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 ofradiology. These abstracts are listed on the NIH Web page (http://www-commons.cit.nih.gov/crisp/) and are printed hereverbatim.

The grant identification number (eg, 1R01AI12345-01) contains a three-digit activity code (in the previous example, R01)that identifies a specific category of extramural activity. All current NIH activity code titles and definitions can beobtained at the NIH 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)refers to the NIH funding source.

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

National Institute of DrugAbuse

Grant Number: 1R21DA021034-01PI Name: Avison, Malcolm J.

Abstract: Prenatal cocaine (PNCE) and alcohol exposure(PNAE) result in sustained behavioral deficits similar inmany respects to attention deficit hyperactivity disorder(ADHD). While this similarity suggests the involvement ofsimilar or overlapping neural circuits in all three groups,subtle differences in the specific deficits and their differentialresponsiveness to stimulants suggest differences in the natureof the disruptions within a specific circuit and/or disruptionsin non-overlapping circuits. Studies in animals suggest thatPNCE results in a post-synaptic defect in dopamine (DA)neurotransmission that is refractory to stimulants, such asamphetamine (AMPH) or methylphenidate (MPH). In humanstudies, the data are less clear, reflecting, at least in part, thedifficulty of identifying subjects with pure PNCE or PNAE,and, in part, the fact that tools for measuring circuit functionhave only recently become available. This project will bringtogether three groups of researchers with expertise in devel-opmental consequences of alcohol and cocaine exposure inutero, functional and structural neuroimaging, and ADHD,with the overarching goal of characterizing the neural corre-lates of ADHD behaviors in PNCE and PNAE individuals,using a combination of detailed neurocognitive testing, ERP,and functional, structural, and diffusion tensor (DTI) MRI.
We will study a well characterized cohort of 18-year-old,
African American adolescents, whose PNCE and PNAEwere ascertained prospectively during gestation. This cohortis unique in that recruitment was stratified to minimize theconfounding of alcohol and cocaine. The study has the fol-lowing Specific Aims: 1) To use fMRI to confirm that indi-viduals with PNCE, PNAE, and idiopathic ADHD have afunctional impairment in fronto-striatal circuits and that addi-tional circuit dysfunctions contribute to behavioral deficits inPNAE; 2) To test the hypothesis that the circuit defect inPNCE-associated ADHD is postsynaptic and, therefore, unre-sponsive to MPH; 3) To use structural MRI and DTI to ex-amine the contribution of structural abnormalities to thefunctional impairment in neural circuitry linked to ADHD-related deficits; 4) To identify the neural correlates of dys-calculia in individuals with PNAE and test the hypothesisthat PNAE is characterized by a specific deficit in activationof parietal networks subserving number processing.

Thesaurus Terms: alcoholism/alcohol abuse, attention defi-cit disorder, brain electrical activity, cocaine, drug abuse,embryo/fetus toxicology, mental health epidemiology, neuro-psychology, neurotoxicology African American, adolescence(12–20), brain disorder diagnosis, brain imaging/visualiza-tion/scanning, brain mapping, child behavior, developmentalneurobiology, early experience, longitudinal human study, neu-ral transmission behavioral/social science research tag, clinicalresearch, diffusion magnetic resonance imaging, functionalmagnetic resonance imaging, human subject, interview

Institution: Vanderbilt UniversityMedical Center
Nashville, TN 372036869
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http://www-commons.cit.nih.gov/crisp/

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

NIDA Academic Radiology, Vol 14, No 8, August 2007

Fiscal Year: 2005Department: Radiology & Radiological ScisProject Start: 30-Sep-2005Project End: 31-Aug-2008ICD: National Institute On Drug AbuseIRG: ZDA1

DOPAMINE D3 RECEPTOR IMAGINGAGENTS FOR PET AND SPECT

Grant Number: 5R21DA016181-04PI Name: Mach, Robert H.

Abstract: Description (provided by applicant): Over the pastfifteen years there has been a tremendous amount of researchconducted in the development of PET and SPECT radiotrac-ers for studying dopamine D2 receptor function in vivo. Thisresearch has been largely driven by the availability of anumber of antipsychotics possessing a high affinity for dopa-mine D2 receptors, and the alteration of D2 receptor densityidentified in postmortem brain samples from a variety ofCNS disorders including schizophrenia, Parkinson’s disease,Alzheimer’s Disease, and substance abuse. However, theradiotracers that have been developed to date are not capableof discriminating between the different subtypes of the D2-class of receptors. For example, [11C]raclopride and[123I]IBZM bind with high affinity to dopamine D2 and D3receptors, and [11C/18F]N-methylspiperone binds potently toD2, D3 and D4 receptors. Therefore, measurement of “D2receptor binding potential” obtained with these radiotracersconsists of a composite of D2, D3, and, in the case of N-methylspiperone, D4 receptor density. Within the D2-class ofreceptors, a great deal of experimental evidence suggests thatthe D3 receptor plays a critical role in a number of CNSdisorders. Furthermore, a number of recent studies suggestthat there are differences in the regulation of D2 and D3 re-ceptors in schizophrenia, Parkinson’s disease, and cocaineabuse. Therefore, the development of radiotracers having ahigh affinity for D3 versus D2 receptors, and vice versa,would be of tremendous interest to the PET and SPECT re-search community. Over the past six years, our group hassynthesized a number of heterocyclic and benzamide ana-logues having a high affinity and modest selectivity for D2versus D3 receptors. The function of this R21/R33 researchproject is to develop PET and SPECT radiotracers, selectivefor the D3 receptor, based on these lead compounds. Thegoal of the R21 component of this project is to synthesizeand characterize in vitro putative PET and SPECT radiotrac-ers. Once potential radiotracers are identified, a series of de-tailed in vitro and in vivo studies will be conducted in theR33 Phase of the project as part of the ligand validation pro-cess. The goal of this research project is to develop one PETand one SPECT radiotracer that can be used in functional
imaging studies of the D3 receptor in vivo. A secondary goal
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of this project is to develop an iodine-125 labeled radiotracerfor in vitro binding studies of the D3 receptor.

Thesaurus Terms: dopamine receptor, imaging/visualiza-tion/scanning, positron emission tomography, radiotracer,single photon emission computed tomography central ner-vous system disorder, receptor binding, receptor expressionMacaca, Sf9 cell line, animal tissue, bioimaging/biomedicalimaging, cell line, laboratory rat

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

Fiscal Year: 2005Department: RadiologyProject Start: 30-Sep-2002Project End: 31-May-2007ICD: National Institute On Drug AbuseIRG: ZRG1

PEDIATRIC FMRI TECHNOLOGYDEVELOPMENT

Grant Number: 5R21DA015900-03PI Name: Stenger, Victor Andrew

Abstract: Description (provided by applicant): Disturbancesin the neural circuitry underlying reward processing and de-cision making are likely to be associated with an increasedrisk common emotional and addictive disorders that havetheir origins in childhood and adolescence. These disordersinclude depression and alcohol and nicotine abuse and de-pendence. It has now become possible to use fMRI to inves-tigate this neural circuitry, together with its developmentaltrajectory and relationship with critical key physiologicalevents such as puberty. However, these studies are severelyhampered by critical methodological limitations, includingthe presence of magnetic susceptibility effects resulting insignal loss in many key brain regions (ventral striatum,amygdala, orbital frontal cortex), as well as issues related tothe cross registration of sub-cortical and orbital frontal brainregions to facilitate the analysis of within and between groupcomparisons. In the present application, our multidisciplinarygroup of investigators will tackle these technical limitationsand develop and validate solutions designed to improve ourability to investigate this brain circuitry and its developmentin healthy as well disordered groups of children and adoles-cents. We will optimize a rapid event-related Reward Con-tingent Decision (RCD) paradigm for acquisition of data inchildren and adolescents. We will also develop a whole-braindata acquisition method for rapid event-related pediatricfMRI at 3T that is robust to susceptibility artifacts by com-bining 3D tailored RF pulse excitations with SENSE acquisi-
tions. Finally, we shall develop a novel volumetric image,

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deformable registration algorithm especially for deep sub-cortical gray matter structures such as the amygdala and thebasal ganglia, including nucleus accumbens. The long termgoals of this research are to take maximal advantage of theopportunity provided by event- related fMRI to achieve abetter understanding of the development of neurobehavioralsystems of reward that influence decision-making and riskappraisal in adolescence, achieve a more mechanistic under-standing of the emergence of sensation seeking, risk-taking,and reckless behavior during adolescent development, and touse these methodological advances in fMRI to provide amore powerful cognitive neuroscientific framework for ourongoing developmental and clinical investigations into emo-tional and substance-use problems emerging during adoles-cence.

Thesaurus Terms: adolescence (12–20), child (0–11), childbehavior, decision making, functional magnetic resonanceimaging, neural information processing, neuroanatomy, neu-ropsychology, technology/technique development amygdala,basal ganglia, brain mapping, nucleus accumbens behavioral/social science research tag, bioimaging/biomedical imaging,clinical research, human subject

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

Fiscal Year: 2004Department: RadiologyProject Start: 27-Sep-2002Project End: 30-Jun-2006ICD: National Institute On Drug AbuseIRG: ZRG1

NEUROMAGING OF NICOTINEWITHDRAWAL

Grant Number: 5K08DA015051-03PI Name: Tanabe, Jody L.

