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 radiologyThese abstracts are listed on the NIH Web page (httpwww-commons citnihgovcrisp) 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 httpsilknihgovsilkbrownbooksactcod

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

NOVEL RF COILS FOR IN VIVO MRAPPLICATIONS AT HIGH FIELD

Grant Number 5R01FB000513-04PI 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 coilrsquos size Theyresult in (i) severe degradation of coil quality factor andNMR sensitivity (ii) limitation for designing large size coilswith high operating frequency and (iii) complex B1 fielddistributions and difficulty for quantifying MRI intensityThese 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 fieldsThe 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 simulation

based on RF field modeling and MRI measurements and study-ing the implications of B1 field on MRI quantification (iii) con-ducting a series of study for systematically evaluating the pro-posed coils in comparison with other existing coils Successfuloutcomes from this research will provide an alternative and sat-isfactory solution of RF coil design at high fields and result insignificant technological advances in high-field RF coil engi-neering for in vivo MR applications

Thesaurus Terms biomedical equipment development im-age enhancement magnetic resonance imaging magneticfield mathematical model radiowave radiation bioimagingbiomedical 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

Imaging And BioengineeringIRG DMG

CRCNS DEVELOPMENT ampOPTIMIZATION OF MAGNETICSOURCE MRI

Grant Number 5R01EB004753-04

PI Name Gao Jia-Hong

e53

Academic Radiology Vol 15 No 4 April 2008

Abstract Description (provided by applicant) This proposalis aimed for development and optimization of a novel neuro-imaging method termed ldquomagnetic source MRIrdquo (msMRI)that uses a conventional MRI scanner in an innovative man-ner to measure electromagnetic signals from populations ofneurons The msMRI technique is based on directly detectingMRI signal changes associated with changes in magneticfields concomitant with neuronal filing Compared withpositron-emission tomography (PET) and functional MRI(FMRI) methods msMRI has improved spatial localizationand significantly better temporal resolution Compared withmagnetoencephalography (MEG) and electrophysiology(EEG) msMRI has superior spatial resolution The goal ofthis project is to systemically characterize rnsMRI signalapply this unique technique in initial human neuroscienceresearch and facilitate the use of msMRI among scientistsinvestigating basic neurophysiological and neuropsychologi-cal phenomena as well as accurate clinical diagnosticinter-vention methodology for brain diseases Three specific aimsare proposed for three years (1) to refine and extend mathe-matical models of msMRI (2) to optimize strategies for dataacquisition and analysis (3) to evaluate the extent to whichmsMRI signal fulfills the requirements of linear systems andits dependence on magnetic field strength This proposal is aperfect match of the mission of the NIBIB because the pro-posed msMRI is an innovative imaging technology thatshould significantly impact on research and clinical develop-ments in the fields of human neuroimaging cognitive neuro-science and neuropathology Magnetic source MRI couldrepresent a substantial advance for these fields and shouldhelp bridge the gap between human neuroimaging and elec-trophysiological methods employed in experiments with non-humans The power provided by msMRI technology is es-sential to understand human cellular neurophysiology and itsimplication on brain diseases

Thesaurus Terms biophysics brain electrical activity brainimaging visualization scanning functional magnetic reso-nance imaging magnetic field mathematical model technol-ogy technique development bioimaging biomedical imag-ing clinical research human subject patient oriented re-search

Institution University Of Chicago5801 S Ellis AveChicago IL 60637

Fiscal Year 2006Department RadiologyProject Start 01-Sep-2004Project End 31-Aug-2008ICD National Institute Of Biomedical

Imaging And Bioengineering

IRG ZRG1

e54

SHAPE OPTIMIZING DIFFEOMORPHISMSFOR COMPUTATIONAL BIOLOGY

Grant Number 1R01EB006266-01PI Name Gee James C

Abstract Description (provided by applicant) This proposalwill contribute a new collaboration for implementing rigor-ous spatiotemporal medical image analysis in a large scalecomputing environment The system will dramatically en-hance the neuroimaging communityrsquos quantitative under-standing of normal and pathological aging and correlatedvariables Medical images capture the changes that occur inan individual over time and samples the range of anatomicaland functional differences visible in a population lifespanOur goal is to associate these differences with causes forexample innate population variability injury pathology orthe effects of genotype on phenotype The recently proposedDiffeomorphometry (DM) system quantifies and relates thesevariables to an optimal spatiotemporal coordinate systemThis novel technique allows the atlas to evolve in time alongwith the population to statistically capture effects of agedisease or other factors This common evolving map spacegives a wealth of prior knowledge allowing one to buildprobabilities describing ranges and types of variation inshape and function These aggregate population attributesmay then be studied and visualized used in research as wellas teaching and diagnosis Our DM method is designed withthe axioms of symmetry (the algorithms must be symmetric)and specificity (the analysis should be optimal in the studyspace) in mind and with the ability to automatically generatedatabase-specific atlases The rigorous and symmetric defini-tion of change given by DM captures differences in neuro-anatomy with superlative accuracy reproducibility and highlevel of detail Consequently a DM study maximizes theinformation extracted from a neuroimaging cohort especiallywhen correlated with for instance genetic or behavioralvariables Furthermore DM satisfies pressing research needsin neuroimaging DM derives optimal atlases from arbitrarilysized databases and gives large deformation optimization ofanatomical correspondence through landmark and statisticalguidance The resources in the UCLA Center for Computa-tional Biology (CCB) will allow these methods to be appliedon the large datasets they were designed for and at an un-precedented resolution and scale The proposed work hasthree distinctive aims collaboration methodology and clini-cal evaluationapplication Instantiate a collaboration betweenUPenn and UCLA where data and algorithms are shared anddisseminated via the Center for Computational Biology De-velop Diffeomorphometry into a cutting-edge large-scalepublicly available computational tool Evaluate and refine thedeveloped methodology as well as compare with CCB brainmapping tools on neuroimaging studies of structure-function

associations under neurodegenerative conditions


Thesaurus Terms aging bioengineering biomedical engi-neering computational biology neuroimaging publicationbrain mapping information system motivation tissue

Institution University Of Pennsylvania3451 Walnut StreetPhiladelphia Pa 19104

Fiscal Year 2006Department RadiologyProject Start 01-Apr-2006Project End 31-Mar-2010ICD National Institute Of Biomedical

Imaging And BioengineeringIRG ZRG1

RESEARCH TRAINING IN MEDICALPHYSICS

Grant Number 5T32EB002103-18PI Name Giger Maryellen L

Abstract Description (provided by applicant) The GraduatePrograms in Medical Physics at the University of Chicagooffers research training at three levels that lead to the Masterof Science degree to the Doctor of Philosophy degree andpostdoctoral training Students working toward a graduatedegree in medical physics are expected to have completedtraining equivalent to that required for the SB degree in theDepartment of Physics at the University of Chicago Post-doctoral trainees are selected from candidates with the PhDdegree in Physics or equivalent fields Primary areas of re-search interests by the program faculty include Physics ofDiagnostic Radiology Physics of Nuclear Medicine Physicsof Magnetic Resonance ImagingSpectroscopy and Physicsof Radiation Therapy Major research facilities are the FrankCenter for Image Analysis the Kurt Rossmann Laboratoriesfor Radiology Image Research the Goldblatt MRI Centerthe NMR labs and the Scientific Visualization amp ImageAnalysis Core Facility in the Department of Radiology andthe Medical Physics Division in the Department of Radiationamp Cellular Oncology Unique features of this program arethe facultyrsquos focused effort on research in medical imagingand radiation oncology and on the training of high-levelmedical physicists Students and trainees are required to takecourse work participate in seminars and journal club meet-ings assist in research projects and complete a researchproject under supervision of a faculty member Researchprojects may be theoretical or experimental studies in digitalradiography diagnostic performance computer-aided diagno-sis magnetic resonance imaging and spectroscopy imagereconstruction nuclear medicine imaging positron emissiontomography computer applications in radiation therapy dosecomputation and verification multi-modality image correla-

tion or dosimetry Beyond the medical physics core courses

all trainees take an ethics course on the responsible conductof research and serve as teaching assistants The number ofcurrent program faculty is 22 The number of current predoc-toral students is 18 There are two NIH postdoctoral traineesin the program at the present The number of trainees forwhich funding is requested is four per year at the predoctorallevel (2 first-year and 2 second-year trainees per year) and 2per year postdoctoral level It should be noted that this is acompetitive renewal application written in the 14th year of amedical physics training grant that initiated in NCI and wastransferred recently to NIBIB

Thesaurus Terms There are no thesaurus terms on file forthis project


Fiscal Year 2007Department RadiologyProject Start 01-Jun-1990Project End 30-Apr-2010ICD National Institute Of Biomedical

Imaging And BioengineeringIRG ZEB1

IMAGING ISLETS IN IMPLANTABLEMICROCAPSULES

Grant Number 1R01EB007456-01PI Name Gimi Barjor

Abstract Description (provided by applicant) The overallgoal of our research project is to develop cubic microcap-sules that can effectively encapsulate individual islets Threeorthogonal surfaces of the microcapsules will be nanoporousto immunoprotect the islet cells from the host while allowingthe free exchange of nutrients waste products glucose andinsulin between the encapsulated islet cells and the host Thethree nanoporous surfaces will also be transparent so as tooptically probe the encapsulated isletrsquos calcium fluxes andmitochondrial response to glucose and test the hypothesisthat encapsulation does not affect islet function On the otherthree surfaces we will mount radio frequency (RF) sensorsfor MRI We will use MRI to image islet function using ac-tivation-based uptake of the contrast agent manganese Wewill test the hypothesis that islet function and viability canbe assessed through MRI post encapsulation The strengthof our approach is that we can provide elements that are cur-rently elusive in encapsulated islet cell therapy 1) immuno-protection of islets from the host through extremely well-controlled porosity of the encapsulation device not achievedwith tortuous polymers 2) a large surface-to-volume ratiothat provides oxygen and nutrients to the individual islets

not achieved with present day MEMS based biocapsules 3)

e55


direct imaging of the viability of encapsulated islets throughoptical methods and 4) direct noninvasive periodic andfunctional imaging of the encapsulated islets Our approachcan be easily adapted to encapsulate any native or geneti-cally modified beta cells and our devices may be mountedwith a plethora of sensors to measure oxygen pH tempera-ture and other environmental conditions in vivo


