RSNA Research & Education Foundation Funds Cutting-Edge Radiology Research

Bright Ideas Get Funded

RSNA Research & Education Foundation

Improving patient care by supporting research and
education in radiology and related scientific disciplines
through funding grants and awards to individuals and
institutions that will advance radiologic research,
education and practice.

2011
rsna grants and awards

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

your foundation—your future
2011 was another outstanding year for the RSNA Research & Education Foundation. Through the generous support of our
individual donors, private practice and academic groups and our corporate partners, the Foundation was able to fund 72
grants 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 its
inception, the Foundation has funded nearly 900 grants totaling well over $34 million. On average, every dollar awarded by
the 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&E
Foundation are performing vital research aimed to improve clinical care and patient outcomes, and ensure the future
of the specialty.

Today, the R&E Foundation’s 2011 grant recipients are conducting research in several exciting areas. A Research Scholar
grantee leads a comparative effectiveness trial on evaluation of pediatric small bowel Crohn disease using MR enterography
and ultrasound elastography—the ﬁrst of its kind in humans—which may mark an important paradigm shift in the radiologic
assessment of Crohn disease. A Research Seed Grant recipient will study the use of DTP FDG-PET/CT in conjunction with
advanced image analysis to quantify in vivo tumor biology, predict clinical outcome, and improve disease staging in patients
with lung cancer. This research may provide a new, practical, informative and readily available diagnostic approach for
these patients. A recipient of a Research Resident Grant will conduct a pilot study on patient-speciﬁc dosimetry in pediatric
and 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 proud
to 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. McCausland

RSNA Research & Education Foundation
Board of Trustees
Back 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, MD
Front 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

recognition and thanks
It is through the generosity of individuals, private practices and industry partners that the
R&E Foundation is able to continue its investment in R&D for radiology. In 2011, grant
awards were specially named to recognize the following individuals and companies for their
contributions 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 Pacesetters

HealthCare

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.


research grant programs
research 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 Technique

Colon cancer is the third most common cause of cancer-related enhanced dual-energy CT (DECT). We hypothesize that intralesional
mortality in the United States. Liver metastases are the main cause iodine concentration may prove to be a more sensitive and earlier
of 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 DECT
in size may, however, be a late manifestation in patients undergo-
imaging can be used to predict and monitor treatment response
ing targeted chemotherapy. Furthermore, different combinations
to antiangiogenic chemotherapy in patients with liver metastases
of 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 drug
minimize toxicity.
response, which could help develop personalized chemotherapy
There is tremendous interest in identifying response-predicting regimens and lead to improved patient outcome. Furthermore, this
factors that can help tailor chemotherapy. The overall aim of this could become a method for the rapid assessment of the efficacy of
project 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 vascularity
as 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 Disease

There is presently a paucity of data comparing magnetic resonance We propose to prospectively compare the diagnostic performance
enterography (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 baseline
ating EnUS have used suboptimal reference standards, including (immediately prior to starting medical management) and serial
ileocolonoscopy 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 MRE
characteristics (ROC) to MRE, this imaging technique could become findings will be documented and assessed for agreement at baseline
standard-of-care due to lower cost, shorter examination time, and and follow-up as well as correlated with a variety of laboratory
lack of need for sedation, contrast materials, and anti-peristaltic inflammatory markers and Pediatric Crohn Disease Activity Index
medication. (PCDAI) scores. Changes in UEI bowel wall stiffness over time will
be correlated with other imaging findings as well as clinical data to
Recently 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 bowel
potential promising clinical applications in humans, including serv-
wall fibrosis. Finally, we will formally survey the children and
ing as an imaging biomarker for both response (and perhaps early
parents in our study concerning their imaging preferences as well
response) 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 influence
the decision to surgically manage certain children.


