University of Pennsylvania

Sidra Medicine

Ravinder Reddy

Hari Hariharan

Ari Borthakur

Ravi Prakash Reddy Nanga

Sridhar R Charagundla

Mohammad Haris

Anup Singh

Kejia Cai

Walter R T Witschey

Feliks Kogan

Puneet Bagga

Catherine DeBrosse

John S Leigh

Mitchell D Schnall

James E Baumgardner

Walter Witschey

Mark A Elliott

Mark Elliot

Jyothsna Charagundla, Legal Representative

Andrew J Wheaton

Erik M Shapiro

B Murat Eyuboglu

Dharmesh R Tailor

Francesco M Marincola

The present disclosure relates to magnetic resonance imaging (MRI) methods comprising (i) obtaining a baseline chemical exchange saturation transfer (CEST) MRI image of a patient, (ii) administering an effective amount of a non-nutritive sweetener to the patient, and (iii) obtaining one or more test CEST MRI image of the patient subsequent to the administering step (ii); wherein the step (i) and (iii) acquisition parameters are substantially the same. The non-nutritive sweetener may include a natural or artificial sugar alcohol, polyol, or combinations or derivatives thereof.

Non-nutritive sweeteners and polyols as imaging agents

A magnetic resonance pulse sequence technique may acquire a water reference spectrum and two water suppressed metabolite spectra and with frequency selective inversion pulse centered at either single frequency, at multiple frequencies, or in a single acquisition. Subtraction of the inverted from non-inverted water suppressed metabolite spectrum results in single or a combination of specific metabolite peak/peaks alone with a flat baseline for easier quantification.

Quantification of in vivo metabolite

CEST imaging technique and MR scanning are used as an MRI method for detecting levels of lactate in vivo by exploiting the exchange of &#x2014;OH protons on lactate with bulk water. In accordance with this method, one first obtains a lactate CEST MRI map of a slice of the body of a patient. A contrast agent such as pyruvate, glucose or glutamine is administered and a post-administration CEST MRI map is obtained. The difference in the spatial maps indicates the level of expression of lactate in the tissue of interest.

Chemical exchange saturation transfer (CEST) imaging of lactate (LATEST)

A non-invasive imaging approach using CEST and MRS may be used to monitor the cleavage of the poly-L-glutamate (PLG) backbone. The cleavage of PLG by cathespsin B can expose exchangeable &#x2014;NH2 protons in the PLG that are then monitored non-invasively through CEST. The technique can provide direct information on malignant tissue and tumor aggressiveness, and can also be used to monitor treatment.

Magnetic resonance imaging of poly-L-glutamate

An endogenous source of magnetic resonance image contrast of biological tissues is provided by modeling a conventional magnetization transfer (CMT) spectrum using z-spectral data and generating magnetization transfer ratio maps from the magnetization transfer spectrum at a frequency of interest. A contribution by the CMT spectrum from the z-spectral data is removed and a direct water saturation component is modeled using the z-spectral data with removed CMT spectrum (z-spectral). When this modeled direct water saturation component contribution is removed from the z-spectral, then the remaining z-spectra reflects new contrast due to chemical exchange saturation transfer (CEST) and magnetization transfer/exchange effect from aliphatic protons probably associated with labile proteins, peptides and lipids, named as novel magnetization transfer (NMT). This technique can be used to illustrate subtle changes in biological tissue as a result of diseases states, provide better visibility of brain white matter plaques, provide improved CEST contrast, provide better visualization of proteins, peptides, and lipids in biological tissue using NMT contrast, improve segmentation of white matter and gray matter in brain images, and the like.

Endogenous magnetization contrast in MRI

CEST imaging technique and MR scanning are used as an MRI method for measuring glutaminase mediated tumors. The method takes advantage of the fact that glutamine does not exhibit a significant Chemical Exchange Saturation Transfer (CEST) effect while glutamate does. In accordance with this method, one first obtains a glutamate CEST MRI map of the area of a tumor. L-glutamine (nontoxic up to several millimolar level) or glutaminase blocker is then injected and a post injection Glutamate CEST map is obtained. The difference in the spatial maps indicates the level of expression of glutaminase in the tumor.

CEST MRI methods for imaging glutaminolysis in cancer

The CEST effect for various neurotransmitters and energy metabolites in the brain and muscles and various endogenous metabolites in the liver, brain, and myocardium are imaged using MR imaging to illustrate a unique CEST effect that may be used to monitor the concentration of the metabolite and hence to characterize and monitor various disease states in the body correlated to the concentration of that metabolite. By adjusting the timing, amplitude, and length of the RF pulse as well as other parameters of the CEST pulse sequence to address the unique chemical shifts and exchange rates of the target, new targets with unique characteristics may be acquired using CEST MR imaging.