Institution University Of Texas Sw MedCtrDallas

Dallas TX 753909105Fiscal Year 2006Department RadiologyProject Start 22-Sep-2006Project End 31-Aug-2009ICD National Institute Of Biomedical

Imaging And BioengineeringIRG ZDK1

IMPROVED PRIORS AND ALGORITHMSFOR ECT RECONSTRUCTION

Grant Number 5R01EB002629-11PI Name Gindi Gene R

Abstract Description (provided by applicant) Our broadlong-term goal is to develop and optimize statistical recon-struction for emission computed tomography (ECT) Onegoal is the development of fast iterative MAP (maximum aposteriori) reconstruction algorithms A second goal is thedevelopment of theoretical methods to rapidly optimize theMAP reconstruction to maximize performance on a varietyof lesion detection tasks for SPECT The two goals arelinked in that scalar figures of merit for lesion detection inMAP-reconstructed images can be quickly calculated by ourtheoretical means While our aims focus on SPECT our fastreconstruction algorithms can also be used for PET We shallcontinue our development of fast convergent ordered-subsetMAP algorithms that free the user from setting hand-tunedparameters such as the relaxation schedules needed by com-peting approaches We will also develop for SPECT theo-retical expressions that incorporate MAP objectives andmodel observers to predict lesion detection performance byhuman observers Established model-observer-based methodsthat use many sample reconstructions can also do this butour theoretical methods can be 2 to 4 orders of magnitudefaster This speed allows a user to quickly optimize lesiondetection with respect to these reconstruction parametersdegree of regularization choice of prior model and systemmodel error in geometric response attenuation and scattercorrection Attenuation and scatter correction modeling re-

quire that we develop methods to propagate the noisy esti-

e56

mates of scatter or attenuation into the system model Thisfast evaluation of image quality allows one to narrow theparameter ranges that control image quality so that humanROC studies can be applied with this reduced parameter setFor SPECT we have developed analytic means for predict-ing detection figures of merit for MAP reconstructions ofsignal-known-exactlybackground-known-exactly objects butwe propose to extend our methods to a variety of more real-istic cases including signal-location unknown and variablesignal size Background variability affects detection and wepropose to use real statistical background models derivedfrom autoradiographic animal data to explore this issue Weshall validate methods using sample and human observerstudies Our contributions lie in new methodologies for opti-mization of reconstructions for lesion detection and in easy-to-use fast reconstruction methods

Thesaurus Terms brain imaging visualization scanningimage enhancement mathematical model model design de-velopment positron emission tomography single photonemission computed tomography statistics biometry diagno-sis design evaluation digital imaging phantom model ani-mal data autoradiography bioimaging biomedical imaginghuman data

Institution State University New York StonyBrook

Stony Brook NY 11794Fiscal Year 2007Department RadiologyProject Start 01-Jun-1995Project End 30-Jun-2009ICD National Institute Of Biomedical

Imaging And BioengineeringIRG BMIT

QUANTITATIVE MT IMAGINGDEVELOPMENT AND APPLICATION

Grant Number 5R01EB001452-02PI Name Gochberg Daniel F

Abstract Description (provided by applicant) The overallgoal of this project is to develop and optimize a magneticresonance imaging (MRI) technique for novel quantitativemeasurements of the macromolecular content and dynamicsin tissues with special relevance to the characterization ofbrain myelin The applicant has demonstrated in previouswork that a novel MRI technique can be used to quantify (heralio of the sizes of macromolecular and free water protonpools in biological systems and provide a quantitative mea-sure of the magnetization transfer (MT) rate constant be-tween these different tissue subcomponents The proposedstudies will further develop and optimize this technique will

compare this technique to other MT techniques and vll use


the optimum technique in combination with multi-componentT2 measurements to investigate the changes in water cem-partmeritation and exchange rates that occur in white matterand demyelinated lesions The specific aims of the projectare as follows to further develop selective inversion re-covery (SIR) and to optimize both SIR and the pulsed satu-ration technique for speed reliability and accuracy for quan-titatively measuring novel tissue properties to compareSIR to pulsed saturation and to validate both these methodsagainst a known standard in a series of measurements onmodel biopolymers to evaluate optimized methods ofquantitative MT imaging in biopolymers and in vivo inhealthy rats to evaluate the sensitivity of quantitative MTimaging to changes in brain matter due to demyelinationinflamation and axonal loss as revealed by histology pro-ducing information that will further develop applications ofMRI in multiple sclerosis

Thesaurus Terms brain disorder diagnosis brain imagingvisualization scanning magnetic resonance imaging mye-lin protein quantitation detection technology techniquedevelopment axon cell death experimental allergic encepha-lomyelitis inflammation macromolecule molecular dynam-ics myelinopathy proteomics laboratory rat

Institution Vanderbilt UniversityMedical CenterNashville TN 372036869

Fiscal Year 2006Department Radiology amp Radiological ScisProject Start 12-Jul-2005Project End 30-Apr-2009ICD National Institute Of Biomedical


HIGHER SPEED FIELD amp SPATIALRESOLUTION BRAIN 3D 1H MRS

Grant Number 5R01EB001015-12PI Name Gonen Oded

Abstract Description (provided by applicant) Changes inmetabolic levels observed with proton-magnetic-resonance-spectroscopy (rsquoH-MRS) are frequently used to augment thehighly sensitive (but not specific) MRI At 15 Tesla MRShas so far linked anatomy from MRI with the underlyingmetabolism in cancer epilepsy Alzheimerrsquos disease multi-ple sclerosis HIV infection stroke and other disorders of thecentral nervous system (CNS) Therefore it was anticipatedthat high-magnetic-field (Bo) 15 T) imagers would providersquoH-MRS a much needed boost in sensitivity Unfortunatelythat has not happened Translating the most useful 2 and 3dimensional (3D) rsquoH-MRS techniques to high-Bos has been

stymied by high radio-frequency (BI) power requirements

short TZ reducing the signal-to-noise-ratio (SNR) gainchemical shift misregistration errors and scarcity of softwareto shim design 3D localization evaluate and display thelarge 3D MRS data sets The long term goal of this compet-ing continuation is to develop and implement 30 rsquoH-MRSmethods to address the above issues and perform better athigher BG They will be extensions of the hybrid techniquesdeveloped in the past two cycles Specific Aim 1 will exploitthe shorter T2s for (a) 3D coverage by optimal interleavingof ldquoslabsrdquo across the volume-of-interest each thin enough toexcite with the available B1 under strong gradients to mini-mize the misregistration error and (b) increase the spatialresolution to ((1 m)voxels and extend coverage all theway to the skull Specific Aim 2 will introduce 3D localiza-tion into our non-echo non-localized whole head rsquoH-MRSto provide a rapid imager-side lower-resolution ldquometaboliclocalizerrdquo Specific Aim 3 will utilize the increased sensitivityto produce very high spatial resolution (05ndash0375 m) vox-els in restricted regions eg the optic nerve or spinal cordboth of which are currently inaccessible Finally SpecificAim 4 will develop novel methods to detect and visualizerelationships between different metabolitesrsquo spatial distribu-tions to simplify the staggering often confusing amount ofinformation generated by 3D rsquoH MRS The health related-ness of this project is its extension of increased spatial reso-lution volume covered and shorter acquisition time 3D rsquoH-MRS methods to high 23 T magnetic fields to support on-going and future studies of CNS metabolism associated withmultifocal and diffuse diseases


Institution New York University School OfMedicine

550 1st AveNew York NY 10016

Fiscal Year 2006Department RadiologyProject Start 22-Jul-1996Project End 31-Aug-2008ICD National Institute Of Biomedical


PROTON RELAXATION AND CONTRASTMECHANISMS IN MRI

Grant Number 5R01EB000214-16PI Name Gore John C

Abstract This proposal aims to continue studies to betterunderstand the factors that affect the NMR relaxation proper-ties of protons in tissues and which determine contrast in

MR images We aim to better understand the factors that

e57


influence the fundamental processes involved in relaxation intissues at the molecular and cellular level In the next phaseof this program we will continue to study processes that arelikely to become more important with increasing fieldstrength We will continue to measure the absolute values ofrates of magnetization transfer andrsquo proton pool sizes of pro-ton pools undergoing exchange using novel transient meth-ods and to distinguish MT effects due to chemically shiftedlabile protons from those due to intact water molecules Weaim to quantify the contributions of different chemical spe-cies to the increased rate of transverse relaxation at highfields We also propose three new directions for better under-standing relaxation in tissues and for developing new imag-ing methods based on novel contrast mechanisms First wewill further develop and understand the information obtain-able from the creation of intermolecular multiple quantumcoherences (IMQC) in water in tissues which has evolved asan important new imaging technique for characterizing tissuestructure We aim to elucidate the signal dependence inIMQC-MRI on tissue structure relaxation times diffusionchemical shift heterogeneity and pulse sequence timingsSecond we will implement T1 rho imaging and make mea-surements of T1 rho dispersion as a function of locking fre-quency in order to probe the importance of slow motionsand slow exchange on relaxation Third we will investigatethe correlation between spatial patterns of quantitative mea-surements of relaxation rates and other NMR parameters andthe corresponding patterns of protein expression as measuredusing imaging mass spectrometry We will develop multipa-rameter high resolution 3D MR imaging techniques at 94Tin mice and use imaging mass spectrometry (MALDI) torecord the spatial distributions of different molecular weightspecies within corresponding tissue slices at comparable spa-tial resolution We will then use multivariate correlationalmethods to explore whether specific patterns of protein ex-pression within tissues correlate with specific tissue charac-teristics measured by quantitative MRI We will study a se-lected group of tissues and biopolymers in different condi-tions and of varied composition Overall this project shouldprovide many new insights into tissue relaxation phenomenato aid in the better understanding of the origin of contrast inNMR images and to motivate new approaches to tissue char-acterization

Thesaurus Terms hydrogen ion image enhancement mag-netic resonance imaging molecular cellular imaging tech-nology technique development three dimensional imagingtopography biophysics brain neoplasm computer programsoftware disease disorder model molecular weight proteinquantitation detection proteomics bioimaging biomedicalimaging laboratory mouse matrix assisted laser desorptionionization nuclear magnetic resonance spectroscopy

