ࡱ>  }AC#` ؖbjbj\.\. o>D>D%A } | & $ $$$P<%%t _fhx&$*$*$*L*,-<- eeeeeee$gh/j e]f N5,@,`5 l5e $*L*gfEEEt5< R$*(f L*`EN5eEE6LLD "f ML*l& h;R$?,MH_/f0_fHM@;k|AP;k8M;k M./:E 12G...eeC..._fN5N5N5N5 ! !  A Prototype Biosensor-Integrated Image-Guided Surgery System Luke A. Reisner1, Brady W. King1, Michael D. Klein2, Gregory W. Auner1, Abhilash K. Pandya1 1 Department of Electrical and Computer Engineering, Wayne State University, Detroit, MI, USA 2 Department of Pediatric Surgery, Childrens Hospital of Michigan, Detroit, MI, USA Correspondence to: Abhilash K. Pandya, 5050 Anthony Wayne Dr. #3160, Detroit, MI 48202, USA E-mail: HYPERLINK "mailto:apandya@ece.eng.wayne.edu"apandya@ece.eng.wayne.edu Abstract Background: In this paper, we investigate the integration of a Raman spectroscopy-based biosensor with an image-guided surgery system. Such a system would provide a surgeon both a diagnosis of tissue being analyzed (e.g. cancer) and localization information displayed within an imaging modality of choice. This type of mutual and registered information could lead to faster diagnoses and enable more accurate tissue resections. Methods: A test bed consisting of a portable Raman probe attached to a passively articulated mechanical arm was used to scan and classify objects within a phantom skull. Results: The prototype system was successfully able to track the Raman probe, classify objects within the phantom skull, and display the classifications on medical imaging data within a virtual reality environment. Conclusion: We discuss the implementation of the integrated system, its accuracy, and improvements to the system that will enhance its usefulness and further the field of sensor-based computer-assisted surgery. Keywords: Sensor integration, image-guided surgery, Raman spectroscopy, cancer diagnosis, medical robotics Introduction Current techniques in image-guided surgery (IGS) rely primarily on visual feedback from the surgical site. In this paper, we address the issue of extending this feedback by adding a sensing modality, Raman spectroscopy, to the already successful techniques of image guidance. It is hypothesized that other modalities of information from the surgical/tumor site based on these non-visual (biochemical) aspects will enhance the surgeons ability to more completely define resection margins. The integration of image-guided surgery with advanced sensor technology has been discussed as having great significance for the future of medical procedures. For example, the necessity for diagnostic-based image-guided systems was clearly stated as one of the major goals by a 2002 NIH workshop report on image-guided interventions  ADDIN EN.CITE NIH/NSF2002525210NIH/NSFJohn W. HallerLaurence ClarkeBruce HamiltonFinal ReportWorkshop on Image-Guided Interventions2002September 12-13Bethesda, MDhttp://imaging.cancer.gov/reportsandpublications/NIH-NSF-Workshop-on-Image-Guided-Interventions2002(1): There is a critical need to improve sampling techniques for verification of the disease status of an organ system or lesion (for example, to permit correlation of molecular signatures using tissue array analysis with in vivo molecular or other imaging/spectroscopy signatures). We believe that the work discussed in this paper represents first steps in accomplishing these goals. Conventional histopathology lacks both the capability for providing immediate feedback and the precision to quantify the extent of disease, particularly in the early stages. Final results usually require 1224 hours. Even the examination of the more immediate frozen sections requires at least 20 minutes from the time the tissue is removed until the time an answer is available. During tumor-removal surgeries (e.g. for brain cancer), this means the patient must remain open for a longer operative time. Raman spectroscopy is a technique capable of detecting normal and abnormal regions of tissue  ADDIN EN.CITE Mahadevan-Jansen19972210Anita Mahadevan-JansenRebecca Richards-KortumRaman Spectroscopy For Cancer Detection: A Review19th International Conference of IEEE/EMBS2722-27281997Oct. 30-Nov. 2Chicago, IL(2). Its near-real-time analysis and the fact that it does not require sample preparation make it highly suited for in vivo applications  ADDIN EN.CITE Molckovsky2003121217Molckovsky, A.Song, L. M.Shim, M. G.Marcon, N. E.Wilson, B. C.Department of Medical Biophysics, Ontario Cancer Institute/University Health Network, University of Toronto, Toronto, Ontario, Canada.Diagnostic potential of near-infrared Raman spectroscopy in the colon: differentiating adenomatous from hyperplastic polypsGastrointestinal EndoscopyGastrointestinal Endoscopy396-402573Adenomatous Polyps/*diagnosisAlgorithmsColon/pathologyColonic Polyps/*diagnosisDiagnosis, DifferentialDiscriminant AnalysisHumansHyperplasia/diagnosisResearch Support, Non-U.S. Gov'tSensitivity and Specificity*Spectroscopy, Near-Infrared*Spectrum Analysis, Raman2003March12612529http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12612529 Haka2006222217Haka, A. S.Volynskaya, Z.Gardecki, J. A.Nazemi, J.Lyons, J.Hicks, D.Fitzmaurice, M.Dasari, R. R.Crowe, J. P.Feld, M. S.George R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts and Cleveland Clinic Foundation, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio.In vivo Margin Assessment during Partial Mastectomy Breast Surgery Using Raman