A method for MRH measurement of vascular pathology by assessing blood perfusion

Abstract

A method for use of Magnetic Resonance Histopathology (MRH) to measure blood prefusion as an indicator of vascular pathology. An initial excitation of tissue is accomplished at time T0 and volume suppression (VS) is applied to tissue around a selected region of interest (ROI) creating a nulled region. After a time delay, td, a MRH pulse sequence is applied at a desired wavelength (k-value) to determine signal in the ROI. Signal as blood flows from a non-nulled region into the nulled region including the ROI is then detected.

Description

Attorney Docket No. 1730.12. WOA METHOD FOR MRH MEASUREMENT OF VASCULAR PATHOLOGY BY ASSESSING BLOOD PERFUSIONCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 726,702, filed December 2, 2024, and is co-pending with U.S. Patent Application No. 18 / 914,340, filed October 14, 2024, entitled MAGNETIC RESONANCE HISTOPATHOLOGY AND NEURAL NETWORK CLASSIFICATION FOR CANCER, having a common assignee with the present application, the disclosures of which are incorporated herein by reference.FIELD

[0002] The disclosed methodology relates to use of Magnetic Resonance Histopathology (MRH) to measure blood prefusion as an indicator of vascular pathology.BACKGROUND

[0003] There are many pathologies that result from / result in, pathologic changes in blood perfusion in vessels in the brain or other organs / tissue. There may be blockages in compromised vessels, or ruptures, leading to breakdown, for example, in the blood brain barrier. Heart attack and heart failure, coronary artery disease, stroke, leg and foot ulcers, atherosclerosis, cerebrovascular disease (CVD) and obesity, diabetes, anemia, high blood pressure, tissue necrosis and shock are all mediated by vascular pathology.

[0004] Any condition that limits blood flow can cause reduced perfusion to vital organs and distal extremities. This reduced blood flow often results in tissue death / degradation, leading to organ damage, loss of limb and, if left untreated, patient death. Early detection by vascular screening is essential. Additionally, ability to accurately assess the angiogenic vasculature that forms around tumors would be a huge step towards grading tumors and assessing tumor progression.

[0005] Currently, there are various methods used to assess vascular pathology, though they often are not able to provide sufficiently high resolution information on early changes in vasculature in response to disease. Vascular pathology can be measured through use of exogenous magneticAttorney Docket No. 1730.12. WO resonance (MR) contrast agents, such as Gadolinium (Gd), to highlight the vessels for imaging. Dynamic Contrast-Enhanced MR Perfusion (DCE) relies on injection of a T1 shortening contrast agent. The MR perfusion parameters are then calculated by evaluating the T 1 -shortening induced by the Gadolinium-based contrast agent bolus passing through tissue. A measure is made of how fast the blood vessels fill, and whether they leak or not. This can be inferred from how fast the contrast builds up after intravascular injection of the contrast agent-and how fast the contrast washes out. However, use of a very complex model is needed to obtain flow and feature size / position-mapping parameters from the contrast imaging. And the spatial resolution is insufficient to determine to high accuracy and sensitivity the positioning in the tissue of the compromised vessel flow.

[0006] Alternatively, certain dyes visible with x-ray imaging can be used as contrast for an x-ray angiogram. However, both the use of Gd, and the use of x-rays, result in an invasive measurement.

[0007] Ultrasound imaging looks at moving blood to create a color map of blood vessels, in an indirect measure which requires making several assumptions towards defining a model of the vessel pathology and is generally restricted to larger vessels than the capillaries.

[0008] An MR-based perfusion diagnostic, ASL (Arterial Spin Labelling), is used to measure vasculature, though signal levels are quite low. Rather than injecting an exogenous contrast agent such as Gd, ASL uses magnetically labelled arterial blood water protons as an endogenous tracer to measure perfusion, hence resulting in a non-invasive diagnostic.

