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Keywords: CEST & MT, Treatment, Glioma

In this prospective clinical study we compared the ability of asymmetry-based amide proton transfer-weighted (APTw) imaging with Lorentzian-fit-based (PeakAreaAPT and MT_const) and relaxation-compensated (MTR_RexAPT and MTR_RexMT) CEST-MRI of the amide proton transfer (APT) and semisolid magnetization transfer (ssMT) at 3T for the prediction of the overall survival of patients with glioma at the first follow-up after completion of radiotherapy. The APTw (HR=4.66, p<0.001) was more strongly associated with survival compared to the MTR_RexAPT (HR=2.44, p=0.056) and MT_const (HR=2.54, p=0.044). The MTR_RexMT and PeakAreaAPT did not display any association with survival.

Yinhang Jia^1,2, Guangxu Han¹, Zejun Wang¹, Yi-Cheng Hsu³, Yi Sun³, Bao Wang⁴, Yingchao Liu^5,6, and Ruiliang Bai^2,7
1Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China, ²School of Medicine, Zhejiang University, Hangzhou, China, ³MR Collaboration, Siemens Healthcare, Shanghai, China, ⁴Department of Radiology, Qilu Hospital of Shandong University, Jinan, China, ⁵Department of Neurosurgery, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China, ⁶Shandong National Center for Applied Mathematics, Shandong University, Jinan, China, ⁷College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China

Keywords: Tumors, Brain, Glioma, Aquaporins-4, transmembrane water-efflux rate, therapy-resistant.

The water-selective channel aquaporin-4 (AQP4) contributes to the migration and proliferation of gliomas, and to their resistance to therapy. Here, we show, in glioma animal models, and in glioma patients, that transmembrane water-efflux rate is a sensitive and specific biomarker of AQP4 expression and can be measured via dynamic-contrast-enhanced magnetic resonance imaging. Water-efflux rates correlated with changes in the heterogeneity of intratumoural and intertumoural AQP4 in human gliomas and following treatment with the AQP4 inhibitor TGN020. Regions with low water-efflux rates contained higher fractions of stem-like slow-cycling cells and therapy-resistant cells, suggesting that maps of water-efflux rates could be used to identify gliomas that are resistant to therapies.

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Gabriel Hoffmann^1,2, Christine Preibisch^1,2, Matthias Günther^3,4,5, Amnah Mahroo³, Matthias JP van Osch^6,7, Lena Václavů⁶, Lena Schmitzer¹, Claus Zimmer^1,2, Benedikt Wiestler¹, and Stephan Kaczmarz^1,2,8
1Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ²TUM-Neuroimaging Center, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ³MR Physics, Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany, ⁴MR-Imaging and Spectroscopy, University of Bremen, Bremen, Germany, ⁵mediri GmbH, Heidelberg, Germany, ⁶C.J. Gorter MRI Center, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, ⁷Leiden Institute of Brain and Cognition, Leiden University, Leiden, Netherlands, ⁸Philips GmbH Market DACH, Hamburg, Germany

Keywords: Tumors, Permeability, Blood Brain Barrier

High-grade glioma are known to cause blood brain barrier (BBB) disruption, facilitating molecular leakage from inside the vessels into tissue. Current methods to probe BBB integrity are either not quantitative or, by using Gadolinium, insensitive to subtle changes. Here, we present first data of arterial spin labelling (ASL)-based BBB mapping of water exchange time (Texch) in brain tumour patients. Results show faster exchange (shorter Texch) in tumorous and even normal-appearing tissue compared to healthy subjects. This highlights the potential of ASL-based water exchange mapping as a proxy measure for BBB integrity, and its potential sensitivity to even subtle impairments.

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Zachary A. Corbin¹, Yanning Liu², Robert K. Fulbright³, Serena Thaw-Poon¹, Joachim M. Baehring¹, Nicholas Blondin¹, Peter Kim¹, Antonio Omuro¹, Veronica L. Chiang⁴, Jennifer Moliterno⁴, Sacit B. Omay⁴, Joseph M. Piepmeier⁴, Douglas L. Rothman³, Robin A. de Graaf³, and Henk M. De Feyter^3
1Department of Neurology, Yale University, New Haven, CT, United States, ²Department of Biomedical Engineering, Yale University, New Haven, CT, United States, ³Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States, ⁴Department of Neurosurgery, Yale University, New Haven, CT, United States

Keywords: Tumors, Metabolism, deuterium

Deuterium metabolic imaging (DMI), a combination of ²H MRSI with administration of a deuterated substrate, was used to map regional metabolism of [6,6’-²H₂]-glucose in 24 patients with multiple types of brain tumors. DMI data were acquired 70-90 minutes after oral intake of the deuterated glucose and revealed strong tumor-to-brain image contrast in high-grade tumors. Our metric, based on the labeling of specific glucose metabolites, reflects the canonical glucose metabolism in aggressive tumors – the Warburg Effect. The Warburg Effect appears higher in high-grade tumors and showed potential as a biomarker of treatment effect.  