Abstract: Description (provided by applicant): Most smok-ers in this country attempt to quit because of concerns abouthealth. However, more than half of those who smoke onepack per day or more fail to quit or even cut back on smok-ing. Contributing to relapse is the desire to alleviate with-drawal, which has been clearly established and related tonicotine. Withdrawal has two components: somatic and af-fective. Avoidance of negative affective symptoms is thoughtto play a bigger role in relapse than avoidance of somaticsymptoms, yet little is known about the physiology or spe-cific brain regions that mediate affective components of nic-otine withdrawal. The mesolimbic dopamine system is in-volved in positive reinforcement, but its role in withdrawal is
poorly understood. Furthermore, somatic withdrawal in ani-
mals cannot be equated with mood in humans. Localizingbrain regions involved in withdrawal in humans will provideuseful information for understanding mechanisms of and di-recting therapy aimed at preventing relapse. The trainingplan outlined in this proposal will give me the skills neededto become an expert in neuroimaging of substance abuse,specifically the effects of nicotine on the brain. I will trainunder distinguished scientific mentors known for their re-search on the biology and genetics of nicotinic receptors andbehavioral pharmacology of substance abuse. The proposedwork represents a qualitatively different phase in my re-search development that complements the skills I have al-ready acquired in advanced MR neuroimaging techniques. Atthe end of this training period, I will be able to conduct in-dependent research in neuroimaging of substance abuse. Thescientific hypothesis tested by this research is that acute nic-otine withdrawal will be associated with changes in cerebralblood flow in mesolimbic dopaminergic brain regions. Thehypothesis will be tested using MR arterial spin labelingmethods to measure changes in cerebral blood flow (CBF)during acute withdrawal and correlating these changes withmood. Three specific aims are: i) Do CBF measurementsprovide an in vivo marker for symptoms of acute nicotinewithdrawal in smokers? ii) Does acute nicotine withdrawalinvolve dopaminergic system or non-dopaminergic regions?iii) Does nicotine replacement reverse the alterations in CBFduring nicotine withdrawal?

Thesaurus Terms: brain imaging/visualization/scanning,brain mapping, drug withdrawal, functional magnetic reso-nance imaging, nicotine, smoking cessation biomarker,brain circulation, dopamine bioimaging/biomedical imag-ing, clinical research, human subject, young adult human(21–34)

Institution: University Of Colorado Denver/HscAurora

Grants And Contracts, Mail Stop F428Aurora, CO 800450508

Fiscal Year: 2005Department: RadiologyProject Start: 20-Sep-2003Project End: 31-Jul-2008ICD: National Institute On Drug AbuseIRG: NIDA

HUMAN IMAGING RESEARCH INNEUROPSYCHIATRY AND DRUG ABUSE

Grant Number: 2K24DA000412-06PI Name: Wong, Dean F.

Abstract: Description (provided by applicant): This is a
competitive renewal of my five year grant, K24 DA00412.
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I have progressed in the three key areas for the K24award including mentorship, especially of patient-orientedresearch, research development, and career development. Ihave had the privilege of mentoring both physicians andbasic scientists, working in the area of patient-orientedresearch from fields such as psychiatry, radiology, andneurology. This has been formalized in my role as ViceChair for Research Administration and Training, where Imaintain a website for grant information and routinelyassist young investigators in their grant submissions andresearch issues. My laboratory has grown and I have ex-panded NIDA related research from drug development andcocaine craving to also include alcoholism, Tourette Syn-drome and Restless Legs Syndrome. I obtained a secondNCRR funded Shared Instrumentation Grant for theHRRT (high resolution research tomograph), supported bythirty NIH grants and several investigators from multipleuniversities. In the next five years, I plan to develop atraining grant designed for Radiology residents eventuallyexpanding to collaborations including Psychiatry for train-ing young physicians in translational research. I plan tobecome a collaborator with the brain PET user group withthe focus of the new HRRT technology as a resource fortraining and research expansion. This will allow the op-portunity to train with other imaging experts, such as inMRI and fMRI, e.g., NIDA Intramural Program and theKKI Brain Center to expand my knowledge of brain im-aging and substance abuse research. Mini-sabbaticals, in-cluding the University of Pittsburg and the University ofPennsylvania, will add to my basic neuroscience and drugabuse training. It is my strong belief that this progresswill be maintained, even accelerated, in my additional fiveyears.

Thesaurus Terms: drug abuse, neuroimaging, neuropharma-cology, neurotransmitter transport, positron emission tomog-raphy Rett syndrome, Tourette’s syndrome, alcoholism/alco-hol abuse, cocaine, cortisol, dopamine, glutamate receptor,mentoring/mentor, nicotinic receptor, relapse/recurrence,serotonin baboon, bioimaging/biomedical imaging, clinicalresearch, functional magnetic resonance imaging, humansubject, magnetic resonance imaging, patient oriented re-search

Institution: Johns Hopkins UniversityW400 Wyman Park BuildingBaltimore, MD 212182680

Fiscal Year: 2005Department: Radiology And Radiological SciencesProject Start: 25-Sep-2000Project End: 31-Aug-2010ICD: National Institute On Drug Abuse
IRG: NIDA
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National Institute on Deafnessand Other Communication

Disorders

CORTICAL CONNECTIVITY USINGMAGNETIC SOURCE IMAGING

Grant Number: 5F31DC006762-02PI Name: Dalal, Sarang S.

Abstract: Description (provided by applicant): The scien-tific goal of this project is to use magnetoencephalography(MEG) to gain a better understanding of the cortical net-works involved in phonetic processing. Cortical sourcesinvolved in phonetic processing using whole-head MEGshall be investigated using novel tools to reconstruct theirlocations and time courses. Key technical developments tofacilitate this work include methods to co-register andnormalize MEG, ECoG, and structural MRI data. Corticalnetwork connectivity during phonetic processing will alsobe examined using neural source reconstructions. To theextent possible, all analyses will be cross-validated withECoG recordings in brain tumor patients. This projectprovides an interdisciplinary approach to studying impor-tant issues of neuronal activation and connectivity, using amultitude of techniques such as MEG, ECoG, and MRI. Italso supports translational research with the potential toimprove preoperative clinical language mappingprocedures.

Thesaurus Terms: brain mapping, cerebral cortex, mag-netoencephalography, method development, neural infor-mation processing, phonology, speech biophysics, brainelectrical activity, brain neoplasm bioimaging/biomedicalimaging, clinical research, electrocorticography, humansubject, magnetic resonance imaging, predoctoral investi-gator

Institution: University Of California SanFrancisco

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

Fiscal Year: 2005Department: RadiologyProject Start: 19-Mar-2004Project End: 18-Mar-2007ICD: National Institute On Deafness And

Other Communication Disorders
IRG: CDRC

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DISTINGUISHING THE NEURAL BASESOF LEXICAL ACCESS

Grant Number: 1F31DC007560-01A2PI Name: Graves, William W.

Abstract: Description (provided by applicant): This researchproposes to distinguish the neural correlates of phonologicaland semantic aspects of lexical (word-level) access. Studiesof patients and functional neuroimaging studies of unim-paired subjects have implicated left-sided perisylvian (infe-rior frontal gyrus (IFG), posterior superior temporal gyrus(pSTG)) and extrasylvian (inferotemporal cortex (IT)) brainareas in lexical access. The specific aims of this applicationare: 1) To identify the neural systems involved in accessinglexical phonology; and 2) To identify the neural systems in-volved in accessing lexical semantics. Phonological wordform (lexical phonology) access has been shown to be mod-ulated by word frequency. With respect to aim 1, we hypoth-esize that producing lower frequency words will correlatewith longer reaction times and greater fMRI activation in leftsuperior IFG, pSTG, and regions of IT. With respect to aim2, we hypothesize that processing more ambiguous wordswill correlate with longer reaction times and greater fMRIactivation in the inferior region of IFG as well as more infe-rior areas of IT partially overlapping those associated withphonological access. This study should lead to a more com-plete neural account of lexical access.