[0009] ASL is employed to obtain a magnetically labeled image (tagged image) and a control image, in which the static tissue images are identical but the magnetization of the inflowing blood is different, enabling separating out the signal of interest. The water molecules in the arterial blood are tagged by using a radiofrequency pulse that saturates water protons. Subtraction between the tagged and the control images eliminates the static signals, and the remaining signals are linear measures of the perfusion, which is proportionate to the cerebral blood flow (CBF). ASL signal- to-noise ratio is very low, because the signal from the tagged blood is only 0.5-1.5% of the entire tissue signals. Various signal acquisition methods, such as Echo Planar Imaging, are used to boost this signal, but the problems of low signal and motion artifacts still plague this diagnostic technique.Attorney Docket No. 1730.12. WOSUMMARY

[0010] In a broad example implementation for brain vasculature, the disclosure herein provides a method for use of Magnetic Resonance Histopathology (MRH) to measure blood prefusion as an indicator of vascular pathology. An initial excitation of tissue is accomplished at time TO and volume suppression (VS) is applied to tissue around a selected region of interest (ROI) creating a nulled region. After a time delay, td, a MRH pulse sequence is applied at a desired wavelength (k- value) to determine signal in the ROI. Signal as blood flows from a non-nulled region into the nulled region including the ROI is then detected.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIG. 1A shows an image of normal blood vessel pathology;

[0012] FIG. IB shows an image of tumor blood vessel pathology;

[0013] FIG. 2 is a schematic representation of application of an MRH analysis of blood perfusion in blood vessels in brain tissue as an example;

[0014] FIG. 3 is a representation of a volume suppression (VS) of tissue with a region of interest (ROI) included in the nulled volume;

[0015] FIG. 4 is an example of a VS and MRH pulse sequence for evaluation of blood perfusion into an ROI from vessels outside the nulled volume;

[0016] FIG. 5 shows a representation of the data structure obtained in the MRH pulse sequence.

[0017] FIGS. 6A-6C are schematic illustrations of different configurations of example MR data processing circuits for MRI systems according to embodiments of the present invention.DETAILED DESCRIPTION

[0018] Across disease, the earlier pathology is diagnosed the better the outcome. MRH provides very accurate and sensitive measure of the microarchitecture of tissue, enabling high resolution and sensitive tracking of disease onset and progression. MRH is a quantitative MRI-based measure which can be mapped in two or three dimensions to develop an image of diseased tissue.

[0019] Standard MR Imaging requires acquisition of data across all of k-space, whereas MRH requires acquisition of only a targeted and small set of k-values that can be markers of disease.

[0020] In brief, the ability of MRH to measure tissue microarchitecture to such high resolution arises because, rather than acquire the huge amount of data needed to form an image, MRHAttorney Docket No. 1730.12. WO requires acquisition of only that data needed to accurately assess the tissue features required to diagnose a specific disease / condition. Using MRH, a much smaller set of data than that needed for imaging can provide sensitive diagnosis of vascular pathology. By acquiring quantitative data a few k-values at a time, the MRH data does not have to be acquired coherently, as is required for forming an MR image. Hence, the MRH measurement is motion immune, enabling the very high resolution possible with this diagnostic.

[0021] In addition to being motion immune, the MRH diagnostic is completely non-invasive and extremely fast (under two minutes on top of an already scheduled exam), providing accurate and sensitive assessment of pathology onset and progression.

[0022] MRH focuses on acquisition of only the wavelengths (k-values) that are required to measure the feature sizes in tissue pathology, comparing the set of features typical of normal tissue and that indicative of pathology onset and progression. MRH is akin to crystal diffraction, in that a specific and reduced set of wavelengths can be used to describe the feature structures of interest. MRH noninvasively probes tissue texture at a microscopic resolution surpassing that of traditional image-based magnetic resonance imaging (MRI). Pulse sequencing and operational methods for Magnetic Resonance MicroTexture (MRpT) scanning which provide the basis for MRH are disclosed in U.S. Patent Nos. 10,061,003; 10,215,827; 10,955,503; and 12,136,217, all having a common assignee with the present application, the disclosures of which are incorporated herein by reference. MRH can achieve resolution of approximately 0.05 mm, about a magnitude greater than traditional MRI, by trading off image acquisition for spectral acquisition that aims to measure texture.

