Julian C. Assman¹, Jeffrey R. Brender², Don E. Farthing¹, Keita Saito², Kathrynne A. Warrick¹, Natella Maglakelidze¹, Hellmut R. Merkle³, Murali C. Krishna², Ronald E. Gress¹, and Nataliya P. Buxbaum^1
1Experimental Transplantation and Immunotherapy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, MD, United States, ²Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, MD, United States, ³Laboratory for Functional and Molecular Imaging, National Institute of Neurological Disorders and StrokNational Institutes of Health, Bethesda, MD, MD, United States

Water is a substrate for many biochemical reactions. If D₂O is ingested, it will be incorporated into proliferating cells. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with ²H which would allow visualization by deuterium MRI following a short in vivo D₂O labeling period. We initiated systemic D₂O labeling in HT-29 and MiaPaCa-2 xenograft models and performed deuterium MRI following 7 and 14 days of in vivo tumor growth and labeling. We show that small tumors could be distinguished from normal tissue by the incorporation D₂O into lipids with a greater sensitivity and selectivity than anatomical MRI. 

Xiao-Hong Zhu¹, Tao Wang¹, Yibo Zhao^2,3, Yudu Li^2,3, Rong Guo^2,3, Yi Zhang¹, Walter Low⁴, Zhi-Pei Liang^2,3, and Wei Chen^1
1CMRR, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, ²Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ³Departments of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Department of Neurosurgery, University of Minnesota, Minneapolis, MN, United States

Noninvasive MR-based metabolic imaging of brain tumor may offer new tools for clinic diagnosis and monitoring of tumor growth or assessment of treatment efficacy. One potential candidate is the dynamic deuterium MRS (DMRS) imaging technique recently developed. To reach its full potential, we integrated advanced data processing with D-MRSI to enhance its sensitivity or spatiotemporal resolution. We demonstrated in this pilot study that quantitative “Warburg Effect” map and kinetic time courses of deuterated metabolites can be achieved with good spatiotemporal scales in rat brain tumor using Deep-SPICE based deuterium MRSI, which could potentially be applied to brain tumor patients.

Kevan L. Ip¹, Monique A. Thomas¹, Akshay Khunte¹, Kevin L. Behar², Robin A. de Graaf¹, and Henk M. De Feyter^1
1Dept. of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States, ²Dept. of Psychiatry, Yale University, New Haven, CT, United States

A high level of intracellular choline is an established marker of malignancy in brain tumors. Here we investigate the uptake of exogenous choline in vitro using high resolution ¹H NMR into rodent glioblastoma cell lines. To map bloodborne uptake in vivo, we used the novel technique Deuterium Metabolic Imaging (DMI), combined with intravenous infusion of [²H₉]-choline in two orthotopic rat (RG2) and mouse (GL261) models of glioblastoma. DMI-based metabolic maps revealed high uptake of choline in the tumors, in a stark image contrast with normal-appearing brain, illustrating the potential of [²H₉]-choline chloride as metabolic imaging agent.

Fanny Chapelin¹, Wenlian Zhu², Benjamin Leach², Hideho Okada³, and Eric Ahrens^2
1Biomedical Engineering, University of Kentucky, Lexington, KY, United States, ²Radiology, University of California San Diego, La Jolla, CA, United States, ³Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

We explore the temporal dynamics of tumor and T cell intracellular partial pressure of oxygen (pO₂) in a murine flank glioma model receiving chimeric antigen receptor (CAR) T cell therapy. Tumor cells or T cells are intracellularly labeled with perfluorocarbon nanoemulsion prior to injection. ¹⁹F MRI relaxation rate measurements are used to elucidate intracellular pO₂ in vivo. The tumor pO₂ peaks at 3 days post-infusion, commensurate with CAR T cell infiltration and tumor cell killing. Moreover, the absolute ¹⁹F signal scales with tumor burden. Overall, ¹⁹F pO₂ MRI measurements can assay cell-mediated apoptosis and provide insight into effector cell function.

Zihao Zhang^1,2,3, Lichao Huang⁴, Xubin Chai^1,2,3, Zhentao Zuo^1,2,3, Zhe Wang^1,2,3, Jing An⁵, Longsheng Pan⁴, and Yan Zhuo^1,2,3
1State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, ²University of Chinese Academy of Sciences, Beijing, China, ³CAS Center for Excellence in Brain Science and Intelligence Technology, Beijing, China, ⁴Department of Neurosurgery, PLA General Hospital, Beijing, China, ⁵Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, China

Follow-up efficacy evaluation of stereotactic radiotherapy (SRT) helps to provide individualized treatment for intracranial tumors. However, biological changes at cytological level happen earlier than structural MRI can detect. Tissue sodium concentration (TSC) is sensitive to changes of tissue metabolic state and cell membrane integrity. In this study, we used sodium MRI at 7T to noninvasively quantify TSC and monitor the evolution of intracranial tumors after SRT. The results demonstrated that quantitative sodium MRI at 7T can reflect the efficacy of SRT, predict the volume change of tumor, and has the potential of finding the relapse of tumors in early stage.

