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IMAGING IN DERMATOLOGY Edited by M R. H ICHAEL AMBLIN P A INAR VCI G K. G AURAV UPTA AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON NEWYORK(cid:129)OXFORD(cid:129)PARIS(cid:129)SANDIEGO SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO AcademicPressisanimprintofElsevier AcademicPressisanimprintofElsevier 125LondonWall,LondonEC2Y5AS,UnitedKingdom 525BStreet,Suite1800,SanDiego,CA92101-4495,UnitedStates 50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom Copyright©2016ElsevierInc.Allrightsreserved. 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Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluatingandusingany information,methods,compounds,orexperimentsdescribedherein.Inusingsuchinformationormethodstheyshouldbe mindfuloftheirownsafetyandthesafetyofothers,includingpartiesforwhomtheyhaveaprofessionalresponsibility. Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assumeanyliabilityforany injuryand/ordamagetopersonsorpropertyasamatterofproductsliability,negligenceorotherwise,orfromanyuseor operationofanymethods,products,instructions,orideascontainedinthematerialherein. LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary ISBN:978-0-12-802838-4 ForinformationonallAcademicPresspublications visitourwebsiteathttps://www.elsevier.com/ Publisher:MicaHaley EditorialProjectManager:LisaEppich ProductionProjectManager:EdwardTaylor Designer:MarkRogers TypesetbyTNQBooksandJournals Dedication To the love of my life, my beautiful wife Angela, to whom I have been devoted for 36years. Michael R. Hamblin To Ari, Afsin, Atul, Thao, Thomo, Theo, Yair and Zehra whose advice, encouragement and support have been genuine and precious. Pinar Avci To my parents, Dr. Ram P Gupta and Sudha Gupta, and my best friend and loving wife, Dr. Tanupriya Agrawal. Gaurav K. Gupta List of Contributors J.Aguirre InstituteofBiological andMedical Imaging, D.L.Farkas SpectralMolecular ImagingInc.,BeverlyHills, HelmholtzZentrumMu¨nchen,Neuherberg,Germany CA,UnitedStates;UniversityofSouthernCalifornia,Los I.Alarcon RamonyCajalHospital, Madrid,Spain Angeles,CA,UnitedStates A.Alavi Hospitalofthe UniversityofPennsylvania, X.Feng University ofMassachusetts, Lowell,MA,United States Philadelphia,PA,UnitedStates Z.Apalla AristotleUniversity,Thessaloniki,Greece S.Gardini ArcispedaleSantaMariaNuova-IRCCS,Reggio Emilia,Italy G.Argenziano SecondUniversity ofNaples,Naples,Italy S.Gholami HospitaloftheUniversityofPennsylvania, P.Avci HarvardMedicalSchool&MassachusettsGeneral Philadelphia,PA,UnitedStates Hospital,Boston,MA,UnitedStates K.E.Go¨bel UniversityMedicalCenterFreiburg,Freiburgim V.Beylergil MetrohealthCampusofCaseWestern Breisgau,Germany;UniversityofFreiburg,Freiburgim University,Cleveland,OH,UnitedStates Breisgau,Germany M.Bonmarin ZurichUniversityofAppliedSciences, V.Goh Guy’sandStThomas’NHSFoundationTrust, Winterthur,Switzerland London,UnitedKingdom;King’sCollegeLondon,London, A.C.Bourgeois TheUniversityofTennesseeGraduate UnitedKingdom SchoolofMedicine, Knoxville,TN,UnitedStates S.Gonza´lez RamonyCajalHospital, Madrid,Spain; Y.C.Bradley TheUniversityofTennesseeGraduateSchool UniversidaddeAlcala´,Madrid,Spain;InstitutoRamo´ny ofMedicine, Knoxville,TN,UnitedStates CajaldeInvestigacio´nSanitaria(IRYCIS),Madrid,Spain; S.A.Burkes UniversityofCincinnati,Cincinnati, OH, MemorialSloan-KetteringCancerCenter,NewYork,NY, UnitedStates UnitedStates C.H.Camp,Jr. NationalInstituteofStandardsand N.Griffin Guy’sandStThomas’NHS FoundationTrust, Technology,Gaithersburg,MD,UnitedStates London,UnitedKingdom S.Campos HospitaldeSantoAnto´niodosCapuchos,Centro G.Guan