Human Brain Tumors: Response To Therapy
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Tuesday May 10th
Room 710B  10:30 - 12:30 Moderators: Meng Law and Brian D. Ross

10:30 244.   Graded functional diffusion maps (fDMs) predict survival in recurrent glioblastoma treated with bevacizumab  
Benjamin M Ellingson1, Timothy F Cloughesy2, Albert Lai2, Phioanh L Nghiemphu2, and Whitney B Pope1
1Radiological Sciences, University of California Los Angeles, Los Angeles, CA, United States, 2Neurology, University of California Los Angeles, Los Angeles, CA, United States

There remains a significant need for sensitive biomarkers that predict response to anti-angiogenic treatment for malignant gliomas. We hypothesize that graded functional diffusion maps (fDMs) are a sensitive biomarker for early prediction of bevacizumab failure in recurrent glioblastoma (GBM). Eighty-five patients with recurrent GBMs were retrospectively examined. The volume of fDM-classified hypo- and hypercellular tissue in various categories were tested to determine if they were predictive of survival. Using graded fDMs, patients having a large volume of voxels exhibiting a subtle decrease in ADC had a significantly shorter progression-free and overall survival compared to those having a lower volume.

10:42 245.   Combined 31P and 1H MRSI in recurrent glioblastomas prior and post antiangiogenetic therapy 
Ulrich Pilatus1, Oliver Bähr2, Joachim Steinbach2, and Elke Hattingen1
1Institute of Neuroradiology, Goethe University Frankfurt, Frankfurt/Main, Germany, 2Senckenbergisches Institut für Neuroonkologie, Goethe University Frankfurt, Frankfurt/Main, Germany

31P and 1H MRSI was performed on recurrent glioblastomas prior and following treatment with the antiangiogenic agent Bevazizumab. Untreated tumor tissue revealed decreased glycerophosphocholine (GPE) and increased pH. In patients who were responding to the therapy (RANO criteria), both parameters reverted to normal levels within 8 weeks of treatment.

10:54 246.   MR Spectroscopy as a Biomarker to Predict the Responses of Glioblastoma to an Anti-angiogenic Treatment 
Heisoog Kim1, Ciprian Catana1, Eva-Maria Ratai1, Ovidiu C. Andronesi1, Tracy T Batchelor2, Rakesh K Jain3, and A Gregory Sorensen1
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

In this study, the changes of predominant metabolites in recurrent glioblastoma (rGBM) were evaluated for predicting tumor responses to an anti-angiogenic treatment. While thirty-one rGBM patients were treated with daily doses of cediranib, chemical shift imaging data were acquired serially at the specific time points of treatment. We measured the concentrations of N-acetyl aspartate (NAA) and choline (Cho) normalized by creatine in normal tissue (norCre) in enhancing tumor by categorizing two different survival groups. Notably, NAA/Cho showed a high prediction to 6-month overall survival in ROC analysis. These observations have important implications for treatment management.

11:06 247.   Increased Blood Flow during anti-VEGF Induced Vascular Normalization 
Kyrre E Emblem1, Pavlina Polaskova1, Dominique L. Jennings1, Elizabeth R. Gerstner2, Tracy T Batchelor2, Rakesh K Jain3, and Gregory Sorensen1
1A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts, United States, 2Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, Massachusetts, United States, 3Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, United States

It is hypothesized that anti-VEGF therapy in combination with radiation and chemotherapy can normalize brain tumor vascularity and restore impaired blood flow characteristics. In this study, we have compared MR-derived flow characteristics in patients treated with an anti-angiogenic agent to that of a patient control group not receiving anti-angiogenic therapy. Our results support the hypothesis of vascular normalization, where the patient group undergoing anti-VEGF treatment showed increased CBF during the vascular normalization window.

11:18 248.   Improved Localization of BOLD Activation in Patients with Brain Tumors using Vasoreactivity Maps 
Henning U. Voss1, Kyung K Peck2, Nicole M Petrovich Brennan2, Amir Iranmahboob2, Bob L. Hou3, and Andrei I Holodny2
1Dept. of Radiology, Weill Cornell Medical College, New York, NY, United States, 2Dept. of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States,3Dept. of Radiology, West Virginia University, Morgantown, VA, United States

In subjects with brain tumors a global hemodynamic response function may not be sufficient to yield the most accurate maps of eloquent cortical areas in presurgical planning fMRI. We propose to assess local vasoreactivity by using a breath-holding paradigm and derive a model that takes altered hemodynamics into account. We obtain altered task response maps as compared to maps obtained without breath-holding information, in particular adjacent to tumors, in half of the studied cases. Our results suggest that the inclusion of vasoreactivity data could enhance BOLD detection in patients with compromised hemodynamics secondary to pathology.