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 Chemotherapy

Nearly 15,000 new cases of sarcoma are diagnosed annually in the will establish imaging biomarkers as early predictors of treatment
U.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 response
and 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 on
is the inability to reliably determine success or failure of pre-oper-
late changes in tumor volume. By determining treatment efficacy
ative (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 individual
result, patients may continue on ineffective chemotherapy regi-
patients, improving quality of life and enhancing disease-free
mens, 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 techniques
Our central hypothesis is that quantitative molecular and func-
to determine success or failure of pre-operative chemotherapy
tional imaging techniques can meet the need for early determination
in soft tissue sarcomas. These imaging techniques ultimately will
of 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 tissue
changes 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 Disorders

Resting state functional MRI (rs-fMRI) measures spontaneous fluc- currently limited. A more clinically relevant issue is whether the
tuations in blood oxygen level dependent (BOLD) signal, thought to features in a single rs-fMRI data set can be used to determine the
reflect fluctuation in underlying neuronal activity. Whole-brain rs- population from which the data originated. That is, can you make
fMRI 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 sets
reproducible 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 the
depression) have demonstrated consistent perturbations of this
basis of their rs-fMRI data. A support vector machine classifier will
temporal synchrony related to the underlying pathology.
be developed from an existing large rs-fMRI data set obtained from
Regarding 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 assessed
at the population level, including long-range interhemispheric for metrics of clinical validity, such as sensitivity, specificity, and
connectivity 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.


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 Specimens

The capability to perform real-time molecular analysis of human that act as proximity sensors for specific molecular targets. We
tumors is expected to enable rational treatment decisions in an era have used this exquisitely sensitive technology to measure DNA
where molecularly targeted therapies are emerging. Attempts to and mRNA, cancer cells, proteins, enzymes, metabolites, drug
profile cancer cells to date largely have been unsuccessful, as exist- concentrations, and bacteria. In preliminary experiments, we have
ing clinical technologies are either too insensitive to distinguish demonstrated the ability of DMR to profile expression of multiple
biomarker 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 techniques
broadly applicable, point-of-care method of diagnostic magnetic such as flow cytometry. The overall goal of this proposal is to
resonance (DMR) that overcomes many of these limitations. evaluate whether DMR can perform real-time molecular analysis
of biomarkers on human cancer cells isolated from percutaneous
The technology utilizes magnetic resonance techniques confined
image-guided fine needle aspiration, and to determine whether
within 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
Molecular Dissection of the Role of Tumor Vasculature in Radiation Sensitivity

Radiation therapy plays a prominent role in the treatment of pa- factors and resistance to radiation therapy, it is unclear if these
tients with prostate cancer. While prostate cancer exhibits signifi- vascular differences reflect the underlying biology of the tumor as
cant 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 to
15 - 20% of all prostate cancers, and it is more common in high-grade radiation therapy using molecular modification of endothelial cell
tumors. PTEN loss has been associated with higher Gleason grade, radiation response and non-invasive imaging of endothelial cell
increased 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 both
growth, which are both common in prostate cancer, are both as- tumor and endothelial cell pathophysiology we propose to evaluate
sociated with radiation resistance and prostate cancer recurrence. this signaling axis as a target for radiation sensitization of both
Neo-angiogenic blood vessel growth and proliferation are also prostate cancer and endothelial cells. Using models by which both
influenced by the PI3K/Akt/mTOR axis, and as a result the mam- tumor and endothelial cells can be individually modulated, we will
malian 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


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 Tumors

Malignant 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 inductively
margins during surgery is imprecise. Current imaging methods are coupled plasma atomic emission spectroscopy. MR detectability will
often limited by inadequate sensitivity, specificity, and/or spatial be assessed in phantom experiments. Further characterization of
resolution. We have developed a new brain tumor imaging strategy MRI-R behavior will include determination of differential uptake
based 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 tumor
imaging with a single nanoparticle injection. We have demonstrated margins will be assessed by careful correlation of in vivo MRI and
the 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 trials
with a single intravenous nanoparticle injection; d) Raman imaging
and hand-held Raman imaging devices have been developed, this
enables 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 animal
models.

Chan Hong Moon, PhD
Radiology HealthCare
University of Pittsburgh
AGFA HealthCare/RSNA Research Scholar Grant
Sodium/Proton MR Imaging of Knee Cartilage in Osteoarthritis

Knee osteoarthritis (OA) is a complex, heterogeneous condition orous testing of sodium quantification must be undertaken. Recent
that is a common cause of disability in the aging population. One technical advances in high-field MRI allow us to acquire morphologic
of the hallmarks of the pathophysiology of OA is the breakdown and physiologic imaging of knee cartilage with improved SNR and
of cartilage in joints. Conventional radiographs are an insensitive spatial resolution, thus facilitating accurate characterization and
measure 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 evaluate
of OA cartilage anatomy and physiology have improved our under-
methods for the quantification and characterization of structural
standing 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 specific
be technically challenging due to the intrinsically low MR signal and aims are to (1) develop and evaluate methods for sodium MRI of
concentration. In order to realize the clinical potential of sodium knee cartilage at 3T and 7T MR, and (2) evaluate and compare the
MRI as a reliable imaging biomarker for the characterization of differences in the sodium concentration and volume and thickness
cartilage quality, the optimization of sodium MRI techniques and rig- of knee cartilage between OA patients and normal controls.


