# US 11,442,127 B2 · System and method for dynamic multiple contrast enhanced, magnetic resonance fingerprinting (DMCE-MRF)

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- Number: US 11,442,127 B2
- Document ID: US11442127B2
- Status: Granted
- Kind: B2
- Application number: 16/603,335
- Filed: 2018-04-06
- Published: 2020-02-06
- Granted: 2022-09-13
- Earliest claimed: 2017-04-07
- Assignees: Case Western Reserve University
- Applicants: Case Western Reserve University
- Inventors: Chris Flask; Christian Anderson; Xin Yu; Nicole Steinmetz; Mark A. Griswold; Susann Brady-Kalnay
- Web page: https://patentgrep.com/patent/US11442127B2

## CPC

- G01R 33/50: based on the determination of relaxation times {, e.g. T1 measurement by IR sequences; T2 measurement by multiple-echo sequences}
- A61B 5/055: involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
- A61K 49/101: {the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals}
- G01R 33/4828: {Resolving the MR signals of different chemical species, e.g. water-fat imaging}
- G01R 33/5601: {involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent}
- G01R 33/5602: {by filtering or weighting based on different relaxation times within the sample, e.g. T1 weighting using an inversion pulse}
- G01R 33/5608: {Data processing and visualization specially adapted for MR, e.g. for feature analysis and pattern recognition on the basis of measured MR data, segmentation of measured MR data, edge contour detection on the basis of measured MR data, for enhancing measured MR data in terms of signal-to-noise ratio by means of noise filtering or apodization, for enhancing measured MR data in terms of resolution by means for deblurring, windowing, zero filling, or generation of gray-scaled images, colour-coded images or images displaying vectors instead of pixels (image data processing or generation, in general G06T)}
- G01R 33/5635: {Angiography, e.g. contrast-enhanced angiography [CE-MRA] or time-of-flight angiography [TOF-MRA]}
- G06T 7/0016: {involving temporal comparison}
- A61B 5/113: occurring during breathing
- A61B 5/7207: {of noise induced by motion artifacts}
- A61B 5/7289: {Retrospective gating, i.e. associating measured signals or images with a physiological event after the actual measurement or image acquisition, e.g. by simultaneously recording an additional physiological signal during the measurement or image acquisition}
- G06T 2207/10096: Dynamic contrast-enhanced magnetic resonance imaging [DCE-MRI]
- G06T 2207/30016: Brain
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL

## Abstract

The present disclosure provides a method of DDCE-MRF. The method can include: a) introducing two or more contrast agents to a region of interest (ROI) of a subject, the two or more contrast agents having different relaxivities; b) measuring a T1 relaxation time and a T2 relaxation time for locations within the ROI using magnetic resonance fingerprinting (MRF); c) determining, using equations that relate the different relaxivities, the T1 relaxation time, the T2 relaxation time, and concentrations of the two or more contrast agents, the concentrations of the two or more contrast agents for each of the locations within the ROI; and d) producing an image depicting the ROI based, at least in part, on the concentrations of the two or more contrast agents.

## Claims

### Claim 1

A method of dynamic, contrast-enhanced, magnetic resonance fingerprinting (MRF), the method including steps comprising:
a) acquiring, with a magnetic resonance imaging (MRI) system using a series of variable sequence blocks that cause one or more resonance species in a region of interest (ROI) of a subject having received a dose of two or more contrast agents having at least two different relaxivities to simultaneously produce individual magnetic resonance signals, the simultaneously produced individual magnetic resonance signals as MRF signal evolutions;
b) comparing, using a computer system, the acquired MRF signal evolutions to a dictionary of signal evolutions to determine quantitative values for two or more parameters of the one or more resonant species based, at least in part, on matching the acquired MRF signal evolutions to a set of known signal evolutions stored in the dictionary, wherein the two or more parameters include at least a T1 relaxation time and a T2 relaxation time;
c) determining, using the computer system and a computer model that relates the different relaxivities, the T1 relaxation time, the T2 relaxation time, and concentrations of the two or more contrast agents, the concentrations of the two or more contrast agents;
d) producing an image depicting the ROI, at least in part, based on the concentrations of the two or more contrast agents; and
wherein the computer model includes the form:
1/T1=1/T10+r1A×[A]+r1B×[B] and 1/T2=1/T20+r2A×[A]+r2B×[B];
wherein T10 is a pre-contrast T1 relaxation value of tissue in the ROI, T20 is a pre-contrast T2 relaxation value of tissue in the ROI; T1 is a post-contrast T1 relaxation value of tissue in the ROI, T2 is a post-contrast T2 relaxation value; [A] is a concentration of a first of the two or more contrast agents; r1A is an r1 relaxivity of first of the two or more contrast agents; r2A is an r2 relaxivity of first of the two or more contrast agents; [B] is a concentration of a second of the two or more contrast agents; r1B is an r1 relaxivity of second of the two or more contrast agents; and r2B is a r2 relaxivity of second of the two or more contrast agents.

