Kim Brewer^1,2, Drew DeBay³, Kerry Lake³, Iulia Dude^3,4, Genevieve Weir¹, Marc Mansour¹, and Chris Bowen^2,3
1Immunovaccine Inc., Halifax, NS, Canada, ²School of Biomedical Engineering, Dalhousie University, Halifax, NS, Canada, ³Institute for Biodiagnostics (Atlantic), National Research Council of Canada, Halifax, NS, Canada, ⁴Physics, University of Waterloo, Waterloo, ON, Canada

Immunotherapies are aimed at potentiating the body’s immune response. DepoVax^TM is an immunotherapy vaccine that encapsulates the tumor-associated antigens in liposomes, which are then suspended in oil. The oil acts as an adjuvant, which improves the potency of the peptides and aids in eliciting a strong immune response. This work investigated whether an increase in the draining lymph node (LN) volume (right inguinal LN) could be used as a biomarker for successful vaccination (i.e. successful tumor suppression). This was done by performing longitudinal LN volumetry using MRI to evaluate changes using receiver operating characteristic (ROC) curves.

Reshmi Rajendran¹, Mei Yee Tang¹, Huang Wei¹, Jie Ming Liang¹, Stephanie Choo¹, Torsten Reese², Hannes Hentze², Susan van Boxtel², Brian Henry², and Kai Hsiang Chuang^1
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, ²Merck Sharp and Dohme, Singapore

We applied optimized Flow-sensitive Alternating Inversion Recovery (FAIR) ASL to non-invasively quantify tumor perfusion in a mouse xenograft model, in which acute (24-hour) and chronic (43-day) treatment effects of the VEGF inhibitor (Avastin®) was investigated. Our data indicate that significant reduction in tumor perfusion was seen after acute dosing (p<0.05 vs. the control group), suggesting FAIR ASL perfusion could be used as an early biomarker for treatment response. Similarly, the chronic treatment of Avastin also led to a decrease in tumor size and perfusion; however, the drug effect varied significantly among the animals, possibly due to the heterogeneity of tumor progression.

Colleen Bailey^1,2, Firas Moosvi^1,2, and Greg J Stanisz^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Intra-to-extracellular water exchange has been shown to increase during apoptotic cell death in vitro. To map exchange in vivo, four flip angles were used during the late near-constant stages of uptake following three separate injections of Gd-DTPA-BMA in rat tumour xenografts. High extracellular water fraction corresponded to low cellularity on H&E. Regions of low water exchange were negative on TUNEL staining, while regions of high water exchange were positive, indicating apoptosis. High water exchange was observed even in cases where cells had not cleared and water fraction did not yet show a change.

Kay Pelletier¹, Kiaran McGee², Jun Chen², Kevin Glaser², Stephen Ansell³, and Richard Ehman^2
1Mayo Graduate School, Mayo Clinic, Rochester, Minnesota, United States, ²Radiology, Mayo Clinic, Rochester, MN, United States, ³Hematology, Mayo Clinic, Rochester, MN, United States

It is appreciated that a significant delay exists from the initiation of chemotherapy to the detection of a response as assessed by changes in tumor volume. In vivo serial measurements in a non-Hodgkin’s lymphoma mouse tumor model have demonstrated that tumor stiffness measured with MR Elastography (MRE) decreases following chemotherapy administration in comparison to saline-treated (placebo) tumors. This difference is statistically significant 48 hours following drug administration. These data suggest that tumor stiffness may be an earlier and more sensitive biomarker of therapeutic response than the current imaging-based methods such as FDG-PET, MRI and CT

Timothy J Graham¹, Rosemary A Fryer², Yann Jamin¹, Emma M Smith², Simon Walker-Samuel³, Faith E Davies², and Simon P Robinson^1
1Cancer Research UK & EPSRC Cancer Imaging Centre, The Institute of Cancer Research, London, Surrey, United Kingdom, ²Haemato-Oncology Research Unit, Division of Molecular Pathology, The Institute of Cancer Research, London, Surrey, United Kingdom, ³Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom

With the development of more targeted therapeutics to treat malignant bone disease has come the associated challenge of developing more clinically relevant pre-clinical models, and identifying new non-invasive techniques capable of assessing the tumour phenotype and treatment response. To this end, a novel mouse model of multiple myeloma, propagated by direct intraosseous injection of cells, has been investigated by quantitative MRI. Tumour growth was localised to the skeleton, and assessed using high-resolution T2-weighted and diffusion-weighted imaging. Response to Bortezomib and Tosedostat was also assessed. Bioluminescence imaging , weekly Igλ serum levels, histology and flow cytometry provided qualification of the MRI data.

