Mor Mishkovsky^1,2, Cristina Cudalbu¹, Arnaud Comment³, Denis Marino⁴, Ivan Radovanovic⁴, Virginie Clément-Schatlo⁵, and Rolf Gruetter^6,7
1Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Department of Radiology, Université de Lausanne, Lausanne, Switzerland, ³Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ⁴Department of Clinical Neurosciences, Université de Genève, Genève, Switzerland, ⁵Department of Clinical Neurosciences, University Hospital of Geneva, Genève, Switzerland, ⁶Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ⁷Department of Radiology, Université de Lausanne et Genève, Lausanne and Geneva, Switzerland, Switzerland

Cultured human glioma initiating cells (GIC) were stereotactically injected into the striatum of immunodeficient nude rats. The developed tumors were characterized by T2-weighted and contrast enhanced T1-weighted imaging. Cerebral metabolism in the tumors was studied using high-field 1H magnetic resonance spectroscopy leading to the identification and quantification of 15 metabolites representative of tumor growth and metabolism.

Noriko Mori¹, Flonné Wildes¹, Kristine Glunde², and Zaver M. Bhujwalla^2
1JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States,²JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States

Increased levels of choline kinase (Chk)-α and phosphocholine (PC) are consistently observed in aggressive cancers. Understanding the roles of Chk and PC in cancer cells provide new insights into the malignant phenotype and can lead to the development of new treatment strategies. We previously showed that a Chk inhibitor which reduces PC had no effect on MDA-MB-231 cell proliferation, but downregulation of Chk with siRNA reduced proliferation. Here we have expanded upon these studies using SUM149 triple negative inflammatory breast cancer cells. These data confirm the importance of the enzyme, but not its activity, in breast cancer cell proliferation.

Kavindra Nath¹, David S. Nelson¹, Andrew M. Ho¹, Stephen B. Pickup¹, Rong Zhou¹, Dennis B. Leeper², and Jerry D. Glickson^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States

Synopsis: Since acidification enhances the activity of nitrogen mustard alkylating agents, as well as of platinum drugs such as cisplatin (CPT) that act by similar mechanisms (adding substituents to and cross-linking DNA), we have evaluated the effect of lonidamine (LND)-induced tumor acidification and response of DB-1 melanoma xenografts to treatment with CPT (7.5 mg/kg, i.v.) or melphalan (LPAM; 7.5 mg/kg, i.v.). This dose of CPT had no effect on tumor growth. Only LND + LPAM produced a significant growth delay of 19.9 ± 2.0 d compared to LND alone of 1.1 ± 0.1 d and LPAM alone of 4.0 ± 0.0 d. These studies point to the potential feasibility of multiple-dose treatment of systemic melanoma by combination chemotherapy with LND + LPAM.

Henk M. De Feyter¹, Robin A. de Graaf¹, Fahmeed Hyder¹, Kevin L. Behar², and Douglas L. Rothman^1
1Diagnostic Radiology, Yale University, New Haven, Connecticut, United States, ²Department of Psychiatry, Yale University, New Haven, Connecticut, United States

The ketogenic diet induces low glucose levels while several-fold increasing plasma ketone bodies and is receiving attention as alternative or additional treatment for the standard management of brain tumors. In contrast to healthy brain cells, tumor cells supposedly lack the enzymes to oxidize ketone bodies and thus have insufficient energy to grow on low glucose. However in vivo evidence for the functional capacity of brain tumors to metabolize ketone bodies is lacking. We therefore applied in vivo ¹H-[¹³C] magnetic resonance spectroscopy with infusion of ¹³C-labeled-hydroxybutyrate in a rat model of malignant glioma to investigate metabolic pathways of ketone bodies in tumorous and non-tumorous brain tissue.

Jadegoud Yaligar¹, Wei W. Teoh², Sanjay K. Verma¹, Kanaga Sabapathy², and Sendhil S. Velan^1
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, Singapore, ²Laboratory of Molecular Carcinogenesis, National Cancer Center, Singapore, Singapore, Singapore

Hepatitis B, hepatitis C, aflatoxin exposure are the major known causes of HCC. Even before tumors are seen, there are crucial metabolic perturbations involving in tumor. In the present study, to assess the independent risk factors of hepatitis B and aflatoxin exposure, we have used three HCC and one control group mice models which closely mimic the human HCC. Carnitine was indentified in liver even before the formation of neoplasm indicating the possibility of potential early marker even before tumors can be seen. Tumor carnitine and choline levels were at higher concentrations in HBsAg+AFB model compared to WT+AFB and HBsAg+Oil HCC model reflecting malignant transformation of tumor. Degree of unsaturation in tumors was lower than normal liver indicating altered lipid composition in tumors

Lu Jiang¹, Jannie P. Wijnen², Tiffany Greenwood¹, W.J.M. van der Kemp², Dennis W. J. Klomp², and Kristine Glunde^3
1Division of Cancer Imaging Research, Department of Radoilogy, Johns Hopkins School of Medicine, BALTIMORE, MD, United States, ²Radiology Department, University Medical Centre Utrecht, Utrecht, Netherlands, ³Division of Cancer Imaging Research, Department of Radoilogy, Johns Hopkins University, BALTIMORE, MD, United States

The adiabatic version of refocused insensitive nuclei enhanced by polarization transfer (BINEPT) and pulse acquire (PA) 31P Magnetic Resonance Spectroscopy (MRS) are compared in MCF-7 and MDA-MB-231 breast cancer xenografts at 9.4 Tesla. After in vivo MRS measurements, the tumors were extracted and high-resolution (HR) 31P MRS was performed. Our data suggest that BINEPT can be advantageous for studying the individual compounds in phospholipid metabolism in both the choline and ethanolamine cycle, in translational research in breast cancer and other cancers in vivo at high magnetic field strength.

Palamadai N. Venkatasubramanian¹, George Iordanescu¹, Paul J. Grippo², Richard Knop¹, and Alice M. Wyrwicz^1
1Center for Basic M.R. Research, NorthShore University HealthSystem, Evanston, IL, United States, ²Robert H Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Although pancreatic ductal adenocarcinoma is associated with marked stromal changes, MR imaging has not been used to characterize those changes. We have examined and quantified pancreatic cancer-associated stromal changes in a mouse model using 3D MR microscopy.

Samata Kakkad^1,2, Jiangyang Zhang³, Alireza Akhbardeh¹, Meiyappan Solaiyappan¹, Venu Raman¹, Dieter Leibfritz², Kristine Glunde⁴, and Zaver M. Bhujwalla^4
1JHU ICMIC Program, Division of Cancer Imaging Research, The Johns Hopkins University SOM, Baltimore, MD, United States, ²Department of Chemistry and Biology, University of Bremen, Bremen, Germany, ³Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University SOM, Baltimore, MD, United States, ⁴JHU ICMIC Program, Division of Cancer Imaging Research, Johns Hopkins University, Baltimore, MD, United States

Hypoxic tumor microenvironments are frequently observed in tumors and are associated with an aggressive phenotype and resistance to radiation and chemotherapy. We previously observed significantly fewer collagen fibers in hypoxic tumor regions. Diffusion tensor imaging is often used to distinguish between normal, benign and malignant breast tissue as a non-contrast imaging technique, since lower water diffusion and diffusion anisotropy parameters are observed in malignant tissue. Here we examined the relationship between low collagen containing hypoxic tumor regions and high resolution DTI and observed lower diffusion and diffusion anisotropy in hypoxic regions compared to normoxic regions within a breast cancer xenograft.

Chi-Long Juang¹, Chuan-Yi Lin^1,2, Sheng-Ching Liu³, Chi-Yu Yang⁴, and Hsiao-Chuan Wen^1
1Department of Radiological Technology, Yuanpei University, Hsin Chu, Taiwan, ²Department of Medical Imaging, Buddhist Tzu Chi General Hospital, New Taipei, Taiwan,³Department of Radiology, Hsinchu Mackay Memorial Hospital, Hsin Chu, Taiwan, ⁴Division of Animal Medicine, Animal Technology Institute Taiwan, Miaoli, Taiwan

Tagitinin C, a major sesquiterpenoid, was isolated from the leaves of Tithonia diversifolia and was identified of its anti-hepatoma ability in our previous data. In this study the anti-metastasis ability of tagitinin C in xenograft models of Hep-G2 carcinoma was investigated by chemical shift imaging (CSI). Our results showed that tumor cells spread throughout all parts of the abdomen and metastasized to many organs of the mice after 5-25 days inoculation. We also found that tagitinin C can not only reduce the choline/creatine level but also keep most of the choline appeared near by the inoculated point.

Hasan Alsaid¹, Tinamarie Skedzielewski¹, Bao Hoang², Mary V. Rambo¹, James Tunstead², Christopher Hopson³, and Beat M. Jucker^1
1Preclinical & Translational Imaging, LAS, PTS, GlaxoSmithKline, King of Prussia, PA, United States, ²Molecular Discovery Research, PTS, GlaxoSmithKline, King of Prussia, PA, United States, ³Oncology R&D, GlaxoSmithKline, Collegeville, PA, United States

In this study, we investigated the optimal ferumoxytol concentration, MRI detection scheme and timeframe of macrophages in CHL-1 melanoma xenograft tumor bearing mice. The results suggest that ferumoxytol-enhanced MRI can be used to detect macrophages in CHL-1 melanoma cell derived xenograft tumors. Ferumoxytol was washed out the tumor after one week of 0.5 mmol Fe/kg injection, reflecting the potential to use ferumoxytol-enhanced MRI on a weekly basis to serially monitor response to drug therapies aimed at increasing cellular phagocytosis. Finally, the lower dose of ferumoxytol may be optimal as there will be greater potential to detect increased cellular iron uptake by scavenging macrophage in the tumor.

Rumiana Bakalova¹, Zhivko Zhelev^1,2, Ichio Aoki¹, Daisuke Kokuryo¹, Veselina Gadjeva², and Tsuneo Saga^1
1Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Chiba, Japan, ²Medical Faculty, Trakia University, Stara Zagora, Stara Zagora, Bulgaria

Redox signalling is crucial for carcinogenesis and our study shows that tissue redox activity can be used as a sensing platform for imaging of cancer, using nitroxide-enhanced MRI. The experiments were conducted on cancer-bearing and healthy mice. The tissues (cancer and non-cancer) of cancer-bearing mice were characterized by a long-lived MRI signal (_1/2>14min.),indicating a high oxidative activity. The tissues of healthy mice were characterized by a short-lived MRI signal (_1/2<3min.), indicating a high reducing activity to the nitroxide. The proposed methodology is applicable on biopsy specimens and blood samples for evaluation of the effectiveness of anti-cancer therapy.

Marie-France Penet¹, Paul T. Winnard Jr.¹, Flonné Wildes¹, Yelena Mironchik¹, Tariq Shah¹, Anirban Maitra², and Zaver M. Bhujwalla^3
1JHU ICMIC Program Division of Cancer Imaging Research The Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Departments of Pathology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³JHU ICMIC Program Division of Cancer Imaging Research The Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, MD, United States

Pancreatic cancer is a very aggressive and lethal neoplasm that often induces cachexia and is typically detected at an advanced stage. Better understanding of the disease, early detection, and new therapeutic targets are urgently needed. Using mouse xenograft models, we have investigated the metabolism of multiple pancreatic tumors, and their effect on body weight. High total choline was observed in tumors that induced significant weight loss in tumor-bearing mice. To understand the interactions between the tumor and normal tissue, we are developing a cell-based optical biosensor using genetically engineered myoblasts to detect the early onset of cachexia-inducing signals.