[0023] Rather than imaging tissue in two dimensions, MRH uses a one-dimensional signal containing spatial frequency information relating to the tissue texture. In one example implementation, MRH is immune to patient motion by measuring a single spatial frequency (k- value) per excitation or a series of k-encodes by modulating the encode for each refocused echo in a multi echo sequence; encoded spins move with the tissue, ensuring accurately localized measurement provided that the excited region remains within the receiver. Repeated excitations are also used to measure multiple k-values (see for example referenced U.S. Patent No. 10,215,827). While patient motion will occur during this time, spatial coherence is not required, since the goal of MRH is to capture texture rather than a full image. In a second example implementation, explained in greater detail below, MRH may use selective excitation of a firstAttorney Docket No. 1730.12. WO slice within the specimen of interest and a second slice selective refocusing sequence to define a rod followed by application of a gradient along an analysis direction sweeping through a small range of k-values with the receiver bandwidth set narrowly to delineate the length of the volume of interest (VOI) and post processing at various bandwidths to define additional VOIs in the rod along the analysis direction (see for example referenced U.S. Patent No. 10,955,503).

[0024] MRI is a widespread technology, and MRH procedures can be conducted on any MRI scanner. For example, an MRH procedure can be added to an mpMRI scanning, which, in tandem, can produce preliminary diagnostic results and enhance targeting of biopsy locations to minimize unnecessary invasive procedures.

[0025] As discussed with regard to the prior art, the ability to measure vascular structure and blood dynamics sensitively and accurately is currently limited by signal to noise considerations and motion artifacts, which limit the resolution available from the measurement. However, these difficulties can be overcome by using the MRH diagnostic to measure vascular health, due to the high resolution and high sensitivity available from this method.

[0026] MRH can measure blood pathology quickly and non-invasively, and with the added ability to measure the dynamics of in-flow of blood into a microvascular network which is indicative of vascular health. Examples of normal blood vessel and tumor blood vessel pathologies are shown in FIGS. 1A and IB. MRH can selectively target portions of the vascular networkbased on feature size based on selection of appropriate k-values - from capillaries (-100 micron spacing) to networks of larger vessels. MRH provides more information on vascular dynamics than does DCE without the need for Gd-containing contrast agents or x-rays. However, MRH may be enhanced and used with various other scanning techniques, for example, to combine images from other techniques, including x-ray imaging or endogenous contrast, such as spin labelled MRI imaging. Although exogeneous contrast imaging is also not needed, and MRH as described herein may render contrast agents unnecessary, in some embodiments, contrast agents may be used in connection with MRH, such as exogenous magnetic resonance (MR) contrast agents, such as Gadolinium (Gd), or xenon Xe 129 Hyperpolarized gas, to highlight the vessels for imaging.

[0027] The basic method for using MRH to measure blood health is via measurement of the parameters associated with blood perfusion into a specific tissue region of interest. This is the speed of perfusion, which reflects the openness of the microvessel, and the strength of the blood signal which indicates amongst other factors the integrity of the BBB (Blood Brain Barrier).Attorney Docket No. 1730.12. WOMeasurement of these parameters is accomplished by nulling the MR signal in a region of tissue including, the ROI, and then measuring the signal from the excited blood flowing from the tissue that has not been nulled, into a region of interest (ROI).

[0028] For measurement of blood perfusion in tissue of interest, blood flows into the capillaries from larger vessels. To measure pathology, a particular vessel size in the capillaries in the downstream vascular network is chosen. However, signal from everything in the tissue, not just the blood vessels of interest for pathology would typically be received. Separation of the characteristic signal from just those blood vessels is needed, to target diagnosis of a specific pathology.

[0029] A schematic representation of a timeline for blood perfusion measurement using MRH is shown in FIG. 2. In order to highlight just the blood signal for assessment, the signal nulling routines on the MRI scanner are used to null the signal in a VOI or region of interest within the tissue.

[0030] Magnetic resonance “outer volume suppression" (OVS), is a technique used in Magnetic Resonance Imaging (MRI) to eliminate unwanted signal from tissues outside a specific region of interest (ROI). OVS is typically achieved by applying saturation pulses in the form of "saturation bands" around the desired imaging area, which has the effect of suppressing signals from surrounding tissues like fat or muscle, thereby improving image quality and signal-to-noise ratio within the target region.

