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2011 grant-and-award-booklet web

  1. 1. Bright Ideas Get FundedRSNA Research & Education FoundationImproving patient care by supporting research andeducation in radiology and related scientific disciplinesthrough funding grants and awards to individuals andinstitutions that will advance radiologic research,education and practice.2011rsna grants and awards
  2. 2. grants and awards Research Grant Programs Research Scholar Grant 4–9 To support junior faculty members who have completed the conventional resident/fellowship training program(s); but have not yet been recognized as independent investigators. The purpose of the funding is to help establish the recipient as an independent investigator, and to collect preliminary data that could lead to further funding through established mechanisms such as the NIH. Recipients will devote a minimum of 40% of their time in the approved research project. $75,000 annually for 2 years ($150,000 total) to be used as salary support for the scholar. Research Seed Grant 10–14 To enable all levels of investigators throughout the world in defining objectives and testing hypotheses in prepa- ration of major grant applications to corporations, foundations, and governmental agencies. The seed data from these projects will indicate feasibility and appropriateness of the research prior to applying for funds from other agencies. Up to $40,000 United States Dollars (USD) for a 1-year project. Open to international applicants. Research Resident/Fellow Grant 15–23 To provide young investigators an opportunity to gain further insight into scientific investigation and to gain competence in research techniques and methods in anticipation of establishing a career in academic radiologic science. Recipients will devote a minimum of 50% of their time in the approved research project under the guidance of a scientific advisor/mentor. $50,000 for a 1-year fellow project or $30,000 for a 1-year resident project to be used for salary and/or other research expenses. Research Medical Student Grant 24–35 To increase the opportunities for medical students to have a research experience in medical imaging and to encourage them to consider academic radiology as an important option for their future. Recipients will gain experience in defining objectives, developing research skills and testing hypotheses before making their final choices for residency training programs. Students are expected to undertake a research project requiring full- time efforts for at least 10 weeks under the guidance of a scientific advisor during personal/vacation time or during a research elective approved by their medical school. $3,000 to be matched by the sponsoring department ($6,000 total) as a stipend for the student. Education Grant Programs Education Scholar Grant 36–39 To provide funding opportunities for individuals with an active interest in radiologic education. Any area of education related to the radiologic sciences is eligible for Education Scholar Grant support. One year grant of up to $75,000 USD for salary support and/or other project costs. In exceptional cases, grants of up to two years will be considered. RSNA/AUR/APDR/SCARD Education Research Development Grant 40–41 To encourage innovation and improvement in health sciences education by providing research opportunities to individuals throughout the world who are in pursuit of advancing the science of radiology education. Up to $10,000 USD for a 1-year project to help cover the costs of research materials, research assistant support, and limited principal investigator salary support. Recognition Awards Roentgen Resident/Fellow Research Award 42–44 To recognize and encourage outstanding residents and fellows in radiologic research during the past year. Each par- ticipating North American residency program will receive an award plaque with space to display brass nameplates for each year’s recipient. The Foundation will also provide a personalized award for the department to present to the selected resident or fellow.RSNA.org/Foundation 1
  3. 3. your foundation—your future2011 was another outstanding year for the RSNA Research & Education Foundation. Through the generous support of ourindividual donors, private practice and academic groups and our corporate partners, the Foundation was able to fund 72grants totaling $2.6 million—the highest amount to date.The cornerstone of the R&E Foundation’s mission is to advance medical imaging research, education and practice. Since itsinception, the Foundation has funded nearly 900 grants totaling well over $34 million. On average, every dollar awarded bythe Foundation results in over $30 of additional funds from sources such as the NIH. With this high return on investment,the R&E Foundation has enabled over $1 billion in radiologic research.Each and every day at institutions throughout North America and abroad, young investigators supported by the R&EFoundation are performing vital research aimed to improve clinical care and patient outcomes, and ensure the futureof the specialty.Today, the R&E Foundation’s 2011 grant recipients are conducting research in several exciting areas. A Research Scholargrantee leads a comparative effectiveness trial on evaluation of pediatric small bowel Crohn disease using MR enterographyand ultrasound elastography—the first of its kind in humans—which may mark an important paradigm shift in the radiologicassessment of Crohn disease. A Research Seed Grant recipient will study the use of DTP FDG-PET/CT in conjunction withadvanced image analysis to quantify in vivo tumor biology, predict clinical outcome, and improve disease staging in patientswith lung cancer. This research may provide a new, practical, informative and readily available diagnostic approach forthese patients. A recipient of a Research Resident Grant will conduct a pilot study on patient-specific dosimetry in pediatricand adult CT—which could guide a larger scale study to create a dose reporting system tailored to individual patients.These diligent individuals are hard at work, and a strong partner is critical to their success. The R&E Foundation is proudto be that partner. To support these investigators, the Foundation offers many vehicles for giving, including individual programs, practice and academic group programs, planned giving opportunities and corporate and exhibitor partnerships. I encourage you to take time to read through the abstracts in this booklet to learn more about our outstanding grant recipients and their innovative projects. Theresa C. McLoud, MD Chair, Board of Trustees RSNA R&E Foundation Not available for group photo: Gregory C. Karnaze, MD; Thomas N. McCauslandRSNA Research & Education FoundationBoard of TrusteesBack row, from left: G. Scott Gazelle, MD, PhD; Hedvig Hricak, MD, PhD, Dr (hc), Treasurer; Burton P. Drayer, MD, RSNA President;James P. Borgstede, MD; E. Russell Ritenour, PhD, Secretary; Valerie P. Jackson, MDFront row, from left: Sarah S. Donaldson, MD; Theresa C. McLoud, MD, Chair; Richard L. Ehman, MD; Vijay M. Rao, MD 2 r&efoundation@rsna.org
  4. 4. recognition and thanksIt is through the generosity of individuals, private practices and industry partners that theR&E Foundation is able to continue its investment in R&D for radiology. In 2011, grantawards were specially named to recognize the following individuals and companies for theircontributions to the R&E Foundation, and the future of the specialty. Derek Harwood-Nash, MD n Peggy J. Fritzsche, MD RSNA Presidents Circle n Silver Anniversary Campaign PacesettersHealthCare MEDICAL Dear Presidents Circle Donors, I wish to express my sincere appreciation for your generous dona- tions, which have made it possible for me to conduct this important research. My grant aims to provide accurate, patient-specific, dose and risk estimates for the entire spectrum of pediatric and adult CT exams. The outcome of this research will serve important functions in promoting justified use of CT radiation, in establishing diagnostic reference levels, and in optimizing CT protocols to minimize dose. Many thanks to you all for enabling me to pursue my goals. With my best regards, Xiang Li, PhD BRIGHT IDEAS. BETTER PATIENT CARE.RSNA.org/Foundation 3
