Adam W Autry¹, Sana Vaziri¹, Marisa LaFontaine¹, Jeremy W Gordon¹, Hsin-Yu Chen¹, Yaewon Kim¹, Javier Villanueva-Meyer¹, Susan M Chang², Jennifer Clarke², Duan Xu¹, Janine M Lupo¹, Peder EZ Larson¹, Daniel B Vigneron^1,3, and Yan Li^1
1Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States, ³Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, United States

This study uses multi-parametric ¹H and hyperpolarized carbon-13 (HP-¹³C) MRI to characterize patients with gliomas that express signature pathologic mutations at the time of recurrence

Rui V Simoes¹, Rafael N Henriques¹, Beatriz M Cardoso¹, Tania Carvalho¹, and Noam Shemesh^1
1Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal

The dynamic interplay between cancer cells and their microenvironment impacts progression. We used dynamic glucose-enhanced deuterium MRS (DGE ²H-MRS) to investigate the association between functional metabolic heterogeneity and cell proliferation in a syngeneic mouse model of GBM. Taking a stepwise approach, from cell culture studies to in vivo mouse MRI/MRS and post-mortem analysis, our results suggest a potential role for glucose oxidation rate as a marker of cell proliferation and vascular stability. Extending this methodology to other GBM models and/or molecular subtypes could create new opportunities for non-invasive phenotyping of the disease.

Jesus Pacheco-Torres¹, Tariq Shah¹, W. Nathaniel Brennen², Flonne Wildes¹, and Zaver M Bhujwalla^1,3,4
1Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Fibroblasts play a pivotal role in cancer progression. In prostate cancer, fibroblasts have been shown to induce growth and increase metastatic potential. To further understand how fibroblasts respond to hypoxic tumor microenvironments that are frequently observed in prostate cancer, we have characterized the effects of hypoxia on normal and cancer associated prostate fibroblast (PCAF) metabolomics and invasion using ¹H MRS/I.  We found that hypoxia increased matrix degradation by normal fibroblasts. Furthermore, hypoxia metabolically reprogrammed normal prostate fibroblasts to mimic the metabolic pattern of PCAFs, highlighting the potential role of hypoxia in the transition of normal fibroblasts to CAFs.

Wilburn E Reddick¹, Jared J Sullivan¹, John O Glass¹, Yian Guo², Julie H Harreld¹, Yimei Li², Giles W Robinson³, Amar Gajjar³, and Thomas E Merchant^4
1Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, United States, ²Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, United States, ³Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, United States, ⁴Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN, United States

The current reproducibility study evaluates 140 children treated for medulloblastoma and 92 age-similar controls using TBSS analysis of FA and dosimetry accounting for age. Treatment included surgery, post-operative standard or high dose craniospinal irradiation and adjuvant chemotherapy. FA measures at baseline after surgery but prior to therapy demonstrated an immediate decrease due to tumor and surgery, which was then accentuated by irradiation. A partial recovery of FA followed, which was attenuated in patients receiving higher doses. These longitudinal profiles need to be considered when conducting cross-sectional studies of patients at time points during or after therapy.

Kumar Pichumani¹, Omkar Ijare¹, Elizabeth Maher², Robert M Bachoo², and David S Baskin^1
1Peak Center, Neurosurgery, Houston Methodist Hospital, Houston, TX, United States, ²UT Southwestern Medical Center, Dallas, TX, United States

Pyruvate recycling is the metabolic pathway that generates pyruvate, lactate and alanine from the tricarboxylic acid (TCA) cycle intermediates, oxaloacetate (OAA) and malate. It is active in the liver and the kidney. Although existence and origin of pyruvate recycling mechanism in human brain has been shown to be active, it still remains controversial. Here, we demonstrate that pyruvate recycling mechanism is active in human GBM patients by ¹³C isotopomer analysis of resected tumor tissues. We have developed a simple method to determine the relative flux of pyruvate recycling with respect to glycolysis using C2 lactate ¹³C isotopomers.

Samuel Bobholz¹, Allison Lowman², Michael Brehler², Savannah Duenweg¹, Fitzgerald Kyereme², Elizabeth Cochran³, Jennifer Connelly⁴, Wade Mueller⁵, Mohit Agarwal², Darren O'Neill², Anjishnu Banerjee⁶, and Peter LaViolette^2,7
1Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, ²Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, ³Pathology, Medical College of Wisconsin, Milwaukee, WI, United States, ⁴Neurology, Medical College of Wisconsin, Milwaukee, WI, United States, ⁵Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States, ⁶Biostatistics, Medical College of Wisconsin, Milwaukee, WI, United States, ⁷Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI, United States

This study investigated the relationship between MRI-intensity values and pathological features of brain cancer using autopsy tissues as ground truth. Mixed effect models were used to examine the association between T1, T1C, FLAIR, and ADC intensity and pathological features (cellularity, cytoplasm density, and extracellular fluid density), as well as to compare the strength of these associations between GBM and non-GBM patients. These analyses confirmed many of the associations seen in prior literature, but with decreased strength than expected. Additionally, this study found that radio-pathomic associations were weaker in GBM patients than non-GBM patients.

