Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ... Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

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THE WHITAKERBIOMEDICAL IMAGINGLABORATORYTHE FISHERLABORATORYINVESTIGATORSAndrew Cwik, B.S.Bernhard Sturm, Ph.D.Robert Holtman, M.S.GRADUATE STUDENTKunio Nakamura, B.S.COLLABORATORSJeff Cohen, M.D. 1Robert Fox, M.D. 1Mike Phillips, M.D. 2Richard Rudick, M.D. 1Lael Stone, M.D. 1Jean Tkach, Ph.D. 2Bruce Trapp, Ph.D. 31Mellen Ctr. for MS Treatmentand Research, Dept. ofNeurology, CCF2Div. of Radiology, CCF3Dept. of Neurosciences, CCFThe objectives of the neuroimaging researchprogram are to develop new imagingtechniques that provide relevant markersand predictors of disease progression in multiplesclerosis (MS) and other neurological diseases.Our research is focused on quantitative methodsfor measurement of tissue injury andneurodegeneration from magnetic resonanceimages (MRIs) of the brain. We also seek thebest ways to apply these methods to improveroutine monitoring and therapy evaluation, aswell as to gain new insights into pathologicprocesses.To quantify brainMRIs, we are workingon the development andvalidation of imageanalysis software forautomated imagesegmentation andregistration, multiprotocollesionquantification, andanatomic labeling. Amajor area of interest inour laboratory isaccurate and reliablemeasurement of brainatrophy, a marker ofirreversible tissuedamage. Application ofa new brain-atrophymeasurement methodhas demonstrated thatatrophy occurs in theearly stages of MS, iscorrelated to concurrentand future disability,and can be slowed bytreatment. Ongoing projects include a longitudinalstudy of brain atrophy, which aims todetermine the clinical, MRI, immunologic, andpathologic correlates of brain atrophy in MSpatients. This 5-year study involves the evalua-The Department of Biomedical EngineeringImaging Provides New Views on MultipleSclerosis and NeurodegenerationElizabeth Fisher, Ph.D.tion of MS patients and normal healthy volunteerswith MRI and clinical examinations. We areworking on improved methods for combinationof information from different types of imagesand more sensitive methods for detection oflesion changes over time. The relationshipsbetween clinical and MRI variables and timecourse of changes in the MRI measurements willbe investigated. A post-mortem imaging protocolhas been incorporated into an MS brain donationprogram to relate the different types of MRImeasurements to the underlying pathology. Othercollaborative research projects include a followupstudy to investigatethe predictive value ofMRI measurements overthe course of 10 years inMS patients and theanalysis of images todetermine associationsbetween specific domainsof cognitive impairmentand MRI measures ofpathology in patients withMS. Software developedin our laboratory is beingused in several clinicaltrials of new treatmentsfor MS, and efforts areunder way to incorporatebrain atrophy measurementsinto clinicalpractice.The newneuroimaging centerlocated at CCF’s MellenCenter will enable us toextend our efforts fromimage analysis into imageacquisition. Future plans include the investigationof newer imaging techniques that will providemore specific information about underlyingdisease processes in MS and other neurologicaldisorders.Fisher, E., Cothren, R.M., Tkach, J.A., Masaryk, T.J., and J.F. Cornhill (1997) Knowledge-based 3D segmentationof MR images for quantitative MS lesion tracking. SPIE Medical Imaging 3034:599-610.Rudick, R.A., Fisher, E., Lee, J.-C. and J. Simon (1999) Use of the brain parenchymal fraction to measurewhole brain atrophy in relapsing-remitting MS. Mutiple Sclerosis Collaborative Research Group. Neurology53:1698-1704.Fisher, E., Rudick, R.A., Cutter, G., Baier, M., Miller, D., Weinstock-Guttman, B., Mass, M.K., Dougherty,D.S., and N.A. Simonian (2000) Relationship between brain atrophy and disability: an 8-year follow-upstudy of multiple sclerosis patients. Multiple Sclerosis 6:373-377.Meier, D., and E. Fisher (2002) Parameter space warping: shape-based correspondence between morphologicallydifferent objects. IEEE Transactions on Medical Imaging 21:31-47.Fisher, E.. Rudick, R.A., Simon, J.H., Cutter, G., Baier, M., Lee, J.C., Miller, D., Weinstock-Guttman, B.,Mass, M.K., Dougherty, D.S., and N.A. Simonian (2002) Eight-year follow-up study of brain atrophy in patientswith MS. Neurology 59:1412-1420.28