  5. 5. research grant programsresearch scholar grant Hersh Chandarana, MD Radiology New York University School of Medicine Siemens Healthcare/RSNA Research Scholar Grant Evaluation and Prediction of Treatment Response in Liver Metastasis Undergoing Chemotherapy with Use of Dual Energy CT Iodine Quantification TechniqueColon cancer is the third most common cause of cancer-related enhanced dual-energy CT (DECT). We hypothesize that intralesionalmortality in the United States. Liver metastases are the main cause iodine concentration may prove to be a more sensitive and earlierof death in these patients. Currently, treatment response is solely indicator of treatment response than traditional RECIST criteria.assessed on the basis of size changes in the target lesions. Change If validated in this study, iodine concentration depicted on DECTin size may, however, be a late manifestation in patients undergo- imaging can be used to predict and monitor treatment responseing targeted chemotherapy. Furthermore, different combinations to antiangiogenic chemotherapy in patients with liver metastasesof chemotherapeutic agents are available, and selection of the right from colon cancer. The potential benefits of this technique would al-combination chemotherapy is imperative to maximize efficacy and low appropriate patient selection and earlier determination of drugminimize toxicity. response, which could help develop personalized chemotherapyThere is tremendous interest in identifying response-predicting regimens and lead to improved patient outcome. Furthermore, thisfactors that can help tailor chemotherapy. The overall aim of this could become a method for the rapid assessment of the efficacy ofproject is to validate the use of quantitative measurement of treat- new antiangiogenic pharmaceutical agents or combination regi-ment response in patients undergoing antiangiogenic chemotherapy mens, allowing for more rapid drug development.for liver metastases from colon cancer, based on tumor vascularityas measured by intralesional iodine concentration on contrast- Jonathan R. Dillman, MD Radiology HealthCare University of Michigan AGFA HealthCare/RSNA Research Scholar Grant Comparative Effectiveness of MR Enterography, Enteric Ultrasound, and Ultrasound Elastography Imaging in the Evaluation of Pediatric Small Bowel Crohn DiseaseThere is presently a paucity of data comparing magnetic resonance We propose to prospectively compare the diagnostic performanceenterography (MRE) and enteric ultrasound (EnUS) in the assess- of EnUS to MRE for the initial diagnosis and follow-up of pediat-ment of pediatric small bowel Crohn disease. Prior studies evalu- ric small bowel Crohn disease. All subjects will undergo baselineating EnUS have used suboptimal reference standards, including (immediately prior to starting medical management) and serialileocolonoscopy and barium studies. If EnUS can be shown to have follow-up physician-performed systematic EnUS (including grey-significant positive agreement and comparable receiver-operating scale and Doppler imaging) and MRE examinations. EnUS and MREcharacteristics (ROC) to MRE, this imaging technique could become findings will be documented and assessed for agreement at baselinestandard-of-care due to lower cost, shorter examination time, and and follow-up as well as correlated with a variety of laboratorylack of need for sedation, contrast materials, and anti-peristaltic inflammatory markers and Pediatric Crohn Disease Activity Indexmedication. (PCDAI) scores. Changes in UEI bowel wall stiffness over time will be correlated with other imaging findings as well as clinical data toRecently published research using an animal model has demon- determine if this imaging technique can serve as a radiologic bio-strated that ultrasound elastography imaging (UEI) has several marker for response to medical therapy and the presence of bowelpotential promising clinical applications in humans, including serv- wall fibrosis. Finally, we will formally survey the children anding as an imaging biomarker for both response (and perhaps early parents in our study concerning their imaging preferences as wellresponse) to medical therapy and the presence of bowel wall fibrosis as compare resource consumption by these imaging tests.in small bowel Crohn disease. It is possible that UEI could influencethe decision to surgically manage certain children. 4 r&efoundation@rsna.org
  6. 6. research scholar grant Qian Dong, MD Radiology University of Michigan Hospitals and Health Centers Bracco Diagnostics/RSNA Research Scholar Grant Quantitative Imaging in Soft Tissue Sarcomas: Use of MRI Diffusion and MRI Perfusion Biomarkers to Predict Early Response to Neoadjuvant ChemotherapyNearly 15,000 new cases of sarcoma are diagnosed annually in the will establish imaging biomarkers as early predictors of treatmentU.S. with a loss of years of life that greatly outweighs the incidence efficacy in patients with soft tissue sarcomas.of these cancers. Although advances in multiagent chemotherapy Our long term goal is to use molecular imaging to assess responseand surgery have improved prognosis, sarcomas still are fatal in up to neoadjuvant chemotherapy within days or even hours of initiat-to 50% of patients. A major obstacle to improving patient outcomes ing chemotherapy, replacing ineffective current methods based onis the inability to reliably determine success or failure of pre-oper- late changes in tumor volume. By determining treatment efficacyative (neoadjuvant) chemotherapy early in the course of treatment, early in the course of therapy, we expect this research will ultimate-prior to surgery and histologic analysis of tumor specimens. As a ly allow oncologists to optimize treatment protocols for individualresult, patients may continue on ineffective chemotherapy regi- patients, improving quality of life and enhancing disease-freemens, experiencing adverse effects of treatment and missing the survival for patients with soft tissue sarcoma.critical opportunity to switch to an alternative protocol. In summary, this research will develop molecular imaging techniquesOur central hypothesis is that quantitative molecular and func- to determine success or failure of pre-operative chemotherapytional imaging techniques can meet the need for early determination in soft tissue sarcomas. These imaging techniques ultimately willof response to therapy in soft tissue sarcomas. We will use diffusion allow treatment protocols to be optimized for individual patients,and dynamic contrast-enhanced MR imaging (DCE-MRI) to measure improving survival and quality of life for patients with soft tissuechanges in cellular architecture and angiogenesis in patients sarcomas.undergoing neoadjuvant chemotherapy for sarcomas. These studies Jason Druzgal, MD, PhD Radiology University of Virginia RSNA Research Scholar Grant Machine Learning Classification of Resting State Functional MRI Data in Autism Spectrum DisordersResting state functional MRI (rs-fMRI) measures spontaneous fluc- currently limited. A more clinically relevant issue is whether thetuations in blood oxygen level dependent (BOLD) signal, thought to features in a single rs-fMRI data set can be used to determine thereflect fluctuation in underlying neuronal activity. Whole-brain rs- population from which the data originated. That is, can you makefMRI of individuals of normal cognitive function has characterized the diagnosis of autism based on features in the rs-fMRI data? Re-many long-range and short-range neural networks that demonstrate cent application of machine learning classification to fMRI data setsreproducible temporal synchrony of resting state BOLD signal. suggests this to be a realistic possibility.Applications of this rs-fMRI technique to several types of cognitive The current project proposes to develop a classifier that discrimi-pathology (including autism, schizophrenia, bipolar disorder, and nates autistic patients from typically developing controls on thedepression) have demonstrated consistent perturbations of this basis of their rs-fMRI data. A support vector machine classifier willtemporal synchrony related to the underlying pathology. be developed from an existing large rs-fMRI data set obtained fromRegarding the autism spectrum, my research group has discovered a well-characterized population of autistic patients and typically de-several features of rs-fMRI temporal synchrony that are perturbed veloping control patients. The classifier will be internally assessedat the population level, including long-range interhemispheric for metrics of clinical validity, such as sensitivity, specificity, andconnectivity and short-range regional homogeneity. These findings accuracy. Then the classifier will be externally validated with rs-certainly advance our understanding of the pathology underlying fMRI data obtained from a separate population of autistic individu-the autism spectrum, but the clinical utility of this information is als, at a different institution.RSNA.org/Foundation 5