Institution Vanderbilt UniversityMedical Center

Nashville TN 372036869

e58

Fiscal Year 2006Department Radiology amp Radiological ScisProject Start 01-Jul-1985Project End 31-Jul-2009ICD National Institute Of Biomedical


PREDOCTORAL TRAINING PROGRAM INBIOMEDICAL IMAGING

Grant Number 5T32EB003817-03PI Name Gore John C

Abstract Description (provided by applicant) This applica-tion seeks support for a comprehensive pre-doctoral trainingprogram in imaging science at Vanderbilt University whichwill be provided by an experienced and expert faculty andresearch staff The field of in vivo medical imaging has de-veloped from early uses of simple X-rays for diagnosis intoa compendium of powerful techniques for patient care andthe study of biological structure and function Imaging inbiomedical applications provides valuable information abouttissue composition morphology and function as well asquantitative descriptions of many underlying biological pro-cesses Continuing technical developments have expandedthe applications of imaging to new areas of biology such asthe study of gene expression in animals There is a criticalneed for imaging specialists trained in different techniquesand modalities and able to relate imaging to applications inbiology and medicine and to make the connections betweenimaging and physiology biological structure metabolismand cellular and molecular processes The program proposedwould provide graduate training in imaging science withinthe context of a leading research medical center and dedi-cated Institute of Imaging Science and strong science andengineering departments We propose a comprehensive train-ing program designed for 12 outstanding predoctoral scien-tists (6 in each of two years) We aim to recruit trainees intoour existing biomedical engineering physics or molecularphysiology and biophysics graduate programs They will re-ceive thorough and exemplary instruction in all of the cog-nate areas relevant to biomedical imaging in a coherent pro-gram that includes 23 PhD teaching faculty experienced inmultimodality biomedical imaging and its applications Thiswill be accomplished through an educational program con-sisting of courses seminars and journal clubs a practicalprogram consisting of faculty-led tutorials and practical rota-tions and a research program in which trainees will be inte-grated into an active research program The research oppor-tunities include active projects in nearly all major imagingmodalities and are especially strong in MRI MRS opticaland nuclear imaging as well as image analysis Trainees will

have access to outstanding facilities including human MR


systems with field strengths of 15 3 and 7T animal MRsystems of 47 7 and 94T multi-system optical imagingincluding OCT bioluminescence and multi-photon micros-copy microCT microSPECT and microPET Trainees willbe mentored in the ethics and methods of biomedical re-search as well as in grant writing and other important careerskills The programs personnel and facilities at Vanderbiltprovide unique opportunities for predoctoral students to re-ceive advanced training in biomedical imaging of the highestcaliber



Fiscal Year 2006Department Radiology amp Radiological ScisProject Start 01-Jul-2004Project End 30-Jun-2009ICD National Institute Of Biomedical


POSTDOCTORAL TRAINING INBIOMEDICAL MRI AND MRS


Abstract Description (provided by applicant) This applica-tion seeks support for a comprehensive postdoctoral trainingprogram in magnetic resonance imaging (MRI) and spectros-copy (MRS) at Vanderbilt University which will be providedby an experienced and expert group of faculty and researchstaff MR methods are well established as amongst the mostpowerful and widespread of biomedical imaging techniquesyet major advancements in technology and increases in theirimpact continue to occur MR methods serve not only as thesingle most important modality in diagnostic imaging butalso provide crucial insights into biological processes andstructure to address fundamental questions in biomedical re-search Advanced MR systems for research are available at alarge number of medical centers and further advances intheir uses will occur inevitably as systems with stronger fieldmagnets become more widespread There is however ashortage and a critical need for appropriately trained scien-tists capable of exploiting the potential of MR techniqueswho are aware of the uses and limitations of MR methodsand of how MRIMRS may be implemented advanced andintegrated with information available from other modalitiesWe propose a comprehensive training program designed for8 outstanding postdoctoral scientists (4 in each of a two-year

program) who will usually have had little previous signifi-

cant experience in biomedical MRI and MRS Postdoctoraltrainees from physics chemistry biology engineering ormedicine will receive thorough and exemplary instruction inall of the cognate areas relevant to biomedical NMR in acoherent program that includes 18 PhD faculty experiencedin biomedical MRIS and their applications This will be ac-complished through an educational program consisting ofcourses seminars and journal clubs a practical programconsisting of faculty-led tutorials and practical training anda research program in which trainees will be integrated intoan active research program These programs illustrate mostmajor aspects of the applications of MR methods in humansand animals and include functional and structural brain im-aging cancer biology studies of basic relaxation phenomenaand diffusion blood flow and perfusion metabolic imagingimage processing and analysis and clinical MRS and MRITrainees will have access to outstanding facilities includinghuman MR systems with field strengths of 15 3 and 7Tanimal MR systems of 47 7 and 94T and other imagingmodalities (including optical imaging microCT and micro-PET) Trainees will be mentored in the ethics and methodsof biomedical research as well as in grant writing and otherimportant career skills The programs personnel and facili-ties at Vanderbilt provide unique opportunities for scientiststo receive advanced training in biomedical NMR of the high-est caliber and will help to ensure that the remarkable in-sights into biology and disease that are possible with MRIand MRS will be realized



Fiscal Year 2006Department Radiology amp Radiological ScisProject Start 30-Sep-2003Project End 30-Apr-2008ICD National Institute Of Biomedical

Imaging And BioengineeringIRG ZGM1

INTEGRATED FUNCTIONAL IMAGING OFTHE HUMAN BRAIN


Abstract Description (provided by applicant) This is anapplication to establish a Bioengineering Research Partner-ship (BRP) to develop and integrate new technologies for thecomprehensive mapping of human brain function These willbe used to study functionally connected networks within the

brain and will provide the information for systems analyses

e59


of the neural bases of normal and abnormal behaviors Theywill be applied to study development in children and infantsas well as the neurobiological basis of various psychiatricdevelopmental and neurological disorders The BRP woulddevelop non-invasive instrumentation techniques and algo-rithms to acquire and combine the information obtainablefrom advanced high field magnetic resonance imaging (MRI)at 4 Tesla near infra-red optical imaging electrophysiology(including evoked responses) trans-magnetic stimulation(TMS) and computer data analysis and image processing Itwould develop and validate novel means of performing func-tional imaging studies and of recording cognitive and physi-ological responses within the environment of a 4T imagingmagnet as well as methods to combine the information fromthe various complementary techniques involved The partner-ship would bring together 6 core laboratories within YaleUniversity the host institution and would also closely in-volve 8 collaborating corporate partners as well as investiga-tors from 8 other universities (Vanderbilt Columbia andNew York Universities UNC UConn Oregon Health Sci-ences Center Medical College of South Carolina and theBronx VA Hospital) The BRP will include physicists engi-neers computer scientists neuroscientists psychologistspsychiatrists pediatricians and radiologists During Year 1advanced functional imaging methods will be implementedat 4T and the equipment needed for ERP and NW will bemodified for use in the magnet Similar developments ofthese modalities of TMS and psychophysical techniqueswill continue through years 2 and 3 The first three years ofthe BRP would focus on the development and validation ofnovel techniques for inducing and assessing brain activationin response to stimuli while years 4 and 5 would focus moreon developing methods for the integration of data obtainableby different means and for their analysis and interpretationin specific applications The establishment of a BRP wouldbe an ideal mechanism for bringing together different ap-proaches to the study of brain function and the integrationof the various methods will provide a valuable new resourcefor neuroscience research whose capabilities will far exceedthe sum of the separate components

Thesaurus Terms brain mapping functional magnetic reso-nance imaging neural information processing neuropsychol-ogy technology technique development brain disorder diag-nosis brain electrical activity computer data analysisevoked potential image processing neuroscience noninva-sive diagnosis psychophysics bioimaging biomedical imag-ing clinical research electrophysiology encephalographyhuman subject transcranial magnetic stimulation


Fiscal Year 2006

Department Radiology amp Radiological Scis

e60

Project Start 01-Jul-2002Project End 31-Mar-2008ICD National Institute Of Biomedical


MAGNETIC LEVITATION OFOSTEOBLASTS

Grant Number 1R21EB003947-01A2PI Name Hammer Bruce E

Abstract Description (provided by applicant) The goal ofthe proposed research is two-fold First does a time-invari-ant magnetic field between 15 Tesla and 17 Tesla affectgene expression and cell differentiation Second is magneticlevitation a suitable ground-based alternative for space-basedorbital freefall experiments For the levitation studies weplan to monitor gene expression via microarray analysis andosteoblast differentiation by quantitative real-time PCR Themurine calvarial osteoblast cell line MC3T3-E1 is themodel biological system for these experiments Magneticlevitation occurs when a magnetic force counterbalances agravitational force Placing a biological (diamagnetic) objectin a strong magnetic field and a strong magnetic field gradi-ent creates a magnetic force on the system A magnetic forceis the only means to reduce the net gravitational force on asystem to less than 1-g Osteoblast cells have a demonstratedsensitivity to gravitational loading conditions These cellswill be cultured in a unique 17 Tesla50 mm warm bore su-perconductive magnet to study the effect of a net rsquogravitationforce varying from 0-g through 2-g on gene expression andosteoblast biochemical markers The magnet is capable ofsustaining continuous levitation for weeks at a time Moni-toring bone osteoblast differentiation and function under con-ditions where net the gravitational force is a variable repre-sents a unique venue for understanding the effect of gravita-tional forces on bone growthresorption This is a new areaof scientific exploration that has not been explored becauseof limited access to magnet systems capable of magneticlevitation Furthermore with this instrument it is now possi-ble to study biological function at 038 g and 0167 g thusproviding ground-based simulations of the gravitationalforces experienced on the surface of mars and the moonrespectively


Institution University Of Minnesota Twin Cities450 Mcnamara Alumni CenterMinneapolis MN 554552070