Ashley M. Stokes^1,2, David A. Hormuth, II^1,3, Thomas E. Yankeelov^1,2, and Christopher C. Quarles^1,2
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States,³Biomedical Engineering, Vanderbilt University, Nashville, TN, United States

Tumor hypoxia, which is associated with poor treatment response and poor long-term prognosis, can be non-invasively imaged using ¹⁸FMISO PET, ⁶⁴Cu-ATSM PET, and quantitative BOLD (qBOLD) MRI. We aimed to determine the optimal method for measuring hypoxic tumor fraction in rat brain tumor models. Preliminary data show promising results, where we found substantial tumor ¹⁸FMISO and ⁶⁴Cu-ATSM activity and much lower qBOLD-derived tumor LSO₂ values compared to surrounding normal tissue. The direct comparison of these imaging modalities is of great clinical interest as their ability to detect hypoxia differs due to the underlying targeting mechanisms in the PET and MRI methods.

Lauren C.J. Baker¹, Carol Box², Arti Sikka¹, Gary Box², Suzanne A. Eccles², and Simon P. Robinson^1
1Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, ²Tumour Biology and Metastasis Team, Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

Resistance to targeted EGFR therapy in squamous cell carcinoma of the head and neck is poorly understood. There is an urgent need to identify patients most likely to respond to therapy, in addition to monitoring those that will develop acquired resistance. The role of non-invasive imaging biomarkers in this area is unclear. Using intrinsic susceptibility MRI, we have investigated functional vasculature and tumor oxygenation in a human tumor xenograft model of acquired resistance to EGFR-tyrosine kinase inhibitors.

Merryl R. Lobo^1,2, Sarah Green³, Matthias C. Schabel², Yancey Gillespie⁴, Randall Woltjer³, and Martin Pike^1,2
1Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, United States, ²Advanced Imaging Research Center, Oregon Health and Science University, Portland, Oregon, United States, ³Department of Pathology, Oregon Health and Science University, Portland, Oregon, United States, ⁴Departments of Surgery, Microbiology and Cell, Developmental & Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States

Despite extensive malignant glioma vascularity, anti-angiogenic therapy largely fails to induce durable responses. Autophagy, a cellular degradation pathway, can promote survival and drug resistance in tumor cells, and its late-stage inhibition can induce cell death. Using a novel treatment combination with the intracranial 4C8 mouse glioma model, we documented a synergistic increase in anti-vascular/anti-tumor efficacy of anti-angiogenic inhibitor Cediranib in combination with the autophagy inhibitor Quinacrine, using a comprehensive DCE/DSC perfusion MRI approach and immunohistology. We a showed markedly decreased tumor perfusion, tumor growth, increased tumor necrosis and improved survival, suggesting a new and promising treatment avenue for malignant glioma.

Ramesh Paudyal¹, Kavindra Nath Pathak¹, Seungcheol Lee¹, Kejia Cai¹, Stephen B. Pickup¹, David Nelson¹, Harish Poptani¹, and Jerry D. Glickson^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States

In this study, we investigated the potential of combining dynamic contrast enhanced MRI and diffusion weighted imaging method for evaluating the response of RCHOP in non- Hodgkin lymphoma. Our results suggest that the change in kinetic model parameters and ADC values after the administration of RCHOP can be used a as an indicator of durable response to RCHOP therapy.

Denise C. Welsh¹, Tyler Teceno¹, Ken Ito¹, Mamuro Yanagimachi¹, Deirdre Scully², Jacob Hesterman², Yasuhiro Funahashi¹, and Paul J. McCracken^1
1Eisai, Andover, MA, United States, ²InVicro, Boston, MA, United States

The effects of eribulin, a microtubule binding drug approved third line therapy for breast cancer, on the vasculature and tumor growth of human breast cancer mouse MX-1 tumors are compared to capecitabine, a cytotoxic. These DCE-MRI data show evidence of antivascular activity at early time points after eribulin treatment and a stabilization of tumor volume. In addition to stabilizing tumor growth over a 5 day period, we demonstrated that a single dose of 3mg/kg i.v. eribulin reduces tumor Ktrans as early as 6hrs followed by a significant increase in Ktrans by days 2 and 5.

Carlos J. Perez-Torres¹, John A. Engelbach¹, Jeremy Cates², Dinesh K. Thotala², Robert E. Drzymala², Joseph J.H. Ackerman^3,4, and Joel R. Garbow^1
1Department of Radiology, Washington University in Saint Louis, Saint Louis, Missouri, United States, ²Department of Radiation Oncology, Washington University in Saint Louis, Saint Louis, Missouri, United States, ³Department of Radiology, Washington University in St. Louis, Saint Louis, Missouri, United States, ⁴Department of Chemistry, Washington University in Saint Louis, Saint Louis, Missouri, United States

Standard anatomical MRI is incapable of differentiating recurring tumor from delayed radiation necrosis, as both lesions are hyperintense. The work presented here investigates mouse models of radiation necrosis and brain tumor with more advanced MRI methodologies, including diffusion-weighted imaging (DWI) and magnetization transfer contrast (MTC). Both tumor and necrosis showed decreases in MTR, with the MTC effect being stronger for tumor than radiation necrosis. The ADCi for tumor was similar to that of healthy brain, while ADCi was elevated in necrosis. A multi-contrast approach that includes both modalities might lead to a framework for differentiating between these pathologies.

Greetje Vande Velde¹, Tom Dresselaers¹, Ellen De Langhe², Jennifer Poelmans¹, Rik Lories², and Uwe Himmelreich^1
1Biomedical MRI unit/ MoSAIC, KU Leuven, Leuven, Flanders, Belgium, ²Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Flanders, Belgium

As the course of pulmonary fibrosis progression in rodent models shows substantial interindividual variation, non-invasive techniques are indispensable to dynamically monitor lung inflammation and fibrosis progression to establish the kinetics of pathogenic events or treatment effects for each animal individually. Because imaging tools for the evaluation of lung disease with good temporal and spatial resolution in vivo are limited (e.g. radiotoxicity concerns in µCT), we evaluated prospectively and retrospectively gated MRI protocols to visualize disease onset and progression in the bleomycin-induced mouse model for lung fibrosis and confirmed our results with in vivo µCT and histology.

Gregory L. Pishko¹, Morad Nasseri¹, Seymur Gahramanov¹, Leslie L. Muldoon¹, and Edward A. Neuwelt^1,2
1Oregon Health & Science University, Portland, OR, United States, ²Veterans Affairs Medical Center, Portland, OR, United States

Timing and sequencing of chemotherapy and anti-angiogenic therapy may play an important role in anti-brain tumor efficacy. A pilot study was conducted to use MRI to elucidate vascular and interstitial fluid differences that correspond with the timing of temozolomide (chemotherapy) and bevacizumab (anti-angiogenic) delivery. Rats with intracerebrally implanted human gliomas were randomized to three treatment groups: control, bevacizumab followed by temozolomide 4 days later, and temozolomide followed by bevacizumab 4 days later. Permeability measurements and T2W imaging demonstrated that it may be more effective to deliver chemotherapy before anti-angiogenic therapy and warrants further study.

Manoj Kumar¹, Sean Arlauckas¹, Sona Saksena¹, Gaurav Verma¹, Ranjit Ittyerah¹, Anatoliy V. Popov¹, Harish Poptani¹, and Edward James Delikatny^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States

Abnormal choline metabolism is a hallmark in cancer diagnosis and is associated with oncogenesis and tumor progression. Increased total choline, predominantly arising from phosphocholine is consistently observed in both pre-clinical tumor models as well as in human tumor studies by 1H MRS. Inhibition of choline kinase using specific choline kinase inhibitors, such as MN58b is a promising new strategy for treatment of brain tumors. We demonstrate the efficacy of MN58b in specifically suppressing total choline levels in an intracranial rat brain tumor model. In-vitro and in-vivo assays were used to characterize the effects of MN58b on tumor cells and on orthotopically grown gliomas in a rat model.

Kimberly Pechman^1,2, Andrew Lozen¹, and Kathleen M. Schmainda^2,3
1Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ²Translational Brain Tumor Program, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ³Radiology and Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Few systematic studies have examined optimal timing for combining anti-angiogenic therapy with radiation for brain tumor treatment. MRI measures of enhancing tumor volume have proven unreliable since decreases in enhancement may be independent of biologic effect. The purpose of this study was to use rCBV, derived from DSC-MRI, and enhancing volume to optimize combination of anti-VEGF agent, B20, and radiation for treatment of U87 brain tumor models. The studies demonstrate optimal combination occurs when radiation before B20 providing the largest survival benefit.

Kimberly Pechman^1,2, Andrew Lozen¹, Mona Al-Gizawiy^2,3, Christopher R. Chitambar⁴, Kathleen M. Schmainda^2,5, and Andrew S. Nencka^6
1Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ²Translational Brain Tumor Program, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ³Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ⁴Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ⁵Radiology and Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ⁶Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Transferrin receptors are highly expressed on glioblastoma cells, making them a target for therapy. Gallium can function as an iron mimetic that binds to transferring and is incorporated into the cells. The purpose of this study was to evaluate gallium maltolate in the treatment of a U87 xenograft brain tumor model by evaluating changes in tumor blood volume and enhancing tumor volume. The studies demonstrate treating tumors with the novel use of gallium maltolate provides inhibition of tumor volume and angiogenesis.

Kavindra Nath¹, Ting Liu¹, David S. Nelson¹, Hoon Choi², I-Wei Chen², Dennis B. Leeper³, Rong Zhou¹, and Jerry D. Glickson^1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ²Materials Science and Engineering, University of Pennsylvania, philadelphia, pennsylvania, United States, ³Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States

Synopsis: In vivo 31P Magnetic Resonance Spectroscopy demonstrates that LNCaP prostate cancer xenografts treated with the putative monocarboxylate transporter (MCT) inhibitor, lonidamine (LND), exhibits a sustained and tumor-selective decrease in intracellular pH (pHi) from 6.87 ± 0.04 to 6.40 ± 0.07 (p = 0.02), extracellular pH (pHe) from 6.97 ± 0.04 to 6.46 ± 0.09 (p = 0.18) and tumor bioenergetics (βNTP/Pi) also decreased by 74.5 ± 0.04% (p = 0.03) relative to the baseline level following LND administration. The decline of pHi, pHe and bioenergetics could be a critical parameter for thermosensitization and/or improving tumor response to alkylating agents.

Kavindra Nath¹, David S. Nelson¹, Andrew M. Ho¹, Stephen B. Pickup¹, Christina Gustafson¹, Cory Alvey², Rong Zhou¹, Dennis B. Leeper³, and Jerry D. Glickson^1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ²Pharmacology, University of Pennsylvania, Philadelphia, PA, United States, ³Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States

Synopsis: We seek to employ the natural tendency of melanomas and other tumors to convert glucose to lactate as a method for selective intracellular acidification of cancer cells and to exploit this effect in potentiating the activity of N-mustard and anthracycline antineoplastic agents.. We performed this study to evaluate whether induction of hyperglycemia could enhance the effects of lonidamine (LND) on inducing intracellular acidification, bioenergetic decline and potentiation of the activity of melphalan (LPAM) against DB1 melanoma xenografts in mice.. Intracellular pH and the bioenergetics were reduced by 0.7 units (p<0.001) and 51.4% (p>0.05), respectively, under hyperglycemic conditions, which is very similar to the effects of LND under normoglycemic conditions. This study demonstrates that while hyperglycemia substantially increases lactic acid production by the tumor, it does not increase the effects of LND on acidification of the tumor because of the strong buffering action of carbon dioxide (the pKa of carbonic acid is 6.39).

