Abstracts of Funded National Institutes of Health Grants

Research Corner

Abstracts of Funded NationalInstitutes of Health Grants

The following abstracts of diagnostic radiology research and training grants funded by the National Institutes of Health (NIH)were awarded to principal investigators (PIs) whose primary appointments are in medical school departments of radiology.These abstracts are listed on the NIH Web page (http://www-commons.cit.nih.gov/crisp/) and are printed here verbatim.

The grant identification number (eg, 1R01AI12345-01) contains a three-digit activity code (in the previous example, R01) thatidentifies a specific category of extramural activity. All current NIH activity code titles and definitions can be obtained at theNIH Web page http://silk.nih.gov/silk/brownbooks/actcod.

IRG (Internal Review Group) refers to the study section that reviewed the application. ICD (Institute, Center, Division) refersto the NIH funding source.

The abstracts of the funded grants are printed alphabetically by author according to the funding institute or center.

TISSUE-SPECIFIC OPTICAL IMAGINGAGENTS AND METHODS

Grant Number: 5R01EB001430-03PI Name: Achilefu, Samuel

Abstract: Description (provided by applicant): Accurate andrapid detection of tumors results in good patient prognosis.An important step towards achieving this goal begins withthe early diagnosis of cancer by molecular imaging of aber-rant genes of proteins in tumors. Although nuclear methodsare conventionally used for molecular imaging of pathologicconditions, the emerging field of optical imaging providesdistinctly new diagnostic capabilities while complementingestablished imaging modalities. Optical imaging in the nearinfrared wavelengths can be used to evaluate superficial le-sions, endoscope-accessible deep organs, surgical exposedtissues and deep tissues within several centimeters from theskin. We propose to develop novel optical imaging agentsthat will enhance tumor visualization in vivo based on thehypothesis that small peptide-based receptor-specific opticalimaging agents will selectively and rapidly accumulate in thetarget receptor-positive tumors relative to surrounding nor-mal tissues, and the resultant fluorescence intensity in vivowill correlate with the relative expression of the targeted re-ceptor proteins in tumor cell membranes. To test this hypoth-esis and to accelerate the applications of optical imagingagents in translational research and eventually in clinical set-tings, we will target somatostatin receptor subtype 2 (STR2)that has been shown to be clinically valuable by nuclearmethods. Accordingly, we will design and synthesize noveltumor-specific optical molecular probes that are useful for
imaging a variety of tumors and other human diseases. The
methods of molecular modeling and 2D NMR will be usedto optimize the selectivity and binding affinity of the mole-cules for STR2. We will evaluate the receptor binding affin-ity, cytotoxicity, receptor-mediated internalization, and sub-cellular distribution of the probes to select promising candi-dates for in vivo studies. The biodistribution and planaroptical imaging of tumor xenografts will be performed byoptical methods to determine the specificity and sensitivityof STR2-mediated optical imaging of pathologic conditions.The optical images will be validated by histology. We antici-pate identifying at least one optical molecular probe fortranslational research. Results of this study will provide atechnology platform for developing other disease-specificoptical molecular probes. Products of this study will also bemade available to other investigators interested in molecular-probe-mediated optical imaging and related medical/pharma-ceutical applications.

Thesaurus Terms: contrast media, fluorescent dye /probe,hormone receptor, image enhancement, infrared radiation,neoplasm /cancer radiodiagnosis, optics, peptide chemicalsynthesis, somatostatin, technology /technique developmentbiomarker, chemical stability, cytotoxicity, histology, neo-plasm /cancer transplantation, protein localization, receptorbinding, xenotransplantation athymic mouse, bioimaging/biomedical imaging, biotechnology, cell line, charge coupleddevice camera, computer simulation, nuclear magnetic reso-nance spectroscopy

Institution: Washington University1 Brookings Dr, Campus Box 1054Saint Louis, MO 631304899

Fiscal Year: 2006

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http://www-commons.cit.nih.gov/crisp/

http://silk.nih.gov/silk/brownbooks/actcod

Academic Radiology, Vol 15, No 3, March 2008

Department: RadiologyProject Start: 01-Sep-2004Project End: 31-Aug-2008ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: ZRG1

IMPROVED MOLECULAR IMAGINGWITH SPECT

Grant Number: 7R01EB001809-04PI Name: Acton, Paul D.

Abstract: Description (provided by applicant): Molecularimaging of small laboratory animals, such as mice and rats,is a vital tool in the study of disease. Mouse models of hu-man diseases, such as cancer, Parkinson’s disease, and Alz-heimer’s disease, are providing important clues to the causes,diagnosis and treatment of these, and many other, disorders.Ultra-high resolution PET and SPECT have enabled the vi-sualization of biochemical processes in vivo in small ani-mals. Despite the important results obtained using pinholeSPECT, it is clear that the sensitivity of SPECT systems issub-optimal. Some sensitivity can be recovered by eitherincreasing the pinhole diameter, resulting in a loss of resolu-tion, or increasing the injected dose, which may lead to radi-ation damage in the subject. This project will develop novel,widely applicable, non-invasive methods for small animalSPECT, using multiple-pinhole techniques to improve theimage statistics, while maintaining the spatial resolution, andpotentially reducing the radiation dose to the animal. Variousmultiple-pinhole configurations will be investigated, includ-ing both overlapping (in which the projection images overlapon the detector face), and non-overlapping (in which thegeometric arrangement of pinholes is designed to produceseparate images on the detector). Monte Carlo computer sim-ulations will be used to optimize the pinhole arrangement,providing high-resolution images, without compromising thesignal-to-noise ratio or introducing image artifacts. The opti-mum design will be application-dependent, and determinedusing quantitative techniques and Hotelling observer studies.Additional image reconstruction improvements, such as cor-rection for depth-of-interaction in the crystal, and pinholeseptal edge penetration, will be investigated using MonteCarlo simulations. Model-based iterative reconstruction tech-niques will be developed to deconstruct the data from themultiple-pinhole systems, and to incorporate the correctionsfor pinhole edge penetration and depth of- interaction. Theoptimized multiple-pinhole system will be constructed andcompared against the single pinhole device in both phantomand animal studies, to validate the multiple-pinhole ap-proach, and to test the reconstruction algorithm. The im-provements in the imaging technology proposed in this ap-
plication will lead to enhanced sensitivity, and improvements
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in the throughput of small animal molecular imaging due tothe decreased imaging time required. It also takes advantageof adapting existing clinical SPECT machines, rather thandeveloping a dedicated small animal imaging system, whichmakes it much less expensive and more widely available.

Thesaurus Terms: biomedical equipment development,computer simulation, image enhancement, image processing,mathematics, single photon emission computed tomographybinding site bioimaging /biomedical imaging, laboratorymouse, phantom model

Institution: Thomas Jefferson University201 South 11th StPhiladelphia, PA 191075587

Fiscal Year: 2005Department: RADIOLOGYProject Start: 10-SEP-2003Project End: 31-JUL-2007ICD: National Institute Of Biomedical


STATISTICAL ANALYSIS OFRADIONUCLIDE IMAGES

Grant Number: 1R01EB002774-01PI Name: Acton, Paul D.

Abstract: Description (provided by applicant): This projectwill develop novel, widely applicable statistical methods forthe accurate differential diagnosis and longitudinal follow-upof dopaminergic function in normal aging in healthy sub-jects, and neuronal degeneration in patients with disorderssuch as Parkinson’s disease (PD), using single photon emis-sion tomography (SPECT). While numerous methods existfor the pixel-based comparison groups of subjects (such asStatistical Parametric Mapping), applying them to the diag-nosis of individual subjects is inaccurate. The techniquesdeveloped in this study will use pixel-based, data-drivenmethods for diagnosing individual subjects. PD is a long-term and devastating disorders, afflicting over a millionAmericans and costing society over $25 billion annually.Existing diagnostic techniques, based on clinical symptomsand anatomical and functional imaging, are inaccurate andcannot easily distinguish the Parkinsonian symptoms associ-ated with this disorder, particularly when the patient presentsat an early stage of the disease. Of particular importance isthe diagnosis of disease at a very early stage, or the screen-ing of “at risk” individuals who may present before clinicalsymptoms become apparent. It is also important to provide astatistically valid analysis of longitudinal follow-up studies,where subjects are studied multiple times to measure the ef-fects of normal aging, or disease progression and the efficacy
of treatment. Conventional region-of-interest (ROI) analysis


techniques are time-consuming and subjective and known tobe prone to operator bias. ROI analysis also dilutes smallfocal changes in brain behavior, reducing the sensitivity andspecificity of the method leading to misdiagnoses. Thisproject will apply and develop novel automated, pixel-basedstatistical techniques leading to accurate and unbiased diag-noses, and improved patient management. Neuronal loss inthe dopaminergic, nigrostriatal system will be monitored us-ing SPECT imaging“ ” of [99m Tc]TRODAT-1 binding todopamine transporters. Two methods, a pixel-based logisticdiscriminant analysis system and a channelized Hotellingobserver, will be “trained” on known images, and then usedto distinguish between patients and controls, based on re-gional differences in neuronal degeneration. The optimalcombination of discriminatory factors will be established forthe disorder, and the methodology applied to patients withmore equivocal diagnoses presenting earlier in the course ofthe disease. In summary, this project will develop widelyapplicable and powerful neuroimaging analysis tools for theaccurate, objective differential diagnosis of neurodegenera-tive disorders, and for the longitudinal analysis of follow-upstudies.

Thesaurus Terms: image enhancement, method development,nervous system disorder diagnosis, radionuclide imaging /scan-ning, single photon emission computed tomography, statistics/biometry Parkinson’s disease, brain imaging /visualization/scanning, data collection methodology /evaluation, diagnosisdesign /evaluation, dopamine transporter, longitudinal humanstudy, neural degeneration automated data processing, bioimag-ing /biomedical imaging, human data, radiotracer

Institution: University Of Pennsylvania3451 Walnut StreetPhiladelphia, PA 19104

Fiscal Year: 2003Department: RadiologyProject Start: 10-Sep-2003Project End: 31-Jul-2007ICD: National Institute Of Biomedical


IMPROVED IMAGING OF BRAINWHITE MATTER

Grant Number: 5R01EB002777-04PI Name: Anderson, Adam W.