  7. 7. research scholar grant Michael S. Gee, MD, PhD Radiology Massachusetts General Hospital Carestream Health/RSNA Research Scholar Grant Evaluation of Diagnostic Magnetic Resonance (DMR) Technology for Molecular Characterization of Cancer Cells from Percutaneous Image-Guided Biopsy SpecimensThe capability to perform real-time molecular analysis of human that act as proximity sensors for specific molecular targets. Wetumors is expected to enable rational treatment decisions in an era have used this exquisitely sensitive technology to measure DNAwhere molecularly targeted therapies are emerging. Attempts to and mRNA, cancer cells, proteins, enzymes, metabolites, drugprofile cancer cells to date largely have been unsuccessful, as exist- concentrations, and bacteria. In preliminary experiments, we haveing clinical technologies are either too insensitive to distinguish demonstrated the ability of DMR to profile expression of multiplebiomarker expression levels or lead to alterations in tumor cell phe- biomarkers on individual cancer cells simultaneously, with molecu-notype, precluding accurate assessment. We have developed a novel, lar sensitivity reaching 10–14 M, better than conventional techniquesbroadly applicable, point-of-care method of diagnostic magnetic such as flow cytometry. The overall goal of this proposal is toresonance (DMR) that overcomes many of these limitations. evaluate whether DMR can perform real-time molecular analysis of biomarkers on human cancer cells isolated from percutaneousThe technology utilizes magnetic resonance techniques confined image-guided fine needle aspiration, and to determine whetherwithin a chip-sized micro-NMR device to measure the relaxation DMR can be used to determine tumor susceptibility to molecularly-time of tumor cell fine needle aspiration samples. The molecular targeted treatments.specificity of DMR is achieved through magnetic nanoparticles Daniel Hamstra, MD, PhD Radiation Oncology The University of Michigan Medical Center RSNA Research Scholar Grant Molecular Dissection of the Role of Tumor Vasculature in Radiation SensitivityRadiation therapy plays a prominent role in the treatment of pa- factors and resistance to radiation therapy, it is unclear if thesetients with prostate cancer. While prostate cancer exhibits signifi- vascular differences reflect the underlying biology of the tumor ascant genetic heterogeneity, inactivation of the PTEN tumor suppres- opposed to a mechanistic resistance to radiation therapy. Therefore,sor gene is one of the more common events, occurring in as many as we first propose to evaluate the role of endothelial cell responses to15 - 20% of all prostate cancers, and it is more common in high-grade radiation therapy using molecular modification of endothelial celltumors. PTEN loss has been associated with higher Gleason grade, radiation response and non-invasive imaging of endothelial cellincreased tumor neo-angiogenesis, increased biochemical failure, growth and response to therapy through bioluminescent imaging.and radiation resistance. Further, tumor hypoxia and neo-vascular Second, given the potential role of the PI3K/Akt/mTOR axis in bothgrowth, which are both common in prostate cancer, are both as- tumor and endothelial cell pathophysiology we propose to evaluatesociated with radiation resistance and prostate cancer recurrence. this signaling axis as a target for radiation sensitization of bothNeo-angiogenic blood vessel growth and proliferation are also prostate cancer and endothelial cells. Using models by which bothinfluenced by the PI3K/Akt/mTOR axis, and as a result the mam- tumor and endothelial cells can be individually modulated, we willmalian target of rapamycin (mTOR) may be a critical player in both assess the impact mTOR inhibition upon both cell-types individu-prostate tumor and prostate cancer stromal pathophysiology. ally and in combination.Despite the clear clinical associations between tumor vascular 6 r&efoundation@rsna.org
  8. 8. research scholar grant Moritz Kircher, MD, PhD Radiology Memorial Sloan-Kettering Cancer Center Bayer HealthCare Pharmaceuticals/RSNA Research Scholar Grant A Dual-Modality MRI-SERS Nanoparticle for Molecular Imaging of Brain TumorsMalignant gliomas, such as glioblastoma multiforme, remain a The MRI-R particle chemistry will first be optimized by interro-therapeutic challenge worldwide. Surgical resection is usually the gating the effect of varying concentrations of Gd and maleimide-initial primary treatment. However, visualization of the tumor DOTA during the incubation procedure, as assessed by inductivelymargins during surgery is imprecise. Current imaging methods are coupled plasma atomic emission spectroscopy. MR detectability willoften limited by inadequate sensitivity, specificity, and/or spatial be assessed in phantom experiments. Further characterization ofresolution. We have developed a new brain tumor imaging strategy MRI-R behavior will include determination of differential uptakebased on a dual-modality MRI-Raman nanoparticle probe (MRI-R) in brain tumor cells in culture, whole body biodistribution studies,that allows combined preoperative MRI and intraoperative Raman and detailed toxicity studies. Accuracy of MRI-R to delineate tumorimaging with a single nanoparticle injection. We have demonstrated margins will be assessed by careful correlation of in vivo MRI andthe unique properties of MRI-R in our preliminary studies: a) MRI-R Raman images with histology.is detectable by MRI and by Raman in the picomolar range in vivo. The conceptual advance presented here could lead to a signifi-b) MRI-R nanoparticles are sequestered by the tumor (> 1 week), al- cant advance in both brain tumor imaging and tumor resection.lowing c) pre-operative and intra-operative imaging to be performed Since gold-silica based nanoparticles are already in clinical trialswith a single intravenous nanoparticle injection; d) Raman imaging and hand-held Raman imaging devices have been developed, thisenables accurate delineation of tumor margins intraoperatively. approach holds significant promise for clinical translation and ap-We propose to 1) optimize nanoparticle chemistry, 2) validate plication by neurosurgeons.nanoparticle imaging in biological systems, and 3) determine the ac-curacy of pre- and intraoperative brain tumor delineation in animalmodels. Chan Hong Moon, PhD Radiology HealthCare University of Pittsburgh AGFA HealthCare/RSNA Research Scholar Grant Sodium/Proton MR Imaging of Knee Cartilage in OsteoarthritisKnee osteoarthritis (OA) is a complex, heterogeneous condition orous testing of sodium quantification must be undertaken. Recentthat is a common cause of disability in the aging population. One technical advances in high-field MRI allow us to acquire morphologicof the hallmarks of the pathophysiology of OA is the breakdown and physiologic imaging of knee cartilage with improved SNR andof cartilage in joints. Conventional radiographs are an insensitive spatial resolution, thus facilitating accurate characterization andmeasure of OA pathology and have not allowed for the evaluation of quantification of structural and physiochemical changes of carti-treatment effects on early structural and physiological changes in lage associated with OA.cartilage. However, recent advances in high-resolution MR imaging The primary objective of this proposal is to develop and evaluateof OA cartilage anatomy and physiology have improved our under- methods for the quantification and characterization of structuralstanding of the patho-physiochemical changes in articular cartilage. and sodium concentration changes in OA knee cartilage using high-In particular, sodium MRI is a promising technique for the detection field proton/sodium MRI. Our central hypothesis is that new dual-of changes in proteoglycan content of cartilage associated with tuned MR imaging permits a precise in-vivo structural and physio-early stage OA. Unfortunately, clinically useful sodium MRI can chemical analysis of knee cartilage associated with OA. The specificbe technically challenging due to the intrinsically low MR signal and aims are to (1) develop and evaluate methods for sodium MRI ofconcentration. In order to realize the clinical potential of sodium knee cartilage at 3T and 7T MR, and (2) evaluate and compare theMRI as a reliable imaging biomarker for the characterization of differences in the sodium concentration and volume and thicknesscartilage quality, the optimization of sodium MRI techniques and rig- of knee cartilage between OA patients and normal controls.RSNA.org/Foundation 7