Martin D. Pickles¹, David J. Manton², Martin Lowry¹, and Lindsay W. Turnbull^1
1Centre for MR Investigations, Hull York Medical School at University of Hull, Hull, East Yorkshire, United Kingdom, ²Medical Physics, Hull & East Yorkshire Hospitals NHS Trust, Hull, East Yorkshire, United Kingdom

Reports have highlighted the prognostic value of MR parameters in predicting survival internals in breast cancer patients. However, the cohort size is generally small with short follow up intervals. The aims of this study were to determine if any associations were noted between MR parameters and survival in a large cohort with a long follow-up interval and additionally to compare their prognostic value against traditional clinical indicators. This work has revealed significant associations between MR parameters and survival intervals. Further, in this cohort MR parameters provided prognostic information superior to traditional clinical indicators as evident from the higher hazard ratios.

Araminta E. W. Ledger¹, Marco Borri¹, Romney Pope², Erica Scurr¹, Toni Wallace¹, Cheryl Richardson², Marianne Usher², Robin Wilson², Steven Allen², Karen Thomas³, Nandita M. deSouza¹, Martin O. Leach¹, and Maria A. Schmidt^1
1CR-UK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ²Department of Radiology, Royal Marsden Hospital, Sutton, Surrey, United Kingdom, ³Clinical Research and Development, Royal Marsden Hospital, Sutton, Surrey, United Kingdom

Contrast agent (CA) uptake curve classification may be considerably affected by movement across dynamic contrast-enhanced breast examinations. This abstract retrospectively considers axillary vessel enhancement to approximate the effect of rigid in-plane registration on CA uptake curves derived from small enhancing structures. The performance of global and local registration and their impact on the shape of the CA uptake curves was investigated. Area under the curve and signal enhancement ratio differed significantly between globally and locally registered image sets versus unregistered data. CA uptake curves derived from small enhancing lesions may therefore be unreliable despite use of global rigid registration.

Jared A. Weis^1,2, Michael I. Miga^1,3, Lori R. Arlinghaus¹, Xia Li¹, A. Bapsi Chakravarthy^4,5, Vandana G. Abramson^5,6, Jaime Farley^5,6, and Thomas E. Yankeelov^1,2
1Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, United States, ²Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, United States, ³Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States, ⁴Radiation Oncology, Vanderbilt University, Nashville, Tennessee, United States, ⁵Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, United States, ⁶Medical Oncology, Vanderbilt University, Nashville, Tennessee, United States

There is currently a paucity of reliable techniques for predicting the response of breast cancer to neoadjuvant chemotherapy. One promising approach to address this clinical need is to integrate quantitative in-vivo imaging data into biomathematical models of tumor growth to predict eventual response based on early measurements during therapy. Using contrast enhanced, diffusion weighted, and structural MRI data acquired before and after the first cycle of therapy, we illustrate a mathematical modeling approach incorporating tissue mechanical properties leads to more accurate predictions of tumor response to therapy than when such properties are ignored.

Zheng Chang¹, Janet Horton¹, and Fang-Fang Yin^1
1Duke University, Durham, NC, United States

Partial breast irradiation has been a convenient alternative to conventionally fractionated whole breast radiotherapy. In this work, single-fraction stereotactic body radiotherapy (SBRT) was used to treat patients with early stage breast cancer, which demands accurate tumor and target delineations. Dynamic contrast-enhanced (DCE) MRI has been demonstrated valuable in diagnosis, and might be useful to aid segmentation of breast tumor and targets for SBRT. In this study, feasibility of computer-aided segmentation of breast target volumes using DCE-MRI was investigated and compared against physician delineation, considered as reference. Preliminary results of five patients indicated good agreement between computer-aided segmentation and physician delineation.

Shandong Wu¹, Susan P. Weinstein², Emily F. Conant², and Despina Kontos^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States

Studies suggest that background parenchymal enhancement (BPE) in breast DCE-MRI is associated with an increased breast cancer risk for high-risk populations. Most previous work on BPE estimation is however, based on readers’ qualitative assessment. The purpose of our study is to develop a fully automated computational method for quantitative BPE estimation and optimize the related parameters to identify the BPE. We estimate BPE through identifying the enhancing voxels in the DCE-MRI images by measuring the relative voxel-wise enhancement. Our algorithm achieves high agreement with manual segmentation and could be used to standardize measures of BPE in clinical applications.

Jeon-Hor Chen^1,2, Ling-Chuan Chang³, Yi-Ting Wu³, Christopher Scott⁴, V. Shane Pankratz⁴, Kathleen Brandt⁵, Chin-Yu Chang³, Peter T. Fwu¹, Xiao-Yong Wang¹, Min-Ying Su¹, and Celine M. Vachon^4
1Center for Functional Onco-Imaging,Department of Radiological Sciences, University of California Irvine, Irvine, CA, United States, ²Department of Radiology, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan, ³Department of Radiology, China Medical University Hospital, Taichung, Taiwan, ⁴Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States, ⁵Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States

The goals of this study were to examine whether breast density and morphological pattern characterized by MRI can differentiate patients with and without cancer, and further to compare their associations with cancer risk based on MRI-density, mammographic density, or combined variables. Early results from this small cohort suggest mammographic density measures are not strongly associated with breast cancer in this symptomatic population. MRI density remains a strong risk factor for breast cancer, which is consistent with results from a prior screening study.

Samata Kakkad^1,2, Alireza Akhbardeh¹, Jiangyang Zhang³, Meiyappan Solaiyappan¹, Dieter Leibfritz², Kristine Glunde⁴, and Zaver M. Bhujwalla^4
1JHU ICMIC Program, Division of Cancer Imaging Research, The Johns Hopkins University SOM, Baltimore, MD, United States, ²Department of Chemistry and Biology, University of Bremen, Bremen, Germany, ³Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University SOM, Baltimore, MD, United States, ⁴JHU ICMIC Program, Division of Cancer Imaging Research, Johns Hopkins University, Baltimore, MD, United States

Collagen 1 fibers are a major component of the tumor extracellular matrix. Col1 fibers play an important role in macromolecular transport and cancer cell dissemination. Our goal was to determine the influence of Col1 fiber distribution on water diffusion in human breast cancer. We have combined high-resolution diffusion tensor imaging of human breast cancer biopsy followed by second harmonic generation microscopy to intrinsically detect Col1 fibers. Using Haralick texture analysis we classified Col1 fiber distribution feature and observed high water diffusion and diffusion anisotropy correlated with regions of high Col1 fibers. Noninvasive DTI may be used to access Col1 fiber architecture.

Martin D. Pickles¹, Peter Gibbs¹, Martin Lowry¹, and Lindsay W. Turnbull^1
1Centre for MR Investigations, Hull York Medical School at University of Hull, Hull, East Yorkshire, United Kingdom

The aim of this work was to determine if there were any associations between pre-treatment MR derived texture parameters with disease free survival (DFS), in a cohort of patients whom had undergone neoadjuvant chemotherapy. Significant associations between MR texture parameters and survival intervals were noted. Moreover when intercorrelations between variables were considered via a Cox’s proportional hazards model only two variables were retained, sum entropy (texture) and MR longest diameter. In conclusion, texture features provide an insight into longer term DFS and for this cohort texture features out performed DCE-MRI parameters and traditional prognostic indicators.

Jun Chen¹, Kathleen Brandt¹, Karthik Ghosh¹, Roger C. Grimm¹, Kevin J. Glaser¹, Jennifer Kugel¹, and Richard Leroy Ehman^1
1Mayo Clinic, Rochester, MN, United States

Early and accurate diagnosis of breast cancer is critical for optimal treatment. There is considerable interest in exploring the potential of MR elastography to enhance the specificity of contrast-enhanced MRI for characterizing breast lesions. However, as previously implemented MR-elastography has used mechanical drivers that require contact and compression of the breasts, which can change breast tissue stiffness. This study summarizes the development of a new noncompressive MR Elastography technique that does not require any contact with or compression of the breasts and reports the results from a preliminary study of 7 healthy volunteers and one patient with invasive ductal carcinoma.

Stephan Gruber¹, Matthias Riha¹, Lenka Minarikova¹, Katja Pinker², Marek Chmelik¹, Siegfried Trattnig¹, Thomas Helbich², and Wolfgang Bogner^1,3
1MRCE, Dept. Radiology, Medical University of Vienna, Vienna, Vienna, Austria, ²Dept. Radiology, Medical University of Vienna, Vienna, Vienna, Austria, ³Dept. Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

Dynamic contrast enhanced imaging (DCE-MRI) is an important tool to detect breast lesions high sensitivity and specificity. In this pilot study we compared DCE-MRI in seven patients with invasive ductal carcinomas at 3 and 7 T. This resulted in bilateral T1w-images with high spatial resolution and good image quality in all patients at both field strengths. The increase in the contrast-to-noise ratio was in average 2.375 times higher at 7T compared to 3T. In addition, the specificity at 7 T was increased. This study suggests that DCE-MRI is possible at 7 Tesla and may further increase diagnostic accuracy in clinical MR imaging of the breast.

Olgica Zaric¹, Bernhard Strasser¹, Stefan Zbýn¹, Katja Pinker¹, Stephan Gruber¹, Siegfried Trattnig¹, and Wolfgang Bogner^1,2
1Department of Radiology, Medical University of Vienna, Vienna, Vienna, Austria, ²Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Boston, Massachusetts, United States

The aim of this study was to investigate the feasibility of performing sodium MR imaging (23Na MRI) of the human breast at 7T in healthy volunteers and to optimize suitable imaging for use in cancer diagnostics and treatment monitoring. Imaging parameters such as in-plane image resolution of 1 mm, high signal-to-noise ratios, reduced imaging artifacts and reasonable imaging time were achieved. 23Na-MRI, has potential to extend MRI beyond information about anatomical imaging by providing information on physiology and cellular metabolism. Based on our initial results, we conclude that 23Na-MRI at 7T has great potential in clinical investigations of breast tumors.

Christian Geppert¹, Christopher B. Glielmi², Ryan Brown³, Linda Moy³, Josef Pfeuffer⁴, and Eric E. Sigmund^3
1Siemens Medical Systems, New York, NY, United States, ²Siemens Medical Solutions, New York, NY, United States, ³NYU Langone Medical Center, New York, NY, United States,⁴Siemens Healthcare, Erlangen, By, Germany

In breast DWI, typically EPI based methods are used which are prone to characteristic artifacts, such as spatial distortion due to gradient nonlinearity or eddy currents. This study demonstrates the use of 2D-selective RF excitation from a 2-channel parallel transmit system (pTX) to a) overcome these distortions and b) allow the user to restrict the acquisition volume to the breast alone (zoomed EPI). In the protocol applied here, the SNR penalty is due to two reasons: 1) increased TE because of the 2D-selective RF pulse but also because it was invested in higher resolution. Further investigations need to be done with respect to an optimal SNR compromise protocol and in particular a quantitative comparison including measured ADC, and reduction of artifacts.