SpectroscopyCancer ResearchCancer Research3317-226662006March 1516540686http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16540686 (3, 4). Image-guided surgery helps the surgeon position and track instruments (such as a Raman probe) inside the body  ADDIN EN.CITE Sauer2005595910Sauer, FrankImage Registration: Enabling Technology for Image Guided Surgery and Therapy27th Annual International Conference of the IEEE Engineering in Medicine and Biology Society7242-72452005September 1-4Shanghai, China0-7803-8741-4(5), making it a natural complement for Raman spectroscopy. Integration of this sensing technology with IGS should help maximize its usefulness for in vivo applications. Thus, this paper investigates the integration of a Raman probe with an image-guided surgery system for the future diagnosis of cancer. Raman Spectroscopy Raman spectroscopy is a near-real-time technique that measures the wavelength and intensity of light inelastically scattered from molecules. In Raman spectroscopy, a specimen is irradiated with a laser light, resulting in the scattering of light due to its interaction with the vibrating molecules in the sample. The majority of scattered light has unchanged frequencies (Rayleigh scattering), whereas the rest is shifted in frequency (Raman scattering) by an amount characteristic of the frequency of the vibrating molecules. These vibrations are a function of molecular conformation, the distribution of electrons in the chemical bonds, and the molecular environment. Disease leads to changes in the molecular composition and morphologic appearance of affected tissues. Since Raman spectroscopy is sensitive enough to detect these molecular changes, it is a logical choice for the diagnosis of cancer  ADDIN EN.CITE Crow20034417Crow, P.Stone, N.Kendall, C. A.Uff, J. S.Farmer, J. A.Barr, H.Wright, M. P.Cranfield Post-Graduate Medical School, Pullman Court, Gloucestershire Royal Hospital, Great Western Road, Gloucester, GL1 3NN, UK. paul_crow@hotmail.comThe use of Raman spectroscopy to identify and grade prostatic adenocarcinoma in vitroBr J CancerBr J Cancer106-8891Adenocarcinoma/classification/*pathology*AlgorithmsBiopsyHumansMaleNeoplasm Staging/*methodsProstatic Neoplasms/classification/*pathologySensitivity and SpecificitySpectrum Analysis, Raman2003Jul 712838309http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12838309 Krafft20035517Krafft, ChristophMiljanic, SnezanaSobottka, Stephan B.Schackert, GabrieleSalzer, ReinerNear-infrared Raman spectroscopy to study the composition of human brain tissue and tumorsProceedings of SPIE-The International Society for Optical EngineeringProceedings of SPIE-The International Society for Optical Engineering230-2365141Diagnostic Optical Spectroscopy in Biomedicine IIProteins Role: DGN (Diagnostic use), BIOL (Biological study), USES (Uses) (Hb-likenear-IR Raman spectroscopy for brain tumor real-time, in vivo, intraoperative diagnosis)BrainBrainDiagnosisHuman (near-IR Raman spectroscopy for brain tumor real-time, in vivo, intraoperative diagnosis)Lipids Role: DGN (Diagnostic use), BIOL (Biological study), USES (Uses) (near-IR Raman spectroscopy for brain tumor real-time, in vivo, intraoperative diagnosis)Raman spectroscopy (near-IRnear-IR Raman spectroscopy for brain tumor real-time, in vivo, intraoperative diagnosis)near IR Raman spectroscopy brain tumor diagnosis2003AN 2003:854145Frank19947717Frank, C. J.Redd, D. C.Gansler, T. S.McCreery, R. L.Department of Chemistry, Ohio State University, Columbus 43210.Characterization of human breast biopsy specimens with near-IR Raman spectroscopyAnal ChemAnal Chem319-26663BiopsyBreast/*chemistryBreast Neoplasms/surgeryCarotenoids/*analysisFemaleFormaldehydeHumansLipids/*analysisMammaplastyMastectomy, Modified RadicalOleic AcidOleic Acids/analysisResearch Support, U.S. Gov't, Non-P.H.S.*Spectrum Analysis, RamanTissue Fixation1994Feb 18135372http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8135372 Stone2002111117Stone, NicholasKendall, CatherineShepherd, NeilCrow, PaulBarr, HughNear-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancersJournal of Raman SpectroscopyJOURNAL OF RAMAN SPECTROSCOPY564-573337Esophagus (Barrett's syndromenear-IR Raman spectroscopy for classification of epithelial pre-cancers and cancers)Diagnosis (cancernear-IR Raman spectroscopy for classification of epithelial pre-cancers and cancers)BladderEsophagusLarynx (carcinomanear-IR Raman spectroscopy for classification of epithelial pre-cancers and cancers)BladderClassificationEsophagusHumanLarynxProstate glandRaman spectroscopyStomachTonsil (near-IR Raman spectroscopy for classification of epithelial pre-cancers and cancers)Raman spectroscopy precancer carcinoma classification2002AN 2002:603304Mahadevan-Jansen1998151517Mahadevan-Jansen, A.Mitchell, M. F.Ramanujam, N.Utzinger, U.Richards-Kortum, R.Biomedical Engineering Program, University of Texas, Austin, USA. anitha@vuse.vanderbilt.eduDevelopment of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivoPhotochem PhotobiolPhotochem Photobiol427-31683BiopsyCalibrationCervix Neoplasms/*diagnosisCervix Uteri/pathology/*physiology/*physiopathologyColposcopyEquipment DesignFemaleFiber OpticsHumansLasersPrecancerous Conditions/*diagnosisReproducibility of ResultsSpectrum Analysis, Raman/*instrumentation/methods1998Sep9747597http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9747597 Gniadecka1997181817Gniadecka, M.Wulf, H. C.Nielsen, O. F.Christensen, D. H.Hercogova, J.Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Denmark.Distinctive molecular abnormalities in benign and malignant skin lesions: studies by Raman spectroscopyPhotochem PhotobiolPhotochem Photobiol418-23664Comparative StudyHumansLipids/chemistryPhotochemistryProtein ConformationResearch Support, Non-U.S. Gov'tSkin Diseases/diagnosis/*metabolismSkin Neoplasms/*chemistry/diagnosisSpectrum Analysis, Raman1997Oct9337612http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9337612 Johansson1999212117Johansson, C. K.Christensen, D. H.Nielsen, O. FaurskovNear-infrared Fourier transform Raman spectral studies of human skinDansk KemiDansk Kemi12-13808Skin (basal cell carcinomanear-IR Fourier transform Raman spectral studies of human skin)Cadaver (mummynear-IR Fourier transform Raman spectral studies of human skin)ArchaeologyDiagnosisSkin (near-IR Fourier transform Raman spectral studies of human skin)Raman spectroscopyRaman spectroscopy (near-IR, Fourier-transformnear-IR Fourier transform Raman spectral studies of human skin)IR spectroscopyIR spectroscopy (near-IR, Raman, Fourier-transformnear-IR Fourier transform Raman spectral studies of human skin)skin cancer diagnosis Raman spectroscopy mummy1999AN 1999:596575Molckovsky2003121217Molckovsky, A.Song, L. M.Shim, M. G.Marcon, N. E.Wilson, B. C.Department of Medical Biophysics, Ontario Cancer Institute/University Health Network, University of Toronto, Toronto, Ontario, Canada.Diagnostic potential of near-infrared Raman spectroscopy in the colon: differentiating adenomatous from hyperplastic polypsGastrointestinal EndoscopyGastrointestinal Endoscopy396-402573Adenomatous Polyps/*diagnosisAlgorithmsColon/pathologyColonic Polyps/*diagnosisDiagnosis, DifferentialDiscriminant AnalysisHumansHyperplasia/diagnosisResearch Support, Non-U.S. Gov'tSensitivity and Specificity*Spectroscopy, Near-Infrared*Spectrum Analysis, Raman2003March12612529http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12612529 Min20053317Young-Kun MinTatsuya YamamotoEhiichi KohdaToshiaki ItoHiro-o Hamaguchi1064 nm near-infrared multichannel Raman spectroscopy of fresh human lung tissuesJournal of Raman SpectroscopyJOURNAL OF RAMAN SPECTROSCOPY7376362005(3, 6-13). This technique is also well-suited for in vivo applications because it is non-destructive and requires no sample preparation or contrast-enhancing agents. These features make it appealing for real-time medical diagnosis. Using recent developments in near-infrared Raman spectroscopy, in vivo real-time cancer diagnosis has been attempted during breast surgery  ADDIN EN.CITE Haka2006222217Haka, A. S.Volynskaya, Z.Gardecki, J. A.Nazemi, J.Lyons, J.Hicks, D.Fitzmaurice, M.Dasari, R. R.Crowe, J. P.Feld, M. S.George R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts and Cleveland Clinic Foundation, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio.In vivo Margin Assessment during Partial Mastectomy Breast Surgery Using Raman SpectroscopyCancer ResearchCancer Research3317-226662006March 1516540686http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16540686 (4). Raman spectroscopy offers many opportunities for the development of sensitive diagnostic tools for rapid identification of pathogenic microorganisms  ADDIN EN.CITE Maquelin2000232317Maquelin, K.Choo-Smith, L. P.van Vreeswijk, T.Endtz, H. P.Smith, B.Bennett, R.Bruining, H. A.Puppels, G. J.Department of General Surgery, Erasmus University, Rotterdam, The Netherlands.Raman spectroscopic method for identification of clinically relevant microorganisms growing on solid culture mediumAnal ChemAnal Chem12-9721Bacteriological TechniquesCulture MediaGram-Positive Bacteria/*classification/*growth & developmentMicroscopy, Confocal/methodsResearch Support, Non-U.S. Gov'tSpectrum Analysis, Raman/*methods2000Jan 110655628http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10655628 (14), assessing tissue specimens including tumor grade types  ADDIN EN.CITE Kalasinsky2005252517Kalasinsky, K. S.Kalasinsky, V. F.Department of Environmental and Infectious Disease Sciences, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.Infrared and Raman microspectroscopy of foreign materials in tissue specimensSpectrochimica Acta A: Mol Biomol SpectroscopySpectrochimica Acta A: Mol Biomol Spectroscopy1707-136172005May15820906http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15820906 Schaeberle1996262617Schaeberle, M. D.Kalasinsky, V. F.Luke, J. L.Lewis, E. N.Levin, I. W.Treado, P. J.Department of Chemistry, University of Pittsburgh, Pennsylvania 15260, USA.Raman chemical imaging: histopathology of inclusions in human breast tissueAnal ChemAnal Chem1829-336811Breast/*pathologyBreast Diseases/*pathologyBreast Implants/*adverse effectsDiagnostic ImagingFemaleHumansResearch Support, Non-U.S. Gov'tSiliconesSpectrum Analysis, Raman1996Jun 18686910http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8686910 (15, 16), performing continuous patient monitoring (e.g. blood analysis), guiding of surgical interventions, and intraoperative tumor border determination. Since the differentiation of tissue is possible, it is predicted that Raman spectroscopy may soon become a valuable tool to assist in clinical pathology  ADDIN EN.CITE