[0031] Because of nulling, there are no remaining spins to excite all available signal is excited but is dephased, so there is no measurable signal. In non-nulled tissue the spins are in a recovered / steady state so that when an excitation is done, a signal is created. This is the case for the blood flowing in from the tissue regions that were not nulled surrounding the ROI. Therefore, a blood signal excited in tissue outside the nulled region, can be measured as it flows in from the surrounding tissue. As an example, the ROI and the entire half plane containing the ROI can be nulled and used as the starting volume to narrow the measurable inflow to the half plane that was not nulled

[0032] In order to selectively assess pathology in blood vessels with a particular repeating pattern feature size in the present method for use with MRH, all the signal is suppressed from tissue in a larger region such as a halfplane, referred to herein as volume suppression (VS). Then, using MRH the blood signal (which has flowed into the vessels in the voxel during a delay time) is excited andAttorney Docket No. 1730.12. WO measured at specific feature sizes in the ROT positioned at the border of the nulled (suppressed) region. In this way, only selected vessel feature sizes are measured until the nulled signal returns at T1 which is typically greater than a few 100 msec. As seen in FIG. 2, initial excitation of the tissue at time To is accomplished and VS 10 is applied to tissue around the ROI 12. In the example implementation, a nulled half plane 20 (as seen in FIG. 3) is created employing VS using the MRI scanning system in a manner similar to OVS. After a time delay, td, a MRH pulse sequence 14 is applied at a desired wavelength (k-value) to determine signal in the ROI. As previously noted, either a single voxel approach with multiple excitations as disclosed in U.S. Patent No. 10,215,827 or a selectively excited rod with VOIs determined by selected bandwidth as disclosed in U.S. Patent No. 10,955,503, and described in the detailed implementation herein, may be used to analyze the ROI. As blood flows from the upper non-nulled region 22 into the nulled region including the ROI, only the signal created by that blood will be detected. The health of the vasculature can be deduced from the speed of blood inflow. Signal from the blood flowing in from the upper half plane but leaks out of the vessels (hence would not provide a signal for the spatial frequencies of the vessels that it leaked from) indicates integrity of the BBB. Multiple MRH measurements, which may be accomplished in less than 70 msec, may be employed at various wavelengths (k-values) to sample blood flow in vessel network of varying spatial frequency, i.e. providing varying size of repeating pattern features, until the signal in the nulled region recovers at Tl.

[0033] A MRH pulse sequence (timing diagram) is shown in FIG. 4 including the initial VS excitation and time delay, td. RF excitations 50 and 52 with an applied low level gradients 54 and 56 in the Y and E axes create the desired volume suppression followed by crusher gradients 58 and 60. Time delay, td, is shown merely as a break in the pulse sequence. In practice, the time delay employed will be in the range of a few ms to a few 100 ms

[0034] For the MRH measurement, as shown in trace 100, RF pulse 101 is a 90° slice selective RF excitation of a first slab (rod width) with application of a gradient pulse 102 in a first magnetic field gradient defined as the Y axis. A negative gradient pulse 104, rephases the excitation within the defined thickness of the slice or slab. A gradient pulse 106 is imposed on the E axis with a 180° RF refocus pulse 108 to define a slab orthogonal to the first slab and generate first spin echo (SE) 110. Preliminary gradient pulse 102 and negative encoding gradient pulse 104 establish a desired k-encode in the analysis direction orthogonal to the second slab (k-encode & rod height) in theAttorney Docket No. 1730.12. WO implementation shown in the figures. The k-encode may be in any direction desired. A read gradient 114 is imposed in the Z axis simultaneous to the SE. An RF pulse 116 with gradient pulse 118 provides a 180° slice selective refocus to generate multiple echoes 120 with associated read gradient 122. In addition to the identified gradient pulses there are crusher gradients 124 around all slice selective 180° refocusing pulses.

