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Chemical Exchange Saturation Transfer (CEST): A Metabolic Imaging Technique Using Magnetic Resonance Imaging (MRI)

Abstract

Chemical exchange saturation transfer (CEST) is an emerging MR imaging technique that is sensitive to the metabolite accumulation/loss. This technique selectively saturates the exchangeable protons in certain molecules. After exchange with water protons, the saturation can be detected by the change of water signal. The primary focus of the work in this dissertation is to make the current CEST techniques clinically translatable and address the challenges for cardiac and lumbar spine applications.

CEST imaging has been applied in the heart for creatine mapping because cardiac dysfunction was linked to loss of metabolites in the creatine kinase system. Validation studies were performed in chronic myocardial infarction animal model using late gadolinium enhancement as reference. It is shown that the infarct region has lower CEST signal compared to remote myocardium. Spatially, the hypointense regions in the CEST contrast maps closely match the bright areas in the LGE images.

Intervertebral disc (IVD) degeneration is one of the leading causes of chronic low back pain. Previous studies associated low pH as the leading cause of discogenic low back pain in degenerate IVDs. We proposed a quantitative CEST (qCEST) imaging protocol for pH assessment in the IVD. It is shown in animal studies that the exchange rate measured from qCEST technique is correlated with the direct pH measurement using tissue pH-meter. In addition, gene analysis of harvested degenerated IVDs revealed strong positive correlation between up-regulation of pain markers and increase in qCEST signal. Collectively, these findings demonstrate that this approach can be used to measure pH in vivo within the IVD and has the potential to be used as a novel non-invasive method for the diagnosis of discogenic pain.

CEST fingerprinting framework was proposed to further improve CEST quantification. This is inspired by the magnetic resonance fingerprinting concept where the signal generated using randomized sequence parameters will be matched directly to a pre-defined dictionary instead of using a repeated, serial acquisition of data to fit to a particular equation. CEST fingerprinting utilizes CEST saturation with varying saturation power B1 amplitude and saturation time to create uniqueness of signal evolution for different exchange rates. Phantom studies demonstrated that CEST fingerprinting was more efficient (5x faster) compared to pulsed qCEST because there is no need for long saturation time and long TR. It is also shown that the proposed CEST fingerprinting technique can quantify exchange rate more accurately in the presence of MT effects.

In summary, with the technical improvements proposed in this dissertation, CEST imaging can be performed more efficiently and more accurately. These techniques can be potentially translated into clinical studies.

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