Quantitative magnetic resonance imaging of the vasculature
Inventors
GHARAGOUZLOO, Codi • Sridhar, Srinivas
Assignees
Northeastern University Boston
Publication Number
US-12121339-B2
Publication Date
2024-10-22
Expiration Date
2036-06-09
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Abstract
A quantitative, ultrashort time to echo, contrast-enhanced magnetic resonance imaging technique is provided. The technique can be used to accurately measure contrast agent concentration in the blood, to provide clear, high-definition angiograms, and to measure absolute quantities of cerebral blood volume on a voxel-by-voxel basis.
Core Innovation
The invention provides a quantitative, ultrashort time to echo, contrast-enhanced magnetic resonance imaging (MRI) technique. This approach utilizes ultrashort time to echo (UTE) pulse sequences to acquire T1-weighted images that are minimally affected by susceptibility artifacts, flow effects, and dephasing, thereby enabling accurate measurement of contrast agent concentration in the blood. The method generates clear, high-definition angiograms and can measure absolute quantities of cerebral blood volume (CBV) on a voxel-by-voxel basis using paramagnetic or superparamagnetic contrast agents, such as iron oxide nanoparticles or gadolinium compounds.
The problem addressed by the invention is the lack of effective MRI techniques capable of absolute and quantitative measurement of blood volume fractions and contrast agent concentrations, especially in scenarios where conventional methods suffer from flow-related artifacts, partial volume errors, field inhomogeneities, and limitations due to the toxicity and rapid clearance of commonly used gadolinium-based contrast agents. Prior art methods are predominantly semi-quantitative and are hindered by nonlinear signal changes, motion artifacts, and the necessity for complex modeling or multiple image subtractions.
In contrast, this invention introduces a method and system that apply a radio frequency pulse sequence with a repetition time (TR) less than about 10 ms and a flip angle from about 10° to 30°, acquiring T1-weighted signals at an ultra-short time to echo (TE) less than about 300 μs. This enables the generation of images where blood pool contrast is positive and quantifiable, with signal intensities directly indicative of both contrast agent concentration and blood volume fraction within each voxel. The method is applicable to various organs and tissues and is suitable for both clinical and research MRI devices.
Claims Coverage
The patent contains two primary independent claim families covering the method for quantitative MRI of blood volume and a system implementing this method. There are multiple inventive features described.
Quantitative measurement of absolute blood volume using ultrashort time to echo (UTE) MRI
A method for positive-contrast magnetic resonance imaging of a subject by: - Acquiring pre-contrast and post-contrast images of a region of interest, with image acquisition parameters including: - Repetition time (TR) less than 10 ms - Time to echo (TE) less than 300 μs - Applying magnetic fields and radiofrequency pulse sequences to excite protons and measure response signals during proton relaxation at the specified TE from the region of interest - Determining image values for voxels in three dimensions for both pre-contrast and post-contrast images - Introducing a paramagnetic or superparamagnetic blood pool contrast agent into vasculature of the region of interest - Calculating a doped-blood fraction (the fraction of blood containing contrast agent) for each subregion based on first (pre-contrast) and second (post-contrast) image values - Determining blood quantity values that represent absolute blood volume in the region of interest based on the calculated doped-blood fraction
Determination of contrast agent concentration using a spoiled gradient echo equation
The method further comprises determining the concentration of the contrast agent on a per subregion basis by: - Using corresponding first and second image values for each subregion - Applying a spoiled gradient echo (SPGR) equation to relate intensity values to image parameters (TE, TR, flip angle θ), longitudinal and transverse relaxation times (T1, T2*), a calibration constant dependent on the MRI device's coil, and proton density of the region - Calculating concentration as a function of these parameters, allowing for direct and quantitative determination of contrast agent presence
Rapid acquisition parameters and imaging conditions enabling quantitative MRI
Setting acquisition parameters including: - Time to echo (TE) from 10 μs to 300 μs - Repetition time (TR) from 2 to 10 ms - Flip angle from 10° to 30° - Optionally acquiring signals along radial trajectories in k-space - Optionally determining contrast to noise ratios, and ensuring acquisition before significant dephasing or T2 decay occurs - Static magnetic field strength ranging from 0.2 T to 14.0 T
System for MRI-based quantitative blood volume measurement
A system comprising: - A magnetic resonance imaging device operative to generate signals for forming an image of the region of interest - One or more processors and memory storing computer-executable instructions to: - Operate the MRI device with the specified UTE pulse sequence (TR < 10 ms, TE < 300 μs) - Determine three-dimensional image values for voxels - Calculate a doped-blood fraction based on image values (pre- and post-contrast) - Determine absolute blood volume in various subregions based on the doped-blood fraction - The system can determine blood quantity values that are independent of vessel orientation and not perturbed by magnetic susceptibility
In summary, the claims cover methods and systems for quantifying absolute blood volume in tissues using UTE MRI with rapid acquisition parameters, including precise calculation of contrast agent concentration via a spoiled gradient echo model and specialized imaging protocols. Both the quantitative measurement process and the implementing system are distinctly protected.
Stated Advantages
Enables accurate, absolute quantitative measurement of blood volume and contrast agent concentration in the vasculature on a voxel-by-voxel basis.
Produces clear, high-definition angiograms with high contrast-to-noise and signal-to-noise ratios.
Minimizes susceptibility artifacts, flow-related artifacts, dephasing, and partial volume effects compared to prior art MRI techniques.
Signals are insensitive to flow direction, vessel orientation, and magnetic susceptibility, enabling measurement independent of these variables.
Reduces or avoids toxicity concerns associated with gadolinium-based contrast agents when superparamagnetic iron oxide nanoparticles are used.
Allows non-invasive, in vivo, and longitudinal measurement of blood pool contrast agent concentration with high precision.
Supports functional imaging of tissue health, disease diagnosis, and assessment of disease progression due to its quantitative nature.
Documented Applications
Accurate measurement of blood volume and contrast agent concentration in the vasculature.
Generation of high-definition angiograms for vascular imaging of organs such as the brain, kidney, lung, heart, liver, pancreas, and tumors.
Quantitative measurement of cerebral blood volume in research and clinical neuroscience, including creation of blood volume atlases.
Functional imaging of brain tissue to assess health, detect disease progression, and provide quantitative information on regional neuropathy.
Diagnosis of diseases or conditions such as neurodegenerative disease, neuropathy, dementia, Alzheimer's disease, cancer, kidney disease, lung disease, heart disease, liver disease, ischemia, abnormal vasculature, hypo-vascularization, hyper-vascularization, and nanoparticle accumulation in tumors.
Imaging and quantification of nanoparticle (e.g., SPION) accumulation in tumors, including assessment of enhanced permeability and retention (EPR) effects.
Longitudinal in vivo measurement of contrast agent pharmacokinetics, including blood half-life, in animal models or clinical subjects.
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