Pappas2000272717Pappas, D.Smith, B. W.Winefordner, J. D.Raman spectroscopy in bioanalysisTalantaTalanta131-144511CellDiagnosisNeoplasmRaman spectroscopy (Raman spectroscopy in bioanal.)Analysis (clin.Raman spectroscopy in bioanal.)review Raman spectroscopy bioanalysis2000AN 1999:792789(17). Our team has been researching the potential of Raman spectroscopy for tumor detection  ADDIN EN.CITE Pandya200430305A. PandyaG. AunerM. MenonS. DasRobotic Technology: a Journey into the FutureRobotic Urologic Surgery793-800312004Elsevier, Inc.Thakur2006323217J. S. ThakurH. DaiN. ShuklaG. K. SerhatkuluA. CaoA. PandyaR. NaikV. NaikG. W. AunerC. FreemanR. RabahM. D. Klein Raman spectral signatures of mouse mammary tissue and associated lymph nodes: normal, tumor, and mastitisJournal of Raman SpectroscopyJOURNAL OF RAMAN SPECTROSCOPY(In press)2006Lorincz2004292917A. LorinczD. HaddadR. NaikV. NaikA. FungA. CaoP. MandaA. PandyaG. AunerR. RabahS. LangenburgM. KleinRaman spectroscopy for neoplastic tissue differentiation: a pilot studyJournal of Pediatric SurgeryJournal of Pediatric Surgery953-9563962004(18-20). In 20056, we studied 143 human tissues samples (22 from normal tissues and 121 from tumors) and collected approximately 1700 Raman spectra. This library of Raman data has been analyzed using a variety of statistical techniques, such as principle component analysis and discriminant function analysis, and we are developing learning algorithms based on artificial neural networks and support vector machines to classify the data. Image-Guided Surgery During complex operations, surgeons must maintain a precise sense of three-dimensional anatomical relationships  ADDIN EN.CITE Bucholz2001333317Bucholz, R. D.Smith, K. R.Laycock, K. A.McDurmont, L. L.Bucholz, R. D. St Louis Univ, Sch Med, Bakewell Sect Image Guided Surg, St Louis, MO 63104 USA St Louis Univ, Sch Med, Bakewell Sect Image Guided Surg, St Louis, MO 63104 USA Medtronic Inc, Surg Navigat Technol, Louisville, CO USAThree-dimensional localization: From image-guided surgery to information-guided therapyMethodsMethodsMethodsMethodsMethodsMethods186-2002522001OctISI:000173696900005<Go to ISI>://000173696900005(21). In addition, they must use their judgment, experience, and pathological evaluation (biopsy) to determine resection boundaries. Image-guided surgery fuses medical imaging, computer visualization, and real-time tracking of medical tools to provide the surgeon with a more detailed view of the patients anatomy. In addition, image-guided surgery has allowed the development of minimally invasive surgical systems, which can greatly reduce cost, surgeon strain, and patient recovery time. There are two different types of visualization technology that we are researching for the medical domain: augmented reality (AR) and virtual reality (VR)  ADDIN EN.CITE Gong2001373710Gong, J.Zamorano, L.Li, Q.Pandya, A.K.Diaz, F.Development of Universal Instrumentation for Advanced Neuronavigation SystemCongress of Neurological Surgeons2001Sept. 29 - Oct. 4San Diego, CAPandya2003353510A. PandyaM. SiadatG. Auner (Invited Speaker)Augmented Reality vs. Neuronavigation: a Comparison of Surgeon PerformanceBiomedical Engineering Symposium 20032003Wayne State UniversityPandya2005616117Pandya, A.Siadat, M. R.Auner, G.Design, implementation and accuracy of a prototype for medical augmented realityComputer Aided SurgeryComputer Aided Surgery23-351012005(22-24). Image guidance is an example of VR. Surgeons can now "see" on a 3D image where their tracked surgical tools are with respect to the lesion responsible for the patient's problems. This technology is now starting to be used in several branches of surgery, such as neurosurgery, spinal surgeries  ADDIN EN.CITE Holly2003383817Holly, L. T.Foley, K. T.Foley, K. T. Univ Tennessee, Image Guided Surg Res Ctr, Methodist Hosp Memphis, Semmes Murphey Clin,Dept Neurosurg, 1211 Union Ave,Suite 200, Memphis, TN 38104 USA Univ Tennessee, Image Guided Surg Res Ctr, Methodist Hosp Memphis, Semmes Murphey Clin,Dept Neurosurg, Memphis, TN 38104 USA Univ Calif Los Angeles, Med Ctr, Div Neurosurg, Los Angeles, CA 90024 USAIntraoperative spinal navigationSpineSpineSpineSpineSpineSpineS54-S6128152003AUG 1ISI:000184712500010<Go to ISI>://000184712500010(25), orthopedic surgery  ADDIN EN.CITE DiGioia1998393917DiGioia, A. M.DiGioia, A. M. Shadyside Hosp, Pittsburgh, PA 15232 USA Shadyside Hosp, Pittsburgh, PA 15232 USAComputer assisted orthopaedic surgery: Medical robotics and image guided surgery - CommentClinical Orthopaedics and Related ResearchClin Orthop Relat RClinical Orthopaedics and Related ResearchClin Orthop Relat RClinical Orthopaedics and Related ResearchClin Orthop Relat R2-43541998SEPISI:000075898000001<Go to ISI>://000075898000001(26), dental surgery, and even some examples of general surgery  ADDIN EN.CITE Cash2003404017Cash, D. M.Sinha, T. K.Chapman, W. C.Terawaki, H.Dawant, B. M.Galloway, R. L.Miga, M. I.Cash, D. M. Vanderbilt Univ, Dept Biomed Engn, Box 351631,Stn B, Nashville, TN 37235 USA Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA Washington Univ, Sch Med, Dept Surg & Cell Biol, Sect Transplantat, St Louis, MO 63110 USA Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA Vanderbilt Univ, Dept Elect Engn & Comp Sci, Nashville, TN 37235 USAIncorporation of a laser range scanner into image-guided liver surgery: Surface acquisition, registration, and