Human Brain Tumors: Diagnosis & Response

Wednesday 24 April 2013

Changho Choi¹, Sandeep Ganji², Akshay Madan¹, Ralph DeBerardinis¹, Bruce Mickey¹, Craig R. Malloy¹, Robert Bachoo¹, and Elizabeth A. Maher^1
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.

Llewellyn E. Jalbert¹, Adam Elkhaled², Joanna J. Phillips³, Susan M. Chang⁴, and Sarah J. Nelson^1,2
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.

Liya Wang^1,2, Juliya Kalinina³, Ruya Zhao², Run Lin^1,2, Shaoxiong Wu⁴, Erwin Van Meir³, and Hui Mao^1,2
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.

Kathleen M. Schmainda¹, Melissa A. Prah¹, Scott D. Rand¹, Jennifer Connelly², Eric S. Paulson³, Peter S. LaViolette¹, Wade Mueller⁴, and Mark G. Malkin^2
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.

Davis C. Woodworth^1,2, Timothy F. Cloughesy³, Robert J. Harris^1,2, Whitney B. Pope¹, Albert Lai³, Phioanh (Leia) Nghiemphu³, and Benjamin M. Ellingson^1,2
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.

Reza Farjam¹, Christina I. Tsien², Felix Y. Feng², Theodore S. Lawrence², and Yue Cao^2
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.

Alexander Radbruch^1,2, Kira Lutz¹, Benedikt Wiestler³, Philipp Bäumer¹, Markus Graf², Ralf Floca², Wolfgang Wick³, Heinz Peter Schlemmer², Martin Bendszus¹, and Sabine Heiland^1
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.

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-Cramer^1
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.

Byeong-Yeul Lee¹, Xiao-Hong Zhu¹, Wei Chen¹, Paul J. Eslinger², and Qing X. Yang^3,4
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.

Sofie Van Cauter¹, Diana M. Sima², Anca R. Croitor Sava², Jelle Veraart³, Stefan Sunaert^1,4, Sabine Van Huffel², and Uwe Himmelreich^5
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.