Jingwen Yao^1,2,3, Talia Oughourlian^1,2,4, Timothy Cloughesy^5,6, Phioanh L. Nghiemphu^5,6, Albert Lai^5,6, Linda M. Liau⁷, Richard G. Everson⁷, Whitney B. Pope², Noriko Salamon², David A. Nathanson⁸, and Benjamin M. Ellingson^1,2,3,4,5
1Brain Tumor Imaging Laboratory (BTIL), Center of Computer Vision and Imaging Biomarker, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, ²Department of Radiological Sciences, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, ³Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, UCLA, Los Angeles, CA, United States, ⁴Neuroscience Interdepartmental Program, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, ⁵UCLA Neuro-Oncology Program, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, ⁶Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, ⁷Department of Neurosurgery, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, ⁸Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States

We simultaneously quantified acidity and hypoxia of human gliomas with IDH, 1p/19q, and EGFR genotypes using CEST-SAGE-EPI. Results suggest IDH mutant gliomas are significantly less acidic and hypoxic than IDH wild-type tumors. Within IDH mutants, 1p/19q codeletion is associated with lower tumor acidity, while IDH wild-type, EGFR amplified tumors were more hypoxic. Both MRI-derived acidity and hypoxia were correlated with patient survival, suggesting metabolic characteristics may be prognostic. CEST-SAGE-EPI may be useful for exploring metabolic changes that result from particular genetic alterations or useful as a biomarker for accelerating drug development in human brain tumors. 

Zongwei Xu¹, Chao Ke², Xiaofei Lv³, Jie Liu¹, Long Qian⁴, Shijie Xu², Xin Liu¹, Hairong Zheng¹, and Yin Wu^1
1Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China, ²Department of Neurosurgery, Sun Yat-Sen University Cancer Center, Guangzhou, China, ³Department of Medical Imaging, Sun Yat-Sen University Cancer Center, Guangzhou, China, ⁴GE Healthcare, Beijing, China

Preoperative assessment of histological tumor characteristics plays an essential role in evaluating prognosis and optimizing therapeutic strategies for glioma patients. This study aims to evaluate the feasibility of DKI and APT in differentiating lower-grade glioma (LGG) from glioblastoma at 3T. Twenty-four untreated patients were recruited and classified into LGG (grade II and III, N=10) and glioblastoma (grade VI, N=14). Results show comparable diagnostic performance of APTw and MK in differentiating the two groups with AUCs>0.85, superior to other DKI indices. Combining them further improves the discrimination accuracy, that may greatly facilitate prompt diagnosis and treatment decisions.

Adam Autry¹, Jeremy Gordon¹, Marisa LaFontaine¹, Hsin-Yu Chen¹, Javier Villanueva-Meyer¹, Susan Chang², Duan Xu¹, Peder EZ Larson¹, Daniel B Vigneron¹, Jennifer Clarke², Janine Lupo¹, and Yan Li^1
1Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

Detection of [1-¹³C]pyruvate metabolism in GBM using hyperpolarized carbon-13 echo-planar imaging in a post-recurrence and pre-surgical setting

Guoqiang Yang¹, Shuaitong Zhang², Xiaochun Wang¹, Yan Tan¹, Jingwei Wei², Xiaoxu Chen³, Jie Tian², and Hui Zhang^1
1Department of Radiology, First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi Province, China, ²Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China, ³School of Economics and Management, Shanxi University, Taiyuan, Shanxi Province, China

To identify the incremental value of MRI features to the key molecular biomarkers for risk stratification of high-grade gliomas (HGGs). A comprehensive radiomics analysis integrated MRI features, clinical characteristics and genetic information was performed on 137 patients from TCGA/TCIA dataset and our institution. The combined model integrated radiomics signature with age and IDH genotype holds the best prognostic value. The radiomics signature has incremental prognostic value beyond the key molecular biomarkers, and could identify risk subgroups in various clinical and molecular subgroups. Our comprehensive radiomics analysis provided a potential tool to guide an individual diagnosis and treatment decisions for HGGs.

Daniel Paech¹, Sebastian Regnery², Nicolas Behl³, Tanja Platt³, Nina Weinfurtner¹, Mark Edward Ladd³, Jürgen Debus², Sebastian Adeberg², and Heinz-Peter Schlemmer^1
1Radiology, German Cancer Research Center, Heidelberg, Germany, ²Radiooncology, University Hospital Heidelberg, Heidelberg, Germany, ³Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany

²³Na MRI provides information on physiologic and pathophysiologically altered tissue sodium concentrations in vivo. In this prospective trial, we investigated the potential of ²³Na MRI at 7.0 Tesla to predict the tumor grade and genetic subtypes (such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine DNA methyltransferase (MGMT) promotor methylation) in a study cohort of 28 glioma patients. We show that that the quantitative ²³Na signal correlates with tissue-specific tumor subcompartments and that the contrast may allow non-invasive assessment of the tumor grade and IDH mutation.

