ISMRM 21st Annual Meeting & Exhibition 20-26 April 2013 Salt Lake City, Utah, USA

Human Brain Tumors: Diagnosis & Response
Wednesday 24 April 2013
Room 150 AG  16:00 - 18:00 Moderators: Patricia M. Desmond, Benjamin M. Ellingson

16:00 0509.   Clinical Utility of in-vivo MRS Measurements of 2-Hydroxyglutarate in IDH-Mutated Gliomas
Changho Choi1, Sandeep Ganji2, Akshay Madan1, Ralph DeBerardinis1, Bruce Mickey1, Craig R. Malloy1, Robert Bachoo1, and Elizabeth A. Maher1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States, 2UT Southwestern Medical Center, Dallas, Texas, United States

Following the finding of the production of 2-hydroxyglutarate (2HG) in IDH-mutated gliomas, several researchers reported in-vivo detection of this onco-metabolite by 1H-MRS. Although the role of 2HG associated with IDH mutation is well established for prognosis, how it can be used for improving the patient care is largely unknown. In this paper, using 2HG data from 30 patients obtained over time, we demonstrate that 2HG is a remarkably sensitive biomarker for monitoring the tumor growth/progression and response to treatment in patients.

16:12 0510.   
Image-Guided Metabolomic Analysis of 2-Hydroxyglutarate in IDH-Mutant Gliomas
Llewellyn E. Jalbert1, Adam Elkhaled2, Joanna J. Phillips3, Susan M. Chang4, and Sarah J. Nelson1,2
1Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States, 2Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 3Pathology, University of California, San Francisco, San Francisco, CA, United States, 4Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

2-hydroxyglutarate (2HG) has proved to be a promising biomarker for IDH1/2 mutations that can be quantified using magnetic resonance. However, little research has been conducted on the affect on 2HG on the cellular metabolome. The goal of this study was to investigate the differences in metabolic profiles between IDH-mutant low-grade gliomas containing 2HG with wild-type IDH tumors using proton High-Resolution Magic Angle Spinning (1H HR-MAS) spectroscopy of 242 image-guided tissue samples that were acquired from 110 patients with recurrent, low-grade gliomas.

16:24 0511.   Investigation of the Correlation of MRS Measurable 2-Hydroxyglutarate (2HG) Concentration and Tumor Progression in Brain Tumors Harboring IDH1/2 Mutations
Liya Wang1,2, Juliya Kalinina3, Ruya Zhao2, Run Lin1,2, Shaoxiong Wu4, Erwin Van Meir3, and Hui Mao1,2
1Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, United States, 2Center for Systems Imaging, Emory University, Atlanta, GA, United States, 3Department of Neurosurgery, Emory University, Atlanta, GA, United States, 4Department of Chemistry, Emory University, Atlanta, GA, United States

Earlier studies suggest the mutation in isocitrate dehydrogenase 1/2 (IDH1/2) is a prognostic marker of glioma patients. The mutant enzyme gains a novel activity of producing the oncometabolite, R(-)-2-hydroxyglutarate (2HG), which can be detected in vivo and ex vivo by magnetic resonance spectroscopy. However, the role of 2HG in tumor development and progression remains to be better understood. This study investigated the relationships of 2HG concentrations obtained from magnetic resonance spectroscopic analysis with tumor progression features obtained from clinical pathology and radiology exams to explore the potential of using 2HG levels with as a biomarker for predicting brain tumor prognosis and responses to the treatment.

16:36 0512.   DSC-MRI Measures of Standardized RCBV Predict Response to Bevacizumab in High-Grade Brain Tumor Patients
Kathleen M. Schmainda1, Melissa A. Prah1, Scott D. Rand1, Jennifer Connelly2, Eric S. Paulson3, Peter S. LaViolette1, Wade Mueller4, and Mark G. Malkin2
1Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, 2Neurology, Medical College of Wisconsin, Milwaukee, WI, United States, 3Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States, 4Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States

Standard measures of tumor volume derived from contrast-enhancing T1-weighted images, or abnormal volumes on T2-weighted images do not reliably predict the response of brain tumors to anti-angiogenic therapies such as bevacizumab. Bevacizumab may result in decreases in enhancing tumor volume without an effect on the tumor biology. In this study we show that standardized relative cerebral blood volume (rCBV) information, derived from DSC MRI, can predict the overall survival (OS) of high-grade gliomas to bevacizumab therapy. If the rCBV is low either before or after treatment, the OS is significantly improved.