Manabu Kinoshita¹, Hideyuki Arita¹, Masamichi Takahashi², Takehiro Uda³, Junya Fukai⁴, Kenichi Ishibashi⁵, Noriyuki Kijima¹, Ryuichi Hirayama¹, Mio Sakai⁶, Atsuko Arisawa⁷, Hiroto Takahashi⁷, Katsuyuki Nakanishi⁶, Naoki Kagawa¹, Kouichi Ichimura⁸, Yonehiro Kanemura⁹, Yoshitaka Narita², and Haruhiko Kishima^1
1Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan, ²Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan, ³Neurosurgery, Osaka City University Graduate School of Medicine, Osaka, Japan, ⁴Neurological Surgery, Wakayama Medical University, Wakayama, Japan, ⁵Neurosurgery, Osaka City General Hospital, Osaka, Japan, ⁶Diagnostic Radiology, Osaka International Cancer Institute, Osaka, Japan, ⁷Radiology, Osaka University Graduate School of Medicine, Suita, Japan, ⁸Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan, ⁹Biomedical Research and Innovation, National Hospital Organization Osaka National Hospital, Osaka, Japan

Although the T2-FLAIR mismatch sign is a promising imaging marker specific for IDHmt, non-CODEL astrocytomas, its low sensitivity and NPV hinder its full clinical application. This study discovered that FLAIR acquisition with TI shorter than 2400 ms in 3T could overcome this issue and that the sensitivity and NPV improved to 67% and 74%. Tuning TI for FLAIR acquisition is such a simple technique that clinicians can easily incorporate this procedure into the daily workflow of glioma imaging. Our proposed method would provide a novel yet clinically feasible glioma imaging method in the era of personalized-molecular medicine of cancer.

Fatemeh Arzanforoosh¹, Paula L. Croal², Karin Van Garderen¹, Marion Smits¹, Michael A. Chappell², and Esther A.H. Warnert^1
1Department of Radiology & Nuclear Medicine, ErasmusMC, Rotterdam, Netherlands, ²Radiological Sciences, Division of Clinical Neurosciences, University of Nottingham, Nottingham, United Kingdom

Reliable insight about tumor microvasculature is important for monitoring of disease progression and treatment response. Derived from Dynamic Susceptibility Contrast MRI, transverse relaxation rates are used for vessel size estimation. In high grade glioma, these signals can artificially change by contrast agent extravasation through a disrupted Blood-Brain-Barrier. In this study the effect of applying Boxerman-Schmainda-Weisskoff leakage correction on vessel size estimation has been investigated on a group of 12 glioma patients. The result shows that in Contrast-Enhanced Tumor area applying leakage correction significantly and noticeably changes the vessel size measurements.

Nan Zhang¹, Qingwei Song², Ailian Liu², Haonan Zhang², Renwang Pu², Jiazheng Wang³, and Zhiwei Shen^3
1The First Affilliated Hospital of Dalian Medical University, Dalian, China, ²The First Affiliated Hospital of Dalian Medical University, Dalian, China, ³Philips Healthcare, Beijing, China, Beijing, China

Amide proton transfer weighted (APTw) imaging is a novel and promising MRI method for brain tumor imaging, but it can be time-consuming. Common parallel imaging methods, like SENSE, can lead to reduced image quality and increased artifact at high acceleration factors. Here, the compressed SENSE (CS) technique with combined strength from both compressed sensing and SENSE was evaluated for the acceleration of APTw imaging in brain. Results showed that it is feasible to apply an CS accelerator factor of 5 to APTw imaging of brain tissue and tumor, which could reduce the scan time to less than 1 min.

Yae Won Park¹, Ji Eun Park², Sung Soo Ahn¹, Seung Hong Choi³, Ho Sung Kim², and Seung-Koo Lee^1
1Yonsei University College of Medicine, Seoul, Korea, Republic of, ²University of Ulsan College of Medicine, Seoul, Korea, Republic of, ³Seoul National University Hospital, Seoul, Korea, Republic of

Epidermal growth factor receptor (EGFR) amplification status of isocitrate dehydrogenase-wildtype (IDHwt) lower-grade gliomas (LGGs; grade II/III) is one of the key molecular markers for diagnosing molecular glioblastoma. Our study shows that infiltrative or mixed pattern, lower ADC, lower 5th percentile of ADC, and higher 95th percentile of nCBF may be useful imaging biomarkers for the EGFR amplification of IDHwt LGGs. Moreover, quantitative imaging biomarkers may add value to qualitative imaging parameters (with AUCs of 0.71 and 0.88, p = 0.020).