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 Glioma

The traditional method of determining response to therapy for anti-angiogenic drugs such as bevacizumab demonstrate a rapid
glioblastoma 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 brain
inadequate 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 and
ment 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 patients
cause an increase in the size of enhancing lesions. It is analogous
with newly diagnosed and recurrent high-grade glioma with the
to 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 progression
occurs in up to 20% of patients who have undergone chemoradiation
of disease, as well as those with true response to therapy, will be
and 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
Incorporating the Effects of Transcytolemmal Water Exchange in Pharmacokinetic
Analysis of DCE-MRI Data in the Prediction of Head and Neck Cancer
Response to Chemoradiation

Preclinical and clinical data suggest that changes in head and neck rect nature of contrast agent detection. To date such models have
squamous cell carcinoma (HNSCC) cell cycle kinetics following a assumed a linear relationship between the measured longitudinal
brief exposure to radiotherapy, either alone or with chemotherapy, (or spin-lattice) relaxation rate constant (1/T1) of water protons
can be used to evaluate treatment efficacy in terms of loco-regional and the concentration of contrast agent. However, this assumption
control, disease-free survival and overall survival. Dynamic is not valid for all concentrations of any contrast agent of interest
Contrast-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 account
after the administration of an intravenous small molecular weight transcytolemmal and transendothelial water exchange during the
gadolinium-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 predict
MRI may reflect a composite of tumor perfusion, vessel permeabil-
treatment outcome in terms of local control and progression-free
ity and the volume of the extravascular-extracellular space. Thus,
survival in patients with loco-regionally advanced HNSCC. This
DCE-MRI may provide a more robust characterization of tumor
preliminary assessment will allow us to identify and appreciate
physiologic behavior rather than its anatomic appearance.
potential study limitations, and derive corrective measures before
Models 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-


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 Study

The incidence of renal cell carcinoma is rising by 3% per year, and metabolic profile of low versus high metastatic potential renal cell
it 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 correlate
options for these small tumors have expanded from surgical resec- with immunohistochemical and histopathological analysis of tumor
tion to include less invasive tumor ablation and active surveillance. aggressiveness. Successful completion of the project will add to our
However, 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 to
The long-term goal of our research is to determine whether hyper- apply for a NIH R01 grant for clinical trials in patients with renal
polarized [1-13C] magnetic resonance spectroscopic imaging (MRSI), tumors using hyperpolarized [1-13C] MRSI. Noninvasive imaging
an 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 and
siveness, and appropriately select those patients who will benefit greatly improve our ability to provide patient and tumor-specific
from 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
Influence of Differential Cellular Heat Shock (Stress) Protein Expression
on Cellular Death from Focal Laser Ablation

Hepatocellular carcinoma (HCC) is the seventh most common can- Our central hypothesis to be tested in the present proposal is that
cer worldwide and third leading cause of cancer-related death. In HCC is resistant to thermal ablation because of increased cellular
HCC, there is overexpression of several heat shock proteins (HSPs), expression of HSPs in cells contained in the ablative margin and
whose 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 proposal
many patients do not meet the inclusion criteria for transplant. will allow us to rapidly translate these findings to clinical trials to
Non-surgical patients are treated with catheter-based or percutane- investigate the efficacy of commercially available HSP inhibitors
ous-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. Recurrences
occur at the edge of the tumor margin and ablative zone.


research 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 Exams

The dramatic increase of diagnostic imaging capabilities over the a patient’s organ dose. We have developed a method to determine
past 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 along
in imaging procedures: wider availability of imaging modalities, in- with measured CTDIvol are used to calculate organ dose estimates
crease in technical capabilities, rise in demand by patients and cli- from abdominal CT scans for eight different patient models. For
nicians, 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 their
of CT exams, with the initial investigation involving abdominal CT abdominal organs.
exams. Current dose measurement methods (i.e. CTDIvol Computed
Tomography 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 Prostate

Photoacoustic (PA) imaging is a new and innovative technique The major objective of this project is to determine if the PA signal
for 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 proposed
coefficients, 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 human
is 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 helps
to characterize different tissue types. This property will also allow The long-term impact of this work is to provide initial data to
photo acoustic spectroscopy (PAS). validate the in vivo use of PA imaging in differentiating malignant
from benign prostate pathologies.