Fiscal Year 2005Department Radiology

Project Start 15-Sep-2005


Project End 31-Aug-2007ICD National Institute Of Biomedical

Imaging And BioengineeringIRG MTE

UNCOVERING THE SPATIAL ORIGIN OFTISSUE-FMRI SIGNALS

Grant Number 5R21EB004460-02PI Name Harel Noam

Abstract Description (provided by applicant) The immenseimpact of the fMRI technique on the neuroscience commu-nity which allows noninvasive localization of active corticalregions is well reflected by the exponential increase of pub-lications utilizing this technique For the past decade greateffort has been put into increasing the spatial resolution andspecificity of fMRI signals from vessel-weighted to moretissue specific signals The working assumption is that theldquotissuerdquo signals closely mirror changes at the neuronal levelWhile great progress has been made the basic and most fun-damental questions remain unanswered Where in the tissuedo these ldquotissue-fMRIrdquo changes occur Do they indeed origi-nate at the site of the most active neuronslayer The aim ofthis study is to identify the spatial and anatomical origin ofthe fMRI signals to the level of cortical layers In this pro-posed study we will correlate high-resolution fMRI signals(015 015 mm2) with the underlying cortical laminar cy-toarchitectonic and microvascular structures in the same ani-mal and cortical section In this proposal a new method foridentifying and extracting the exact cortical tissue corre-sponding to the fMRI plane will be developed Once ex-tracted the corresponding cortical slab will undergo standardhistological staining procedures to uncover the laminar andvascular structures Thus based on histological criteria ob-tained from the matching tissue the spatial origin of tissuefMRI hemodynamic signals will be determined The impactand outcome of this study will greatly enhance our under-standing of the fMRI signal source This in return will openthe opportunity to study brain function and cerebral hemody-namic regulation at the laminar resolution levels that arecurrently unattainable

Thesaurus Terms brain circulation brain mapping functionalmagnetic resonance imaging gray matter hemodynamics im-age enhancement microcirculation neurophysiology visualcortex biological model capillary electrophysiology neuralinformation processing visual stimulus bioimaging biomedicalimaging cat histology microelectrode


Fiscal Year 2006

Department Radiology

Project Start 01-Jul-2005Project End 30-Jun-2007TCD National Institute Of Biomedical


MRS MEASUREMENTS OF GABA INTEMPORAL LOBE EPILEPSY

Grant Number 1R21EB005438-01A1PI Name Hetherington Hoby P

Abstract Description (provided by applicant) As the pri-mary inhibitory neurotransmitter in mammalian brainGABA its content and its receptor systems are the targets ofa number of anti-epileptic drugs Although Petroff and col-leagues have studied the effects of various anti-epileptics onbrain GABA levels in the occipital lobe a site distant fromthe epileptogenic region to date little information exists re-garding GABA levels in the epileptogenic region of patientswith temporal lobe epilepsy This data has largely shownthat brain GABA levels are decreased in patients with poorcontrol in comparison to healthy controls and are responsiveto a variety of anti-epileptic medications Conversely recentpreliminary microdialysis studies have shown that ECFGABA is higher in patients with sclerosis as opposed tothose without sclerosis (6) Additionally our preliminary datahas shown a similar correlation with ECF GABA inverselycorrelated with hippocampal NAA levels (ie higher ECFGABA levels are seen in patients with lower NAA levelsTo what extent total GABA in the epileptogenic region isincreased or decreased relative to control is unknown Simi-larly it is unknown if total GABA levels in the epileptogenicparallel GABA levels distant from the seizure focus Clearlythese questions may have significant impact on our under-standing of the factors leading to epileptogenic activity inthe seizure focus and also provide measures that may aidin the therapeutic management of epilepsy patients There-fore the development of robust methods for measuringGABA from the temporal lobe in patients with temporal lobeepilepsy would be of significant benefit


Institution Yeshiva University500 W 185th StNew York NY 10033

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


IRG ZRG1

e61


DIGITAL HAND ATLAS IN ASSESSMENTOF SKELETAL DEVELOPMENT

Grant Number 5R01EB000298-09PI Name Huang HKK

Abstract Description (provided by applicant) Bone ageassessment is a procedure frequently performed on pediatricpatients to evaluate their growth It is an important procedurein the diagnosis and management of endocrine disordersdiagnostic evaluation of metabolic and growth abnormalitiesdeceleration of maturation in a variety of syndromes malfor-mations and bone dysplasias It is also used for consultationin planning orthopedic procedures The most common clini-cal method for bone age assessment is atlas matching by aleft-hand wrist radiograph against a small reference set ofatlas patterns of normal standards developed by Greulich andPyle in the 1950s based on data collected in the first half ofthe 20th century (The Tanner-Whitehouse method is a sec-ond method that requires extensive measurement and com-parison of 20 bones against 9 possible stages of develop-ment It is tedious and unsuitable for a clinical environmentand thus rarely used) Unfortunately the Greulich and Pylereference radiographs do not reflect skeletal development inchildren and adolescents of todayrsquos European African His-panic or Asian descent Increasing racial diversity in theUnited States as well as changing nutritional and behavioralhabits of children show a need for reevaluation of the use ofskeletal age standards Our preceding efforts have validatedand confirmed the need for continued study This applicationis the third phase of our continuing effort and intends tocomplete the development of a flexible more relevant digitalhand atlas system that exploits novel trends in both demog-raphy and technology The digital atlas will be a large stan-dard set of normal hand and wrist images of children of fourdiverse ethnic groups It is comprised of 1080 (already col-lected and read) 400 (to be collected) reference imagesand computer-extracted bone objects and quantitative fea-tures removes the disadvantages of the out-of-date ethni-cally constrained Greulich-Pyle atlas and the tediousness ofTanner and Whitehouse scoring method These images arecollected from evenly distributed normal 1 to 18 years ofage male and female European African Hispanic andAsian descent A Web-based computer-aided diagnostic sys-tem for bone age assessment will be implemented wherequantitative features similar to those in the atlas are ex-tracted on a Web sewer and then compared with patternsfrom the digital atlas database as well as computer generatedscores to assess the bone age By the end of this study wewill have completed a digital hand atlas fully integrated witha Web-based sewer for quantitative consistent and reliablebone age assessment that can be performed anywhere any-time The user interface will be simple to apply and resem-

ble current bone age assessment procedures Two immediate

e62

benefits will be realized improved real-time clinical boneage assessment and the production of a research tool thatwill allow for ongoing evaluation of the traditional goldstandard techniques for bone age assessment These advan-tages combined with higher accuracy and fast turn aroundtime in diagnosis would gain acceptance by both pediatricradiologists and other clinicians

Thesaurus Terms age difference biomedical equipmentdevelopment bone development computer assisted diagno-sis computer program software computer system designevaluation digital imaging hand rapid diagnosis wrist Af-rican Asian European Hispanic American Internet com-puter network gender difference racial ethnic differencebioimaging biomedical imaging children clinical researchhuman subject

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

Fiscal Year 2006Department RadiologyProject Start 01-May-1997Project End 28-Feb-2008ICD National Institute Of Biomedical

Imaging And BioengineeringIRG ZLM1

BIOMEDICAL IMAGING INFORMATICSTRAINING PROGRAM

Grant Number 1T32EB004308-01A1PI Name Huang HKK

Abstract Description (provided by applicant) Medical Im-aging Informatics is the branch of imaging science that stud-ies imagedata information gathering processing manipula-tion storage transmission management distribution andvisualization as well as knowledge discovery from large-scale biomedical imagedatasets Recent advances in medicalimaging science and technology have made knowledge ofimaging informatics an essential tool in the synthesis andmanagement of medical images for patient care Althoughthere exist training programs in medical imaging and medi-cal informatics focused training dedicated to imaging infor-matics is limited because of its novelty This application pro-poses the development of a Medical Imaging InformaticsTraining Program leveraging the strengths of three existingacademic structures at the University of Southern California(USC) with modifications to suit the needs and requirementsof each trainee The three programs are Biomedical Engi-neering Department (BME) School of Engineering Radiol-ogy Department and the Joint MDPhD program located atthe School of Medicine By integrating the various assets

from these programs a powerful novel training program will


be created Unique strengths within these programs are 1Medical imaging and imaging informatics expertise andtraining facilities within the BME the Radiology ResidencyProgram and the Imaging Processing and Informatics Labo-ratory 2 Academic program administrative hierarchy USCOutreach Program established recruitment procedure oftrainees existing medical imaging and imaging informaticscourse curriculum and elective clinical rotations and alarge pool of potential candidates within the three aca-demic programs The trainees will benefit from the uniqueblending of two differing traditional educational culturesand methods at the Engineering and Medical Schools andas a group derives optimal career development adjustedfor each individual through the mixed and rich environ-ments The Application requests for five years with 4 66 6 6 trainees per year respectively equally divided forPhD degree candidates and Postdoctoral Fellowships TheBiomedical Engineering Dept will grant the PhD degreeswhile Fellowship Certificates will be granted by the Radi-ology Department





DOSE AND IMAGE QUALITY IN ADULTAND PEDIATRIC CT

Grant Number 5R01EB000460-03PI Name Huda Walter

Abstract Description (provided by applicant) CT accountsfor 10 of radiological exams but contributes 70 of themedical population dose Little work has been done to deter-mine doses to children CT scans are currently not opti-mized with scans performed at the same voltage (120 kV)irrespective of patient size and diagnostic task We will mea-sure doses and image quality when adult amp pediatric patientsundergo CT examinations Experiments will be performed onsix anthropomrphic phantoms (ie adult male amp female 10yo five yo one yo and a newborn)Radiation dose measure-ments in single 25 cm thick slabs permit determination ofenergy imparted (e) effective dose (E) as functions of pa-tient age and body region Accurate measures of patient en-

ergy imparted will take into account the size and characteris-

tics of the specific individual undergoing a CT examinationWe will validate our approach to CT dosimetry by conduct-ing field trials which will also yield data on individual organdoses (and uncertainties) that could be used in future epi-demilogical studies to investigate radiation risks Our anthro-pomphic phantoms will permit measurement of signal tonoise ratios (SNR) for important detection tasks in CT Vari-ations in SNR will be studied as a function of kVp mAs andpitch ratio (PR) Three human observer models will be in-vestigated to identify the one that best predicts observer per-formance The human observer model will be applied to is-sues of inter-scanner variability and the optimal reconstruc-tion filter for the detection of small low contrast lesionsDosimetery and image quality information will be combinedto identify which CT parameters result in the lowest patientdoses at equal imaging performance We will also investigatethe detection of simulated nodules in chest CT images toquantify the relative importance of structurequantum in clin-ical CT examinations Our image quality measurements willbe performed in all body regions (head chest abdomen pel-vis) and patients who range from the newborn to the adultThese dose amp image quality data will affect radiologicalpractice in three ways 1 Permit development of imagingprotocols to ensure that patient doses are to kept as low asreasonably achievable (ALARA) 2 Determine the choice ofkVpmAs and PRmAs that minimize patient doses with noloss of diagnostic performance 3 Help the Radiology com-munity to balance the confliciting requirements of imagequality and patient doses in clinical CT

