The Johns Hopkins University

Kennedy Krieger Institute, Inc.

City University of Hong Kong

Peter C Van Zijl

Michael T McMahon

Guanshu Liu

Nirbhay Yadav

Kannie Wai Yan Chan

Jiadi Xu

Yoshinori Kato

Dmitri Artemov

Assaf A Gilad

Qin Qin

Jianpan Huang

Josh Friedman

Joseph S Gillen

Mina Kim

Yang Zhou

Lin Chen

Michael C Mcmahon

Some embodiments provide a method for magnetic resonance imaging of polysaccharide molecules, that includes providing a magnetic field that is sufficiently homogeneous over an imaging volume, generating a spatial encoding in the magnetic field, and acquiring one or more water proton signal intensity measurements at each of multiple voxels within the imaging volume. The signal intensity measurements are acquired at one or more irradiation frequencies at lower parts-per-million (ppm) than a baseline frequency associated with free water protons. The method includes generating, based on the water proton signal intensity measurements in each voxel, a water proton signal intensity map of the relayed Nuclear Overhauser Effect (rNOE) exchange process of aliphatic protons in the polysaccharide molecules to free water protons in the imaging volume, and generating, using a calibration of the water proton signal intensity measurements for the rNOE exchange process, a concentration map of the polysaccharide molecules in the imaging volume.

Magnetic resonance imaging of glycogen and other polysaccharides by magnetic coupling with water

A method of assessing the brain lymphatic or glymphatic system and the glucose transporter function on blood-cerebrospinal fluid barrier (BCSFB) of a subject using D-glucose or a D-glucose analog. A spatial map is generated of water MR signals that are sensitized to changes in D-glucose or a D-glucose analog in cerebrospinal fluid (CSF) of the subject. The spatial map is observed at one or more time points before, one or more time points during, and one or more time points after, raising the blood level of the D-glucose or a D-glucose analog in the subject CSF. A difference is detected between the MR signals of the spatial map before, during, and after raising the blood level of D-glucose or a D-glucose analog. A physiological parameter associated with the brain lymphatic or glymphatic system and the glucose transporter function on BCSFB of the subject is ascertained based on the detected difference.

D-glucose and its analogs as tracers to assess the glucose transporter function on blood-cerebrospinal fluid barrier and the functioning of the brain lymphatic system

A method to detect transient binding of a substrate molecule of interest in solution to a molecular target includes selecting the substrate molecule of interest and the molecular target such that the substrate molecule of interest can transiently bind to the molecular target; placing one of a sample or a subject of interest in a magnetic resonance (MR) apparatus, the sample or the subject of interest containing the substrate molecule of interest so as to be in contact with the molecular target; providing magnetic labelling of non-exchangeable or slowly exchangeable MR sensitive nuclei of the substrate molecule of interest; receiving an MR signal from the MR sensitive nuclei of the solvent molecules using the MR apparatus; and analyzing the MR signal to obtain a quantity associated with the transient binding of the substrate molecule of interest to the molecular target.

Magnetic resonance method for detecting molecular binding with enhanced sensitivity

A method for magnetic resonance (MR) imaging or spectroscopy on a MR scanner to detect tissue physiological parameters in one or more tissue areas in a human or non-human subject includes administering to the subject a contrast enhancing physiologically tolerable amount of a sugar that is non-labeled, subjecting the subject to an MR procedure capable of generating MR signals encoding at least one tissue area in the subject in which the sugar either passes or is taken up, detecting a temporal variation in the MR signals in the at least one tissue area after the administering the sugar, determining at least one tissue-related parameter from the temporal variation, and ascertaining whether the at least one tissue-related parameter is abnormal.

Use of non-labeled sugars and detection by MRI for assessing tissue perfusion and metabolism

The present invention is directed to a system and method for magnetic resonance imaging including an extended Fourier transform-based velocity-selective pulse train design with a pair of refocusing pulses within each velocity encoding step and accompanying phase cycling between different velocity encoding steps. The present invention is robust to B0/B1 field inhomogeneity and eddy current effects. The utility of this technique, through a velocity-selective inversion pulse, is demonstrated in a 2D velocity-selective arterials spin labeling study, which shows a reasonable agreement in CBF quantification with the standard PCASL method.

