ISMRM 23rd Annual Meeting & Exhibition • 30 May - 05 June 2015 • Toronto, Ontario, Canada

Scientific Session • Cancer: Preclinical Studies of Animal Models

Monday 1 June 2015

Room 716 A/B

16:30 - 18:30


Zaver M. Bhujwalla, Ph.D., E. Jim Delikatny, Ph.D.

16:30 0220.   Tumour Response to Cabozantinib in a Transgenic Mouse Model of Neuroblastoma Assessed by Multiparametric MRI
Gilberto S. Almeida1, Philippa King2, Yann Jamin1, Albert Hallsworth2, Hannah Webber2, Sergey Popov3, Louis Chesler2, and Simon P. Robinson1
1Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, 2Clinical Studies, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, 3Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

Both Vascular Endothelial Growth Factor (VEGF) and the Hepatocyte Growth Factor (HGF)/c-MET signalling pathway are implicated in the progression of human neuroblastoma. In this study we demonstrate the efficacy of cabozantinib, a small-molecule kinase inhibitor active against both VEGFR2 and MET and currently in clinical trials against neuroblastoma, in the Th-MYCN genetically engineered mouse model of neuroblastoma and established both native spin lattice relaxation time T1 and transverse relaxation rate R2* as early non-invasive biomarkers of response, which were associated with significant increase in necrosis, and significant decrease in microvessel density.

16:42 0221.   Diffusion Weighted MRI for Early Detection and Progression Monitoring of Prostate Cancer in a Transgenic Mouse Model
Deborah K. Hill1,2, Eugene Kim1,2, Jose R. Teruel1,2, Siver A. Moestue1,2, and Tone F. Bathen1
1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Sør Trøndelag, Norway, 2St. Olavs University Hospital, Trondheim, Sør Trøndelag, Norway

The effectiveness of DW-MRI for both detecting early onset of prostate cancer (PCa) and for characterising disease progression was investigated for the transgenic adenocarcinoma of the mouse prostate (TRAMP) model in mice. DWI facilitated early detection of tumour onset in TRAMP mice prostates before lesions were seen on high-resolution T2W images. Histograms are sensitive to distinguishing cancer from prostate tissue, where bimodal distributions were clearly visible in the case of cancer onset. Median ADC values of prostate regions were in agreement with literature values for different stages of PCa progression, thus providing a non-invasive means to assess cancer aggressiveness.

16:54 0222.   
In vivo and ex vivo diffusion tensor imaging parameters follow Collagen 1 fiber distribution in breast cancer xenograft model
Samata M Kakkad1,2, Jiangyang Zhang1, Alireza Akhbardeh1, Desmond Jacob1, Meiyappan Solaiyappan1, Michael A Jacobs1, Venu Raman1, Dieter Leibfritz2, Kristine Glunde1, and Zaver M Bhujwalla1
1Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2University of Bremen, Bremen, Germany

Col1 fibers play an important role in molecular transport and cancer cell dissemination. We investigated the influence of Col1 fibers on water diffusion, using a breast cancer xenograft fluorescing under hypoxia. We observed that hypoxic regions contained significantly fewer Col1 fibers, and were characterized by a lower ADC and FA compared to normoxic tumor regions. In vivo DTI distribution patterns were spatially similar to those observed ex vivo, suggesting that noninvasive DTI parameters provided noninvasive indices of Col1 fiber distribution in tumors.

17:06 0223.   Investigating the Impact of a Primary Tumor on Metastasis and Dormancy Using MRI: New Insights into the Mechanism of Concomitant Tumor Resistance
Paula Foster1,2, Amanda Hamilton1, and Carmen Simedrea1
1Imaging, Robarts Research Institute, London, Ontario, Canada, 2Medical Biophysics, Western University, London, Ontario, Canada

MRI was used to track growth of brain metastases and dormant (non proliferative) cancer cells in a mouse model of concomitant tumor resistance. Our major result was that the presence of a primary mammary fat pad tumor limited the development of secondary metastases in the brain.

17:18 0224.   
Iron-Oxide Driven Decrease in T2 Relaxation Times Correlates with Tumor Associated Macrophages (TAMs) in Postpartum Pregnancy Associated Breast Cancer Xenografts
J C Montejano1, K M Huber1, V F Borges1, P J Schedin2, and N J Serkova1
1University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States, 2Oregon Health and Science University, Oregon, United States

In this study, superparamagnetic iron nanoparticles (SPION) were used as a contrast agent for the imaging of macrophage driven inflammation in postpartum pregnancy associated breast cancer (PPABC) by T2-MRI. A cohort of immunocompetent BALB/C mice were injected with a murine breast cancer cell line and injected with SPION contrast 24 hours prior to imaging. When compared to virgin counterparts, postpartum mice showed a large decrease in T2 relaxation times. This study has shown that SPIONs are an appropriate contrast agent for the assessment of the TAM-rich tumor microenvironment in PPABC.

