Abstracts of Funded National Institutes of Health Grants

National Institute OfBiomedical Imaging And

Bioengineering

RECONSTRUCTION ALGORITHM FORMULTI-SLICE SPIRAL X-RAY CT

Grant Number: 5R21EB000568-03PI Name: Noo, Frederic

Abstract: Description (provided by applicant): This projectinvolves the development of reconstruction algorithms formultislice CT using helical data acquisition. With the recentintroduction of multi-row detectors and the ability to acquiredata over 360 degrees in less than 500 ms, x-ray CT is un-dergoing a new phase of rapid innovation. Compared to sin-gle-slice CT scanners, CT scanners with multi-row detectorscan cover larger volumes, achieve higher axial resolution,avoid motion artifacts due to respiration, and improve thedetectability of low-contrast details. These advantages havebeen identified with 4-row scanners and will become increas-ingly significant with greater numbers of detector rows.Eventually, a powerful imaging system with the capability ofachieving early and reliable diagnosis of numerous diseaseswill be available for biomedical research. With more than 4rows it is known that the cone-beam (CB) divergence of thebeams cannot be neglected during reconstruction. However,from a mathematical point-of-view, designing an algorithmthat accurately accounts for this divergence poses a chal-lenge. The design of helical CB reconstruction algorithms is

not a priority for CT manufacturers due to the numeroustechnological problems hindering the development of scan-ners with multi-row detectors. However, the future of multi-slice CT depends on progress that can be made in this field.Highly accurate reconstruction algorithms are needed to real-ize the full potential and development of multi-row scanners.This research project aims to satisfy that need. The specificaims are (1) to implement, characterize, and compare exist-ing helical CB reconstruction algorithms, using a collectionof figures-of-merit, and to disseminate the coded algorithms;(2) to derive, implement, and characterize new helical CBreconstruction algorithms that provide 3D images with iso-tropic spatial resolution and high local temporal resolution(� 300 ms); and (3) to derive, implement and characterizenew helical CB reconstruction algorithms that provide 3Dimages with isotropic spatial resolution and high detectabilityof low-contrast details (possibly at the expense of temporalresolution). Indirectly, this project will have significant im-pacts on all aspects of medical imaging - particularly in on-cology, angiography, evaluation of infections and cardiacdiseases, trauma, and radiotherapy.

Thesaurus Terms: X ray, computed axial tomography, com-puter program/software, computer system design/evaluationInternet, information dissemination bioimaging/biomedicalimaging

Institution: University Of UtahSalt Lake City, UT 84102

Fiscal Year: 2004Department: RadiologyProject Start: 01-Aug-2002Project End: 31-Jul-2005

e41

Research Corner

Abstracts of Funded NationalInstitutes of Health Grants

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

The grant identification number (eg, 1RO1AI12345-01) contains a three-digit activity code (in the previous example, RO1)that identifies a specific category of extramural activity. All current NIH activity code titles and definitions can be ob-tained at the NIH Web page http://silk.nih.gov/silk/brownbooks/actcod.

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

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

ICD: National Institute Of BiomedicalImaging And Bioengineering

IRG: ZRR1

NON ITERATIVE METHODS FOR 3DSPECT IMAGE RECONSTRUCTION

Grant Number: 5R01EB002765-09PI Name: Pan, Xiaochuan

Abstract: Description (Verbatim from Applicant’s Abstract):Single-photon emission computed tomography (SPECT) isplaying an increasingly important role in modern medicinefor imaging the brain, liver, kidneys, prostate, and other or-gans. The broad objectives of the project are to develop non-iterative methods for accurate and efficient reconstruction ofthree-dimensional (3D) images in SPECT and to evaluatethese methods in clinical applications. Non-iterative methodsfor image reconstruction in SPECT are inherently computa-tionally efficient. They are attractive in practice because theyavoid problems that plague other methods. Most importantly,they can facilitate a closed-form: analysis of image statisticsand aliasing, allowing the development of strategies for opti-mal suppression of the effects of noise, aliasing, and othererrors. The research on non-iterative methods will signifi-cantly enhance the ability of SPECT to detect subtle lesionsand to quantify accurately physiologic parameters in researchand clinical applications. This proposal is intended specifi-cally for further development of non-iterative, statisticallyoptimal, computationally efficient, and numerically robustreconstruction methods in 3D SPECT and for evaluation ofthese methods in clinical SPECT studies such as In-111Prostascint SPECT imaging of prostate cancer. We expectthat the proposed methods will adequately compensate forthe effects of photon attenuation, distance dependent spatialresolution, and data noise. We will apply methods developedby other investigators to compensate for scatter. We believethat our research will significantly strengthen the ability ofSPECT for detecting subtle lesions in clinical applications.The specific aims of the proposed research are (1) to furtherdevelop non-iterative methods for optimal estimation of theideal sinogram, (2) to develop adaptive and robust filteringapproaches, (3) to investigate and mitigate the effects of ad-ditional sources of error, (4) to evaluate the proposed meth-ods using phantom studies, and (5) to evaluate the proposedmethods in clinical studies.

Thesaurus Terms: image processing, method development,single photon emission computed tomography, computersimulation, phantom model, prostate neoplasm bioimaging/biomedical imaging, human data

Institution: University Of Chicago5801 S Ellis AveChicago, IL 60637

Fiscal Year: 2004Department: RadiologyProject Start: 01-Apr-1996Project End: 31-Mar-2006ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: DMG

POST PROCESSING FOR IMPROVEDVESSEL DETAIL IN MRA

Grant Number: 8R01EB002639-07PI Name: Parker, Dennis L.

Abstract: Our intent in this project has been to improve thesmall vessel visibility in MIP images of 3D TOF MRA stud-ies. During the first 3 years we tested the effectiveness of anon-linear vessel enhancing filter applied to the original 3DTOF MRA image data. In trying to understand the strengthof the MIP algorithm in vessel display and to understandingthe properties of vessels, we noticed the striking differencebetween the nature of “vessels” and background in the MIPdepth buffer (the matrix of z-locations of points projected inthe MIP). Vessels are predominantly smooth and connectedwhile background is “rough”. In trying to utilize this prop-erty to enhance the probability of vessel pixels, we have de-veloped an algorithm which nearly completed extracts vesselvoxels from the 3D MRA data, and excludes nearly all back-ground. Using these extracted voxels, we have been able togenerate X-ray like projection images of the 3D MRA imagedata which inherently contained more information than theMIP, leading to a striking improvement in vessel appearance.Nearly every vessel seen in the original MAP and some notseen are visible in these reproject images with the exact ap-pearance of a digital subtraction X-ray angiogram (DSA). Inthe next funding period we will perform a large series oftasks designed at refining this new depth buffer segmentation(DBS) algorithm. After refining the algorithm, we will testthe extent to which the DBS algorithm improves the accu-racy and efficiency of detection and management of a varietyof intracranial pathologies such as aneurysms and vasculitis.We will also study the application to other vascular systems.Because the algorithm extracts the image coordinates of thevoxels that make up the vessels for which segments are visi-ble in the MIP, we will develop algorithms which convertthese lists of segmented voxels to a cubic spline representa-tion, where the anatomic labels of the vessels are included.We will study methods to use this knowledge of the patientsvascular anatomy to develop techniques to assist in the opti-mized presentation of the MRA information for improveddiagnostic accuracy and efficiency. We will also test the ap-plication of the 3D vessel structure obtained from the DBSalgorithm to improve surgical procedure planning and otherapplications. We believe that an improved version of this

NIBIB Academic Radiology, Vol 12, No 4, April 2005

e42

exciting new algorithm will improve the efficiency and accu-racy of MRA in general. Experiments to characterize, im-prove and clinically evaluate this algorithm are described inthis proposal.

Thesaurus Terms: angiography, cardiovascular disorderdiagnosis, cerebrovascular disorder diagnosis, diagnosis de-sign/evaluation, diagnosis quality/standard, magnetic reso-nance imaging aneurysm, blood vessel, mathematical model,method development, model design/development, vasculitis bio-imaging/biomedical imaging, clinical research, human subject


Fiscal Year: 2003Department: RadiologyProject Start: 01-Sep-1995Project End: 31-Jan-2005ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: RNM

FMRI BOLD CONTRAST RELATIONSHIPTO CEREBROVASCULAR TONE

Grant Number: 5R01EB002449-02PI Name: Parrish, Todd B.