trackingMedical PhysicsMed PhysMedical PhysicsMed PhysMedical PhysicsMed Phys1671-16823072003JULISI:000184209200014<Go to ISI>://000184209200014(27). An AR system generates a composite view for the user that includes the live view fused (registered) with either pre-computed data (e.g. 3D geometry) or other registered sensed data  ADDIN EN.CITE Pandya2002414125A. PandyaL. ZamoranoAugmented Tracking Using Video, Computer Data and/or Sensing Technologies200301793082002USAWayne State Universityapplication 20030179308(28). AR is an extension of VR that represents a middle ground between computer graphics in a completely synthetically-generated world (as in VR) and the real world  ADDIN EN.CITE Pandya2003434310Pandya, A.K.Siadat, M.Ye, Z.Prasad, M.Auner, G.Zamorano, L.Klein, M.Medical Robot Vision AugmentationA PrototypeMedicine Meets Virtual Reality852003Newport Beach, CaliforniaAligned Management Associates, IncPandya2001444410Pandya, A.K.Siadat, M.Zamorano, L.Gong, J.Li, Q.Maida, J.C.Kakadiaris, I.Augmented Robotics for NeurosurgeryAmerican Association of Neurological Surgeons2001April 21-26Toronto, OntarioPandya2001454510Pandya, A.K.Zamorano, L.Siadat, M.Li, Q.Gong, J.Maida, J.C.Augmented Robotics for Medical and Space ApplicationsHuman Systems2001June 19NASA Johnson Space Center, Houston, TX(29-31). Recently, we have developed a system that simultaneously allows the surgeon to have both an AR and VR view of the patients data  ADDIN EN.CITE Pandya2005474710Abhilash PandyaGregory AunerSimultaneous Augmented and Virtual Reality for Surgical NavigationNorth American Fuzzy Information Processing Society Annual Conference429-4352005June 22-25Ann Arbor, Michigan(32). Merging visualization technology with sensor technology will enable surgeons to accurately locate and classify tissues within the body. Hence, we believe the next step is to integrate visualization with sensor technology, specifically a Raman probe. Technology that integrates imaging and sensor information in real-time will add new dimensions to what can be done to diagnose and treat patients  ADDIN EN.CITE Samset2003484817Samset, E.Hirschberg, H.Samset, E. Natl Hosp Norway, Intervent Ctr, N-0027 Oslo, Norway Univ Oslo, Natl Hosp Norway, Intervent Ctr, Oslo, Norway Univ Oslo, Natl Hosp Norway, Dept Neurosurg, Oslo, NorwayImage-guided stereotaxy in the interventional MRIMinimally Invasive NeurosurgeryMinim Invas NeurosurMinimally Invasive NeurosurgeryMinim Invas NeurosurMinimally Invasive NeurosurgeryMinim Invas Neurosur5-104612003FEBISI:000181855100002<Go to ISI>://000181855100002Nakao2003494917Nakao, N.Nakai, K.Itakura, T.Nakao, N. Wakayama Med Univ, Dept Neurol Surg, 811-1 Kimiidera, Wakayama 6410012, Japan Wakayama Med Univ, Dept Neurol Surg, Wakayama 6410012, JapanUpdating of neuronavigation based on images intraoperatively acquired with a mobile computerized tomographic scanner: Technical noteMinimally Invasive NeurosurgeryMinim Invas NeurosurMinimally Invasive NeurosurgeryMinim Invas NeurosurMinimally Invasive NeurosurgeryMinim Invas Neurosur117-1204622003AprISI:000183246500012<Go to ISI>://000183246500012(33, 34). Materials and Methods The goal of this work is to create a system to detect cancerous tissue in the human body. However, since this paper focuses on the integration and visualization of Raman spectroscopy with image-guided surgery, we can use a phantom model instead of actual tissue. Once the work is more developed, we can test it on animal and human models. We know from other literature and our own research that Raman spectroscopy is capable of detecting cancerous tissue quickly and accurately  ADDIN EN.CITE Lorincz2004292917A. LorinczD. HaddadR. NaikV. NaikA. FungA. CaoP. MandaA. PandyaG. AunerR. RabahS. LangenburgM. KleinRaman spectroscopy for neoplastic tissue differentiation: a pilot studyJournal of Pediatric SurgeryJournal of Pediatric Surgery953-9563962004Thakur2006323217J. S. ThakurH. DaiN. ShuklaG. K. SerhatkuluA. CaoA. PandyaR. NaikV. NaikG. W. AunerC. FreemanR. RabahM. D. Klein Raman spectral signatures of mouse mammary tissue and associated lymph nodes: normal, tumor, and mastitisJournal of Raman SpectroscopyJOURNAL OF RAMAN SPECTROSCOPY(In press)2006Haka2006222217Haka, A. S.Volynskaya, Z.Gardecki, J. A.Nazemi, J.Lyons, J.Hicks, D.Fitzmaurice, M.Dasari, R. R.Crowe, J. P.Feld, M. S.George R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts and Cleveland Clinic Foundation, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio.In vivo Margin Assessment during Partial Mastectomy Breast Surgery Using Raman SpectroscopyCancer ResearchCancer Research3317-226662006March 1516540686http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16540686 Mahadevan-Jansen19972210Anita Mahadevan-JansenRebecca Richards-KortumRaman Spectroscopy For Cancer Detection: A Review19th International Conference of IEEE/EMBS2722-27281997Oct. 30-Nov. 2Chicago, ILStone2002111117Stone, NicholasKendall, CatherineShepherd, NeilCrow, PaulBarr, HughNear-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancersJournal of Raman SpectroscopyJOURNAL OF RAMAN SPECTROSCOPY564-573337Esophagus (Barrett's syndromenear-IR Raman spectroscopy for classification of epithelial pre-cancers and cancers)Diagnosis (cancernear-IR Raman spectroscopy for classification of epithelial pre-cancers and cancers)BladderEsophagusLarynx (carcinomanear-IR Raman