[0035] The resulting structure of the data obtained is shown in FIG. 5. A selectively excited rod 150 with axis along the E axis and k-encode along the Z axis is defined by the 90° slice selective excitation of a first slab to define rod width and 180° slice selective refocus to define rod height and generation of the k-encode along the Z axis by applying the gradient pulse to place the rod in the desired ROI as shown in FIG. 3. Imposing a read gradient along the E axis during recording of the spin echo generates a frequency gradient long the rod and provides a means to assign signals to individual VOIs 151 along the rod (a 20 voxel bandwidth 152 is shown).

[0036] FIGS. 6A-6C are schematic illustrations of different configurations of an MRI imaging system 10 according to embodiments of the present invention. The MRI imaging system 10 comprises an MR scanner 20 with a high-magnetic field magnet 20m and includes a workstation 60. The workstation 60 communicates with an image acquisition, and / or image processing module 10M, or controller, and can contain the software to generate the pulse sequence to operate the MR scanner 20, including MRH pulse sequences, and acquire data, including MRH data, and optionally post-process the acquired data as described herein according to embodiments of the inventive concept. The workstation 60 can include a display 60d. The system 10 can include a circuit 10c with at least one processor for processing the obtained MR and / or MRH data that is / are onboard or remote from the workstation 60 and comprises the module 10M.

[0037] FIG. 6A illustrates that the system 10 can include at least one workstation 60 that has a portal for accessing the circuit 10c and / or module 10M. The circuit 10c may include at least one processor lOp configured to provide the pulse sequences, analyze the raw signal and / or provide quantitative measurements. The module 10M can be held on a remote server 10S accessible via a LAN, WAN or Internet, and may be provided in a cloud-based environment. The workstation 60 can communicate with the MR scanner 20. The MR scanner 20 typically directs the operation of the pulse sequence and image acquisition using an RF coil and at least on transmit / receive switch as is well known to those of skill in the art. The RF coil is not required to be an anatomical RF coil. The workstation 60 can include a display 60d with a GUI (graphic user input) and an accessAttorney Docket No. 1730.12. WO portal 60p. The workstation 60 can access the module 10M via a relatively broadband high-speed connection using, for example, a LAN or may be remote and / or may have lesser bandwidth and / or speed, and for example, may access the data sets via a WAN and / or the Internet. Firewalls may be provided as appropriate for security.

[0038] FIG. 6B illustrates that the module 10M can be partially or totally included in the MR scanner 20 (i.e., a control console or computer) which can communicate with a workstation 60. The module 10M can be integrated into the control cabinet of the MR scanner 20 to use MRH to measure blood perfusion as an indicator of vascular pathology with optional image processing circuitry comprising at least one processor lOp. The workstation 60 can be in the magnet room and / or the control room of an MRI suite or may be remote from the MRI suite.

[0039] FIG. 6C illustrates that the module 10M can be integrated into one or more local or remote workstations 60 that communicates with the MR Scanner 20. Although not shown, parts of the module 10M and any processor(s) lOp, circuit 10c, can be held on both the scanner 20 and one or more workstations 60, which can be remote or local.

[0040] Some, or all, of the module 10M can be held on at least one server 10S that can communicate with one or more MR scanners 20. The at least one server 10S can be provided using cloud computing which includes the provision of computational resources on demand via a computer network. The resources can be embodied as various infrastructure services (e.g., compute, storage, etc.) as well as applications, databases, file services, email, etc. In the traditional model of computing, both data and software are typically fully contained on the user's computer; in cloud computing, the user's computer may contain little software or data (perhaps an operating system and / or web browser) and may serve as little more than a display terminal for processes occurring on a network of external computers. Firewalls and suitable security protocols can be followed to exchange and / or analyze patient data.

[0041] Embodiments of the present inventive concept provides a method that allows measurement of vessel integrity / pathology by nulling the signal from all tissue and blood in a region for analysis and measuring the rate of return of signal from blood flowing into the vessels from outside the nulled region, which is indicative of blood flow. Measurement can be accomplished at successive time points following nulling, tracking the signal level at successive delay times as the new blood flows back into the vessels. Using this flow rate, which is affected by vessel blockages and thinning of the vessel walls which results in vessel leakage, provides anAttorney Docket No. 1730.12. WO indicator of vessel health.