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Keywords: Tumors, Deuterium, glioma

Dynamic glucose-enhanced deuterium MRS (DGE ²H-MRS) coupled with Marchenko-Pastur PCA (MPPCA) denoising has been recently applied to immunocompetent mouse glioblastoma subtypes (GL261 and CT2A), demonstrating the ability to measure glucose metabolism through glycolysis and mitochondrial oxidation non-invasively, and its association with tumor proliferation. Here, we extend this approach to DGE Deuterium Metabolic Imaging (DGE-DMI) coupled with tensor MPPCA (tMPPCA) denoising, to map glucose fluxes in the same mouse models of glioblastoma. Our results demonstrate a strong association between glycolytic rates and MRI and histologic features of inter/intra-tumor heterogeneity.

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Gilbert Hangel^1,2,3, Philipp Lazen^1,2, Sukrit Sharma², Cornelius Cadrien^1,2, Thomas Roetzer-Pejrimovsky⁴, Eva Niess², Lukas Hingerl², Stephan Gruber², Bernhard Strasser², Barbara Kiesel¹, Adelheid Woehrer⁴, Matthias Preusser⁵, Julia Furtner^6,7, Wolfgang Bogner², Siegfried Trattnig², Karl Rössler¹, and Georg Widhalm^1
1Department of Neurosurgery, Medical University of Vienna, Vienna, Austria, ²High-field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ³Christian Doppler Laboratory for MR Imaging Biomarkers, Vienna, Austria, ⁴Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria, ⁵Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, ⁶Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ⁷Medical Image Analysis und AI, Danube Private University, Krems, Austria

Keywords: Tumors, Spectroscopy

Research indicates that glutamate (Glu) and glutamine (Gln) play a role in the infiltrative properties of diffuse gliomas. Overcoming limitations of previous MRSI techniques, our 7T MRSI approach allows high-resolution Glu imaging. We investigated intra- and peritumoral Glu and Gln in a cohort of 36 patients and found significant increases in peritumoral Glu/tNAA, Gln/tNAA, Glu/tCr, and Gln/tCr compared to a NAWM control region. We established peritumoral Dice similarity coefficients of 0.67 for Glu/tNAA and Gln/tNAA compared to 0.31 for tCho/tNAA.

Our results that Glu/Gln imaging could investigate the metabolism of infiltrative gliomas.

Noriaki Minami¹, Donghyun Hong¹, Celine Taglang¹, Georgios Batsios¹, Anne Marie Gillespie¹, Pavithra Viswanath¹, Nicholas Stevers², Joseph F Costello², and Sabrina M Ronen^1
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, ²Department of Neurological Surgery, UCSF, San Francisco, CA, United States

Keywords: Tumors, Brain, Glioblastoma, GBM, TERT, GABP, imaging, MRI, MRS, NMR

TERT promoter mutation is a genetic hallmark of glioblastoma, and targeting TERT or its upstream transcriptional factor GABPB1 are considered ideal therapeutic targets. Accordingly, establishing reliable imaging modalities that will enable monitoring of TERT silencing are needed as early indicators of target engagement and response to these molecular targeting therapies. Here, we demonstrate that using ¹³C MRS to monitor the metabolism of hyperpolarized δ-[1-¹³C] gluconolactone via the pentose phosphate pathway to 6-phosopho-[1-¹³C]gluconate (6PG) provides such a noninvasive imaging readout of TERT or GABPB1 silencing in glioblastoma.

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Adhithyan Rajendran¹, Chidambaranathan Natesan², Lavanya Yegnaraman², Rakesh Jalali³, Rashmi Rao⁴, Manikandan Mariyapillai⁵, Prashant Jawahar¹, Roopesh Kumar⁶, Srinivas Chilukuri⁷, and Sushma Patil^8
1Radiology, Apollo Proton Cancer Centre, Chennai, India, ²Radiology, Apollo Hospitals Greams Road, Chennai, India, ³Radiation Oncology, Apollo Proton Cancer Centre, chennai, India, ⁴Radiology, Philips India Ltd, Bangalore, India, ⁵Philips India Ltd, Chennai, India, ⁶Neurosurgery, Apollo Proton Cancer Centre, Chennai, India, ⁷Radiation Oncology, Apollo Proton Cancer Centre, Chennai, India, ⁸Pathology, Apollo Proton Cancer Centre, Chennai, India

Keywords: Tumors, CEST & MT, Amide Proton Transfer Imaging

Atypical features of Pilocytic astrocytoma (PA) on conventional MR imaging are often challenging and can be mistaken as High-grade glioma. Advanced Novel techniques of Amide Proton Transfer (APT) and Arterial spin labelling (ASL) have shown promising results in the grading of gliomas. This study to explore the added value and utility in characterizing the atypical form of PA, if these two non-contrast techniques are combined in the clinical practice. Mismatch between  APT and ASL signals, was seen in all the cases of PA and this unique imaging appearance of APT ASL imaging mismatch could be a biomarker for pilocytic astrocytoma.