CEST MRI methods for imaging of metabolites and the use of same as biomarkers

Prior approaches have deliveredOto a subject by inhalation, but the relationship between local signal changes and metabolism has been complicated by HO created in non-cerebral tissues. During a brief pulse ofOinhalation, this arterial input function for HO is negligible due to convective transport delays. Additional delays in the arterial input function due to restricted diffusion of water makes pulsed inhalation ofOeven more effective. Accordingly, ventilator system are provided to deliverOas a brief pulse to a subject. Subsequent MR imaging demonstrates delayed appearance of HO in the cerebral ventricles, suggesting that the arterial input function of HO is delayed by restricted water diffusion in addition to convective transit delays. Delivery as a brief pulse therefore offers significant advantages in relating MR signal changes directly to metabolism.

[object Object]

Methods of, and systems for, magnetic resonance imaging of diagnostic mapping of tissues, where sodium mapping is performed individually, as well as in combination with other images of tissue, such as T1&#x3c1;, T2, and/or T1-weighted images. In one method embodiment, a sodium image of the tissue is acquired during the same scanning session. Maps are constructed of each of the first and sodium images individually, and in combination, and further facilitate viewing in combination with each other as a single, blended image of the tissue. Maps of the images may be displayed individually or in combination with each other.

Magnetic resonance imaging for diagnostic mapping of tissues

A spin locked balanced steady-state free precession (slSSFP) pulse sequence combines a balanced gradient echo acquisition with an off-resonance spin lock pulse for fast MRI. The transient and steady-state magnetization trajectory is solved numerically using the Bloch equations and is shown to be similar to balanced steady-state free precession (bSSFP) for a range of T2/T1 and flip angles, although the slSSFP steady-state could be maintained with considerably lower RF power. In both simulations and brain scans performed at 7T, slSSFP is shown to exhibit similar contrast and SNR efficiency to bSSFP, but with significantly lower power.

Spin locked balanced steady-state free precession (slSSFP) with off-resonance spin locked pulses interleaved with imaging gradients

Provided are methods and systems for rapid MRI imaging-scanning that provides 2D or 3D coverage, high precision, and high-temporal efficiency, without exceeding SAR limits. In one embodiment, a pulse sequence process is performed that includes a Tpreparation period, followed by a very rapid image acquisition process, which acquires multiple lines of k-space data. The combination of Tpreparation and acquisition of multiple lines of k-space, allows scan times to be shortened by as much as 3- or 4-fold or more, over conventional MRI scanning methods.

Reducing imaging-scan times for MRI systems

Methods of, and systems for, simultaneously compensating for external-magnetic-field inhomogeneity as well as radiofrequency magnetic-field inhomogeneity in an MRI system. In one method embodiment, a pulse sequence is applied when the transmitter-reference frequency is delivered on resonance. The pulse sequence includes radiofrequency pulses which may be applied at arbitrary-excitation-flip angles that are not necessarily 90&#xb0; degrees. The pulse sequence also includes spin-locking pulses applied in concert with a refocusing-composite pulse. In another method embodiment, a pulse sequence is applied when the transmitter-reference frequency is delivered off resonance. This off-resonance-pulse sequence includes radiofrequency pulses which may be applied at arbitrary-excitation-flip angles that are not necessarily 90&#xb0; degrees. Sandwiched between the excitation-flip angles are at least two off-resonance-spin-lock pulses applied at an inverse phase and frequency from each other.

System and method for minimizing MRI-imaging artifacts

Provided is a T-weighted pulse sequence with reduced specific absorption rate for magnetic resonance imaging (MRI). Also provided is a method of reducing the specific absorption rate in T-weighted MRI.

Provided are pulse imaging sequences and methods for 2D multi-slice T -weighted and 3D T -weighted magnetic resonance imaging (MRI). Further provided is a self-compensating spin-locking sequence for correcting and reducing artifacts in T -weighted imaging. Also provided is a sequence combining 3D T -weighted MRI with a self-compensating spin-locking pulse for facilitating T -weighted imaging with surface coils.

Pulse imaging sequences and methods for T1p-weighted MRI

A magnetic resonance-electrical impedance tomography (MREIT) technique for determining the local conductivity of an object. The MREIT technique combines magnetic resonance current density imaging (MRCDI) with electrical impedance tomography (EIT) in order to obtain the benefits of both procedures. The MREIT technique includes the step of current density imaging by performing the steps of placing a series of electrodes around the patient or object to be imaged for the application of current, placing the patient or object in a strong magnetic field, and applying an MR imaging sequence which is synchronized with the application of current through the electrodes. Next, the electric potentials of the surface of the object or patient are measured simultaneously with the MR imaging sequence, as in EIT. Then, the MR imaging signal containing information about the current and the measured potential are processed to calculate the internal conductivity (impedance) of the object or patient.

Growing community of inventors

Gladwyne, PA, United States of America

Ravinder Reddy