Emma L. Reeves¹, Jin Li¹, Jessica K. R. Boult¹, Barbara Blouw², David Kang², Jeffrey C. Bamber¹, Yann Jamin¹, and Simon P. Robinson^1
1Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom, ²Halozyme Therapeutics, San Diego, CA, United States

Degradation of hyaluronan by PEGPH20 can improve stromal-dense tumour response to therapy. Given PEGPH20 treatment is associated with a reduction in tumour water content, we hypothesised that T₁, T₂, MTR and ADC may inform on PEGPH20 response. MRI was performed before and after PEGPH20 treatment in 4T1 HAS3 and MDA-MB-231 LM2-4 orthotopic breast tumours. T₁, T₂, and ADC significantly decreased, and MTR significantly increased following PEGPH20 treatment in 4T1 HAS3 tumours. PEGPH20 significantly decreased ADC but did not change T₁, T₂ or MTR in MDA-MB-231 LM2-4 tumours. These data suggest that ADC can detect breast tumour response to PEGPH20.

Paola Porcari¹, Ellen Ackerstaff¹, Dov P Winkleman¹, Suresh Veeraperumal¹, Natalia Kruchevsky¹, H. Carl Lekaye¹, and Jason A. Koutcher^1,2,3,4
1Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ²Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ³Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ⁴Weill Cornell Medical College, Cornell University, New York, NY, United States

Intracellular iron, essential for cancer cell proliferation and metabolism, is modified in cancer cells. Triple-negative breast cancers are metastatic cancers associated with a high recurrence rate, poor prognosis and lack of effective targeted therapies. We are investigating the potential of Deferiprone, a clinically approved intracellular iron chelator for non-cancer related diseases, to improve chemotherapeutic treatment response in triple-negative breast cancer by altering iron-dependent proliferation and metabolism. The effectiveness of Deferiprone to impair triple-negative breast cancer cell growth and affect cellular metabolism was evaluated by monitoring live cells, exposed to Deferiprone, in an MR-compatible cell bioreactor using multi-nuclear MRS.

Aliya Qayyum¹, Rony Avritscher², Rizwan Aslam¹, Jingfei Ma³, Mark Pagel⁴, Jia Sun⁵, Yehia Ibrahim Mohammed⁶, Manal Hassan⁷, Hesham Amin⁸, Asif Rashid⁹, Sunyoung Lee⁶, Robert A Wolff⁶, James C Yao⁶, Richard L Ehman¹⁰, Gabriel Daniel Duda¹¹, and Ahmed Omar Kaseb^12
1Radiology, MD Anderson, Houston, TX, United States, ²Interventional Radiology, MD Anderson, Houston, TX, United States, ³Imaging Physics, MD Anderson, Houston, TX, United States, ⁴Cancer Systems Imaging, MD Anderson, Houston, TX, United States, ⁵Biostatistics, MD Anderson, Houston, TX, United States, ⁶GI Medical Oncology, MD Anderson, Houston, TX, United States, ⁷Epidemiology, MD Anderson, Houston, TX, United States, ⁸Hemopathology, MD Anderson, Houston, TX, United States, ⁹Pathology, MD Anderson, Houston, TX, United States, ¹⁰Radiology, Mayo Clinic, Rochester, MN, United States, ¹¹Radiation Oncology, Massachusetts General Hospital, Boston, MA, United States, ¹²MD Anderson, Houston, TX, United States

Newer systemic treatments for advanced hepatocellular carcinoma (HCC) include immune checkpoint blockade (ICB) which act through increasing cytotoxic T-cell mediated response to tumor. There is a lack of biomarkers of ICB response and treatment outcomes are not correlated with change in tumor size. We evaluated MRI imaging features of HCC and change in tumor stiffness after 6 weeks immunotherapy in surgical and non-surgical patients. An increase in HCC stiffness on MRE after 6 weeks treatment was significantly correlated with treatment response. Longitudinal measurement of tumor stiffness on MRE provides a novel technique for early immunotherapy response assessment.

Puneet Bagga¹, Stephen Pickup¹, Denis Migliorini², Neil E Wilson¹, Mohammad Haris^3,4, Suyash Mohan¹, Avery D Posey², and Ravinder Reddy^1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, United States, ³Sidra Medicine, Doha, Qatar, ⁴LARC, Qatar University, Doha, Qatar

With the advent of clinically effective CD19 based chimeric antigen receptor (CAR) T cell immunotherapies, there are incidents of associated neurotoxicity. In this study, we report the use of gadolinium enhanced MRI to image BBB disruption caused by CD1928z CAR-T cell on target action against brain pericytes of immunodeficient non-tumor bearing NSG mice. Pericytes are mural cells that wrap endothelial cells and are critical for maintaining blood-brain-barrier (BBB) integrity and express CD19. The MRI results were also found to corroborate with the Evans blue dye BBB permeability assay.

