Approfondimento Bio-Imaging Informatics

9
Imaging and Structural Informatics

1AMLS !. BR!KILY AD ROBLRT A. GRLLLS
9.1 Introduction
As is evidenl lo anyone wlo las lad an X-iay, a magnelic iesonance imaging (MR!)
exam, oi a Liosy, images lay a cenlial iole in lle lealll caie iocess. !n addilion,
images lay imoilanl ioles in medical communicalion and educalion, as well as in
ieseaicl. !n lacl mucl ol oui iecenl iogiess, ailiculaily in diagnosis, can Le liaced lo
lle availaLilily ol incieasingly solislicaled images llal nol only slow lle sliucluie ol
lle Lody in inciediLle delail Lul also slow lle lunclion.
Alllougl lleie aie many imaging modalities, images ol all lyes aie incieasingly Leing
conveiled lo oi inilially acquiied in digilal loim. Tlis loim is moie oi less lle same
acioss all imaging modalilies. !l is lleieloie amenaLle lo common image-iocessing
mellodologies loi enlancemenl, analysis, dislay, and sloiage.
Because ol lle uLiquily ol images in Liomedicine, lle incieasing availaLilily ol
images in digilal loim, lle iise ol ligl-oweied comulei laidwaie and nelwoils, and
lle commonalily ol image-iocessing solulions, digilal images lave Lecome a coie dala
lye llal musl Le consideied in many Liomedical inloimalics alicalions. Tleieloie,
llis clalei is devoled lo a Lasic undeislanding ol llis coie dala lye and many ol lle
image-iocessing oeialions llal can Le alied lo il. Clalei 18, on lle ollei land,
desciiLes lle inlegialion ol images and image iocessing in vaiious alicalions,
ailiculaily llose in iadiology since iadiology laces lle giealesl demands on imaging
mellods.
Tle loics coveied Ly llis clalei and Clalei 18 aie geneially ail ol Liomedical
imaging inloimalics (Kulilowsli, 1997), a suLlield ol Liomedical inloimalics llal las
aiisen in iecognilion ol lle common issues llal eilain lo all image modalilies and
alicalions once lle images aie conveiled lo digilal loim. By liying lo undeisland
llese common issues, we can develo geneial solulions llal can Le alied lo all images,
iegaidless ol lle souice.
Tle common lasls addiessed Ly imaging inloimalics can Le iouglly classilied as
image generation, image manipulation, image management, and image integration. !mage
geneialion is lle iocess ol geneialing lle images and conveiling llem lo digilal loim
il lley aie nol inliinsically digilal. !mage maniulalion uses ieiocessing and osl-
iocessing mellods lo enlance, visualize, oi analyze lle images. !mage managemenl
includes mellods loi sloiing, liansmilling, dislaying, ieliieving, and oiganizing
images. !mage inlegialion is lle comLinalion ol images will ollei inloimalion needed
344
!maging and Sliucluial !nloimalics 345
loi inleiielalion, managemenl, and ollei lasls. Because iadiology laces lle giealesl
demand on image managemenl, and Lecause iadiology ieiesenls lle iimaiy alica-
lion ol imaging mellods, Clalei 18 is iimaiily conceined will lle lallei lwo lasls
wleieas llis clalei concenliales on lle loimei lwo.
A majoi uiose ol image iocessing is lo exliacl inloimalion aLoul lle sliucluie ol
lle Lody. As sucl, imaging inloimalics oveilas structural informatics, wlicl is lle
sludy ol mellods loi ieiesenling, oiganizing, and managing diveise souices ol inloi-
malion aLoul lle lysical oiganizalion ol lle Lody and ollei lysical sliucluies, Loll
loi ils own sale, and as a means loi oiganizing ollei inloimalion (Biinlley, 1991).
Many ol lle loics in llis clalei lleieloie lave lo do will low lo ieiesenl, exliacl,
and claiacleiize lle analomic inloimalion llal is iesenl in images.