16:48 0513.   Post-Bevacizumab Capital Greek DeltaT1 Maps Detect Residual Contrast Enhancement and Predict Survival in Recurrent Glioblastoma
Davis C. Woodworth1,2, Timothy F. Cloughesy3, Robert J. Harris1,2, Whitney B. Pope1, Albert Lai3, Phioanh (Leia) Nghiemphu3, and Benjamin M. Ellingson1,2
1Dept. of Radiological Sciences, UCLA, Los Angeles, CA, United States, 2Biomedical Physics, UCLA, Los Angeles, CA, United States, 3Neurology, UCLA, Los Angeles, CA, United States

Bevacizumab, a VEGF inhibitor, is a common second line treatment for glioblastoma after recurrence; however, bevacizumab results in reduction in contrast enhancement, which makes it difficult to assess true tumor burden and response to therapy. In the current study we explore the use of post-bevacizumab delta-T1 maps, where pre-contrast T1w images are subtracted from post-contrast T1w images, in 101 patients with recurrent glioblastoma. Results suggest delta-T1 maps reliably detect subtle contrast enhancement not apparent on normal post-contrast T1w images. Further, patients with a volume of delta-T1 hyperintense tumor greater than 15cc have a significantly shorter progression-free and overall survival.

17:00 0514.   
DCE-MRI Defined Subvolumes of a Tumor for Therapy Assessment
Reza Farjam1, Christina I. Tsien2, Felix Y. Feng2, Theodore S. Lawrence2, and Yue Cao2
1Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States, 2Radiation Oncology, University of Michigan, Ann Arbor, MI, United States

Analyzing the model-based physiological parameter maps derived from the DCE-MRI time series data is time consuming and may involve a series of uncertainties. Hence, we aim to develop a PCA-based model-free approach for delineating the response-driven subvolumes of a tumor by directly analyzing the DCE-MRI data for therapy assessment and guidance. Our results indicate that the PCA-defined subvolume of a tumor could predict the tumor response to therapy similar to the physiological-defined one while the PCA-defined subvolume can be delineated more quickly for guidance of the therapy.

17:12 0515.   Combined Visualization of ADC Diffusion Maps and CBV Perfusion Maps in Patients with Newly Diagnosed Glioblastoma -permission withheld
Alexander Radbruch1,2, Kira Lutz1, Benedikt Wiestler3, Philipp Bäumer1, Markus Graf2, Ralf Floca2, Wolfgang Wick3, Heinz Peter Schlemmer2, Martin Bendszus1, and Sabine Heiland1
1Department of Neuroradiology, Heidelberg University Medical Center, Heidelberg, Germany, 2Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany,3Department of Neurooncology, Heidelberg University Medical Center, Heidelberg, Germany

Areas of decreased apparent diffusion coefficient (MinADC) on diffusion MRI (DWI) and areas of increased cerebral blood volume (MaxCBV) on dynamic-susceptibility-contrast perfusion MRI (DSC) are supposed to present the most malignant parts of glioblastoma. However, it is still unclear if the identified regions on DWI and DSC overlap. We assessed 20 patients with glioblastoma with a new postprocessing technique and found an average overlap in 34.7 +/- 10.9 percent. Furthermore we found that areas of MaxCBV are located mostly in the enhancing region while areas of MinADC are located mostly in the surrounding area.