Abstract: Description (provided by applicant): Functionalmagnetic resonance imaging (fMRI) relies on the coupling ofblood flow changes to neuronal activity. These blood flowchanges in turn alter the concentration of oxygen in the localblood pool surrounding the neurons. Because the susceptibil-ity of oxyhemoglobin and deoxyhemoglobin are different, itis possible to make the MR signal sensitive to oxygen con-centration; this is termed blood oxygenation level dependent(BOLD) signal. The BOLD signal change from the rest con-dition to the active condition is approximately 1-3%. Detec-tion of the BOLD signal requires a robust paradigm, prepro-cessing of the signal, and statistical modeling to generateactivation maps. All of this is necessary because of the weakBOLD contrast that exists in hemodynamically normal sub-jects. When a subject has compromised vasculature and im-paired vasoreactivity from a carotid stenosis or occlusion, wehave demonstrated that the BOLD signal response is absentor severely altered beyond normal detection. This is a veryimportant issue as fMRI moves into the clinical setting andis used to study stroke recovery or aging populations. Forexample, in stroke recovery one may detect activation in-creases over time and assume they are due to neuronal re-cruitment or rehabilitation; however, the activations may bethe result of developing collateral flow or recovery of vaso-reactivity. One of the goals of this proposal is to investigateand characterize the BOLD response in the face of alteredhemodynamics. A limitation to the field of functional MRI is

the small difference in BOLD signal used to detect activa-tions. We have shown that the physiologic interaction of caf-feine significantly increases the BOLD contrast (�40% at1,5T and 80-170% at 3T). In this proposal, the mechanismsof caffeine will be explored in normal subjects using fMRI,MR based perfusion and transcranial Doppler ultrasound tocharacterize the BOLD signal and the cerebral blood flowresponse. Individual components will be investigated in orderto create a simple model of the interactions with BOLD con-trast. The improvement in BOLD contrast can be used toimprove the temporal and spatial resolution or to allow theinvestigation of more subtle cognitive paradigms. The themeof this proposal is to investigate the impact of physiologicmechanisms (reactivity, flow, hematocrit, neuronal activity)on the generation of BOLD signal and more importantlyBOLD contrast.

Thesaurus Terms: brain circulation, caffeine, cerebrovascu-lar system, hemodynamics, oxygen transport, biologicalmodel, blood cell count, cerebrovascular disorder, diuretic,evoked potential, hemoglobin, model design/development,oxygen clinical research, functional magnetic resonance im-aging, human subject, neuropsychological test, perfusion,statistics/biometry, ultrasound

Institution: Northwestern UniversityOffice Of Sponsored ResearchChicago, IL 60611

Fiscal Year: 2004Department: RadiologyProject Start: 27-Sep-2003Project End: 31-Jul-2007ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: BDCN

HYBRID X-RAY/MR SYSTEMS FORIMAGE-GUIDED PROCEDURES

Grant Number: 5R01EB000198-02PI Name: Pelc, Norbert J.

Abstract: Description (provided by applicant): Image-guidedminimally invasive procedures have made a substantial im-pact in improving patient management, reducing the cost,morbidity and mortality of treatments, and malung therapiesavailable to patients who would otherwise have no option.X-ray fluoroscopy and MRI are two powerful tools for guid-ing interventional procedures, but they have very differentstrengths and weaknesses. X-ray fluoroscopy offers very highspatial and temporal resolution and is excellent for guidingand deploying devices. However, it offers little in the way ofsoft tissue contrast. MR offers tomographic imaging withcomplete freedom of plane orientation, outstanding soft tis-sue discrimination, and the ability to portray physiology and

Academic Radiology, Vol 12, No 4, April 2005 ABSTRACTS OF NIH GRANTS

e43

directly observe the effect of therapies. However, it not idealfor imaging devices and is limited in spatial resolution. As aresult of these disparate characteristics, the choice of guid-ance modality involves a compromise. Our preliminary workhas shown that it is feasible to fully integrate an x-ray fluo-roscopy system into the bore of an interventional MR scan-ner. The two systems can have congruent fields of view, en-abling the physician to seamlessly and flexibly choose themodality that is best suited to each phase of the procedure.This type of hybrid system could have enormous impact inthe diagnosis and treatment of oncologic, cardiovascular, andother disorders. The proposed work will take the system be-yond proof of concept and into the clinic. We will developand implement more powerful and reliable x-ray subsystems,perfect their MR compatibility, develop x-ray tube designswith increased immunity to magnetic field alignment, andmore thoroughly integrate the two modalities by implement-ing graphic prescription of MR slices from x-ray projections.We believe this technology will have significant benefit to anumber of important applications, ranging from endovascularprocedures to biopsies and diagnostic studies. However, weare using two applications (TIPS placement and chemoembo-lization) as models with which to develop this technology,and as part of the proposed work we will conduct small clin-ical trials of these procedures. The hybrid system, once per-fected, will remove the compromise involved in choosing aguidance modality, improving and enabling new minimallyinvasive procedures.

Thesaurus Terms: biomedical equipment development, flu-oroscopy, magnetic resonance imaging, surgery material/equipment cardiovascular shunt surgery, human therapy eval-uation, patient care management, therapeutic blood vesselocclusion bioimaging/biomedical imaging, clinical research,human subject, patient oriented research

Institution: Stanford UniversityStanford, CA 94305

Fiscal Year: 2003Department: RadiologyProject Start: 30-Sep-2002Project End: 31-Aug-2005ICD: National Institute Of Biomedical


MEDICAL IMAGE PRESENTATION:STRUCTURAL IMAGE ANALYSIS

Grant Number: 5P01EB002779-14PI Name: Pizer, Stephen M.

Abstract: Description (provided by applicant) Followingstrong successes in all 3 projects of our present program, wehave decided to increase the focus of our program project by

building our new program on one of them and are seekingseparate funding for the other two. In particular, we focusthis program on segmentation and discrimination of the geo-metric structure of 3D objects in medical images by ourprincipled and innovative methods working at multiple levelsof scale and based on training image sets. The program con-sists of four projects and three cores. One of the projectsfocuses on development and extension of image analysismethods based on single and multiple object models at mul-tiple levels of scale, with the middle levels of scale specifi-cally designed to represent the figural aspects of objects. Be-cause of the successes of our image analysis methodology, itis now time for three projects to pursue medical uses of suchmethods. Two of these three focus on the segmentation ofstructures in the brain and discrimination of disease fromtheir geometric structure in relation to the diagnosis of men-tal illnesses. The other medical project continues our presentprogram’s focus on radiotherapy treatment planning. To sup-port the evaluation of the image analysis methods both geo-metrically and in medical terms, we continue the core onbiostatistics, and we add a core on the development of meth-odology for validation of image analysis methods. Finally, afacilities and administration core provides infrastructure forthe other projects.

Thesaurus Terms: computer data analysis, image process-ing, method development bioimaging/biomedical imaging,clinical research, human data

Institution: University Of North Carolina ChapelHill

Aob 104 Airport Drive Cb#1350Chapel Hill, NC 27599

Fiscal Year: 2004Department: RadiologyProject Start: 03-Jul-1988Project End: 28-Feb-2007ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: NCI

SPIN-LOCK IMAGING OF CARTILAGE

Grant Number: 5R21EB000480-02PI Name: Reedy, Ravinder

Abstract: Description (provided by applicant): OA is a ma-jor cause of morbidity in the population over 50 and affectsmore than 40 million Americans. Although evidence impli-cates cartilage degeneration as the primary cause for OA, nocure exists as yet. Current treatments relieve symptoms butdo not inhibit disease progression. However, if the disease isdetected in early stages then appropriate therapeutic interven-


e44

tion may be possible. Currently, there are no noninvasivemethods to detect early biochemical changes in cartilage.This lack of noninvasive diagnostic methods also hamperedthe research in the development of potential chondroprotec-tive agents. To develop sensitive, noninvasive diagnostictools that target early degenerative changes, one needs tounderstand the structural and biochemical changes that occurduring degeneration and correlate these properties to measur-able parameters obtained by a noninvasive method. In thisapplication we propose to exploit proton magnetic resonance(MR) relaxation under spin-locking condition to develop anovel MR technique to monitor structural and biochemicalchanges in cartilage that occur during early OA. Both spec-troscopic and imaging measurements will be performed oncartilage tissue models, normal bovine cartilage, on enzymat-ically degraded bovine cartilage (which are subjected to se-lective degradation of varying degrees of proteoglycans (PG)or collagen to mimic the structural and biochemical changesthat occur in OA). The results obtained from the extracellu-lar matrix (ECM) model systems will enable one to deter-mine contributions from different components of ECM to theobserved relaxation and dispersion behavior, and underlyingmechanism. The data from the selective enzymatic degrada-tion studies will provide the signal changes and contrast inspin-lock-weighted images and will help in developing opti-mal imaging parameters to measure changes induced by spe-cific macromolecular degradation. Since the measured MRproperties rely not only on tissue contrast, but are also de-pendent on structural and biochemical changes, this proposedresearch will aid in the development of a sensitive non-inva-sive technique for early diagnosis of OA as well as aid inthe development/evaluation of potential chondroprotectivedrugs and treatment therapies.