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 Function

The management of renal masses, especially small lesions has Data from this study will be analyzed to evaluate three possible
changed 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 patients
contrast enhanced ultrasound scans will provide adequate char-
with compromised renal function
acterization of renal masses and provide information relevant for
surgical planning in patients with compromised renal function. 2) Semiquanitative data being analyzed to identify any
We propose that contrast enhanced ultrasound may be able to dif- differentiating factors between low and high grade
ferentiate different types of renal masses. renal carcinomas, malignancies from lesions such as
angiomyolipomas and oncocytomas. If proven, this would
Aim 1: Can CEUS provide adequate characterization of renal
be an effective way of monitoring effects of anti angiogenic
masses 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 of
lance in this group? preoperative embolization on renal masses.
Aim 2: Does dynamic and semi-quantitative evaluation of renal
masses during CEUS lead to better characterization of renal
masses? Are there specific patterns that are reproducible?

Ron C. Gaba, MD
Radiology
University of Illinois at Chicago
Polymeric Iohexol Nanoconjugates for Targeted Transcatheter Drug Delivery:
Quantitative CT Analysis of Spatial Distribution in a Rabbit VX2 Liver Tumor Model

Transcatheter arterial chemoembolization (TACE) is an established and sustained drug release characteristics as compared to other
treatment 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 of
therapy 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 characterizing
drug penetration into tumor due to peripheral or inhomogeneous
the biodistribution of unique radiodense PLA encapsulated iohexol
microsphere deposition as well as mechanical vessel occlusion and
nanoconjugates after nanoparticle TACE in a rabbit VX2 tumor
concomitant 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 within
that holds promise for improving drug delivery by enhancing tumor has implications on the understanding of nanoparticle drug
chemotherapy penetration into tumor without causing vascu- delivery and deposition during TACE, and will permit future basic
lar ischemia. Biodegradable polylactide (PLA) nanoconjugates science and clinical translational studies aimed at assessing and
represent a novel nanoparticle system with superior drug loading optimizing tumor drug delivery using these agents.


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 Response

Lung cancer continues to be the leading cause of cancer death chectic inflammatory state are both drivers of tumor development
worldwide. 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) Assess
For decades, it has been perceived that inflammation is a key con-
the influence of cachexia on lung tumor progression and radiation
tributor to lung cancer development. Less emphasis has been placed
resistance with this inducible murine system; and 3) Identify vital
on evaluating how systemic inflammation could also significantly
secretory proteins that are expressed during cachexia and critical
influence radiation sensitivity through the modulation of tumor
to lung cancer radiation resistance. The inherent biology and role
suppressive mechanisms including autophagy and DNA damage
of cachexia in influencing lung cancer patient performance status,
signaling.
disease progression, response to therapy, and survival outcomes
Cachexia is an inflammatory process which is often associated with is still an open ended question. It is not misleading to surmise that
intermediate 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
RSNA Research Seed Grant
Computed Tomography Perfusion Imaging of Lung Cancer

The 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 in
treatment success. Contrast-enhanced computed tomography has re- a 64 row multi-detector CT unit, one image will be acquired every 3
cently 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 left
which 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 classify
Correlating 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 demonstrated
measurements still needs to be determined, before the method is by directly correlating tumor perfusion parameters before and after
applied 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 current
In 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


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 Study

Non-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 two
any 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. After
insulin on fatty liver.
baseline metabolic measurements by blood sampling, transient
This study is conducted to test the hypothesis that in type 2 diabetic ultrasound elastography, MRI and MRS, all subjects will be given
adults 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 liraglutide
reduction 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 establish
evaluate 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
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 Cancer