[0042] Additionally, using MRH to measure signal from the returning blood, enables simultaneous measure of vessel perfusion and vessel microstructure to provide a measurement of vascular pathology.

[0043] Use of the MRH diagnostic measurement to measure both blood flow in the vasculature and vessel microarchitecture in the same measurement, enables measurement of blockages and narrowing in the vessels, to enable mapping of vascular pathology across a tissue region of interest. Making this measurement at several positions (size scales) within the vasculature network enables mapping of the vasculature pathology profile across a tissue slab.

[0044] Using MRH to measure blood flow at various positions within the tissue using the described method, enables identification of the position and the severity of vessel blockages and leaks within the vasculature, hence enabling a direct measure of disease severity. Measurement of the development of tissue changes associated with vessel pathology provides a means for developing a grading system for vascular disease and may be used to measure vascular changes associated with CVD (Cerebro Vascular Disease) as well as dementias. CVD is a group of conditions that affect blood flow and blood vessels in the brain, similar to and including vascular dementia. Vascular dementia symptoms vary depending on the part of the brain in which blood flow is impaired and applying the MRH measurement to measuring blood flow changes in vascular dementia can be used to determine the position in the brain of compromised vasculature.

[0045] The method described may be employed for determining vessel pathology in various neurologic conditions, specifically application in measuring vascular damage in vascular dementias, in the white matter damage of traumatic brain injury, in Alzheimer’s disease and in frontotemporal dementia, in cardiovascular pathology and to assess the state of the pathologic vasculature that forms around tumors. This angiogenic vasculature can be identified by its lack of order, the random structure being prone to crossed and blocked vessels that result in major blockage to organized blood flow.

[0046] Application of disclosed herein in applying the bandwidth method of referenced U.S. Patent No. 10,955,503 allows acquisition of data from a reasonably larger volume of tissue and post processing the data to enable assessment of vessel health in separate VOIs.

[0047] Analysis of MRH data by application of Al methods enables comparison of normal vasculature to pathologic vessels to develop calibration of the MRH perfusion measurementAttorney Docket No. 1730.12. WO ability.

[0048] MRH perfusion measurements as described herein may be used to diagnose or characterize any condition that includes features of vasculature changes or pathologies, including blockages in compromised vessels, or ruptures, leading to breakdown, for example, in the blood brain barrier. Examples of conditions that may be diagnosed or characterized according to some embodiments include heart attack and heart failure, coronary artery disease, stroke, leg and foot ulcers, atherosclerosis, cerebrovascular disease (CVD) and obesity, diabetes, anemia, high blood pressure, tissue necrosis and shock. The vasculature pathologies or changes characterized by MRH techniques as described herein may be used to evaluate or diagnose conditions including cancer or other pathologies of the brain, liver, lung, bone tissue, prostate, or other organ tissue. Other conditions that may be evaluated or diagnosed include osteoporosis, neuropathologies, including neurodegenerative disease (e.g., Alzheimer’s disease), liver cirrhosis, cardiovascular disease, including evaluation after Sars-CoV-2 infection.

[0049] Having now described various implementations in detail as required by the patent statutes, those skilled in the art will recognize modifications and substitutions to the specific embodiments disclosed herein. Such modifications are within the scope and intent of the present invention as defined in the following claims.

Claims

Attorney Docket No. 1730.

12. WOCLAIMS:

1. A method for use of Magnetic Resonance Histopathology (MRH) to measure blood prefusion as an indicator of vascular pathology, the method comprising: accomplishing an initial excitation of tissue at time TO and applying volume suppression (VS) to tissue around a selected region of interest (ROI) creating a nulled region; after a time delay, td, applying a MRH pulse sequence at a desired wavelength (k-value) to determine signal in the ROI; and detecting signal as blood flows from a non-nulled region into the nulled region including the ROI.

2. The method of claim 1, wherein the step of applying VS comprises employing VS using an MRI scanner to create a nulled lower half plane containing the ROI and the non-nulled region comprises the upper half plane.