Thesaurus Terms: cartilage, cartilage disorder, magneticresonance imaging, noninvasive diagnosis, osteoarthritis,skeletal disorder diagnosis articular cartilage, biochemistry,collagen, early diagnosis, extracellular matrix, histology,method development, protein degradation, protein proteininteraction, proteoglycan bioimaging/biomedical imaging,cow, nuclear magnetic resonance spectroscopy, tissue/cellculture

Institution: University Of Pennsylvania3451 Walnut StreetPhiladelphia, PA 19104


Imaging And BioengineeringIRG: ZRR1

SEVERE ACETABULAR DEFECTS:IMAGE-GUIDED RECONSTRUCTION

Grant Number: 5R21EB003266-02PI Name: Robertson, Douglas D.

Abstract: Description (provided by applicant): Acetabularrevision of total hip replacements (THR) is one of the mostchallenging problems in orthopedic surgery today. Despitegreat advances in imaging, preoperative visualization andassessment of even the most difficult cases is still performedjust like the first revision over forty years ago, using subjec-tive examination of anteroposterior (AP) radiographs. Thispresents an opportunity for improving clinical out-come, es-pecially given the widely-held orthopaedic surgery tenet thatclinical success is directly related to the thoroughness andaccuracy of preoperative planning. Ideally, revision surgicalplanning should determine defect type, describe amount andlocation of remaining bone (to select the best mechanically-sound reconstruction option), and confirm whether recon-struction should be performed. Lack of a validated, quantita-tive assessment that provides structural information limits theusefulness of current systems and leads to worse clinical out-comes, added cost, and wide intra- and inter-surgeon vari-ability in selecting reconstruction options. Therefore, thenext step for biomedical imaging is to move beyond out-dated radiograph-based evaluations and onto mechanicallyand clinically relevant structural imaging. Our goal is to re-place conventional radiograph-based planning with structuralimaging in order to guide surgical reconstruction and im-prove the clinical outcomes of individuals with deficient ace-tabular bone. Our broad hypothesis is that advanced CTtechniques increase the predictive power of preoperative as-sessments, link defect type with mechanical effects, and im-prove clinical outcomes. We seek to develop image-guidedtechniques that are mechanically-relevant and based on exist-ing imaging technologies. This R21 proposal’s specific aimis: Aim 1: Develop and validate objective CT-based struc-tural-imaging techniques to guide surgery by describing hostbone and its mechanical environment. Hypothesis: CT-basedstructural-imaging accurately (� 2mm linear measurements,� 3% volume measurements, �15 % bone density errors)and reliably (inter-observer, kappa �0.80) define 3D struc-ture and mechanical consequence. Future research aims in-clude clinical implementation, outcome and cost benefit anal-yses, and development of minimally invasive surgery. Com-pletion of this project will create an accurate CT-basedtechnique to guide surgery by structurally assessing the mor-phology, density, and mechanics of the deficient acetabulae.This is the first and important step toward improving surgi-cal planning, execution, and clinical outcomes of these diffi-cult cases.

Thesaurus Terms: bone imaging/visualization/scanning,image guided surgery/therapy, orthopedics, technology/tech-nique development hip surgery, pelvis bioimaging/biomedical


e45

imaging, computed axial tomography, human tissue, post-mortem

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


Imaging And BioengineeringIRG: ZRG1

MICRORADIOGRAPHIC GUIDANCE OFFLOW MODIFYING STENTS

Grant Number: 5R01EB002873-02PI Name: Rudin, Stephen

Abstract: Description (provided by applicant): The aim ofthis project is to build a new very high spatial resolution,rapid frame rate region of interest (ROI) x-ray detector sys-tem, the micro-angiographic fluoroscope (MAF) and to use itfor guiding and evaluating new stents used for flow modifi-cation in the treatment of intracranial aneurysms. The detec-tor due to its large adjustable gain will be capable of acquir-ing 30 fps at both fluoroscopic exposures in the fractionalmicroR and higher range as well as at angiographic expo-sures in the mR range. The detector will have adjustablepixel size and be capable of pixel sizes less than 50 mu/mand will have high-contrast spatial resolution greater than 10lp/mm while operating at typical angiographic kVp’s. TheMAF will have a viewing field of at least 5 cm diametersufficient for viewing small regions where interventions andin particular flow modifying interventions are occurring. TheMAF will be compatible with existing commercial angio-graphic x-ray sources and be mounted in such a way as tobe interposed between the x-ray image intensifier, X/I, of thecommercial system and the phantom, animal, or patient sothat the MAF can be used when its high resolution ROI ca-pabilities are needed, usually at critical times during inter-ventional procedures. Additionally, the MAF will be used forcone-beam rotational microangiography and micro-computedtomography (CT) for determining vessel lumens needed foraccurate flow assessment. Also, the new imaging capabilityfor accurate localization will allow the development and im-plementation of new devices: asymmetric, variable porositystents for treatment of cerebral aneurysms by modifying an-eurysm blood flow characteristics. To optimize the new stentdesign, flow reduction in aneurysms needed to induce throm-bosis will be explored. Also details of flow and flow modifi-cation will be investigated using advanced theoretical andexperimental methods. Finally clinical application of the

high-resolution microfluoroscopic detector will be used toevaluate the use of stents for flow modification in the cere-brovasculature of human patients.

Thesaurus Terms: X ray, biomedical equipment develop-ment, blood vessel prosthesis, microradiography, aneurysm,cerebrovascular imaging/visualization angiography, bioengi-neering/biomedical engineering, bioimaging/biomedical im-aging, clinical research, computed axial tomography, dog,fluoroscopy, human subject

Institution: State University Of New York AtBuffalo

Suite 211 Ub CommonsBuffalo, NY 14228



BLOOD FLOW IN SMALL ANIMALS BYULTRASOUND

Grant Number: 5R01EB001713-02PI Name: Sehgal, Chandra M.

Abstract: Description (provided by applicant): This applica-tion proposes to develop an ultrasound technique that usesmicrobubble-based contrast agents to measure blood flow inmouse tumors. Towards this goal, the investigators have de-veloped a multigating pulse sequence that allows acquisitionof ultrasound images at a variable frame rate during bolusinjection of the contrast agent. The rate at which the micro-bubbles are destroyed as a function of image acquisition isused to measure contrast flow. The overall goal is to validatethis approach and to develop it to a form that can be used tomeasure flow on a routine basis. The proposed research hasfive specific aims involving (i) further refinement of thetechnique, (ii) its validation by comparison with true flow inphantoms and mouse tumors, (iii) establishing the influenceof various imaging and contrast agent properties on the mea-surements, (iv) establishing the limits imposed by inter- andintra- subject variability in the measurements and (v) demon-strating the feasibility of the technique for measuring changein blood flow in response to physiological and therapeuticinterventions. At the completion of this project the investiga-tors anticipate having a thoroughly evaluated method for theassessment of blood flow using ultrasound contrast agents.With the approval of various contrast agents for use in clin-ics by the regulatory agencies impending, this technology istimely and is likely to useful in the diagnosis and treatmentof many cancers and cardiovascular diseases.


e46

Thesaurus Terms: neoplasm/cancer, neoplasm/cancer bloodsupply, technology/technique development, ultrasound bloodflow measurement contrast media, image processing, phan-tom model bioimaging/biomedical imaging, cell line, labora-tory mouse




HIGH FIELD MRI: LIMITATIONS ANDSOLUTIONS

Grant Number: 5R01EB000454-03PI Name: Smith, Michael B.

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

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

Institution: Pennsylvania State Univ Hershey MedCtr

500 University DriveHershey, PA 170330850



IMAGING THE NEOCORTEX WITHVISIBLE LIGHT SPECTROSCOPY

Grant Number: 5R21EB001800-02PI Name: Springett, Roger J.