Nkiruka C Atuegwu^1,2, Lori R Arlinghaus^1,2, Xia Li^1,2, E Brian Welch^1,2, A Bapsi Chakravarthy³, and Thomas E Yankeelov^1,2
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ³Radiation Oncology, Vanderbilt University, Nashville, TN, United States

Sequential diffusion weighted MRI (DW-MRI) and dynamic contrast enhanced MRI (DCE-MRI) data were acquired on twelve patients with localized invasive breast cancer undergoing neoadjuvant chemotherapy. The DW-MRI and DCE-MRI data were incorporated into the logistic model of tumor growth to extract the proliferation rates of the tumors and this was then used to calculate the number of cells at the conclusion of therapy. The simulated and the experimentally estimated number of cells at the conclusion of therapy were then compared.

Naranamangalam Raghunathan Jagannathan¹, Rani G Sah¹, Uma Sharma¹, Rajinder Parshad², and Vurthaluru Seenu^2
1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India, ²Department of Surgery, All India Institute of Medical Sciences, New Delhi, Delhi, India

Sequential MRI and MRS before therapy and after I, II and neo-adjuvant chemotherapy (NACT) was carried out in 41 breast cancer patients to evaluate the potential of total choline (tCho), ADC and tumor volume to predict tumor response. Our data revealed significant decrease in tCho and ADC after I NACT compared to pre-therapy in responders compared to non-responders. Percentage reduction in tCho was significantly higher compared to ADC and volume in responders after I NACT, which demonstrated early change in metabolic activity compared to structural changes. The combined specificity of all the 3 parameters was higher than the individual parameter.

Dingxin Wang^1,2, Ron Gaba³, Brian Jin⁴, Robert Lewandowski^4,5, Robert Ryu⁴, Kent Sato⁴, Laura Kulik⁶, Mary Mulcahy^5,7, Andrew Larson^4,5, Riad Salem^4,5, and Reed Omary^4,5
1Siemens Medical Solutions USA, Inc., Minneapolis, Minnesota, United States, ²Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, United States, ³Department of Radiology, University of Illinois at Chicago, Chicago, Illinois, United States, ⁴Department of Radiology, Northwestern University, Chicago, Illinois, United States, ⁵Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, United States,⁶Department of Hepatology, Northwestern University, Chicago, Illinois, United States, ⁷Department of Medicine, Northwestern University, Chicago, Illinois, United States

In this study, we tested the hypothesis that TRIP-MRI monitored tumor perfusion changes during TACE can predict overall survival in patients with unresectable HCC. Our study shows the evidence of association between intra-procedural tumor perfusion reduction during TACE and overall survival. TACE provided better survival benefit when relative perfusion reduction was 35-85%. The present results also suggest that TRIP-MRI performed within an integrated MR-DSA unit may serve as an intra-procedural imaging biomarker to predict survival in patients with unresectable HCC at the time of TACE procedure.

Martijn Intven¹, Onne Reerink¹, and Marielle E.P. Philippens^1
1Radiation Oncology, UMC Utrecht, Utrecht, Netherlands

Standard therapy for rectal cancer is neo-adjuvant therapy followed by resection. Evidence for organ-sparing therapy for good treatment responders after neo-adjuvant therapy is growing. Reliable selection of candidates for organ-sparing treatment is vital to prevent undertreatment of patients. In this study in 44 patients the predictive potential of diffusion-weighted MR Imaging for the selection of favorable responders was assessed. Both low pre-therapy ADC values and high relative ADC change (ÄADC) after neo-adjuvant therapy corresponded with pathological good response. The positive predictive value for predicting a good response was 89% for the ÄADC.

Janelle M Meyer¹, Brooke R Beckett¹, Xin Li¹, Luminita A Tudorica¹, Aneela Afzal¹, Stephanie Hemmingson¹, Yiyi Chen¹, Megan L Holtorf¹, William J Woodward¹, Charles S Springer¹, Christopher W Ryan¹, and Wei Huang^1
1Oregon Health & Science University, Portland, Oregon, United States

Nine soft-tissue sarcoma patients underwent DCE-MRI scans during the course of a phase I trial of antiangiogenic potentiatiated preoperative chemoradiotherapy. MRI data were acquired before therapy, after two weeks of antiangiogenic therapy only, and after eight more weeks of antiangiogenic therapy plus chemoradiotherapy. The % changes in tumor ROI and histogram median ÄKtrans values after two weeks provided superior early prediction of therapy pathologic response compared to those in tumor size, ADC, and other DCE-MRI parameters. ROI and median ÄKtrans changes after two weeks also exhibited a linear relationship with the % necrosis at surgery after ten weeks.