Johns Hopkins University

Kennedy Krieger Institute, Inc.

The United States of America, as Represented by the Secretary, Department of Health and Human Services

Michael T McMahon

Xiaolei Song

Kannie Wai Yan Chan

Justin Scot Hanes

Martin Gilbert Pomper

Tao Yu

Peter C Van Zijl

Guanshu Liu

Nikita Oskolkov

Xing Yang

Sangeeta Ray

Ming Yang

Assaf A Gilad

Dmitri Artemov

Jeff W M Bulte

Yoshinori Kato

Joel Patrick Schneider

Sridhar Nimmagadda

Jiadi Xu

Wojciech Lesniak

Kannie Wai-Yan Chan

Himatkumar Patel

Kannie M Y Chan

Michael Christopher Giano

Amnon Bar-Shir

The present invention provides novel hydrogels through peptides, which are designed to self-assemble and produce magnetic resonance (MR) contrast through chemical exchange saturation transfer (CEST). The location and integrity of these gels could consequently be tracked using MR imaging. The self-assembly of the peptides into hydrogels can be brought about by a change in pH, ionic strength, temperature, and concentration of ions.

Peptide hydrogels generating chemical exchange saturation transfer MRI contrast and uses thereof

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

PAMAM dendrimer based CEST imaging agents, pharmaceutical compositions comprising the same and methods of uses thereof are disclosed.

PAMAM dendrimer based CEST imaging agents and uses thereof

The invention features a novel non-invasive approach for imaging, detecting and/or sensing metal ions with improved sensitivity and specificity in a biological sample or tissue. In certain embodiments, the invention provides a MR contrast-based approach for imaging, detecting and/or sensing metal ions in the biological sample/tissue containing various background ions by usingF-based chemical exchange saturation transfer (CEST) technique.

Non-invasive sensing of free metal ions using ion chemical exchange saturation transfer

Salicylic acid-based polymeric CEST contrast agents targeting prostate-specific membrane antigen, pharmaceutical composition comprising the same and methods of use thereof are disclosed.

Salicylic acid-based polymeric CEST contrast agents targeting prostate-specific membrane antigen and uses thereof

Surface conjugated diamagnetic Chemical Exchange Saturation Transfer (diaCEST) agent carriers and methods of making and using are described herein. The particles are safe alternatives to conventional paramagnetic or superparamagnetic metal-based MRI contrast agents that are often toxic and therefore not biocompatible. The carriers described herein can provide simultaneous monitoring of multiple particle types labeled with 'multicolor' diaCEST contrast agents. In some embodiments, the carriers are micro- and/or nanoparticles. In other embodiments, the carriers are liposomes. In some embodiments, the particles and/or liposomes are mucus penetrating. In other embodiments, the particles and/or liposomes are not mucus penetrating.

Nanoparticles for magnetic resonance imaging tracking and methods of making and using thereof

Mucus-penetrating liposomal nanoparticles and methods of making and using thereof are described herein. The nanoparticles contain one or more lipids, one or more PEG-conjugated lipids, and optionally one or more additional materials that physically and/or chemically stabilize the particles. The nanoparticle have an average diameter of about 100 nm to about 300 nm, preferably from about 100 nm to about 250 nm, more preferably from about 100 nm to about 200 nm. The particles are mobile in mucus. The liposomes can further contain one or more therapeutic, prophylactic, and/or diagnostic agent to be delivered to a mucosal surface, such as the CV tract, the colon, the nose, the lungs, and/or the eyes. The liposomes can further contain one or more CEST agents to allow real time imaging of the particles in a live animal. The particles may also further contain an imaging agent, such as a fluorescent label.

Lipid-based drug carriers for rapid penetration through mucus linings

A novel approach for CEST MR imaging is called Multi-echo Length and Offset VARied Saturation (Me-LOVARS) CEST. This method allows efficient collection of additional CEST data without penalty in scan time, which could be useful for enhancing the contrast, increasing the specificity or improving quantification of exchange. As CEST-MRI has shown promise at both the pre-clinical and clinical levels, including for detecting and grading brain tumors and evaluating ischemia, using either endogenous CEST contrast or through administration of CEST contrast agents. This fast and robust imaging method is suitable for accelerating image collection and widening the scope of applications for CEST-MRI.

Multi-echo length and offset varied saturation (Me-LOVARS) method for chemical exchange saturation transfer (CEST) MR imaging

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

CEST MR imaging, called Multi-echo Parametric VARiation Saturation (Me-PaVARS) CEST places multiple image readouts in between a series of saturation pulses. The saturation pulse parameters are varied in a designated systematic pattern, which allows the generation of CEST contrast maps by encoding the patterns of signal loss into the images for better discrimination between various CEST imaging agents. The saturation parameter changes include, but are not limited to, saturation amplitude (B), saturation length (t), number of pulses, shape of saturation pulses, amplitude of saturation pulses, saturation offset frequency, or a combination of these variations.

Multi-echo parametric variation saturation (MePaVARS CEST imaging and other MR imaging

Compositions and methods for chemical exchange saturation transfer (CEST) based magnetic resonance imaging (MRI) or frequency labeled exchange (FLEX) imaging are disclosed. Beta-hydroxycarboxylate and beta-aminocarboxylate derivatives including salicylic acid, salicylates, salicylic acid prodrugs, N-alkyl/aryl/acyl/sulfonyl-anthranilic acid analogs, and any aromatic compound with OH/NH group ortho to the carboxylic acid group are disclosed. Such compounds can be used as general MRI organic contrast agents and produce significantly improved contrast in MR images detectable through CEST or FLEX.

Compositions and methods for chemical exchange saturation transfer (CEST) based magnetic resonance imaging (MRI)

An embodiment in accordance with the present invention provides a method for obtaining a magnetic resonance image (MRI) or spectrum. The method includes a step of performing a chemical exchange saturation transfer (CEST) or magnetization transfer (MT) magnetic labeling experiment of a subject using an MRI machine. When performing the CEST or MT magnetic labeling experiment aspects of a saturation pulse or a serial saturation pulse sequence, such as length (t), number (N), offset (&#x394;&#x3c9;), modulation frequency (&#x3c9;) and power (B) can be varied in specific-designed schemes. Data is generated from the CEST magnetic labeling experiment and is transmitted to a data processing unit. The data is processed to generate a visual representation of the data.

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Columbia, MD, United States of America

Michael T McMahon