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Yaoming Qu¹, Qin Qin^2,3, and Zhibo Wen^1
1Radiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China, ²The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA, Baltimore, MD, United States

Keywords: Tumors, Perfusion

Velocity selective arterial spin labeling (VSASL) has shown comparable CBF measurements in brain gliomas with DSC-PWI. As CBV derived from DSC-PWI is the most widely adopted perfusion marker of brain tumor angiogenesis, the clinical utility for neurooncology imaging of VSASL based CBV quantification worth investigation. This study on preoperative patients with brain gliomas demonstrated that VSASL provided highly correlated quantifications of relative tumor blood volume (R²=0.83) compared to DSC-PWI, and further improved diagnostic performance than VSASL derived relative tumor blood flow measurements (ROC AUC=0.94 vs. 0.89), indicating its potential as a viable non-contrast alternative to DSC-PWI for brain tumor applications.

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Qianqi Huang^1,2, Jingpu Wu^1,3, Yiqing Shen^1,2, Nhat Le^1,2, Pengfei Guo^1,2, Karisa Schreck⁴, David Kamson⁴, Lindsay Blair⁴, Hye Young Heo¹, Xu Li^1,5, Wenbo Li^1,5, Haris Sair¹, Jaishri Blakeley⁴, John Laterra⁴, Matthias Holdhoff⁶, Stuart Grossman⁶, Debraj Mukherjee⁷, Chetan Bettegowda ⁷, Peter van Zijl ^1,5, Jinyuan Zhou¹, and Shanshan Jiang^1
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ²Department of Computer science, Johns Hopkins Univeristy, Baltimore, MD, United States, ³Department of Applied Mathematics and Statistics, Johns Hopkins Univeristy, Baltimore, MD, United States, ⁴Department of Neurology, Johns Hopkins University, Baltimore, MD, United States, ⁵Department of Radiology, Kennedy Krieger Institute, Baltimore, MD, United States, ⁶Department of Oncology, Johns Hopkins University, Baltimore, MD, United States, ⁷Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, United States

Keywords: Tumors, Treatment

We explored non-contrast-enhanced MRI performances of APTw, DWI, SWI, and pCASL at 3 Tesla in glioma patients post-treatment. APTw, ADC, QSM, and CBF histogram parameters from volumetric ROIs were recorded. Multivariable logistics regression with principal component analysis (PCA) was built for differentiating treatment effect from tumor recurrence. Results showed that the regression model trained on the combination of APTw, CBF, and QSM achieved the highest classification performance, with an AUC of 0.90.

Kun Wang¹, Yujie Yu¹, Maoxue Wang¹, Ming Li¹, Xiance Zhao², Peng Wu², and Kan Deng^3
1The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, ²Philips Healthcare, Shanghai, China, ³Philips Healthcare, Guangzhou, China

Keywords: Tumors, Brain

Diusion weighted imaging (DWI) has high sensitivity in the dierential diagnosis of nasopharyngeal carcinoma. However,the DWI based on SE-EPI has poor imaging quality in the nasopharynx. A combination of Multi-Vane (MV) and SPLICE(MV-SPLICE) were developed to reduce ELT, as well as improve SNR and the imaging quality of DWI. This study compares theDWI images of three acquisition sequences in nasopharynx,including DWI TSE without SPLICE(TSE), TSE with SPLICE(TSE-XD), and TSE with MV-SPICE(TSE-XD-MV) and proves that TSE with MV-SPLICE DWI based TSE with MV-SPLICE provides anexcellence imaging scheme of DWI for the clinical diagnosis of nasopharyngeal diseases.