Thesaurus Terms: Brain mapping, neural information pro-cessing, phonology, semantics brain electrical activity, func-tional magnetic resonance imaging, neuroanatomy, temporallobe/cortex clinical research, human subject, predoctoral in-vestigator

Institution: University Of IowaIowa City, IA 52242

Fiscal Year: 2005Department: RadiologyProject Start: 01-Sep-2005Project End: 31-Jul-2006ICD: National Institute On Deafness And

Other Communication DisordersIRG: CDRC

ODORS MAPS IN OLFACTORY BULBBY FMRI

Grant Number: 5R01DC003710-08PI Name: Hyder, Fahmeed

Abstract: Progress in understanding the neurobiological ba-sis of olfaction has been enhanced by development of neuro-
imaging methods in the olfactory bulb. These methods have
provided quite convincing evidence to suggest that informa-tion carried by odorant molecules is partially encoded in spa-tial activity patterns of glomeruli, and significant progresshas been made to obtain the structural, functional, and mo-lecular basis of these glomerular patterns. However, notice-able gaps in understanding arise from the absence of full 3Dlocalizations of neural activity in individual glomerulae andthe neuroenergetic basis of these maps. The functional MRI(fMRI) method allows 3D mapping with relatively high tem-poral and spatial resolution. In the previous funding periodwe developed and applied this technology to the study ofolfaction, and we obtained reproducible glomerular levelfMRI data at 7T from the rat olfactory bulb. In the presentproposal we propose to take advantage of these develop-ments and findings to address the following questions aboutthe functional neuroarchitecture of the bulb. How is informa-tion about odorant identity and concentration encoded in theglomerular spatial activity pattern? Is there feedback inhibi-tion of the glomerular and inner layers of the bulb duringodorant exposure? What is the neuroenergetic cost of spatialactivity patterns in the bulb? This last question is importantfor understanding olfactory bulb function because our recent13C studies have shown that neuronal activity is energeti-cally expensive in the cerebral cortex. In this grant we pro-pose to further develop the fMRI methodology to provideglomerular resolution maps with high temporal ana spatialresolution. The fMRI signal will be calibrated and then vali-dated using 13C methods we pioneered in studying the so-matosensory cortex to provide quantitative maps of func-tional neuroenergetics and neuronal activity (as measured byextracellular electrical recordings and Ca2� imaging of neu-rotransmitter release at the glomerulus). The 3D maps ofindividual glomerular function will be used to explore thedependence of the spatial activity patterns on odorant struc-ture, concentration, and the mechanisms of time-dependentadaptation and feedback inhibition on these glomerular pat-terns. Activity of single glomeruli can help elucidate mecha-nisms of olfactory processing.

Thesaurus Terms: brain imaging/visualization/scanning,brain mapping, chemical structure function, functional mag-netic resonance imaging, neural information processing, neu-ron, neurophysiology, odor, olfaction, olfactory lobe alcohol,aldehyde, bioenergetics, brain electrical activity, calciumflux, cell population study, hemodynamics, method develop-ment, neuropil, neuroregulation, respiratory oxygenation, ste-reoisomer bioimaging/biomedical imaging, electrical mea-surement, laboratory rat

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

Fiscal Year: 2005Department: Diagnostic Radiology
Project Start: 01-Apr-1998
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Project End: 31-Mar-2007ICD: National Institute On Deafness And

Other Communication DisordersIRG: ZRG1

NEURAL MECHANISMS OF AUDITORYFEEDBACK DURING SPEECH

Grant Number: 1R01DC006435-01A1PI Name: Nagarajan, Srikantan S.

Abstract: Description (provided by applicant): Understand-ing how auditory feedback is processed during speaking pro-vides insights into fundamental mechanisms underlyingspeech production and perception. This knowledge mightalso ultimately contribute to the early detection and lead totreatment strategies for a number of prevalent clinical condi-tions where impairments in abnormal processing of auditoryfeedback have been reported (e.g. stuttering, Parkinson’s dis-ease, schizophrenia). While many behavioral studies haveexamined how auditory perception affects speech production,only recently have functional neuroimaging studies begunexamining how producing speech affects the neural pro-cesses serving auditory perception. Recent studies haveshown that in auditory cortex and other areas in the superiortemporal plane, speaking causes “speaking-induced suppres-sion” (SIS): response to self-produced speech is suppressedwhen compared to identical speech from an external source.In our recent work, we have shown that SIS in auditory cor-tex does not result from overall inhibition of this area duringspeaking. Rather, SIS appears to be a neural correlate of afeedback prediction error (FPE) - a comparison between ac-tual auditory input and an internal “speaking-induced predic-tion” (SIP) of that auditory input. SIS expression in auditorycortex has led to the hypothesis that SIS reflects auditorydiscrimination of self-produced from externally producedstimuli (Self-non-Self Hypothesis). However, refinements inour understanding of auditory feedback in speech motor con-trol, that are supported by behavioral studies and our prelim-inary data, suggest that SIS may also reflect feedback pro-cessing for speech motor control (Speech Motor ControlHypothesis). We have developed a unifying conceptualmodel that embodies both hypotheses, and our proposed ex-periments use SIS to test the neural correlates and the valid-ity of this model. The specific aims are to determine howSIS is modulated by 1) altered feedback, 2) speech targetdynamics and 3) speech motor adaptation. These manipula-tions not only help us to unravel the functional significanceof SIS but also help us determine if there is a differentiationof the function of SIS across the superior temporal plane.Furthermore, how activity in other parts of the brain is af-fected by our experimental manipulations will allow us to
determine the neural correlates of the mechanisms that gen-
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erate SIS. Our approach capitalizes on unique real-timespeech feedback alteration methods used with functionalmagnetic resonance imaging (fMRI) and magnetic sourceimaging (MSI). The excellent spatial resolution of fMRI willenable reconstruction of spatial locations of activity related toSIS and SIP while the excellent temporal resolution of MSI willenable us to reconstruct the sequence of activation in theseareas.

Thesaurus Terms: auditory cortex, auditory feedback, neu-ral information processing, sound perception, speech sensori-motor system, sound frequency, temporal lobe/cortex,vocalization behavioral/social science research tag, clinicalresearch, data collection methodology/evaluation, functionalmagnetic resonance imaging, hearing test, questionnaire, sta-tistics/biometry



Fiscal Year: 2004Department: RadiologyProject Start: 15-Jul-2004Project End: 30-Jun-2009ICD: National Institute On Deafness And

Other Communication DisordersIRG: MFSR

National Center forComplementary & Alternative

Medicine

ROLE OF ENDOGENOUS OPIOID SYSTEMIN THE PLACEBO EFFECT

Grant Number: 5R01AT001433-03PI Name: Campbell, James N.

Abstract: Description (provided by applicant): The placeboeffect in pain treatment can lead to enhanced efficacy andthereby confound the evaluation of analgesic medications inclinical trials. Whether viewed in the context of a con-founder for clinical trials or a desirable phenomenon in thetreatment of pain, the biochemical mechanisms underlyingthe placebo effect are poorly understood. The brain opioidsystem is involved in mediating the effects of opiate analge-sics and plays a role in the endogenous modulation of nox-ious stimuli. Considerable evidence indicates that the endog-
enous opioid system also plays a role in the analgesia pla-

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cebo effect. For example, many, but not all, studies haveshown that the placebo effect may be inhibited by the opiateantagonist naloxone. Yet, there is no direct evidence thatendogenous brain opioids are released during a placebo re-sponse, nor is it known which brain regions mediate opioid-mediated placebo effects. Furthermore, naloxone is not anopioid receptor subtype selective antagonist and therefore,other techniques are needed to examine more thoroughly therole of the opioid system in the placebo response. PET imag-ing of opioid receptors, originally developed by our labora-tory, is an excellent method to examine the role of the brainopioid system in mediating the placebo effect. Behavioraland psychological factors that relate to belief, conditioning,expectancy and meaning response are increasingly realizedto be important components of the placebo response, butknowledge of their relation to biological pathways is incom-plete. There is large intersubject variability in observing aplacebo effect during a placebo condition, but there is cur-rently no reliable way of predicting which individuals willdisplay a placebo effect. Elucidation of the role of the brainopioid system in the placebo response could significantlyimprove knowledge of this important mind-brain interaction.Accordingly, the specific aims of this study are to: 1) Com-pare regional mu opioid receptor availability measured byPET under a placebo condition vs. a non-placebo conditionin healthy human subjects who demonstrate a placebo re-sponse. 2) Determine the relationships between regional muopioid receptor availability and the magnitude of the placeboeffect. 3) Identify relationships between the magnitude of theplacebo response and regional mu opioid receptor availabil-ity in a non-painful condition.

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


Fiscal Year: 2005Department: Radiology And Radiological SciencesProject Start: 01-Apr-2003Project End: 31-Dec-2006ICD: National Center For Complementary

& Alternative MedicineIRG: ZRG1

MECHANISMS UNDERLYINGMILLIMETER WAVE THERAPY

Grant Number: 1P01AT002025-01A2PI Name: Ziskin, Marvin C.

Abstract: Description (provided by applicant): Millimeter
waves (MW) have been shown to produce biological effects
and are being used for medical treatment. Due to shallowpenetration, MW interact primarily with the skin structures.It was accepted that exposures at intensities of 10 mW/cm2and higher were able to produce thermal effects on biologi-cal substances due to temperature elevation and a high heat-ing rate. The latter factor could play an important role instimulating nerve endings in the skin. Recent theoreticalanalyses showed that due to thermal noise, the direct interac-tion of MW on molecular and cellular levels at exposureintensities less than 10 mW/cm2 could not affect biologicalsystems. Hence, to identify the mechanisms of biologicaleffects of MW, it is very important to characterize quantita-tively the power density and absorption at different pointswithin the skin, and the temperature elevations and heatingrates in the locations of thermosensitive structures of theskin. As the wavelength of MW is comparable with thethicknesses of skin layers, the frequency-dependent absorp-tion of MW differs for layers. Non-homogeneous structuresof the skin such as blood vessels and sweat ducts can disturbthe power density in nearby areas. Thus, the present studiesare designed to determine the frequency dependence of theMW energy deposition within different layers and non-ho-mogenous appendages of the skin. Using multilayer tissuemodels, we will investigate theoretically and experimentallythe MW heating of the skin under different exposure condi-tions and effect of blood flow and water evaporation on thetemperature elevation. We will also examine the capabilityof MW to elicit local vasodilatation in the skin. Some do-simetry methods such as specific absorption rate measure-ments, which were widely used for quantifying the absorp-tion energy through entire radiofrequency spectrum, are notappropriate for shallow penetrating MW, and they should bemodified when applied to MW frequencies. The new meth-ods developed in our study for determination of MW energydeposition and heating of the skin will be used for establish-ing adequate dosimetry. The results of the proposed projectwill be utilized in evaluation of the biophysical mechanismsof the MW interaction with skin structures, and for improv-ing dosimetry in the animal studies of the other projects ofthe Center.