Lung cancer is a prevalent and deadly cancer with a wide spectrum invasive quantitative diagnostic methods to quantify in vivo lung
of 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 prognosis
establish risk stratifications among lung cancer patients do not
and to improve disease staging accuracy, although still suboptimal
account for all observed variability in lung cancer-related survival,
in diagnostic performance. We therefore propose to prospectively
and tumors with identical clinicopathological characteristics can be
evaluate dual time point (DTP) FDG-PET/CT, a modified version
associated with different expression profiles and clinical outcomes.
of FDG-PET/CT, in conjunction with advanced image analysis
Conventional 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 of
patient outcome, and have suboptimal sensitivities and specificities
tumor biology, improved clinical outcome prediction, and improved
for detection and characterization of sites of metastatic disease in
disease staging. The results, if successful, will have significant
anatomical 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 scale
but do not provide regional spatial information relevant to disease
research studies.
staging. Thus, there is an urgent need for new yet practical non-


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 Resection

Surgical resection remains the most effective treatment for many Area with Wernicke’s Area. We will develop a solution to import the
patients 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. Accurate
their inadvertent injury can cause profound neurological deficits. noninvasive prediction of the arcuate fasiculus may lead to changes
Two 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 the
MRI (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 and
tion.
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 sequences
eloquent 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 brain
data and display white matter fiber trajectories in 3D space. We will tumors such as edema, tumor infiltration and abnormal vascularity
compare 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.

research 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 Infiltration

Arrhythmogenic right ventricular dysplasia (ARVD) is a genetic as a noninvasive imaging criterion. In this proposal, we seek to
cardiomyopathy histopathologically characterized by fibrofatty re- investigate the use of T1 mapping of the myocardium using MRI in
placement of the myocardium and is an important cause of exercise- ARVD. T1 mapping has been developed for other cardiomyopathies
related 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 effects
diagnosis 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 the
due 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 patients
logic, 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 modified
toms of ARVD (tachyarrhythmia, palpitations, and syncope) are Look-Locker T1 mapping technique for patients referred for MRI
common. 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 in
MRI 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 Spectroscopy

Choline 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 with
PET/CT and MR spectroscopy represent novel methods for quantify-
histopathological endpoints for musculoskeletal soft tissue masses
ing in vivo choline metabolism non-invasively. We hypothesize that
(STMs). Patients from Aim 1 will also undergo C-11 PET/CT prior to
these methods can be used prospectively to characterize musculo-
biopsy. Histopathologic endpoints will be the same as for Aim 1. We
skeletal soft tissue masses (STMs) as benign or malignant prior to
will determine the diagnostic accuracy of C-11 choline PET/CT for
biopsy.
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 variations
choline concentration as measured by MR spectroscopy correlate in C-11 choline uptake correlate with intralesional variations in
with 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 predictive
by clinical and conventional imaging work-up) will be included,
models utilizing non-invasive measures of choline metabolism may
and absolute choline concentration will be quantified by single
allow more selective and/or more effective biopsy of STMs in the
voxel MR spectroscopy. Histopathologic measures will include final
future.
pathologic diagnosis as well as Ki-67 indexing. We will determine
the diagnostic accuracy of MRS for distinguishing benign from


Alessandro Furlan, MD
Radiology
Siemens Healthcare/RSNA Research Fellow Grant
Assessment of Transplanted Kidney using Quantitative Sodium MR Imaging

Renal allograft dysfunction requires prompt and accurate diagnosis concentration gradient are associated with renal pathophysiology
to 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 normal
biopsy is currently the only diagnostic tool to differentiate ATN volunteers and three kidney transplant patients. CMSG will be
from 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 measurement
medullary sodium gradient that allows for water reabsorption and along the corticomedullary gradient. CMSG will then be measured
urine concentration. In this project we propose to develop in vivo from transplanted kidneys and compared between renal allograft
quantitative 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 the
sodium 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 to
The hypotheses of the study are that 1) sodium MR imaging can
diagnose renal allograft ATN and AR.
accurately and reproducibly measure sodium concentration
gradient (CMSG) in kidney, and that 2) variations in renal sodium

Randall J. Kimple, MD, PhD
Human Oncology
University of Wisconsin-Madison
Molecular Mechanisms of Radiation Response Modulation by Human Papillomavirus in
Head and Neck Squamous Cell Carcinoma