### Claim 2 (depends on 1)

The method of claim 1 wherein the image indicates contrast attributable to two different tissue compartments in the ROI or two different molecular targets in the subject.

### Claim 3 (depends on 1)

The method of claim 1 wherein step a) includes performing a fast imaging with steady-state free precession (FISP) acquisition kernel.

### Claim 4 (depends on 3)

The method of claim 3 wherein performing the FISP acquisition kernel includes sampling k-space using spiral trajectories.

### Claim 5

A system comprising:
a magnet system configured to generate a polarizing magnetic field about at least a portion of a subject;
a magnetic gradient system including a plurality of magnetic gradient coils configured to apply at least one magnetic gradient field to the polarizing magnetic field;
a radio frequency (RF) system configured to apply an RF field to the subject and to receive magnetic resonance signals from the subject using a coil array;
a computer system programmed to:
control the magnetic gradient system and the RF system to perform a series of variable sequence blocks that cause one or more resonance species in a region of interest (ROI) of a subject having received a dose of two or more contrast agents having at least two different relaxivities to simultaneously produce individual magnetic resonance signals to acquire the simultaneously produced individual magnetic resonance signals as MRF signal evolutions;
compare the acquired MRF signal evolutions to a dictionary of signal evolutions to determine quantitative values for two or more parameters of the one or more resonant species based, at least in part, on matching the acquired MRF signal evolutions to a set of known signal evolutions stored in the dictionary, wherein the two or more parameters include at least a T1 relaxation time and a T2 relaxation time;
determine, using a model that relates the different relaxivities, the T1 relaxation time, the T2 relaxation time, and concentrations of the two or more contrast agents, the concentrations of the two or more contrast agents;
a display configured to display at least one image of the ROI showing the concentrations of the two or more contrast agents; and
wherein the computer model includes the form:
1/T1=1/T10+r1A×[A]+r1B×[B] and 1/T2=1/T20+r2A×[A]+r2B×[B];
wherein T10 is a pre-contrast T1 relaxation value of tissue in the ROI, T20 is a pre-contrast T2 relaxation value of tissue in the ROI; T1 is a post-contrast T1 relaxation value of tissue in the ROI, T2 is a post-contrast T2 relaxation value; [A] is a concentration of a first of the two or more contrast agents; r1A is an r1 relaxivity of first of the two or more contrast agents; r2A is an r2 relaxivity of first of the two or more contrast agents; [B] is a concentration of a second of the two or more contrast agents; r1B is an r1 relaxivity of second of the two or more contrast agents; and r2B is a r2 relaxivity of second of the two or more contrast agents.

### Claim 6 (depends on 5)

The system of claim 5 wherein the at least one image is generated by the computer system to indicate contrast attributable to two different tissue compartments in the ROI or two different molecular targets in the subject.

### Claim 7 (depends on 5)

The system of claim 5 wherein the computer system is further configured to perform a fast imaging with steady-state free precession (FISP) acquisition kernel to acquire the signal evolutions.

### Claim 8 (depends on 7)

The system of claim 7 wherein performing the FISP acquisition kernel includes sampling k-space using spiral trajectories.