Frank G Zoellner¹, Kyrre E Emblem^2,3, and Lothar R Schad^1
1Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, ²Department of Radiology, MGH-HST A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ³The Interventional Center, Oslo University Hospital, Oslo, Norway

DSC-MRI is a method of choice to differentiate high-grade from low-grade gliomas. Recently, support vector machine (SVM) learning have been introduced as means to prospectively characterize gliomas based on the rCBV histograms. In our study, we have assessed the diagnostic accuracy of the different histogram features used in the SVM analysis (peak height, skewness, etc). By using correlation analysis to reduce 95% of the feature information, a classification accuracy of 88.1% was yielded. Our results suggest that a careful examination of the features in SVM based glioma grading could reduce the number of features substantially, thereby improving the effectiveness of the SVM analysis while maintaining a good classification score.

Changho Choi¹, Sandeep Ganji¹, Ralph DeBerardinis¹, Zoltan Kovacs¹, Robert Bachoo¹, Juan Pascual¹, Ivan Dimitrov^1,2, Bruce Mickey¹, Craig Malloy^1,3, and Elizabeth Maher^1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Philips Medical Systems, ³VA North Texas Health Care System

Recent studies indicate that a high fraction of gliomas contain mutations in the metabolic enzymes, isocitrate dehydrogenase-1 and -2, IDH1 and IDH2. As a result, 2-hydroxyglutarate (2HG), which is normally present in vanishingly small quantities, can be elevated by orders of magnitude in gliomas bearing IDH1 or IDH2 mutations. Here, we report for the first time in vivo detection of this oncometabolite in human brain tumors by 1H-MRS at 3T. 2HG was detected with CRLB < 20% in 38 spectra out of 122 spectra from 49 tumor patients (29 GBM, 9 anaplastic astrocytoma, and 11 low-grade glioma), the concentrations being 2 - 8 mM.

Adam Elkhaled¹, Llewellyn Jalbert¹, Hikari Yoshihara¹, Gabriella Bourne¹, Joanna Phillips², Soonmee Cha¹, Susan M Chang³, Radhika Srinivasan¹, and Sarah J Nelson^1,4
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ²Department of Pathology, University of California, San Francisco, ³Department of Neurological Surgery, University of California, San Francisco, ⁴Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco

Low grade gliomas with mutations in the isocitrate dehydrogenase-1 (IDH1) gene carry a significant survival advantage, and have recently been shown to manifest excessive production of 2-hydroxyglutarate (2HG). Given the potential prognostic value of 2HG as an onco-metabolite, we sought to characterize differences in metabolite levels between gliomas of distinct origin and grade using proton high-resolution magic-angle-spinning (1H HR-MAS) spectroscopy. Results indicated that: grade 2 glioma positive for 2HG possess a distinctive metabolic profile; 2HG presence can distinguish between primary and secondary GBM; and transformation to a higher grade can be characterized metabolically

Llewellyn Jalbert¹, Adam Elkhaled¹, Joanna Phillips², Hikari Yoshihara¹, Radhika Srinivasan¹, Gabriela Bourne¹, Susan Chang³, Soonmee Cha¹, and Sarah Nelson^1,4
1Department of Radiology and Biomedical Imaging, University of California - San Francisco, San Francisco, CA, United States, ²Department of Pathology, University of California - San Francisco, ³Department of Neurological Surgery, University of California - San Francisco, ⁴Department of Bioengineering and Therapeutic Sciences, University of California - San Francisco

Significant survival advantage is conferred to glioma patients harboring mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), resulting in the excessive production of the onco-metabolite 2-hydroxyglutarate (2HG). We aimed to determine whether 2HG could be detected in recurrent low-grade glioma samples using proton High-resolution Magic Angle Spinning (¹H HR-MAS) spectroscopy, and to correlate the results with IDH1 mutation status assessed by immunohistochemistry. We have confirmed 2HG presence by 1D and 2D ¹H HR-MAS in concordance with IDH1 status; its presence gives rise to a complicated spectral pattern that may be of significant clinical utility as a novel biomarker in glioma.

Rajakumar Nagarajan¹, Michael Albert Thomas¹, Whitney B Pope¹, Robert M Prins², Neil Wilson¹, Noriko Salamon¹, and Linda M Liau^2
1Radiological Sciences, University of California Los Angeles, Los Angeles, California, United States, ²Neurosurgery, University of California Los Angeles

The mutation observed in the isocitrate dehydrogenase1 (IDH1) gene, which occurs in the majority of grade II and grade III gliomas and secondary glioblastomas shows significant elevation of 2-hydroxyglutarate (2HG) in the brain tumors. We have quantified 2HG in the brain tumor patients using proton (1H) MR spectra recorded on a 3T MRI/MRS scanner and post-processed by LC-model algorithm. In this study, we show increased 2HG in the mutant type compared to wild type tumors. 1H MRS enables a non-invasive measure of 2HG in gliomas, which may serve as a potential biomarker for monitoring patients with IDH1 mutant brain tumors.