Hatef Mehrabian¹, Wilfred W Lam¹, Hany Soliman^1,2,3, Sten Myrehaug^2,3, Arjun Sahgal^1,2,3, and Greg J Stanisz^1,4
1Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ²Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ³Radiation Oncology, University of Toronto, Toronto, ON, Canada, ⁴Medical Biophysics, University of Toronto, Toronto, ON, Canada

Brain metastases are treated with single fraction stereotactic radiosurgery (sf-SRS) or hypofractionated radiation therapy (HFTR). CEST was previously shown to identify responders to sf-SRS within one-week post-treatment. This study investigated the differences in CEST and MT properties of brain metastases treated with sf-SRS and 5 fraction HFRT (5f-HFRT) one week after treatment. We observed statistically significantly larger reduction in CEST properties of tumours treated with sf-SRS compared to those treated with 5f-HFRT. However, changes in MT properties of the two cohort were similar. Such differences should be considered when evaluating response of brain metastases to radiotherapy using CEST and MT.

Dina Sikpa¹, Jérémie P. Fouquet¹, Luc Tremblay¹, Réjean Lebel¹, Benoit Paquette¹, and Martin Lepage^1
1Université de Sherbrooke, Sherbrooke, QC, Canada

We studied the late radiation effect of a low radiation dose on the healthy mouse brain using MRI and histology. MRI enables the visualisation of early inflammation and late radiation necrosis. Histological analysis confirmed tissue damage and revealed that cellular (astrocytes, microglia) and molecular activation (ICAM-1, VCAM-1) as a result of neuro-inflammation precedes the formation of the necrotic core.

Elavarasan Subramani¹, Chloe Najac¹, Georgios Batsios¹, Marina Radoul¹, Pavithra Viswanath¹, Abigail Molloy¹, Donghyun Hong¹, Anne Marie Gillespie¹, Russell O. Pieper^2,3, Joseph Costello², and Sabrina M Ronen^1,3
1Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Department of Neurological Surgery, Helen Diller Research Center, University of California San Francisco, San Francisco, CA, United States, ³Brain Tumor Research Center, University of California San Francisco, San Francisco, CA, United States

Temozolomide (TMZ) is most commonly used for the treatment of primary glioblastoma but is now being considered for the treatment of low-grade glioma that harbor mutations in the cytosolic isocitrate dehydrogenase 1 (IDH1) gene. Though the treatment of IDH1 mutant patients with TMZ improves survival, there is a need for complementary metabolic imaging approaches to help in assessing early response to therapy. Hyperpolarized ¹³C magnetic resonance spectroscopy-based metabolic profiling of mutant IDH1 cells treated with TMZ revealed that [1-¹³C]/[5-¹³C] glutamate production from [1-¹³C] α-ketoglutaric acid/[2-¹³C] pyruvate could serve as translatable biomarkers of response to therapy.

Yves De Deene¹, Morgan Wheatley², Gary Liney³, David Waddington⁴, Urszula Jelen³, and Bin Dong^3
1Engineering, Macquarie University, North Ryde - Sydney, Australia, ²Macquarie University, North Ryde - Sydney, Australia, ³Ingham Institute, Liverpool, Australia, ⁴The University of Sydney, Sydney, Australia

4D radiation dosimetry using a highly radiation-sensitive polymer gel dosimeter with real-time quantitative MRI readout is presented as a technique to acquire the accumulated radiation dose distribution during image guided radiotherapy (IGRT) in an MRI-Linac. Optimized T₂ weighted TSE scans are converted to quantitative R₂ maps and subsequently to radiation dose maps. A further increase in temporal resolution using a keyhole imaging approach is proposed. The potential use of real-time 4D radiation dosimetry for safeguarding image guided radiotherapy (IGRT) of moving and deforming targets in an MRI-Linac will be discussed.

David Waddington^1,2, Nicholas Hindley¹, Neha Koonjoo^2,3, Tess Reynolds¹, Bo Zhu^2,3, Chiara Paganelli⁴, Matthew Rosen^2,3,5, and Paul Keall^1
1ACRF Image X Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia, ²A. A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ³Department of Physics, Harvard University, Cambridge, MA, United States, ⁴Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy, ⁵Harvard Medical School, Boston, MA, United States

MRI-Linacs are new cancer treatment machines integrating radiotherapy with MRI. Dynamically adapting the radiation beam on the basis of MR-detected anatomical changes (e.g. respiratory and cardiac motion) promises to increase the accuracy of MRI-Linac treatments. A key challenge in real-time beam adaptation is accurately reconstructing images in real time. Historically, reconstruction of data acquired with accelerated techniques, such as compressed sensing, has been very slow. Here, we use AUTOMAP, a machine-learning framework, to quickly and accurately reconstruct radial MRI data simulated from a digital thorax phantom. These results will guide development of real-time adaptation technologies on MRI-Linacs.

Benjamin C Rowland¹, Steven Jackson², David Cobben^1,2, Hanna Maria Hanson¹, Ahmed Saleem¹, Kathryn Banfill², Lisa McDaid², Michael Dubec², and Marcel van Herk^1
1University of Manchester, Manchester, United Kingdom, ²The Christie NHS Trust, Manchester, United Kingdom

We investigated three different Deep Learning techniques for performing retrospective fat suppression in T2 weighted imaging of lung cancer. The methods considered were two U-nets, using an L1 cost function or a conditional GAN, and a CycleGAN. The networks were trained on 900 images and then 16 test images were scored by 3 oncologists and a research radiographer. The L1 U-net and CycleGAN were scored at 73% and 72% respectively, relative to a gold standard of 80% for prospectively fat saturated images, and the scorers indicated they would be happy to use the generated images for radiotherapy target delineation.