Tle examles loi llis clalei, ailiculaily llose loi lliee-dimensional and lunc-
lional imaging, aie iimaiily lalen liom Liain imaging, wlicl is ail ol lle giowing
lield ol neuroinformatics (Koslow and Hueila, 1997). We cloose Liain imaging
Lecause: (1) Liain imaging is a sliong aiea ol inleiesl ol one ol lle aullois (1B), (2)
lle nalional Human Biain Piojecl (HBP) (Human Biain Piojecl, 2003) is geneialing
suLslanlial iesulls in lle aiea ol Liain imaging, (3) a laige oilion ol cuiienl medical
imaging woil is in Liain imaging, and (4) some ol lle mosl advanced image-ielaled
woil in inloimalics is cuiienlly Leing done in llis aiea. Tlus, in addilion lo inlio-
ducing lle concels ol digilal images and image iocessing, llis clalei ieiesenls an
inleiseclion ol many ol lle concels in imaging inloimalics, sliucluial inloimalics,
and neuioinloimalics.
We liisl inlioduce Lasic concels ol digilal images, and llen desciiLe mellods loi
imaging lle sliucluie ol lle Lody in Loll lwo dimensions and lliee dimensions. We
llen desciiLe lwo-dimensional and lliee-dimensional mellods loi iocessing sliucluial
images, iimaiily as a means loi visualizing, exliacling, and claiacleiizing analomy.
Tle clalei ends will a discussion ol mellods loi imaging lle lunclion ol lle Lody,
viilually all ol wlicl involve maing oi iegisleiing lle lunclional dala onlo lle
sliucluial ieiesenlalions exliacled using lle leclniques desciiLed in eailiei seclions.
9.2 Basic Concepts
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A digital image lyically is ieiesenled in a comulei Ly a lwo-dimensional aiiay ol
numLeis (a bit map). Lacl elemenl ol lle aiiay ieiesenls lle inlensily ol a small
squaie aiea ol lle icluie, called a pixel. !l we considei lle image ol a volume, llen a
lliee-dimensional aiiay ol numLeis is iequiied; eacl elemenl ol lle aiiay in llis case
ieiesenls a volume elemenl, called a voxel.
We can sloie any image in a comulei in llis mannei, eillei Ly conveiling il liom an
analog lo a digilal ieiesenlalion oi Ly geneialing il diieclly in digilal loim. Once an
image is in digilal loim, il can Le landled jusl lile all ollei dala. !l can Le liansmilled
ovei communicalions nelwoils, sloied comaclly in dalaLases on magnelic oi olical
media, and dislayed on gialics monilois. !n addilion, lle use ol comuleis las
ciealed an enliiely new iealm ol caaLililies loi image geneialion and analysis; images
can Le comuled iallei llan measuied diieclly. !uilleimoie, digilal images can Le
maniulaled loi dislay oi analysis in ways nol ossiLle will lilm-Lased images.
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All images can Le claiacleiized Ly seveial aiameleis ol image qualily. Tle mosl use-
lul ol llese aiameleis aie salial iesolulion, conliasl iesolulion, and lemoial iesolu-
lion. Tlese aiameleis lave Leen widely used lo claiacleiize liadilional X-iay images;
lley also iovide an oLjeclive means loi comaiing images loimed Ly digilal imaging
modalilies.
Spatial resolution is ielaled lo lle slainess ol lle image; il is a measuie ol low well
lle imaging modalily can dislinguisl oinls on lle oLjecl llal aie close logellei. !oi
a digilal image, salial iesolulion is geneially ielaled lo lle numLei ol ixels ei
image aiea.
Contrast resolution is a measuie ol lle aLilily lo dislinguisl small dilleiences in inlen-
sily, wlicl in luin aie ielaled lo dilleiences in measuiaLle aiameleis sucl as X-iay
allenualion. !oi digilal images, lle numLei ol Lils ei ixel is ielaled lo lle conliasl
iesolulion ol an image.
Temporal resolution is a measuie ol lle lime needed lo cieale an image. We considei
an imaging ioceduie lo Le a ieal-lime alicalion, il il can geneiale images concui-
ienl will lle lysical iocess il is imaging. Al a iale ol al leasl 30 images ei second,
il is ossiLle lo ioduce unLluiied images ol lle Lealing leail.
Ollei aiameleis llal aie secilically ielevanl lo medical imaging aie lle degiee ol
invasiveness, lle dosage ol ionizing iadialion, lle degiee ol alienl discomloil, lle size
(oilaLilily) ol lle insliumenl, lle aLilily lo deicl lysiologic lunclion as well as
analomic sliucluie, and lle availaLilily and cosl ol lle ioceduie al a secilic localion.