System and method for velocity selective pulses with arbitrary shape using MRI

An embodiment in accordance with the present invention provides a method of non-invasively detecting and imaging temperature or temperature changes by assessing the temperature induced shifts in the saturation spectrum of water using MRI, namely saturation shift referencing. This procedure includes the MRI procedures to assess water saturation spectrum and the data processing steps to determine the temperature induced shifts of water resonance frequency and consequently to estimate the temperature change. This procedure also includes the procedure of assessing fat saturation spectrum and estimating fat resonance frequency. This method can be used as a clinical procedure for temperature mapping in multiple applications, especially where a significant amount of fat is present. One application is to monitor the temperature of the targeted tumor and its surrounding tissues during the procedure of hyperthermia. Such local hyperthermia can be applied, using high-intensity focus-ultrasound for deep-seated tissues or heating supplies for superficial tissues.

Non-invasive temperature mapping using temperature-responsive water saturation shift referencing (T-WASSR) MRI

An embodiment in accordance with the present invention provides a new MRI method to image the buildup of exchange transfer processes from nuclei in mobile solute molecules in tissue via another molecule (e.g. solvent such as water). The pulse sequence can detect Chemical Exchange Saturation Transfer (CEST), relayed Nuclear Overhauser Enhancement (rNOE) CEST, and selective induced exchange transfer processes. Further, the proposed MRI pulse sequence involves acquiring two or more images with a difference in waiting period (delay) after a radiofrequency excitation, saturation pulse, or series of such pulses. This produces a series of exchange transfer images sensitive to the speed of transfer of changes in magnetization. Subtracting two images or fitting a time series produces maps with minimum interference from direct water saturation and from semi-solid magnetization transfer and other fast exchanging protons.

Magnetic resonance system and method for detecting the buildup of the transfer of changes in magnetization from nuclei in mobile solute molecules in tissue

An embodiment of the current invention provides a method for magnetic resonance (MR) imaging or spectroscopy, comprising: (a) selectively exciting exchangeable solute protons or protons of exchangeable solute-based water molecules within a frequency range in a subject using at least one frequency-selective radio frequency (RF) pulse, wherein the frequency range encompasses characteristic resonance frequencies of the exchangeable solute protons or protons of exchangeable solute-based water molecules, wherein the frequency range is substantially non-overlapping with a characteristic resonance frequency of bulk water protons in the subject, wherein the at least one frequency selective RF pulse performs a substantially minimal excitation on the bulk water protons, and wherein the at least one frequency-selective RF pulse, sometimes in combination with a time period that separates the at least one frequency-selective RF pulse, magnetically labels the exchangeable solute protons or the exchangeable solute-based water molecules; (b) allowing a portion of the magnetically labeled exchangeable solute protons to exchange with the bulk water protons or allowing the magnetically labeled exchangeable solute-based water molecules to exchange with bulk water molecules; (c) repeating (a) and (b) a plurality of times to enhance a population size of the magnetically labeled exchangeable solute protons or the magnetically labeled exchangeable solute-based water molecules; (d) irradiating the subject under observation with a water excitation RF pulse that is adapted to excite the bulk water protons; (e) recording a magnetic resonance (MR) signal from the subject under observation in response to the water excitation RF pulse; and (f) analyzing the recorded MR signal to estimate a quantity associated with the exchangeable solute protons or the exchangeable solute-based water molecules.

Magnetic resonance imaging and spectroscopy of low concentration solutes with exchangeable protons using label transfer modules: frequency transfer, inversion transfer, and dephasing transfer

A water saturation shift referencing (WASSR) technique performed using a magnetic resonance scanner comprises: acquiring a spatial map of Z spectra that encompass the water center frequency using sufficiently low saturation power and sufficiently short duration selected such that symmetry of the Z spectra is not obscured by magnetization transfer but dominated by direct water saturation effects so that the spectrum is substantially symmetric; and performing a symmetry analysis on the substantially symmetric Z spectra to generate a spatial map of the water center frequency. WASSR-corrected chemical exchange saturation transfer (CEST) imaging is disclosed as an illustrative example.

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Baltimore, MD, United States of America

Peter C Van Zijl