Institution: Temple University1601 N. Broad StreetPhiladelphia, PA 19122

Fiscal Year: 2005Department: Diagnostic ImagingProject Start: 30-Sep-2005Project End: 31-Aug-2009ICD: National Center For Complementary

& Alternative Medicine
IRG: ZAT1
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National Institute of Arthritisand Musculoskeletal and Skin

Diseases

VERTEBRAL FRACTURE: TRABECULARBONE STRUCTURE ASSESSMENT

Grant Number: 5R01AR049701-04PI Name: Majumdar, Sharmila

Abstract: Description (provided by applicant): Osteoporosisis a condition characterized by a reduction in the bone min-eral density, impaired bone quality and frequent occurrenceof fractures resulting from minor trauma. Current assessmentof osteoporotic fracture risk is based on bone densitometrytechniques that do not entirely predict fracture risk or theimpact of a particular intervention. Bone quality encom-passes bone geometry and macro-architecture, trabecularbone structure, matrix calcification, bone turnover. The quan-titative analysis of bone structure and the elucidation of rela-tionships between structural parameters and bone strengthmay have a major impact upon the prediction of fracture riskand evaluation of different therapies. In this application, weare proposing to extend our previous work and make use ofrecent advances in hardware and software, to obtain three-dimensional (3-D) magnetic resonance (MR) images withresolutions of approximately 100 � 100 � 300 microns soas to accurately quantify the 3-D architecture of the trabecu-lar bone network in the radius, calcaneus and proximal fe-mur, and perform a rigorous evaluation of the impact ofthese data on the pathophysiological changes in skeletal boneand trabecular micro-architecture in aging, osteoporosis andfracture susceptibility. The specific aims of this study will beto establish non-invasive, reproducible imaging surrogatesthat can be used to assess bone quality in vivo. MR imagederived parameters of trabecular micro-architecture at thedifferent measurement sites will be related to age, meno-pause status and osteoporotic status in a cohort of 250 sub-jects. The primary question that will be addressed is whetherMR assessment of trabecular micro-architecture at the radius,calcaneus and proximal femur, combined with bone mineraldensity, provide a means to explain the discrepancy betweenbone mineral density and fracture occurrence. We will assesswhether using MR derived measures of trabecular bone at thedifferent skeletal sites show site specific differences, relationshipbetween structure and bone mineral density at these sites, andwhether these measures may be used to complement bone min-eral density measurements in the study of osteoporosis.

Thesaurus Terms: bone density, bone fracture, bone imag-ing/visualization/scanning, substantia spongiosa aging, com-
puter simulation, image processing, noninvasive diagnosis,
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osteoporosis, postmenopause, vertebrae clinical research,densitometry, human subject, magnetic resonance imaging,photon absorptiometry



Fiscal Year: 2005Department: RadiologyProject Start: 30-Sep-2002Project End: 31-Aug-2007ICD: National Institute Of Arthritis And

Musculoskeletal And Skin DiseasesIRG: ZAR1

National Institute ofEnvironmental Health Sciences

12TH ANNUAL SFRBM MEETING

Grant Number: 1R13ES014554-01PI Name: Buettner, Garry R.

Abstract: Description (provided by applicant) The investiga-tors request partial funding for the 12 Annual Meeting of theSociety for Free Radical Biology and Medicine (SFRBM;formerly The Oxygen Society) to be held November 16–20,2005 at the Hilton Austin in Austin, Texas. Funds will sup-port travel, lodging, and registration fees of invited speakersso that funds from the SFRBM operating budget and annualmeeting income can be directed toward supporting the travel,registration, and participation of students, fellows, and otherinvestigators. The meeting will be preceded by a workshopon “Rigorous Detection and Identification of Free Radicalsin Biology and Medicine,” providing lectures by experts inthe field to young and other interested investigators on theconcepts, techniques, and interpretations of state-of-the-art-experimental approaches for detecting free radicals and re-lated oxidants in sells/tissues/organisms. The body of thefour-day meeting will then begin, featuring invited plenarylectures in the morning and oral presentations of selectedabstracts in three parallel afternoon/evening sessions. Thethemes of the four plenary sessions are: Redox Regulation ofGene Expression and Chromatin Remodeling; Formation,Metabolism and Novel Signaling Pathways of Leukotrienesand Prostanoids; Coping with Oxygen Through Birth, Devel-opment and Aging; and Frontiers in Free Radical Research.As a new feature, the first two plenary lectures on the finalday of the conference will be delivered by the recipients of
the SFRBM Lifetime Achievement Award and SFRBM Dis-

Academic Radiology, Vol 14, No 8, August 2007 NIEHS

covery Award. Before the plenary lectures each morning, theSunrise Free Radical School will be held, a distinct charac-teristic of the SFRBM Annual Meetings, featuring seniorscientists in the field addressing fundamental aspects of freeradical chemistry and biology to an audience of students,fellows, and other interested investigators. The lectures de-livered in the afternoon/evening sessions will be selectedfrom abstracts submitted by Society members and nonmem-bers at large. Each afternoon/evening session will be chairedby selected young investigators in the field. Abstracts notselected for oral presentation will be presented in three one-day poster sessions. Posters will be open for discussion inthe evenings. Overall, SFRBM ’05 will address a broadrange of research topics related to the diverse roles that reac-tive oxygen and nitrogen species play in biology and medi-cine. Research data presented will have a significant impacton our understanding of aging, cancer, diabetes, inflamma-tion and immunity, and cardiovascular diseases, and willprovide new insights into mechanisms by which antioxidantsand therapeutics can be used to help prevent or treat theseconditions. The conference provides a forum for exchange ofthe most recent basic and applied research results in freeradical chemistry, biology, and medicine as well as an op-portunity for scientists in the field to network and arrangefor new collaborations.

Thesaurus Terms: free radical, meeting/conference/sympo-sium travel


Fiscal Year: 2005Department: RadiologyProject Start: 15-Sep-2005Project End: 31-Aug-2006ICD: National Institute Of Environmental

Health SciencesIRG: EHS

THE XP VARIANT: A HUMAN MUTATORGENE FOR UV DAMAGE

Grant Number: 5R01ES008061-08PI Name: Cleaver, James E.

Abstract: Description (Provided by Applicant): Xerodermapigmentosum (XP) is a disease in which a genetic deficiencypredisposes patients to sunlight induced cancers of the skin,including squamous and basal cell cancers and melanomas.XP is a multigenic disease involving at least 8 genes: XPgroups A through G represent deficiencies in nucleotide ex-cision repair (NER) of sunlight (UVB) damage to the DNAof the skin, and XPV represents a deficiency in replication of
damaged DNA. XP cells all show elevated UV-induced mu-
tagenesis, which correlates with the increased risk for sun-light induced cancer. The XPV gene encodes a DNA poly-merase, hRad3O, po1 n, homologous to the UMUC, D’ classof polymerases in E.coli, and functions in an error-free path-way for UV damage. The enzyme is a distributive polymer-ase with a high error-rate on even undamaged DNA. Wehave mapped the gene to 6p2l, identified 10 coding exons,and an untranslated exon I. Exon II is deleted in some nor-mal transcripts and in an XP patient. We observe that thepromoter has multiple AP1 and SP1 sites, suggesting a dam-age-responsive regulation. We found expression from a con-stitutive promoter to be toxic, but have achieved functionalcorrection of several XPV phenotypes (UV survival, apopto-sis) using expression of a fusion protein. We have also foundthat DNA replication after UV damage in XPV cells in-volves a double strand repair/recombination system involvinghMre1 1/hRad50/Nbs1 and depends on p53. Understandinghow a polymerase with such a high error-rate contributes toerror-free replication of UV damaged DNA, and how it isregulated to avoid rampant error generation and toxicity is ofmajor importance and the emphasis of this project. Our spe-cific aims are: Aim I: To understand the mechanisms bywhich the low fidelity hRad3O polymerase is regulated tomaintain genetic stability in normal and transformed cells.We will design expression vectors that complement XPVphenotypes in vitro, and use these to identify binding part-ners in control and UV damaged cells. Aim II: To under-stand the role of recombination in the S phase checkpoint(s)in cells deficient in hRad3O. We will determine the role ofhMre 11 recombination in specific stages of the S phase andidentify components of the S phase signal transduction path-ways. Aim III: To develop mouse strains defective inhRad3O functions. We will express hRad3O on the keratin14 promoter for over-expression in the skin, and make tar-geted knockout of mRad3O in vivo to identify roles forhRad3O in promoting and preventing carcinogenesis.