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Giacomo Annio^1,2, Robin Bugge³, Siri Fløgstad Svensson ³, Omar Darwish⁴, Giorgio Seano⁵, Donata Biernat ⁶, Karoline Skogen ⁶, Jon Ramm-Pettersen ⁷, Einar Vik-Mo ⁷, Katharina Schregel ⁸, Kyrre Eeg Emblem³, and Ralph Sinkus^1
1INSERM - King's College, Paris, France, ²School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom, ³Department of Diagnostic Physics, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway, ⁴Department of Biomedical Engineering, King's College London, London, United Kingdom, ⁵U1021 INSERM, Institut Curie, Paris, France, ⁶Department of Radiology Ullevål, Division of Radiology and Nuclear Medicine,, Oslo University Hospital, Oslo, Norway, ⁷Department of Neurosurgery, Division of Clinical Neuroscience,, Oslo University Hospital, Oslo, Norway, ⁸Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany

Keywords: Tumors, Elastography

The reciprocal interaction between cancer cells and the surrounding creates a tumorigenic feedback loop capable of shifting the anti-neoplastic feature of the microenvironment towards a tumour growth-promoting one. Unfortunately infiltrating tumours, like GBMs, do not have discrete boundaries and intra-axial metastases are not visible on conventional MR images. However they are expected to change the tissue biomechanics. Here we explored tumour microenvironment biomechanics non-invasively using MRE in a cohort of 23 patients with brain tumours - 13 meningiomas, 10 glioblastomas. We show how MRE provides a comprehensive characterization of the tumour microenvironment, explaining histological features and tumour invasive features.

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Poonam Choudhary¹, YuXiang Zhou², Sudarshan Ragunathan³, Ethan Mathew¹, Aliya Anil¹, Natenael Semmineh⁴, Belinda Gutierrez¹, John P Karis⁵, Leland S. Hu², Kathleen M. Schmainda⁶, Ashley M. Stokes¹, and C. Chad Quarles^4
1Division of Neuroimaging Research and Barrow Neuroimaging Innovation Center, Barrow Neurological Institute, Phoenix, AZ, United States, ²Department of Radiology, Mayo Clinic College of Medicine, Phoenix, AZ, United States, ³Hyperfine Inc., Guilford, CT, United States, ⁴The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁵Neuroradiology, Southwest Neuroimaging at Barrow Neurological Institute, Phoenix, AZ, United States, ⁶Department of Biophysics Medical College of Wisconsin, Milwaukee, WI, United States

Keywords: Tumors, DSC & DCE Perfusion, sequence

Single-echo pulse sequences are commonly employed for DSC-MRI. The multi-echo spin and gradient echo (SAGE) sequence can be useful in multi-contrast and multi-scale imaging of morphologic and functional features of brain tumor vasculature.  The goal of this study is to establish harmonized SAGE sequence and analysis protocol across  primary MRI vendors to facilitate multi-site clinical trials. In this work, we present initial results of SAGE sequence multi-site reproducibility and repeatability in phantom, healthy volunteers and high-grade glioma patients.

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Liam S. P. Lawrence¹, Rachel W. Chan¹, James Stewart², Mark Ruschin², Aimee Theriault², Sten Myrehaug², Jay Detsky², Pejman J. Maralani³, Chia-Lin Tseng², Hany Soliman², Mary Jane Lim-Fat⁴, Sunit Das⁵, Greg J. Stanisz^1,6, Arjun Sahgal², and Angus Z. Lau^1
1Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ²Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ³Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁴Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁵Department of Surgery, St. Michael's Hospital, Toronto, ON, Canada, ⁶Department of Neurosurgery and Paediatric Neurosurgery, Medical University, Lublin, Poland

Keywords: Tumors, Diffusion Tensor Imaging

Diffusion tensor imaging was implemented on a 1.5T MR-Linac and used to scan ten glioma patients and four healthy volunteers. Mean diffusivity and fractional anisotropy (FA) measurements were compared to those at 3T in 35 glioma patients. FA values surrounding the tumour and in white matter structures (genu, splenium, and body of corpus callosum) were investigated for the detection of tumour infiltration and radiation-induced damage, respectively. There was no evidence of dose-dependent white matter changes, in contrast to previous literature. Peritumoural FA changes occurred more frequently for high-grade compared to low-grade gliomas.

Ivar J.H.G. Wamelink^1,2, Hugo Hempel¹, Elsmarieke van de Giessen^1,3, Mark Vries¹, Philip de Witt Hamer^2,4, Frederik Barkhof^1,5, and Vera C. Keil^1,2,3
1Radiology & Nucleaire Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands, ²Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands, ³Neuroscience, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands, ⁴Neurosurgery, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands, ⁵UCL institutes of Neurology and Healthcare Engineering, London, United Kingdom

Keywords: Tumors, Challenges, Patient experience

Glioma patient experience of MRI scans, repeated follow-up, and gadolinium-based contrast agents (GBCA) are unknown, despite the vulnerability of this patient group and relevant implications for clinics and science. This cross-sectional survey questioned 100 patients with primary brain tumors and found generally positive experiences with neuro-oncological scans. Age, diagnosis, and number of previous scans had little impact on the patient experience. However, women found MRI and intravenous injection significantly more uncomfortable. Also, patients would prefer GBCA-free MRIs if diagnostically equivalent. Patient knowledge towards GBCAs was limited and better information  regarding GBCA and the MRI itself is needed.