UniversityofDundee,Dundee,Scotland,United HospitalardeLisboaCentral,Lisboa,Portugal Kingdom;UniversityofWashington,Seattle,WA,United States G.C.Casazza UniversityofUtahSchoolofMedicine, Salt LakeCity,Utah,UnitedStates G.K.Gupta HarvardMedicalSchool&Massachusetts GeneralHospital,Boston,MA,UnitedStates F.Castagnetti ArcispedaleSantaMariaNuova-IRCCS, ReggioEmilia, Italy M.R.Hamblin HarvardMedicalSchool&Massachusetts GeneralHospital,Boston,MA,UnitedStates G.Charles-Edwards Guy’sandStThomas’NHS FoundationTrust,London,UnitedKingdom;King’sCollege J.Hegyi In(cid:1)stitu´t klinickejaexperimenta´lnej London,London,UnitedKingdom dermatovenerolo´gie,Bratislava,Slovakia K.Chen NanyangTechnologicalUniversity,Singapore V.Hegyi In(cid:1)stitu´tklinickej aexperimenta´lnej dermatovenerolo´gie,Bratislava,Slovakia R.Cicchi National InstituteofOptics,NationalResearch Council(INO-CNR),Sesto Fiorentino,Italy;European H.W.HigginsII Brown University,Providence, RI,United LaboratoryforNon-linearSpectroscopy(LENS),Sesto States Fiorentino,Italy D.Ho UniversityofCaliforniaatDavis,Sacramento, CA, A.Doronin UniversityofOtago,Dunedin,NewZealand UnitedStates;SacramentoVAMedicalCenter,Mather,CA, UnitedStates K.P.Eaton UniversityofCincinnati, Cincinnati,OH,United States Z.Huang UniversityofDundee,Dundee,Scotland,United Kingdom B.M.Erovic MedicalUniversity ofVienna,Vienna, Austria D.Ioannides Aristotle University,Thessaloniki, Greece C.L.Evans HarvardMedicalSchool&Massachusetts GeneralHospital,Boston,MA,UnitedStates S.L.Jacques OregonHealth&ScienceUniversityPortland, OR,UnitedStates S.Fardin Hospital oftheUniversity ofPennsylvania, Philadelphia,PA,UnitedStates xiii xiv LISTOFCONTRIBUTORS J.Jagdeo UniversityofCaliforniaatDavis,Sacramento,CA, V.Ntziachristos InstituteofBiologicalandMedicalImaging, UnitedStates;SacramentoVAMedicalCenter,Mather,CA, HelmholtzZentrumMu¨nchen,Neuherberg,Germany UnitedStates;StateUniversityofNewYorkDownstate M.Omar Institute ofBiologicalandMedicalImaging, MedicalCenter,Brooklyn,NY,UnitedStates HelmholtzZentrumMu¨nchen,Neuherberg,Germany N.Jain KayaSkinClinic,Mumbai,India Y.H.Ong NanyangTechnologicalUniversity,Singapore G.B.E.Jemec ZealandUniversityHospital, Roskilde, J.R.Osborne MemorialSloanKetteringCancerCenter,New Denmark York,NY,UnitedStates;Weill-CornellMedicalCollege, L.Kadletz MedicalUniversityofVienna,Vienna,Austria NewYork,NY,UnitedStates D.Kapsokalyvas EuropeanLaboratory forNon-linear AlexandruD.P.Papoiu TherapeuticsInc.,SanDiego, CA, Spectroscopy(LENS),SestoFiorentino,Italy UnitedStates U.Khopkar KayaSkinClinic,Mumbai,India A.S.Pasiak TheUniversityofTennesseeGraduateSchoolof E.Kraeva Sacramento VAMedicalCenter,Mather,CA, Medicine, Knoxville,TN,UnitedStates;TheUniversityof TennesseeMedicalCenter,Knoxville,TN,UnitedStates UnitedStates A.Lallas Aristotle University,Thessaloniki, Greece F.S.Pavone NationalInstitute ofOptics,National Research Council (INO-CNR),SestoFiorentino,Italy;European E.Lazaridou Aristotle University,Thessaloniki, Greece LaboratoryforNon-linearSpectroscopy(LENS),Sesto T.K.Lee BCCancerAgency,Vancouver,BC,Canada; Fiorentino,Italy VancouverCoastalHealthResearchInstituteandUniversity G.Pellacani UniversityofModenaandReggioEmilia, ofBritishColumbia,Vancouver,BC,Canada Modena,Italy F.A.LeGal Geneva UniversityHospital, Geneva, J.A.Perez MemorialSloanKetteringCancerCenter,New Switzerland York,NY,UnitedStates A.Lencastre HospitaldeSantoAnto´niodosCapuchos, B.Peters UniversityHospitalAntwerp,Edegem,Belgium; CentroHospitalardeLisboaCentral,Lisboa,Portugal AZSint-Maarten,Mechelen-Duffel,Belgium R.M.Levenson UCDavisMedicalCenter,Sacramento,CA, B.W.Petersen BrownUniversity,Providence, RI,United UnitedStates States