Abstract: Description (provided by applicant): This workaims to develop and evaluate new tools for non-invasiveanalysis of white matter fiber bundles in the brain. Diffusionweighted magnetic resonance imaging (MRI) provides infor-mation on fiber orientation because the diffusion of tissue
water is faster parallel than perpendicular to axons. In addi-
tion, the diffusion measurement is sensitive to cellular prop-erties such as cell type, size, and volume fraction. Diffusiontensor imaging (DTI) has been widely used to assess whitematter development and pathology, as well as to reconstructfiber paths in the brain. However, it has become clear thatthe technique has two major limitations. First, image noiseproduces both noise and bias in the estimated diffusion ten-sor. This complicates comparisons of DTI parameters be-tween subjects, and leads to errors in estimated fiber paths.Second, conventional DTI is based on the assumption that asingle tensor describes the diffusion in each image voxel.The single-tensor model is inappropriate in regions of thebrain with complicated fiber structure (e.g., crossing orsplaying fibers). An alternative method, ‘q-space’ imaging,can be used to quantify diffusion using very few assump-tions, but requires impractically long scans for most clinicalor pediatric studies. Extended q-space experiments show thatthe single-tensor model is generally inappropriate, but atpresent there are no established alternatives suitable for rou-tine clinical use. The studies in this proposal aim to evaluateand mitigate the effects of noise and partial volume averag-ing in DTI. Specifically, we propose the following: (1) totest theoretical predictions of the effects of noise on the dif-fusion tensor and estimated fiber paths, and to quantify theperformance of a tensor denoising algorithm. (2) To develophigh spatial resolution DTI using navigated, multiple shotecho planar imaging. (3) To develop a time-efficient ap-proach to DTI that uses a multiple-tensor model of diffusionin each voxel, and test its reliability in phantom and humanstudies. (4) To develop approaches to fiber tracking and seg-mentation using the new multiple-tensor information, andtest these in phantom and human subjects. We expect thatthe resulting methods will significantly improve the sensitiv-ity of DTI studies. Overall this work will help to define thecapabilities and limitations of fiber characterization usingMRI, which represents a powerful new approach for study-ing the structure of neural tissue.

Thesaurus Terms: brain imaging /visualization /scanning,brain mapping, image enhancement, magnetic resonance im-aging, technology /technique development axon, diagnosisdesign /evaluation, diffusion, myelin, noninvasive diagnosis,phantom model bioimaging /biomedical imaging, clinicalresearch, human subject

Institution: Vanderbilt UniversityMedical CenterNashville, TN 372036869

Fiscal Year: 2006Department: Radiology & Radiological ScisProject Start: 01-Sep-2003Project End: 31-Jul-2008ICD: National Institute Of Biomedical

Imaging And Bioengineering
IRG: ZRG1
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PET EVALUTAION OF HEMORRHAGICSHOCK AND RESUSCITATION

Grant Number: 5R21EB005187-03PI Name: Awasthi, Vibhudutta

Abstract: Description (provided by applicant): In the USA,trauma kills approximately 150,000 people each year. De-spite such an impact on health care, fluid resuscitation intrauma continues to be a debatable issue. Crystalloids or col-loids are commonly used and these fluids augment O2 deliv-ery only by increasing preload. The only fluids that can in-crease both O2- carrying capacity and preload are hemoglo-bin based products. Thus, the long-term goal of this researchis to develop encapsulated hemoglobin as a complete anduniversal resuscitative fluid to address multifaceted patho-physiology of hemorrhagic shock. Liposome encapsulatedhemoglobin (LEH), as well as other hemoglobin-based O2carriers (HBOCs), have undergone extensive evaluation. But,an efficient O2 carrier is not necessarily an efficient O2 de-livery vehicle. PET has the capability to visually, quantita-tively and noninvasively assess O2 delivery and metabo-lism in response to resuscitation. HYPOTHESES 1) LEHdelivers O2 to the brain in the same fashion as RBCs,2) cerebral O2 delivery from LEH is sustained for a longerperiod of time than the unencapsulated HBOCs, and 3) LEHencapsulating high-affinity hemoglobin delivers more O2 tothe brain than LEH containing low-affinity hemoglobin insevere blood loss. SPECIFIC AIMS are: 1). Develop andvalidate image-derived cardiac time-activity curve as an arte-rial input function in micro-PET investigation of rat cerebraloxygen metabolism (CMRO2). 2). Investigate the effect ofoxygen affinity of hemoglobin in LEH on cerebral oxygenmetabolism after resuscitation in a rat model of hemorrhagicshock. 3). Evaluate the improvement in CMRO2 and energymetabolism after LEH resuscitation against standard resusci-tative fluids in a rat model of hemorrhagic shock. We willperform micro-PET imaging with O-15 radiotracers (O2 gas,CO gas and H2O) to determine CMRO2 and CBF. A ratmodel of hemorrhagic shock will be resuscitated with LEH,whole blood, Ringer’s lactate solution and 5% albumin. Ce-rebral energy metabolism will be established by tissue mark-ers of aerobic metabolism. This is an innovative proposalthat utilizes state-of-the-art imaging technology in a smallanimal model. The study will not only address importantissues pertaining to oxygen metabolism in shock and resusci-tation, it may also be useful in evaluation of other artificialoxygen carriers undergoing preclinical and clinical trials.

Thesaurus Terms: There are no thesaurus terms on file forthis project.

Institution: UNIVERSITY OF OKLAHOMAHLTH SCIENCES CTR

HEALTH SCIENCES CENTER
OKLAHOMA CITY, OK 731171213
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Fiscal Year: 2007Department: Pharmaceutical SciencesProject Start: 01-Aug-2006Project End: 31-Jul-2008ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: MEDI

PERCUTANEOUS MR GUIDED CREATIONOF A MESO-CAVAL SHUNT

Grant Number: 5K08EB004348-02PI Name: Arepally, Aravind

Abstract: Description (provided by candidate): The Men-tored Clinical Scientist Development Award will support theprogram outlined in this proposal, a program that will enablethe Principal Investigator, an Interventional Radiologist, tocombine his clinical skills and training with interventionalmagnetic resonance imaging (MRI) research and become anindependent clinical scientist in the field of interventionalMR (iMR). Research will be focused on the development ofan innovative, minimally invasive mesocaval shunt that willnot only provide safe and accurate implementation of thenew shunt, but also serve as a vehicle for delivery of thera-peutics to the liver, spleen, and pancreas. The candidate’simmediate goal is to gain expertise and knowledge of Mag-netic Resonance Imaging techniques as they relate to vascu-lar imaging, as well as research methodology. The candi-date’s long-term goal is to become an independent biomedi-cal researcher who is focused on translational research iniMR. To achieve these goals, the candidate and his mentor,Ergin Atalar, Ph.D., have developed a career developmentplan that includes: a) protected research time (75 percent);b) didactic coursework on MR vascular imaging and re-search techniques; and c) an advisory panel of establishedmultidisciplinary investigators, with expertise in severalfields related to this proposal. As a clinician trained in inter-ventional procedures, the candidate has had experience withthe interventions required as a result of complications fromcirrhosis of the liver. Due to the development of portal hy-pertension, decompression of the portal venous system hastraditionally been accomplished with either a surgical shuntor a percutaneous transjugular intrahepatic portosystemicshunt (TIPS). In addition, minimally invasive access to thespleno-meso-portal venous system creates the opportunity forthe development of novel therapies for diseases of the pan-creas, liver, and spleen. Using only real-time MR guidance,the candidate will work closely with his assembled team tocreate a minimally invasive meso-caval shunt The followingspecific aims will support these goals: (1) Develop a novelintravascular needle system to perform MR-guided vena cavapunctures; (2) Develop and implement an MRI protocol that
will provide complete real-time 3D anatomical definition of


devices and target vessels in order to safely perform MR-guided interventions; (3) Demonstrate that a,meso-cavalshunt can be constructed and implemented safely under MRguidance using a novel anastomotic device; and (4) Deter-mine that injection therapies can be delivered accurately tothe pancreas, liver, and spleen under MR guidance. The De-partment of Radiology, with its long history of groundbreak-ing achievements in Radiology research, will provide a sup-portive and nurturing environment in which the PrincipalInvestigator can establish a future as an independent clinicalscientist.

