ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: Human Brain Tumours: Diagnosis & Response to Therapy

Monday, May 9, 2016
Room 334-336
16:30 - 18:30
Moderators: Ravikanth Balaji, Natalie Serkova

Multi-Center and Multi-Vendor Study of Long-TE 1H MRS at 3T for Detection of 2-Hydroxyglutarate in Brain Tumors In Vivo
Changho Choi1, Thomas Huber2, Anna Tietze3, Byung Se Choi4, Jung Hee Lee5, Seung-Koo Lee6, Alexander Lin7, and Sunitha Thakur8
1UT Southwestern Medical Center, Dallas, TX, United States, 2Technical University of Munich, Munich, Germany, 3Aarhus University Hospital, Aarhus, Denmark, 4Seoul National University College of Medicine, Seongnam, Korea, Republic of, 5Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of, 6Yonsei University College of Medicine, Seoul, Korea, Republic of, 7Harvard Medical School, Boston, MA, United States, 8Memorial Sloan-Kettering Cancer Center, New York, NY, United States
The non-invasive identification of elevated 2-hydroxyglutarate (2HG) in IDH-mutated gliomas by 1H MRS in vivo is a major breakthrough in brain tumor research. Studies have shown that optimized long-TE approaches may confer advantages over short-TE MRS for detecting 2HG. Here we report an evaluation of the feasibility of long-TE 2HG MRS in Philips, Siemens and GE 3T scanners. Echo times were optimized, with numerical simulations and phantom validation, for the vendor-specific RF pulses. In-vivo data from IDH-mutated glioma patients, obtained in the three vendors, are discussed.

Metabolic Profiling of Malignant Transformation and IDH-mutation in Diffuse Infiltrating Gliomas
Llewellyn Jalbert1, Adam Elkhaled1, Joanna J Phillips2, Evan Neill3, Marram P Olson3, Mitchel S Berger4, John Kurhanewicz1,3, Susan M Chang4, and Sarah J Nelson1,3
1Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco (UCSF), San Francisco, CA, United States, 2Department of Pathology, University of California, San Francisco (UCSF), San Francisco, CA, United States, 3Department of Radiology & Biomedical Imaging, University of California, San Francisco (UCSF), San Francisco, CA, United States, 4Department of Neurological Surgery, University of California, San Francisco (UCSF), San Francisco, CA, United States
Patients diagnosed with infiltrating low-grade glioma have a relatively long survival, and a balance is often struck between treating the tumor and impacting quality of life. Aggressive treatments are typically reserved for lesions that have undergoing malignant transformation (MT) to a higher-grade lesion. Mutations in the isocitrate dehydrogenase 1 & 2 oncogenes and production of 2-hydroxyglutarate further characterize these tumors and are associated with improved outcome and treatment sensitivity. In this study, we found distinct metabolic profiles associated with patients' tumors that had undergone MT, as well as contained the IDH­-mutated genotype, using proton HR-MAS spectroscopy.

Noninvasive Assessment of IDH Mutational Status in Glioma using MR Elastography
Kay Pepin1, Arvin Arani1, Mona El Sheikh1, Nikoo Fattahi1, David Lake1, Armando Manduca1, Kiaran McGee1, Ian Parney1, Richard Ehman1, and John Huston1
1Mayo Clinic, Rochester, MN, United States
MR elastography (MRE) has been used to characterize the mechanical properties of normal and diseased brain tissue (1-4). This study evaluated MRE for the noninvasive characterization of gliomas, specifically investigating the relationship between tumor stiffness and mutations in the IDH1 gene, an important prognostic biomarker for improved outcome. Eighteen patients were enrolled in this study. MRE examinations were performed at 3T using an EPI-MRE sequence and 60Hz vibration frequency. Tumor stiffness was quantified and compared to IDH mutation status, as determined by histology. Twelve tumors were identified as IDH1 mutation positive and were significantly stiffer than tumors with non-mutated IDH1.  

Amide-Proton-Transfer-Weighted (APTw) MRI as a Surrogate Biomarker to Detect Recurrent High-grade Gliomas after Treatment with Chemoradiation: Validation by Image-Guided Stereotactic Biopsy
Shanshan Jiang1,2, Charles Eberhart3, Jaishri Blakeley4, Lindsay Blair4, Huamin Qin 3, Michael Lim5, Alfredo Quinones-Hinojosa5, Hye-Young Heo1, Yi Zhang1, Dong-Hoon Lee1, Xuna Zhao1, Zhibo Wen2, Peter C.M. van Zijl1, and Jinyuan Zhou1
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 2Department of Radiology, Southern Medical University Zhujiang Hospital, Guangzhou, China, People's Republic of,3Department of Pathology, Johns Hopkins University, Baltimore, MD, United States, 4Department of Neurology, Johns Hopkins University, Baltimore, MD, United States, 5Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, United States
We explored the imaging features of treatment effects and active tumor in glioma patients after surgery and chemoradiation using amide-proton-transfer-weighted (APTw) imaging at 3 Tesla. Needle biopsy samples were obtained for pathological validation. Corresponding APTw signal intensities were recorded. Results showed that APTw signal intensities had strong positive correlations with cellularity and proliferation. The active tumor had significantly higher APTw signal intensity, compared to treatment effects. The area-under-curve (AUC) for APTw intensities to differentiate treatment effects from active tumor was 0.959. APT imaging has potential for molecular image-guided biopsy for post-treatment glioma patients to distinguish pseudoprogression from tumor recurrence.