C.Li UniversityofDundee,Dundee,Scotland,United S.Piana ArcispedaleSantaMariaNuova-IRCCS,Reggio Kingdom;UniversityofWashington,Seattle,WA,United Emilia,Italy States M.Ragazzi ArcispedaleSantaMariaNuova-IRCCS,Reggio Q.Liu NanyangTechnologicalUniversity,Singapore Emilia,Italy C.Longo Arcispedale SantaMariaNuova-IRCCS,Reggio R.RandallWickett University ofCincinnati, Cincinnati, Emilia,Italy OH,UnitedStates H.Lui UniversityofBritishColumbiaandVancouver A.H.Rook HospitaloftheUniversity ofPennsylvania, CoastalHealth ResearchInstitute, Vancouver,BC,Canada; Philadelphia,PA,UnitedStates BCCancerAgency,Vancouver,BC,Canada C.Rowlands MassachusettsInstitute ofTechnology N.MacKinnon Spectral MolecularImagingInc.,Beverly Hills,CA,United States M.Schwarz Institute ofBiological andMedicalImaging, HelmholtzZentrumMu¨nchen,Neuherberg,Germany A.Mamalis University ofCaliforniaatDavis, Sacramento, A.Sidoroff MedicalUniversityofInnsbruck,Innsbruck, CA,UnitedStates;SacramentoVAMedicalCenter,Mather, Austria CA,UnitedStates I.Markhvida VancouverCoastalHealthResearchInstitute P.T.C.So MassachusettsInstituteofTechnology;Laser andUniversityofBritishColumbia,Vancouver,BC,Canada BiomedicalResearchCenter;Singapore-MITAlliancefor ScienceandTechnology(SMART)Center D.I.McLean UniversityofBritishColumbiaandVancouver L.Tchvialeva VancouverCoastalHealth ResearchInstitute CoastalHealth ResearchInstitute, Vancouver,BC,Canada; andUniversityofBritishColumbia,Vancouver,BC,Canada BCCancerAgency,Vancouver,BC,Canada I.Meglinski UniversityofOtago,Dunedin,NewZealand; L.Themstrup ZealandUniversityHospital, Roskilde, UniversityofOulu,Oulu,Finland Denmark M.M.Monroe UniversityofUtahSchoolofMedicine,Salt J.W.Tunnell UniversityofTexasatAustin,Austin,TX, UnitedStates LakeCity,Utah,UnitedStates A.J.Moy UniversityofTexasatAustin,Austin,TX,United F.M.Vanhoenacker UniversityHospitalAntwerp, Edegem, Belgium;AZSint-Maarten,Mechelen-Duffel,Belgium; States UniversityHospitalGhent,Ghent,Belgium V.A.Neel MassachusettsGeneralHospital, Boston,MA, UnitedStates F.Vasefi SpectralMolecularImagingInc.,BeverlyHills,CA, UnitedStates S.F.Nemec Medical UniversityofVienna,Vienna,Austria xv LISTOFCONTRIBUTORS M.O.Visscher UniversityofCincinnati, Cincinnati,OH, A.N.Yaroslavsky UniversityofMassachusetts,Lowell,MA, UnitedStates UnitedStates;MassachusettsGeneralHospital,Boston,MA, H.Wang HarvardMedicalSchool&MassachusettsGeneral UnitedStates Hospital,Boston,MA,UnitedStates E.Yew Singapore-MITAllianceforScienceandTechnology L.V.Wang Washington University inSt.Louis,St.Louis, (SMART)Center Missouri,UnitedStates C.Yuen NanyangTechnologicalUniversity,Singapore R.Wang UniversityofWashington,Seattle,WA,United H.Zeng UniversityofBritishColumbiaandVancouver States CoastalHealth ResearchInstitute, Vancouver,BC,Canada; T.J.Werner HospitaloftheUniversity ofPennsylvania, BCCancerAgency,Vancouver,BC,Canada Philadelphia,PA,UnitedStates J.Zhao UniversityofBritishColumbiaandVancouver O.Westerland Guy’sandStThomas’NHSFoundation CoastalHealth ResearchInstitute, Vancouver,BC,Canada; BCCancerAgency,Vancouver,BC,Canada Trust,London,UnitedKingdom X.Wortsman UniversityofChile,Santiago,Chile Y.Zhou Washington UniversityinSt.Louis,St. Louis, Missouri,UnitedStates C H A P T E R 1 Introduction to Imaging in Dermatology M.R. Hamblin, P. Avci, G.K. Gupta Harvard Medical School & Massachusetts General Hospital,Boston, MA,United States O U T L I N E References 4 Dermatology is one of the most important medical Alibert (1768e1837) was a pioneer of dermatology in specialties. The prevalence of skin diseases exceeds France. Alibert was personal physician to Louis XVIII thatofobesity,hypertension,andcanceraddedtogether