Thesaurus Terms: cardiovascular imaging /visualization,cardiovascular shunt surgery, image guided surgery /ther-apy, magnetic resonance imaging drug delivery system,intravenous administration bioimaging /biomedical imag-ing, swine

Institution: Johns Hopkins UniversityW400 Wyman Park BuildingBaltimore, MD 212182680

Fiscal Year: 2006Department: RadiologyProject Start: 01-Apr-2005Project End: 31-Dec-2009ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: ZEB1

MONITORING HEPATITIS ANDCIRRHOSIS BY 23NA MRS/MRI

Grant Number: 1R01EB005964-01A1PI Name: Bansal, Navin

Abstract: Description (provided by applicant): The overallgoal of this research is to develop and validate noninvasiveNa magnetic resonance (MR) techniques to detect and moni-tor the progression of liver diseases to hepatitis and cirrhosis.Liver diseases are the 8th leading cause of death in theUnited States. Regardless of cause, the 3 major pathologicstages in many liver diseases are: 1) steatosis (fat accumula-tion), 2) hepatitis (inflammation and necrosis), and 3) cirrho-sis (fibrosis and irreversible damage). 1H MRI provides ex-cellent methods to quantitatively image fat and water in theliver, but steatosis is a “benign” condition and does not cor-relate with the severity of liver disease or predict its progres-sion. Currently, there are no reliable noninvasive methodsfor monitoring the progression of liver diseases. A trans-membrane Na� gradient is essential for cell survival and isdisrupted by cellular damage. Because MR signal fromboth intra- and extracellular sodium (Nai� and Nae�) isisochronous, either a shift reagent (SR) or the multiple-quantum-filter (MQF) technique is necessary to discrimi-
nate between the 2. An MQF Na MR signal is observed
when the correlation time of Na� is slower than its Lar-mar period. Because of the high macromolecule concen-tration inside the cells, a majority of MQF signal comesfrom Naj�, with only a small contribution from Nae�.The 3 main hypotheses of this proposal are that: 1) steato-sis alone does not cause any changes in the transmem-brane Na� gradient, cellular energetics, or pH; 2) hepati-tis leads to an increase in total MQF 23Na signal, due toboth an increase in [Nai�] and a change in the intracellu-lar environment, and no change in the MQF Nae� signal,although an increase in extracellular space may lead to anincrease in the single-quantum (SQ) Nae� signal; and3) development of cirrhosis/fibrosis leads to an increase inthe MQF Nae� signal due to an increase in the numberof extracellular Na� binding sites resulting from the in-crease in extracellular matrix components. If these hy-potheses are true, then MQF 23Na MR spectroscopy andimaging can provide techniques to monitor progress ofhepatitis and cirrhosis noninvasively. The hypotheses willbe tested in rodent models of fatty liver, hepatitis, cirrho-sis, fibrosis, and cholestasis using an in vivo Na SR, Tm-DOTP5”. 1H and 31P MR techniques will also be used toexamine the correlation between fat accumulation, bioen-ergetics, and Na� and pH gradients. The results of MRexperiments will be correlated with histology and bloodtests for liver function. In addition, SQ and MQF 23NaMRI will be implemented and optimized on a 3T clinicalscanner, and the feasibility of quantitative 23Na MRI ofthe liver in humans will be demonstrated. The overwhelm-ing advantage of MQF 23Na MR is that it can be readilytranslated to human studies. Thus, the proposed 23Na MRtechniques will be very helpful in both experimental stud-ies and diagnosis of liver diseases. They may also proveuseful for monitoring response to therapy, which will helptremendously in designing more effective strategies fortreatment of hepatitis and cirrhosis. The proposed researchwill also enhance our understanding of the interrelation-ship between energy status and ion physiology in variousstages of liver disease.


Institution: Indiana Univ-Purdue Univ AtIndianapolis

620 Union Drive, Room 618Indianapolis, IN 462025167

Fiscal Year: 2006Department: RadiologyProject Start: 01-Jul-2006Project End: 30-Apr-2010ICD: National Institute Of Biomedical

IRG: MEDI
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ROBUST ASSESSMENT OF CEREBRALGABA LEVELS USING MRS

Grant Number: 5R21EB005302-02PI Name: Bhattacharyya, Pallab K.

Abstract: Description (provided by applicant): The overallgoal of this project is to develop a robust magnetic reso-nance spectroscopy (MRS) methodology to reliably measurecerebral GABA concentration in both the clinical and re-search settings. At present GABA spectroscopy sequencesare limited by large voxel size and long imaging times. Thepresent proposal seeks to develop a spectroscopy methodol-ogy, which can be used to look at a definite functionally rel-evant portion of brain parenchyma in a time short enoughfor the patient to remain consistently still; it also needs toremain sensitive to changes in GABA produced by the un-derlying pathology. The project also aims to demonstrate thatthe developed methodology is sensitive enough to detect a20% change in GABA concentration with a 95% confidenceinterval. Upon completion, this methodology should be use-ful in studying GABA level at specific cortical regions in anumber of neuropsychiatric patient populations (e.g. depres-sion, hepatic encephalopathy, focal dystonia, cocaine abusepatients, juvenile myoclonic epilepsy, and panic disorder)marked by reduction in GABA concentration. This studyaims to develop a MRS methodology based on MEGA-PRESS sequence for GABA editing to reliably measureGABA for the first time in the motor cortex of a normalcontrol population. First year of this two year long study willbe dedicated in developing the methodology by scanningphantoms and normal controls in a 3 Tesla Siemens Trioscanner and in the second year more scans will be performedto demonstrate the sensitivity of the methodology.


Institution: Cleveland Clinic Lerner Col/Med-Cwru

P84Cleveland, OH 44195

Fiscal Year: 2007Department: RadiologyProject Start: 01-Jul-2006Project End: 30-Jun-2008ICD: National Institute Of Biomedical


IMAGING APOPTOSIS IN VIVO WITHTECHNETIUM 99M ANNEXIN

Grant Number: 5R01EB000898-08
PI Name: Blankenberg, Francis Gerard
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Abstract: Description (provided by applicant): Phosphatidyl-serine (PS) is a membrane phospholipid that is selectivelyredistributed to a cell’s outer surface during apoptosis. PSexpression can be imaged with radiolabeled annexin V, anendogenous human protein, which has a high affinity formembrane bound PS in vivo. Despite extensive study thereis much that is still not fully understood about annexin Vimaging. In this proposal we will to determine the sensitiv-ity, specificity, and reproducibility of technetium-99m(99mTc)-annexin V radionuclide imaging in two models ofapoptosis; the first a rodent model of unilateral middle cere-bral artery (MCA) ischemic injury, the second BCL-1 tumorbearing mice undergoing chemotherapy. In the first modelwe will address the sensitivity, test and retest variability of99mTc-annexin V uptake in regions of neuronal injury fol-lowing unilateral mild, moderate, and severe MCA stroke inrats with and without neuroprotective therapy. We will use adedicated small animal micro-SPECT (single photon emis-sion computed tomography) system for imaging. These datawill be correlated with lesion(s) size and location(s) as de-fined by histologic analyses to permit calculation of the sen-sitivity and specificity of annexin V imaging for ischemia.Test and retest variability will be determined from two serialannexin V imaging studies performed within a 24 hour pe-riod. We will then study the BCL-1 syngeneic lymphomacell line, a line engineered to express both GFP (green fluo-rescent protein) and luciferase for real time direct non-inva-sive visualization of tumor using BLI (bioluminescence im-aging). We will first define the time course of annexin Vuptake in the spleen following chemotherapy in BCL-1 tu-mor bearing mice with micro-SPECT, biodistribution andautoradiographic assays in relation to serial BLI measure-ments of tumor burden. Next we will use fluorescent (red)-annexin V co-injected with radiotracer in combination withflow cytometry, to directly quantify the number of tumorcells that are stressed (PS positive without features of apo-ptosis or necrosis), apoptotic or necrotic in response to che-motherapy and correlate these results with micro-SPECT forcalculation of sensitivity and specificity of annexin V fortumor cell apoptosis. Completion of this proposal will aid inthe design and planning of clinical trials that will study theuse of serial annexin V imaging as a non-invasive marker ofcellular injury and therapeutic efficacy.

Thesaurus Terms: annexin, apoptosis, brain imaging /visu-alization /scanning, brain injury, cerebral ischemia /hypoxia,radionuclide imaging /scanning, technetium bioluminescence,brain disorder diagnosis, cerebral artery autoradiography,bioimaging /biomedical imaging, flow cytometry, fluores-cence microscopy, green fluorescent protein, immunocyto-chemistry, laboratory mouse, laboratory rat, single photonemission computed tomography

Institution: Stanford UniversityStanford, CA 94305

Fiscal Year: 2007


Department: RadiologyProject Start: 01-Jul-1999Project End: 31-Jul-2008ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: RNM

MR SIGNAL AMPLIFICATION FORRECEPTOR IMAGING

Grant Number: 5R01EB000858-05PI Name: Bogdanov, Alexei A.

Abstract: Description (provided by applicant): The ability toimage specific molecular biomarkers in vivo would have im-portant applications in the earliest detection of cancer, inassessing specific targeted therapies and for monitoring dy-namic changes in expression patterns during disease progres-sion. Many of such molecular biomarkers however, exist atlow concentrations, necessitating novel amplification strate-gies. The overall goal of the proposal is to investigate a newenzyme-mediated MR signal amplification strategy (Mramp)for imaging model molecular targets associated with vascularand extravascular targets in tumors. The strategy relies onenzyme-mediated polymerization of paramagnetic substratesyielding products with significantly higher atomic relaxivity(r1 and r2). This method potentially has several advantages:1) it utilizes low molecular weight lanthanide complexeswhich are converted into large molecules “on site”, 2) thedevelopment of these low MW precursors is clinically via-ble, 3) the so far observed relaxivity changes are higher thanwith other amplification strategies, 4) the oligomerized prod-ucts can be designed to reside locally and 5) the method canbe used in a variety of generic ways potentially allowing theread-out of many different targets. So far, we have shownthat the method holds promise in the 1) MR detection of amodel ligand using an enzyme-linked immunoadsorbent as-say format and 2) in imaging of a pro-inflammatory marker,E-selectin on the surface of endothelial cells. Two primarytargets will be investigated in proposed research: a mutant,constitutively active deltaEGFR and angiogenesis-modulatedE-selectin. deltaEGFR expression strongly upregulates VEGFexpression which, in turn, upregulates E-selectin and tubeformation in endothelial cells. These targets were chosenbecause of their importance in tumor proliferation, modula-tion by chemotherapy (e.g. EGFR tyrosine kinase inhibitors[Chan, 2002 #2547]) and the current absence of imagingmarkers directed against them. To further increase the sensi-tivity of MRamp we will investigate novel paramagneticsubstrates exploiting changes in T1 (Gd) and T2/T2* effect(Dy), The latter may be of particular interest for imaging athigher resolution and higher field strengths.