Abstract: Description (provided by applicant): We will builda visible light spectroscopy (VLS) system to probe the neo-cortex of mice and immature rats. This system will use mul-tiple optical fibers placed on the exposed skull and measurecomplete attenuation spectra from 500 to 630nm betweenpairs of fibers using white light illumination and a multi-channel imaging spectrograph equipped with a cooled CCDdetector. We have developed and validated a novel algorithmto calculate the concentration of reduced cytochrome c andreduced cytochrome oxidase as well as absolute hemoglobinconcentration and saturation directly from these attenuationspectra. We will use this algorithm to reconstruct a topo-graphic map of the cortex between pairs of optodes and ex-tend this algorithm to reconstruct a full 3 dimensional tomo-graphic image of the cortex. The topographic system willconsist of 25 transmit fibers and 16 receive fibers with aspacing of 1.25mm allowing us to span 7�7mm of the neo-cortex. We will use nearest neighbor pairs of optodes to mapthe neo cortex with a spatial resolution of 1.56mm 2. Tem-poral resolution will be 1 second. The tomographic systemwill consist of an array of 36 fibers spaced lmm apart span-ning an area x5mm across the neocortex. We will sequencethrough all 36 fibers making each one in turn a transmit fiberand the remaining 35 receive fibers. We will apply a tomo-graphic reconstruction based on a Monte-Carlo simulation ofthe transport of light through the tissue to reconstruct the


e47

gray matter of the cortex in 3 dimensions. We expect suffi-cient signal to make measurements up to fourth nearestneighbor allowing an in-plane resolution of lmm 2 and adepth resolution of 0.25mm. Temporal resolution will be 1.5seconds. The ability to directly image signals from the mito-chondria will make this system unique and will be invalu-able in following the metabolic consequences of spreadingdepression and seizure propagation as well probing themechanisms of ischemic and excitotoxic cell death.

Thesaurus Terms: biomedical equipment development,brain imaging/visualization/scanning, brain mapping, color-imetry, neocortex, three dimensional imaging/topography,tomography charge coupled device camera, cytochrome c,cytochrome oxidase, hemoglobin bioimaging/biomedical im-aging, laboratory mouse, statistics/biometry

Institution: Dartmouth College11 Rope Ferry Rd. #6210Hanover, NH 03755



MR ELASTOGRAPHY USING TIMEREVERSED ACOUSTICS

Grant Number: 5R21EB002787-02PI Name: Swanson, Scott D.

Abstract: Description (provided by applicant): The overallgoal of this proposal is to combine the principles of timereversed acoustics (TRA) with MR detection of shear wavepropagation in order to create a robust and quantitative as-sessment of tissue elasticity. As is well known, the mechani-cal properties of tissue are often important surrogate mea-sures of disease burden. To address these concerns, recentadvances in Magnetic Resonance Elastography (MRE) haveshown promise in visualizing breast cancers and other tissuepathologies. The research proposed here will develop newmethods to measure tissue elasticity of acoustically hiddenorgans such as brain or liver. To achieve this overall goal wewill: 1) Conduct laboratory studies on heterogeneous tissuemimicking phantoms to evaluate technical requirements toMR Shear Wave Elasticity Imaging (SWEI) system and de-fine specification for the TRA focusing system. 2) Constructan MR compatible TRA system for highly localized remotegeneration of radiation force in tissue phantoms. 3) Integratethe MR compatible TRA system with the MRI system anddemonstrate the principle and the feasibility of the MRSWEI system based on TRA.

Thesaurus Terms: elasticity, magnetic resonance imaging,method development, tissue electromagnetic radiation, phan-tom model bioimaging/biomedical imaging

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



MEASUREMENT OF PO2 IN TISSUES INVIVO AND IN VITRO

Grant Number: 2P01CA091597-07A2PI Name: Swartz, Harold M.

Abstract: Description (provided by applicant) EPR oximetryis an emerging technology that can make repeated and accu-rate measurements of pO2 from the same site in viable sys-tems, using particulate oxygen-sensitive paramagnetic materi-als. This revised competing renewal aims to bring this poten-tially very productive technique to a level of maturity whereits special capabilities can be applied to the numerous areasof research that will benefit significantly from the availabilityof such measurements, and to develop the technology to fa-cilitate its adoption by other scientists for experimental andpotential clinical uses. It will especially focus on making itfeasible to use these capabilities to advance progress in theunderstanding and therapy of cancer. The progress achievedin the first six years of the PPG has verified the usefulnessand also the need for such an approach, as we have bothachieved significant new experimental results and delineatedsome critical aspects of the technology that need further de-velopment. The rationale for carrying out these studies in aPPG is based on the need to have an integrated and syner-gistic set of studies that together provide the range of capa-bilities needed to develop fully this very promising tech-nique. The PPG involves collaborative efforts at three differ-ent sites. It is based at Dartmouth where there is a leadingNIH supported center for the broad development of in vivoEPR spectroscopy, which provides very strong and economi-cal instrumental support for the proposed studies. The projectat Dartmouth also has appropriate expertise and experienceto carry out several inter-related aspects of the research, in-cluding making comparisons of EPR oximetry with compli-mentary methods for the direct and indirect measurements ofoxygen in tissues and in preparing the technique for applica-tions in the clinic. The project at the U. Of Illinois providesunique capabilities in the development and characterization


e48

of paramagnetic materials, especially chars, for use both asoximetric sensors per se and to understand the characteristicsthat control the properties of oximetric particulate materials.The project at the U. Of Louvain provides unique expertisein the coating of paramagnetic materials and in pharmaceuti-cal aspects to facilitate the use of EPR oximetry in experi-mental animals and, eventually, in patients. The key person-nel involved in the PPG have an established record of effec-tive productive collaboration and are highly committed tocarrying out the crucial next steps to make this technologyfully effective and available for use by other investigators.

Thesaurus Terms: biomaterial development/preparation,electron spin resonance spectroscopy, oximetry, oxygen ten-sion

Institution: Dartmouth College11 Rope Ferry Rd. #6210Hanover, NH 03755

Fiscal Year: 2002Department: RadiologyProject Start: 15-May-1995Project End: 30-Jun-2007ICD: National Cancer InstituteIRG: ZCA1

TISSUE VIABILITY IN STROKE BYSODIUM MR IMAGING

Grant Number: 8R01EB002628-04PI Name: Thulborn, Keith R.

Abstract: Tissue sodium concentration (TSC), as measuredby sodium imaging, will be correlated with diffusion (appar-ent diffusion coefficient, ADC) and perfusion (relative cere-bral blood volume, rCBV; tissue transit time, TTT; arrivaltime, TA) from proton MRI over the first 12 hours of em-bolic stroke in a non-human primate model. These quantita-tive MR imaging parameters will be correlated with histolog-ical markers of tissue status including TTC, H&E andTUNEL staining. The goal is to establish if TSC an be usedas a measure of tissue viability in assessment of acute stroke.Early intervention with thrombolysis enhances the clinicaloutcome if the tissue is still viable. As reperfusion of in-farcted tissue increases the risk of adverse hemorrhage, theFDA approves a limited window of acceptable risk-benefitratio of 3 hours from the onset of neurological symptoms ina non-hemorrhagic stroke. A rapid method for assessment oftissue viability in this setting would aid in tailoring clinicalmanagement to the pathophysiology of each patient. Thecentral hypothesis is that there is a critical increase in TSCdue to loss of sodium ion homeostasis in a region of re-stricted diffusion (reduced ADC) that indicates a significantloss of tissue viability in stroke. An acute embolic strokemodel in a non-human primate is used to determine if a crit-

ical threshold of TSC defines tissue viability during the natu-ral progression of stroke thereby predicting recovery follow-ing reperfusion after thrombolysis with recombinant tissueplasminogen activator (rt-PA) This animal model is requiredto establish the magnitude and rate of change of TSC in awell-controlled setting that can be applied in the clinical set-ting. Other proton MRI parameters used clinically in strokeare water diffusion and perfusion. The same comprehensive,yet efficient MRI protocol as I have used in MRI examina-tions of both acute and sub-acute stroke patients, allowsTSC, ADC and blood pool perfusion parameters or rCBV,TTT and TA to be correlated in this acute stroke model andcompared to histological parameters of necrosis and apopto-sis. The novel twisted projection imaging acquisition pro-duces high quality, high-resolution sodium images whileecho-planar imaging is used for diffusion and perfusion im-aging. A dual-frequency, dual-quadrature, 23NA/1H RF coilensures co-registration of images and maps in minimum timewithout moving the subject. This well-controlled animalmodel examines if there is a critical TSC threshold that ac-curately predicts tissue viability as part of this comprehen-sive MR imaging protocol being used for clinical manage-ment of acute stroke.