The Department of Biomedical EngineeringQuantitative Microscopy andHigh-Resolution Imaging of BoneTHE WHITAKERBIOMEDICAL IMAGINGLABORATORYOsteoporosis, a disease characterized bylow bone mass and loss of structuralintegrity of bone tissue, can ultimatelylead to bone fracture. Osteoporosis is responsiblefor 1.5 million fractures annually inAmerica. The annual cost for treatingosteoporotic fractures worldwide is estimatedto be 10-15 billion U.S. dollars. Significantmorbidity and mortality are associated withosteoporotic fractures, and 80% of thoseaffected by osteoporosis are women.Micro-computed tomography (micro-CT)is a three-dimensional (3D) x-ray imagingtechnology used to evaluatethe trabecular structure ofcancellous bone both in vivoand ex vivo specimens fromhumans and animals. As anoninvasive imagingmodality, it is suitable formonitoring varioustreatment effects in smallanimals over time. It hasbeen used to study in vivochanges in trabeculararchitecture of the tibia inOVX rats and the effects ofsubsequent hormonereplacementtherapy inestrogen-depletedosteopenic rats. Our grouphas recently designed anddeveloped a high-resolutionmicro-CT imaging system toevaluate the microarchitectureof bone ex vivoin specimens and in vivo insmall animal models.Working closely with basic and clinicalscientists, we are developing novel highresolutionimaging and post-processingtechniques that will aid in evaluating early bone lossand bone formation in small-animal models ofosteoporosis and in monitoring the effects ofvarious treatments longitudinally. We propose todevelop: 1) high-resolution 3D fluorescencemicroscopy and micro-CT imaging techniques foranalyzing in vivo and excised bone over largeregions of interest; 2) intra- and multimodalityregistration technique for spatially aligninglongitudinal micro-CT images and 3D colorhistology images of trabecular bone; 3) real-timevisualization and graphic manipulation tools forsimultaneously displaying 3D color-histology and4D micro-CT images;and 4) novel measuresto identify early boneloss/formation fromdirect measurement oflongitudinal micro-CTimages of bonetrabecula. Theseimaging tools willallow bone researchersto visualize two ormore spatially aligned3D micro-CT imagesets as well as the 3Dcolor histology withthe micro-CT imagessimultaneously. Mostimportantly, it willprovide a mechanismfor interactivelyreviewing, localizing,and quantifyinginformation obtainedfrom different imagingmodalities at differentspatial resolutions.Kimerly A. Powell, Ph.D.THE POWELLLABORATORYRESEARCH ENGINEERLarry Latson, M.S.COLLABORATORSSuneel S. Apte, Ph.D. 1Bradley Clymer, Ph.D .2Ronald J. Midura, Ph.D. 1George F. Muschler, M.D. 1Don Stredney 31Dept. of BiomedicalEngineering, CCF2Dept. of Electrical Engineering,Ohio State University,Columbus, OH3The Ohio SupercomputerCenter, Columbus, OHLatson, L., Powell, K.A., Sturm, B., Schvartzman, P.R., and R. D. White (2001) Clinical validation of anautomated boundary tracking algorithm on cardiac MR images. Int. J. Cardiac Imaging 17:279-286.Obuchowski, N.A., Graham, R.J., Baker, M.E, and K.A. Powell (2001) Ten criteria for effective screening:their application to multislice CT screening for pulmonary and colorectal cancers. AJR Am. J. Roentgenol.176:1357-1362.Sivaramakrishna, R., Obuchowski, N.A., Chilcote, W.A., and K.A. Powell (2001) Automatic segmentationof mammographic density. Acad. Radiol. 8:250-256.Sturm, B., Powell, K., Stillman, A.E., and R.D. White (2002) Registration of 3D CT angiography MRimages in coronary artery disease patients, Int. J. Cardiovasc. Imaging, accepted.Muschler, G.F., Nitto, H., Matsukura, Y., Boehm, C., Valdevit, A., Kambic, H., Davros, W., Powell, K., andK. Easley (2003) Spine fusion using cell matrix composites enriched in bone marrow-derived cells. Clin.Orthop. (407):102-118.29