Thesaurus Terms: DNA damage, neoplasm/cancer genetics,radiation carcinogenesis, ultraviolet radiation, xeroderma pig-mentosum DNA repair, biological signal transduction, ge-netic promoter element, nucleic acid sequence, transfection/expression vector gene targeting, genetic strain, geneticallymodified animal, laboratory mouse



Fiscal Year: 2005Department: RadiologyProject Start: 01-Feb-1998Project End: 30-Jun-2006ICD: National Institute Of Environmental

Health Sciences
IRG: CPA
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MR-BASED STUDY OFHYPOMYELINATION BY LEADPOISONING

Grant Number: 5R01ES012665-03PI Name: Mori, Susumu

Abstract: Description (provided by applicant): The overallgoal of this project is to establish the usefulness of magneticresonance microimaging as a tool to study myelination toxi-cology and apply it to investigate hypomyelination caused bylead poisoning. Myelination is a very complex process; my-elination starts at the different time point with different ratesfor each white matter tract. As a result, comprehensive char-acterization of myelination status, even of the normal state,is not a straightforward task. This poses a great challenge fortoxicological assessment of myelination. In this project, wewill use the ex vivo high-resolution MRI and a rat neonatemodel to characterize the temporal and spatial profile of themyelination process. Using this technique following threeaims will be pursued. Aim 1: Characterization of temporaland spatial profile of the normal rat myelination process us-ing MRI and fixed brain samples. Hypothesis: “Ex vivohigh-resolution MRI can reveal the dynamic process of my-elination three-dimensionally in a tract-by-tract basis. Themicroimaging technique will be applied to a series of normalbrain samples at different development stages to monitor themyelination process. The observed changes of MR parame-ters will be correlated with histology to confirm the hypothe-sis. Aim 2: Study of the myelination abnormality by high-dose lead administration. Hypothesis”: “Ex vivo high-resolu-tion MRI can sensitively and efficiently detect myelinationabnormalities” Hypomyelination by lead uptake has beenpreviously reported and our preliminary data show that MRIcan sensitively detect the hypomyelination of specific whitematter tracts. We will use this system to compare MRI find-ings and histology data and to validate the hypothesis. Aim3: Study of the temporal, spatial, and dose profiles of themyelination abnormality by low-dose lead administration.Hypothesis: “Low-dose lead uptake induces the myelinationabnormality, which is independent of malnutrition. Hypomy-elination by lead uptake has been considered as one of theimportant developmental impairments by the lead uptake.However, to date, it has not been clear whether the observedhypomyelination is secondary to the concomitant malnutri-tion and weight loss. Using the MRI-based technique andnormative database established under Aim 1 and 2, we willperform comprehensive myelination studies to examine thehypothesis”

Thesaurus Terms: developmental neurobiology, lead poi-soning, myelination, myelinopathy, neurotoxicology neuro-toxin electron microscopy, histology, laboratory rat, magneticresonance imaging, newborn animal, three dimensional imag-
ing/topography
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Fiscal Year: 2006Department: RadiologyProject Start: 30-Sep-2004Project End: 31-May-2008ICD: National Institute Of Environmental

Health SciencesIRG: ALTX

National Center for ResearchResources

HIGH FIELD WHOLE BODY MRISCANNER FOR MULTI-NUCLEAR MRI

Grant Number: 1S10RR019907-01PI Name: Boada, Fernando E.

Abstract: Description (provided by applicant): This applica-tion requests funds for supplementing the purchase of a highfield (7T), whole body scanner for improved proton and non-proton, metabolic imaging studies in humans. The applica-tion is in response to the “High End Instrumentation Grant”RFA and corresponds to a proposal previously reviewed bythe standard Shared Instrumentation Grant RFA panel. Thescanner is intended to improve the research infrastructure ofthe MR Research Center (MRRC) of the University of Pitts-burgh Medical Center (UPMC). The MRRC is a researchdedicated MRI facility that was established 9 years ago bythe UPMC in response to the increased demand for neuroim-aging studies at the University of Pittsburgh and neighboringCarnegie Mellon University. The MRRC operates two stateof the art whole body MRI scanners. The scanners are FDA-approved, use the same scanning software platform and oper-ate at field strengths of 1.5 and 3.0 Tesla, respectively. Sincethe inception of the MRRC in 1994, several of the investiga-tors listed in this proposal have been engaged in researchrelying on the use of novel MRI imaging strategies to under-stand the role of specific proton and non-proton metabolitesin normal and diseased human physiology. The evolution ofthese projects has led the PI and his collaborators into re-search directions that require the use of improved signal-to-noise ratio (SNR) and spatial resolution for further character-izing the MRI signal from such metabolites in vivo. This invivo characterization is, at this point, of paramount impor-tance in order to fully understand all the issues involved inthe interpretation and quantification of the images in the con-text of normal and disease physiology. The proposed instru-
ment will allow this characterization process to take place in

Academic Radiology, Vol 14, No 8, August 2007 NCRR

an efficient and timely fashion so that the aforementionedimaging techniques can be further optimized for operation atlower, more clinically relevant, field strengths. The chosen7.0T scanner will allow prompt progress of the imagingprojects to be served by the instrument, as its software envi-ronment will be (upon installation) identical to that of the1.5 and 3.0T scanners already available at the MRRC.

Thesaurus Terms: biomedical equipment purchase, mag-netic resonance imaging bioimaging/biomedical imaging

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

Fiscal Year: 2004Department: RadiologyProject Start: 01-Jul-2004Project End: 30-Jun-2006ICD: National Center For Research

ResourcesIRG: ZRG1

MICRO COMPUTERIZED TOMOGRAPHYIMAGING SYSTEM

Grant Number: 1S10RR019253-01PI Name: Conti, Peter S.

Abstract: Description (provided by applicant):Recent engi-neering advances in the instrumentation for medical imaginghave produced miniaturized versions of x-ray, radionuclearand magnetic resonance scanners for studies in small labora-tory animals. This, coupled with increasingly sophisticated,transgenic mouse models, is driving a revolution in the in-vestigation of disease and developmental processes in vivo atthe whole-animal level. This interdisciplinary proposal re-quests funding for a small-animal x-ray computed tomogra-phy scanner (“microCT”). The users are in the fields of radi-ology/nuclear medicine, medicine, pathology, biochemistry/molecular biology, orthopedic surgery, thoracic surgery,oncology and dentistry. The projects relate to bone develop-ment and osteoporosis, as well as to chemo- and antiangiog-nesis therapy of cancer. Applications of the proposed mi-croCT scanner will include anatomic imaging for correlationwith functional images from in vivo, small-animal PET andoptical imagers; serial monitoring of metastatic tumor devel-opment in animal models; serial, in vivo, quantitative moni-toring of normal and pathologic bone development and theeffects of diet and genetic alteration on bone growth intransgenic murine models; and ultra-high resolution, in vitro,quantitative imaging of bone specimens in relation to bonedevelopment and response to diet and genetic modifications.During the last several years, a Molecular Imaging Center
has been established at USC with support from an NIH/
NCIP20 planning grant. The requested microCT scanner willbe housed and operated in Center’s Molecular Imaging Lab-oratory, where it will complement small-animal PET andoptical imaging systems purchased with previous grants fromthe NCRR. The particular microCT unit requested is wellsuited for both the in vitro and in vivo applications presentedby the users, viz., it provides ultra-high (10 fm) spatial reso-lution and sophisticated analysis software for bone studies,acceptable radiation dosage for serial scanning applicationsin living animals, physiologic gating capability for high reso-lution in vivo scanning and large bore to accommodate therange of animal species used for micro PET studies. Addi-tion of the requested instrument will greatly enhance the in-formation provided by the existing small-animal molecularimaging facility as well as increase the productivity of as-sembled PHs-funded investigators at USC and Loma LindaUniversity who are working in the areas of cancer and bonedevelopment/disease.

Thesaurus Terms: X ray, biomedical equipment purchase,miniature biomedical equipment, tomography bone imaging/visualization/scanning bioimaging/biomedical imaging

Institution: University Of Southern CaliforniaDepartment Of Contracts And GrantsLos Angeles, CA 90033

Fiscal Year: 2004Department: RadiologyProject Start: 15-May-2004Project End: 31-May-2006ICD: National Center For Research

ResourcesIRG: ZRG1

MICRO CT FOR VARIABLE SPATIAL-TEMPORAL RESOLUTION

Grant Number: 1S10RR019242-01PI Name: Hoffman, Eric A.