Thesaurus Terms: acute disease/disorder, cytotoxicity, mag-netic resonance imaging, prognosis, sodium, stroke, apopto-sis, biomarker, blood volume, cell population study, diffu-sion, disease/disorder model, fibrinolysis, homeostasis, necro-sis, pathologic process, plasminogen activator, reperfusion,sodium ion Macaca mulatta, angiography, bioimaging/bio-medical imaging, histopathology, terminal nick end labeling

Institution: University Of Illinois At Chicago1737 West Polk StreetChicago, IL 60612

Fiscal Year: 2003Department: RadiologyProject Start: 20-Apr-2000Project End: 31-Jan-2005ICD: National Institute Of Biomedical


MAMMO & CARDIAC SPECT W/ROTATINGSLANT HOLE COLLIMATOR

Grant Number: 5R01EB001983-05PI Name: Tsui, Benjamin M.

Abstract: Description (provided by applicant): This is a re-submission of a competitive renewal grant application whosegoal is to develop a unique 3D SPECT imaging techniqueusing rotating multi-segment slant-hole (RMSSH) collima-tors. The major advantage for the innovative technique is itsability to provide substantial increase in detection efficiency


e49

for the same spatial resolution as compared to parallel-holeSPECT in imaging small organs such as breasts and heart.(For a 4- segment slant-hole collimator, the gain is -3 timeshigher than that of a standard parallel-hole collimator withthe same resolution.) In addition, the technique allows fully3D image reconstruction of RMSSH projection data acquiredwith the camera rotating over a limited angular range. Theacquisition strategy is particularly suitable for imaging thebreast and heart of very sick patients in NM clinics, emer-gency room and intensive care units. During the last 3 years,we have (1) designed, constructed and evaluated a RMSSHcollimator for 3D imaging of the breast, (2) developed andevaluated new 3D analytical and iterative reconstruction al-gorithms for projection data acquired using a RMSSH colli-mator, (3) developed a Monte Carlo simulation softwarepackage that allows us to design and evaluate the instrumen-tation, data acquisition strategies and image reconstructionmethods for RMSSH SPECT, and (4) performed experimen-tal phantom studies that provide preliminary evaluation ofRMSSH SPECT for clinical imaging of the breast and heart.In this renewal application, we propose to continue the de-velopment of RMSSH in breast imaging from theoretical,simulation and experimental to clinical studies. In addition,we propose extend the application of RMSSH SPECT tocardiac imaging of very sick patients in NM clinics, emer-gency room and intensive care units. This competitive re-newal application has 6 specific aims. They are: (1) to de-sign optimized MSSH and MSVSH collimators for breastand cardiac SPECT, (2) to develop 3D image reconstructionmethods for RMSSH and RMSVSH SPECT that include cor-rection for attenuation, collimator-detector blur and scatter,(3) to evaluate data acquisition strategies and image recon-struction methods for the two RMSSH SPECT imaging tech-niques of the breast and heart using phantom studies, (4) toevaluate the applications of the two RMSSH SPECT imag-ing techniques for the breast and heart using Hotelling andhuman observers on simulated data, (5) to evaluate the appli-cation of the two RMSSH SPECT techniques to clinicalbreast imaging, and (6) to evaluate the application of the twoRMSSH SPECT techniques to clinical cardiac SPECT imag-ing.

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

Institution: Johns Hopkins University3400 N Charles StBaltimore, MD 21218

Fiscal Year: 2004Department: RadiologyProject Start: 09-Jul-1999Project End: 31-Jul-2007ICD: National Institute Of Biomedical


FUNCTIONAL MRI IN HUMANS AT 7TESLA

Grant Number: 5R01EB000331-03PI Name: Ugurbil, Kamil

Abstract: To date, owing to their wide availability,1.5T sys-tems are used for the majority of fMRI studies althoughhigh-field (3T and 4T) systems have also been used. Concep-tual considerations of BOLD mechanism predict a funda-mental dependence on magnetic field strength and led to thesuggestion that the sensitivity, contrast, and spatial specific-ity of the BOLD response to neural activity increase with thefield strength. These predictions, however, have only beenexamined so far in a relatively few studies all based on ani-mal models. While animal studies provide us with data thatcan elucidate the biophysics of fMRI in certain models, theyare not necessarily fully applicable to the human brainBOLD fMRI. First, most animal studies are conducted underanesthesia, where the physiological parameters are differentfrom that of awake human subjects. Second, the signal-to-noise ratio as well as spatial and temporal resolutionsachievable with animals are much more than that achievablein humans, making the translation of animal results to hu-mans inappropriate. Third, paradigms that can be applied toanimal models are mostly limited to sensory stimulation.Fourth, the vascular architecture in animals differs from thatin humans with respect to all vessels except capillaries. Forthese reasons, it is important to investigate fMRI in humansat ultra high magnetic fields to elucidate the field depen-dence of various attributes of fMRI and ascertain the advan-tages of high magnetic field. With the availability of a 7Tesla whole-body imager, it is now possible to investigatethese issues directly in the human brain for the first time.The overall goal of the present application is to investigatethe characteristics of fMRI at ultra high magnetic fields andutilize these potential advantages for high resolution fMRIthat can probe neuronal function at the millimeter to sub-millimeter spatial scale. As ultrahigh field human systemsare still in their experimental stage, technical development isneeded to make use of its capabilities. To realize the antici-pated increase in sensitivity and spatial specificity, it is nec-essary to develop methodology for high-resolution fMRI atultrahigh fields. In addition, as physiological noise may scalewith the signal in the data, become dominant, and mitigatethe advantages of high field, it is important to understand itand to develop improved methods to reduce it. Thus the firstaim of this project will focus on these two technical aspects.Our second aim will then investigate the field dependence ofsensitivity and specificity and how these issues affect spatialand temporal resolutions. For these studies we propose tofocus on high resolution fMRI of brain regions rather thanthe whole brain at this stage since the latter goal presents anadditional set of challenges that are beyond the scope of this


e50

application. With these considerations in mind, our specificaims are 1) technical development and understanding of sig-nal fluctuations in fMRI at high fields and 2) characterizationof the BOLD response at ultrahigh magnetic field with highspatial and temporal resolution.

Thesaurus Terms: evaluation/testing, functional magneticresonance imaging, technology/technique development, brainmapping, magnetic field, neurophysiology bioimaging/bio-medical imaging, clinical research, human subject

Institution: University Of Minnesota Twin Cities200 Oak Street SeMinneapolis, MN 554552070

Fiscal Year: 2004Department: RadiologyProject Start: 01-Jul-2002Project End: 30-Apr-2006ICD: National Institute Of Biomedical


FUNCTIONAL MAGNETIC RESONANCESTUDIES OF THE BRAIN

Grant Number: 8R01EB002634-11PI Name: Van Zijl, Peter Cm.

Abstract: It is believed that early intervention is the key tosuccessful therapeutic outcome in stroke, which is the thirdmost frequent cause of mortality in western society. Thus,the ability to diagnose ischemic brain tissue with a high de-gree of specificity and sensitivity is critical. Magnetic Reso-nance Imaging (MRI) and Spectroscopy (MRS) hold greatpromise for noninvasive assessment of brain damage. How-ever, if MR is to become useful for prognosis, it is essentialto determine whether reversible or irreversible damage hasoccurred during and after ischemic periods. In addition toassessing large- and small-vessel perfusion using MR an-giography (MRA) and dynamic contrast imaging, it is essen-tial to have access to MR parameters that reflect reversibleand irreversible tissue damage during and after ischemic pe-riods. Spin-Density/T2-weighted imaging is a good indicatorof edema (hyperintensity), but is not sensitive in the acutephase. It is therefore important to develop new functionalimaging methods that can quantitatively assess tissue statuswhen neurologic recovery is still possible. Diffusion imagingcan detect ischemic tissue within minutes post-onset, butcontrary to early expectations based on animal studies, clini-cal results generally show that regions of reduced diffusionproceed to infarction at follow-up. In addition, perfusion im-ages generally show an area of reduced flow larger than theregion of compromised diffusion, the so-called perfusion-diffusion mismatch. Because it is essential to assess the risk

of infarction in this region, which often evolves to reduceddiffusion, there is a need for new functional modalities todiagnose this mismatch area at the time of clinical evalua-tion. Based on recent results obtained by us, we have de-signed the following hypotheses: (1) quantification of oxygenextraction ratio (OER) can predict the risk for tissue infarc-tion based on the principle of flow thresholds; (2) changes inprotein synthesis are reflected in the proton magnetizationtransfer rate between proteins and water, which can be im-aged through the MRI relaxation rate T1rho; (3) It is possi-ble to measure pH using proton MRS, which will provide anadditional tissue parameter for stroke evaluation on a stan-dard clinical scanner (proton only). Our corresponding threeaims are to develop new methodologies to measure OER,T1rho, and pH, and to subsequently test our three hypothesison cat brain models of reduced blood flow and of transientglobal and focal ischemia. Our fourth and final aim is to im-plement the new technologies on the clinical scanner and tooptimize their use for a fast and specific clinical strokeexam.