Thesaurus Terms: biomarker, image enhancement, mag-
netic resonance imaging enzyme linked immunosorbent as-
say, epidermal growth factor, growth factor receptor, oxi-doreductase, polymerization, selectin, vascular endothelialgrowth factor, vascular endothelium bioimaging /biomedicalimaging, biomagnetism measurement, genetic strain, hollowfiber separation technique, laboratory rat, phantom model,tissue /cell culture

Institution: Univ Of Massachusetts Med SchWorcester

Worcester, MA 01655Fiscal Year: 2006Department: RadiologyProject Start: 01-Apr-2003Project End: 31-Aug-2007ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: DMG

BREAST CT SCANNER FOR EARLIERCANCER DETECTION

Grant Number: 5R01EB002138-05PI Name: Boone, John M.

Abstract: Description (provided by applicant): Breast canceris a disease with high incidence in the U.S. and elsewhere,and population-level methods of fighting this disease areaimed primarily on screening, using mammography for earlydetection. The median size of breast cancer found usingmammography is approximately 11 mm. Based on extensivepreliminary studies involving computer simulations, physicalmeasurements, and cadaver breast imaging, we have foundthat breast CT may be able to routinely detect much smallerbreast tumors, in the 3 to 5 mm range. Importantly, the radi-ation dose of breast CT performed at 80 kVp was found indetailed studies to be comparable to that of mammography.It is not possible to image the breast alone on a live womanusing a clinical CT scanner. Therefore, in this Bioengineer-ing Research Partnership proposal, we have teamed with sci-entists from around the country to design, build, and test aCT scanner designed to image the breast. A team comprisedof medical physicists, physicians, mechanical and electricalengineers, and breast cancer advocates will collaborate onthe design of the breast CT scanner. Cone beam flat paneltechnology will be used to produce a scanner capable of 10second breast scanning, and the scanner development willalso include a breast immobilization system (acrylic cylin-ders), a breast CT table, a fast reconstruction computer, anda computer workstation customized for efficient viewingbreast CT images. The scanner will be built, tested, and opti-mized at UC Davis over a period of 3 years involving 9 spe-cific aims. After the breast CT scanner is tested in a briefphase I trial (2 specific aims), it will be moved to the breast
imaging clinic for a phase II trial where approximately 120
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women will be imaged (4 specific aims). This phase II trialwill evaluate the efficacy of breast CT for the early detectionof breast cancer in a group of women likely to have breastcancer (BIRADS 4 & 5). Additionally, the breast image datawill be studied for its utility in automating the analysis ofthe normal breast architecture, and for computerized cancerdetection. In year 5 of the proposed research, two specificaims utilize the breast CT data and corresponding mammog-raphy images (on -240 breasts) to evaluate the ideal observerperformance and human (mammographer) detection perfor-mance attributes of the breast CT scanner. At the end of theproposed research involving 17 specific aims, the potential ofbreast CT will have been evaluated both qualitatively andquantitatively. A tested, high quality prototype breast CTscanner would be ready to be enlisted in a phase III trial(beyond the scope of this proposed research), if further test-ing is warranted. Performance data acquired in the presentstudy would allow the proper design (power, etc.) of a phaseIII trial. If breast CT lives up to its enormous potential basedon initial imaging, breast cancer would be detectable far be-fore metastases occurs - for example, a 3 mm tumor containsonly 2 percent of the cell count of an 11 mm lesion, and a 5mm lesion contains only 9 percent of the cell count. Basedon a 100 day volume doubling time, detection of a 5 mmlesion would lead to 0.93 year earlier detection, and routinedetection of 3 mm lesions would result in 1.5 year earlierdetection over mammography. Surgical removal of early can-cers will effectively result in cure for the majority of womenscreened using this technology. While breast CT would prob-ably improve cancer detection in all women, some womenmay have risk factors (dense breasts, genetic markers, etc.)that particularly warrant screening using breast CT. ThePhase II trial will shed more light on this issue.

Thesaurus Terms: biomedical equipment development,breast neoplasm /cancer diagnosis, computed axial tomogra-phy, diagnosis design /evaluation, early diagnosis biomedicalequipment safety, clinical trial phase I, computer system de-sign /evaluation, diagnosis quality /standard, image enhance-ment, mathematics, radiation dosage X ray, bioengineering/biomedical engineering, clinical research, computer assisteddiagnosis, computer simulation, female, human subject, pa-tient oriented research, women’s health

Institution: University Of California DavisOffice Of Research - Sponsored

ProgramsDavis, CA 95618

Fiscal Year: 2006Department: RadiologyProject Start: 01-Sep-2002Project End: 31-Aug-2008ICD: National Institute Of Biomedical

IRG: ZRG1
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ENGINEERING APPROACH TOINDIVIDUALLY TAILORED MEDICINE

Grant Number: 5R01EB000362-18PI Name: Bui, Alex

Abstract: Description (provided by applicant): Technologi-cal advances in medicine, particularly imaging, have resultedin early detection, objective documentation, and overall bet-ter insight into medical conditions. These advances, however,have also led to an increasingly complex medical record.Physicians now spend a significant portion of their time re-trieving, structuring, organizing, and analyzing patient data,inaccurately and inefficiently: current information manage-ment systems in clinical medicine do not adequately supportthese functions, critical to the real-world practice of evi-dence-based medicine. Objective evidence, tailored to anindividual patient, must be readily available to physicians aspart of routine practice if true evidence-based medical prac-tice is to become a reality. This proposal details the develop-ment and evaluation of several innovative technologies, pro-viding solutions for the information management problemsfaced by physicians: 1) a distributed XML-based peer-to-peer medical record architecture, to enable portability andaccessibility of patient information, regardless of geographi-cal location; 2) a natural language processing (NLP) systemfor free-text medical reports, to automatically structure andcharacterize the contents of medical documents; 3) a phe-nomenon-centric data model, which supports the problem-solving tasks of the physician through explicit linking of ob-jective findings (e.g., images, lab values) to medical prob-lems; and 4) a time-based, problem-centric, context-sensitivevisualization of the medical record, supporting a “gestalt”view of the patient, with access to detailed patient data whenneeded. Together, these technologies will form a comprehen-sive system facilitating evidence-based medicine in a real-world environment. System evaluation will proceed in twoparts. Technical evaluation focuses on each of the proposedtechnologies individually, gauging classical performancemetrics: scalability of the distributed medical record; NLPprecision/recall; expressibility/comprehensibility of the datamodel; and the usability of the new medical record user in-terface. Clinical evaluation will follow a time series studydesign (“off-on-off”), with implementation of the entire sys-tem in a real-world clinical environment, the UCLA ClarkUrological Center. Clinical evaluation will measure the ef-fectiveness of the system as a whole on intermediate out-comes (process of care) including the number of visits, num-ber of procedures performed, and time to final diagnosis(disposition), as well as the impact on physician efficiency(time required to gather information and review charts).

Thesaurus Terms: informatics, medical record, patient caremanagement automated medical record system, computerassisted medical decision making, data collection methodol-
ogy /evaluation, information display, information system


analysis, mathematical model, outcomes research, perfor-mance clinical research, human data

Institution: University Of California Los AngelesOffice Of Research AdministrationLos Angeles, CA 90095

Fiscal Year: 2007Department: Radiology-Radiological SciencesProject Start: 01-Aug-1984Project End: 30-Jun-2008ICD: National Institute Of Biomedical


DEVELOPING A CEST REPORTER GENE

Grant Number: 5R21EB005252-02PI Name: Bulte, Jeff W.

Abstract: Description (provided by applicant): Non-invasiveimaging of cell migration, trafficking, and homing is anemerging new field that can provide us with a deeper insightinto the dynamics of cell-tissue interactions, as well as pro-vide guidance to the development of novel cell therapies us-ing stem cells and progenitors. Compared to other imagingmodalities (i.e., PET, SPECT, and bioluminescent imaging),MR imaging has the highest spatial resolution and can pro-vide both anatomical and functional information, but it suf-fers from a severely high signal-to noise threshold for thedetection of cells using suitable labels/tracers. To a certaindegree, this limitation has been resolved using intracellularendosomal tagging with super-paramagnetic nanoparticles.However, the magnetic susceptibility-based T2 (*) contrastinduced this way has significant drawbacks, including thecreation of hypointense “black holes” (obscuring tissue mor-phology), difficult differentiation between live and deadcells, the presence of hypointense imaging artifacts, uncer-tainty about long-term metal toxicity, and, most important,dilution of label following cell proliferation. We are propos-ing a new approach for the MR detection of labeled cellsusing a CEST (Chemical Exchange Saturation Transfer) re-porter gene. The method is based on the expression ofamide-enriched artificial proteins, i.e., lysine-rich protein(LRP) and argenine-rich protein (ARP) that can be detectedby CEST imaging in the nanomolar range. The advantagesof using these molecular probes are: 1) the gene product canbe visualized directly without the need of a substrate (notissue penetration needed); 2) detection sensitivity is not lim-ited by cell proliferation; 3) only live cells should provideCEST contrast; 4) the contrast can be “switched-on” and“switched-off” repeatedly; and 5) double- or triple-cell label-ing strategies may be pursued. We have initial data showingthat a CEST reporter gene can be cloned, expressed in trans-
fected cells, and specifically detected by MR CEST imaging
in phantoms, without affecting cell viability or proliferation.We hypothesize that this detection is also possible in vivo.To achieve this goal, our aim is to synthesize novel, moreefficient CEST reporter genes, and to detect double-labeledLRP/ARP transfected glioma cells and neural stem cells in-dividually in live animals.

Thesaurus Terms: contrast media, magnetic resonance im-aging, molecular /cellular imaging, molecular probe, reportergene, technology /technique development cell differentiation,cell migration, cell proliferation, cytotoxicity, gene expres-sion, glioma, nerve stem cell NIH Roadmap Initiative tag,NOD mouse, SCID mouse, bioimaging /biomedical imaging,molecular cloning, nanotechnology, transfection




OBSERVER STUDIES INVOLVINGSEARCH: MODELING AND ANALYSIS

Grant Number: 5R01EB005243-02PI Name: Chakraborty, Dev P.