spectroscopy for classification of epithelial pre-cancers and cancers)BladderClassificationEsophagusHumanLarynxProstate glandRaman spectroscopyStomachTonsil (near-IR Raman spectroscopy for classification of epithelial pre-cancers and cancers)Raman spectroscopy precancer carcinoma classification2002AN 2002:603304(2, 4, 9, 19, 20). Therefore, this work has the potential to extend to real tissue. Thus, in order to evaluate the integration of Raman spectroscopy and image-guided surgery, we developed a system utilizing several components (see  REF _Ref144902566 \h Figure 1). A portable Raman spectrometer was attached to a passively articulated mechanical arm. We also implemented classification algorithms for Raman spectra. The results of the classification are sent to a medical visualization system. Once these systems were integrated together, testing was done with a phantom skull (shown in  REF _Ref143007974 \h Figure 2). The skull was filled with various plastic and rubber objects, and CT images were obtained. The entire system was then used to scan objects in the skull, classify the resulting spectral data, and then place markers within our visualization system. Each of the subsystems is described in greater detail below. Tracking Arm To track the position of a Raman spectrometer, we attached one to a passively articulated arm, a MicroScribe G2X (Immersion, San Jose, CA), as shown in  REF _Ref143007974 \h Figure 2. This arm has five degrees of freedom and, based on our previous research  ADDIN EN.CITE Pandya2005616117Pandya, A.Siadat, M. R.Auner, G.Design, implementation and accuracy of a prototype for medical augmented realityComputer Aided SurgeryComputer Aided Surgery23-351012005(24), provides joint feedback with an accuracy of 0.87 mm. It was chosen because it is simple to use and its tracking accuracy is within acceptable limits.  Figure  SEQ Figure \* ARABIC 2: The Raman probe, attached to the end of the tracking arm, is used to scan a plastic cup and other objects within the phantom skull We developed a software application that registers the MicroScribe with patient imaging data and tracks the location of its end-effector. The tracking is accomplished by passing the arms angular joint feedback through a forward kinematics model of the MicroScribe. The tracking data is relayed in real-time to our visualization system. In the following section, the technical details of our tracking software are presented. Tracking Algorithms Our forward kinematics model of the MicroScribe is expressed in Craigs modified DenavitHartenberg (DH) notation  ADDIN EN.CITE Craig198960606Craig, J. J.Introduction to Robotics: Mechanics and Control2nd1989Addison-Wesley Longman Publishing Co., Inc. Boston, MA, USA(35). DH notation provides a compact way to represent the structure of a robot (including link lengths, joint types, and joint angles). The DH parameters of the MicroScribe are shown in  REF _Ref143529452 \h Table 1. Homogeneous transformation matrices are efficient mathematical structures that can be used to translate between different frames of reference  ADDIN EN.CITE Craig198960606Craig, J. J.Introduction to Robotics: Mechanics and Control2nd1989Addison-Wesley Longman Publishing Co., Inc. Boston, MA, USA(35). Our tracking system uses these matrices to establish the spatial relationships among the MicroScribe arm, Raman probe, patient (phantom skull), and patient imaging (CT scan data). This enables us to track the location of the MicroScribe with respect to the phantom skull and overlay this information on the CT scan data in our visualization system. In order to track the MicroScribes end-effector relative to the skull, we execute a pair-point-matching algorithm between seven common fiducials on the phantom skull and its CT scan data. The algorithm uses an iterative LevenbergMarquardt optimization method to establish a homogeneous transformation from the skull (S) to the base of the MicroScribe (B), TS, B. The next step in tracking the MicroScribe is to determine the location of its end-effector (EE) relative to its base. This is done by multiplying a series of transformation matrices that represent the position and orientation of each of the MicroScribes joints (Ji) relative to the previous joint (Ji-1):  EMBED Equation.3  Equation  SEQ Equation \* ARABIC 1 Each transformation matrix is generated via the following formula, which uses the joint angles (i) and other DH parameters given in the rows of  REF _Ref143529452 \h Table 1:  EMBED Equation.3  Equation  SEQ Equation \* ARABIC 2 Finally, we can combine the transformation from the skull to the base with the transformation from the base to the end-effector to produce the desired transformation from the skull to the end-effector:  EMBED Equation.3  Equation  SEQ Equation \* ARABIC 3 This transformation from the phantom skull to the end-effector allows our visualization system to display the location of the MicroScribes tip relative to the 3D CT imaging of the skull. To track the Raman probe, which is attached to the MicroScribe, the kinematic model for the MicroScribe was extended by adding an extra transformation from the end-effector to the tip of the Raman probe (RP):  EMBED Equation.3  Equation  SEQ Equation \* ARABIC 4 Combining  REF _Ref145238749 \h Equation 3 and  REF _Ref145238760 \h Equation 4 allows the computation of the transformation