Thesaurus Terms computed axial tomography diagnosisquality standard pediatrics radiation dosage abdomen headimage enhancement imaging visualization scanning pelvisphantom model thoracic radiography bioimaging biomedicalimaging

Institution Upstate Medical UniversityResearch AdministrationSyracuse NY 13210

Fiscal Year 2006Department RadiologyProject Start 01-Aug-2004Project End 31-Jul-2008ICD National Institute Of Biomedical


HIGH RESOLUTION DTI USING 3DSINGLE-SHOT ACQUISITION

Grant Number 1R21EB005705-01A1PI Name Jeong Eun-Kee

Abstract Description (provided by applicant) Diffusion

tensor imaging (DTI) provides information about the organi-

e63


zation of white matter tracts in the central and peripheralnervous systems DTI has been successfully applied to trac-tography of the brain and has potential usefulness in earlydiagnosis of white matter disorders Early changes in diffu-sion tensors may precede white matter changes visible onconventional MRI scans in diseases such as multiple sclero-sis However limitations in current DTI techniques have pre-vented its use in much of the brain and in the spinal cordoptic nerves and peripheral nerves where early changes ofMS may be manifest Diffusion tensor imaging requires longdata acquisitions and is therefore susceptible to image arti-facts arising from field inhomogeneity and patient motionThese artifacts are reduced with faster imaging Single- shotdiffusion tensor imaging methods have been developed toimage with greater speed thus reducing motion and inhomo-geneity artifacts at the cost of image resolution Multi-shotmethods have been developed to attain higher resolution butthese methods are subject to artifacts caused by phase incon-sistencies between multiple acquisitions We have developeda novel DTI technique three-dimensional single shot diffu-sion weighted imaging with stimulated echo acquisition(3D ss-DWSTEPI) which obtains diffusion information in asingle shot acquisition over a limited imaging volume Toour knowledge this is the first report on singleshot acquisi-tion of three dimensional volume This technique has thepotential to overcome limitations of currently used DTI tech-niques Three-dimensional imaging can give improved SNRand no loss of signal at the slice boundary in comparisonwith two-dimensional imaging The use of volume-selectiveexcitation to create interleaved three-dimensional subvolumeswill allow faster imaging with optimal echo train lengths Inthis project realtime navigation is proposed to monitor anyexcessive motion related error which may reduce DTI mea-surement accuracy and rejectreacquire the specific data Theproposed technique has the potential to make DTI possiblein important areas such as the spinal cord peripheral nervesoptic nerves and regions of the brain not currently accessi-ble by current DTI methods allowing earlier diagnosis ofwhite matter diseases such as multiple sclerosis


Institution University Of Utah75 South 2000 EastSalt Lake City UT 84112



IRG ZRG1

e64

PULMONARY GAS FLOW MEASUREMENTBY 3HE MRI

Grant Number 5R21EB004380-02PI Name Johnson Glyn

Abstract Description (provided by applicant) Broad long-term objectives To develop methods of measuring regionalpulmonary gas flow and volume using hyperpolarized 3HeMRI Health Relatedness Small airway disease is responsi-ble for considerable morbidity and mortality Current meth-ods of assessing lung disease are either global rather thanregional or reveal lung anatomy rather than function and aretherefore often of limited use particularly in assessment ofsmall airway disease This project will develop a potentiallymuch more sensitive method of assessing regional lung func-tion Specific Aims 1) To develop methods of dynamic im-age co-registration to project images acquired at differentpoints in the breathing cycle onto a single reference frame2) To adapt algorithms based on indicator dilution theory tothe measurement of gas flow Research Design 1) A combi-nation SPAMM tagged proton MRI and spirometry will beused to measure lung position during the respiratory cycleAffine transformations will then be applied to map lung po-sitions to a reference image frame 2) Dynamic spiral 3HeMRI will be performed during inhalation of hyperpolarized3He Standard indicator dilution algorithms will be appliedto the dynamic 3He images to calculate gas flow and volumeon a pixel by pixel basis

Thesaurus Terms image processing magnetic resonanceimaging respiratory airflow measurement respiratory imag-ing visualization technology technique development he-lium mathematical model respiratory gas bioimaging bio-medical imaging clinical research human subject





HIGH SPECTRALSPATIAL RESOLUTIONIMAGING BREAST CANCER


PI Name Karczmar Gregory S


Abstract Description (provided by applicant) Conventionalmagnetic resonance imaging has good sensitivity for detect-ing breast lesions but its specificity is inadequate High spec-tral and spatial resolution (HISS) Magnetic Resonance Imag-ing (MRI) of water and fat signals is a new approach thatmay increase both sensitivity and specificity of MRI HiSSMRI equals or exceeds the spatial resolution of conventionalMRI and provides detailed spectra of the water and fat ineach voxel The water and fat lineshapes are analyzed toproduce images proportional to resonance linewidth peakheight integral changes following contrast media injectionand other parameters HiSS MRI images are acquired withclinically acceptable run times using echo-planar spectro-scopic methods Previous work in this laboratory demon-strated quantitatively that contrast edge delineation and sen-sitivity to contrast agents in breast images derived fromHiSS data are improved compared to conventional imagesAlthough these results are promising the methods used fordata acquisition and processing were not optimal In addi-tion there has been very limited experience with imagingsmall breast lesions Therefore the present application pro-poses technical improvements to HiSS and tests of themethod for imaging small breast lesions in women who arelater biopsied Technical improvements to HiSS imagingData acquisition rates will be increased by sampling twolines of k-space in parallel Improved data filtering methodsand corrections for errors in k-space sampling will be imple-mented Methods for generating images of Fourier compo-nents of the water resonance in each voxel will be developedand tested Scans of small breast lesions HiSS will be incor-porated into the clinical breast imaging protocol used at theUniversity of Chicago In women who are known to havesmall breast lesions based on mammographic findings HiSSscans will be performed before contrast media injection at 3minutes after contrast media injection and at 20 minutesafter injection Images derived from HiSS datasets will bequantitatively compared to conventional images to determinewhether HiSS improves sensitivity to features of lesions thatare associated with malignancies such as spiculations andinhomogeneous contrast media uptake In addition the exper-iments will determine whether addition of HiSS imaging toclinical scans significantly improves sensitivity and specific-ity

Thesaurus Terms breast neoplasm breast neoplasm cancerdiagnosis contrast media diagnosis design evaluation diag-nosis quality standard magnetic resonance imaging bioim-aging biomedical imaging clinical research female humansubject patient oriented research


Fiscal Year 2006


Project Start 15-Sep-2003Project End 31-Jul-2008ICD National Institute Of Biomedical


NEW TECHNOLOGY FOR COMPUTEDRADIOGRAPHY

Grant Number 5R01EB004015-03PI Name Karellas Andrew

Abstract Description (provided by applicant) This researchis aimed at exploring developing and evaluating a new typeof computed radiography (CR) for digital mammographyThis approach is designed to overcome the well-known limi-tations of current CR technology that are associated withsupoptimal spatial resolution and dose efficiency CR tech-nology is the low cost approach to digital mammography butit has never been used clinically in the US due to the slowpace of development and the lack of a trully innovative ap-proach The proposed approach represents a radical departurefrom prior technology It incorporates readily-available com-ponents and integration can be inexpensive The results ofour extensive computational and experimental work thatsuggest good image quality and dose efficiency will be usedto develop a prototype that incorporates the components forscanning CR plates This would enable high optical signalcapture efficiency faster readout good spatial resolutioncompact size and low cost Evaluation of the electronic op-tical and mechanical characteristics of the system will beperformed that will prompt modifications for improved per-formance Universally accepted methodology such as modu-lation transfer function and detective quantum efficiency willbe applied for the evaluation of the imaging capabilities andoverall performance of the new imaging system Thresholdcontrast detail studies will be conducted to compare its per-formance with current technologies It is anticipated that thisnew digital x-ray imaging approach will enable greater con-trast and spatial resolution than existing state-of-the-art CRtechnology that has been attempted for digital mammogra-phy CR technology is ideally suited and desperately neededfor cost efficient digital mammography but the current tech-nology has not yet met the high image quality standards thatare required for this task This research deals not only withthe development of a protoype but also with the theoreticalformulation to predict the performance of the proposed andaother types of CR devices under a variety of conditionsThis would enable the development of state-of-the art CRdevices that are equivalent or better to other x-ray imagingmodalities with the added advantage of portatbility and easeof integration The potential impact of this inherently low-cost high resolution CR plate reader in a cassette-like pack-age can be very high as it can be easily adapted to the needs

of current clinical practice

e65


Thesaurus Terms computer system design evaluation dig-ital imaging image enhancement mammography radiogra-phy technology technique development biomedical equip-ment development clinical biomedical equipment healthcare cost financing pediatrics portable biomedical equip-ment radiation dosage radiodiagnosis thoracic radiographywhole body imaging scanning bioimaging biomedical imag-ing

Institution Emory University1599 Clifton Road 4th FloorAtlanta GA 30322

Fiscal Year 2007Department RadiologyProject Start 20-Sep-2005Project End 31-Jul-2009ICD National Institute Of Biomedical