Abstract: Description (provided by applicant): Since theinception of the paradigm in 1961 the analysis of FROC(free-response receiver operating characteristic) data (i.e.,mark-rating pairs) has remained an unsolved problem in im-aging science. Since the radiologist must search patient im-ages for localized lesions, intrinsically FROC data is gener-ated in virtually all imaging studies in radiology. Currentlythere is great interest in evaluating different computer aideddetection (CAD) algorithms for lung cancer screening withhelical CT scans. This task also involves search and depend-ing on the CAD in use there are approximately 4 to 20 sus-picious areas reported per patient While in the past the re-ceiver operating characteristic (ROC) paradigm has been thestandard method for the evaluation of diagnostic imagingsystems, its limitation to one report per patient is now beingincreasingly felt. This is a proposal to develop the scienceand perform the requisite testing of the FROC paradigm byaccomplishing the following aims. (1) Develop a statisticalmodel for FROC data that includes the effect of search andother relevant perceptual factors and which reduces to thestandard ROC model in non-search tasks. (2) Use the modelto validate and evaluate currently proposed methods for ana-
lyzing location and ratings data, and in particular determine
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their statistical power. (3) Develop an algorithm to determinethe parameters of the model from clinical FROC data and tomake statistical inferences regarding the modalities beingtested; verify that the estimated search parameters correlatewith values inferred from eye-movement recordings. (4) Pro-vide practical and validated software to the user communitythat will offer more statistical power and therefore requirefewer resources of cases and readers. The significance of theproposed work is that on the scale of previous developments,the potential gain in statistical power by the FROC methodis very large. Also, the explicit modeling of search and theability to estimate search related parameters from observerdata should open up new areas of vision research that allresearchers can exploit.

Thesaurus Terms: computer assisted diagnosis, image pro-cessing, mathematical model, model design /development,radiography computer program /software, computer systemdesign /evaluation, diagnosis quality /standard, health carepersonnel performance, lung neoplasm bioimaging /biomedi-cal imaging

Institution: University Of Pittsburgh At Pittsburgh350 Thackeray HallPittsburgh, PA 15260

Fiscal Year: 2006Department: RadiologyProject Start: 01-Aug-2005Project End: 31-May-2009ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: BMIT

APOPTOSIS AND INFLAMMATIONIMAGING

Grant Number: 1K08EB006702-01PI Name: Chen, Delphine L.

Abstract: Description (provided by candidate): The purposeof this project is to develop a new method of imaging apo-ptosis, or programmed cell death. Programmed cell death isa regulated process that occurs normally within the bodyduring which cells die in response to certain triggers withoutaffecting neighboring healthy cells. Necrosis, another formof cell death, occurs when cells have been suddenly injured,leading to inflammation and extensive damage to surround-ing tissues as a result. In many diseases there is either anexcess of cell death, such as in sepsis where normally pro-tective immune cells die, leaving the patient without an ef-fective defense system to fight off the existing infection, orthere is inadequate cell death, such as in cancer in whichgrowing cells do not respond to normal cell death triggers.Therefore, it would be helpful to develop new imaging tech-
niques which detect apoptosis specifically to identify tissues
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that are undergoing this process and would likely respond totreatments targeting this particular cell death pathway. Thisproject will focus on the evaluation of two new classes ofcompounds that bind specifically in cells undergoing apopto-sis and that can be used for positron emission tomographicimaging of cell death. The development of this technique forimaging cell death will have multiple clinical uses in helpingphysicians diagnose and treat disease. For example, this im-aging technique may allow physicians to see whether a tu-mor responded to chemotherapy or not earlier, allowing thephysician to change the chemotherapy treatment after justone cycle if needed instead of having to wait until finishingthe entire chemotherapy course. In critically ill patients withsepsis, identifying the presence of severe apoptosis earlymay allow physicians to identify patients that need more ag-gressive care before organs begin failing. In neurodegenera-tive diseases, seeing how many neurons are dying may alsohelp identify people who need more aggressive treatmentand may also help physicians determine whether a treatmentis working or not, again before significant damage occurs.


Institution: Washington University1 Brookings Dr, Campus Box 1054Saint Louis, MO 631304899



NOVEL RF COILS FOR IN VIVO MRAPPLICATIONS AT HIGH FIELD

Grant Number: 5R01EB000513-04PI Name: Chen, Wei

Abstract: Description (provided by applicant): Technicaldevelopments in high-field magnetic resonance imaging(MRI) and spectroscopy (MRS) have been accelerated be-cause of the advantage of high sensitivity that significantlyimproves the capability and reliability for human applica-tions. This advancement is further stimulated by the uniqueimage contrasts available at high fields for fMRI and clinicaldiagnosis. However, to fully realize the advancement, manychallenges must be resolved. Major problems associated withhigh fields are the difficulty of radiofrequency (RF) coil de-signs and the complex magnetic fields (B1) of RF coil whenthe wavelength of RF wave approaches RF coil’s size. Theyresult in (i) severe degradation of coil quality factor and
NMR sensitivity, (ii) limitation for designing large size coils


with high operating frequency and (iii) complex B1 fielddistributions and difficulty for quantifying MRI intensity.These complications necessitate innovative strategies to over-come the problems associated with RF coils at high fields. Incollaboration with Dr. Yang from Penn State University, acomprehensive project is proposed in this grant applicationfor addressing the RF engineering challenges at high fields.The major goals will focus on (i) developing a host of robustand efficient high-field RF coils for human and animal stud-ies using an innovative design based on the microstrip trans-mission line (MTL) approach, (ii) studying the B1 field be-havior in human head at high fields using computer simula-tion based on RF field modeling and MRI measurements,and studying the implications of B1 field on MRI quantifica-tion, (iii) conducting a series of study for systematicallyevaluating the proposed coils in comparison with other exist-ing coils. Successful outcomes from this research will pro-vide an alternative and satisfactory solution of RF coil de-sign at high fields and result in significant technological ad-vances in high-field RF coil engineering for in vivo MRapplications.

Thesaurus Terms: biomedical equipment development, im-age enhancement, magnetic resonance imaging magneticfield, mathematical model, radiowave radiation bioimaging/biomedical imaging, clinical research, human subject

Institution: University Of Minnesota Twin Cities450 Mcnamara Alumni CenterMinneapolis, MN 554552070

Fiscal Year: 2006Department: RadiologyProject Start: 01-Jul-2003Project End: 30-Apr-2008ICD: National Institute Of Biomedical


BIOMEDICAL IMAGING FOR CLINICIANSCIENTISTS

Grant Number: 5T32EB001631-03PI Name: Coakley, Fergus V.

Abstract: Description (provided by applicant): This applica-tion is to establish a structured intensive one-year trainingprogram in Biomedical Imaging based in the Department ofRadiology at UCSF. The program will be open to Radiologyresidents who are in or have completed training. The primarylong-term objective of this training program is to produce acadre of academic radiologists who will become leaders inBiomedical Imaging, and help address the current lack ofsuch clinical scientific investigators. More specifically, theprogram will recruit candidates who will be mentored by a
designated team of clinical radiologists, basic scientists, and
clinicians. Each trainee will be affiliated with one of the ex-isting sections within the Department of Radiology, and col-laborate as appropriate with researchers from the departmen-tal laboratories and clinicians from other departments. TheDepartment is ideally positioned to provide such a trainingprogram, given the long history of interdisciplinary collabo-ration at UCSF, the depth and diversity of the clinical andresearch faculty within the Department, and the existing highlevel of NIH research funding. Trainees will also be able toavail of exciting new developments in the Department andthe University, including the China Basin extension of theRadiology Department, which will be adjacent to the new43-acre Life Sciences Mission Bay campus of UCSF. Thesenew resources will further increase the ability of the depart-ment and institution to attract researchers and continue thelong tradition of ground breaking, cutting edge BiomedicalImaging at UCSF.


Institution: University Of California SanFrancisco

3333 California St., Ste 315San Francisco, CA 941430962

Fiscal Year: 2007Department: RadiologyProject Start: 01-Jul-2005Project End: 30-Jun-2010ICD: National Institute Of Biomedical


HIGH FIELD MRI: LIMITATIONS ANDSOLUTIONS

Grant Number: 5R01EB000454-05PI Name: Collins, Christopher M.

Abstract: Description (provided by applicant): The long-term objective of this research is to understand and developengineering solutions to the difficulties presented to magneticresonance imaging (MRI) at high magnetic field strength.Specific Aim 1: Develop and validate a methodology to ana-lyze, quantify, and eliminate static field distortion artifactsproduced in high field MR images by regional differences inmagnetic susceptibility. This information will be used to de-velop artifact-correction techniques for high-speed functionalMRI and distortion-free high field MRI of human, animal,and cellular anatomy. Specific Aim 1: Develop and validatemodels and methods to analyze and quantify radio frequency(RF) magnetic field distortions occurring in the human headand body of men, women, children, and fetuses in utero.These analyses will be used to evaluate regional RF power
deposition from specific pulse sequences for patient safety
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and to develop methods to minimize RF inhomogeneity. Inthe spirit of the Bioengineering Research Partnership thisproposal will draw expertise and partnership from the Centerfor Magnetic Resonance Research at the University of Min-nesota (a premiere 7.0 Tesla whole body MRI research facil-ity), REMCOM (a magnetic field modeling software com-pany), and the National High Magnetic Field Laboratory (aNational Research Laboratory incorporating 17.8 Tesla MRImicroscopy and 11.7 Tesla small animal imaging). The re-sults of these studies will aid a wide array of researchers inhigh speed distortion-free functional MRI, anatomical studiesat both low and high field strengths, MR microscopy in ani-mals and intact cells, evaluation of patient safety, and inmany cases, reclaim techniques which have proven problem-atic at high field strengths.