Nkiruka Atuegwu^1,2, Lori R. Arlinghaus¹, Xia Li¹, A. Bapsi Chakravarthy³, Richard G. Abramson^1,2, Vandana G. Abramson⁴, and Thomas E. Yankeelov^1,2
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Radiology, Vanderbilt University, Nashville, TN, United States, ³Radiation Oncology, Vanderbilt University, Nashville, TN, United States, ⁴Medical Oncology, Vanderbilt University, Nashville, TN, United States

DCE-MRI, DW-MRI, and FDG-PET can provide information on tumor perfusion, microvascular vessel wall permeability, blood volume fractions, cellularity and glucose consumption. These data were collected in breast cancer patients using separate MRI and PET scanners at multiple time points during neoadjuvant chemotherapy. Using a combination of rigid and non-rigid registration algorithms developed in our laboratory we were able to successful align these data to a common imaging space while keeping the tumor size and shape from being substantially altered. The ability to integrate such data may provide unique insights into tumor status and therapy monitoring.

Amy Melsaether¹, Akshat C. Pujara², Rajan Rakheja², Mohammed Shaikh², Eric E. Sigmund², Sungheon Kim², Christian Geppert², and Linda Moy^2
1Radiology, NYU, New York, NY, United States, ²NYU, New York, NY, United States

This study describes and compares the novel modality, 18FDG-PET/MRI, with 18FDG-PET/CT and whole body MRI alone in the evaluation of multi-organ system metastatic breast cancer. Results suggest PET/MRI provides similar sensitivity and confidence for suspicious lesions across organ systems as compared with PET/CT and increased specificity as compared with PET/CT and MRI alone, also across organ systems, for lower confidence lesions. Although PET/MRI detects more incidentalomas, the MRI data is usually sufficient for characterization and additional tests are not frequently required. PET/MRI can provide this information at approximately one-half the radiation dose of 18FDG-PET/CT.

Guillaume Gilbert^1,2, Isabelle Trop¹, Marko K. Ivancevic³, and Gilles Beaudoin^1
1Department of Radiology, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada, ²MR Clinical Science, Philips Healthcare, Montreal, Quebec, Canada, ³MR Clinical Science, Philips Healthcare, Best, Netherlands

B1 inhomogeneity is a known issue when performing breast MRI at 3T using standard quadrature transmission. Consequently, parallel transmission was proposed as way to improve B1 homogeneity. The aim of this study was to evaluate and compare in a cohort of women undergoing both 1.5T and 3T breast MRI the B1 homogeneity achieved at 1.5 and 3T, and for both quadrature and dual-source parallel transmission at 3T. It was found that 3T MRI with dual-source parallel transmission offers an overall B1 homogeneity for breast imaging that is better than that obtained at 1.5T and at 3T with quadrature transmission.

Yeun-Chung Chang¹, Yan-Hao Huang², Chin-Ho Lin², Chiun-Sheng Huang³, Jeon-Hor Chen⁴, and Ruey-Feng Chang^2
1Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, Taiwan, ²Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan, Taiwan, ³Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, Taiwan, ⁴Tu and Yuen Center for Functional Onco-Imaging and Department of Radiological Science, University of California Irvine, Irvine, California, United States

To compare the performance of a new computer-aided algorithm for the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the diffusion-weighted magnetic resonance imaging (DWI) in differentiating benign from malignant breast lesions.

Xiutao Shi¹, Tejan Diwanji¹, Karen E. Mooney¹, Warren D. D'Souza¹, and Nilesh Mistry^1
1Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, United States

Accurate tracking of tumors in lung cancer is crucial for safe and effective delivery of radiation treatment. In the current study, an automated template matching technique has been applied to track respiration induced tumor motion based on cine MRI images. The performance of the technique is compared to manual estimates of tumor position. For tumors smaller than 50 mm in the longest dimension, the prediction error is < 3.9 mm (less than two pixels) and is in the order of intra-operator or inter-operator variability during manual tracking. Further hardware developments can enable clinical translation.

Xue Yu¹, Elaine Yuen Phin Lee¹, and Vincent Lai^1
1Diagnostic Radiology, University of Hong Kong, Hong Kong, China

This purpose of the study is to evaluate the diagnostic performance of FDG-PET/CT and DWI with conventional MRI in peritoneal metastases detection and to assess the correlation between SUV and ADC measured by FDG-PET/CT and DWI with conventional MRI, respectively, in peritoneal metastases. The prospective study recruited patients with suspected peritoneal metastases, and the acquired FDG-PET/CT and DWI/MRI images were reviewed independently by two radiologists. Results showed no significant differences between FDG-PET/CT and DWI/MRI in peritoneal metastases detection, and statistically significant inverse correlation was found between SUV and ADC.

Hao Han¹, Lihong Li², Chaijie Duan³, Hao Zhang¹, and Zhengrong Liang^1
1Dept. of Radiology, Stony Brook University, Stony Brook, NY, United States, ²Dept. of Engineering Science & Physics, College of Staten Island of the City University of New York, Staten Island, NY, United States, ³Dept. of Biomedical Engineering, Tsinghua University, Shenzhen, Guangdong, China

Bladder cancer is the fifth leading cause of cancer related death, especially for aged males in the United States. Early detection of bladder lesion is so crucial that advanced techniques are required to precisely and safely differentiate tumors from the normal bladder wall. In this work, we developed a novel approach to precisely segment the inner border and outer border of the bladder wall, and it was shown that our new approach outperforms the previous approach developed in our group. The bladder lesion can be visualized through a 3-D rendering model on wall thickness calculated from the segmented bladder wall.

Patrick W. Hales¹, Øystein E. Olsen², Neil J. Sebire³, and Christopher A. Clark^1
1Imaging and Biophysics, University College London, London, London, United Kingdom, ²Radiology Department, Great Ormond Street Hospital, London, London, United Kingdom,³Histopathology Department, Great Ormond Street Hospital, London, London, United Kingdom

We investigated whether properties of the histogram of ADC values within a Wilms’ tumour, obtained from diffusion weighted imaging (DWI) at presentation, could be used to predict the histologically-determined tumour subtype, and response to chemotherapy. Median, skewness, kurtosis and full width at half maximum of the ADC histogram were used in a multinomial logistic regression model, to discriminate three tumour subtypes (stromal, blastemal, mixed), with 91% accuracy. The same parameters showed good predictive power when used in a multiple linear regression model, to predict the tumour’s response to chemotherapy, assessed by either change in volume, or shift in ADC.

Kay Pelletier¹, Jun Chen¹, Kevin J. Glaser¹, Stephen Ansell¹, Richard Leroy Ehman¹, and Kiaran P. McGee^1
1Mayo Clinic, Rochester, MN, United States

Change in tumor mechanical properties may be an early indication of therapeutic response. Previous studies demonstrated a measurable change in tumor stiffness following chemotherapy treatment. We propose that MRE can be used to determine sub lethal dose response and overall tumor viability. Following a sub-lethal dose of chemotherapy, tumor stiffness initially decreases and subsequently increases with tumor recovery and growth. Stiffness is also dependent on viability of the host, as the stiffness increased significantly within 1 hour post-mortem.

Jin Li¹, Yann Jamin¹, Craig Cummings¹, Jessica K.R. Boult¹, John C. Waterton², Jose Ulloa², Ralph Sinkus³, Jeffery C. Bamber¹, and Simon P. Robinson^1
1Division of Radiotherapy & Imaging, The Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, United Kingdom, ²Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom, ³Centre de Recherche Biomedicale Bichat Beaujon, Clichy, France

Magnetic resonance elastography was used to assess the viscoelastic response in vivo of SW620 xenografts associated with massive central hemorrhagic necrosis induced 24 hours after treatment with the vascular disrupting agent ZD6126. Treatment resulted in a highly significant reduction in the complex shear modulus, elasticity and viscosity, which correlated with a pathologically confirmed necrosis.

Florence Colliez¹, Julie Magat¹, Marie-Aline Neveu¹, Bernard Gallez¹, and Bénédicte F. Jordan^1
1Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, University of Louvain, Brussels, Belgium

A beneficial association between radiotherapy and CA4 has been suggested. Non-invasive mapping of tumor oxygenation before and after treatment with CA4 for the optimization of treatment combination and scheduling seems therefore particularly relevant. We recently exploited a highly sensitive endogenous contrast to map variations in tumor oxygenation, a technique that we called “MOBILE” (Mapping of Oxygen By Imaging Lipids relaxation Enhancement), based on the changes in the relaxation properties of the tissue lipids. The purpose of the current work was to test the ability of the “MOBILE” technique to monitor adequately a decrease in tumor oxygenation following administration of the anti-vascular agent CA4 in MDA-MB-231 mammary tumors, in comparison with EPR oximetry.

Guihua Zhai¹, Clinton Grubbs¹, Cecil Stockard¹, Heidi Umphrey¹, Timothy Beasley¹, and Hyunki Kim^1
1University of Alabama at Birmingham, Birmingham, AL, United States

Tamoxifen is a clinically approved hormonal therapeutic agent for ER+ breast cancer in both neoadjuvant and adjuvant settings. However, a wide range of tamoxifen sensitivity has been observed among patients, and therefore it would be necessary to select patients favorably responding to tamoxifen ideally based on non-invasive imaging techniques. Diffusion-weighted imaging (DWI) was employed to assess the early tumor response following tamoxifen therapy in a methylnitrosourea (MNU)-induced breast-cancer rat model. Also, significant correlation between ER-beta density and early ADC change was verified, suggesting ER-beta as a prognostic biomarker for effective tamoxifen therapy as well.

Jesper Folsted Kallehauge¹, Erik M. Pedersen², Kari Tanderup¹, Finn Rasmussen², Jacob Lindegaard¹, Lars Fokdal¹, Søren Haack¹, and Thomas Nielsen^1
1Department of Oncology, Experimental Clinical Oncology, Århus, Denmark, ²Department of Radiology, Department of Radiology, Århus, Denmark

Stratification of advanced cervical cancer patients based on perfusion MRI parameters has been succesfull. This abstracts compares different model parameters in the search for the parameter that is easiest to implement in a clinical routine.

Julien Bouvier^1,2, Nicolas Coquery¹, Sylvie Grand^1,3, Irène Troprès⁴, David Chechin², Jean-François Le Bas^3,4, Olivier François⁵, Alexandre Krainik^1,3, and Emmanuel Luc Barbier^1
1INSERM U836, Grenoble Institute of Neurosciences, Grenoble, France, ²Philips Healthcare, Suresnes, France, ³CHU de Grenoble, Clinique Universitaire de Neuroradiologie et d’IRM, Grenoble, France, ⁴Plate-forme IRMaGe, UJF – INSERM US17 – CNRS UMS 3552, Grenoble, France, ⁵UMR 5525, TIMC-IMAG, Grenoble, France

In clinical monitoring of brain tumors, Perfusion Weigthed Imaging (PWI) contributes to tumor grading and to assess the response to treatment, as early as possible. Beyond tumor perfusion, tumor hypoxia has been shown to determine the reponse of various therapeutic approaches including radiotherapy. The aim of this study is to evaluate in patients how tissular oxygen saturation (StO2), assessed with a multiparametric qBOLD approach, could contribute to characterize brain tumors using a model-based cluster approach.

