Alexander Peter Lin PhD, Presenter: Nothing to Disclose

Raymond Y. Huang MD, PhD, Abstract Co-Author: Nothing to Disclose

Sai Merugumala MS, Abstract Co-Author: Nothing to Disclose

Huijun Vicky Liao BS, Abstract Co-Author: Nothing to Disclose

Xi Long MD, Abstract Co-Author: Nothing to Disclose

Srinivasan Mukundan MD, PhD, Abstract Co-Author: Institutional research support, Siemens AG Institutional research support, Toshiba Corporation Consultant, Toshiba Corporation

David A. Reardon MD, Abstract Co-Author: Research support, F. Hoffmann-La Roche Ltd Advisory Board, F. Hoffmann-La Roche Ltd

Patrick Y. Wen MD, Abstract Co-Author: Research Consultant, F. Hoffmann-La Roche Ltd

Nils David Arvold MD, Abstract Co-Author: Nothing to Disclose

Gliomas are the most common primary malignant brain tumor, yet MRI provides limited functional information regarding tumor viability/activity and represents a major research and clinical challenge. Recent studies have shown that magnetic resonance spectroscopy can be used to non-invasively measure 2-hydroxyglutarate (2HG) in gliomas that harbor the isocitrate dehydrogenase 1 (IDH1) mutation, thus providing a highly specific measure for diagnosis.  

In this study we utilize two methods of measuring 2HG: 1) 2D chemical shift imaging (2D-CSI) with an optimal echo time of 97 ms to measure the 2HG resonance at 2.25 ppm from which spatial metabolic maps can be produced (7 min scan). 2) 2D spectral MRS using single-voxel localized correlated spectroscopy (2D-COSY) of 64 increments of 0.8 ms with a starting TE=30 ms and 8 averages (12 min scan).   15 subjects with pathologically confirmed gliomas were recruited and examined on a 3T Siemens Skyra using a 32 channel head coil. 2D-CSI was post-processed using clinically available software on the MRI platform (Syngo, Siemens) as well as LCmodel (Provencher). 2D-COSY was processed using commercially available software (FelixNMR) and crosspeaks at 2.25-4.0 and 1.9-4.0 ppm were measured. IDH status was compared with both MRS analyses.

Results using bothof the methods were compared with histology: 10 IDH1-mutant, 5 IDH1-wildtype. 2D-CSI provided useful metabolite maps of the 2HG signal that were highly specific. However, there were several cases in IDH1-mutant gliomas in which baseline and phasing issues resulted in difficulty detecting 2HG. Fortunately in those cases where 2D-CSI failed, 2D-COSY was able to detect 2HG signal due to the use of multiple crosspeaks that can be used for analysis that are disambiguated from surrounding spectral signal. However, 2D-COSY suffers from partial volume effects due to the large voxel size required for adequate SNR, but this is complimented by 2D-CSI which provides excellent spatial coverage.

The combination of 2D-CSI to provide spatial resolution and 2D-COSY to provide spectral resolution, provided the greatest sensitivity and specificity for the characterization of 2HG in IDH1-mutant gliomas.

Developing MRS methods to detect 2HG for the diagnosis of IDH1-mutant gliomas presents a tremendous opportunity, and might serve as a molecular imaging biomarker of glioma treatment response.  

Lin, A, Huang, R, Merugumala, S, Liao, H, Long, X, Mukundan, S, Reardon, D, Wen, P, Arvold, N, Detection of 2-Hydroxyglutarate in Gliomas Using Spatial and Spectral 2D MR Spectroscopy: Translation to the Clinic.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14016640.html