Thesaurus Terms: image processing, magnetic field, mag-netic resonance imaging, method development body region,computer simulation, computer system design /evaluation,functional magnetic resonance imaging, head, model design/development, neuron, patient safety /medical error, radio-wave radiation Aplysia, adult human (21�), bioengineering/biomedical engineering, bioimaging /biomedical imaging,clinical research, human subject, laboratory rat, middle child-hood (6–11), patient oriented research

Institution: Pennsylvania State Univ Hershey MedCtr

500 University DriveHershey, PA 170330850



HIGH RESOLUTION MR IMAGING OFDAMAGED MYOCARDIUM IN PATIENTSWITH ARRHYTHMIA

Grant Number: 1K23EB006481-01PI Name: Desjardins, Benoit

Abstract: Description (provided by applicant): This proposaldescribes a five-year multidisciplinary career developmentprogram, which will enable the Principal Investigator, anMRI and cardiovascular radiologist, to become a productiveindependent patient-oriented investigator in cardiovascularimaging. Cardiac arrhythmias, frequent in patients with isch-emic heart disease, may lead to sudden cardiac arrest, whichclaims over 450 000 lives per year in the US. They can be
prevented by medication, which has a high failure rate and
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frequent toxicity, or corrected by an Implantable Cardio-verter Defibrillator (ICD). 150 000 ICDs were implanted inthe US in 2003, number that is growing every year. ICDshave a significant impact on quality of life, as the dischargefrom an ICD is described as similar to being kicked in thechest by a horse. Radiofrequency ablation under guidance ofcardiac electrical mapping, a therapy rapidly growing in im-portance and popularity, can be used to cure non-life threat-ening arrhythmias, and minimize or even eliminate the pain-ful discharges experienced by patients with prospectiveICDs. The focus of this research is the development and ap-plication of novel magnetic resonance imaging (MRI) tech-niques to improve cardiac ablation therapy. The principalaims are: (1) to develop novel techniques to perform highresolution MRI to assess myocardial damage, (2) to showthat MRI can predict the distribution of abnormalities oncardiac electrical mapping due to myocardial damage, mak-ing cardiac ablation therapy more efficient, and (3) use MRIto characterize the distribution and progression of cardiacablation lesions, in order to predict failure of therapy andcomplications. The career development program has two ma-jor components: a technical component, and a translationalcomponent. The technical component involves the develop-ment of the imaging techniques, to be performed under thementorship of a leading scientist in biomedical imaging. Thetranslational component involves a didactic component, pro-vided by the University of Michigan’s Training Program inClinical Research, which leads to a Masters degree in Clini-cal Research Design and Statistical Analysis, and a clinicalresearch component, that involves the testing of the imagingtechniques in clinical studies in cardiac electrophysiology,under the mentorship of an internationally recognized pio-neer in the field. The program would take place in an envi-ronment which has a long tradition of support for juniorpatient-oriented investigators, and which is at the cuttingedge of both medical imaging and cardiac electrophysiology,with extensive clinical, educational and research resources.Relevance: MRI has the potential to make cardiac ablationtherapy more efficient and to predict failure and complica-tions of this therapy. This can dramatically improve the livesof people with arrhythmias.


Institution: University Of Michigan At Ann Arbor3003 South State Street, Room 1040Ann Arbor, MI 481091274

Fiscal Year: 2006Department: RadiologyProject Start: 01-Aug-2006Project End: 31-Jul-2011ICD: National Institute Of Biomedical

IRG: ZEB1


MONTE CARLO SIMULATION OF HIGHENERGY PHOTON IMAGING

Grant Number: 5R01EB001994-07PI Name: Dewaraja, Yuni K.

Abstract: Description (provided by applicant): The broadlong-term objective of this work is to substantially improveimaging, quantification and dosimetry of high-energy single-photon emitters imaged with gamma cameras. A specific long-term objective is to verify the hypothesis of a highly significantcorrelation between tumor regression and calculated tumor radi-ation absorbed dose in two radionuclide therapies 1) 1-131 anti-B1 radioimmunotherapy (RIT), and 2) 1-131 metaiodobenzyl-guanidine (MIBG) therapy. At our institution, a phase II 1-131labeled anti-B1 RIT trial for follicular lymphoma, showed a97% response rate and a 63% complete response rate. The suc-cess of 1-131 RIT and MIBG therapy has renewed interest in1-131 imaging for accurate internal dose estimates. During theprevious period a Monte Carlo code for modeling single-photonimaging of I-131 was optimized and validated. Simulation stud-ies demonstrated the current limitations to accurate I-131 activ-ity quantification using single photon computed tomography(SPECT). The focus for the next period will be on using MonteCarlo to develop highly patient-specific methods that will sig-nificantly improve the two main steps in tumor/organ dosime-try: activity quantification and absorbed dose calculation. Thepatient-specific methods will be implemented by integratinginformation from SPECT and co-registered CT. Specifically wepropose to implement 1) patient-specific partial volume correc-tion; 2) a Monte Carlo based forward projector, which includespatient-specific scatter; 3) 3-D patient-specific dose estimation.In addition, we will continue evaluation of a 3D OSEM recon-struction, which includes detector response and we will generatedata for a multi-center evaluation of conjugate-view activityquantification methods. The work will culminate with phantomstudies that establish the optimum methods for 1-131 SPECTquantification and dose estimation and with the application ofthe methods to existing RIT patient data to possibly reveal astatistically significant relationship between dose and tumor vol-ume reduction. In addition, we will attempt to correlate newlyavailable parameters from the 3-D dosimetry, such as dose non-uniformity and minimum dose, with tumor volume reduction. Astrong dose-response relationship has not yet been demonstratedin any 1-131 RIT clinical study possibly due to poor dose esti-mation. Here we propose to combine and expand many tools tosignificantly improve the estimate and make advances towardsindividualized treatment planning.


Institution: University Of Michigan At Ann Arbor3003 South State Street, Room 1040Ann Arbor, MI 481091274

Fiscal Year: 2006

Department: RadiologyProject Start: 01-Apr-1999Project End: 05-Jul-2007ICD: National Institute Of Biomedical


FUNCTIONAL NEUROIMAGING OFVISUAL CORTEX

Grant Number: 5R01EB000843-13PI Name: Deyoe, Edgar A.

Abstract: Description (Provided by applicant): The long-range goal of this continuing project is to develop and applythe technology of functional magnetic resonance imaging(FMRI) to the study and characterization of neural mecha-nisms responsible for normal visual perception and attention.The project will concentrate on developing a set of neuro-physiological principles that characterize the attention-relatedcontrol of cortical visual processing in humans. (1,2) In apair of initial experiments, two fMRI-based measures ofcortical activity will be critically evaluated for their abil-ity to accurately reflect the behavioral effects of attention.We will examine the ability of these measures to accu-rately depict the intensive and topographic properties ofattention under three different types of attention-intensivetasks: absolute detection, increment detection and featureconjunction detection. We hypothesize that these measureswill reflect the specific attentional demands of the tasks.(3) Next, these measures will be used to observe the “top-down” effects of volitional control of attention, first inisolation, then in conjunction with the bottom-up influ-ences of single and multiple objects in the field of view.A novel method for visualizing the “attentional field” willbe introduced. (4) In a fourth set of experiments, this ap-proach will be used to test the hypothesis that attentiontopography can reflect both spatial and object-relatedcharacteristics of the visual display. The latter will betested with occlusion, color, and stereoscopic cues for ob-ject segmentation to determine if the induced attentionaltopography is cue-invariant. (5) An experiment based on“attentional crowding” will be used to identify the corticalsite (or sites) of attentional selection. (6) In a final study,we examine the effects of attending to different spatialreference frames (retinal vs object-oriented) on corticalactivity. We hypothesize that occipital visual areas will beunaffected by the subject’s reference frame but that por-tions of parietal and/or frontal cortex will be affected. To-gether, the results of these studies will significantly ad-vance our understanding of the neurophysiological basisof visuospatial attention and the mechanisms controlling
the access of visual information to conscious awareness.
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Thesaurus Terms: attention, brain mapping, functionalmagnetic resonance imaging, neural information process-ing, vision disorder, visual cortex, visual perception bio-medical equipment development, form /pattern perception,neurophysiology, space perception, visual stimulus behav-ioral /social science research tag, bioimaging /biomedicalimaging, clinical research, computer program /software,human subject

Institution: Medical College Of Wisconsin8701 Watertown Plank RdMilwaukee, WI 532260509

Fiscal Year: 2006Department: RadiologyProject Start: 01-Jul-1993Project End: 31-Mar-2008ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: VISB

DYNAMIC MRI FOR MYROCARDIALPERFUSION AND VIABILITY

Grant Number: 5R01EB000177-04PI Name: Di Bella, Edward Vr.

Abstract: Description (provided by applicant): This proposalseeks to improve the accuracy of noninvasive diagnosis andprognosis of coronary artery disease by using MRI and agadolinium-based paramagnetic contrast agent. First-passMRI with the modeling methods proposed here may be ableto provide absolute regional blood flows at a high spatialresolution. These first-pass studies may also offer uniqueviability information. The specific aims are (1) To developand optimize acquisition strategies to obtain data tailored forcompartmental modeling (2) To develop clinically practicalmethods for analyzing the cardiac contrast MRI data withmodels (3) To compare the flow estimates from the MRImethods developed here to an MRI upslope perfusion indexand to absolute blood flow measurements obtained with dy-namic N-13-ammonia PET. (4) To add viability measuresfrom the first pass modeling approach to delayed images todetermine if such an approach improves prediction of viabil-ity. Methods: (1) Systematic analysis of temporal samplingstrategies and the use of reduced k-space acquisitions to in-crease volume coverage, reduce artifacts, and maintain signaland high spatial resolution will be pursued using realisticcomputer simulations and human studies. (2) Linked activecontours combined with temporal clustering methods will bedeveloped to automatically segment the endocardium andepicardium in the time series data. Methods for blind identi-fication of the input function (input functions are inaccurateat high gadolinium concentrations) will be developed and
validated. Two different physiological models will be devel-
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oped and compared in their ability to provide absolute flowvalues and reliable extracellular volume estimates. (3) Thecomparisons with MRI upslope and PET perfusion will beperformed using 34 human studies. (4) The first-pass viabil-ity measures and three integrated viability measures will becompared to delayed enhancement Gd MRI images and topost-revascularization data in 17 patients. The outcome ofthis project will be validated imaging protocols and softwarefor use with first-pass MRI studies, and practical and accu-rate methods for myocardial perfusion and viability assess-ment in vivo. Such methods will be invaluable for improvedhealth care and for improved basic science research, such astracking nascent flow changes in gene therapy.