Chen-Yi Liu¹, Yen-Peng Liao², Yu-Shi Lin^1,3, Shy-Chyi Chin⁴, and Ho-Ling Liu^1,4
1Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan, ²Department of Medical Imaging, Taipei Medical University - Shuang Ho Hospital, Taipei, Taiwan, ³Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Keelung, Taiwan, ⁴Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

This study aimed to investigate the variability of physiological parameters estimated by the AATH and the mTK models in DCE-MRI. Computer simulation were performed using multiple path, multiple tracer, indicator dilution, 4 region (MMID4) model with various noise added. In addition, the two models were applied in nasopharyngeal carcinoma patients for comparison. Computer simulation quantified the error and variations of the two models, which demonstrated that the AATH was more accurate but less precise than the mTK. Clinical results agreed with the simulation, which showed smaller Ktrans and Veand larger Vp with the AATH than with the mTK model.

Tobias Heye¹, Elmar M. Merkle², Caecilia S. Reiner¹, Matthew S. Davenport³, Jeff J. Horvath¹, Sebastian Feuerlein⁴, Steven R. Breault¹, Peter Gall⁵, Mustafa R. Bashir¹, Brian M. Dale⁶, Attila Kiraly⁷, and Daniel T. Boll^1
1Department of Radiology, Duke University Medical Center, Durham, NC, United States, ²Klinik für Radiologie und Nuklearmedizin, Universitätsspital Basel, Basel, Kanton Basel, Switzerland, ³Department of Radiology, University of Michigan Health System, Ann Arbor, MI, United States, ⁴Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, VA, United States, ⁵Imaging & Therapy Division, Healthcare Sector, Siemens AG, Erlangen, -, Germany, ⁶MR R&D Collaborations, Siemens Healthcare, Morrisville, NC, United States, ⁷Corporate Research and Technology, Siemens Corporation, Princeton, NJ, United States

Inter-observer variability is a considerable factor of measurement variation in any quantitative imaging approach in particular multi-center studies. Many of the contributors to the overall variation in DCE-MRI results are technical or mathematical in nature and their influence is systematic, thus allowing for estimation, correction and optimization of the error. However, unlike these more predictable sources, the observer imparts a more variable contribution to the overall error in the entire process of DCE-MRI. We could shown that a guided measurement method can reduce inter-observer variability significantly (relative reduction by 42.5%) compared to manual ROI placement (16.4% versus 28.5%, respectively).

Parastou Foroutan¹, Christopher L. Cubitt^2,3, Jillaina L. Menth³, Damon Reed^2,4, Marilyn M. Bui², David L. Morse¹, Douglas G. Letson⁴, Daniel Sullivan², Robert J. Gillies¹, and Gary V. Martinez^1
1Imaging, H. Lee Moffitt Cancer Center, Tampa, FL, United States, ²Experimental Therapeutics Program, H. Lee Moffitt Cancer Center, Tampa, FL, United States, ³Translational Research Lab, H. Lee Moffitt Cancer Center, Tampa, FL, United States, ⁴Sarcoma Program, H. Lee Moffitt Cancer Center, Tampa, FL, United States

Using MRI at 7T, the therapeutic effect of Dasatinib and Triciribine were evaluated in Ewing’s Sarcoma mouse xenografts. Following treatments, tumor growth increased significantly for ctrl and Tri compared to Das and combination groups. The two responsive groups also showed significant increases in ADC as well as altered skewness and kurtosis while the Ctrl and Tri remained relatively constant. Interestingly, correlation of T2 intensity, ADC and volume suggested that alterations in T2, in addition to ADC, may serve as an early indicator of treatment response. In agreement, histology demonstrated significantly higher necrosis and lower cell viability in Das and Comb.

Søren Haack¹, Kari Tanderup², Lars Fokdal², Jesper Folsted Kallehauge³, Jacob Lindegaard², Sune N. Jespersen^4,5, and Erik M. Pedersen^6
1Dept. of Clinical Engineering, Aarhus University Hospital, Aarhus, Denmark, ²Dept. of Oncology, Aarhus University Hospital, Aarhus, Denmark, ³Dept. of Medical Physics, Aarhus University Hospital, Aarhus, Denmark, ⁴CFIN/MindLab, Aarhus University, Aarhus, Denmark, ⁵Dept. of Physics and Astronomy, Aarhus University, Aarhus, Denmark, ⁶Dept. of Radiology, Aarhus University, Aarhus, Denmark

Diffusion weighted MRI has shown great potential in diagnostic cancer imaging and may also have value for monitoring tumor response during radiotherapy. Patients with advanced cervical cancer are treated with external beam radiotherapy followed by brachytherapy. This study evaluates the value of DW-MRI for predicting outcome of patients with advanced cervical cancer at time of brachytherapy. Volume of hyper-intensity on highly diffusion sensitive images and resulting ADC value for treatment responders and non-responders is compared. The change of ADC and volume of hyper-intensity over time of BT is also evaluated.

Xiaobing Fan¹, Aytekin Oto¹, and Gregory S. Karczmar^1
1University of Chicago, Chicago, IL, United States

The nonlinearity of two-compartment model (TCM) of dynamic contrast-enhanced MRI (DCE-MRI) was studied using computer simulations and an example of clinical prostate DCE-MRI. Even when each individual contrast media concentration v.s. time curve (C(t)) within a region of interest (ROI) satisfies the TCM, the averaged C(t) over the ROI may not satisfy the TCM. Our computer simulation results showed that the Ktrans derived from fitting the averaged C(t) was 20% to 30% smaller than average of all of the Ktrans values for each pixel in the ROI. This is substantial error, and the error for many individual patients will be even higher, leading to errors in diagnosis.

Eito Kozawa¹, Masahiro Takahasi¹, Tomomi Kato², Masanori Yasuda³, Keiichi Fugiwara⁴, and Fumiko Kimura^5
1Imaging Diagnosis, Saitama Medical University, International Medical Center, Hidaka-shi, Saitama, Japan, ²Pathologic Diagnosis, Saitama Medical University, International Medical Center, Hidaka-shi, Saitama, Japan, ³Pathologic Diagnosis, Saitama medical University,International Medical Center, Hidaka-shi, Saitama, Japan, ⁴Gynecologic Oncology, Saitama Medical University, International Medical Center, Hidaka-shi, Saitama, Japan, ⁵Imaging Diagnosis, Saitama Medical University,International Medical Center, Hidaka-shi, Saitma, Japan

Ovarian endometrioid adenocarcinoma and sertoliform endometrioid adenocarcinoma belong to the surface epithelial-stromal tumors. Sertoliform endometrioid adenocarcinoma is an uncommon variant, and comprises a portion resembling endometrioid adenocarcinoma and a portion resembling sex-cord stromal tumor. The aim of this study was to investigate differential imaging features between ovarian endometrioid adenocarcinoma and sertolifolm endometrioid adenocarcinoma on magnetic resonance imaging. In quantitative assessment, SIR values of sertoliform endometrioid adenocarcinoma reflecting T2-low signal intensity yielded low values than those of endometioid adenocarcinoma. MR imaging findings of endometrioma were more likely endometrioid adenocarcinoma, whereas SIR of seltoliform ednometrioid adenocarcinoma yielded low values.

Lionel Mignion¹, Prasanta Dutta², Gary V. Martinez², Parastou Foroutan³, Robert J. Gillies³, and Benedicte Jordan^1
1Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Universite Catholique de Louvain, Brussels, Belgium, ²Department of Imaging Research, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States, ³Department of Imaging Research, H. Lee Moffitt Cancer Center, Tampa, Florida, United States

This study assesses the response to a multikinase inhibitor, Sorafenib, using a combined hyperpolarized 13C-fumarate and 13C-pyruvate in comparison with diffusion weighted-MRI (DW-MRI). In MDA-MB-231 mammary xenografts, hyperpolarized MRS using 13C-fumarate is an early in vivo marker of response to Sorafenib and is positively correlated with DW-MRI, with a higher sensitivity for 13C-fumarate with respect to DW-MRI. Results are in accordance with ex vivo H&E analysis. The lactate to pyruvate ratio does not seem to be an in vivo marker of tumor response to the multikinase inhibitor in this tumor model.

Matthew R. Orton¹, Matthew Gwilliam¹, Christina Messiou², David John Collins¹, Veronica A. Morgan², Helen Young³, Nandita M. De Souza¹, and Martin O. Leach^1
1CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research, Sutton, Surrey, United Kingdom, ²Radiology Department, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ³AstraZeneca, Macclesfield, Cheshire, United Kingdom

This observational report describes statistically significant increases in the contrast arrival time measured using DCE-MRI in a cohort of patients with liver metastases after 1 week and 4 weeks of treatment with an anti-VEGF agent. This result highlights the importance of acquiring data with adequate temporal sampling rates, and the use of robust methods of arrival time estimation when deriving DCE-MRI parameters.

Parastou Foroutan¹, Jenny M. Kreahling², Damon Reed^2,3, Mark C. Lloyd⁴, Soner Altiok^2,3, Gary V. Martinez¹, and Robert J. Gillies^1
1Imaging, H. Lee Moffitt Cancer Center, Tampa, FL, United States, ²Experimental Therapeutics Program, H. Lee Moffitt Cancer Center, Tampa, FL, United States, ³The Sarcoma Program, H. Lee Moffitt Cancer Center, Tampa, FL, United States, ⁴Analytic Microscopy, H. Lee Moffitt Cancer Center, Tampa, FL, United States

MRI at 7T was employed to evaluate the therapeutic effects of MK1775 and gemcitabine (Gem) in patient derived xenograft mouse models for osteosarcoma. ROI analysis showed significantly smaller tumor volumes for the treated animals compared to controls, particularly the Gem and Combination (Comb) groups. Significant increases in mean ADC for these groups were observed immediately following the first treatment, which also correlated with changes in skewness and kurtosis. Histology also showed significantly higher apoptosis and DNA damage in Comb and while tumor volume correlated well with these insults, changes in ADC indicating treatment response occured at earlier time points.

Huiyan Shao¹, Li Guo², Xiaoying Wang², Rui Li¹, Chun Yuan^1,3, and Huijun Chen^1
1Tsinghua University, Beijing, Beijing, China, ²Peking University First Hospital, Beijing, Beijing, China, ³University of Washington, Seattle, WA, United States

Neoadjuvant Chemotherapy (NAC), locally enforced before the surgery, plays a significant role in the multimodality therapy of breast cancer. To predict whether a patient will have a complete response after the early NAC in-vivo is critical for the therapy plan. Diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) have been reported great potential to predict NAC responder. However, most studies used the diffusion or perfusion imaging alone for prediction. In this study, we employed neural network and logistic regression to predict the final treatment response by using the changes of DW-MRI and DCE-MRI parameters after the early NAC cycles.

Jiayu Sun¹, Rui Xia¹, Fabao Gao¹, Jie Zheng², and Bing Wu^1
1Department of Radiology, West China Hospital,Sichuan University, Chengdu, Sichuan, China, ²Mallinckrodt Institute of Radiology,Washington University School of Medicine in St. Louis, St.Louis, Missouri, United States

6 patients with hepatic cell carcinoma confirmed on liver biopsy were scanned on a Siemens Trio 3.0 T whole body scanner. A novel B0- and B1-insensitive multi-contrast T1rho imaging with segmented trueFISP readout was performed on the slice of the central tumor during end-inspiratory breath holding,Correlation between mean T1¦Ñ and pathological grading was excellent in all cases for liver tumors.The longer T1rho ratio in tumor tissue may add additional dimension for staging tumors and treatment monitoring.