17:24 0516.   
Voxel-Wise Repeatability of Apparent Diffusion Coefficient in Patients with Newly Diagnosed Glioblastoma
Pavlina Polaskova1, Kourosh Jafari-Khouzani1, Alexander R. Guimaraes1, Steven M. Stufflebeam1, Patrick Y. Wen2, Tracy T. Batchelor3, Bruce R. Rosen1, Elizabeth R. Gerstner3, and Jayashree Kalpathy-Cramer1
1Radiology, Athinoula A. Martinos Center for Biomedical Imaging / Massachusetts General Hospital, Charlestown, Massachusetts, United States, 2Neuro-oncology, Brigham and Women's Hospital / Harvard Medical School, Boston, Massachusetts, United States, 3Neurology, Massachusetts General Hospital / Harvard Medical School, Boston, Massachusetts, United States

We assessed the voxel-wise repeatability of ADC values in patients with newly diagnosed glioblastoma in relation to functional diffusion mapping technique. Although the intra-class correlation coefficients are relatively high, the variability of the tumor values exceeds the thresholds for stable voxels, as proposed by functional diffusion mapping, suggesting the absolute thresholding be re-evaluated.

17:36 0517.   
Treatment Effect on Delay in Growth of Superior Frontal Lobe in Childhood Acute Lymphoblastic Leukemia
Byeong-Yeul Lee1, Xiao-Hong Zhu1, Wei Chen1, Paul J. Eslinger2, and Qing X. Yang3,4
1Center for Magnetic Resonance Research (CMRR), Radiology Department, University of Minnesota, Minneapolis, MN, United States, 2Neurology Department, Penn State University College of Medicine, Hershey, PA, United States, 3Center for NMR Research, Radiology Department, Penn State University College of Medicine, Hershey, PA, United States, 4Neurosurgery Department, Penn State University College of Medicine, Hershey, PA, United States

Recent advances in effective treatments for pediatric Acute Lymphoblastic Leukemia (ALL) have improved the survival rate. However, side effects of treatment have become an important focus of investigation. Our research was to investigate the long-term effects of chemotherapy on the cerebral structural alterations and plasticity. We studied brain anatomic images of young children with ALL who were treated with prophylactic CNS-directed chemotherapy. Our volumetric analysis uncovered a significant decrease in bilateral WM volume of the superior frontal lobe (SFL) in all ALL cohorts compared to controls. Thus, developmental delay in its growth in the SFL may be mainly responsible for deficits in attention, working memory, academic achievement in childhood ALL.

17:48 0518.   Comparison of Diffusion Kurtosis Imaging, Dynamic Susceptibility Weighted Imaging and Short Echo Time Chemical Shift Imaging for Grading Gliomas
Sofie Van Cauter1, Diana M. Sima2, Anca R. Croitor Sava2, Jelle Veraart3, Stefan Sunaert1,4, Sabine Van Huffel2, and Uwe Himmelreich5
1Radiology, University Hospitals of Leuven, Leuven, Vlaams-Brabant, Belgium, 2ESAT-PSI, Department of Electrical Engineering, Catholic University of Leuven, Heverlee, Vlaams-Brabant, Belgium,3Vision Lab, Department of Physics, University of Antwerp, Antwerp, Antwerp, Belgium, 4Translational MRI, University Hospitals of Leuven, Leuven, Vlaams-Brabant, Belgium, 5Biomedical NMR Unit/Molecular Small Animal Imaging Center, Department of Medical Diagnostic Sciences, KU Leuven, Leuven, Vlaams-Brabant, Belgium

Current routinely used MR techniques are often insufficient in accurate grading of glioma. Hence, in most cases a biopsy is warranted in order to obtain a definitive diagnosis. In this study, we assessed the diagnostic accuracy of diffusion kurtosis imaging, dynamic susceptibility-weighted magnetic resonance imaging and short echo time chemical shift imaging for grading gliomas. The most accurate parameters for determination of glioma grade were mean kurtosis and mean relative regional cerebral blood flow. However, a combination between calculated parameters could still provide a better differentiation between high- and low-grade glioma in this data set.