17:30 0225.   In-vivo quantification of iron oxide nanoparticles at high concentration in a murine breast tumor model using positive contrast
Jinjin Zhang1, Alicia A. Petryk2, Russell Reeves3, Djaudat Idiyatullin1, Hattie L. Ring1,4, P. Jack Hoopes2,3, and Michael Garwood1
1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, 2Thayer School of Engineering, Dartmouth College, NH, United States, 3Geisel School of Medicine, Dartmouth College, NH, United States, 4Department of Chemistry, University of Minnesota, MN, United States

The ability to accurately and sensitively image tumor iron oxide nanoparticles (IONPs) is essential for their use as a therapeutic modality in clinical cancer medicine. In this study, the quantification of IONPs in a murine breast tumor model at high, but clinically relevant, concentrations was done by using positive contrast from SWIFT sequence. IONPs were administered by intra-tumoral (IT) or intravenous (IV) injection. Polyethylene glycol (PEG) and low dose radiation enhanced IONP tumor uptake. The T1 maps measured by the SWIFT sequence provided quantitative and qualitative estimations of IONP at concentrations significantly higher (x30) than previously reported.

17:42 0226.   
Combined PET-MRI: is it possible to quantify FDG perfusion based on Gd-DTPA pharmacokinetics?
Marie Anne Richard1, Vincent Turgeon1, Jérémie P. Fouquet1, Luc Tremblay1, Réjean Lebel1, and Martin Lepage1
1Centre d’imagerie moléculaire de Sherbrooke (CIMS), Université de Sherbrooke, Sherbrooke, Québec, Canada

Signal in PET imaging is modulated by the perfusion and metabolism of the radiotracer. It would be possible to decouple these parameters through combined PET-MRI using an unmetabolized MRI contrast agent with similar perfusion kinetics as the radiotracer. Sequential MRI and PET scans were performed in rats using Gd-DTPA and FDG. Pharmacokinetic parameters were extracted based on a two-tissue model and statistical analysis was performed to determine if perfusion and elimination are correlated between both probes. Preliminary results suggest that perfusion is correlated, whereas elimination is not.

17:54 0227.   Dynamic Contrast Enhanced Magnetic Resonance Imaging Evaluates Early Therapeutic Effect of Anti-EMMPRIN Antibody with Cisplatin or X-radiation in Head and Neck Cancer Mouse Models
Hyunki Kim1, Yolanda Hartman1, Guihua Zhai1, Thomas Chung1, Melissa Korb1, Tong Zhou1, and Eben Rosenthal1
1University of Alabama at Birmingham, Birmingham, AL, United States

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) showed that tumor microvascular perfusion was significantly suppressed by anti-EMMPRIN antibody alone or in combination with X-radiation or cisplatin in head and neck cancer mouse models. The early change of tumor perfusion parameters following anti-EMMPRIN therapy with/without cisplatin was significantly correlated with the tumor volume change, proliferation cell density, and microvessel density, but not when X-radiation treated group was included. Therefore DCE-MRI may be used to predict the therapeutic efficacy of anti-EMMPRIN antibody with/without cisplatin, but not with X-radiation.

18:06 0228.   Effect of oxygen challenge on MR imaging of tumor microenvironment
Zhongwei Zhang1, Qing Yuan1, Heling Zhou1, and Ralph P Mason1
1Department of Radiology, UT Southwestern Medical Center, Dallas, TX, United States

Few studies have been performed to reveal the changes of tumor microenvironment such as diffusion and perfusion parameters in response to oxygen challenge. The purpose of this study was to evaluate the effect of oxygen challenge on tumor heterogeneity, diffusion and perfusion parameters at the microscopic level. The current study demonstrated that IVIM diffusion MRI provided powerful insight into tumor perfusion. On the other hand, diffusion stretched-exponential model was sensitive to the changes of tumor heterogeneity, Combining these two models may serve as potential biomarker to evaluate tumor responses to oxygen.

18:18 0229.   MR Microscopy - Ultra-High Resolution 7T MRI in Pathologic Analysis of Resected Breast and Lymph Tissue
Brittany Dashevsky1, Krishna Juluru1,2, Timothy D'Alfonso1, Elizabeth Sutton2, Eric Aronowitz1, Ashley E. Giambrone1, and Doug Ballon1
1Weill Cornell Medical College, New York, NY, United States, 2Memorial Sloan Kettering Cancer Center, New York, NY, United States

With 7T MR imaging of ex vivo fresh unfixed breast and lymph specimens at a spatial resolution of 60 x 60 x 90µm, we identified characteristic features of both benign and malignant lesions compared with a light microscopy standard. Ultra-high resolution MRI offers a new tool in the management of breast cancer in ways that include defining pathology, delineating tumor margins, and optimizing specimens for pathologic processing. This tool promotes a novel approach to radiology - pathology collaboration and demonstrates the capabilities of 7T MR.