Abstract: Description (provided by applicant): Small ani-mals, particularly genetically engineered mice, are increas-ingly becoming the preferred laboratory model to gain fur-ther understanding of human health and diseases. Major ef-forts are being made to link the genome to the much morecomplex phenotypic expression in both form and function(“Physiome”). Also, significant efforts have been directed tostudies of large animals and humans, and the knowledge ac-quired from these need to be associated with imaging ofsmall animals to support the understanding of genomic ef-fects. And finally, small animal imaging offers the opportu-nity to evaluate pathologic progression in a much-com-pressed time frame and with a much finer spatial resolution.
Over the past several years there has been an explosive
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growth in the development of micro-imaging technologies,including micro-CT. In this proposal, we request a micro-CTscanner and associated reconstruction hardware to supportthe ongoing cellular/molecular level research and the inte-grated, in vivo organ level work funded by the NIH at theUniversity of Iowa (UI). X-ray CT, rather than any one ofthe other micro imaging modalities, meets the specific needsof the major user group which, to date, is heavily orientedtowards lung and bone. Although the UI is strongly fundedby the NIH (32ndin terms of the total NIH funding), wehave not had local access to any micro-CT imaging system.Recently, there has been an increasingly urgent need for amicro-CT facility from a growing number of NIH funded UIinvestigators. The system we plan to purchase has been spe-cifically designed based upon the diversified and sophisti-cated requirements of UI NIH researchers. The system iscommercially built by a leading micro- CT Company. Thescanner features include: (1) a variable resolution rangingfrom 7 to 30 microns to correlate low resolution in vivo datato high resolution in vitro anatomy; (2) a high data acquisi-tion speed; (3) a high though-put image reconstruction en-gine to allow iterative protocol selection according to priorin vivo imaging results. The micro-CT system will be lo-cated in an Imaging Center dedicated to x-ray CT-imaging-based research that is currently under construction with a 2.0million dollar investment from the Ul College of Medicine.The Internal Advisory Committee consists of established in-vestigators and experienced administrators, and will assistthe facility director in establishing policy and future direc-tions of the micro-CT facility. The well-qualified staff willprovide technical assistance and necessary training.

Thesaurus Terms: biomedical equipment purchase, com-puted axial tomography


Fiscal Year: 2004Department: RadiologyProject Start: 01-Apr-2004Project End: 31-Mar-2005ICD: National Center For Research

ResourcesIRG: ZRG1

INTEGRATED CENTER FOR IN VIVOMICROSCOPY

Grant Number: 5P41RR005959-15PI Name: Johnson, G. Allan

Abstract: Description (provided by applicant): The enor-mous growth in the use of small animals for basic biomedi-
cal research has created a compelling need for new ap-
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proaches to structural and functional phenotyping in the ro-dent. We propose continuation of the Duke Integrated Centerfor In Vivo Microscopy, an NIH/NCRR National Resourcewith an explicit focus on meeting this need. We propose fourintegrated cores that will provide researchers from aroundthe world new image-based methods for structural and func-tional phenotyping using magnetic resonance microscopy(MRM). Core A: We will develop functional microscopy inthe rodent to support cardiac motion analysis, pulmonaryperfusion using arterial spin tagging and pulmonary ventila-tion using hypcrpolarized gas imaging. Core B: We will de-velop more efficient encoding strategies to increase ourthroughput for MR Histology by at least 500%. We will de-velop methods for actively staining fixed tissues for 3D MRhistology. We will develop methods to measure regionalneurodegeneration in the mouse brain. Core C: We will de-velop a new generation of technologies for physiologic sup-port and monitoring of small animals permitting mutlimodal-ity imaging (MRM. MicroPET, microCT, etc.) and imageregistration and long term studies on animals with compro-mised immunologic systems. Core D: We will develop visualinformatics tools to permit effective archive, access, andanalysis of very large multidimensional image sets frommultiple modalities. The technologies will support a total of16 collaborators anxious to use small animal imaging to ex-tend the horizons of topics ranging from cancer to neurobiol-ogy. An aggressive education and dissemination program isincluded that will include undergraduate and graduate stu-dents, as well as post-doctoral fellows.

Thesaurus Terms: biomedical resource, imaging/visualiza-tion/scanning, microscopy, technology/technique develop-ment bioimaging/biomedical imaging

Institution: Duke UniversitySuite 1103Durham, NC 27705

Fiscal Year: 2004Department: RadiologyProject Start: 01-Sep-1990Project End: 30-Jun-2008ICD: National Center For Research

ResourcesIRG: ZRG1

HIGH FIELD GE EXPERIMENTAL MRSCANNER

Grant Number: 1S10RR019887-01PI Name: Moseley, Michael E.

Abstract: Description (provided by applicant): This proposalis in response to NCRR High End Instrumentation Program
(RFA: RR-03-009) to reinforce our investment in improved

Academic Radiology, Vol 14, No 8, August 2007 NCRR

instrumentation for the advancement of biomedical researchin Stanford’s interdisciplinary approach. The acquisition ofthe proposed General Electric “microSigna 7.0” 7T High-Field Small-Bore MR Signa LX scanner will address ourneeds for a high-end MR experimental scanner to supportand drive the research of our community of basic and clini-cal scientists within the multimodality imaging facility forlaboratory animal imaging called the Stanford Center forInnovation in In-vivo Imaging (SCI3). This resource hasbeen successfully established as an integral part of the Medi-cal School and larger Stanford community. The SCI3 is sup-ported by the Stanford NCRR P41 (Glover, PI), the StanfordNCI Small Animal Imaging Research Proposal (SAIRP,Contag, Moseley, Co-PI’s), and the newly-created MolecularImaging Program at Stanford (MIPS, Gambhir, PI). The ad-vanced MR scanner to be acquired will together with ourmicroPET, microCT, and microSPECT platforms permit usto better monitor both structural and functional changes insmall animal models non-invasively and in real-time. Stateof the art MR imaging within the SCI3 is necessary to en-hance detection sensitivity and resolution; our strong MR-oriented faculty within the P41 will help develop new MRadaptations to support a growing number of crucial biomedi-cal experimental studies now being done on our 1.5T and 3Twhole-body GE Signa LX scanners. The acquisition of thisnew high-field, small bore (310mm bore) experimental scan-ner that brings the best in clinical consoles (the LX 11,EXCITE2, 8-channel multi-coil platform) and all GE andStanford-derived LX pulse sequences together with a newdesign in high-speed gradients (25cm, 500mT/m) with8-channel multi-coil RF arrays will greatly enhance our MRprogram at Stanford by providing a route for translationalresearch from the top down, that is, by bringing all the pow-erful scanning tools available on clinical research scanners toour routine-to-advanced animal MR scanning. The result willbe improved imaging technologies that push the limits ofcurrently available bioimaging MR methods combined withthe easy-to-use yet powerful LX console that will greatlyfacilitate the introduction of researchers and young investiga-tors to state-of-the-art MR imaging, and also support astrong multi-modality Stanford Center for Innovation in In-vivo Imaging (SCI3).

Thesaurus Terms: biomedical equipment purchase, mag-netic resonance imaging biological model bioimaging/bio-medical imaging

Institution: Stanford University1215 Welch Road, Mod BStanford, CA 943055402

Fiscal Year: 2004Department: RadiologyProject Start: 15-Jul-2004
Project End: 14-Jul-2006
ICD: National Center For ResearchResources

IRG: ZRG1

3 T WHOLE BODY MAGNETICRESONANCE SCANNER

Grant Number: 1S10RR019186-01PI Name: Narayana, Ponnada A

Abstract: Description (provided by applicant): This applica-tion seeks partial funding from NIH and NSF for purchasinga 3 Tesla, whole body magnetic resonance scanner for invivo imaging (MRI) and spectroscopy (MRS) in humans andnonhuman primates. The scanner will be housed in the Uni-versity of Texas Medical School at Houston, which is lo-cated in the Texas Medical Center, home of four major re-search institutions and five hospitals. This scanner will beequipped with body and head RF coils and high performancegradient system that is capable of producing maximum gra-dient amplitudes of 40 mT/m with a slew rate of 200 mT/m/s. In addition, it will incorporate five-second order roomtemperature shims for improved field homogeneity. This highperformance system will allow us to implement advancedMR imaging techniques such as diffusion tensor imaging(DTI), functional MRI (fMRI), and spectroscopic imaging(MRSI). Processing software for DTI, fMRI, and MRSI (2D,3D, multislice and with a variety of k-space scanning tech-niques) will be included with the scanner. A full researchagreement with the manufacturer will be executed for accessto all the source codes for the pulse sequences and recon-struction algorithm to modify the existing sequences and im-plement newer sequences on the scanner. These will bemade available to all the users. In addition, the scanner willprovide access to the raw data for testing advanced imageprocessing techniques. This high field and high performanceMR scanner will be used for investigating 1) various neuro-logical disorders, 2) techniques for improving learning anddevelopment in normal school age children by fusing infor-mation from MRI and MEG, and 3) advanced automatic im-age processing. The neurological disorders that will be inves-tigated include neurodevelopmental disorders in humans andnonhuman primates, psychiatric disorders, and demyelinatingdiseases such as multiple sclerosis. Twenty-one projects byfourteen users who are Pl’s on NIH and NSF funded grantswith significant MR component have been identified. Whilethe main thrust of the proposed projects is neuroimaging, weanticipate that future projects would include body imaging,particularly cardiovascular imaging. Strong institutional com-mitment and financial plans for operating the scanner, partic-ularly the long-term maintenance, are described.