from the skull to the tip of Raman probe:  EMBED Equation.3  Equation  SEQ Equation \* ARABIC 5 This transformation allows the probe to be tracked in our visualization system relative to the skulls CT scan data. Table  SEQ Table \* ARABIC 1: Denavit Hartenberg parameters for the MicroScribe G2X mechanical arm. The non-zero (i) terms represent variable joint angles. iai-1 (mm)di (mm)i-1 (rad)i (rad)10210.820(1)224.18 22.530.4999(2)3260.68 0.30 0.0002(3)413.89234.700.4972(4)5 10.268.10 0.5007(5)610.16 134.16 0.49940Raman Spectrometer The portable Raman spectrometer we use is a Verax (InPhotonics, Norwood, MA). It is shown in  REF _Ref143022119 \h Figure 3. This device uses a fiber optic probe and a 785 nm, 300 mW laser beam to obtain Raman spectra with an accuracy up to 4 cm1. The end of the probe is a long tube, 1 cm in diameter, thus making it suitable for a test bed for minimally invasive surgery. In addition, the probe can be sterilized via an autoclave. The Raman probe (shown in  REF _Ref143007974 \h Figure 2) was affixed to the MicroScribe using a simple clamping system. The end-effector of the MicroScribe was marked to ensure consistent placement, allowing the probe to be detached and reattached.  Figure  SEQ Figure \* ARABIC 3: The Verax portable Raman spectrometer with an attached fiber optic probe Raman Classification Many techniques have been developed for the classification of Raman spectra. For our implementation, we used a method based on artificial neural networks, which have been shown to perform well for Raman classification  ADDIN EN.CITE Gniadecka2004545417Gniadecka, M.Philipsen, P. A.Sigurdsson, S.Wessel, S.Nielsen, O. F.Christensen, D. H.Hercogova, J.Rossen, K.Thomsen, H. K.Gniadecki, R.Melanoma Diagnosis by Raman Spectroscopy and Neural Networks: Structure Alterations in Proteins and Lipids in Intact Cancer TissueJournal of Investigative DermatologyJournal of Investigative Dermatology443-4491222004de Paula Jr2005555517de Paula Jr, A. R.Sathaiah, S.Raman spectroscopy for diagnosis of atherosclerosis: a rapid analysis using neural networksMed Eng PhysMed Eng Phys237-442732005Sigurdsson2004565617Sigurdsson, S.Philipsen, P. A.Hansen, L. K.Larsen, J.Gniadecka, M.Wulf, H. C.Detection of skin cancer by classification of Raman spectraIEEE Transactions on Biomedical EngineeringIEEE Transactions on Biomedical Engineering1784-179351102004(36-38). A variety of preprocessing tasks are performed on the raw Raman spectral data, including background fluorescence subtraction (via adaptive polynomial fitting), median noise filtering, normalization, and peak extraction. Due to the high dimensionality of Raman spectra, we used principle component analysis to select the most significant spectral peaks for algorithm consideration. Our neural network is a two-layer feedforward perceptron network. There is one input for each spectral peak extracted during the preprocessing phase and one output for each possible class (e.g. plastic vs. rubber or healthy vs. cancerous tissue). The hidden layer uses hyperbolic tangent activation functions, and the output layer has logistic sigmoid activation functions. For this application, the network used 10 hidden neurons and was trained via backpropagation. The final output was the classification of the scanned tissue/material and a percentage indicating the confidence of the neural network. Visualization The visualization for our image-guided surgery system is implemented using 3D Slicer ( HYPERLINK "http://www.slicer.org/" www.slicer.org), an open-source application for displaying medical data. 3D Slicer provides a virtual reality environment in which various imaging modalities (e.g. CT or MRI data) can be presented. The software includes the ability to display the locations of objects with respect to 3D models that are derived from segmentation of the medical imaging. We modified 3D Slicer in several ways to adapt it to our application. First, we developed a TCP/IP interface that receives the tracking data for the MicroScribe and displays its position in the VR environment relative to the medical imaging data. This allows us to track the Raman probe in real-time. Second, we developed a way to place colored markers that indicate tissue/material classification on the medical imaging data. The combination of these modifications enables us to denote the location and classification of tissue/material scanned with the probe in near-real-time. Results As described in the Materials and Methods section, we used the completed system to scan objects within a phantom skull. The MicroScribe and probe were positioned manually and tracked in real-time during this test. The collected Raman spectra were classified and displayed as colored markers in our visualization system. This is shown in  REF _Ref143012389 \h Figure 4. The system performed as expected. The tracking of the probe, the classification of the Raman spectra, and the display of the colored markers all occurred in real-time. The only major delay was caused by the scanning of the tissue by the Raman probe, which requires roughly 5 seconds to produce a scan with a reasonable signal-to-noise ratio. The Raman scans were able to distinguish between the plastic and the rubber objects. The corresponding markers in the visualization display correctly reflected the classifications that were made. The positions of