module that:
receives transcranial impedance data derived from the neurovascular measurements collected from the left electrodes and the right electrodes,
applies the transcranial impedance data to a model to determine a characteristic of intracranial perivascular pathways, and
responsive to the characteristic of the intracranial perivascular pathways, performs at least one of: a) displaying the characteristic of the intracranial perivascular pathways on a display, and b) administering a therapeutic intervention.

### Claim 22 (depends on 21)

The brain monitoring system of claim 21, wherein the computing module further receives electroencephalogram data derived from neurophysiological measurements collected by the left electrodes and the right electrodes, and
wherein the model is derived from the electroencephalogram data.

### Claim 23 (depends on 21)

The brain monitoring system of claim 21, wherein the computing module performs the administering of the therapeutic intervention and wherein the therapeutic intervention is a neuromodulation intervention.

### Claim 24 (depends on 23)

The brain monitoring system of claim 23, wherein the computing module modifies an intensity of the neuromodulation intervention.

### Claim 25 (depends on 23)

The brain monitoring system of claim 23, wherein the computing module further determines and displays a measure of an effect of the neuromodulation intervention.

### Claim 26 (depends on 21)

The brain monitoring system of claim 21, further comprising an input device that receives instructions for the therapeutic intervention.

### Claim 27 (depends on 21)

The brain monitoring system of claim 21, further comprising a flexible band, wherein the left electrodes and the right electrodes are coupled to the flexible band.

### Claim 28 (depends on 21)

The brain monitoring system of claim 21, wherein the computing module further determines and displays an effect of a pharmaceutical intervention.

### Claim 29 (depends on 28)

The brain monitoring system of claim 28, wherein the pharmaceutical intervention comprises a dosage of dexmedetomidine.

### Claim 30 (depends on 21)

The brain monitoring system of claim 21, wherein an initial therapeutic intervention is administered to the patient while the neurovascular measurements are collected from the patient's head during the sleep interval.