The Department of Biomedical EngineeringQuantitative Microscopy andHigh-Resolution Imaging of BoneTHE WHITAKERBIOMEDICAL IMAGINGLABORATORYOsteoporosis, a disease characterized bylow bone mass and loss of structuralintegrity of bone tissue, can ultimatelylead to bone fracture. Osteoporosis is responsiblefor 1.5 million fractures annually inAmerica. The annual cost for treatingosteoporotic fractures worldwide is estimatedto be 10-15 billion U.S. dollars. Significantmorbidity and mortality are associated withosteoporotic fractures, and 80% of thoseaffected by osteoporosis are women.Micro-computed tomography (micro-CT)is a three-dimensional (3D) x-ray imagingtechnology used to evaluatethe trabecular structure ofcancellous bone both in vivoand ex vivo specimens fromhumans and animals. As anoninvasive imagingmodality, it is suitable formonitoring varioustreatment effects in smallanimals over time. It hasbeen used to study in vivochanges in trabeculararchitecture of the tibia inOVX rats and the effects ofsubsequent hormonereplacementtherapy inestrogen-depletedosteopenic rats. Our grouphas recently designed anddeveloped a high-resolutionmicro-CT imaging system toevaluate the microarchitectureof bone ex vivoin specimens and in vivo insmall animal models.Working closely with basic and clinicalscientists, we are developing novel highresolutionimaging and post-processingtechniques that will aid in evaluating early bone lossand bone formation in small-animal models ofosteoporosis and in monitoring the effects ofvarious treatments longitudinally. We propose todevelop: 1) high-resolution 3D fluorescencemicroscopy and micro-CT imaging techniques foranalyzing in vivo and excised bone over largeregions of interest; 2) intra- and multimodalityregistration technique for spatially aligninglongitudinal micro-CT images and 3D colorhistology images of trabecular bone; 3) real-timevisualization and graphic manipulation tools forsimultaneously displaying 3D color-histology and4D micro-CT images;and 4) novel measuresto identify early boneloss/formation fromdirect measurement oflongitudinal micro-CTimages of bonetrabecula. Theseimaging tools willallow bone researchersto visualize two ormore spatially aligned3D micro-CT imagesets as well as the 3Dcolor histology withthe micro-CT imagessimultaneously. Mostimportantly, it willprovide a mechanismfor interactivelyreviewing, localizing,and quantifyinginformation obtainedfrom different imagingmodalities at differentspatial resolutions.Kimerly A. Powell, Ph.D.THE POWELLLABORATORYRESEARCH ENGINEERLarry Latson, M.S.COLLABORATORSSuneel S. Apte, Ph.D. 1Bradley Clymer, Ph.D .2Ronald J. Midura, Ph.D. 1George F. Muschler, M.D. 1Don Stredney 31Dept. of BiomedicalEngineering, CCF2Dept. of Electrical Engineering,Ohio State University,Columbus, OH3The Ohio SupercomputerCenter, Columbus, OHLatson, L., Powell, K.A., Sturm, B., Schvartzman, P.R., and R. D. White (2001) <strong>Clinic</strong>al validation of anautomated boundary tracking algorithm on cardiac MR images. Int. J. Cardiac Imaging 17:279-286.Obuchowski, N.A., Graham, R.J., Baker, M.E, and K.A. Powell (2001) Ten criteria for effective screening:their application to multislice CT screening for pulmonary and colorectal cancers. AJR Am. J. Roentgenol.176:1357-1362.Sivaramakrishna, R., Obuchowski, N.A., Chilcote, W.A., and K.A. Powell (2001) Automatic segmentationof mammographic density. Acad. Radiol. 8:250-256.Sturm, B., Powell, K., Stillman, A.E., and R.D. White (2002) Registration of 3D CT angiography MRimages in coronary artery disease patients, Int. J. Cardiovasc. Imaging, accepted.Muschler, G.F., Nitto, H., Matsukura, Y., Boehm, C., Valdevit, A., Kambic, H., Davros, W., Powell, K., andK. Easley (<strong>2003</strong>) Spine fusion using cell matrix composites enriched in bone marrow-derived cells. Clin.Orthop. (407):102-118.29

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