Human papillomavirus (HPV)-associated head and neck squamous Aim 1 seeks to explain why HPV-positive HNSCC is more sensitive
cell carcinoma (HNSCC) is a growing public health concern. These than traditional HNSCC to ionizing radiation using standard assays
patients 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 be
paradoxically have improved outcomes. The mechanisms underly- investigated while focusing on an enhanced apoptotic response in
ing these improved outcomes remain unclear. The work proposed HPV-positive HNSCC. Alterations in patterns of gene expression
has two primary goals: 1) to provide for the continued career devel- following radiation will be used to identify potential therapeutic
opment of the principal investigator (PI) and establish his inde- targets. Aim 2 examines the ability of inhibitors of the epidermal
pendence so that he can lead a research program investigating the growth factor receptor (EGFR) to sensitize HPV-positive HNSCC
radiation response in virally associated cancers; and, 2) to under- to radiation in vitro and in vivo. Effects of EGFR inhibition on
stand how HPV-positive HNSCC differs in its response to radiation downstream signaling pathways will be assessed to identify critical
therapy 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 of
man papillomavirus biology, and mouse models of cancer to enable
increased sensitivity to radiation and will identify important
him to compete for independent funding following completion of his
targets for the development of novel therapies to improve outcomes
research fellowship.
of patients with both HPV-positive and HPV-negative head and neck
cancer.


Bela Kis, MD, PhD
Radiology
Brigham & Women’s Hospital
Effects of Focused Ultrasound on Cerebral Microvascular Endothelial Cells
and Pericytes - Investigating the Molecular Mechanisms of Focused
Ultrasound-Induced Blood-Brain Barrier Opening

The blood-brain barrier (BBB) is a functional unit of cells which study in the in vivo complexity of the brain. First, we will study the
maintains the stability of the brain microenvironment by strictly effect of FUS treatment on BBB permeability for different marker
controlling the movement of molecules and cells between the blood molecules to determine the quality and time course of FUS-induced
and 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 of
gies. It has been shown that focused ultrasound (FUS) is capable FUS on organization of major cytoskeletal proteins in CECs and
of 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 intracellular
largely unknown. signaling pathways (Ca2+ and cAMP) which are instrumental in
BBB permeability.
The goals of the proposed experiments are to study the molecular
mechanism of BBB opening induced by FUS in cerebral endothelial The proposed experiments will shed light on the mechanisms of this
cells (CECs) and pericytes, the two major constituents of the BBB. therapeutically very important phenomenon, FUS-induced BBB
We 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 study
those intracellular mechanisms which are extremely difficult to

Aaron So, PhD
Diagnostic Imaging
St. Joseph’s Health Care London
Validation of Quantitative CT Myocardial Perfusion Measurement
with Dual Energy CT Scanning

Coronary 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 detectors
myocardial 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 spectral
ing MPF measurement into CTA protocol for comprehensive CAD contamination between projection views. Because DECT scanning
evaluation 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 of
following a bolus injection. Although post-reconstruction correction MPF will be more accurate, which is a prerequisite for using CT, a
algorithm 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.


research 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 Cancer

Advances 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. Taken
HER2 and estrogen signaling inhibition. However, radiation and together, SmgGDS emerges as a promising target to alter breast
chemotherapy 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 differentially
activation 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 breast
cells 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 splice
variants, 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 small
splice variants in breast cancer cells significantly diminishes cell
GTPase activity and treatment responses in breast cancer.
proliferation and anchorage-independent cell growth, and increases
doxorubicin-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 Imaging

Ghosting or streaking artifacts due to motion can obscure impor- ly, for the rectilinear trajectory the transition will be automatically
tant clinical information in magnetic resonance images. MR ab- detected by an abrupt decrease in correlation coefficients between
dominal imaging is especially adversely affected by motion artifact the acquired PE lines and the GRAPPA navigators. For the radial
due to breathing, and breath holds are often long and difficult for MARs algorithm, the echo magnitude also demonstrates a sharp
patients even with fast imaging methods. In addition, failed breath change at the time breathing resumes. Preliminary studies using
holds are almost always identified only after image acquisition, and rectilinear MARs have demonstrated decreased motion artifact with
no robust method for salvaging the images is available. Assuming the cost of decreased resolution. We aim to further optimize the
that 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 two
by motion due to breathing. alternative forced choice paradigm. Should the diagnostic quality of
MARs corrected images prove superior to uncorrected images, this
We 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-


research resident grant
Scott Bratman, MD, PhD
Radiation Oncology
Stanford University Medical Center
Philips Healthcare/RSNA Research Resident Grant
Stromal Contributions to Self-renewal and Radiation
Resistance of Breast Cancer Stem Cells