Thesaurus Terms: brain imaging/visualization/scanning,cerebral ischemia/hypoxia, cerebrovascular disorder diagno-sis, diagnosis design/evaluation, functional magnetic reso-nance imaging, magnetic resonance imaging, stroke, technol-ogy/technique development brain metabolism, disease/disor-der model, disease/disorder proneness/risk, noninvasivediagnosis, oxygen consumption, prognosis, protein biosynthe-sis, rapid diagnosis, transient ischemic attack bioimaging/biomedical imaging, cat, clinical research, diffusion, humansubject, nuclear magnetic resonance spectroscopy


Fiscal Year: 2003Department: RadiologyProject Start: 10-Jun-1992Project End: 30-Nov-2005ICD: National Institute Of Biomedical


CONE-BEAM METHODS FOR DYNAMICVOLUMETRIC X-RAY CT

Grant Number: 5R01EB002667-02PI Name: Wang, Ge

Abstract: Description (provided by applicant): Currently,medical CT scanners are under rapid development with anincreasingly larger cone angle, while biomedical micro-CTscanners are already in cone-beam geometry. Despite theimportance of cone-beam CT, cone-beam image reconstruc-tion algorithms are not fully developed. There is a critical


e51

and immediate need for a dynamic volumetric performanceof cone-beam CT, subject to multiple constraints such asdose, noise, range, contrast, etc. The overall goal of thisproject is to develop and optimize analytic cone-beam algo-rithms with an emphasis on high temporal resolution andshort scan range, and directly applicable to major applica-tions such as cardiac imaging, CT fluoroscopy, perfusionstudies, CT angiography, oncologic imaging, small animalimaging, as well as PET and SPECT. This project is basedon the latest cone-beam CT results, and focuses on both ap-proximate and exact reconstruction in the Feldkamp-type,Grangeat-type and Katsevich-type frameworks respectively.The specific aims are to (1) improve Feldkamp-type algo-rithms for less than half-scan data by scanning pattern designand weighting scheme optimization; (2) extend Grangeat-type half-scan algorithms for long object reconstruction bycorrecting cone-beam data, and transform the Radon spacebased reconstruction into the filtered back-projection format;(3) modify Katsevich-type algorithms for dynamic recon-struction by detection coverage minimization and n-PI geom-etry-based formulation; and (4) evaluate and validate theproposed cone-beam algorithms in theoretical analysis, nu-merical simulation and phantom experiments, and demon-strate their feasibility and utilities in mouse and patient stud-ies. On completion, superior and practical cone-beam algo-rithms will have been systematically developed withexcellent image quality for dynamic volumetric CT and mi-cro-CT. These proposed algorithms will have been imple-mented on a PC cluster. The advantages of the algorithmswill have been demonstrated in mouse and patient studies.

Thesaurus Terms: X ray, computed axial tomography, im-aging/visualization/scanning, method development, computerprogram/software, computer simulation, phantom model ani-mal data, bioimaging/biomedical imaging, clinical research,human data, mathematics

Institution: University Of IowaIowa City, IA 52242



DEVELOPMENT AND INTEGRATION OFBIOLUMINESCENT CT

Grant Number: 1R21EB001685-01PI Name: Wang, Ge

Abstract: Description (provided by applicant): Small ani-mals, particularly genetically engineered mice, are of in-

creasing importance to understand the biologic basis forpathologic disease manifestations. Major efforts are beingmade to link the genome to the phenotypic expression inboth form and function (“Physiome”). Small animal imagingoffers the opportunity to evaluate pathologic progression in amuch-compressed time frame and with a much-improvedresolution. In this R21/R33 proposal, we plan to develop andintegrate the first bioluminescent CT (BLCT) device for im-aging gene expression and a state-of-the-art micro-CT scan-ner for studies of the lung in the living mouse model. Ourlong term goal is to advance molecular and micro imagingtechnology, and make the proposed integrated system an invivo tool in biomedical applications, especially for smallanimal tomography. The specific aims of the R21 Phase areto (1) develop a data acquisition module for bioluminescentimaging of the mouse lung; (2) establish the forward modelfor bioluminescence based on the optical properties of themouse as derived from its CT volume; (3) demonstrate thefeasibility of bioluminescent tomography in numerical simu-lation and phantom experiments. The specific aims of theR33 Phase are to (1) prototype a bioluminescent CT devicewith I0 CCD cameras, and develop an iterative algorithm fora spatial resolution on the order of 1 ram; (2) build a multi-resolution micro-CT scanner with dual imaging, and developanalytic algorithms for high quality reconstructions, includ-ing the in vivo mode with about 20 micron spatial resolutionand 20 second temporal resolution and a maximal spatialresolution on the order of 5 microns; (3) integrate the twocutting-edge CT modalities (optical and X-ray), and demon-strate the feasibility and utility of the integrated system insmall animal studies. Upon completion of the R21/33project, a unique micro-tomography system will have beendeveloped with molecular, multi-resolution, multi-energy,dynamic and bioluminescent imaging capabilities. We willdemonstrate, through example projects, the utility of the sys-tem in generating critical physiological and pathological in-formation of the lung.

Thesaurus Terms: X ray, bioluminescence, biomedicalequipment development, computed axial tomography, imag-ing/visualization/scanning gene expression, lung bioimaging/biomedical imaging, laboratory mouse

Institution: University Of IowaIowa City, IA 52242


Imaging And BioengineeringIRG: ZCA1


e52

TRAINING IN QUANTITATIVE MAGNETICRESONANCE IMAGING

Grant Number: 5T32EB000814-07PI Name: Wehrli, Felix W.

Abstract: Description (Provided By Applicant): Training InQuantitative Magnetic Resonance Imaging Magnetic reso-nance imaging (MRI) has, since its inception over two de-cades ago, been used mainly as a qualitative imaging tech-nique practiced by radiologists utilizing predominantly quali-tative criteria for establishing a diagnosis or excludingdisease. This approach is fraught with problems, its maindisadvantage being the subjective nature of the result, i.e.,sensitivity to reader experience and judgment. Many prob-lems in diagnostic medicine require a quantitative assess-ment. Among these are the sizing of vascular stenoses, themeasurement of a perfusion deficit, or the evaluation of re-sidual disease burden during regression of disease in re-sponse to therapeutic intervention in the treatment of tumors,white matter disease, etc. Moreover, for many diagnostic orstaging problems, quantitation of an observation is notmerely a better alternative to qualitative assessment, but thequalitative approach is entirely unsuited. Examples are non-focal systemic disorders such as osteoporosis where a quanti-tative measurement of some physiologic parameter, e.g.,bone mineral density, has to be made. In diagnostic imagingin general, and MRI in particular, quantitative approachesrequire the tools of post-processing of arrays of images, typi-cally performed off-line on workstations. This process ismultidisciplinary, requiring close cooperation among physi-cians, MR physicists, and computer scientists, which is notpossible without effective cross-training. Physicists, engi-neers and computer scientists usually lack an understandingof the medical problem and are often unable to translate ab-stract concepts to the physician. The problem is exacerbatedby language barriers since the members of the exact sciencesoften have difficulties in effectively communicating withphysicians, as their terminology is outside the scope of medi-cine. This project aims to train basic science students at thepre- and post-doctoral level in quantitative magnetic reso-nance methodology and, conversely, medical science traineesin the use of quantitative MR imaging tools for diagnosisand treatment monitoring. Training modalities involve acombination of colloquia, structured teaching and hands-onlaboratory training, with particular emphasis on preceptor-directed research. The training faculty consists of both basicscientists and physicians who have a record of successfulmultidisciplinary research training.

