University of Twente Student Theses


Non-invasive detection of hepatic acetylcarnitine by 1H-MRS

Haans, F. (2022) Non-invasive detection of hepatic acetylcarnitine by 1H-MRS.

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Abstract:Purpose: Acetyl coenzyme A (acetyl-CoA) is an intermediate of fatty acid and glucose oxidation and accumulates in situation of substrate overabundance. It has been suggested that acetyl-CoA accumulation may be central in the development and progression of chronic metabolic disease, such as non-alcoholic fatty liver disease (NAFLD). Indeed, acetyl-CoA has a regulatory role in various hepatic cellular processes that are implicated in the development of insulin resistance, type 2 diabetes and NAFLD. Non-invasive quantification of acetyl-CoA should help our understanding of its role in these processes and allow the study of this metabolite in relation to development of several metabolic diseases. However, it is technically demanding to quantify acetyl-CoA in vivo due to very low concentrations. Acetylcarnitine is used intracellular to buffer acetyl-CoA, meaning it could function as a surrogate marker to acetyl-CoA. Previous approaches that used T1 [1] and T2 [2] editing to quantitively visualise acetylcarnitine are not applicable in the liver, as these approaches are too sensitive to motion. We aim to develop a 1H-MR spectroscopy method to assess intrahepatic acetylcarnitine content. Methods: A MATLAB simulation of the precession of the resonances of interest (water, acetylcarnitine, lipids) in combination with simulated RF pules was created to find a sequence that can suppress lipid resonances that overlay the acetylcarnitine resonance whilst also suppressing water signal. This sequence we named iVAPOR. Next, the iVAPOR sequence was tested in a phantom series, in which acetylcarnitine concentrations differed and lipid content was the same between phantoms. The results were also quantified using a fitting script to fit the spectrum and obtain measurements of the acetylcarnitine content. In addition, the sequence was tested on the vastus lateralis of a healthy volunteer to assess in vivo feasibility. Additionally, the scans were compared to the previous T1 editing approach. Conclusion: The iVAPOR technique developed in this study is able to suppress lipids overlaying the acetylcarnitine resonance and uncover acetylcarnitine, both in vitro and in vivo. The sequence developed is less motion sensitive than previous approaches, meaning it allows the study of acetylcarnitine in the liver. Study of this metabolite in the liver will further our understanding of the development of metabolic diseases and in term also help us to develop patient specific treatment protocols.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:44 medicine
Programme:Technical Medicine MSc (60033)
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