Andrew D James^1,2, Theresa K Leslie^1,2, Marie-Christine BD Labarthe³, Michaela Nelson¹, Frank Riemer⁴, Gabrielle Baxter⁵, Joshua D Kaggie⁵, Fiona J Gilbert⁵, William Brackenbury^1,2, and Aneurin J Kennerley^2,3
1Biology, University of York, York, United Kingdom, ²York Biomedical Research Institute, University of York, York, United Kingdom, ³Chemistry, University of York, York, United Kingdom, ⁴MMIV, Haukeland University Hospital, Bergen, Norway, ⁵Department of Radiology, University of Cambridge, Cambridge, United Kingdom

Here we applied ²³Na MRI, as part of a multiparametric imaging approach to measure ionic sodium concentration ([Na⁺]) levels in a longitudinal in-vivo mouse model of breast cancer. We investigated tumour [Na⁺] in response to neoadjuvant chemotherapy and ion channel inhibitors as a novel therapeutic means of reducing metastasis. Results show that [Na⁺] is decreased in tumour-bearing mice receiving standard chemotherapy. Data suggest that elevated tumour [Na⁺] in breast cancer may represent a potential imaging biomarker for malignancy and response to chemotherapy.

Elise Lepicard¹, Jessica Boult¹, Yann Jamin¹, Konstantinos Zormpas-Petridis¹, Adam Featherstone², Carol Box¹, Rafal Panek³, James O'Connor², and Simon Robinson^1
1Radiotherapy & Imaging, Institute of Cancer Research, Sutton, United Kingdom, ²Centre for Imaging Sciences, University of Manchester, Manchester, United Kingdom, ³Nottingham University Hospital, Nottingham, United Kingdom

Oxygen-enhanced (OE)-MRI was used to map and quantify hypoxia in head and neck squamous cell carcinoma xenografts, a tumour type in which hypoxia adversely affects patient prognosis. Application of a refined OE-MRI protocol revealed a markedly high proportion of voxels refractory to hyperoxia-induced changes in R₁, shown to be hypoxic in imaging-aligned tissue sections stained for the hypoxia marker pimonidazole.

Didi de Gouw¹, John Hermans², Bastiaan Klarenbeek ¹, Marnix Maas², Atsushi Nakamoto³, Tom Scheenen², and Camiel Rosman^1
1surgery, Radboudumc, Nijmegen, Netherlands, ²radiology and nuclear medicine, Radboudumc, Nijmegen, Netherlands, ³radiology, Osaka University Graduate School of Medicine, Osaka, Japan

Lymph node dissections during esophagectomy may be omitted or minimized in patients with esophageal cancer without or with limited lymph node metastases, thereby reducing associated morbidity. A promising technique to detect lymph node metastases is T2*-weighted MRI after the injection of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO, ferumoxtran-10). The aim of this study is to evaluate the feasibility of USPIO-enhanced MRI in the detection of locoregional lymph node metastases in patients with esophageal cancer whom underwent nCRT, and to study the effect of nCRT on the evaluation of USPIO-enhanced MRI.

Geke Litjens¹, Atsushi Nakamoto², Lodewijk Brosens^3,4, Erwin van Geenen⁵, Marnix Maas¹, Mathias Prokop¹, Tom Scheenen¹, Patrik Zámecnik¹, Kees van Laarhoven⁶, Jelle Barentsz¹, and John Hermans^1
1Radiology and Nuclear Medicine, Radboudumc, Nijmegen, Netherlands, ²Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan, ³Pathology, Radboudumc, Nijmegen, Netherlands, ⁴Pathology, UMC Utrecht, Utrecht, Netherlands, ⁵Gastroenterology and Hepatology, Radboudumc, Nijmegen, Netherlands, ⁶Surgery, Radboudumc, Nijmegen, Netherlands

Detecting lymph node metastases is important but challenging in patients with pancreatic or periampullary carcinoma. USPIO-MRI is a promising tool to detect lymph node metastases. In 13 patients we detected on USPIO-MRI 86/307 suspect lymph nodes (28/78 regional and 58/229 distant). All patients with suspect regional lymph nodes had positive regional lymph nodes at histopathology. In evaluation of paraaortic lymph nodes discrimination between ganglions and lymph nodes showed to be important. Node-to-node analysis and follow-up of this study will give more accurate information on the value of USPIO-MRI for the detection of lymph node metastases in these patients.