Thesaurus Terms: biomedical equipment purchase, mag-netic resonance imaging, whole body imaging/scanning func-
tional magnetic resonance imaging, image processing, neuro-
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NLM Academic Radiology, Vol 14, No 8, August 2007

imaging, nuclear magnetic resonance spectroscopy bioimag-ing/biomedical imaging

Institution: University Of Texas Hlth Sci CtrHouston

Box 20036Houston, TX 77225

Fiscal Year: 2004Department: RadiologyProject Start: 15-Apr-2004Project End: 14-Apr-2005ICD: National Center For Research

ResourcesIRG: ZRG1

DEDICATED HIGH PERFORMANCEHUMAN BRAIN/PRECLINICAL PET

Grant Number: 1S10RR017219-01A1PI Name: Wong, Dean F.

Abstract: Description (provided by applicant): This proposalrequests a new state of the art high performance positronemission tomography (PET) scanner to replace the GE Ad-vance whole body scanner currently used in our PET center.The new scanner will be dedicated to greatly enhanced hu-man brain imaging, pre-clinical studies of the CNS, and pre-clinical studies from other disciplines, including cancer. Ourfunded and pending research studies encompass multiple uni-versities, institutes, and schools within and outside JohnsHopkins University including international collaborations.Imaging of non human primate and human CNS neuro-re-ceptors has been the major focus of our previous research,with studies of groups including: children with mental retar-dation, young adults with schizophrenia, depression, and sub-stance abuse, and diseases in the elderly, including depres-sion, and Parkinson’s Disease. A major program of publichealth and medical significance involves studies of neuro-toxicity. All of these studies require exquisite 3-D resolutionsensitivity axial sampling to provide the maximum recoveryof radiotracer binding to small structures. Our research planhas four major areas: brain imaging and substance abuse (in-cluding alcohol and cocaine), mental illnesses (includingschizophrenia and depression), neurological and developmen-tal disorders, and pre-clinical studies for radioligand develop-ment in cancer and the CNS. Almost 30 currently fundedNIH grants including RO1’s, program projects, and centergrants, are represented in this application. The scientificscope of our PET program and the number of investigatorsinvolved has increased dramatically over the past severalyears. With many new radiotracers available and increasedinterest in pre-clinical pharmaceutical collaboration, the op-portunities for multiple receptor radiotracers for brain imag-
ing is a reality. These measurements cannot be reproduced
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by any other methodology with the same degree of quantifi-cation, sensitivity, or specificity. These studies go beyondpathophysiology to include drug development and treatmentmonitoring of neuro-psychiatric disorders. As more is knownabout brain neurochemistry, the demands for imaging smallerand more intricate structures becomes increasingly important.The new high performance PET camera with advanced crys-tal designs, larger bore size, and great improvements in 3Dresolution and sensitivity over our existing HRRT (CPS In-novations, Knoxville) will allow us to address these chal-lenging issues.

Thesaurus Terms: biomedical equipment purchase, brainimaging/visualization/scanning, positron emission tomogra-phy three dimensional imaging/topography bioimaging/bio-medical imaging


Fiscal Year: 2004Department: RadiologyProject Start: 01-Apr-2004Project End: 31-Mar-2006ICD: National Center For Research

ResourcesIRG: ZRG1

National Library of Medicine

MEDICAL IMAGE/DATE SECURITYASSURANCE - DIGITAL ENVELOPE

Grant Number: 5R01LM007606-04PI Name: Huang, H.K. K.

Abstract: Description (provided by applicant): Health Datasecurity, characterized in terms of data privacy, authenticity,and integrity, is a vital issue when digital images and otherpatient information are transmitted through public networksin teleradiology and other telehealth applications. Mandatesfor ensuring health data security have been issued by thefederal government (e.g. HIPAA [Health Insurance Portabil-ity and Accountability Act]), and guidelines such as DICOM(Digital Imaging and Communication in Medicine) standardcontinue to be published by organizing bodies in healthcare(e.g. American College of Radiology); however, there hasnot been a systematic research and development effort withinthe medical imaging community to address this critical mat-ter. Over the past six years, members in the Image Process-ing and Informatics Laboratory/Children’s Hospital Los An-
geles/University of Southern California (PI/CHLA/USC) has

Academic Radiology, Vol 14, No 8, August 2007 NLM

actively researched image security issues related to PACS(Picture Archiving and Communication System) and tele-health with very encouraging results. This application repre-sents an organized and rigorous approach to further researchon this topic based on this experience. The proposal outlinesthe systematic development of the digital envelope (DE)concept to assure data integrity, authenticity, and privacyduring image/data transmission through public networks. TheDE includes the digital signature (DS) of the image as wellas encrypted patient information from the DICOM imageheader. The proposal delineates eight specific tasks, includ-ing review and selection of digital security technologies suit-able for medical imaging applications, revamping our exist-ing DE security algorithm based on these new selections,designing the DE to be DICOM compliant, and performing athree-phase evaluation from the laboratory, to intra-hospital, andfinally inter-hospital environments. The three-year research planwill culminate in the delivery of a portable, self-contained, andevolving DE package available for the medical image commu-nity to use in telemedicine and teleradiology applications. Fortelemedicine and teleradiology, since data cannot be limitedwithin a private local area network protected by a firewall, theDE package offers the most useful security assurance. Thismethod also provides additional image/data assurance to con-ventional network security protections.

Thesaurus Terms: information system, telecommunication,telemedicine bioimaging/biomedical imaging, computer net-work, computer program/software, confidentiality, data col-lection methodology/evaluation, data quality/integrity, infor-mation dissemination, medical record, online computerclinical research, human data

Institution: University Of Southern CaliforniaDepartment Of Contracts And GrantsLos Angeles, CA 90033

Fiscal Year: 2004Department: RadiologyProject Start: 01-Jul-2003Project End: 30-Sep-2006ICD: National Library Of MedicineIRG: ZLM1

TRAINING PROGRAM FOR IMAGINGBASED MEDICAL INFORMATICS

Grant Number: 5T15LM007356-05PI Name: Kangarloo, Hooshang

Abstract: Description (provided by applicant): An imag-ing-based medical informatics training program is pro-posed by a consortium of institutions with strong researchand teaching backgrounds in this field. Building from an
existing Biomedical Physics Graduate Program, the pro-
posal extends the current curriculum with biomedical in-formatics-specific classes; candidates completing the pro-gram will become knowledgeable in basic and advancedmedical imaging, information system architectures, dataand process modeling, knowledge representations, infor-mation retrieval and visualization, image communicationand security, and health services research issues - all inthe context of current and future healthcare environmentsand technologies. The program provides students with op-portunities in numerous existing research projects, andleads to either an MS degree (approximately two years)and/or a PhD degree (approximately five years). This pro-gram also supports postdoctoral trainees from basic sci-ence and medical backgrounds, providing research andteaching opportunities for qualified individuals to partakein imaging-based informatics. UCLA is the lead institu-tion of this consortium, with faculty participating from theDepartments of Radiological Sciences (with an accreditedbiomedical physics program), Computer Science, Informa-tion and Library Sciences, and Health Services Research,including Rand Corporation. The consortium also includesthe University of Southern California (USC), with itsstrong background and current research in image process-ing and informatics, and an active medical imaging andtelemedicine graduate program. The consortium is com-pleted with the participation of the Charles R. Drew Uni-versity, assuring recruitment of minority students from amedical school; this affiliation will enable under-repre-sented students to achieve a combined MS/MD degree,leading to higher acceptance into competitive residencyprograms. Together, these three universities provide theresources, research, and teaching infrastructure for an op-portunity to establish a unique national-level training pro-gram in imaging-based medical informatics in SouthernCalifornia.


Institution: University Of California Los AngelesOffice Of Research AdministrationLos Angeles, CA 90024

Fiscal Year: 2006Department: RadiologyProject Start: 01-Jul-2002Project End: 30-Jun-2007ICD: National Library Of MedicineIRG: ZLM1

REFUGEE HEALTH INFORMATIONNETWORK

Grant Number: 5G08LM007854-03
PI Name: Mun, Seong K.
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Abstract: Description (provided by applicant): The PrincipalObjectives of the REFUGEE HEALTH INFORMATIONNETWORK (RHIN) are: 1) To improve a) access and b)exchange of medical information by state and local publichealth departments and other health professionals, refugeeservice providers, and refugee consumers. 2) To develop adatabase of refugee health information. 3) To identify andmake accessible culturally and linguistically appropriatehealth and medical information in order to improve healthservices for refugees. 4) To develop and elaborate new meth-ods for the electronic interchange of relevant information. 5)To enable and encourage a “culture of information sharingand communications” among health care providers who spe-cialize in refugee health. To do this, a collaborative partner-ship will be formed to develop an information network thatwill enable resettled refugees, their health care providers andpublic health administrators to gain access to informationrelevant to refugee health. This network will include asearchable web site and database, and will be linked to exist-ing sites specializing in refugee health, as well as medicalinformation sites from the National Library of Medicine andother credible sources of health information. The proposedsystem will also facilitate communication between healthprofessionals involved in refugee health by using email anda list serve to keep all subscribed users informed and in con-tact with each other.


