# US 11,896,392 B2 · Systems and methods for non-invasive fat composition measurement in an organ

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,896,392 B2
- Document ID: US11896392B2
- Status: Granted
- Kind: B2
- Application number: 17/692,002
- Filed: 2022-03-10
- Published: 2022-09-15
- Granted: 2024-02-13
- Earliest claimed: 2021-03-10
- Assignees: Livivos Inc.
- Applicants: Livivos Inc.
- Inventors: Pablo Jose Prado; Alejandro Bussandri
- Web page: https://patentgrep.com/patent/US11896392B2

## CPC

- A61B 5/4872: {Body fat}
- A61B 5/055: involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
- A61B 5/4244: {liver}
- A61B 5/4869: {Determining body composition}
- G01R 33/3806: {Open magnet assemblies for improved access to the sample, e.g. C-type or U-type magnets}
- G01R 33/4828: {Resolving the MR signals of different chemical species, e.g. water-fat imaging}
- G01R 33/50: based on the determination of relaxation times {, e.g. T1 measurement by IR sequences; T2 measurement by multiple-echo sequences}
- G01R 33/56341: {Diffusion imaging}
- G01R 33/5602: {by filtering or weighting based on different relaxation times within the sample, e.g. T1 weighting using an inversion pulse}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)

## Abstract

Systems and methods are provided for determine the fat composition in an organ of interest using a non-invasive health measurement system. The non-invasive health measurement system may include an open magnet NMR apparatus. The NMR apparatus may measure NMR signals in a sensitive volume of a patient. The sensitive volume may coincide with an organ of interest, such as a liver. Systems and methods disclosed herein may provide for separation of the water contribution and the fat contribution to the measured NMR signal. Diffusion based separation, T2 based separation, and T1 based separation may each serve as different methods for separating the water and fat contributions to the signal. Separating the water and fat contributions to the single may allow for computation of a proton density fat fraction which may reflect the fat composition of the organ of interest.

## Claims

### Claim 1

A non-invasive health measurement system comprising:
an open magnet Nuclear Magnetic Resonance (“NMR”) apparatus to obtain NMR response signals generated by atomic nuclei of substances comprising an organ, the NMR response signals comprising a fat contribution signal and a water contribution signal;
a processor; and
a memory communicably coupled to the processor and storing instructions that, when executed by the processor, cause the processor to:
transmit radio frequency (“RF”) pulses in a presence of a field gradient into the organ with the open magnet NMR apparatus;
obtain the NMR response signals; and
separate contributions of water and fat to the NMR response signals based on a difference in diffusion coefficients of water and fat to determine a water composition and a fat composition of the organ by measuring the NMR response signals' amplitude dependence with diffusion time and determining amplitude and diffusion coefficients of fat and water contributions using the measured amplitude dependence with diffusion time.

### Claim 2 (depends on 1)

The system of claim 1 wherein separating the water and fat signal contributions based on the diffusion coefficients of water and fat further comprises computing a proton density fat fraction (“PDFF”) based on the determined amplitudes.

### Claim 3 (depends on 1)

The system of claim 1 wherein the diffusion coefficient of fat is known and wherein separating the water and fat signal contributions based on the diffusion coefficients of water and fat further comprises computing a PDFF by suppressing water amplitude using a high b-value to compute fat amplitude based on the known diffusion coefficient of fat.

### Claim 4 (depends on 1)

The system of claim 1 wherein the processor is further caused to measure a fat proton relaxation time (T2f).

### Claim 5 (depends on 4)

The system of claim 4 wherein measuring a fat proton relaxation time (T2f) comprises:
performing diffusion encoded NMR measurements at high b-values to suppress the water contribution; and
computing a fat relaxation time (T2f) based on a single exponential fit of the diffusion encoded NMR measurements.

### Claim 6 (depends on 1)

The system of claim 1 wherein measuring the NMR signal amplitude dependence with diffusion time:
performing diffusion encoded NMR measurements at varying b-values;
performing a double exponential fit to the NMR signal at each b-value; and
computing the amplitude of the NMR signal at each b-value based on the double exponential fit.