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


Fiscal Year: 2004Department: RadiologyProject Start: 25-Aug-1998Project End: 30-Jun-2008ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: NCI

HIGH RESOLUTION T2 WEIGHTED BOLDfMRI IN HUMANS

Grant Number: 5R21EB000565-02PI Name: Yacoub, Essa

Abstract: Description (provided by applicant): Functionalmagnetic resonance imaging (fMRI) has the ability to moni-tor the vascular response to neuronal activity. The vascularresponse, changes in local blood flow, blood volume andoxygen consumption, is measured by the correspondingchanges in oxygenation levels The paramagnetic nature ofdeoxygenated hemoglobin serves as a contrast agent formonitoring hemodynamic changes accompanying neural ac-tivity. Blood oxygen level dependent (BOLD) contrast hasbeen widely utilized and the method of choice for non-inva-sive imaging of brain function, specifically in humans. Withthe application of BOLD fMRl to high spatial resolutionmapping of brain function, it is becoming increasingly im-portant to understand the specificity limitations of the vascu-lar response and how to exploit these limits of specificitywhen using BOLD fMRI. BOLD fMRI may be performedusing either T2 or T2’ weighted images, both of which havesensitivity, although different, to BOLD effects. Our long-range goal is to realize the limitations of BOLD signals forthe purpose of increasing the accuracy of mapping high reso-lution functional structures in the human brain. The centralhypothesis of the proposed research is that T2 weightedBOLD fMRl can be efficiently implemented for high spatialresolution applications in humans and at high magnetic fieldsmaximizes the specificity of the BOLD response. This hy-pothesis has been formulated from a substantial amount ofpreliminary data, which suggest feasibility of high resolutionT2 weighted BOLD fMRl in humans, and theoretical consid-erations which predict advantages in specificity and sensitiv-ity for T2 weighted BOLD signals at high magnetic fields.The central hypothesis will be tested and the objective of theapplication will be accomplished by pursuing three specificaims: 1) Develop a high-resolution T2 weighted imagingsequence for use in the human brain, 2) assess the vascularnature of the T2 response as it changes with fields strength,and 3) to determine whether or not T2 weighted BOLDfMRl is more suited, than conventional T2’ weighted BOLDfMRl, for high spatial resolution applicants in humans. Therationale for the proposed research is: T2 weighted BOLDfMRl can provide more detailed and more specific informa-


e53

tion on microvascular and hemodynamic changes associatedwith functional brain activation. As an advanced MR center,we are uniquely positioned to undertake the proposed re-search. Our laboratory has well-established expertise in func-tional imaging, advanced hardware and software develop-ment, and specialized RF coil design. The proposed researchis innovative as high resolution T2 weighted BOLD fMRl inthe human brain at submillimeter resolutions has not beenfeasible to date. We expect that T2 weighted BOLD fMRIwill be the imaging method of choice for high spatial resolu-tion applications. This is significant because of the increasingdemands to reliably map high resolution functional structuresin the human brain. It will advance the field of non-invasivebrain mapping to unmatched levels of specificity and sensi-tivity to neuronal activity.

Thesaurus Terms: biomedical equipment development,blood oxygenator, brain imaging/visualization/scanning,functional magnetic resonance imaging, neurophysiologybrain mapping, cardiovascular function, contrast media, he-modynamics, visual cortex bioimaging/biomedical imaging,clinical research, human subject

Institution: University Of Minnesota Twin Cities200 Oak Street SeMinneapolis, MN 554552070

Fiscal Year: 2003Department: RadiologyProject Start: 01-Aug-2002Project End: 31-Jul-2004ICD: National Institute Of Biomedical


HIGHER OXIDATION STATE ASTATINE-211 RADIOPHARMACEUTICALS

Grant Number: 1R21EB002980-01PI Name: Yordanov, Alexander T.

Abstract: Description (provided by applicant): Astatine-211,an alpha-emitter with a half-life of 7.2 h, is among the mostpromising radionuclides under development as a radiophar-maceutical for the treatment of malignant disease because ofits convenient half-life and the shorter penetration of its al-pha emissions. A pivotal issue in designing an optimal radio-pharmaceutical remains the choice of the chemistry to conju-gate the radionuclide to the carrier molecule. The linker musthold the radionuclide firmly so that there is no prematurerelease of the isotope in vivo. A number of acylation agentsfor At-211 labeling of proteins, peptides and small mole-cules, have been developed over the last ten years. Althoughthese labeling reagents have shown encouraging results intactmAbs and have allowed for the initiation of the first clinicaltrials involving At-211 in our institution, questions remain

about the unusually high accumulation of At-211 in sometissues, such as lings and spleen, when antibody fragmentsor small molecules are used. Clearly, new and improvedtechniques for At-211 labeling of smaller radionuclide carri-ers are urgently needed. The objective of this proposal is thepreparation and evaluation of higher oxidation states At-211labeling as a novel approach in the preparation of At-211radiopharmaceuticals. To this end there are four specificaims: i) to develop the optimal chemistry for isolation andconcentration of higher oxidation states At-211; 2) to investi-gate the in vitro and in vivo biological behavior of higheroxidation states At-211; 3) to synthesize, identify and purifyorganic molecular carriers radiolabeled with higher oxidationstates At-211; and 4) to investigate the in vitro and in vivobiological stability of organic molecular carriers radiolabeledwith higher oxidation states At-211. The in vivo biologicalbehavior of all At-211 inorganic species and radiolabeledsmall organic molecules will be evaluated in BALB/c mice.

Thesaurus Terms: method development, neoplasm/cancerradionuclide therapy, oxidation, radiopharmacology, biomate-rial development/preparation, bismuth, particle accelerator,laboratory mouse

Institution: Duke UniversityDurham, NC 27710



IMAGE RECONSTRUCTION WITH SOLIDSTATE SPECR

Grant Number: 5R33EB001489-02PI Name: Zeng, Lawrence G.

Abstract: The main objective of this project is the develop-ment and evaluation of image reconstruction methods for arotating, strip gamma camera for SPECT (single photonemission computed tomography). The strip gamma cameraconsists of a CdZnTe detector and a tungsten slat collimator.This solid-state detector is photomultiplier-tube free and hashigher energy resolution (about 3% FWHM at 140 keV pho-topeak) than a regular Anger camera. In order to reduce thecost of CdZnTe material, the detector is a narrow rectangularstrip. Instead of using a parallel-hole collimator, a set of par-allel slats that define a series of planes are used to collimatethe incoming photons. As a result, the measured projectiondata are planar integrals as opposed to the line integrals thatare generally encountered in traditional Anger camera appli-cations. The measured planar integral of the radioactivity


e54

distribution is weighted by a factor l/r, where r is the dis-tance from the point of interest to the detector. One impor-tant goal of this proposal is to develop reconstruction algo-rithms that can exactly compensate for the detectors distancedependent sensitivity. Another important goal of this pro-posal is to develop algorithms that make the images immunefrom truncation errors. This will make our imaging system alocal tomographic device. Still another important goal of thisproposal is to evaluate the performance of the combinationof the new detector and reconstruction algorithms. Specialemphasis will be placed on developing a novel solid-stateimaging system that will provide nearly scatter-free and trun-cation-error-free images. High image spatial resolution willbe achieved by using convergent slat collimators. The workhas the potential to significantly improve the diagnostic ca-pabilities of SPECT imaging. This proposal will (a) promotethe development of very novel (high risk, high gain) technol-ogies, including continued support for their maturation andfull exploitation, (b) promote system integration of technolo-gies for targeted applications, and (c) improve technology trans-fer by promoting partnerships between academia and industry.

Thesaurus Terms: image enhancement, single photon emis-sion computed tomography, technology/technique develop-ment computer program/software, computer simulation, com-puter system design/evaluation, image processing, lead,mathematics, nuclear medicine, phantom model, tungstenbioimaging/biomedical imaging

Institution: University Of UtahSalt Lake CITY, UT 84102

Fiscal Year: 2004Department: RadiologyProject Start: 17-Mar-2003Project End: 28-Feb-2006ICD: National Institute Of Biomedical

Imaging And BioengineeringIRG: ZCA1

BREAST CANCER IMAGING USING ASOLID-STATE SPECT CAMERA

Grant Number: 5R21EB003298-02PI Name: Zeng, Lawrence G.

