Magnetic resonance spectroscopy (MRS) provides an effective tool for detecting bio-chemicals in living systems noninvasively. Dr. Choi’s lab focuses on the technical and clinical development of MR spectroscopy (MRS) in the brain in vivo.
Many low-concentration metabolites are difficult to measure reliably using standard MRS approaches because MR signals from brain metabolites overlap extensively (largely due to J coupling effects). Our strategy is to design metabolite-specific MRS techniques for improving the detectability of clinically-important metabolites.
We use an in-house spin-dynamics simulation tool (Matlab) for MRS sequence design, which incorporates experimental scan parameters (i.e., shaped RF and gradient pulses as well as the J coupling effects). Therefore, the calculated MR signals are nearly identical to experimental signals. This congruence permits precise evaluation of metabolite signals in the in vivo data.
Detecting Oncometabolites in Tumors
Our recent research has been dedicated to in vivo MRS in brain tumor patients, in collaboration with clinicians. Following the discovery of 2-hydroxyglutarate (2HG) production in gliomas harboring mutations in isocitrate dehydrogenase (IDH) (Dang et al. Nature 2009;462:739-744), our MRS development was focused on 2HG and we published the preliminary result (Choi et al. Nature Medicine 2012).
Beyond simple detection of 2HG, we extended our 2HG study to examine the clinical utility of this oncometabolite, focusing on whether the 2HG level is stable over time in clinically/radiographically stable tumors and whether 2HG level changes with tumor growth/progression and in response to treatment.
The data indicated that 2HG is an unprecedented biomarker for monitoring the tumor and may have great potential for use in clinical practice (manuscript under review). In addition to 2HG, the data also showed that glycine (Gly), which is elevated in high-grade tumors, may serve as a great tool for monitoring the tumor progression and response to treatment in both IDH mutated gliomas and IDH wild-type gliomas.
Furthermore, we reported for the first time that citrate (Cit) is increased in adult glioma patients.
Oncometabolites and Patient Care
We aim to examine the clinical utility of 2HG, Gly, and Cit in gliomas to understand how these oncometabolites can be used to improve patient care.
3D evaluation of the cancer biomarkers using MRS imaging will provide biological insights into how metabolite levels within the tumor mass change during progression and treatment.
Many prior studies investigated the applicability of MRS, largely focusing on easily detectable metabolites, such as choline, N-acetylaspartate (NAA), creatine, lactate, etc. But these metabolites are not tumor-specific; their concentrations are also altered in many other brain diseases.
The metabolites that we study are different:
- 2HG is directly implicated in cancer genetic mutation.
- Gly is a maker of malignancy.
- Cit may be a new biomarker with great clinical potential.
MRS evaluation of these newly-emerging cancer biomarkers on top of commonly measured metabolites will help improve patient management and may provide advancement in understanding tumor biology.
In addition, we examine the disease specificity of 2HG by conducting 2HG MRS in non-tumor neurological disorders. The success of this study will provide experimental evidence for use of non-invasive 2HG imaging as a triaging tool in the workup.
Relevant Publications
- Choi et al. 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat Med 2012;18:624-629.
- Choi et al. A comparative study of short- and long-TE 1H MRS at 3 T for in vivo detection of 2-hydroxyglutarate in brain tumors. NMR Biomed 2013;26:1242-1250.
- Ganji et al. In vivo detection of 2-hydroxyglutarate in brain tumors by optimized PRESS at 7T. Magn. Reson Med (in press)
- An et al. Detection of 2-hydoroxyglutarate in brain tumors by triple-refocusing MRS at 3T in vivo. Magn Reson Med (under review)
- Choi et al. Measurement of glycine in the human brain in vivo by 1H-MRS at 3T: Application in brain tumors. Magn Reson Med 2011;66:609-618.
- Ganji et al. In vivo 1H MR spectroscopic imaging of glycine in brain tumors at 3T. Magn Reson Med 2016;75:52-62.
- Choi et al. In vivo detection of citrate in brain tumors by 1H MRS at 3T. Magn Reson Med 2014;72:316-323.