Amide Proton Transfer (APT) Imaging of Brain Tumors using 3D Fast Spin-Echo Dixon Method: Comparison with Separate B0 Mapping
Osamu Togao1, Akio Hiwatashi1, Jochen Keupp2, Koji Yamashita1, Kazufumi Kikuchi1, Masami Yoneyama3, and Hiroshi Honda1
1Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 2Philips Research, Hamburg, Germany, 3Philips Electronics Japan, Tokyo, Japan
Recently, the FSE Dixon APT acquisition protocol with intrinsic ?B0 correction was developed and implemented on 3T clinical MRI scanners. This technique allows simultaneous acquisition of APT imaging and intrinsic B0 mapping without increasing scan time. In the present study, we demonstrated the quantitative performance of the 3D FSE Dixon APT imaging of brain tumors in comparison with the separate B0 mapping method. 

Introducing steady state blood volume mapping using ferumoxytol, a new MRI tool to assess the intravascular space in brain tumors and other intracranial pathologies
Csanad Varallyay1, Daniel Schwartz2, Joao Prola Netto1, Prakash Ambady2, Andrea Horvath2, and Edward Neuwelt2
1Diagnostic Radiology and Neurology, Oregon Health and Science University, Portland, OR, United States, 2Neurology, Oregon Health and Science University, Portland, OR, United States
Steady state blood volume (SS-CBV) mapping using the blood pool agent ferumoxytol as an MRI contrast agent is feasible in brain tumors and other intracranial pathologies. It allows high resolution, distortion free blood volume maps, which can be a useful MRI tool to improve diagnosis and assessment of response to therapy. Ferumoxytol dose and MRI sequences may be optimized for various clinical applications. 

Semi-quantitative MRI Assessment of anti-PD1 Immunotherapy Response in Recurrent Glioblastoma
Lei Qin1,2, Xiang Li2,3, Amanda Stroiney4, David A Reardon1,2, and Geoffrey Young2,3
1Dana-Farber Cancer Institute, boston, MA, United States, 2Harvard Medical School, boston, MA, United States, 3Brigham and Women's Hospital, Boston, MA, United States, 4Northeastern University, Boston, MA, United States
The purpose of this study is to evaluate the predictive value of quantitative and semi-quantitative MRI biomarkers in determining patient benefit in anti-PD1 immunotherapy treatments. Longitudinal MRIs were performed on patients diagnosed with recurrent GBM. Volumetric analysis of abnormal tissue from contrast enhanced T1, FLAIR, and ADC revealed two distinct patterns: a) progressive increase volume in patients who derived no significant benefit, and b) a transient increase in the volume, followed by a delayed decrease in patients with >6 mo survival on trial. In this preliminary study (n=10), the data suggest that the volume of abnormal tissue on ADC seems to correlate better with patient benefit than abnormality on FLAIR and T1. 

Serial 3D H-1 MRSI of Patients with Newly Diagnosed GBM being Treated with Radiation, Temozolomide, Erlotinib and Bevacizumab
Sarah Nelson1, Yan Li1, Janine Lupo1, Marram Olson1, Jason Crane1, Annette Molinaro2, Ritu Roy3, Soonmee Cha1, and Susan Chang2
1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 2Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States, 3Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, United States
Patients with newly diagnosed GBM are typically treated with a combination of radiation and temozolomide in conjunction with a variety of investigational agents. Assessing the effectiveness of such therapies is complicated by differences in their mechanisms of action that lead to ambiguities in the interpretation of conventional anatomic images and difficulties in assessing the spatial extent of tumor.  The results of this study demonstrate that integrating 3D lactate edited H-1 MRSI into routine MR examinations and applying quantitative analysis methods allows for the objective evaluation of changes in tumor burden and the early assessment of outcome.  

Differential imaging biomarker response to sunitinib across tumor histologies in a prospective trial of brain metastases
Caroline Chung1, Brandon Driscoll1, Warren Foltz1, Cynthia Menard1, David Jaffray1, and Catherine Coolens1
1Princess Margaret Cancer Centre, Toronto, ON, Canada
Our preclinical study of sunitinib (SU) in combination with conformal large single fraction radiation in an orthotopic murine brain tumor model, discovered that changes in apparent diffusion coefficient (ADC), AUC and Ktrans were promising imaging biomarkers that could predict response to SU as well as combined SU and radiation. Based on our preclinical findings, we designed a prospective phase I trial of SU and radiosurgery (SRS) for brain metastases that incorporated translational investigation of these imaging biomarkers.  Here we summarize our discovery of differential ADC and AUC responses to sunitinib between renal cell cancer and other histology brain metastases.

Optimal time-window and perfusion protocol for MRI in early assessment of high grade glioma treatment response
Christopher Larsson1,2, Jonas Vardal1, Inge Rasmus Groote3, Magne Mørk Kleppestø1,2, Petter Brandal4, and Atle Bjørnerud1,5
1The Intervention Centre, Oslo University Hospital, Oslo, Norway, 2Faculty of Medicine, University of Oslo, Oslo, Norway, 3Department of Psychology, University of Oslo, Oslo, Norway, 4Department of Cancer Medicine, Surgery & Transplantation, Oslo University Hospital, Oslo, Norway, 5Faculty of Physics, University of Oslo, Oslo, Norway
Due to limitations in structural MRI in assessment of overall survival (OS) in high grade glioma interest in more advanced functional MRI methods has risen. A prospective longitudinal high grade glioma study including structural imaging and T1/T2* perfusion was performed in 27 patients to investigate the optimal time-window and most sensitive MRI perfusion method for early OS analysis.

No structural imaging, DSC or absolute perfusion parameter was found significant for early OS assessment. Change in median Ktrans and CBF from baseline to eight weeks was found significant and CBF change >15% most accurate predictor for poor OS.


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