PATIENT MOTION DETECTION ANDCOMPENSATION IN SPECT

Grant Number 5R01EB001457-04PI Name King Michael A

Abstract Description (provided by applicant) Patient mo-tion is an ever-present potential cause of artifacts that canlimit the accuracy of diagnostic imaging The problem isespecially significant for imaging modalities such as SPECTand PET which require the patient to remain motionless forprotracted periods of time Compensation strategies for mo-tion that rely exclusively on the emission data itself al-though commercially available are inadequate for robustclinical usage The goal of the proposed investigations is todetermine if information from a visual-tracking-system willprovide a robust compensation for patient motion as part ofiterative reconstruction By visual-trackingsystem it is meanta computational system that processes stereo-images takenby optical cameras thereby providing a source of motion in-formation that is independent of the SPECT system Motionof the chest and abdomen will be determined by tracking thelocations of a pattern that is part of a stretchy garmentwrapped about these portions of the patient The types ofpatient motion for which compensation will be investigatedwith the visual-tracking-system are rigid-body motion non-rigid-body motion respiratory motion upward-creep of theheart and motion between sequential emission and transmis-sion CT or MRI imaging The ultimate test of the success ofthe visual-tracking-system based compensation will be physi-cian-observer ROC studies comparing the detection accuracyof coronary artery disease with and without motion compen-

sation for patients undergoing SPECT perfusion imaging

e66

The first specific aim is to perfect the visual-tracking-systemand determine its accuracy for tracking rigid-body motionThe second specific aim is to modify the visual-tracking-system to include compensation for respiratory motion andupward-creep of the heart The third specific aim is to inves-tigate the need for non-rigid-body motion and whether themotion of the locations in the pattern on the garment canpredict the internal motion of structures when coupled withknowledge of the individual patientrsquos anatomy from multi-modality imaging on the same imaging bed The fourth spe-cific aim is to develop a motion-compensation algorithm thatemploys the information from the visual-tracking-system tocompensate for the above motions as part of list-mode itera-tive reconstruction The fifth specific aim is to determinewhether the visual-tracking-system and motioncompensationalgorithm are able to improve the diagnostic accuracy of car-diac-perfusion SPECT imaging as determined by human-observer ROC studies with clinical images

Thesaurus Terms biomedical equipment developmentbody movement image enhancement single photon emissioncomputed tomography computer assisted diagnosis diagnosisdesign evaluation optics patient monitoring device photog-raphy bioimaging biomedical imaging clinical research hu-man subject patient oriented research

Institution Univ of Massachusetts Med SchWorcester

WORCESTER MA 01655Fiscal Year 2006Department RadiologyProject Start 01-Jun-2003Project End 31-May-2008ICD National Institute Of Biomedical


ULTRAFAST LASER-BASED X-RAYIN-VIVO PHASE-CONTRAST MICRO-CT

Grant Number 5R21EB005055-02Project TitlePI Name Krol Andrzej

Abstract Description (provided by applicant) Emergingphotonic technologies such as ultrafast lasers provide a newparadigm for overcoming the limitations of traditional bio-medical imaging modalities In this project we propose todevelop in-line x-ray phase-contrast micro-CT system thatwill utilize an ultrafast laser-based x-ray (ULX) source Thisnew source produces x-rays through irradiation of a solidtarget by the laser beam Any solid (metal or non-metal) canbe used as a target ULX delivers more power in x-rays thana conventional microfocal tube is able to provide thus al-

lowing for much faster scans Further ULX generates nar-


row x-ray spectra that consist mainly of characteristic linesThese can be easily tailored (by changing laser beam target)to the imaging task The phase-contrast micro-CT will allowhigh-resolution measurements of the spatial distribution ofthe real (x-ray phase-shift) and the imaginary (x-ray absorp-tion) components of the x-ray refractive index in a livinganimal This is in contrast to conventional micro-CT using amicrofocal x-ray tube which can only map 3D distributionof the x-ray absorption coefficient Therefore we expectthatrsquoopening the new channel of information provided by thex-ray phase-shift 3D mapping in addition to conventionalabsorption map measurement will significantly increase softtissue low-contrast resolution of micro-CT without any doseincrease thus allowing improved imaging of cancer in smallanimal models In due course this method could be ex-panded to clinical CT scanners providing that the high aver-age power ultrafast lasers become available Compact ro-bust ultrafast lasers are commercially available and theircharacteristics are rapidly improving We plan to constructand explore imaging performance of an in vivo in-line x-rayphase-contrast ULX micro-CT system This goal will be ac-complished by completing the following tasks i) design andoptimization via computer simulations of the optimal systemgeometry and the focal spot size and shape ii) design andoptimization via computer simulations of ULX spectraiii) experimental implementation and optimization of the se-lected system design iv) development of image processingtools for correction extraction enhancement and fusion ofthe extracted phase-contrast and absorption tomographic dataand improved fusion of absorption and phase-contrast im-ages v) assemble a cone-beam ULX phase-contrast mi-cro-CT system (with optimized geometry energy focal spotand detector) and begin exploration of the imaging perfor-mance of the whole system and comparison with conven-tional micro-CT using phantoms and in vivo imaging of oralcancer mouse model

Thesaurus Terms computed axial tomography imageprocessing laser technology technique developmentthree dimensional imaging topography computer simula-tion image enhancement mouth neoplasm phantommodel radiation dosage bioimaging biomedical imaginglaboratory mouse




IRG BMIT

NEW IMAGING AGENTS FOR STUDYINGGENE EXPRESSION

Grant Number 1R21EB005242-01A1PI Name Kung Hank F

Abstract Description (provided by applicant) We proposeto develop F-18 and 1-123 labeled nucleosides as selectivesubstrates of herpes simplex thymidine kinase (HSV1-TK) inconjunction with positron computed tomography (PET) In-troduction of HSV1- TK in tumor followed by gancyclovir(GCV) treatment has been successfully tested as a suicidegene therapy for cancer therapy Labeled nucleosides (suchas [1-123124]FIAU and [F-18JFHBG) selectively targetingthe HSV1-TK enzyme are useful as reporter probes for mea-suring HSV1-tk gene expression in vivo by PET or SPECTimaging Based on this approach HSV1-tk gene expressioncan also be used as a surrogate marker gene for expressionof other genes (transgenes) determined by the labelednucleosides as in vivo imaging probes The objective of thisproject is to design synthesize and characterize a series ofnovel labeled nucleosides 2=-deoxyuridine and FIAU ana-logs (group A and B) as superior imaging agents for mea-suring in vivo gene expression Currently [F-18]FIAU ismore effective for imaging HSV1-TK but the synthesis ofthis F-18 probe is very long and difficult [F-18]FHBG iseasier to prepare but only effective for imaging a mutantHSV1-TK(sr39) The purposes of developing these novelnucleosides are 1) to prepare F-18 radiolabeled group A andB nucleosides 2) to identify improved F-18 nucleosideprobes with desired in vivo kinetics for higher target to non-target ratio and a higher selectivity between the human TKvs viral HSV1-TK enzyme and 3) to test the correlation be-tween gene expression and probe-uptake in a doxycyclineinducible HSV1-TK expressing cell line It is likely that thenew probes can be selectively phosphorylated by the viralenzyme as such they may be superior for measuring theconcentration of HSV1-TK enzyme levels in the tumor cellsThey will have several useful properties ability to cross thecell membrane and a minimum influence from other meta-bolic steps of nucleosides and nucleotides Efforts will bemade to select tracers predominantly trapped in the targetedcells by the native HSV1-TK only and confounding signalsfrom other processes from native hTK1 and hTK2 enzymesare minimized In conjunction with PET these new imagingagents may enhance our ability to measure tk gene expres-sion in vivo thus they may enhance the probability of de-veloping new gene therapy approaches for various diseases


Institution University Of Pennsylvania3451 Walnut StreetPhiladelphia PA 19104

Fiscal Year 2006

e67


Department RadiologyProject Start 01-Apr-2006Project End 31-Mar-2008ICD National Institute Of Biomedical

Imaging And BioengineeringIRG MEDI

IMAGING VESICULAR MONOAMINETRANSPORTERS IN THE BRAIN

Grant Number 5R01EB002171-03PI Name Kung Hank F

Abstract Description (provided by applicant) Imaging ofvesicular monoamine transporter 2 (VMAT2) sites in thebrain by [C-11]DTBZ (dihydrotetrabenazine) in conjunctionwith PET (positron emission tomography) is useful in thediagnosis and monitoring of neurodegenerative diseases suchas Parkinsonrsquos and Huntingtonrsquos diseases In addition PETimaging of VMAT2 binding sites is also important for un-derstanding the mechanisms of regulation of monoamines inthe brain and its relationship with drug abuse and psychiatricdisorders Since C-11 is a short lived isotope with a half-lifeof 20 minutes the usefulness of this tracer is limited by arequirement for an onsite cyclotron and a team of skilledresearchers To overcome the technical barrier of using thisotherwise very useful tracer and to provide ready access forPET clinics to perform this type of study F-18 DTBZ ana-logs with a half-life of 110 min are proposed The newVMAT2 imaging agents could be manufactured by radiop-harmacies and distributed widely on a routine basis Synthe-sis radiolabeling and resolution of diastereomers and enanti-omers of novel F-18 labeled DTBZ derivatives are proposedThey will be selected and optimized by comparing bindingaffinity using in vitro binding assay In vivo biodistributionstudy in the brain of normal and lesioned rats after iv injec-tion of the tracers will be determined In vivo PET imagingstudy and kinetic modeling of VMAT2 in the brain of non-human primates will be evaluated for selected candidatesUltimately it is expected that a VMAT2PET imaging agentwill be developed for phase I clinical trial by the end of thethird year of this project The objective of this project is tosolve a problem in supplying an effective PET tracer forroutine clinical use If successfully developed the proposednovel tracers may have a high impact on the diagnosis ofvarious abnormalities of brain function and diseases relatedto changes of the storage of monoamine neurotransmittersThis is a collaborative project between the research groupsof the PI in University of Pennsylvania and Dr Michael Kil-bourn University of Michigan Combining the strength oftwo laboratories will greatly enhance the chance of reachingthe goals proposed in this project

Thesaurus Terms brain imaging visualization scanning

fluorine glycoprotein positron emission tomography radio-

e68

nuclide radiotracer technology technique development tet-rabenazine Huntingtonrsquos disease Parkinsonrsquos disease bind-ing site biological transport chemical synthesis drug designsynthesis production neural degeneration neurotransmitterpharmacokinetics radiochemistry baboon bioimaging bio-medical imaging high performance liquid chromatographylaboratory rat