  9. 9. research scholar grant Mark S. Shiroishi, MD Radiology, Division of Neuroradiology Keck School of Medicine, University of Southern California GE Healthcare/RSNA Research Scholar Grant Assessing the Value of Perfusion and Permeability MR Imaging to Characterize Pseudoprogression and Pseudoresponse in Patients with High-Grade GliomaThe traditional method of determining response to therapy for anti-angiogenic drugs such as bevacizumab demonstrate a rapidglioblastoma is based on the MacDonald criteria. This relies on decrease in contrast enhancement and edema without a true anti-changes in enhancement characteristics and has been shown to be tumor effect. This is likely a result of “repairing” of the blood braininadequate in distinguishing between true progression of disease barrier.and treatment related effects. This uncertainty complicates treat- In order to better distinguish between true disease progression andment decisions as well as clinical trial design. A phenomenon has pseudoprogression, as well as between true response and pseudo-recently been recognized in which chemoradiation treatment may response, we will conduct a prospective investigation of patientscause an increase in the size of enhancing lesions. It is analogous with newly diagnosed and recurrent high-grade glioma with theto delayed radiation necrosis, but occurs much earlier—usually in goal of evaluating the added benefit of advanced MR techniques,the first 12 months of therapy. In these cases, there is no true tumor such as perfusion and permeability MRI as well as MR spectros-progression; hence, the entity is termed “pseudoprogression.” It copy and diffusion tensor imaging. Patients with true progressionoccurs in up to 20% of patients who have undergone chemoradiation of disease, as well as those with true response to therapy, will beand can explain about half of all cases of increasing lesions and included as controls. Overall survival estimated using the Kaplan-enhancement after this treatment. Meier method will be compared. Standard Student’s t test will be“Pseudoresponse” is also a newly described condition in which initially used to compare the perfusion and permeability measures,some patients with recurrent high-grade glioma treated with metabolite ratios, and diffusion metrics for all groups of patients. James A. Tanyi, PhD Radiation Medicine Knight Cancer Institute, Oregon Health & Science University RSNA Research Scholar Grant Incorporating the Effects of Transcytolemmal Water Exchange in Pharmacokinetic Analysis of DCE-MRI Data in the Prediction of Head and Neck Cancer Response to ChemoradiationPreclinical and clinical data suggest that changes in head and neck rect nature of contrast agent detection. To date such models havesquamous cell carcinoma (HNSCC) cell cycle kinetics following a assumed a linear relationship between the measured longitudinalbrief exposure to radiotherapy, either alone or with chemotherapy, (or spin-lattice) relaxation rate constant (1/T1) of water protonscan be used to evaluate treatment efficacy in terms of loco-regional and the concentration of contrast agent. However, this assumptioncontrol, disease-free survival and overall survival. Dynamic is not valid for all concentrations of any contrast agent of interestContrast-Enhanced Magnetic Resonance Imaging (DCE-MRI), the in tissue. The proposed study will investigate a novel pharmaco-acquisition of serial magnetic resonance images before, during and kinetic model (the “Shutter-speed” model) that takes into accountafter the administration of an intravenous small molecular weight transcytolemmal and transendothelial water exchange during thegadolinium-based contrast agent, can be used to measure these assessment of contrast enhancement dynamics.changes. For a tumor, the signal intensity measurements of DCE- We will test the hypothesis that DCE-MRI can be used to predictMRI may reflect a composite of tumor perfusion, vessel permeabil- treatment outcome in terms of local control and progression-freeity and the volume of the extravascular-extracellular space. Thus, survival in patients with loco-regionally advanced HNSCC. ThisDCE-MRI may provide a more robust characterization of tumor preliminary assessment will allow us to identify and appreciatephysiologic behavior rather than its anatomic appearance. potential study limitations, and derive corrective measures beforeModels have been developed for the analysis of DCE-MRI data that embarking on a large-scale trial.typically neglect the compartmental nature of tissue and the indi- 8 r&efoundation@rsna.org
  10. 10. research scholar grant Zhen Jane Wang, MD Radiology and Biomedical Imaging University of California, San Francisco Medical Center GE Healthcare/RSNA Research Scholar Grant Noninvasive Assessment of Renal Tumor Aggressiveness Using Hyperpolarized [1-13C] Magnetic Resonance Spectroscopic Imaging: a Pilot StudyThe incidence of renal cell carcinoma is rising by 3% per year, and metabolic profile of low versus high metastatic potential renal cellit is recognized that many of these are small (< 4cm), indolent, and carcinomas in a murine xenograft tumor model; and 2) the meta-may not require aggressive treatment. Therefore the management bolic profiles determined by hyperpolarized [1-13C] MRSI correlateoptions for these small tumors have expanded from surgical resec- with immunohistochemical and histopathological analysis of tumortion to include less invasive tumor ablation and active surveillance. aggressiveness. Successful completion of the project will add to ourHowever, triage of therapies is currently difficult due to our inabil- understanding of the biology of renal tumors.ity to reliably determine renal tumor aggressiveness noninvasively. We will use the data and experience gained from this project toThe long-term goal of our research is to determine whether hyper- apply for a NIH R01 grant for clinical trials in patients with renalpolarized [1-13C] magnetic resonance spectroscopic imaging (MRSI), tumors using hyperpolarized [1-13C] MRSI. Noninvasive imagingan extraordinary new technique that highlights the increased glycoly- characterization of tumor biological behavior using metabolic bio-sis in cancer, can noninvasively characterize renal tumor aggres- markers will advance the state-of-the-art in oncologic imaging andsiveness, and appropriately select those patients who will benefit greatly improve our ability to provide patient and tumor-specificfrom less invasive treatment or active surveillance. care.The specific aims of this pre-clinical study are to test the hy-potheses that 1) hyperpolarized [1-13C] MRSI can distinguish the David Woodrum, MD, PhD Radiology Mayo Clinic RSNA Research Scholar Grant Influence of Differential Cellular Heat Shock (Stress) Protein Expression on Cellular Death from Focal Laser AblationHepatocellular carcinoma (HCC) is the seventh most common can- Our central hypothesis to be tested in the present proposal is thatcer worldwide and third leading cause of cancer-related death. In HCC is resistant to thermal ablation because of increased cellularHCC, there is overexpression of several heat shock proteins (HSPs), expression of HSPs in cells contained in the ablative margin andwhose function is to inhibit cellular death, promote angiogenesis, that inhibition of these proteins will increase the thermosensitiv-and increase thermotolerance. The current gold standard for defini- ity of these neoplastic cells, leading to increased ablation efficacy.tive treatment of HCC is orthotopic liver transplantation; however, The knowledge gained by successful completion of this proposalmany patients do not meet the inclusion criteria for transplant. will allow us to rapidly translate these findings to clinical trials toNon-surgical patients are treated with catheter-based or percutane- investigate the efficacy of commercially available HSP inhibitorsous-based ablative techniques. Unfortunately, the “Achilles heel” of combined with ablative techniques to treat patients with HCC.these techniques is high recurrence rate after ablation. Recurrencesoccur at the edge of the tumor margin and ablative zone.RSNA.org/Foundation 9
