In vivo MRS measurement of 2-hydroxyglutarate in patient-derived IDH-mutant xenograft mouse models versus glioma patients.

To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.

Tiwari V ，Mashimo T ，An Z ，Vemireddy V ，Piccirillo S ，Askari P ，Hulsey KM ，Zhang S ，de Graaf RA ，Patel TR ，Pan E ，Mickey BE ，Maher EA ，Bachoo RM ，Choi C ... -  《-》

Noninvasive assessment of isocitrate dehydrogenase mutation status in cerebral gliomas by magnetic resonance spectroscopy in a clinical setting.

Tietze A ，Choi C ，Mickey B ，Maher EA ，Parm Ulhøi B ，Sangill R ，Lassen-Ramshad Y ，Lukacova S ，Østergaard L ，von Oettingen G ... -  《-》

Echo-planar spectroscopic imaging with dual-readout alternated gradients (DRAG-EPSI) at 7 T: Application for 2-hydroxyglutarate imaging in glioma patients.

To develop echo-planar spectroscopic imaging (EPSI) with large spectral width and accomplish high-resolution imaging of 2-hydroxyglutarate (2HG) at 7 T. We designed a new EPSI readout scheme at 7 T. Data were recorded with dual-readout alternated gradients and combined according to the gradient polarity. Following validation of its performance in phantoms, the new readout scheme, together with previously reported 2HG-optimized magnetic resonance spectroscopy (point-resolved spectroscopy echo time of 78 ms), was used for time-efficient and high-resolution imaging of 2HG and other metabolites in five glioma patients before treatment. Unsuppressed water, acquired with EPSI, was used as reference for multichannel combination, eddy-current compensation, and metabolite quantification. Spectral fitting was conducted with the LCModel using in-house calculated basis sets. Using a readout gradient strength of 9.5 mT/m and slew rate of 90 mT/m/ms, dual-readout alternated gradients EPSI permitted 1638-Hz spectral width with 6 × 6 mm2 in-plane resolution at 7 T. Phantom data indicated that dual-readout alternated gradients EPSI provides proper metabolite signals and induces much less frequency drifts than conventional EPSI. For a spatial resolution of 0.5 mL, 2HG was detected in tumors with precision (Cramer-Rao lower bound < 10%). The 2HG was estimated to be 2.3 to 3.3 mM in tumors of three patients with biopsy-proven isocitrate dehydrogenase (IDH) mutant gliomas. The 2HG was undetectable in an IDH wild-type glioblastoma. For a radiographically suggested glioma, the estimated 2HG of 2.3 ± 0.2 mM (Cramer-Rao lower bound < 10%) indicated that the lesion may be an IDH mutant glioma. The data indicated that the dual-readout alternated gradients EPSI can provide reliable high-resolution imaging of 2HG in glioma patients at 7 T in vivo. Magn Reson Med 79:1851-1861, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

An Z ，Tiwari V ，Ganji SK ，Baxter J ，Levy M ，Pinho MC ，Pan E ，Maher EA ，Patel TR ，Mickey BE ，Choi C ... -  《-》

In vivo 2-hydroxyglutarate-proton magnetic resonance spectroscopy (3 T, PRESS technique) in treatment-naïve suspect lower-grade gliomas: feasibility and accuracy in a clinical setting.

Cuccarini V ，Antelmi L ，Pollo B ，Paterra R ，Calatozzolo C ，Nigri A ，DiMeco F ，Eoli M ，Finocchiaro G ，Brenna G ，Tramacere I ，Bruzzone MG ，Anghileri E ... -  《-》

2-Hydroxyglutarate magnetic resonance spectroscopy in adult brainstem glioma.

Iwahashi H ，Nagashima H ，Tanaka K ，Uno T ，Hashiguchi M ，Maeyama M ，Somiya Y ，Komatsu M ，Hirose T ，Itoh T ，Sasaki R ，Sasayama T ... -  《-》