Institution University of Pennsylvania3451 Walnut StreetPhiladelphia PA 19104


Imaging And BioengineeringIRG NPAS

HYPERPOLARIZED 13C NMR STUDIESOF PROSTATE CANCER

Grant Number 5R21EB005363-02PI Name Kurhanewicz John

Abstract Description (provided by applicant) An extraordi-nary new technique utilizing hyperpolarized 13C labeledprobes has the potential to revolutionize the observation ofkey cellular metabolic processes non-invasively in vivo byMR Proof-of-principle animal studies have demonstrated upto 40000 fold polarization enhancements of 13C labeledpyruvate providing sufficient signal for rapid imaging of thetumor metabolites alanine and lactate In this collaborativeproject with GE Healthcare scientists we aim to for the firsttime combine hyperpolarized 13C labeled probes such aspyruvate and acetate with high field human MR scannersoptimized rf receivers and fast spectroscopic imaging pulsesequences to obtain an approximately 4 order of magnitudeincrease in sensitivity for 13C metabolic imaging of prostatecancer The accurate detection and characterization of pros-tate cancer remains a major problem in the clinical manage-ment of individual prostate cancer patients and in monitoringtherapy While a combination of MRI and 1H MR spectro-scopic imaging has shown great promise for improving pros-tate cancer detection and characterization prior to and fol-lowing therapy the value of this technique is currently lim-ited by its coarse spatial and spectral resolution The useof 13C labeled pyruvate and acetate provide the potentialto simultaneously assess changes in metabolic fluxesthrough multiple biochemical pathways (glycolysis citricacid cycle and fatty acid synthesis) simultaneously Allthree of these pathways have been shown to have meta-bolic perturbations associated with the evolution and pro-

gression of human prostate cancer In a series of studies


involving ex vivo HR-MAS spectroscopic analysis of in-tact human prostate biopsies human prostate cell linescultured with 13C labeled substrates and transgenic miceinjected with 13C labeled substrate we will (1) determinethe key 13C labeled metabolites that best identify thepresence of prostate cancer and characterize its aggres-siveness and (2) determine the kinetics of incorporationof I3C labels into the key metabolites as well as the T1and T2 relaxation times of the I3C labeled metabolitesThis data will be combined with specialized rf detectorsfast 13C spectroscopic imaging pulse sequences and datareconstruction and analysis protocols to detect hyperpolar-ized 13C labeled metabolic imaging probes in preliminarystudies of prostate cancer patients

Thesaurus Terms carbon molecular cellular imaging mo-lecular probe nuclear magnetic resonance spectroscopyprostate neoplasm stable isotope technology technique de-velopment Krebsrsquo cycle acetate fatty acid biosynthesis gly-colysis pyruvate NIH Roadmap Initiative tag bioimagingbiomedical imaging biopsy cell line clinical research ge-netically modified animal human subject laboratory mouse

Institution University Of California SanFrancisco

3333 California St Ste 315San Francisco CA 941430962



EFFECT OF CAFFEINE ON FUNCTIONALAND PERFUSION MRI

Grant Number 5R01EB003880-02PI Name Laurienti Paul

Abstract Description (provided by applicant) Caffeine isthe most widely used neurostimulant in the world and it hasbeen shown that 79 of the population in the United Statesdrinks coffee at least occasionally This high incidence ofuse is of considerable significance because caffeine can mod-ulate multiple physiological imaging measures The effectsof caffeine are due to the nonselective antagonism of adeno-sine receptors acting not only as a vasoconstrictor but alsoas a neurostimulant It has been proposed that the caffeine-induced decrease in resting cerebral perfusion will allow fora greater difference between resting and active states in aBOLD study thus increasing the magnitude of the signalHowever it is well known that chronic caffeine use causes

an upregulation of adenosine receptors Thus the administra-

tion of caffeine as a BOLD signal enhancer is likely compli-cated by neural and vascular responses and by differences inreceptor numbers dependent on the individualrsquos dietary caf-feine consumption In fact resting perfusion decreases havebeen found to produce variable effects including both in-creases decreases or no consistent change in the BOLD sig-nal amplitude The conflicting results are likely due the factthat previous studies have either not controlled for caffeineconsumption or have been limited to withdrawal states Thebroad long-term objective of this project is to gain a morethorough understanding of the effects of caffeine and adeno-sine on brain activity and blood flow and how such effectsmodulate physiological brain imaging measures Our primaryhypothesis is that caffeine modulates neural activity-inducedchanges in regional cerebral blood flow through 2 mecha-nisms 1) caffeine indirectly increases blood flow by block-ing neural receptors and increasing neural activity and 2)caffeine directly decreases blood flow by producing vasocon-striction through the blockade of vascular receptors

Thesaurus Terms brain circulation caffeine cerebrovascu-lar imaging visualization functional magnetic resonanceimaging magnetic resonance imaging purinergic receptoradenosine image enhancement oxygen tension pharmacoki-netics receptor expression vasoconstriction vasoconstrictorbioimaging biomedical imaging clinical research humansubject

Institution Wake Forest University HealthSciences

Medical Center BlvdWinston-Salem NC 27157

Fiscal Year 2006Department RadiologyProject Start 18-Apr-2005Project End 31-Jan-2009ICD National Institute Of Biomedical


NEW SCINTILLATION LIGHT DETECTIONCONCEPTS FOR PET

Grant Number 5R33EB003283-05PI Name Levin Craig S

Abstract Description (provided by applicant) We proposeto explore novel scintillation light detection concepts anddevelop a high performance imaging detector module suit-able for a positron emission tomography (PET) system de-signed to image small laboratory animals If successful thisinnovative detector will enable us to push the performancelimits of high resolution PET Recent studies suggest PET isa useful tool for molecular imaging of small laboratory ani-

mal models for human disease Limitations of currently

e69


available PET systems for molecular imaging are non-opti-mal sensitivity and spatial resolution for identifying molecu-lar signals of interest from minute structures in a reasonabletime Higher sensitivity may be achieved by bringing detec-tors closer and covering a larger fraction of the animal Spa-tial resolution may be improved by using finer scintillationcrystal array elements Currently there are several groupsdeveloping PET scintillation arrays with 1 mm crystal pixelsThe challenge with going to finer crystals is extracting suffi-cient light to maintain adequate detection signal-to-noise ra-tio (SNR) If the crystals are kept long to maintain high de-tection efficiency using finer crystals results in significantlylower light collection efficiency and SNR As long as theresulting light signals are sufficiently above noise the finercrystals may still be resolved and the desired intrinsic resolu-tion may be achieved However high spatial resolution aloneis not sufficient Weak light signals mean non-optimal sensi-tivity since more pulses are now below the detection thresh-old and non-optimal energy and time resolutions whichmay result in significant image contrast degradation We pro-pose a novel detector concept for PET that will facilitate ultra-high spatial resolution ( 1 mm) high coincidence count sensi-tivity (14) and optimal light collection efficiency (95)all at once The design uses scintillation crystals coupled in aninnovative manner to novel semiconductor photodetector arraysand custom readout electronics The new scintillation detectionconcepts will be investigated during the R21 phase During theR33 phase two high performance imaging detectors will bebuilt and studied If successful the proposed design will signifi-cantly improve efficiency of converting scintillation light intoelectrical signals Together with the high sensitivity and spatialresolution proposed the implications for its use in high resolu-tion PET are substantial

Thesaurus Terms image enhancement optics technologytechnique development disease disorder model electromag-netic radiation light emission semiconduction bioimagingbiomedical imaging positron emission tomography

Institution Stanford UniversityStanford CA 94305

Fiscal Year 2007Department RadiologyProject Start 15-Jul-2003Project End 30-Jun-2008ICD National Institute Of Biomedical

Imaging And BioengineeringIRG ZRR1

HIGH RESOLUTION PET DETECTORSFOR ONCOLOGY APPLICATIONS

Grant Number 2R01EB002117-06A1

PI Name Lewellen Thomas K

e70

Abstract Description (provided by applicant) This proposalfocuses on development of technology that is suited for bothultra-high resolution animal imaging systems and other highresolution applications such as human breast and head imag-ing An integral part of our work to date is the developmentof a highly modular approach to the detectors and supportingelectronics This approach assures that imaging resourcesbuilt using the technology can easily adapt to the changingdemands of the biological research In the previous fundingperiod cost effective designs of detector modules electron-ics and reconstruction algorithms to provide 1mm3 vol-ume resolution were completed In this renewal applicationwe propose to further develop detector modules electronicsand reconstruction algorithms to support a depth-of-interac-tion design (dMiCE) that is an extension of our MiCES sys-tem designs A major focus is on cost effective designs andtherefore our dMiCE module is based on a single-endedreadout of light with light sharing between pairs of crystalsto provide the depth-of-interaction (DOI) information Theproposal includes a careful optimization of light sharingtechniques investigation of multi-anode photomultipliertubes (PMTs) position sensitive PMTs and pixelated andposition sensitive avalanche photodiodes as photoreceptorsnew electronics designs moving essentially all pulse process-ing (integration pileup correctionprevention timing pickoff)into field programmable gate arrays (FPGAs) and extensionsof our reconstruction algorithms to support DOI The overallgoal is to achieve spatial resolutions 12 mm with sensi-tivity in a typical small animal configuration of 15 Theeffort will also include the development of maximum likeli-hood estimators for crystal-of-interaction and depth-of-inter-action in segmented crystal module designs as well as bettermethods for optimization of our DOI approach An importantaspect of the work is to extend the DOI designs to investi-gate potential applications in time- of-flight (TOP) systemsby both implementing FPGA based electronics that can pro-vide timing resolutions of 300 ps (the best values reportedfor current scintillatorsPMTs for practical tomograph de-signs) and utilize DOI based TOP correction to improve theoverall timing resolution of potential TOP scanner designsThe net result of our work will be contributions to the gen-eral knowledge of options for detector and electronics designfor high-resolution detector systems as well as insight intomethods to optimize TOP performance for different detectormodule designs