andCharlesX,andwasappointedProfessorofMateria [1]. Skin disease accounts for 12.4% of primary care Medica and Therapeutics in Paris in 1823 [9]. Alibert visits in the United States, and it is estimated that one introduced a classification system for skin diseases out of three people in the United States has a skin dis- that became known as the “Tree of Dermatoses.” He easeatanygiventime.Althoughthenumberofderma- produced the first illustrated atlas of dermatology tologists has grown more quickly than the US called Descriptions des maladies de la peau: observe´es a` population (increasing from 1.9 to 3.2 per 100,000 per- l’HoˆpitalSaint-Louis,etexpositiondesmeilleuresme´thodes sons between 1970 and 2010, respectively) [2], there is suivies pour leur traitement in 1806 [10]. The Vienna still considered to be an overall shortage of dermatolo- School of Dermatology was founded by Ferdinand gists [3]. von Hebra in the mid-19th century [11] and became The origins of dermatology have always relied the one of leading academic centers for the study of heavily onvisualobservationof theskin. InTheCanon dermatology. of Medicine by Avicenna (who was also known as Ibn In the last half of the 19th century and going on into Sina) written in Persia in 1025, treatments were the20thcentury,dermatopathologyassumedanincreas- described for a variety of skin conditions, including ingly important role in dermatology, and microscopic skincancer[4].In1572,GirolamoMercurialepublished examination of biopsies became the gold standard for inVenice,Italy,Demorbiscutaneis(OntheDiseasesofthe diagnosisofawiderangeofdermatologicalconditions. Skin), considered to be first scientific work to be However,nowthatwearewellintothe21stcentury,this devoted to dermatology [5]. Daniel Turner, who was statusquomaybebeginningtochange.Oneofthemain born in London, received the first doctoral degree reasonsforthischangeisthealmostunbelievablerisein fromtheCollegeoftheAcademyofYaleinConnecticut theuseofnoninvasive imagingin(almost) allbranches in the American colonies (later to become the United of medicine. States) [6]. Interestingly, Turner also published a book Theoriginofthisexplosivegrowthinmedicalimag- ofthesamenameDemorbiscutaneis,subtitledATreatise ing can be traced back to the discovery of X-rays. Wil- ofDiseasesIncidenttotheSkinin1712.Thisworkwasthe helm Conrad Ro¨ntgen (1845e1923) discovered this firstbookpublishedinEnglishdevotedtodermatology highlypenetratingformofradiationin1895,andcalled [7].In1777Anne-CharlesLorry(1726e1783)published themX-rays(signifyinganunknownquantity),although the700pageTractatusdemorbiscutaneisandforthefirst many others referred to them as “Ro¨ntgen rays.” time referred to the skin as an organ [8]. Jean-Louis Ro¨ntgen was awarded the Nobel Prize for Physics in ImaginginDermatology http://dx.doi.org/10.1016/B978-0-12-802838-4.00001-7 1 Copyright©2016ElsevierInc.Allrightsreserved. 2 1. INTRODUCTIONTOIMAGINGINDERMATOLOGY 1901.Itdidnottakelongbeforethenewscienceofradi- potassiuminlivingcellsledhimtohisfirstexperiments ologywasputtopracticaluse.IntheGreco-Turkishwar with NMR, which caused him to first propose the MR of 1897, battlefield radiographic imaging was used to bodyscannerin1969.Damadiandiscoveredthattumors detect bullets in injured soldiers. The radiographs and normal tissue could be distinguished in vivo by were produced by an apparatus manufactured by the NMR because of the longer relaxation times in tumors, LondoncompanyMillerandWoods,thatwasthenship- bothT1(spin-latticerelaxation)orT2(spinespinrelaxa- ped to Piraeus in 15 crates and powered by electricity tion)[19].Damadianwasthefirsttoperformafullbody from