Lingyun Hu¹, Ashley Aronow², Lakshmi Raj², and Erica C. Henning^1
1Global Imaging Group, Novartis Institutes for Biomedical Research (NIBR), Cambridge, MA, United States, ²Biologics Center, Novartis Institutes for Biomedical Research (NIBR), Cambridge, MA, United States

In this study, we employed combined MDEFT/RARE for non-invasive, longitudinal monitoring of HCC progression with high sensitivity and reliability. We were able to diagnose and quantify primary HCC tumor volume and secondary liver metastasis without contrast agent and without respiratory triggering. We achieved higher CNR than previous reports employing Gd-DTPA or Gd-EOB-DTPA, with a detection limit of 1mm diameter HCC versus 2mm reported. With easy setup and no contrast agent or respiratory triggering required, MDEFT/RARE provides a powerful alternative for accurate quantification of HCC, with relatively high throughput, improved study power, and reduction in animal use.

Feng Zhang¹, Thomas Le¹, Xia Wu¹, Tong Zhang¹, Han Wang¹, Stephanie Soriano¹, Donghoon Lee¹, and Xiaoming Yang^1
1Radiology, University of Washington, Seattle, WA, United States

This study validated the feasibility of using 14 Tesla MRI to monitor mice cholangiocarcinoma response to radiofrequency heating(RFH)-enhance chemotherapy. Apparent diffusion coefficient(ADC) is a very useful biomarker for predicting the response of cholangiocarcinoma to RFH-enhanced chemotheray, which was confirmed by subsequent MRI-histology correlation. This new technique may open new revenues for MRI monitored intrabiliary RFH-enhanced chemotherapy for pancreatobiliary malignancies.

Lydia Wachsmuth¹, Sonja Schäfers², Thomas Viel², Sven Hermann², Niclas Kremer², Michael Schäfers², Klaus Schäfers², Andreas H. Jacobs², Carsten Müller-Tidow³, and Cornelius Faber^1
1Clinical Radiology, Experimental NMR, University Hospital Münster, Münster, Germany, ²European Institute for Molecular Imaging, Münster, Germany, ³Molecular Hematology/Oncology, University Hospital Münster, Münster, Germany

Diffusion-weighted magnetic resonance imaging (DW-MRI) and (18F-FLT) PET examinations were subsequently performed in a human lung carcinoma xenograft mouse model without change in animal position between scans in order to directly relate tracer accumulation to local diffusion coefficients. Tumor tissue heterogeneity was reflected by regional changes in ADC. Much higher 18F-FLT uptake in the proliferative rim of the tumor, showing low diffusion constants, compared to low radiotracer accumulation in the tumor core with high ADC values, support the assumption that high ADC values in the tumor core represent necrotic areas. Bimodal imaging findings were confirmed by immunohistochemistry.

Hasan Alsaid¹, Charity Atkins², Sarah Lee³, Tinamarie Skedzielewski¹, Mary V. Rambo¹, Shu-Yun Zhang², David J. Figueroa², Brandon Whitcher³, Rakesh Kumar², and Beat M. Jucker^1
1Preclinical & Translational Imaging, LAS, PTS, GlaxoSmithKline, King of Prussia, PA, United States, ²Oncology R&D, GlaxoSmithKline, Collegeville, PA, United States, ³Mango Solutions, London, United Kingdom

The eukaryotic initiation factor 2-alpha kinase 3 (EIF2AK3) or PERK is one of three mediators of the unfolded protein response signal transduction pathway. GSK2656157 is the first-in-class, small molecule inhibitor of PERK enzyme activity in cells with an IC50 in the range of 10-30 nM as reflected by inhibition of stress-induced PERK autophosphorylation. In this study, we investigated the pharmacological effect of GSK2656157 on tumor growth and angiogenesis using dynamic contrast enhanced MRI (DCE-MRI) in the BxPc3 xenograft tumor model. The results suggest DCE-MRI can be used as a PD marker to monitor the antiangiogenic effect of a PERK inhibition in human subjects.

Marnix C. Maas¹, Mariët J. Koopman¹, Geert J.S. Litjens¹, Alan J. Wright¹, Kirsten M. Selnæs², Ingrid Susann Gribbestad², Masoom A. Haider³, Katarzyna J. Macura⁴, Daniel J.A. Margolis⁵, Berthold Kiefer⁶, Jurgen J. Fütterer¹, and Tom W.J. Scheenen^1
1Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ²Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway, ³Joint Department of Medical Imaging, Princess Margaret Hospital, University Health Network and Mount Sinai Hospital, Toronto, ON, Canada, ⁴Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ⁵Department of Radiology, UCLA David Geffen School of Medicine, Los Angeles, CA, United States, ⁶Siemens AG Healthcare Sector, Erlangen, Germany

This work presents initial results of a multi-center trial aimed at assessing the diagnostic accuracy of 3T multi-parametric MR imaging and spectroscopy (mpMRI) in distinguishing clinically significant prostate cancer from other prostatic tissue, with whole-mount section histopathology as the gold standard. Multi-center mpMRI with identical protocols at 3T without ERC provided homogeneous quantitative parameters for non-cancer tissues and detected significant differences between these tissues. The validation part of this prospective trial will be used to determine the parameters contributing most to the detection and localization of clinically significant PCa as well as their optimal cutoff values.

Tobias Penzkofer^1,2, Kemal Tuncali¹, Andriy Fedorov¹, Junichi Tokuda¹, Sang-Eun Song¹, Nobuhiko Hata¹, Sandeep Narendra Gupta³, Robert Mulkern⁴, Fiona Fennessy^1,5, and Clare Tempany^1
1Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States, ²Diagnostic and Interventional Radiology, RWTH Aachen University Hospital, Aachen, NRW, Germany, ³GE Global Research, Niskyuna, NY, United States, ⁴Department of Radiology, Boston Children's Hospital, Boston, MA, United States, ⁵Department of Radiology, Dana Farber Cancer Institute, Boston, MA, United States

We present the analysis of the utility of mpMRI including quantitative imaging parameters in prostate cancer detection, and the discriminating power of the individual parameters between the biopsy sample pathology-confirmed cancer and non-cancer areas. The multireader setting yielded a high number of additional cancer diagnoses. While for all parameters scores were on average higher for histologically malignant lesions, only T2, ADC500, ADC1400, Subtraction, Ktrans, Ve and TTP showed a significant difference in score.

Kiri Sandler¹, Charles Lynne², Merce Jorda³, Alan Pollack¹, and Radka Stoyanova^1
1Department of Radiation Oncology, University of Miami, Miami, FL, United States, ²Department of Urology, University of Miami, Miami, FL, United States, ³Department of Pathology, University of Miami, Miami, FL, United States

With a trend towards more conservative management of prostate cancer, it is vital to be able to identify those men on active surveillance with tumors that warrant conversion to treatment. We use functional MRI to identify suspicious lesions, and MRI-guided real-time ultrasound image fusion to target and biopsy them. Using this strategy, we identified a patient on active surveillance with Gleason 3+4 disease in the prostate apex which was not palpable by digital rectal exam, and had not been sampled with traditional transrectal ultrasound-guided biopsy.

Yahui Peng¹, Yulei Jiang¹, Tatjana Antic², Maryellen L. Giger¹, Scott Eggener³, and Aytekin Oto^1
1Radiology, The University of Chicago, Chicago, IL, United States, ²Pathology, The University of Chicago, Chicago, IL, United States, ³Surgery, The University of Chicago, Chicago, IL, United States

We previously identified from Phillips MR images three quantitative multi-parametric endorectal MR image features effective for differentiation between prostate cancer and normal peripheral zone tissue regions of interest (ROIs), and moderately correlate with tumor ROI-specific Gleason score. We now validate these image features on GE MR images of 71 prostate cancer patients. Results show for both Philips and GE scanners that the 10th percentile, and average, ADC values, and T2-weighted signal-intensity histogram skewness are effective in differentiating prostate cancer from normal peripheral zone tissue ROIs, and that the ADC features correlate moderately and negatively with tumor ROI-specific Gleason scores.

Satish Viswanath¹, Dan Sperling², Herbert Lepor³, Jurgen J. Futterer⁴, and Anant Madabhushi^1
1Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States, ²Radiology, New Jersey Institute of Radiology, Carlstadt, New Jersey, United States, ³Urology, NYU Langone Medical Center and School of Medicine, New York, New York, United States, ⁴Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

We present a quantitative image analysis framework which enables high-resolution evaluation of treatment-related changes in vivo for patients undergoing laser interstitial thermal therapy (LITT). Our computerized decision support framework brings different MP-MRI parameters into alignment and differentially weights their contributions for treatment evaluation. Preliminary results suggest that our framework can accurately quantify changes in MP MRI imaging markers. The integrated MP-MRI difference map showed excellent utility in quantifying the extent and types of focal treatment-related changes, in vivo.

Pallavi Tiwari¹, John Kurhanewicz², and Anant Madabhushi^1
1Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States, ²Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States

In this work, we present an image analysis framework to quantiatively evaluate changes in strucutral, functional, and metabolic markers (obtained via T2-w, DWI, MRS respectively) to (a) identify MRI markers that correlate the most with treatment related changes post-radiation therapy (RT) in prostate cancer (CaP) patients, and (b) compute a weighted MP-MRI map by optimally combining contributions of strucutral (T2-w), functional (DWI), metabolic (MRS) markers, based on their ability to accurately capturing post-RT changes.

Chengyan Wang¹, Juan Hu², He Wang², Hui Zhang¹, Rui Wang², Wenchao Cai², Wei Wang², Xiaoying Wang^1,2, Jue Zhang^1,3, and Jing Fang^1,3
1Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China, ²Department of Radiology, Peking University First Hospital, Beijing, China, ³College of Engineering, Peking University, Beijing, China

In the present study, we propose a multi-layer artificial neural network (ANN) model integrating MR images (T2 weighted images£¬diffusion weighted images, dynamic contrast enhanced images and MR spectroscopy) and clinical examination (Total PSA value, free/total PSA ratio and age) for prostate cancer detection. The new model is able to provide high accuracy in detection of prostate cancer through proper training. Significant improvement in the AUC can be produced when compared to clinical-only model, and this demonstrates the capacity of MRI for computer-aided prostate cancer identification.

Sophie F. Riches¹, Geoffrey S. Payne¹, Charlie Jameson², Christopher Ogden³, Mike Partridge⁴, Veronica A. Morgan¹, Sharon L. Giles¹, and Nandita M. deSouza^1
1CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ²Department of Histopathology, University College London Hospitals, London, London, United Kingdom, ³Department of Surgery, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ⁴Gray Institute for Radiation Oncology and Biology,Department of Oncology, University of Oxford, Oxford, Oxfordshire, United Kingdom

Currently the use of a boosted radiation dose to tumour in localised prostate cancer is limited by the accuracy of tumour localisation within the prostate on anatomical imaging; functional imaging is therefore being explored. This study shows that a model combining parameters from multiple functional MR techniques gives greater accuracy in discriminating between tumour and normal prostate tissues than individual parameters. The average accuracy of prediction of tissue type for individual patients is lower than that suggested by the population ROC curve due to high inter-patient variability within the population.