Institution University Of WashingtonOffice Of Sponsored ProgramsSeattle WA 98105


Project Start 01-Jul-2000


Project End 31-Jan-2010ICD National Institute Of Biomedical


GRADUATE TRAINING PROGRAM FORMAGNETIC RESONANCE IMAGING

Grant Number 5T32EB005170-02PI Name Li Debiao

Abstract Description (provided by applicant) The proposedNorthwestern University magnetic resonance imaging (MRI)training program will provide trainees opportunities to learnMRI basics and perform MRI research in diversified disci-plines The preceptors of the program come from variousdepartments and background Research interests include(1) Cardiac imaging (2) Vascular Imaging (4) MRI-guidedendovascular interventions (4) Neuro imaging (5) Physio-logical imaging including perfusion diffusion and oxygenconsumption (6) Breast imaging (7) Liver imaging (8) Tar-geted molecular imaging (9) Spectroscopy and (10) Signaland image analysis The trainees will be graduate studentspursuing PhD in Biomedical Engineering Department withbasic background in an engineering discipline or a relatedfield The training program will last for 5 years We willenroll 3 trainees in the first year and 5 trainees for years2ndash5 The training program will include didactic instructionslaboratory research rotations clinical rotations industrialexperience seminar series and mentored dissertation re-search The strengths of our program include the wide rangeof research interests (technical developments and medicalapplications basic scientific investigations and clinicalstudies morphological functional and molecular imaginganimal experiments and human studies) close interactionsbetween MR physicists and clinicians strong ties to in-dustrial partners and unsurpassed access to state-of-the-art MRI systems


Institution Northwestern University750 N Lake Shore Drive 7thChicago IL 60611



IRG ZEB1

MAGNETIC RESONANCE IMAGING OFCORONARY ARTERIES AT 3OT

Grant Number 5R01EB002623-04PI Name Li Debiao

Abstract Description (provided by applicant) Coronaryartery disease is the leading cause of death in the UnitedStates The overall objective of the proposed project is todevelop optimize and validate a high resolution magneticresonance (MR) imaging protocol to evaluate coronary arterydisease noninvasively The long-term goal is to provide anoninvasive screening test for coronary artery disease Thistest could potentially be combined with other hemodynamicfunctional and metabolic studies available from MRI toform a comprehensive examination of coronary artery dis-ease for improved patient care and cost savings The specificgoal of the project is to improve the spatial resolutionspeed and signal intensity of coronary artery images Wewill acquire the images on a 30-Tesla scanner which cangenerate images with high signal intensity than conventional15-Tesla systems We will develop and validate the coro-nary artery imaging techniques on 30T and compare with15T to verify the improved performance Finally patientswill be studied to determine the capability of the new tech-nique in detecting functionally significant coronary arterystenoses by comparing with conventional x-ray angiographyPositive results from this study will provide the foundationfor further technical improvements and clinical validationThe specific aims of the project are Aim 1 To develop afast coronary artery angiography protocol on 30T capable ofacquiring high-resolution images to accurately define vessellumen size Aim 2 To verify that the developed coronaryMRA protocol on 30T can accurately depict coronary arterystenoses in pigs image SNR and accuracy of stenosis detec-tion on 30T are better than those on 15T Aim 3 To dem-onstrate that the developed imaging protocol on 30T canaccurately detect coronary artery disease in patients

Thesaurus Terms coronary artery coronary disorder diag-nosis design evaluation diagnosis quality standard heartdisorder diagnosis heart imaging visualization scanningmagnetic resonance imaging noninvasive diagnosis rapiddiagnosis artery stenosis image enhancement image pro-cessing angiography bioimaging biomedical imaging clini-cal research data collection methodology evaluation humansubject phantom model swine


Fiscal Year 2006Department RadiologyProject Start 25-Sep-2003

Project End 31-Jul-2008

e71


ICD National Institute Of BiomedicalImaging And Bioengineering

IRG ZRG1

STATISTICAL METHODS FOREVALUATION AND VALIDATION OFDIAGNOSTIC TESTS

Grant Number 1R01EB004079-01A2PI Name Lu Ying

Abstract Description (provided by applicant) This multi-disciplinary effort by biostatisticians radiologists and medi-cal physicists aims to develop innovative statistical methodsfor evaluation and validation of new and low cost diagnosticmodalities Specific Aims are (1) statistical methods for de-termining non-inferiority of diagnostic techniques (2) statis-tical design and analysis methods for rapid and accurateevaluation of the chronological association and treatmentefficacy of new radiological markers with disease outcome(3) applying the statistical methods to clinical research anddeveloping user-friendly software Specific Aim 1 studiesevaluation of non- inferiority for a new diagnostic test basedon the receiver operating characteristics curve under variousconditions (missing data mixed data types and clustereddata) effects of covariates (non-inferiority after adjustmentof covariates and identification of subgroups within whichthe new test is inferior superior or equivalent) and Bayesianutility models Specific Aim 2 studies a new cross-sectionalcase-control short- term follow-up (CSCCSTFU) design andanalysis methods to estimate the chronological odds ratio ofa new diagnostic test for a rare outcome It will also proposemethods to estimate the lower boundary of treatment efficacyfor patients diagnosed by the new test Mathematical theory

and simulation studies will be used to understand the condi-

e72

tions in which the estimated odds ratio of the CSCCSTFUdesign can be generalized Specific Aim 3 will apply resultsfrom Specific Aim 1 to data from the Study of OsteoporoticFractures and the Osteoporosis and Ultrasound Study to testwhether and when quantitative ultrasound peripheral bonemineral density (BMD) and biochemical bone markers canserve as non-inferior or equivalent techniques to BMD of hipand spine for assessing osteoporotic fracture risks It willalso use results of Specific Aim 2 to determine whether thevolumetric breast density and structural parameters of thenew single X-ray absorptiometry technique can prospectivelypredict breast cancer in an on-going study of 15000 womenAn advisory committee of internationally recognized leadersin osteoporosis and breast cancer research will advise theresearch team on outreach to physicians and opportunitiesfor ancillary studies Research results will be disseminatedthrough publication of software research and tutorial papersin both clinical and statistical journals and by influencingposition papers of professional organizations






IRG BMIT


Abstract Description (provided by applicant) This proposalis aimed for development and optimization of a novel neuro-imaging method termed ldquomagnetic source MRIrdquo (msMRI)that uses a conventional MRI scanner in an innovative man-ner to measure electromagnetic signals from populations ofneurons The msMRI technique is based on directly detectingMRI signal changes associated with changes in magneticfields concomitant with neuronal filing Compared withpositron-emission tomography (PET) and functional MRI(FMRI) methods msMRI has improved spatial localizationand significantly better temporal resolution Compared withmagnetoencephalography (MEG) and electrophysiology(EEG) msMRI has superior spatial resolution The goal ofthis project is to systemically characterize rnsMRI signalapply this unique technique in initial human neuroscienceresearch and facilitate the use of msMRI among scientistsinvestigating basic neurophysiological and neuropsychologi-cal phenomena as well as accurate clinical diagnosticinter-vention methodology for brain diseases Three specific aimsare proposed for three years (1) to refine and extend mathe-matical models of msMRI (2) to optimize strategies for dataacquisition and analysis (3) to evaluate the extent to whichmsMRI signal fulfills the requirements of linear systems andits dependence on magnetic field strength This proposal is aperfect match of the mission of the NIBIB because the pro-posed msMRI is an innovative imaging technology thatshould significantly impact on research and clinical develop-ments in the fields of human neuroimaging cognitive neuro-science and neuropathology Magnetic source MRI couldrepresent a substantial advance for these fields and shouldhelp bridge the gap between human neuroimaging and elec-trophysiological methods employed in experiments with non-humans The power provided by msMRI technology is es-sential to understand human cellular neurophysiology and itsimplication on brain diseases

Thesaurus Terms biophysics brain electrical activity brainimaging visualization scanning functional magnetic reso-nance imaging magnetic field mathematical model technol-ogy technique development bioimaging biomedical imag-ing clinical research human subject patient oriented re-search




IRG ZRG1

e54

SHAPE OPTIMIZING DIFFEOMORPHISMSFOR COMPUTATIONAL BIOLOGY

Grant Number 1R01EB006266-01PI Name Gee James C

Abstract Description (provided by applicant) This proposalwill contribute a new collaboration for implementing rigor-ous spatiotemporal medical image analysis in a large scalecomputing environment The system will dramatically en-hance the neuroimaging communityrsquos quantitative under-standing of normal and pathological aging and correlatedvariables Medical images capture the changes that occur inan individual over time and samples the range of anatomicaland functional differences visible in a population lifespanOur goal is to associate these differences with causes forexample innate population variability injury pathology orthe effects of genotype on phenotype The recently proposedDiffeomorphometry (DM) system quantifies and relates thesevariables to an optimal spatiotemporal coordinate systemThis novel technique allows the atlas to evolve in time alongwith the population to statistically capture effects of agedisease or other factors This common evolving map spacegives a wealth of prior knowledge allowing one to buildprobabilities describing ranges and types of variation inshape and function These aggregate population attributesmay then be studied and visualized used in research as wellas teaching and diagnosis Our DM method is designed withthe axioms of symmetry (the algorithms must be symmetric)and specificity (the analysis should be optimal in the studyspace) in mind and with the ability to automatically generatedatabase-specific atlases The rigorous and symmetric defini-tion of change given by DM captures differences in neuro-anatomy with superlative accuracy reproducibility and highlevel of detail Consequently a DM study maximizes theinformation extracted from a neuroimaging cohort especiallywhen correlated with for instance genetic or behavioralvariables Furthermore DM satisfies pressing research needsin neuroimaging DM derives optimal atlases from arbitrarilysized databases and gives large deformation optimization ofanatomical correspondence through landmark and statisticalguidance The resources in the UCLA Center for Computa-tional Biology (CCB) will allow these methods to be appliedon the large datasets they were designed for and at an un-precedented resolution and scale The proposed work hasthree distinctive aims collaboration methodology and clini-cal evaluationapplication Instantiate a collaboration betweenUPenn and UCLA where data and algorithms are shared anddisseminated via the Center for Computational Biology De-velop Diffeomorphometry into a cutting-edge large-scalepublicly available computational tool Evaluate and refine thedeveloped methodology as well as compare with CCB brainmapping tools on neuroimaging studies of structure-function

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Abstracts of Funded National Institutes of Health Grants

Documents