Santosh Kumar Yadav¹, Sumei Wang², Shadi Asadollahi², MacLean Nasrallah³, Steven Brem⁴, Mohammad Haris¹, Suyash Mohan², and Sanjeev Chawla^2
1Research, Sidra Medicine, Doha, Qatar, ²Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, ³Department of Pathology and Lab Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, ⁴Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States

Accurate identification of isocitrate dehydrogenase (IDH) mutant high-grade glioma is clinically important. We investigated the combined utility of diffusion (DTI) and perfusion (DSC-PWI) MR imaging in distinguishing IDH mutant from IDH wild-type high-grade gliomas. Treatment naïve patients (n=30) with IDH-mutant (n=14) and IDH-wild-type (n=16) high-grade gliomas were recruited. A classification model comprising of mean diffusivity, coefficient of planar anisotropy and maximum relative cerebral blood volume differentiated two genotypes of gliomas with an accuracy of 85%, a sensitivity of 87.2%, and a specificity of 81.5%. Combined analysis of DTI and DSC-PWI may be helpful in distinguishing IDH profiles of high-grade gliomas.

Marzena Wylezinska-Arridge^1,2, Enrico De Vita^2,3, Laura Mancini^1,2, Ovidiu Andronesi⁴, Wolfgang Bogner⁵, Bernhard Strasser⁴, Tarek Yousry^1,2, John Thornton^1,2, and Sotirios Bisdas^1,2
1Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom, ²Institute of Neurology, University College London, London, United Kingdom, ³Department of Biomedical Engineering. School of Biomedical Engineering and Imaging Sciences, Kings College London, London, United Kingdom, ⁴Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, ⁵High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria

 It has been established that 2-hydroxyglutarate (2GH) MRS is important for non-invasive diagnosis of isocitrate dehydrogenase (IDH) status that holds prognostic value for the patient and is important for treatment planning. The purpose of  this work was to investigate whether the threshold determination for identification of IDH mutation could be improved by using ‘control’ spectra from normal-appearing white matter, NAWM , in multi-voxel 3D MEGA-LASER acquisitions.  The proposed approaches to threshold determination for 2HG detection in the tumour voxels provided increased sensitivity and specificity as compared with the cut-off thresholds based on CRLB% relative error.  

Pengcheng Yu¹, Tianyao Wang², Yujie Hu¹, Yudu Li^3,4, Rong Guo^3,4, Yibo Zhao^3,4, Ziyu Meng^1,3, Hong Zhu⁵, Jun Liu⁶, Xin Yu⁷, Zhi-Pei Liang^3,4, and Yao Li^1
1Institute for Medical Imaging Technology, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ²Radiology Department, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China, ³Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁵Department of Radiation Oncology, Minhang Branch of Cancer Hospital, Fudan University, Shanghai, China, ⁶Radiology department, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China, ⁷Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States

Differentiation between glioblastomas (GBMs) and cerebral metastases based on MR structural images is often challenging due to the poor specificity. MRSI is a useful tool for mapping the metabolic fingerprints of tumors. In this study, we investigate the use of a high-resolution MRSI technique known as SPICE for differentiation between GBMs and cerebral metastases in 28 patients. Our results show the metabolic biomarkers are different between GBMs and metastases as well as in the enhancing ring and the core of neoplasms. SPICE potentially provides a non-invasive metabolic measure to differentiate GBMs from cerebral metastases with high resolution.

Esin Ozturk-Isik^1,2, Banu Sacli Bilmez¹, Ayca Ersen Danyeli^2,3, Cengiz Yakicier⁴, Alpay Ozcan^2,5,6, M. Necmettin Pamir^2,5,7, Koray Ozduman^2,5,7, and Alp Dincer^2,5,8
1Institute of Biomedical Engineering, Bogaziçi University, Istanbul, Turkey, ²Brain Tumor Research Group, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ³Department of Pathology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ⁴Department of Molecular Biology and Genetics, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ⁵Center for Neuroradiological Applications and Research, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ⁶Department of Medical Device Technologies, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ⁷Department of Neurosurgery, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ⁸Department of Radiology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey

Isocitrate dehydrogenase (IDH) mutation highly affects the overall survival of gliomas.  In addition to the IDH mutation, the tumor histologic grade might play a role in patient prognosis. The aim of this study was to assess the metabolic variations between different tumor grades within IDH mutant (IDH-mut) and IDH wild-type (IDH-wt) gliomas using proton MR spectroscopy. Higher glycine in glioblastoma (GBM) within IDH-mut, and lower Cr and mIns in GBM within IDH-wt were the only statistically significant differences. Our study indicated similar metabolic profiles of different grades within IDH mutational subgroups, supporting IDH as a better predictor of clinical outcome.

Eduardo Coello¹, Raymond Huang¹, Molly F. Charney¹, Wufan Zhao¹, Huijun Liao¹, Changho Choi², and Alexander Lin^1
1Radiology, Brigham and Women's Hospital, Boston, MA, United States, ²Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States

This work introduces the concept of MR metabolic phenotyping (MRMP), a method that combines the high-resolution anatomical context of MRI and the highly specific metabolic information of MR spectroscopic imaging via unsupervised learning. The value of this technique was shown for the long‑term follow up of IDH‑mutated low‑grade gliomas where high sensitivity to changes in the metabolic composition of the major tissue compartments was achieved.