Thesaurus Terms: coronary disorder, diagnosis design/evaluation, heart imaging /visualization /scanning, magneticresonance imaging angiocardiography, computer assisted di-agnosis, contrast media, diagnosis quality /standard, heartdisorder diagnosis, image enhancement, noninvasive diagno-sis, perfusion bioimaging /biomedical imaging, blood flowmeasurement, clinical research, human subject, patient ori-ented research, positron emission tomography

Institution: University Of Utah75 South 2000 EastSalt Lake City, UT 84112

Fiscal Year: 2006Department: RadiologyProject Start: 07-Apr-2003Project End: 30-Jun-2007ICD: National Institute Of Biomedical


SUB-VOXEL TISSUE CHARACTERIZATIONWITH IN-VIVO MRI

Grant Number: 5R01EB001744-04PI Name: Does, Mark D.

Abstract: Description (provided by applicant): The overallaims of this project are to develop and implement novelmethods for quantitative, in vivo characterization of tissue bymagnetic resonance imaging (MRI). The microscopic com-partition of water in tissues reflects potentially importantstructural properties that may be probed by diverse MRImeasurements. In particular, water diffusion and nuclearmagnetic resonance (NMR) relaxation cannot be describedby single components in many tissues. With some limitedsuccess, multiple component characterization of these at-tributes has been proposed and studied in an attempt to ex-tract specific information about the micro-anatomical watercompartments from which they are derived. The further de-velopment of efficient and effective methods for acquiring
and analyzing subvoxel characteristics promises to be useful


for assessing structure and pathophysiology in various tis-sues, particularly nerve and muscle. The studies proposedherein will provide faster, more accurate, and more informa-tive techniques for compartmental studies using MRI. Exper-imental studies on model tissues will establish comprehen-sive and quantitative in vivo descriptions of water diffusion,longitudinal relaxation and transverse relaxation, and howthey correlate to each other and the physical compartmentsfrom which they are derived. These observations will then beused to design novel MRI methods, which are more specificfor depicting tissue microstructure in vivo. One example,amongst others, is the aim to develop rapid and easily imple-mented MRI methods of visualizing and quantifying myelincontent in the brain based on detailed compartmental modelsof relaxation and diffusion in white matter.

Thesaurus Terms: magnetic resonance imaging, relaxationspectrometry, technology /technique development body wa-ter, brain imaging /visualization /scanning, myelin, nuclearmagnetic resonance spectroscopy, structural biology bioimag-ing /biomedical imaging, laboratory rat

Institution: Vanderbilt UniversityMedical CenterNashville, TN 372036869

Fiscal Year: 2006Department: Radiology & Radiological ScisProject Start: 30-Sep-2003Project End: 31-Jul-2008ICD: National Institute Of Biomedical


IMPROVEMENTS IN SPIRAL MRIMAGING

Grant Number: 5R01EB004637-03PI Name: Duerk, Jeffrey L.

Abstract: Description (provided by applicant): Using a state-of-the-art 1.5T MR system, the main goal of the proposedproject is to create significant improvements in spiral MRIvia novel techniques that reduce imaging time, improve im-munity to motion artifact, and improve off-resonance (andchemical shift) reconstruction so that new and/or improvedcardiac, brain and body imaging applications will be en-abled. The specific aims are to: (1) improve spiral MR mo-tion artifact immunity by developing efficient reductions inspiral MRI acquisition time through parallel imaging meth-ods and reconstruction (e.g., SENSE, GRAPPA, conjugategradient) at high acceleration; (2) develop new rapid off-resonance correction techniques with improved performanceand reduced computation time when compared to conven-tional frequency segmented methods, (3) create robust spiral
fat/water separation methods that prevent off-resonance blur-
ring and provide superior performance and reduced acquisi-tion time when compared to spatial spectral techniques, and,(4) develop methodologies for Pareto-optimal /(-space trajec-tory design based on minimizing time, aliasing energy, flowsensitivity, off-resonance blurring and/or other image qualitymeasurements. Our project will show that use of new spiralacquisition, new post-processing methods and new trajectorydesign techniques using/(-space and/or image data can re-duce imaging time and significantly improve cardiac, brainand abdominal imaging. Preliminary results show that signif-icant improvements in motion immunity through parallel im-aging are possible. Significant work remains to explore im-provements in reconstruction algorithms, amount of accelera-tion, and reliability. Off-resonance computational burden canbe reduced by using a block regional correction method. Forexample, further improvements in performance and speedwill explore use of regional information to control the com-putational block size. Our fat suppression methods will giverise to reductions in scan time by up to a factor of 2-4Xwith superior performance as compared to commonly usedspatial spectral approaches; the efficiency/robustness of 2ptand 3pt Spiral Dixon methods (at equal scan time) are ex-plored. These alone will enable improved abdominal andcardiac imaging when compared to conventional rectilinearor spiral methods. Uniquely, our advanced non-rectilineartrajectory, design method is that the inter-relationship be-tween off-resonance, motion and kappa-space sampling den-sity effects are formally linked to image domain artifacts,thereby enabling unique waveform parameterizations andformal optimization to create superior trajectories (and hencebetter images) than those designed conventionally. We be-lieve successful attainment of these aims will give rise tosignificant improvements in spiral MR and hence greaterutilization of this important MR method.

Thesaurus Terms: computer program /software, image pro-cessing, magnetic resonance imaging abdomen, adipose tis-sue, brain imaging /visualization /scanning, computer simula-tion, evaluation /testing, functional magnetic resonance imag-ing, heart imaging /visualization /scanning, imageenhancement bioimaging /biomedical imaging, clinical re-search, human subject

Institution: Case Western Reserve University10900 Euclid AveCleveland, OH 44106

Fiscal Year: 2007Department: RadiologyProject Start: 15-Sep-2005Project End: 31-Jul-2009ICD: National Institute Of Biomedical

IRG: BMIT
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BIOIMAGING AND INTERVENTION INNEOCORTICAL EPILEPSY

Grant Number: 5R01EB000473-05PI Name: Duncan, James S.

Abstract: Description (provided by application): Magneticresonance functional and spectroscopic imaging (fMRI,MRS) of the brain provides tremendous opportunities in thestudy and treatment of epilepsy. In neocortical epilepsy,where the epileptogenic region is highly variable in size,structure and location, deeper insight into the biochemicaland functional characteristics of the region and surroundingtissue may provide critical data to assist the neurosurgeonand neurologist in localization and treatment. To fully utilizethe multiple forms of information (MR and EEG), these datamust be transformed into a common space and integratedinto the intraoperative environment. We will develop highresolution MRS and fMRI at 4T and advanced analysis andintegration methods to better define the epileptogenic tissueand surrounding regions, and enhance our understanding ofthe biochemical mechanisms underlying the dysfunction inneocortical epilepsy. We will validate these measurementsagainst the gold standard of intracranial electrical recording.These goals will be achieved in this bioengineering researchpartnership (BRP) by bringing together six partners from 3academic institutions (Yale (lead institution), Albert Einsteinand the Univ. of Minnesota) and 1 industrial partner(Medtronics SNT) to carry out four integrated programs ofscientific investigation and bioengineering development inthe area of bioimaging and intervention: 1) development ofhigh resolution fMRI and MRS at 4T for the study of epi-lepsy; 2) investigation with MRS of the relationship betweenneuronal damage or loss through the measurement ofN-acetylaspartate (NAA), alterations in neurotransmitter me-tabolism through the measurement of gamma amino butyricacid (GABA) and glutamate, and abnormalities in electricalactivity in the epileptogenic region and surrounding tissue;3) investigation of the relationship between fMRI activationamplitude and the cognitive task, underlying cortical struc-ture, cortical metabolic state, and physiology, and the impactof epilepsy on these factors; 4) development of integrationmethodologies for fusing multimodal structural and func-tional (image- and electrode-derived) information for thestudy and treatment of epilepsy. We anticipate that by devel-oping and integrating these high resolution functional andmetabolic images of neocortical epilepsy, we will improveour understanding and treatment of this difficult disorder.The first year’s effort will include high resolution coil andintegrated software platform design and development, as wellas the acquisition of normal control studies. In years 2through 5, the coils will be incorporated into the MR imag-ing platforms, the software platform will be fully developed
and hypotheses related to the biochemical makeup of neocor-
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tical epileptogenic tissue and its relation to brain functionwill be evaluated.

Thesaurus Terms: brain imaging /visualization /scanning,brain mapping, epilepsy, functional magnetic resonance im-aging, neocortex, nuclear magnetic resonance spectroscopy,technology /technique development aspartate, biomedicalequipment development, brain disorder diagnosis, cognition,computer data analysis, computer program /software, com-puter system design /evaluation, electrophysiology, imageprocessing, method development, neural degeneration, neuro-physiology, neurotransmitter metabolism bioengineering /bio-medical engineering, bioimaging /biomedical imaging, elec-troencephalography, human subject, patient oriented research

Institution: Yale University47 College Street, Ste 203New Haven, CT 065208047

Fiscal Year: 2006Department: Diagnostic RadiologyProject Start: 15-Apr-2002Project End: 15-Apr-2007ICD: National Institute Of Biomedical


IMAGE ANALYSIS FOR ADAPTIVEPROSTATE RADIOTHERAPY

Grant Number: 5R01EB002164-06PI Name: Duncan, James S.