accumulators (a forerunner of lead-sulfuric acid scanofahumanbeingin1977todiagnosecancer.How- batteries)[12]. ever Damadian’s point scanning approach called field In the same year as Ro¨ntgen’s discovery, Henri Bec- focused NMR (FONAR) was time-consuming, and it querel(1852e1908,ProfessorofPhysicsatMuse´umNa- was the rival device of Paul C. Lauterbur and Sir Peter tional d’Histoire Naturelle in Paris) was studying Mansfield, which was based on field gradients and phosphorescent uranium salts. He initially thought was able to provide linear localization, that eventually thatthepenetratingradiationhefoundwasphosphores- succeeded. In a controversial decision, the Nobel Com- cence emission from the salt produced by exposure to mitteeawardedtheNobelPrizeinPhysiologyorMedi- bright sunlight, but soon realized that the radiation cine of 2003 to Lauterbur and Mansfield only, whereas camefromtheuraniumitselfwithoutanyexternalexci- Damadian was excluded [20]. It was remarked upon tation. This discovery of radioactivity earned him the by commentators that the Nobel citation was able to NobelPrizeinPhysicsin1903inconjunctionwithMarie include up to threerecipients. Curie and herhusband PierreCurie [13]. Positron emission tomography (PET) is a nuclear For the first half of the 20th century radiographs medicine imaging technique that produces a three- remained the only widely employed imaging modality. dimensional image of active processes occurring in the Inthe1950snuclearmedicineemergedasamedicalspe- body. The system detects pairs of gamma rays emitted cialty after radionuclides (radioactive isotopes) were whenapositronemittedfromaparticulartypeofradio- first produced for medical use by the Oak Ridge Na- nuclide isotope decomposes. The PET isotope is intro- tional Laboratory in Tennessee. The development of duced into the body as a tracer by tagging it to a therectilinearscannerandthegammascintillationcam- biologically active molecule. Three-dimensional images era helped establish nuclear medicine as a fully devel- of tracer concentration within the body are then con- oped medical imagingspecialty [14]. structedbycomputeranalysis.InmodernPET-CTscan- Conventional tomography (rotating the X-ray tube ners,three-dimensionalimagingisenabledwiththeaid and the film synchronously in opposite directions) had of a concurrent CTradiography scan performed on the been described in a patent issued in 1922 to the French patient in the same machine [21]. In 1953, Sweet and dermatologist Andre Bocage (1892e1953) [15]. Howev- Brownellreportedtheuseofpositron-emitting isotopes er,itwasnotuntildevelopmentofsufficientcomputing to localize brain tumors [22], The use of 2-fluoro-2- powerin the1970s that radiographic computed tomog- deoxy-D-glucose (18F) as a glucose-analog tracer was raphy(CT)emergedastheoneofthedominantimaging introducedbyacollaborativegroupconsistingofMartin modalitieswithitsabilitytoimagesofttissueaswellas Reivich,DavidKuhl,andAbassAlaviattheHospitalof bone. The first CTscan took place on a patient with a theUniversityofPennsylvaniaandAlfredWolfatBroo- suspected frontal lobe brain tumor in 1971 at Atkinson khaven National Laboratory [23]. The compound was Morley’s Hospital, in London, England. The patient first administered to two normal human volunteers by was scanned with a prototype scanner developed by AlaviinAugust1976attheUniversityofPennsylvania. Godfrey Hounsfield and his team at EMI Central Brain images obtained with an ordinary (non-PET) nu- Research Laboratories inHayes [16]. clear scanner demonstrated the concentration of 18F- ProfessorIsidorI.Rabi(1898e1988),whileworkingin fluorodeoxyglucose (FDG) in that organ [24]. The PET- the Pupin Physics Laboratory in Columbia University, CT scanner was developed by Dr. David Townsend, NewYorkCity,in1937observedthequantumphenom- Dr. Ronald Nutt, et al. [25] and was named by Time enon dubbed nuclear magnetic resonance (NMR). He Magazine as the medical invention ofthe year in 2000. discovered that atomic nuclei (particularly hydrogen Ultrasound as used for diagnostic imaging is called atoms)willabsorbandemitradiowaveswhenexposed ultrasonography. English-born physicist John Wild to a sufficiently strong magnetic field. He received the (1914e2009)firstusedultrasoundtoassessthethickness Nobel Prize in Physics in 1944 for this work [17]. Ray- of bowel tissue as early as 1949 [26]; he has been mond Vahan Damadian (born on March 16, 1936) is an described as the “father of medical ultrasound” [27]. American of Armenian origin, credited with being the ProfessorIanDonaldetal.attheGlasgowRoyalMater- inventor of the principle of the magnetic resonance im- nity Hospital were the first to use ultrasound to diag- aging (MRI) device [18]. His research into sodium and noselivevolunteerpatientswithabdominalmasses[28]. 3 REFERENCES Donald and Dr. James Willocks then refined their fluorescence in the detection and localization of poorly techniques to obstetrical applications including fetal demarcated skin lesions. In Chapter 10, Longon et al. head measurement to assess the size and growth of the describe the clinical applications of the novel imaging fetus [29]. technique of ex vivo fluorescence confocal microscopy Optical imaging covers such a large field that it is (FCM). In Chapter 11, Wang and Evans describe difficult to decide what was the first medical applica- coherentRamanscattering,microscopywhichprovides tion.Coulditbesaidthattheintroductionofspectacles not only the morphological/structural information of in1270,inFlorence,Italywasthefirstuseofopticalim- the skin, but also the chemical and molecular informa- aging in medicine? Or the introduction in 1590 of the tion. Zhao et al., in Chapter 12, present a rapid real- compound microscope by the father and son team of time Raman system and an imaging-guided confocal Hans and Zacharias Janssen in the Netherlands? It is Raman system, both of which can be utilized for more likely that optical imaging (as understood by the invivoskinevaluation.Chenandassociates,inChapter general scientific community) and the application of 13, introduce the concept of surface-enhanced Raman biomedical optics to diagnose various diseases, came spectroscopy and discuss how nontoxic nanoscale sub- to prominence with the discovery of optical coherence strates and a variety of strategies can bring the sub- tomography (OCT) in the 1990s [30], although there strates and target molecules together for intradermal hadbeenavarietyoffluorescenceandothersimpleop- measurements.InChapter14,Campgivesanoverview ticalimagingtechniquesbeingsporadicallyexploredfor of broadband coherent anti-Stokes Raman scattering many years earlier. Now there are many sophisticated microspectroscopy.InChapter15,Alarconetal.describe optical imaging methodologies being studied and reflectanceconfocalmicroscopy,whichenablestheanal- explored for diagnosis, such as in vivo confocal micro- ysis of the skin horizontally with a nearly histological scopy [31], optical frequency domain imaging [32], resolution. Hyperspectral and multispectral imaging in diffuse optical imaging [33], fluorescence tomography dermatology is described by Vasefi et al. in Chapter 16. [34], Brillouin microscopy [35], Cerenkov imaging [36], Hyperspectral imaging generates a three-dimensional polarization sensitive techniques [37], photoacoustic data cube that contains absorption, reflectance, or fluo- techniques[38], andsoon. rescence spectrum data for each image pixel. Moy and Thepresentvolumeattemptstogathertogetherinfor- Tunnell, in Chapter 17, cover diffuse reflectance spec- mationontheuseofavarietyofmedicalimagingtech- troscopy and its applications in dermatology, including nologiesappliedto the general areaof dermatology. skincancer,portwinestain,erythema,sunscreenevalu- Thistextbookhasbeendividedintoeightbroadsec- ation,andburns.Moreover,futuredirectionscombining tions.Thefirstsection describes simpleopticalimaging diffuse reflectance with other optical methods are also modalitiesincludingdermoscopy,trichoscopy,andony- presented. In Chapter 18, Ho et al. provide a broad choscopy that are routinely used in clinical practice. In description of spectral imaging in vivo and ex vivo Chapter 2, Sidoroff discusses the current function and skin specimens. So et al. discusse the uses of multi- role of clinical photography in dermatology. In photon imaging to study skin immunoresponse, aging, Chapter3,Lallasetal.provideanoverviewofthebasic and regeneration in Chapter 19. In Chapter 20, Cicchi dermoscopicfindingsseeninmelanocyticandnonmela- et al. mainly describe use of two-photon microscopy, nocytic tumors, as well as the inflammatory and infec- second-harmonicgenerationmicroscopy,andtheircom- tious skin diseases. In Chapter 4, Khopkar and Jain binationfordifferentiationofepidermallayersandchar- highlight the diagnostic features of noncicatricial and acterization of the skin dermis. In Chapter 21, Jacques cicatricial alopecias and genetic hair shaft disorders, as highlights the principles of confocal reflectance and well as psoriasis and seborrheic dermatitis. In Chapter polarizedlightimaging.Yaroslavskyetal.giveanover- 5, Lencastre and Campos describe dermatoscopic find- view of polarization optical imaging of skin pathology ingsintumorsofthenailapparatus aswellasbacterial andaginginChapter22.Huangetal.definemechanical and fungal nail infections and inflammatory nail dis- characterization of skin using surface acoustic waves, a eases.ThemstrupandJemec,inChapter6,reviewappli- novel combination of phase-sensitive OCT technology cations of OCT in nonmelanoma skin cancer, with an withasimplemechanicalimpulsesurfacewavestimula- emphasis on basal cell carcinoma and actinic keratosis. tion in Chapter 23. In Chapter 24, Zhou and Wang InChapter7,Mamalisetal.focus onaspecific applica- discuss use of photoacoustic tomography of both pri- tion of OCT, assessment of skin fibrosis. In Chapter 8, mary and metastatic melanomas. Wortsman summa- Leeatal.discussetheutilizationofinterferenceandpo- rizes use of ultrasound in detection of common skin, larization techniques for evaluation of skin roughness, nail,andhairdiseasesinChapter25.Rasterscanoptoa- which aids in differentiating melanoma from other coustic mesoscopy, a high-resolution optical imaging benign skin lesions, such as seborrheic keratoses. In technique that can penetrate several millimeters in tis- Chapter 9, Hegyi and Hegyi cover the use of sues is described by Schwarz et al. in Chapter 26. 4 1. INTRODUCTIONTOIMAGINGINDERMATOLOGY Chapter27byPetersenandHigginsexplicatestheuseof [13] Dutreix J, Dutreix A. Henri Becquerel (1852e1908). Med Phys totalbodyphotographyandserialdigitaldermoscopyin 1995;22(11Pt2):1869e75. [14] WilliamsLE.Anniversarypaper:nuclearmedicine:fiftyyearsand dermatology.Papoiuintroducesutilizationoffunctional stillcounting.MedPhys2008;35(7):3020e9. MRIindetectionofbrainprocessingofitch inChapter [15] Editorial. 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