  11. 11. research grant programsresearch seed grant Gholam R. Berenji, MD Nuclear Medicine VA Greater Los Angeles Healthcare System Philips Healthcare/RSNA Research Seed Grant DICOM Structured Report to Track Patient’s Radiation Dose to Organs from Abdominal CT ExamsThe dramatic increase of diagnostic imaging capabilities over the a patient’s organ dose. We have developed a method to determinepast decade has contributed to increased radiation exposure to pa- CTDIvol normalized organ doses using a set of organ specific expo-tient populations. Several factors have contributed to the increase nential regression equations. These exponential equations alongin imaging procedures: wider availability of imaging modalities, in- with measured CTDIvol are used to calculate organ dose estimatescrease in technical capabilities, rise in demand by patients and cli- from abdominal CT scans for eight different patient models. Fornicians, favorable reimbursement, and lack of guidelines to control each patient, organ dose and CTDIvol are estimated for an abdomi-utilization. The primary focus of this research is to provide in-depth nal CT scan. We will then develop a DICOM SR (Structured Report)information about radiation doses that patients receive as a result to store the pertinent patient information on radiation dose to theirof CT exams, with the initial investigation involving abdominal CT abdominal organs.exams. Current dose measurement methods (i.e. CTDIvol ComputedTomography Dose Index) do not provide direct information about Vikram S. Dogra, MD Radiology University of Rochester Toshiba America Medical Systems/RSNA Research Seed Grant Photoacoustic Imaging and Spectroscopy of ProstatePhotoacoustic (PA) imaging is a new and innovative technique The major objective of this project is to determine if the PA signalfor the evaluation of biological tissues. It is dependent on opti- and PAS from prostate tissue measured ex vivo can differentiate be-cal properties of soft tissue mainly the absorption and scattering tween malignant and benign prostate tissue. The research proposedcoefficients, which in turn are dependent on tissue structure and has the follow-ing specific aims:composition. In PA imaging, tissue is irradiated with near-infrared Aim 1: Fabricate a PA Imaging Camera to study the PA properties of(NIR) laser beam. Interaction of NIR beam in the tissue generates excised human prostate tissue specimens.acoustic wave (PA signal), which can be detected using conven-tional ultrasound (US) technology. Strength of PA signal detected Aim 2: Perform PA Imaging and PAS analysis of excised humanis highly dependent on the laser wavelength used to irradiate the prostate tissue samples and correlate with histology.tissue. Mapping of PA signal variability on laser wavelength helpsto characterize different tissue types. This property will also allow The long-term impact of this work is to provide initial data tophoto acoustic spectroscopy (PAS). validate the in vivo use of PA imaging in differentiating malignant from benign prostate pathologies. 10 r&efoundation@rsna.org
  12. 12. research seed grant Vinay Duddalwar, MD, FRCR Radiology University of Southern California Hitachi Medical Systems/RSNA Research Seed Grant Assessing the Role of Contrast Enhanced Ultrasound in the Evaluation and Management of Renal Masses in Patients with Poor Renal FunctionThe management of renal masses, especially small lesions has Data from this study will be analyzed to evaluate three possiblechanged dramatically with the concept of active surveillance. future directions:The role of imaging is critical in these patients. We propose that 1) CEUS as an imaging modality of choice in patientscontrast enhanced ultrasound scans will provide adequate char- with compromised renal functionacterization of renal masses and provide information relevant forsurgical planning in patients with compromised renal function. 2) Semiquanitative data being analyzed to identify anyWe propose that contrast enhanced ultrasound may be able to dif- differentiating factors between low and high gradeferentiate different types of renal masses. renal carcinomas, malignancies from lesions such as angiomyolipomas and oncocytomas. If proven, this wouldAim 1: Can CEUS provide adequate characterization of renal be an effective way of monitoring effects of anti angiogenicmasses and provide additional information relevant for surgical chemotherapy on patients who only receive chemotherapy.planning in patients with compromised renal function? In addition,can it identify patients who would be suitable for active surveil- 3) CEUS data could be used to identify the efficacy oflance in this group? preoperative embolization on renal masses.Aim 2: Does dynamic and semi-quantitative evaluation of renalmasses during CEUS lead to better characterization of renalmasses? Are there specific patterns that are reproducible? Ron C. Gaba, MD Radiology University of Illinois at Chicago Philips Healthcare/RSNA Research Seed Grant Polymeric Iohexol Nanoconjugates for Targeted Transcatheter Drug Delivery: Quantitative CT Analysis of Spatial Distribution in a Rabbit VX2 Liver Tumor ModelTranscatheter arterial chemoembolization (TACE) is an established and sustained drug release characteristics as compared to othertreatment for surgically unresectable hepatocellular carcinoma nanoparticle devices. These agents, which have not been previously(HCC). This therapy exploits the predominant hepatic arterial per- applied in the study of liver TACE, may be loaded with a radi-fusion of hypervascular liver cancer to administer targeted tumor opaque contrast agent, such as iohexol, for non-invasive imaging oftherapy using chemotherapeutic agents. Contemporary TACE utiliz- nanoparticle distribution.es drug-eluting beads (DEBs) for delivery of doxorubicin to neoplas- The goal of this proposed project is to validate the use of PLA nano-tic tissue, but current therapy is potentially limited by incomplete conjugates for transcatheter liver embolotherapy by characterizingdrug penetration into tumor due to peripheral or inhomogeneous the biodistribution of unique radiodense PLA encapsulated iohexolmicrosphere deposition as well as mechanical vessel occlusion and nanoconjugates after nanoparticle TACE in a rabbit VX2 tumorconcomitant risk for cancer neovasculogenesis. animal model of HCC. Development of therapeutic PLA nanoconju-Nanoparticles represent a new transcatheter treatment platform gates and non-invasive confirmation of their accumulation withinthat holds promise for improving drug delivery by enhancing tumor has implications on the understanding of nanoparticle drugchemotherapy penetration into tumor without causing vascu- delivery and deposition during TACE, and will permit future basiclar ischemia. Biodegradable polylactide (PLA) nanoconjugates science and clinical translational studies aimed at assessing andrepresent a novel nanoparticle system with superior drug loading optimizing tumor drug delivery using these agents.RSNA.org/Foundation 11
  13. 13. research seed grant Puneeth Iyengar, MD, PhD Radiation Oncology UT Southwestern Medical Center-Dallas RSNA Research Seed Grant Use of an Inducible Cancer Cachexia Mouse Model to Study Inflammatory Effects on Lung Cancer Radiation ResponseLung cancer continues to be the leading cause of cancer death chectic inflammatory state are both drivers of tumor developmentworldwide. Our ability to control lung disease has not changed and therapeutic resistance.much in the last 30 years, suggesting a need for new intervention. With this study, we hope to 1) Model cachexia in vivo; 2) AssessFor decades, it has been perceived that inflammation is a key con- the influence of cachexia on lung tumor progression and radiationtributor to lung cancer development. Less emphasis has been placed resistance with this inducible murine system; and 3) Identify vitalon evaluating how systemic inflammation could also significantly secretory proteins that are expressed during cachexia and criticalinfluence radiation sensitivity through the modulation of tumor to lung cancer radiation resistance. The inherent biology and rolesuppressive mechanisms including autophagy and DNA damage of cachexia in influencing lung cancer patient performance status,signaling. disease progression, response to therapy, and survival outcomesCachexia is an inflammatory process which is often associated with is still an open ended question. It is not misleading to surmise thatintermediate and late stage lung cancer and includes symptoms reversing some of the pathophysiologic consequences and mecha-of weight loss, muscle atrophy, and fat loss. There are not many nisms of cachexia may help in all four areas –performance status,treatment options for lung cancer patients with cachexia even disease progression, therapy outcome, and survival. To that end,though new studies have demonstrated improved survival for these believing that cachexia represents one end of the systemic inflam-patients through aggressive palliation. We believe that unique, yet matory spectrum, we propose evaluating the relevant pathophysiol-undetermined, systemic molecules that are components of the ca- ogy of cachexia in an inducible mouse model. Friedrich Knollmann, MD, PhD Radiology University of Pittsburgh RSNA Research Seed Grant Computed Tomography Perfusion Imaging of Lung CancerThe treatment of advanced stage lung cancer is limited by a lack standard CT series of the chest and a CTP protocol of the tumor. Fol-of predictive methods that would allow an early assessment of lowing the injection of a 30cc bolus of an iodinated contrast agent intreatment success. Contrast-enhanced computed tomography has re- a 64 row multi-detector CT unit, one image will be acquired every 3cently been established as a robust method to assess regional tissue seconds over a 40s period at 100 kV, and 100mA tube current.blood flow, and should offer direct insight into tumor blood flow, The perfusion sequence will be repeated after the patient has leftwhich is the target of anti neo angiogenic therapy. the exam room to determine the reproducibility of the test.Computed Tomography Perfusion (CTP) Imaging has the potential Images will be evaluated using standard CT blood flow software.to improve patient management by predicting treatment response. Color-encoded maps of regional blood flow will be used to classifyCorrelating tumor response during cancer therapy with patient the blood flow pattern, and mean tumor blood flow derived.survival is the most stringent approach to validate CTP as a predic-tive marker for treatment outcome. However, the accuracy of such The ultimate patient value of the CTP method will be demonstratedmeasurements still needs to be determined, before the method is by directly correlating tumor perfusion parameters before and afterapplied on a wider scale to predict patient survival. the initiation of chemotherapy with patient survival, in comparison to the prognostic value of measuring tumor size with the currentIn comparing the CTP blood flow measurements in lung cancer with standard of care CT method.changes in tumor size, 30 subjects will be examined with both a 12 r&efoundation@rsna.org
  14. 14. research seed grant An Tang, MD Radiology University of Montreal Toshiba America Medical Systems/RSNA Research Seed Grant Randomized Trial of Liraglutide and Insulin Therapy on Hepatic Steatosis as Measured by MRI and MRS in Metformin-treated Patients with Type 2 Diabetes: an Open Pilot StudyNon-alcoholic fatty liver disease (NAFLD) can now be identified in steatosis. The primary outcome measure is defined as an improve-70% of patients with type 2 diabetes. Insulin can be introduced at ment in steatosis of 5% before and after treatment between the twoany point in the treatment of diabetes, but is potentially lipogenic. treatment groups.Preliminary studies have shown conflicting results on the impact of Thirty-six patients will be randomized to either study group. Afterinsulin on fatty liver. baseline metabolic measurements by blood sampling, transientThis study is conducted to test the hypothesis that in type 2 diabetic ultrasound elastography, MRI and MRS, all subjects will be givenadults with NAFLD who are resistant to metformin, treatment with metformin with a starting dose of 500 mg in one tablet twice daily.liraglutide in combination with metformin will cause an absolute In addition, patients will be randomized to receive either liraglutidereduction in liver fat superior to insulin-metformin treatment or insulin glargine for a duration of 3 months.within a 3-month period, as measured by in vivo MRI and MRS. The results of this study will provide preliminary data for a large-This will be a prospective, open label, randomized parallel trial to scale study comparing the two therapeutic regimens and establishevaluate whether 12 weeks of treatment with liraglutide-metformin the utility of MRI and MRS to monitor medical treatment in dia-will improve steatosis in type 2 diabetic adults with NAFLD betic patients with fatty liver disease.compared to treatment with insulin-metformin. Before and post-treatment MRI and MRS will be read blindly for quantification of Drew A. Torigian, MD, MA Radiology University of Pennsylvania School of Medicine Philips Healthcare/RSNA Research Seed Grant Utility of DTP FDG-PET/CT and Advanced Image Analysis to Quantify In Vivo Tumor Biology, Predict Clinical Outcome, and Improve Disease Staging in Lung CancerLung cancer is a prevalent and deadly cancer with a wide spectrum invasive quantitative diagnostic methods to quantify in vivo lungof biological behavior, such that some patients with early stage cancer tumor biology, to improve prediction of clinical outcome,disease may survive a long time after surgical treatment whereas and to improve disease staging.others may experience disease recurrence and shortened survival. Single time point (STP) FDG-PET/CT is routinely used in lung can-TNM staging and clinicopathological prognostic markers used to cer patients to provide some information about patient prognosisestablish risk stratifications among lung cancer patients do not and to improve disease staging accuracy, although still suboptimalaccount for all observed variability in lung cancer-related survival, in diagnostic performance. We therefore propose to prospectivelyand tumors with identical clinicopathological characteristics can be evaluate dual time point (DTP) FDG-PET/CT, a modified versionassociated with different expression profiles and clinical outcomes. of FDG-PET/CT, in conjunction with advanced image analysisConventional structural imaging approaches at the time of diag- techniques in patients with surgically resectable lung cancer to as-nosis provide limited information about tumor biology or future sess its utility for simultaneous improved in vivo quantification ofpatient outcome, and have suboptimal sensitivities and specificities tumor biology, improved clinical outcome prediction, and improvedfor detection and characterization of sites of metastatic disease in disease staging. The results, if successful, will have significantanatomical sites such as the lymph nodes. Laboratory assays of mo- implications for optimizing individualized patient management,lecular expression may be useful to help predict clinical outcome, and will provide requisite preliminary data for future, larger scalebut do not provide regional spatial information relevant to disease research studies.staging. Thus, there is an urgent need for new yet practical non-RSNA.org/Foundation 13
  15. 15. research seed grant Robert J. Young, MD Radiology Memorial Sloan-Kettering Cancer Center Fujifilm Medical Systems/RSNA Research Seed Grant Using Functional MRI and Diffusion Tensor Imaging of the Language Pathway to Optimize Brain Tumor ResectionSurgical resection remains the most effective treatment for many Area with Wernicke’s Area. We will develop a solution to import thepatients with primary and secondary brain tumors, improving both tractography results into the neuronavigation software, then corre-the length and quality of survival. Surgery must maximize tumor late the fMRI- and DTI-identified loci with the intraoperative stimu-resection while avoiding adjacent eloquent brain structures, since lation loci to determine the accuracies of our techniques. Accuratetheir inadvertent injury can cause profound neurological deficits. noninvasive prediction of the arcuate fasiculus may lead to changesTwo noninvasive functional techniques can identify the eloquent in the surgical approach and help preserve patient function.brain and facilitate surgical planning for these patients: Functional The data gathered in this pilot study will be used to help support theMRI (fMRI) to identify the eloquent cortex is useful in guiding deci- development of an R01 grant, which will seek to deliver rapid auto-sion making about whether to attempt a resection, determining the mated or semiautomated analyses to the neurosurgeon in real-time.neurosurgical approach, and guiding the intraoperative stimula- The current grant will provide us with invaluable experience andtion. preliminary data to submit a competitive grant in 18 - 24 months.Diffusion Tensor Imaging (DTI) is a new technique to identify the Further work will be necessary to optimize the imaging sequenceseloquent white matter, which is less accessible and less reliable to and analyses, and incorporation into the neuronavigational system,stimulate at surgery. Tractography programs can analyze the DTI and to study and develop corrections for factors presented by braindata and display white matter fiber trajectories in 3D space. We will tumors such as edema, tumor infiltration and abnormal vascularitycompare two different tractography algorithms (standard vs. proba- and permeability.bilistic) in mapping the arcuate fasciculus that connects Broca’s My interest lies in the area of liver cancer and minimally invasive transcatheter treatment methods—obtaining the RSNA Research Seed Grant will allow me to focus on the investigation of drug delivery in minimally invasive oncologic therapy. As hepatocellular carcinoma (HCC) represents a significant public health problem and because of the importance of interventional radiologic catheter directed drug delivery in treating this disease, I believe development and application of novel, forward-thinking delivery vehicles, such as nanoparticle platforms, and imaging devices and agents to better understand, optimize, and confirm targeted liver cancer therapy are of significant importance. Clinical translation into human patients would be a long-term goal after validation of methodology in animal models. Ron C. Gaba, MD BRIGHT IDEAS. BETTER PATIENT CARE. 14 r&efoundation@rsna.org
