Ovidiu C. Andronesi MD, PhD, Presenter: Nothing to Disclose

Franziska Loebel MD, Abstract Co-Author: Nothing to Disclose

Wolfgang Bogner MSC, Abstract Co-Author: Nothing to Disclose

Malgorzata Marjanska PhD, Abstract Co-Author: Nothing to Disclose

Elizabeth Gerstner MD, Abstract Co-Author: Nothing to Disclose

Andrew S Chi MD,PhD, Abstract Co-Author: Nothing to Disclose

Tracy T. Batchelor MD, Abstract Co-Author: Nothing to Disclose

Daniel P Cahill, Abstract Co-Author: Nothing to Disclose

Bruce R. Rosen MD, PhD, Abstract Co-Author: Research Consultant, Siemens AG

The hallmark metabolic alteration of mutant IDH gliomas is the production of 2-hydroxyglutarate (2HG) which may play a central role in downstream effects. Hence, 2HG may be an ideal biomarker for both diagnosing IDH mutations and monitoring response to treatment. 2HG can be measured in-vivo by magnetic resonance spectroscopy and there is significant interest in developing methodology that performs reliably in patients. Here we present results obtained with a new 3D MR spectroscopic imaging (MRSI) sequence that maps 2HG over the entire volume of the tumor during treatment.

A robust  3D MRSI sequence for 2HG imaging was newly developed by integrating adiabatic J-difference spectral editing, spiral imaging, and real-time motion correction. The acquisition parameters were: TR=1.6s, TE=68ms, FOV=200x200x200 mm3, acquisition matrix 10x10x10, NA=20, acquisition time TA=9:55 min:s. Spectra were fitted with LCModel software. Measurements were performed on a 3T MR scanner. 3D MRSI was performed in 20 patients with mutant IDH1 gliomas (WHO grades II-IV)  consented with an approved IRB protocol. A baseline scan was done after surgery and before start of adjuvant treatment. At the moment 9 patients have completed a second post-treatment scan. Adjuvant treatment included radiotherapy and/or chemotherapy. The post-treatment scan was done in a time interval of 1-3 months after treatment.

Detectable levels of 2HG were measured in all patients that did not have gross total resection of tumor. 3D metabolic maps were obtained for 2HG, choline, N-acetyl-aspartate, glutamate-glutamine, and lactate.  In 9 patients who have undergone both pre- and post-treatment scans, 4 demonstrated marked decrease (30-50%) in the levels of 2HG after completion of adjuvant therapy as shown in Figure 1. The remainder showed partial reduction of 2HG, with no patients showing increased 2HG levels.

We demonstrate for the first time that 3D imaging of 2HG is clinically feasible in patients with IDH1 mutated gliomas. Quantification of 2HG levels in a cohort of mutant IDH glioma patients shows measurable changes during treatment.

2HG imaging could be used to answer clinically important questions of true-/pseudo-response and true-/pseudo-progression in mutant IDH glioma patients. 3D mapping of 2HG and other metabolites is important to capture tumor heterogeneity and reduce variability in longitudinal studies.

Andronesi, O, Loebel, F, Bogner, W, Marjanska, M, Gerstner, E, Chi, A, Batchelor, T, Cahill, D, Rosen, B, Longitudinal 3D MR Spectroscopic Imaging of 2-Hydroxyglutarate in Patients with Mutant IDH1 Glioma Undergoing Radiochemotherapy.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14013806.html