Abstract: Description (provided by applicant): The mainobjective of this project is the development of breast cancerimaging methods using a rotating gamma camera for SPECT(single photon emission computed tomography). The gammacamera consists of a CdZnTe detector and a tungsten or leadslat collimator; therefore this solid-state detector does notuse photomultiplier-tubes. Instead of using a parallel-holecollimator, a set of parallel slats that define a series of planesare used to collimate the incoming photons. As a result, themeasured projection data are planar integrals as opposed to

the line integrals that are generally encountered in traditionalAnger camera applications. One advantage of this newgamma camera is its higher energy resolution (about 3%FWHM at 140 keV photopeak) than a regular Anger camera(about 10% FWHM at 140 keV photopeak). Therefore weare able to acquire nearly Compton scatter free data. Anotheradvantage is that the resultant SPECT image will be local.This means that the reconstructed region-of-interest (ROI) isnot affected by the radioactivities outside the ROI and inother organs. The radioactivities in the heart and liver areusually high and usually contaminate the projection data ofthe breast. Our reconstruction algorithm is able to excludethe activities outside the ROI. The overall goal of the projectis to develop efficient and accurate three-dimensional SPECTreconstructions for breast imaging using the new CdZnTecamera. The work has the potential to significantly improvethe detection of small cancerous lesions in the breast, andsignificantly improve the diagnostic capabilities of SPECTimaging of the breast. This proposal promotes the develop-ment of very novel (high risk, high gain) technologies, in-cluding continued support for their maturation and full ex-ploitation, and promote system integration of technologiesfor targeted applications.

Thesaurus Terms: biomedical equipment development,breast neoplasm/cancer diagnosis, clinical biomedical equip-ment, mammary gland, method development, single photonemission computed tomography diagnosis design/evaluation,diagnosis quality/standard, image enhancement, scintillationcamera bioimaging/biomedical imaging, computer program/software, computer simulation, mathematical model, phantommodel



Imaging And BioengineeringIRG: ZRR1

FLAT-PANEL X-RAY IMAGING DETECTORWITH AVALANCHE GAIN

Grant Number: 5R01EB002655-02PI Name: Zhao, Wei

Abstract: Description (provided by applicant): The objec-tives of this proposal are to demonstrate the feasibility of anindirect flat-panel detector with programmable gain based onstructured scintillator - cesium iodide (Csl), avalanche amor-phous selenium (a-Se) photoconductor (which we callHARP) with increased gain and active matrix (AM) thin film


e55

transistor (TFT) readout, and improve the low dose imagingperformance of flat-panel x-ray imaging detectors. We callthe detector under investigation SHARP-AMFPI (ScintillatorHARP Active Matrix Flat Panel Imager). It will provide bet-ter image quality in fluoroscopy, behind dense breasts inmammography, and digital tomosynthesis, where existingflat-panel detectors fall short of quantum noise limitation.Furthermore the inherent high electric field and charge car-rier mobility in HARP allows better temporal imaging per-formance which leads to less image artifacts and better diag-nosis accuracy. The specific aims are to: (1) understand andoptimize the fundamental imaging properties of Csl andHARP for different x-ray imaging applications; (2) demon-strate the excellent low dose and high speed performance ofSHARP using a prototype HARP tube optically coupled tooptimized Csl layers; (3) identity potential practical difficul-ties for constructing SHARP-AMFPI and develop engineer-ing methods for solving them; (4) demonstrate the practicalfeasibility of the proposed detector. Our research design andmethods are to develop experimental and modeling tech-niques to investigate the fundamental imaging properties ofCsl and HARP, verify the validity of models with experi-mental results so that the model can be used to optimize de-tector design parameters. We will investigate the feasibilityof the detector using three gradual steps: First, the advantageof avalanche gain on image quality will be demonstratedusing the matured electron beam readout technology forHARP, then a hybrid prototype detector will be made basedon existing TFT array and HARP layer deposition technol-ogy so that compatibility issues between these two devicescan be fully investigated, and finally a integrated prototypedetector will be constructed using procedure that is scalableto large areas to demonstrate the ultimate feasibility ofSHARP-AMFPI. Its x-ray imaging performance will be eval-uated and compared to existing FPI technologies, so that itsimproved performance at low dose and high frame rates canbe demonstrated.

Thesaurus Terms: biomedical equipment development, im-age enhancement, radiation detector, radiography bioengi-neering/biomedical engineering, fluoroscopy, mammography,mathematical model, model design/development, photocon-duction, scintillation camera, tomography bioimaging/bio-medical imaging, electrical measurement

Institution: State University New York StonyBrook

Stony Brook, NY 11794Fiscal Year: 2004Department: RadiologyProject Start: 07-Sep-2003Project End: 31-Jul-2008ICD: National Institute Of Biomedical


HUMAN BRAIN PROTEIN MR IMAGINGAND SPECTROSCOPY AT 3T

Grant Number: 5R21EB002666-02PI Name: Zhou, Jinyuan

Abstract: Description (provided by applicant): Despite theabundance of proteins inside many cell types, these proteinsdo not provide intense signals in proton magnetic resonance(MR) spectra, and little has been studied about cellular pro-teins in vivo or in cells, in particular, there are presently nomagnetic resonance imaging (MRI) methods to spatially as-sess protein content and status in vivo. Yet, most cellularactivities are performed by proteins, and various lesions,such as those found in cancer and stroke, may show changesin protein content and amide proton exchange properties, andthus the interpretation of the nature of these proteins is im-portant for earlier detection, better spatial definition, and im-proved characterization of diseases. We will develop novelMRI and MRS (magnetic resonance spectroscopy) methodsfor studying mobile cellular proteins and their properties intissue. We hypothesize that detection sensitivity enhancementthrough selective saturation transfer via water-exchangeableamide protons of mobile proteins allows spatial assessmentof protein content and status in biological tissue via the wa-ter signal. The overall goal of this study is to develop acompletely new MRI technique, called amide proton transfer(APT) imaging, which opens the possibility of adding intrin-sic protein-based contrast to the diagnostic capability ofhigh-field MRI. The clinical use of this type of imaging willfirst be demonstrated for human brain tumors. Therefore, thespecific aims of this application are: (1) To develop new MRspectroscopy methods with a WATERGATE detectionscheme and to quantify amide proton content and exchangerates in the human brain on a 3T clinical MRI system. (2)To develop and implement a new single-slice amide protontransfer imaging technique and to quantify amide protontransfer contrast for imaging of brain tumors on a 3T humanMRI system. (3) To determine brain tumor boundary andvolume using multi-slice amide proton transfer imaging on a3T human MRI system. APT imaging can be used to study ahost of potentially abnormal proteins in cancer, stroke, meta-bolic disorders, and other diseases. The successful outcomeof this application will offer a sensitive and specific modalityin the clinical MRI examination of diseases.

Thesaurus Terms: brain imaging/visualization/scanning,magnetic resonance imaging, method development, nerve/myelin protein, nuclear magnetic resonance spectroscopy,protein quantitation/detection, amide, brain neoplasm, hydro-gen ion bioimaging/biomedical imaging, clinical research,human subject, phantom model



e56



ASSESSMENT OF STEM CELL THERAPYOF INFARCTED MYOCARDIUM

Grant Number: 5R21EB002473-02PI Name: Zhou, Rong

Abstract: Description (provided by applicant): Stem cellsbear great promise for treatment of myocardial infarctions.Before this therapy becomes a reality in the clinics, in vivostudies using animal models are necessary to address impor-tant questions such as 1) whether the microenvironment inwhich stem cells are grafted provides enough stimuli forthem to differentiate into cardiac myocytes, 2) whether adultstem cells (e.g. bone marrow derived mesenchymal stemcells) in addition to embryonic stem cells can undergo a fullcardiogenic differentiation, 3) to what extent after grafting,the cardiac functions can be stabilized or improved. To ad-dress the above questions, this project will develop a non-invasive imaging system that allows repetitive, in vivo moni-toring of the fate of stem cells and assessment of their po-tential therapeutic effect. By utilizing cardiac specific markergenes detectable by imaging, we will test whether the micro-

environment into which stem cells are grafted providesenough cues for them to differentiate into the target tissue(i.e., cardiac muscle cells). By developing cine-based taggedMR imaging techniques, changes of regional myocardialcontractile function resulted from the stem cell grafting willbe assessed non-invasively. Finally, developing these imag-ing techniques on a murine myocardial infarct model allowsthe utilization of transgenic or knockout mouse models inthe future.

Thesaurus Terms: cardiac myocyte, cardiovascular disordertherapy, cardiovascular imaging/visualization, cell differenti-ation, heart contraction, myocardial infarction, noninvasivediagnosis, stem cell transplantation, technology/techniquedevelopment biological signal transduction, embryonic stemcell, gene expression, genetic marker, bioluminescence, labo-ratory mouse, molecular cloning, transfection/expression vec-tor





e57

Date post:	03-Jan-2017
Category:	Documents
Upload:	donhan
View:	214 times
Download:	0 times

Abstracts of Funded National Institutes of Health Grants

Documents