  16. 16. research grant programsresearch fellow grant Jeremy Burt, MD Radiology Johns Hopkins University School of Medicine Silver Anniversary Campaign Pacesetters Research Fellow Grant Diagnosis of Arrhythmogenic Right Ventricular Dysplasia using T1 Mapping for Identification of Myocardial Fibrofatty InfiltrationArrhythmogenic right ventricular dysplasia (ARVD) is a genetic as a noninvasive imaging criterion. In this proposal, we seek tocardiomyopathy histopathologically characterized by fibrofatty re- investigate the use of T1 mapping of the myocardium using MRI inplacement of the myocardium and is an important cause of exercise- ARVD. T1 mapping has been developed for other cardiomyopathiesrelated sudden death in young individuals. The condition is most - to detect collagen deposition. T1 mapping has the potential for - -frequently diagnosed between ages 20 to 40. The implications of improved tissue discrimination in ARVD due to additive T1 effectsdiagnosis are need for a permanently implanted cardiac defibrilla- of both fat and collagen (both causing T1 shortening). Quantifica-tor and risk of sudden death. The diagnosis of ARVD is challenging tion of postcontrast myocardial T1 time may help standardize thedue to the variability of imaging findings, disease expression, and diagnosis of this life-threatening condition.clinical presentation. Current diagnosis is based upon histopatho- In this work, we will perform a retrospective analysis of patientslogic, imaging, and electrocardiographic criteria proposed by the in the Johns Hopkins database who previously had MRI examina-Task Force of Cardiomyopathies. tions for ARVD using the Look-Locker technique for T1 mapping.MRI is frequently requested to “rule out” ARVD, since early symp- In addition, we will perform a prospective study using a modifiedtoms of ARVD (tachyarrhythmia, palpitations, and syncope) are Look-Locker T1 mapping technique for patients referred for MRIcommon. Unfortunately, misdiagnosis by imaging physicians is fre- diagnosis of ARVD. The goal of this project is to provide a validated,quent. One reason for misdiagnosis is the current lack of validated quantitative method for myocardial tissue characterization inMRI features compared to histopathology. Both fat and fibrosis ARVD.are histologic hallmarks of ARVD, yet neither has been validated Daniel J. Durand, MD The Russell H. Morgan Department of Radiology and Radiological Sciences Johns Hopkins University School of Medicine RSNA Research Fellow Grant Molecular Imaging of Choline Metabolism in Musculoskeletal Soft Tissue Masses by C-11 Choline PET/CT and MR SpectroscopyCholine is an essential nutrient that plays a key role in cell mem- malignant disease using receiver operator characteristic (ROC)brane biosynthesis and cell proliferation. Concentrations of choline analysis.and its related metabolites are elevated in malignant tissue due Aim 2: We will determine whether quantitative changes in cho-primarily to increased cell membrane synthesis. Both C-11 choline line uptake as measured by C-11 choline PET/CT correlate withPET/CT and MR spectroscopy represent novel methods for quantify- histopathological endpoints for musculoskeletal soft tissue massesing in vivo choline metabolism non-invasively. We hypothesize that (STMs). Patients from Aim 1 will also undergo C-11 PET/CT prior tothese methods can be used prospectively to characterize musculo- biopsy. Histopathologic endpoints will be the same as for Aim 1. Weskeletal soft tissue masses (STMs) as benign or malignant prior to will determine the diagnostic accuracy of C-11 choline PET/CT forbiopsy. distinguishing benign from malignant disease using ROC analysis.Aim 1: We will determine whether quantitative changes in absolute In addition, we will determine whether intralesional variationscholine concentration as measured by MR spectroscopy correlate in C-11 choline uptake correlate with intralesional variations inwith histopathological endpoints for musculoskeletal soft tissue histopathology.masses (STMs). STMs referred for biopsy (deemed indeterminate Overall, the goal of this research is to determine whether predictiveby clinical and conventional imaging work-up) will be included, models utilizing non-invasive measures of choline metabolism mayand absolute choline concentration will be quantified by single allow more selective and/or more effective biopsy of STMs in thevoxel MR spectroscopy. Histopathologic measures will include final future.pathologic diagnosis as well as Ki-67 indexing. We will determinethe diagnostic accuracy of MRS for distinguishing benign fromRSNA.org/Foundation 15
  17. 17. research fellow grant Alessandro Furlan, MD Radiology University of Pittsburgh Siemens Healthcare/RSNA Research Fellow Grant Assessment of Transplanted Kidney using Quantitative Sodium MR ImagingRenal allograft dysfunction requires prompt and accurate diagnosis concentration gradient are associated with renal pathophysiologyto avoid graft loss over time. It is particularly important to distin- (ATN vs. AR). Accuracy and reproducibility of the sodium measure-guish between acute tubular necrosis (ATN) and acute rejection ments obtained with our method will be tested respectively using(AR), because treatment differs between the two disorders. Because a dedicated phantom study, and repeated imaging of three normalbiopsy is currently the only diagnostic tool to differentiate ATN volunteers and three kidney transplant patients. CMSG will befrom AR, there is a need for a non-invasive method. Renal function quantified calculating the mean medulla-to-cortex sodium concen-is strictly dependent on the creation and maintenance of a cortico- tration ratio, and more precisely with a pixel-by-pixel measurementmedullary sodium gradient that allows for water reabsorption and along the corticomedullary gradient. CMSG will then be measuredurine concentration. In this project we propose to develop in vivo from transplanted kidneys and compared between renal allograftquantitative sodium MR imaging of human kidney using ultra- with normal (n=5) and histologically (biopsy) proven ATN (n=5)short TE sequence and dedicated multi-channel, dual-tuned proton/ and AR (n=5). The success of our proposed study will lead to thesodium RF coil at clinic 3T scanner, and to apply this technique for development of accurate and reproducible renal sodium MR imag-the non-invasive evaluation of renal allograft function. ing technique, the advancement of our knowledge on renal allograft pathophysiology, and the application of a new imaging biomarker toThe hypotheses of the study are that 1) sodium MR imaging can diagnose renal allograft ATN and AR.accurately and reproducibly measure sodium concentrationgradient (CMSG) in kidney, and that 2) variations in renal sodium Randall J. Kimple, MD, PhD Human Oncology University of Wisconsin-Madison RSNA Research Fellow Grant Molecular Mechanisms of Radiation Response Modulation by Human Papillomavirus in Head and Neck Squamous Cell CarcinomaHuman papillomavirus (HPV)-associated head and neck squamous Aim 1 seeks to explain why HPV-positive HNSCC is more sensitivecell carcinoma (HNSCC) is a growing public health concern. These than traditional HNSCC to ionizing radiation using standard assayspatients are younger and present with more advanced disease than of radiation survival and both in vitro and in vivo model systems.patients with traditional tobacco and alcohol associated HNSCC, yet The molecular pathways underlying radiation sensitivity will beparadoxically have improved outcomes. The mechanisms underly- investigated while focusing on an enhanced apoptotic response ining these improved outcomes remain unclear. The work proposed HPV-positive HNSCC. Alterations in patterns of gene expressionhas two primary goals: 1) to provide for the continued career devel- following radiation will be used to identify potential therapeuticopment of the principal investigator (PI) and establish his inde- targets. Aim 2 examines the ability of inhibitors of the epidermalpendence so that he can lead a research program investigating the growth factor receptor (EGFR) to sensitize HPV-positive HNSCCradiation response in virally associated cancers; and, 2) to under- to radiation in vitro and in vivo. Effects of EGFR inhibition onstand how HPV-positive HNSCC differs in its response to radiation downstream signaling pathways will be assessed to identify criticaltherapy from traditional HNSCC. During his research fellowship, molecular pathways.the PI is obtaining additional training in molecular virology, hu- These studies will provide details regarding the mechanism ofman papillomavirus biology, and mouse models of cancer to enable increased sensitivity to radiation and will identify importanthim to compete for independent funding following completion of his targets for the development of novel therapies to improve outcomesresearch fellowship. of patients with both HPV-positive and HPV-negative head and neck cancer. 16 r&efoundation@rsna.org