3. The method of claim 1, further comprising applying additional MRH pulse sequences at varying wavelengths to determine signal in the ROI to sample blood flow in vessels of varying size of repeating pattern features until signal in the nulled region recovers at Tl.

4. The method of claim 1, wherein applying VS comprises: applying RF excitations with applied gradients in Y and S axes to create a desired volume suppression followed by crusher gradients.

5. The method of claim 4, wherein applying an MRH pulse sequence comprises: applying a first RF pulse as a 90° slice selective RF excitation of a first slab with application of a first gradient pulse in a first magnetic field gradient defined as a Y axis; rephasing the excitation within a defined thickness of the first slab with a negative gradient pulse, the first gradient pulse and negative gradient pulse also establishing a desired k- encode in an analysis direction; imposing a gradient pulse on a H axis with a 180° RF refocus pulse to define a second slab orthogonal to the first slab and generate first spin echo (SE);Attorney Docket No. 1730.

12. WO imposing a read gradient in a Z axis simultaneous to the SE; and imposing an RF pulse with a third gradient pulse to provide a 180° slice selective refocus to generate multiple echoes with an associated read gradient.

6. The method of claim 1, further comprising evaluating tissue in the region of interest (ROI), wherein the tissue in the region of interest includes cardiac, liver, brain, prostate, and bone tissue.

7. The method of claim 1, further comprising evaluating the region of interest (ROI) to characterize a condition including osteoporosis, neuropathologies, including neurodegenerative disease including Alzheimer’s disease, liver cirrhosis, cardiovascular disease, and evaluation after Sars-CoV-2 infection.

8. A magnetic resonance (MR) system for acquiring Magnetic Resonance Histopathology (MRH) data to measure blood prefusion as an indicator of vascular pathology, the system comprising: a magnetic resonance imaging (MRI) scanner; a controller in communication with the magnetic resonance imaging (MRI) scanner, the controller configured to accomplish an initial excitation of tissue at time TO and to apply volume suppression (VS) to tissue around a selected region of interest (ROI) creating a nulled region, wherein the controller is further configured to after a time delay, td, apply a MRH pulse sequence at a desired wavelength (k-value) to determine signal in the ROI and detect signal as blood flows from a non-nulled region into the nulled region including the ROI.

9. The MR system of claim 8, wherein the controller is configured to apply VS by employing VS using the MRI scanner to create a nulled lower half plane containing the ROI and the non-nulled region comprises the upper half plane.

10. The MR system of claim 8, wherein the controller is configured to apply additional MRH pulse sequences at varying wavelengths to determine signal in the ROI toAttorney Docket No. 1730.

12. WO sample blood flow in vessels of varying size of repeating pattern features until signal in the nulled region recovers at Tl.

11. The MR system of claim 8, wherein the controller is configured to apply VS by applying RF excitations with applied gradients in Y and 3 axes to create a desired volume suppression followed by crusher gradients.

12. The MR system of claim 11, wherein the controller is configured to apply an MRH pulse sequence by controlling the MRI scanner to: apply a first RF pulse as a 90° slice selective RF excitation of a first slab with application of a first gradient pulse in a first magnetic field gradient defined as a Y axis; rephase the excitation within a defined thickness of the first slab with a negative gradient pulse, the first gradient pulse and negative gradient pulse also establishing a desired k-encode in an analysis direction; impose a gradient pulse on a 3 axis with a 180° RF refocus pulse to define a second slab orthogonal to the first slab and generate first spin echo (SE); impose a read gradient in a Z axis simultaneous to the SE; and impose an RF pulse with a third gradient pulse to provide a 180° slice selective refocus to generate multiple echoes with an associated read gradient.

13. The MR system of claim 8, wherein the signal detected by the controller is analyzed by a processor to evaluate tissue in the region of interest (ROI), wherein the tissue in the region of interest includes cardiac, liver, brain, prostate, and bone tissue.

14. The MR system of claim 8, wherein the signal detected by the controller is analyzed by a processor to evaluate the region of interest (ROI) to characterize a condition including osteoporosis, neuropathologies, including neurodegenerative disease including Alzheimer’s disease, liver cirrhosis, cardiovascular disease, and evaluation after Sars-CoV-2 infection.

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