Josephin Otto¹, Gregor Thörmer¹, Martin Reiss-Zimmermann¹, Nikita Garnov¹, Lars-Christian Horn², Thomas Kahn¹, Michael Moche¹, and Harald Busse^1
1Diagnostic and Interventional Radiology Department, Leipzig University Hospital, Leipzig, Saxony, Germany, ²Institute of Pathology, University of Leipzig, Leipzig, Saxony, Germany

Multiparametric MRI of the prostate has become a reliable technique for the detection, staging and characterization of prostate cancer (PCa). So far, however, there is no consensus about the minimal MR equipment needed for improved prostate diagnostics. In particular, the use of an endorectal coil (ERC) at higher field strengths is discussed controversially. This work demonstrates that the additional use of an ERC at 3 T improves image quality measures related to the localization and staging of PCa. The use of an ERC intraindividually improves the detection of cancer-suspicious lesions (PI-RADS≥3) and the tumor detection rate per patient.

Lauren J. Bains¹, Maria Triantafyllou¹, Johannes M. Froehlich¹, Giuseppe Petralia¹, Daniel Chong¹, and Harriet C. Thoeny^1
1Department of Diagnostic, Interventional, and Pediatric Radiology, Inselspital University Hospital Bern, Bern, Bern, Switzerland

In this study we performed an assessment the sensitivity and specificity of the detection of primary prostate tumours in patients with and without primary prostate cancer, using prostatectomy as a gold standard. Inter-reader agreement between 3 independent readers was good ( = 0.57). Sensitivity was 88-91% overall and specificity was 56-72%, despite the presence of TN in this cohort. High grade (Gleason score  7) cancers were detected with a better sensitivity. False positives were related to the presence of prostatic hyperplasia and neoplasia, while false negatives were related to small tumours with low Gleason score.

Natalie Korn¹, John Kurhanewicz^1,2, Suchandrima Banerjee³, Emine U. Saritas⁴, and Susan Noworolski^1,2
1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ²Graduate Group in Bioengineering, University of California, Berkeley, Berkeley, California, United States, ³GE Healthcare, San Francisco, California, United States, ⁴Bioengineering, University of California, Berkeley, Berkeley, California, United States

Diffusion-weighted imaging (DWI) increases both sensitivity and specificity in detecting prostate cancer in multiparametric MR studies. However, susceptibility artifact at interfaces between the prostate and air, blood, or fecal matter confounds DWI images. A novel, reduced field-of-view pulse sequence to reduce distortion in DWI was evaluated in 27 prostate cancer patients. Visually-assessed distortion was reduced in 75% of patients (p<0.0003) and contrast between tumor and healthy tissue was significantly improved (p<0.02) as compared to the standard DWI sequence.

Satoru Takahashi¹, Yoshiko Ueno¹, Kazuhiro Kitajima², Tomoyuki Okuaki³, and Kazuro Sugimura^2
1Radiology, Kobe University Hospital, Kobe, Hyoto, Japan, ²Radiology, Kobe University Graduate School of Medicine, Kobe, Hyoto, Japan, ³Philips Electronics Japan, Minato, Tokyo, Japan

Although diffusion tensor imaging (DTI) with a smaller FOV is desirable for visualizing tiny neurovascular bundles (NVBs) around the prostate, a conventional excitation technique limits the minimum size of FOV due to aliasing artifact. We conducted this preliminary study to evaluate the ability of selective radiofrequency excitations technique (zoom DTI) for the demonstration of the NVB using fiber tractography technique with small FOV. We found that tractography with zoom DTI technique of the prostate was feasible and could elucidate the periprostatic fiber tract detail, although further study is required to correlate DTI findings to gold standard anatomic specimens.

Chiharu Tamura¹, Hiroshi Shinmoto¹, Shigeyoshi Soga¹, Teppei Okamura¹, Sadahiro Watanabe¹, Tatsumi Kaji¹, Tomoyuki Okuaki², Makoto Obara², Yuxi Pang³, and Hiroki Sato^4
1Department of Radiology, National Defense Medical College, Saitama, Japan, ²Philips Electronics Japan, Tokyo, Japan, ³Philips Healthcare, Cleveland, Ohio, United States,⁴Department of Preventive Medicine and Public Health, National Defense Medical College, Saitama, Japan

We have clarified the differences in parameters among prostate cancer (PC), benign prostatic hyperplasia (BPH), and benign peripheral zone (PZ) using diffusion kurtosis imaging (DKI). Seventeen patients who were histologically proven to have PC and had undergone total prostatectomy after DKI-MRI were investigated. Although it was difficult to distinguish between PC and BPH, especially BPH-low, the parameter K obtained from DKI was significantly higher in PC than in benign PZ, BPH-mix, and BPH-high and trended toward being higher in PC than in BPH-low. DKI may contribute to the diagnosis of PC, especially in the differential diagnosis of PC and BPH.

Harsh K. Agarwal^1,2, Kinzya Grant², Baris I. Turkbey², Yuxi Pang³, Marcelino Bernardo^2,4, Julien Sénégas⁵, Dagane Daar^2,4, Junaita Weaver^2,4, Jochen Keupp⁵, Maria J. Merino⁶, Bradford Wood⁷, Peter A. Pinto⁸, and Peter L. Choyke^2
1Philips Research North America, Briarcliff Manor, NY, United States, ²Molecular Imaging Program, NCI, National Institute of Health, Bethesda, MD, United States, ³Philips Healthcare, Cleaveland, OH, United States, ⁴SAIC Frederick Inc., Frederick, MD, United States, ⁵Philips Research Laboratories, Hamburg, Germany, ⁶5Laboratory of Pathology, NCI, National Institute of Health, Bethesda, MD, United States, ⁷NIH Center for Interventional Oncology, National Institute of Health, Bethesda, MD, United States, ⁸Urologic Oncology Branch, National Institute of Health, Bethesda, MD, United States

ADC maps estimated from single compartment analysis of DW-MRI have been successfully used in prostate oncology to identify and stage the tumor aggressiveness with its Gleason score. However, at higher b-values the multi-compartment diffusion nature of the tumor tissue becomes apparent providing good contrast between the tumor and the normal prostate tissue due to the complete suppression of the normal tissue. Simple ADC measures such as ADC from b=0 and 2000 and ADC from 0 and 1000 b value DW-MRI images were compared with ADC from regular DW-MRI images b=0,188,350,563 and 750 to show similar tumor grading performance with better background suppression with high b value DW-MRI.

Guanzhong Liu¹, Karen Xie², Yi Sui^1,3, Winnie Mar², Virgilia Macias⁴, John Groth⁴, Andre A. Kajdacsy-Balla⁴, Leslie Deane⁵, and Xiaohong Joe Zhou^1
1Center for MR Research, University of Illinois Hospital & Health Sciences System, Chicago, IL, United States, ²Radiology, University of Illinois Hospital & Health Sciences System, Chicago, IL, United States, ³Bioengineering, University of Illinois at Chicago, Chicago, IL, United States, ⁴Pathology, University of Illinois Hospital & Health Sciences System, Chicago, IL, United States, ⁵Urology, University of Illinois Hospital & Health Sciences System, Chicago, IL, United States

We investigated the utility of diffusion MR imaging in prostate, using a fractional order calculus (FROC) model, to differentiate normal peripheral zone, areas of chronic prostatitis, benign prostatic hypertrophy (BPH), and prostate cancer. Twenty-five patients were included in the study. Guided by conventional MRI and histopathologic findings, diffusion MR imaging data were analyzed using the FROC model, generating a new diffusion parameter β, based on tissue heterogeneity and complex microenvironment. A significant difference in β values in different tissue types were observed, demonstrating the feasibility of an imaging biomarker for characterizing and differentiating normal, benign and malignant processes in prostate.

Hui Zhang¹, Huijun Chen¹, Wenchuan Wu¹, Xiaoying Wang², Feiyu Li², Chun Yuan^1,3, and Hua Guo^1
1Center for Biomedical Imaging Research & Department of Biomedical Engineering, Tsinghua University, Beijing, China, ²Departement of Medical Imaging, Peking University First Hospital, Beijing, China, ³Department of Radiology, University of Washington, Seattle, WA, United States

Single-shot EPI diffusion weighted imaging, as a traditional method for assessment of disease aggressiveness in clinical application, is burdened by severe distortion as well as low resolution and SNR. In this study, we introduced the interleaved variable density spiral diffusion weighted imaging (VDS-DWI) into the prostate application first time and compares with traditional clinical EPI DWI with different b values and higher resolution. We found that it can provide images with well-reserved structure details and higher SNR and resolution and considerable scan time even in high b value. Our findings indicate that VDS-DWI might be a desirable technique to improve the anatomy structures retention and resolution with considerable SNR and time in clinical prostate and urinary bladder wall detection.

Guro F. Giskeødegård^1,2, Helena Bertilsson^3,4, Kirsten M. Selnæs^1,2, Alan Wright⁵, Tone Frost Bathen^1,2, Trond Viset⁶, Jostein Halgunset^3,6, Anders Angelsen⁴, Ingrid Susann Gribbestad^1,2, and May-Britt Tessem^1,2
1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway, ²St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, ³Department of Laboratory Medicine and Children's and Women's Helath, Norwegian University of Science and Technology, Trondheim, Norway,⁴Department of Urology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, ⁵Department of Radiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands, ⁶Department of Pathology and Medical Genetics, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

Metabolite profiles of human prostate and normal adjacent tissue obtained with high resolution magic angle spinning (HR-MAS) MRS can be used to identify metabolic biomarkers for prostate cancer aggressiveness. Multivariate analysis of metabolite profiles and absolute quantification of individual metabolites were used to examine the metabolic changes and predict cancer aggressiveness. The detailed metabolite profiles distinguished cancer and normal adjacent tissues and the profiles were related to prostate cancer aggressiveness. Spermine and citrate are proposed as biomarkers for separating indolent from aggressive prostate cancers.

Emily Decelle¹, Yannick Berker¹, Tilman Schwessinger^1,2, Shulin Wu¹, W. Scott McDougal¹, Chin-Lee Wu¹, and Leo L. Cheng^1
1Massachusetts General Hospital, Boston, Massachusetts, United States, ²Charité Universitätsmedizin, Berlin, Germany

Prostate cancer is the most frequently diagnosed malignancy in men worldwide. Radiological imaging is currently unable to detect suspicious areas for targeted biopsy, so randomly conducted biopsies often result in false negatives for early-stage PCa patients. Results from our previous studies of intact tissue samples from PCa patients suggested the existence of metabolic or metabolomic fields, i.e. PCa metabolic information are observed to delocalize from PCa glands and into the surrounding structures that are benign tissue according to histology. In the current study, we test the metabolomic field hypothesis by evaluating prostate biopsy cores for patients suspicious of harboring PCa.

Emily Decelle¹, Johannes Kurth^1,2, W. Scott McDougal¹, Chin-Lee Wu¹, and Leo L. Cheng^1
1Massachusetts General Hospital, Boston, Massachusetts, United States, ²Charité Universitätsmedizin, Berlin, Germany

Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide. Our study of human PCa metabolomics using intact tissue high resolution magic angle spinning MRS showed the potential to improve sensitivity in PCa detection and characterization, including identifying cancer recurrence status. In these studies, we discovered that PCa metabolomic information could delocalize from cancer glands to surrounding histologically benign structures to generate PCa metabolomic fields. The current study is designed to evaluate the ability of metabolomics to reveal PCa clinical and pathological status through the presence of metabolomic fields.