  18. 18. research fellow grant Bela Kis, MD, PhD Radiology Brigham & Women’s Hospital RSNA Research Fellow Grant Effects of Focused Ultrasound on Cerebral Microvascular Endothelial Cells and Pericytes - Investigating the Molecular Mechanisms of Focused Ultrasound-Induced Blood-Brain Barrier OpeningThe blood-brain barrier (BBB) is a functional unit of cells which study in the in vivo complexity of the brain. First, we will study themaintains the stability of the brain microenvironment by strictly effect of FUS treatment on BBB permeability for different markercontrolling the movement of molecules and cells between the blood molecules to determine the quality and time course of FUS-inducedand the brain. While BBB is a necessary physiological gatekeeper, - - BBB opening. Second, we demonstrate FUS-induced cellular shape -this barrier is a real obstacle to deliver drugs to treat brain patholo- changes in CECs and pericytes. Third, we will study the effect ofgies. It has been shown that focused ultrasound (FUS) is capable FUS on organization of major cytoskeletal proteins in CECs andof temporary and localized BBB disruption. FUS combined with pericytes. Fourth, we will demonstrate the subcellular re-distribu-MRI-guidance can provide a noninvasive targeted drug delivery to tion of tight-junction proteins in CECs following FUS treatment.the brain. However, the mechanism of FUS-induced BBB opening is And fifth, we will study the effect of FUS on major intracellularlargely unknown. signaling pathways (Ca2+ and cAMP) which are instrumental in BBB permeability.The goals of the proposed experiments are to study the molecularmechanism of BBB opening induced by FUS in cerebral endothelial The proposed experiments will shed light on the mechanisms of thiscells (CECs) and pericytes, the two major constituents of the BBB. therapeutically very important phenomenon, FUS-induced BBBWe will use primary cultures of rat CECs and pericytes and differ- opening, which is much needed information to advance this technol-ent co-culture systems which represent the closest possible pheno- ogy towards clinical use.type to the in vivo BBB. These in vitro settings allow us to studythose intracellular mechanisms which are extremely difficult to Aaron So, PhD Diagnostic Imaging St. Joseph’s Health Care London RSNA Research Fellow Grant Validation of Quantitative CT Myocardial Perfusion Measurement with Dual Energy CT ScanningCoronary CT angiography (CTA) has become a routine non-invasive Dual energy CT (DECT) scanning allows reconstruction of monoen-procedure for detecting coronary artery disease (CAD) by anatomic ergetic (keV) images, which are free of beam hardening artifacts,visualization of stenosis severity. The use of dynamic contrast en- from two polyenergetic CT scans acquired at two different kVps.hanced CT imaging (CT perfusion) for quantitative measurement of Advances in detector technology have resulted in X-ray detectorsmyocardial perfusion (MPF) in CAD patients can provide additional with fast scintillation decay time which permits ‘interlaced’ acqui-information regarding the fuctional significance of a coronary le- sition of projections at two kVps to minimize patient motion error,sion detected by coronary CTA. One of the obstacles for incorporat- which is important for cardiac imaging and to minimize spectraling MPF measurement into CTA protocol for comprehensive CAD contamination between projection views. Because DECT scanningevaluation has been inaccuracies in the measurement due to beam can minimize beam hardening artifact by projection-based deriva-hardening arising from high density contrast in the heart chambers tion of monoenergetic images, we posit that DECT measurement offollowing a bolus injection. Although post-reconstruction correction MPF will be more accurate, which is a prerequisite for using CT, aalgorithm has been developed to reduce beam hardening artifact in widely available imaging modality, for the comprehensive assess-CT images, such correction method is suboptimal because the X-ray ment of CAD.path length through high density contrast can only be approxi-mately modeled.RSNA.org/Foundation 17
  19. 19. research grant programsresearch resident grant Carmen Bergom, MD, PhD Radiation Oncology Medical College of Wisconsin RSNA Research Resident Grant SmgGDS and Altered Small GTPase Prenylation as Novel Radiosensitization Targets in Breast CancerAdvances in understanding the molecular basis of breast cancer in breast cancer also correlate with a lower likelihood of com-progression and resistance have led to new treatments, such as plete pathologic response with neoadjuvant chemotherapy. TakenHER2 and estrogen signaling inhibition. However, radiation and together, SmgGDS emerges as a promising target to alter breastchemotherapy resistance remain major challenges in managing cancer therapeutic responses.local-regional and distant disease. Small GTPases, which are mem- Our overall hypothesis is that SmgGDS attenuates irradiation-in-bers of the Rho, Rac, Ras, and Rap families, regulate breast cancer duced cell death, revealing a new target for breast cancer radio-development and progression and can alter sensitivity to radiation sensitization. This hypothesis will be tested in the following aims.and chemotherapy. Identifying new ways to suppress small GTPase Aim 1: Determine whether SmgGDS splice variants differentiallyactivation in breast cancer may provide new treatment approaches. promote radiation resistance in cultured breast cancer cells. Aim 2:The proposed research is based on our discovery that breast cancer Determine whether SmgGDS splice variants sensitize human breastcells express elevated levels of SmgGDS, a unique protein known tumor xenografts to radiation, and determine whether radiosensi-to activate multiple members of the small GTPase families. We tization is due to acute cell death in vivo using a novel radiotracer,discovered that breast cancer cells express two SmgGDS splice 99mTc-duramycin. This study will define the role of SmgGDS splicevariants, SmgGDS-558 and SmgGDS-607, which differentially affect variants in breast cancer radiation resistance. The anticipated find-small GTPase prenylation. Silencing expression of these SmgGDS ings are expected to uncover new therapeutic targets to alter smallsplice variants in breast cancer cells significantly diminishes cell GTPase activity and treatment responses in breast cancer.proliferation and anchorage-independent cell growth, and increasesdoxorubicin-induced apoptosis. Increased SmgGDS mRNA levels Candice A. Bookwalter, MD, PhD Radiology University Hospitals Case Medical Center/Case Western Reserve University Peggy J. Fritzsche, MD Research Resident Grant Motion Artifact Removal by Retrospective Resolution Reduction for Applications in Body ImagingGhosting or streaking artifacts due to motion can obscure impor- ly, for the rectilinear trajectory the transition will be automaticallytant clinical information in magnetic resonance images. MR ab- detected by an abrupt decrease in correlation coefficients betweendominal imaging is especially adversely affected by motion artifact the acquired PE lines and the GRAPPA navigators. For the radialdue to breathing, and breath holds are often long and difficult for MARs algorithm, the echo magnitude also demonstrates a sharppatients even with fast imaging methods. In addition, failed breath change at the time breathing resumes. Preliminary studies usingholds are almost always identified only after image acquisition, and rectilinear MARs have demonstrated decreased motion artifact withno robust method for salvaging the images is available. Assuming the cost of decreased resolution. We aim to further optimize thethat a patient can initially hold their breath but may fail sometime rectilinear MARs algorithm and develop a radial MARs algorithm.during the acquisition, there will be a transition between uncor- Finally, we proposed to compare the corrected and uncorrected rec-rupted data, where the patient is not breathing, and data corrupted tilinear and radial images by independent observer ratings in a twoby motion due to breathing. alternative forced choice paradigm. Should the diagnostic quality of MARs corrected images prove superior to uncorrected images, thisWe have developed a novel algorithm called Motion Artifact Remov- method would solve an unmet need in body imaging.al by Retrospective Resolution Reduction (MARs) which automati-cally detects the transition and removes corrupted data. Specifical- 18 r&efoundation@rsna.org