Changho Choi¹, Thomas Huber², Anna Tietze³, Byung Se Choi⁴, Jung Hee Lee⁵, Seung-Koo Lee⁶, Alexander Lin⁷, and Sunitha Thakur^8
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.

Llewellyn Jalbert¹, Adam Elkhaled¹, Joanna J Phillips², Evan Neill³, Marram P Olson³, Mitchel S Berger⁴, John Kurhanewicz^1,3, Susan M Chang⁴, and Sarah J Nelson^1,3
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.

Kay Pepin¹, Arvin Arani¹, Mona El Sheikh¹, Nikoo Fattahi¹, David Lake¹, Armando Manduca¹, Kiaran McGee¹, Ian Parney¹, Richard Ehman¹, and John Huston^1
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.  

Shanshan Jiang^1,2, 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 Zhou^1
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.

Osamu Togao¹, Akio Hiwatashi¹, Jochen Keupp², Koji Yamashita¹, Kazufumi Kikuchi¹, Masami Yoneyama³, and Hiroshi Honda^1
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. 

Csanad Varallyay¹, Daniel Schwartz², Joao Prola Netto¹, Prakash Ambady², Andrea Horvath², and Edward Neuwelt^2
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. 

Lei Qin^1,2, Xiang Li^2,3, Amanda Stroiney⁴, David A Reardon^1,2, and Geoffrey Young^2,3
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. 

Sarah Nelson¹, Yan Li¹, Janine Lupo¹, Marram Olson¹, Jason Crane¹, Annette Molinaro², Ritu Roy³, Soonmee Cha¹, and Susan Chang^2
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.  

Caroline Chung¹, Brandon Driscoll¹, Warren Foltz¹, Cynthia Menard¹, David Jaffray¹, and Catherine Coolens^1
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.

Christopher Larsson^1,2, Jonas Vardal¹, Inge Rasmus Groote³, Magne Mørk Kleppestø^1,2, Petter Brandal⁴, and Atle Bjørnerud^1,5
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.