the markers were also accurate with respect to the locations from which scans were taken. Since the setup of the system is very similar to that of our previous work  ADDIN EN.CITE Pandya2005616117Pandya, A.Siadat, M. R.Auner, G.Design, implementation and accuracy of a prototype for medical augmented realityComputer Aided SurgeryComputer Aided Surgery23-351012005(24), we estimate that the probe tracking accuracy is around 1 mm. Discussion In a paper discussing the future of computer-assisted and robotic surgery  ADDIN EN.CITE Taylor2003505017Russell H. TaylorDan StoianoviciMedical Robotics in Computer-Integrated SurgeryIEEE Trans on Robotics and AutomationIEEE Trans on Robotics and Automation765-7821952003October(39), Taylor and Stoianovici stated that it will become increasingly important to design systems that can incorporate a wide range of biomedical sensors and that can work with multiple imaging modalities. We provide an example of this goal with the successful integration of Raman spectroscopy with an image-guided surgery system, demonstrated using a phantom skull. Our system, which tracks an image-registered Raman probe, is developed in a manner that allows the results of neural network-classified Raman data to be displayed directly on any imaging modality of the phantoms anatomy, all in near real-time. This paper demonstrates that Raman spectroscopy and image-guided surgery can be combined to provide a powerful diagnostic system. Even though we have used a phantom model, the underlying technologies have been previously shown to work with human tissue. With further research, we believe this system will be suitable for human applications. For now, we will continue to develop and test the system using phantom models. In the future, we plan to evaluate the system with animal testing. Eventually, we hope to apply our work to human cases. If the results continue to be positive, we believe that Raman spectroscopy has the potential to be a powerful complement to conventional histopathology. To our knowledge, there have been no other prototypes in the literature that attempt to combine Raman spectroscopy and image-guided surgery. We conjecture that a system based on these technologies could eventually provide many benefits in the surgical environment. These benefits could include faster diagnoses and more accurate resections, hence producing better patient outcomes. However, there are certain issues that need detailed research and development. One key issue is the size of the Raman probe. Ideally, the entire instrument should be about the size of a scalpel for easy manipulation by the surgeon. Existing portable systems are still too bulky as real-time diagnostic tools for certain applications. The availability of miniaturized hand-held devices would create a platform for a wider range of research on real-time tissue diagnostics. Once developed, this technology will enable the creation of a whole new field of real-time, in vivo spectroscopic diagnostics of tissue. Another relevant issue is the positional accuracy of the image-guided Raman system. Although the tip of our Raman probe can be tracked to within an acceptable accuracy for neurosurgery, there is an uncertainty of about 5 mm (the diameter of the probes transmission window) as to exactly where the human-held probe actually measures the point of interest. A system in which the actual point of interest could be better determined and more accurately placed would be much more useful. The issues of placement accuracy and the requirement of holding the sensor still during acquisition can be alleviated by the closely related field of medical robotics. A robot can accurately place and steadily hold a probe in the surgical environment. Thus, we plan to expand the work described in this paper to include the Aesop 3000 medical robot (Intuitive Surgical, Sunnyvale, CA). This robot will be used to actively position the Raman probe instead of the passive MicroScribe arm. This will provide several benefits over the current system. First, the Aesop will be able to hold the probe completely steady during a scan, which is important considering scans can take 5 or more seconds. Second, the Aesop will be able to position the probe more accurately using medical imaging data, enabling the surgeon to precisely scan the tissue of interest. Third, automated scanning will be possible, in which the Aesop moves among numerous points over a defined area of tissue, taking a Raman scan at each. Our work with the Aesop 3000 will include a detailed human (surgeon) factors study. Tests will be performed to ensure that the system is beneficial to surgeons. For example, we will verify that the speed and accuracy of tissue diagnoses are improved through the use of the system, and several visualization techniques will be implemented and compared to find the best one. We believe that such testing is necessary during research and development to ensure that the results are a useful addition to the field. Acknowledgements This work was supported in part by the Endowment for Surgical Research (ENSURE) at the Childrens Research Center of Michigan. The authors would also like to thank Alex Cao and Rachel Weber for their help with Raman spectra processing and Dr. Gulay Serhatkulu for her assistance in collecting Raman spectra. 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