Abstract: Description (provided by applicant): More pre-cisely delivering higher doses to the target volume at eachtreatment fraction, while limiting exposure to surroundingnormal tissue, is the key goal for external beam prostate ra-diotherapy. Efforts to quantitatively assess this process haveshown that a variety of uncertainties in the treatment setupincluding patient positioning, patient organ motion, charac-teristics of the treatment beam and operator variability issuesmake achieving this goal difficult. Previous efforts on thisgrant and by others have attempted to use the registration ofplanning day 3D computed tomographic images and intra-treatment megavolt portal images to try to account for someof these uncertainties, sometimes augmented by ultrasoundimaging to try to estimate organ motion. While results are attimes promising, these technologies are limited in their util-ity. Furthermore, while the ability to deliver more precisely-shaped plans has advanced significantly due to the advent ofintensity modulated radiotherapy (IMRT) systems, the ad-vanced development of image-guidance systems necessary toaccurately deliver these more complex plans has been lack-ing. However, IMRT treatment systems with kilovolt (kV)3D cone-beam CT (3DCBCT) imaging on the same platform
have been developed, promising high quality imaging of


both bone and soft tissue at each treatment fraction. We pro-pose here to develop an advanced image analysis strategythat will permit the fully automatic nonrigid registration ofplanning day 3DCT images to 3DCBCT images acquired ateach treatment day, while simultaneously and automaticallysegmenting the prostate, rectum and bladder in the treatmentimages. It is our view that this will ultimately facilitate theoptimal, image-guided adaptation of an initial plan to eachtreatment day image, taking full advantage of these high res-olution datasets. The approach will be validated using im-ages formed from simulated deformations and evaluated us-ing sets of patient images acquired at two different facilitiesover 6 weeks of treatment.

Thesaurus Terms: image guided surgery /therapy, neoplasm/cancer radiation therapy, prostate neoplasm, therapy design/development, three dimensional imaging /topography bio-medical automation, bladder neoplasm, image processing,neoplastic transformation, rectum neoplasm bioimaging /bio-medical imaging, clinical research, human subject, male, pa-tient oriented research

Institution: Yale University47 College Street, Ste 203New Haven, CT 065208047

Fiscal Year: 2006Department: Diagnostic RadiologyProject Start: 03-Feb-2000Project End: 30-Jun-2009ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: BMIT

RESEARCH TRAINING IN NUCLEARMOLECULAR IMAGING

Grant Number: 5T32EB001632-05PI Name: Fischman, Alan J.

Abstract: Description (provided by applicant): The purposeof the program here proposed is to provide training experi-ence in the techniques of nuclear/molecular imaging researchas well as a working knowledge of related nuclear medicalscience to physicians who wish to become researchers inmolecular imaging with radioisotopes. Physicians who aretrained in these areas will be in the best position to definethe future research directions in the field. The proposed pro-gram includes formal training in the fundamentals of nuclearmedical science, advanced formal training in selected areasdefined by the trainee’s interests and goals and an extendedresearch experience in the form of a mentored researchproject, or projects, that will span his/her tenure in the pro-gram. The proposed training program will be based in Har-vard Medical School’s Joint Program in Nuclear Medicine.
This program encompasses Nuclear Medicine and related
activities in six major Harvard teaching hospitals as well asthe University itself. The joint program and its affiliates in-cludes a nuclear medicine residency program as well as sev-eral NIH training programs for scientists as well as graduatestudents thereby giving trainees in the proposed program alarge pool of peers with whom to share experience andknowledge. The program faculty consisting of 29 active re-searchers and practitioners is a unique resource for the train-ing of physician-researchers. These faculty supervise a num-ber of federally funded research programs in which traineesmay participate. The training experience is expected to ex-tend over two years. Three positions are requested during thefirst year with a total of six trainee slots requested duringyear 2 through year 5. The resources available to the pro-posed program through the Harvard Medical School JointProgram in Nuclear Medicine are unique in terms of facultysize, extent of research activities and teaching/ mentoringexperience of the faculty.


Institution: Harvard University (Medical School)Medical School CampusBoston, MA 02115

Fiscal Year: 2007Department: RadiologyProject Start: 16-Sep-2003Project End: 30-Jun-2008ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: ZGM1

SIMULANEOUS DUAL ISOTOPE SPECTW/CROSS TALK CORRECTION

Grant Number: 5R01EB000288-07PI Name: Frey, Eric C.

Abstract: Description (provided by applicant): One uniquefeature of SPECT is the ability to use two pharmaceuticalslabeled with different isotopes emitting photons with differ-ent energies to make simultaneous measurements of differentphysiological processes. Simultaneous acquisition of projec-tion data from two isotopes has the advantage that it allowsmeasurement of two potentially related processes (e.g., restand stress perfusion or perfusion and receptor density) at thesame time. This may add additional diagnostic informationand, in addition, there are practical advantages such as in-creased patient throughput, elimination of problems with reg-istration and results in common patient motion in the twostudies. However, due to scatter in the patient and gammacamera and the poor energy resolution of conventionalgamma cameras, dual isotope acquisition will result in cross
talk contamination of the two sets of projection data. In this
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work we hypothesize that we can develop methods for si-multaneously acquiring and reconstructing dual isotope im-ages that can reduce the effects of this cross talk to the pointwhere the images have diagnostic image quality close to thatwhich they would have if acquired separately. We have cho-sen to focus on two specific applications: dual isotope Tc-99m/ TI-201 stress/rest myocardial perfusion SPECT anddual isotope Tc-99m/I-123 brain SPECT, with major empha-sis on Tc-99m/TI-201 imaging. Toward this end we proposeto: (1) Develop methods for optimizing and evaluating si-multaneous TI-201/Tc-99m imaging (2) Develop and imple-ment improved cross talk compensation methods for simulta-neous dual isotope SPECT (3) Develop optimized acquisitionmethods for Tc-99m/TI-201 myocardial perfusion SPECT;(4) To evaluate these methods using simulated data andmathematical observers; (5) To evaluate simultaneous dualisotope Tc-99m/I-123 SPECT using phantom experimentsand quantitative measures of image quality; and (6) To per-form a clinical evaluation of simultaneous and separate ac-quisition of dual isotope rest/stress myocardial perfusionSPECT. Given the frequency with which this procedure isperformed and the significant improvement in both patientcomfort and clinical throughput, we believe this would havea substantial impact on clinical practice. We also will havedeveloped techniques for simultaneous Tc-99m/I-123 brainimaging that may prove important as new I-123 and Tc-99mlabeled brain agents are developed and marketed.

Thesaurus Terms: image enhancement, method develop-ment, single photon emission computed tomography brainimaging /visualization /scanning, diagnosis design /evalua-tion, heart imaging /visualization /scanning bioimaging /bio-medical imaging, clinical research, human data


Fiscal Year: 2004Department: Radiology And Radiological SciencesProject Start: 01-Feb-1999Project End: 31-Jan-2008ICD: National Institute Of Biomedical


MULTIDISCIPLINARY TRAININGPROGRAM IN HUMAN IMAGING

Grant Number: 5T32EB000817-04PI Name: Fullerton, Gary D.

Abstract: The goal of this proposal is to develop a Multidis-ciplinary Human Imaging (MDHI) research training programthat integrates the investigational activities of physician, im-
aging scientist and medical physicist teams working on basic
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science and patient oriented clinical investigations of the ex-ceptional health needs of the predominantly Hispanic SouthTexas community. We accomplish this goal with three spe-cific aims: (1) develop a rigorous recruiting and mentoringprogram for physicians and imaging scientists training inbiomedical imaging of humans and/or animal models of hu-man disease, (2) expand and build on the success of ourgraduate program in Radiological Sciences by extension ofthe new Resident MD/PhD (R-MD/PhD) track in HumanImaging to include clinical studies arising from the ResearchImaging Core of the Frederic C. Bartter General ClinicalResearch Center (GCRC) and (3) increase the numbers ofethnically diverse students, particularly Mexican-Americansand other Hispanic groups, trained in the conduct of humanimaging research. A distinguishing feature of the program isdirect integration of Ph.D. graduate research education andclinical resident training in the same academic curriculum.Resident MD/PhD students from multiple medical schooldepartments join the pre-existing graduate program for medi-cal physics and radiation biology. MDHI students are men-tored by a network of established investigators (many withNIH funding) through collaborations fostered by five HumanImaging Research Mentorship Cores. The research cores pro-vide infrastructure that bridges the gulfs between basic sci-ence research, translational research and patient clinical care.The Candidate Selection and Advisory Committee (CSAC)consists of 15 senior investigators from the Medical, Gradu-ate and Dental Schools with strong interest in applying bio-medical imaging research methods. The CSAC selects MDHIrecipients and evaluates the performance of both the studentsand their junior faculty mentors. Trainees supported by theMDHI Program will be expert in the design and conduct ofbiomedical imaging research involving direct interactionsbetween investigators and human subjects. The MDHI Pro-gram promotes fundamental discoveries in biomedical imag-ing by fostering an integrated and coordinated program ofresearch and research training that can be applied to a broadspectrum of biological processes, disorders and diseases andacross organ systems.


Institution: University Of Texas Hlth Sci Ctr SanAnt

San Antonio, TX 78229Fiscal Year: 2007Department: RADIOLOGYProject Start: 01-SEP-2004Project End: 31-AUG-2009ICD: NATIONAL INSTITUTE OF

BIOMEDICAL IMAGING ANDBIOENGINEERING

IRG: ZRG1

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Abstracts of Funded National Institutes of Health Grants

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