Kirsten M. Selnæs^1,2, Ingrid Susann Gribbestad^1,2, Helena Bertilsson^3,4, Alan Wright⁵, Anders Angelsen⁴, Arend Heerschap^1,5, and May-Britt Tessem^1,2
1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway, ²St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, ³Department of Laboratory Medicine and Children's and Women's Helath, Norwegian University of Science and Technology, Trondheim, Norway,⁴Department of Urology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, ⁵Department of Radiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands

MR metabolic profiling of the prostate is promising as an additional diagnostic approach to separate indolent from aggressive prostate cancer. MR metabolite ratios (choline+creatine+spermine/citreate) obtained non-invasively from patients in vivo by magnetic resonance spectroscopic imaging (MRSI) and from tissue samples ex vivo by high resolution magic angle spinning (HR-MAS) MR spectroscopy (MRS) correlate to Gleason score (=0.77 and =0.69, respectively, p<0.001). There is also a strong positive correlation between metabolite ratios from in vivo and ex vivo MR spectra of matched regions.

Mariska P. Luttje¹, Michel Italiaander¹, Catalina S. Arteaga de Castro¹, Wybe J.M. van der Kemp¹, Marco van Vulpen¹, Peter R. Luijten¹, Uulke A. van der Heide², and Dennis W.J. Klomp^1
1Imaging Division, Univerity Medical Center, Utrecht, Netherlands, ²Department of Radiotherapy, the Netherlands Cancer Instituut - Antoni van Leeuwenhoek hospital, Amsterdam, Netherlands

In this study at 7T, we implemented a double tuned ERC as a quadrature ¹H transceiver and ³¹P transceiver. As the T1 values of the detectable phospholipids are similar, a progressive saturated pulse acquire sequence (i.e. short TR and optimized flip angle) was used to ensure a uniform and broadband detection of the phospholipid metabolites. Validated by phantom experiments, the detection of both ¹H and ³¹P MR spectra in a patient with prostate cancer using the ¹H/³¹P ERC has been demonstrated

Eline K. Vos¹, Marnix C. Maas¹, Miriam W. Lagemaat¹, Stephan Orzada², Andreas K. Bitz², and Tom W.J. Scheenen^1,2
1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands, ²Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen, Germany

T2-weighted imaging was performed in thirteen prostate cancer patients at both 3T and 7T. Image quality, image contrast and the visibility of cancer lesions at 7T were directly compared with clinical 3T images. In general, prostate cancer lesions are detectable on T2-weighted images at 7T, despite differences in image contrast and thus appearance of anatomical details compared to 3T images. Therefore, imaging at 7T has future potential for the detection of prostate cancer.

Catalina S. Arteaga de Castro¹, Ozlem Ipek¹, Alexander Raaijmakers¹, Mariska P. Luttje¹, Marco van Vulpen¹, Peter R. Luijten¹, Uulke A. van der Heide², and Dennis W. J. Klomp^1
1Imaging Division, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, ²Radiotherapy, The Netherlands Cancer Institute, Amsterdam, Amsterdam, Netherlands

The already low coupling between an external coil array and an endorectal coil, makes it possible to obtain uniform MRI of the human prostate when transmitting only with the external array and receiving with all elements, while for prostate MR spectroscopy, all coil elements can be used as transceivers using active decoupling. Therefore, uniform extended field of view MRI and high B1, low TE MRSI can be acquired from the prostate location at 7T.

Tryggve Holck Storås¹, Andre Bongers², Carl Power², and Roger Bourne^3
1Interventional Centre, Oslo University Hospital, Oslo, Norway, ²Biomedical Resource Imaging Laboratory, University of New South Wales, Sidney, Australia, ³Discipline of Medical Radiation Sciences,Faculty of Health Sciences, University of Sydney, Sidney, Australia

Prostate tissue show bi-exponential decay in both T2 and diffusion in vivo. In this pilot study we investigated whether T2 and T1 decay characteristics are changed after prostatectomy and formalin fixation. Prostatectomy specimen were imaged at 9.4T immediately after resection and then again after formalin fixation. T2 and T1 decay curves were acquired using multi echo and variable TR techniques. Mono- and biexponential models were fitted and compared. We found that signal fractions of fresh tissue are comparable to in vivo results, while fixed tissue show altered signal fractions.

Amy Johnson¹, Arash Latifoltojar¹, Valentin Hamy¹, Heather Fitzke¹, Shonit Punwani¹, and Karin Shmueli^2
1Centre for Medical Imaging, University College London, London, United Kingdom, ²Medical Physics and Bioengineering, University College London, London, United Kingdom

R2* has been proposed to measure hypoxia in prostate cancer but the relative contribution of R2 and R2’ to the increased tumour R2* is unknown, although we expect R2’ to dominate via static dephasing in hypoxia-induced field inhomogeneities. We measured R2*, R2 and R2’ at 1.5T in tumour and healthy tissue ROIs in 50 patients. R2* and R2 were significantly increased in tumours. However, there was no significant difference in R2’. Field inhomogeneities probably affected R2 more than R2’ due to irreversible diffusive dephasing in the longer SE echo-times used here. Future studies are needed to separate R2 and R2’.

Rami R. Hallac¹, Bishoy A. Gayed², Qing Yuan¹, Ramy F. Youssef², Yao Ding¹, Franto Francis³, Claus Roehrborn², Ganesh Raj², Robert D. Sims¹, and Ralph Peter Mason^1
1Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Urology, University of Texas Southwestern Medical Center, Dallas, TX, United States,³Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States

Oxygen sensitive MRI may provide insights into tumor characteristics. We evaluated the changes in MR contrast and R2* of human prostate cancer in patients accompanying oxygen breathing challenge at 3T MR and correlated observations with resected pathological specimens. BOLD MRI revealed vastly different R2* values between patient tumors, but remarkable similarity to the prostate itself. A strong correlation was found between baseline R2* and Gleason score. We believe these preliminary results warrant further testing as to how R2* and its response to oxygen–breathing challenge correlate with location, pathology, and potentially staging of tumors.

Asha Singanamalli¹, Rachel Sparks¹, Mirabela Rusu¹, Natalie Shih², Amy Ziober², John Tomaszewski³, Mark Rosen⁴, Michael Feldman², and Anant Madabhushi^1
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Department of Pathology, University of Pennsylvania, Philadelphia, PA, United States, ³Department of Pathology & Anatomical Sciences, University of Buffalo, University of Buffalo, Buffalo, United States, ⁴Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

Prostate cancer is the second leading cause of cancer mortality in men. Measures such as gleason scores and microvascular density (MVD) are well established indicators of CaP outcome. However, invasive procedures are necessary to obtain these measures. In this study, we seek to identify DCE MRI perfusion parameters that correlate with MVD using sophisticated image analysis and registration methods in order to establish non-invasive methods of assessing tumor outcome.

Huarui Du¹, Wenchao Cai², Jue Zhang^1,3, Xiaoying Wang², and Jing Fang^1,3
1College of Engineering, Peking University, Beijing, China, ²Peking University First Hospital, Beijing, China, ³Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, Beijing, China

The aims of this study are to (a) obtain more robust Ktrans and ve map by proposing reference local voxel cluster (RLVC) model as an alternative strategy, which can overcome over-strong assumptions in Tofts model and avoid arterial input function (AIF) or reference tissue (b)prove whether kinetic parameters extracted by RLVC are valid for the detection of bone metastases in patients with prostate carcinoma. Results demonstrate that kinetic parameters are effective on the detection of BM from prostate cancer and extracted Ktrans map could be a potential tool for detection of early bone metastasis.

John M. Pavlina¹, Jens Groebner², Tetiana Dadakova¹, Erik Dumont³, and Michael Bock^1
1Madeizin Physik, Universität Klinikum Freiburg, Freiburg, BW, Germany, ²Madeizin Physik, University Medical Centre Freiburg, Freiburg, BW, Germany, ³Image Guided Therapy, Pessac, France

This work describes the design and simulation of an endorectal oil for MR-guided HIFU therapy of the prostate. MR-guided high intensity focused ultrasound (HIFU) is increasingly being investigated as a treatment option for prostate cancer. Due to space restrictions in the rectum, current prostate HIFU systems use external coils only. In this work an endorectal HIFU transducer is combined with an endorectal receive coil in a simulation study to assess the coil performance.

Eleftheria Panagiotaki¹, Daniel C. Alexander², and Roger Bourne^3
1Centre for Medical Image Computing, University College London, London, United Kingdom, ²Centre for Medical Image Computing, Dept Computer Science, University College London, London, United Kingdom, ³Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, Sydney, Australia

This study used high-field high-gradient diffusion-weighted (DW) MRI of fixed prostate tissue to explore the key components of an accurate biophysical model for obtaining future biomarkers of cancer and other pathology. We acquired DW-MRI with a rich imaging protocol and selected for modelling two tissue types (from the central and peripheral zone ) to compare four diffusion models.

Fiona M. Fennessy^1,2, Andriy Fedorov¹, Tobias Penzkofer^1,3, and Clare Tempany^1
1Radiology, Brigham and Women's Hospital, Boston, MA, United States, ²Radiology, Dana Farber Cancer Institute, Boston, MA, United States, ³Radiology, RWTH Aachen University Hospital, Aachen, Germany

Spatial correlation and evaluation of the diagnostic accuracy of the mpMR sequences in prostate imaging is not trivial and not always feasible in patients undergoing a routine clinical evaluation mpMR prostate protocol and routine histology processing. This exhibit outlines the challenges in detailed correlation of pathology findings with individual mpMR sequences in prostate cancer staging. It underscores the need for a large clinical cohort, and makes audience aware of the limitations of mpMR correlation with routine histology/biopsy reports when prospective dedicated whole mount pathology is not available. This exhibit also underscores the need for further development and validation of imaging registration technology to facilitate development of mpMR as a biomarker for prostate cancer.

Arash Latifoltojar¹, Rowland Illing¹, Alex Kirkham¹, and Shonit Punwani^1
1Centre for Medical Imaging, UCL, London, London, United Kingdom

Post biopsy prostate haemorrhage significantly alter the T1 and T2 MRI signal which makes it challenging to interpret these images. Moreover the temporal changes of T1 and T2 MRI signal characteristics is unclear. Prostatic post-biopsy ADC maps quantitative signal changes has not been widely investigated.In this prospective study, the longitudinal signal changes of prostate multi-parametric MRI is analysed.

Robert Toth^1,2, John Kurhanewicz³, and Anant Madabhushi^2
1Biomedical Engineering, Rutgers University, Piscataway, NJ, United States, ²Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States,³Radiology, UCSF, San Francisco, CA, United States

In this work we utilize a finite element model with forces on the surface of the prostate to register pre-, post- IMRT MR images for determining pixel-by-pixel changes to the MRI markers, and to quantify the specific local deformations which have occurred as a result of radiation treatment. Results on 7 IMRT MR images demonstrate a RMS error of 2.73 mm with manually selected fiducials and a center of mass distance of 1.84 mm.