CAI²R Researchers Devise Method for Enhancing CEST MRI

CAI²R researcher Ravinder Regatte along with other NYU colleagues have created a novel way to enhance MRI by reducing interference from large macromolecules that can often obscure images generated by current chemical exchange saturation transfer (CEST) methods.

Their work, which appears in the Nature publishing group journal Scientific Reports, has the potential to improve MRI for cartilage as well as for brain tissue.

"We have found a way to eliminate signals of certain molecules and thereby clean up the image of parts of the body that could be used by medical professionals in order to make diagnoses," explained Alexej Jerschow, a professor in NYU's Department of Chemistry.

The study's authors were: Ravinder Regatte, professor, Departments of Radiology and Orthopedic Surgery, NYU Langone Medical Center; Prodromos Parasoglou, a post-doctoral research fellow, and Ding Xia, an assistant research scientist, at the Center for Biomedical Imaging, Department of Radiology at NYU Langone Medical Center; and Jae-Seung Lee, an NIH research fellow, who holds appointments in NYU's Department of Chemistry and NYU Langone Medical Center.

The researchers' work aims to improve a decade-old method, chemical exchange, which has been used to enhance MRI techniques. Under this approach, scientists exploit the movement of atoms from their natural molecular structure to water in the body in order to enhance their visibility.

However, these efforts have often been hindered by the presence of macromolecules, which continue to obscure the smaller molecules that are of interest to doctors and other health-care professionals in making assessments. The macromolecules' interference is the result of two phenomena: their size and their frequencies.

Neutralizing the macro-molecular frequency interference was the focus of the NYU method reported in Scientific Reports recently.

Previously, Jerschow, Regatte, and colleagues created a non-invasive imaging technique for glycosaminogycans (GAGs), which are molecules that serve as the building blocks of cartilage and are involved in numerous vital functions in the human body. Here, under chemical exchange, they separated out the GAG protons from those of water, creating an inherent contrast agent. Testing the idea in tissue samples, the researchers found that the available GAG protons provided an effective type of contrast enhancement, allowing them to readily monitor GAGs through a clinical MRI scanner.

In the Scientific Reports work, the researchers again focused on improving visibility of GAGs through MRI. But, in this effort, they sought to block the signaling impact of the macromolecules that obscure the observation of GAGs.

To do so, they took advantage of macromolecules' broad frequency spectrum—a trait that allows for easy detection and neutralization. Specifically, the researchers could, in effect, "bleach" the signal out by simultaneously using multiple irradiation frequencies. As a result, macromolecular interference diminished and enhanced the quantitative assessment of GAGs.

"This method gives us the opportunity to correct existing CEST methods by focusing on molecular signals of interest with much better precision than currently exists," explains Regatte.

The research was supported by grants from the National Institutes of Health (grants K25AR060269, R21AR055724, R01AR053133, R01AR056260, and R01AR060238) and the National Science Foundation (grant CHE0957586).

 

Abstract

The development of chemical exchange saturation transfer (CEST) has led to the establishment of new contrast mechanisms in magnetic resonance imaging, which serve as enablers for advanced molecular imaging strategies. Macromolecules in tissues and organs often give rise to broad and asymmetric exchange effects, called magnetization transfer (MT) effects, which can mask the CEST contrast of interest. We show here that the saturation of these macromolecular pools simultaneously at two distinct frequencies can level out the asymmetric MT effects, thus allowing one to isolate the CEST effects in vivo. For the first time, clean CEST contrast for glycosaminoglycans (gagCEST) in cartilage in the human knee joint is presented. In addition, the method allows one to clearly demarcate glycosaminoglycan measurements from cartilage and synovial fluid regions. This uniform-MT CEST methodology has wide applicability in in vivo molecular imaging (such as brain, skeletal muscle, etc).

Article Link: http://www.nature.com/srep/2013/130423/srep01707/full/srep01707.html

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We gratefully acknowledge generous support for radiology research at NYU Langone Health from:
 
• The Big George Foundation
• Raymond and Beverly Sackler
• Bernard and Irene Schwartz

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