Rishi Awasthi¹, Ram Kishan Singh Rathore², Jitesh Kumar Singh², Nuzhat Husain³, Priyanka Soni³, Rohit Kumar Singh⁴, Sanjay Behari⁴, Rakesh Kumar Gupta¹, and Shaleen Kumar^5
1Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, Lucknow, Uttar Pradesh, India, ²Mathematics & Statistics, Indian Institute of Technology, Kanpur, Kanpur, Uttar Pradesh, India, ³Pathology, Chatrapati Sahu ji Maharaj Medical University, Lucknow, Uttar Pradesh, India, ⁴Neurosurgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, Lucknow, Uttar Pradesh, India, ⁵Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, Lucknow, India

Forty-four untreated patients with a definitive histopathological diagnosis of glioblastoma multiforme were imaged using conventional, DT and DCE MRI. It was possible to segment the tumor tissue by using DCE derived CBV maps and DTI derived MD maps. From these segmented regions, four combinations of CBV and MD values were obtained which represents different tumoral components also evident on immunohistochemistry. We conclude that the combination of DTI and DCE-MRI allows segmentation which classifies different tissue types within the tumor which in turn may prove to be valuable in targeted therapy in future

Heisoog Kim^1,2, Ciprian Catana¹, Kim Mouridsen¹, Div Bolar¹, Elizabeth R Gerstner³, Tracy T Batchelor³, Rakesh K Jain⁴, Bruce R Rosen^1,2, and A Gregory Sorensen^1
1Radiology, A. A. Martinos Center, Charlestown, MA, United States, ²HST/NSE, Massachusetts Institute of Technology, Cambridge, MA, United States, ³Neurology, Massachusetts General Hospital, Boston, MA, United States, ⁴Radiation Oncology, Massachusetts General Hospital, Boston, MA, United States

Cerebral metabolic rate of oxygen (CMRO2) is one of the characteristics utilized to investigate metabolic changes in tumor oxygenation under different baseline physiologies. Based on simultaneous BOLD-ASL measurements, relative CMRO2 in hyperoxia in glioblastoma (GBM) were quantitatively evaluated. Elevated BOLD and reduced CBF signal changes during 100% oxygen breathing were observed in glioblastoma. Our data validated the coupling between BOLD and CBF in Davis’ model in GBM patients. Remarkably, oxygen-induced relative CMRO2 estimated from these measurements showed a significant increase (44%) in tumor and peritumoral regions. It implies that hyperbaric oxygen administration manipulates the oxygenation metabolism in cancer cells.

Heisoog Kim¹, Ciprian Catana¹, Grae Arabasz¹, Div Bolar¹, Elizabeth R Gerstner², Tracy T Batchelor², Rakesh K Jain³, Bruce R Rosen¹, and A Gregory Sorensen^1
1Radiology, A. A. Martinos Center, Charlestown, MA, United States, ²Neurology, Massachusetts General Hospital, Boston, MA, United States, ³Radiation Oncology, Massachusetts General Hospital, Boston, MA, United States

The specific goal of this study was to evaluate relative CMRO2 changes in relation to hypoxia level based on FMISO uptake in newly diagnosed glioblastoma (nGBM) patients undergoing chemo-, radio- and anti-angiogenic therapy using an integrated MRI-PET scanner. We observed a significant increase of relative CMRO2 (42%) and FMISO uptake (2.45 SUV) around the enhancing tumor at the baseline. However, the relative CMRO2 (19%) and FMISO uptake (1.55 SUV) largely decreased with tumor regression by the combined treatment. Our preliminary findings have important implications for the role of oxygen in supporting tumor metabolism and angiogenesis.

Nigel Paul Davies^1,2, Simrandip Gill^2,3, Theodoros N Arvanitis^3,4, Dorothee Auer⁵, Richard Grundy^6,7, Franklyn A Howe⁸, Darren Hargrave⁹, Tim Jaspan⁷, Lesley MacPherson³, Kal Natarajan^1,3, Geoffrey Payne^9,10, Dawn Saunders¹¹, Yu Sun^2,3, Martin Wilson^2,3, and Andrew C Peet^2,3
1Medical Physics, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, ²Cancer Sciences, University of Birmingham, Birmingham, United Kingdom, ³Birmingham Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom, ⁴Department of Electrical, Electronic, and Computer Engineering, University of Birmingham, Birmingham, United Kingdom, ⁵Academic Radiology, University of Nottingham, Nottingham, United Kingdom, ⁶Children's Brain Tumour Research Centre, University of Nottingham, Nottingham, United Kingdom, ⁷University Hospital Nottingham, Nottingham, United Kingdom, ⁸St. George's University of London, London, United Kingdom, ⁹Royal Marsden Hospital, London, United Kingdom, ¹⁰Institute of Cancer Research, London, United Kingdom, ¹¹Great Ormond Street Hospital, London, United Kingdom

1H MRS provides non-invasive metabolite profiles of brain tumours aiding diagnosis and potentially improving characterisation. In this study we perform a large prospective multicentre evaluation of 1H MRS as a diagnostic tool for grading childhood brain tumours. The classifier was trained on metabolite profiles derived using TARQUIN from 123 single-voxel MRS acquired using a standard protocol on two 1.5T scanners in a single centre. Testing was performed using 110 cases acquired prospectively across 4 different centres with some variations in echo time and field strength. The overall classification accuracy for identifying high grade versus low grade tumours was 86%.

Manabu Kinoshita¹, Testu Goto¹, Hideyuki Arita¹, Naoki Kagawa¹, Yasunori Fujimoto¹, Haruhiko Kishima¹, Yoichi Saitoh², Jun Hatazawa³, Naoya Hashimoto¹, and Toshiki Yoshimine^1
1Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan, ²Neuromodulation and Neurosurgery, Center for Advanced Science and Innovation, Osaka University, Suita, Osaka, Japan, ³Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

Use of DTI has been proposed for the detection of glioma cell invasion. However, other reports have questioned its value. We have been able to segment areas with and without tumor cell invasion in the T2-high intensity area in malignant gliomas using a voxel-wise analysis of 11C-methionine and FDG PET. We also showed the profile of FA and ADC does not differ between these two. Our results suggest the possibility of using voxel-wise analysis of 11C-methionine and FDG PET for tumor cell invasion in the T2-high intensity area in glioma patients and questioning the use of DTI for this purpose.