11:30 249.   Serial Changes in Diffusion Imaging Parameters Vary with Treatment Regimen for Patients with Newly Diagnosed Glioblastoma Multiforme 
Laleh Jalilian1, Emma Essock-Burns2, Yan Li1, Soonmee Cha1,3, Susan Chang3, Michael Prados3, Nicholas Butowski3, and Sarah J. Nelson1,2
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, 2Bioengineering, UCSF, San Francisco, CA, United States, 3Neurological Surgery, UCSF, San Francisco, CA, United States

Despite advances in treatment modalities, patients with glioblastoma multiforme have an overall survival of 15 months. Anti-angiogenic therapies administered with temozolomide have been reported to cause restriction on diffusion-weighted imaging (DWI), which may serve as an adjunct to the assessment of therapy response. In this study, 100 newly diagnosed GBM patient were administered either a) temozolomide alone, b) temozolomide and a protein kinase C inhibitor, or c) temozolomide and a VEGF antibody. The results demonstrate that imaging biomarkers used to predict response and prognosis to therapy need to be tailored to take into account the specific treatment regimen being considered.

11:42 250.   How Blood Perfusion maps are analyzed can greatly improve the predictive potential for assessing survival in patients treated for gliomas 
Benjamin Lemasson1, Stefanie Galbán2, Christina Tsien2, Charles R Meyer1,3, Timothy D Johnson4, Thomas Leonard Chenevert1, Alnawaz Rehemtulla1,2, Brian Dale Ross1, and Craig J Galbán1
1Radiology, University of Michigan, Ann Arbor, Michigan, United States, 2Radiation Oncology, University of Michigan, Center for Molecular Imaging, Ann Arbor, Michigan, United States, 3Biomedical, University of Michigan, Center for Molecular Imaging, Ann Arbor, Michigan, United States, 4Biostatistics, University of Michigan, Ann Arbor, Michigan, United States

We tested the hypothesis that the method used to analyze the physiological parameter can improve the parameter’s predictive value. As such we compaired the parametric response (PRM) map to several common methods for assessing response. In addition, we evaluated the impact of the volume of interest (VOI) and the time the mid-treatment rCBV map was acquired on the predictive value of one-year and overall survival in a cohort of glioma patients. Only PRM was predictive of response. In addition, PRM is shown to be robust with negligible sensitivity to the VOI or the time the mid-treatment rCBV map was acquired.

11:54 251.   Treatment effects of diffuse intrinsic pontine gliomas on tumor and normal appearing cortical gray matter assessed by arterial spin labeling perfusion and 3D volumetric measurements 
Jan Sedlacik1,2, Claudia M Hillenbrand1, and Alberto Broniscer3
1Radiological Sciences, St. Jude Children’s Research Hospital, Memphis, TN, United States, 2Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 3Oncology, St. Jude Children’s Research Hospital, Memphis, TN, United States

In a clinical trial of combined antiangiogenic and local radiation therapy (RT) of brainstem gliomas changes in tumor and cortical grey matter (GM) perfusion were closely monitored by arterial spin labeling and volumetric measurements. Median tumor perfusion was found to be increased and showing a higher variance directly after RT suggesting different tumor responses to treatment compared to tumor volume which decreased in all patients. A temporary drop in cortical GM perfusion and volume was found directly after baseline which may be caused by steroids, given at the beginning of therapy.

12:06 252.   UDP-GlcNAc and UDP-GalNAc, as detected by 1H MRS, increase in the early phase of cisplatin –induced cell death in brain tumour cells 
Xiaoyan Pan1,2, Martin Wilson1,2, Carmel McConville1, Julian L Griffin3, Theodoros N Arvanitis2,4, Andrew C Peet1,2, and Risto A Kauppinen5
1Cancer Sciences, University of Birmingham, Birmingham, United Kingdom, 2Oncology, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom,3Biochemistry, University of Cambridge, Cambridge, United Kingdom, 4School of Electronic, Electrical and Computer Engineering, University of Birmingham, Birmingham, United Kingdom, 5Department of Radiology, Dartmouth College, Hanover, New Hampshire, United States

In this work, four brain tumour cell lines with different sensitivity to cisplatin were studied. DAPI-stained nuclei of cisplatin treated cells were demonstrated to identify cell death. 1HMRS was performed on the cisplatin treated brain tumour cells to investigate the metabolic change with treatment. The peaks at 7.98, 5.98 and 2.09 ppm assigned to UDP-GlcNAc and UDP-GalNAc were found to increase in the responding cells in the early events of cell death but not in non-responders. They change with similar kinetics to the 1HMRS-detected lipids during cell death.

12:18 253.   Characterization of microbleed formation from normal brain microvasculature after radiation therapy 
Janine M. Lupo1, Susan M Chang2, Soonmee Cha1,2, and Sarah J Nelson1,3
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States, 2Department of Neurological Surgery, University of California, San Francisco, CA, United States, 3Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, United States

Although a mainstay in the standard-of-care for malignant gliomas, the potential effects of radiation therapy on normal brain tissue and quality-of-life is not well characterized. This study uses SWI to evaluate the evolution of microbleeds in normal-appearing brain due to radiation therapy in 12 glioma patients, 6 of who received concurrent anti-angiogenic therapy. Microbleed counts were found to increase linearly as a function of time since receiving radiation, with the rate of microbleed formation escalating after 2 years. The addition of an anti-angiogenic agent appeared to stall this processes. Microbleed size varied both within and across patients with time.