Breast cancer is diagnosed in one out of nine women over the tion, and resistance to ionizing radiation. First, normal and tumor-
course of their lifetime and accounts for over 40,000 deaths annually associated fibroblasts from primary normal and tumor murine
in the United States. Radiation therapy and chemotherapy, which breast tissues will be isolated, and their effects on TIC functions
generally target rapidly dividing cells, have improved outcomes -
-
will be assayed in a 3D culture system and an orthotopic mouse
-
and extended survival in breast cancer patients, yet recurrence and model. Next, we will test the impact of the stromal fibroblasts on
treatment resistance remain frequent. Breast tumor initiating cells TIC viability after irradiation, and this will be correlated with
(TICs), sometimes called cancer stem cells, and the tumor-associ- changes in reactive oxygen species levels and IR-induced DNA dam-
ated stroma have largely been ignored in drug development. Prior age. Finally, we will identify secreted factors responsible for these
work has demonstrated that TICs from diverse tumor types are effects; specifically, we will test SDF-1 and HGF—known secreted
relatively resistant to ionizing radation. Normal stem cells depend stromal factors that promote tumor growth—for effects on TIC func-
on stromal cells for the formation of a stem cell “niche”, but the role tion and radiation resistance. Altogether, this research proposal,
of the stromal cells in breast TIC function and treatment resistance which will better characterize the unique microenvironment within
has not been explored. the TIC-stromal niche, has the potential to lead to the development
of novel radiation sensitizers and other classes of cancer therapeu-
Here, we propose a set of experiments, which aim to define the
tics.
effects of stromal fibroblasts on breast TIC self-renewal, differentia-

Albert Chang, MD, PhD
Radiation Oncology
Washington University School of Medicine/Barnes Jewish Hospital
Varian Medical Systems/RSNA Research Resident Grant
64Cu-Radiolabeled Somatostatin Analogs for Targeted Imaging and Therapy
of Medulloblastoma

Medulloblastoma is the most common pediatric brain malignancy. Radiolabeled SSTr2 ligands were also investigated as targeted
Although patient survival has increased, current treatments cause agents. Treatment with Yttrium-90 and Lutetium-177 radiolabeled
long-term impairments. Standard imaging techniques provide good somatostatin analogs demonstrated responses including significant
anatomic detail but minimal biological information. Small lesions tumor regression or remission. The administered activity was
can be missed and treatment effect is often difficult to discern from limited due to renal toxicity.
tumor progression. Therefore, improved imaging and therapeutic
The positron and beta minus decay of 64Cu allow for the develop-
options are necessary. Medulloblastoma overexpresses the soma-
ment of radiopharmaceuticals with both imaging and therapeutic
tostatin subtype 2 receptor (SSTr2). The goal is to characterize and
properties. Our preliminary results demonstrate the potential of
evaluate Copper-64 (64Cu) radiolabeled somatostatin analogs for
64Cu-radiolabeled somatostatin analogs for imaging and radio-
targeted imaging and therapy of medulloblastoma. The impact is
therapy in xenograft models with colorectal tumors engineered to
improvement in the detection and monitoring of medulloblastoma
overexpress SSTr2. In the proposed research, 64Cu-radiolabeled
and improvement in outcome with reduction in treatment-related
somatostatin analogs will be characterized and evaluated for in vivo
side effects.
PET imaging and targeted radiotherapy of medulloblastoma.
111In-DTPA-octreotide is FDA-approved for SPECT imaging of
Hypothesis: 64Cu-radiolabeled SSTr2 agonists are effective agents
tumors overexpressing somatostatin receptors, but image resolu-
for in vivo PET imaging and targeted radiotherapy of medulloblas-
tion and sensitivity are lacking. Somatostatin analogs labeled with
toma.
positron emitters demonstrated promising results with higher
resolution images and greater sensitivity than 111In-DTPA-OC.


RSNA Research & Education Foundation Funds Cutting-Edge Radiology Research

RSNA Research & Education Foundation Funds Cutting-Edge Radiology Research

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RSNA Research & Education Foundation Funds Cutting-Edge Radiology Research