Magnetic resonance spectroscopy (MRS) provides an effective tool for detecting bio-chemicals in living systems noninvasively. Dr. Choi’s lab focuses on 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 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 by means of MRS imaging will provide biological insights on 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 clearly 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. Success of this study will provide an experimental evidence for use of non-invasive 2HG imaging as a triaging tool in the workup.