### Claim 7 (depends on 1)

The system of claim 1 wherein determining the amplitude and diffusion coefficients of fat and water comprises:
performing a double exponential fit to the total measured signal amplitude dependence with diffusion time;
computing the amplitudes of the water and fat contributions based on the double exponential fit; and
computing the diffusion coefficients of water and fat based on the double exponential fit.

### Claim 8 (depends on 1)

The system of claim 1 wherein the organ is a liver.

### Claim 9 (depends on 8)

The system of claim 8 wherein the organ is a liver of a human patient.

### Claim 10 (depends on 8)

The system of claim 8 wherein the NMR apparatus is applied to a human patient while the human patient is lying down.

### Claim 11 (depends on 1)

The system of claim 1 wherein the NMR apparatus is applied to a patient and wherein the NMR apparatus comprises a band to guide positioning of the patient.

### Claim 12 (depends on 11)

The system of claim 11 wherein the band comprises an elastomeric band.

### Claim 13 (depends on 1)

The system of claim 1 wherein accuracy of the NMR signal measurement performed by the NMR apparatus is evaluated by:
applying the NMR apparatus to a patient;
moving the patient laterally relative to a placement of the NMR apparatus;
performing an NMR signal measurement with the NMR apparatus; and
evaluating an amplitude of the signal measurement to determine the accuracy of the patient's position.

### Claim 14

A method for using an open magnet Nuclear Magnetic Resonance (“NMR”) apparatus to obtain NMR response signals generated by atomic nuclei of substances comprising an organ, the NMR response signals comprising a fat contribution signal and a water contribution signal, the method comprising:
transmitting radio frequency (“RF”) pulses in a presence of a field gradient into the organ with the open magnet NMR apparatus;
obtaining the NMR response signals; and
measuring the NMR response signals' amplitude dependence with diffusion time;
determining amplitude and diffusion coefficients of fat and water contributions using the measured amplitude dependence with diffusion time;
computing a proton density fat fraction (“PDFF”) based on the determined amplitudes; and
determining water and fat composition of the organ based on the PDFF.

### Claim 15 (depends on 14)

The method of claim 14, wherein the diffusion coefficient of fat is known and wherein separating water and fat signal contributions based on the diffusion coefficients of water and fat further comprises computing a PDFF by suppressing the water amplitude using a high b-value to compute the fat amplitude based on the known diffusion coefficient of fat.

### Claim 16 (depends on 14)

The method of claim 14, further comprising measuring a fat proton relaxation time (T2f).

### Claim 17 (depends on 16)

The method of claim 16, wherein measuring the fat proton relaxation time (T2f) comprises:
performing diffusion encoded NMR measurements at high b-values to suppress the water contribution; and
computing a fat relaxation time (T2f) based on a single exponential fit of the diffusion encoded NMR measurements.

### Claim 18 (depends on 14)

The method of claim 14, wherein measuring the NMR signal amplitude dependence with diffusion time comprises:
performing diffusion encoded NMR measurements at varying b-values;
performing a double exponential fit to the NMR signal at each b-value; and
computing the amplitude of the NMR signal at each b-value based on the double exponential fit.

### Claim 19 (depends on 14)

The method of claim 14, wherein determining the amplitude and diffusion coefficients of fat and water comprises:
performing a double exponential fit to the total measured signal amplitude dependence with diffusion time;
computing the amplitudes of the water and fat contributions based on the double exponential fit; and
computing the diffusion coefficients of water and fat based on the double exponential fit.

### Claim 20 (depends on 14)

The method of claim 14, wherein accuracy of the NMR signal measurement is evaluated by:
applying the NMR apparatus to a patient;
moving the patient laterally relative to a placement of the NMR apparatus;
performing an NMR signal measurement with the NMR apparatus; and
evaluating an amplitude of the signal measurement to determine the accuracy of the patient's position.