Institution: Georgetown University37th And O Sts NwWashington, DC 20057

Fiscal Year: 2005Department: RadiologyProject Start: 01-Jun-2003Project End: 31-May-2006ICD: National Library Of MedicineIRG: BLR

CONTENT BASED NEURO IMAGECLASSIFICATION

Grant Number: 5R03LM007963-02PI Name: Sinha, Usha

Abstract: Description (provided by applicant): The goal ofthis proposal is the automated classification of imaging stud-ies of patients with tumors. As the role of imaging becomesincreasingly important in medical care, effective methods forstoring and retrieving key images will become critical. Imageclassification and subsequent summarization proffers amethod to compress imaging studies by selecting only perti-
nent image slices that objectively document a patient’s con-
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dition, while preserving the full integrity of the original data;as such, its applications include multimedia electronic medi-cal records, telemedicine, and teaching files. This proposaldetails an innovative method to accomplish image classifica-tion based on principal component analysis. A training set ofimages classified by experts will be used to generate a basisset of images that captures the variance among the images.The projection on this basis set of images, called eigenim-ages, is used as an image index for classification and re-trieval. Two key aspects critical to the success of accurateimage classification are described: normalization of both im-age spatial and intensity properties. A modification to thismethodology is also proposed to handle images with smallabnormalities: image sub-regions that are ’abnormal’ are lo-cated by searching the query image for the region that bestmatches a training set of sub-images of ’abnormal regions’.The target domain for the proposal is MR imaging studies ofpatients with brain tumors; in future work, this research willbe extended to cover other neurological conditions, imagingmodalities, and anatomical regions. Technical evaluation willbe performed by comparing the automated methods with thatof experts.

Thesaurus Terms: brain imaging/visualization/scanning,brain neoplasm, data management, information retrieval,magnetic resonance imaging, neoplasm/cancer classification/staging automated medical record system, computer program/software, data collection methodology/evaluation, interactivemultimedia, training aid bioimaging/biomedical imaging, hu-man data

Institution: University Of California Los AngelesOffice Of Research AdministrationLos Angeles, CA 90024

Fiscal Year: 2004Department: RadiologyProject Start: 01-Sep-2003Project End: 31-Aug-2006ICD: National Library Of MedicineIRG: ZLM1

HIGH DIMENSIONAL INDEXING INMEDICAL IMAGE DATABASES

Grant Number: 2R01LM006911-04A1PI Name: Tagare, Hemant D.

Abstract: Description (provided by applicant): NHANES II,which is maintained by the National Library of Medicine,contains a database of 17,000 cervical and lumbar spine x-ray images. The aim of this proposal is to create graphicalretrieval mechanisms for NHANES II so that images may beretrieved on the basis of anterior osteophyte severity and
malalignment. Two retrieval mechanisms are proposed: a

Academic Radiology, Vol 14, No 8, August 2007 NLM

graphical query mechanism, where an example image is usedto indicate the osteophyte severity and malalignment, and agraphical category mechanism, where osteophyte severityand malalignment are categorized using expert classificationand the categories are used for retrieval. Graphical queriesfor osteophyte severity and malalignment require retrieval bysimilarity of shape. Shape belongs to high-dimensional shapespaces and indexing for retrieval in such spaces is an openproblem. The P.I. has developed a mathematical frameworkfor indexing in such spaces. This framework is unique inthat it guarantees that the indexing tree that is best adaptedto the given data distribution in high dimensional spaces willbe found. The extension of this framework and its applica-tion to NHANES H is one of the main goals of the proposedresearch. Graphical categories for osteophyte severity andmalalignment can also be constructed from shape indexingtrees. The idea is to approximate the category by a union ofnode covers in the indexing tree. Such a category creationmechanism with controllable error rates is proposed and itsapplication to NHANES II is suggested. Expert classificationavailable from NHANES H and from the co-investigator(who has expertise in interpreting spine x-rays) will be usedto train the graphical category. Validation for graphical que-ries and categories with NHANES II images is proposed.Validation will be carried out with the help of the co-investi-gator who is an expert in this domain.

Thesaurus Terms: bone imaging/visualization/scanning,image processing, indexing, information retrieval, informa-tion system, morphology, radiography computer graphics/printing, mathematical model bioimaging/biomedical imag-ing, human data

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

Fiscal Year: 2003Department: Diagnostic RadiologyProject Start: 30-Sep-2003Project End: 29-Sep-2006ICD: National Library Of MedicineIRG: BLR

DECISION SUPPORT SYSTEMS FOR MAG3RENOGRAPHY

Grant Number: 5R01LM007595-03PI Name: Taylor, Andrew T.

Abstract: Description (provided by applicant): The currenthealth care system requires physicians to master an ever-expanding knowledge base while the hours available to mas-ter this knowledge base and apply it to specific tasks (e.g.,
image interpretation, seeing a new patient) are steadily
shrinking. The convergence of an expanding knowledge baseand escalating time constraints poses a serious problem thatwill inevitably lead to physician errors. Solutions to thisproblem require the development of new tools and processesto save physician time and facilitate the application of abroad and sophisticated knowledge base to speci5c clinicalproblems. Our long-term objective is to improve the care ofnephrourology patients and we propose to meet this objec-tive by developing new tools (Decision Support Systems) to(1) assist and educate physicians and trainees to appropri-ately perform and interpret Tc-99m mercaptoacetyltriglycine(MAG3) renography and (2) to process, check quality con-trol and actually interpret MAG3 renograms. Specijkally, wehypothesize that we can develop Decision Support Systemsto interpret adult MAG3 scans as well as a panel of experts.We have chosen to develop Decision Support Systems forMAG3 renography because (1) the vast majority of the esti-mated 400,000 radionuclide renal scans performed annuallyin the United States are interpreted by radiologists who lackthe time to develop the needed expertise and (2) MAG3 isused in over 70% of studies. We propose to develop twoseparate Decision Support Systems using totally differentapproaches, a heuristic model (knowledge based expert sys-tem) and a predictive statistical system. These Systems willbe developed from a database of 3500–4000 MAG3 studiesand will be designed to acquire the study, generate imagesand curves from a dynamic radionuclide renogram, check forerrors, extract the relevant quantitative data and then usethese data to interpret the study. Moreover, the user will beable to query the Systems to obtain the supporting data andrules justifying a specific interpretation. The heuristic andpredictive statistical approaches will clarify the relative mer-its of each approach and will provide a template for the de-velopment and application of similar diagnostic and educa-tional aids in the future. Finally, the Decision Support Sys-tems will allow us to calculate the incremental contributioneach parameter makes to the diagnostic accuracy, delete su-perfluous measurements, minimize the time and effort re-quired to acquire, process and interpret renal scans, providean objective analysis of renogram data, facilitate wide dis-semination of interpretative criteria, foster standardized inter-pretation, teach physicians and trainees to perform and inter-pret renal scans as competently as experts, encourage moreappropriate utilization and, most of all, improve the accuracyof MAG3 scan interpretation and thereby enhance the careof nephro-urology patients.

Thesaurus Terms: computer assisted medical decision mak-ing, computer system design/evaluation, kidney imaging/visualization computer assisted diagnosis, informatics, inter-active multimedia bioimaging/biomedical imaging, clinicalresearch, human data, patient oriented research

Institution: Emory University1784 North Decatur Road, Suite 510
Atlanta, GA 30322
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Fiscal Year: 2004Department: RadiologyProject Start: 01-Sep-2002Project End: 31-Aug-2006ICD: National Library Of MedicineIRG: DMG

INFORMATION SYSTEMS INTEGRATION--POINT-OF-CARE DELIVERY

Grant Number: 5F37LM007912-02PI Name: Tellis, Wyatt M.

Abstract: Description (provided by applicant): Recent ad-vances in information technology and process reengineeringhold the promise of improving both the efficiency andthroughput of medical organizations as well as reducing thepotential for medical errors. This research project will lookat the effectiveness of mobile computing technology in facil-itating radiology and emergency department (ED) communi-cation with the intended goal of improving the quality of theemergency department patient care. This project will exam-ine radiology department workflow to determine what digitalalternatives might act as more efficient replacements of thetraditional paper and phone-based notification systems. Theproject will proceed in four stages. The first is the imple-mentation of a system of timely notification for radiologistsof the arrival of urgent ED radiology exams. In the secondstage development of a system to capture the preliminary
note and transmit it to the requesting ED physician associ-
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ated with that exam will be developed. Expanding on theprevious stages, the third stage will consist of building amechanism for flagging a mismatch in findings between thefinal radiology report and the preliminary note, and subse-quently notifying the ED. The fourth and final stage involvesthe development of a PDA based radiology order entry sys-tem to permit ED physicians to place orders at the point ofcare. The appropriateness of specific mobile computing solu-tions in facilitating communication between the ED and Ra-diology Department will be evaluated. A successful solutionwill need to be flexible enough to allow a physician to bemobile and still remain connected, as well support bi-direc-tional communication. Due to the nature of the system de-ployment this study will have a pre/post study design. Met-rics for comparison will be gathered from existing clinicalinformation systems as well as through the applications builtfor the project.




Fiscal Year: 2004Department: RadiologyProject Start: 01-Jun-2004Project End: 31-May-2005ICD: National Library Of Medicine
IRG: BLR

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