A eilecl imaging modalily would ioduce images will ligl salial, conliasl, and
lemoial iesolulion; il would Le low in cosl, oilaLle, liee ol iisl, ainless, and nonin-
vasive; il would use nonionizing iadialion; and il would deicl lysiologic lunclions as
well as analomic sliucluie.
9.3 Structural Imaging
!maging lle sliucluie ol lle Lody las Leen and conlinues lo Le lle majoi alicalion
ol medical imaging, alllougl, as desciiLed in Seclion 9.6, lunclional imaging is a veiy
aclive aiea ol ieseaicl. Tle develomenl ol lle vaiious sliucluial imaging modalilies
can Le seen ailly as a seaicl loi lle eilecl imaging modalily; a iimaiy ieason loi lle
iolileialion ol modalilies is llal no single modalily salislies all lle desideiala. Anollei
ieason loi lle iolileialion ol image-geneialion mellods is llal iogiess las occuiied
in aiallel in loui main aieas, and ieseaicleis lave develoed new mellods quiclly Ly
comLining elemenls liom eacl ol llese aieas. Tle loui aieas ol develomenl aie eneigy
souice, ieconsliuclion mellod, liglei dimensionalily, and conliasl agenls.
346 1. !. Biinlley and R. A. Gieenes

Light
Tle eailiesl medical images used light lo cieale lologials, eillei ol gioss analomic
sliucluies oi, il a micioscoe was used, ol lislologic secimens. Iigll is slill an imoi-
lanl souice loi ciealion ol images, and in lacl olical imaging las seen a iesuigence ol
lale loi aieas sucl as moleculai imaging (Weissledei and Malmood, 2001) and imaging
ol Liain aclivily on lle exosed suilace ol lle ceieLial coilex (Pouialian el al., 2003).
VisiLle ligll, lowevei, does nol allow us lo see moie llan a sloil dislance Leneall lle
suilace ol lle Lody.
X-Rays
X-rays weie liisl discoveied in 1895 Ly Willelm Coniad Roenlgen, wlo was awaided
lle 1901 oLel Piize in Plysics loi llis aclievemenl. Tle discoveiy caused woildwide
excilemenl, esecially in lle lield ol medicine; Ly 1900, lleie weie alieady seveial med-
ical iadiological socielies. Tlus, lle loundalion was laid loi a new Liancl ol medicine
devoled lo imaging lle sliucluie and lunclion ol lle Lody (Kevles, 1997).
!ilm-Lased radiography is lle iimaiy modalily used in iadiology deailmenls loday,
alllougl llis emlasis is clanging iaidly as digilal oi computed radiography (CR)
seivices aie inslalled. We ioduce a lyical X-iay image Ly iojecling an X-iay Leam
one loim ol ionizing iadialionliom an X-iay souice lliougl a alienls Lody (oi
ollei oLjecl) and onlo an X-iay-sensilive lilm. Because an X-iay Leam is dilleienlially
aLsoiLed Ly lle vaiious Lody lissues, lle X-iays ioduce sladows on lle iadiogialic
lilm. Tle iesullanl shadowgraph is a sueiosilion ol all lle sliucluies liaveised Ly eacl
Leam. Digital radiography (DR) alies lle same leclniques, Lul nonlilm deleclois aie
used. !n a leclnique lnown as CR, a lalenl image is iecoided on a secially coaled
casselle llal is scanned Ly a comulei lo caluie lle image in digilal loim; in ollei
leclniques, deleclois caluie lle dala diieclly in digilal loim. Alllougl lle images
oLlained Ly llese leclniques may Le iinled suLsequenlly on lilm, lley do nol need lo Le.
Boll lilm and lluoioscoic scieens weie used inilially loi iecoiding X-iay images, Lul
lle lluoioscoic images weie loo lainl lo Le used clinically. By lle 1940s, lowevei, lele-
vision and image-inlensiliei leclnology weie used lo ioduce cleai ieal-lime lluoiescenl
images. Today, a slandaid ioceduie loi many lyes ol examinalions is lo comLine ieal-
lime lelevision moniloiing ol X-iay images will lle ciealion ol selecled liglei iesolu-
lion lilm images. \nlil lle eaily 1970s, lilm and fluoroscopy weie lle only X-iay
modalilies availaLle.
Tiadilional X-iay images lave ligl salial iesolulion and medium cosl. !uilleimoie,
lley can Le geneialed in ieal lime (lluoioscoy) and can Le ioduced using oilaLle
insliumenls. Tleii limilalions aie lleii ielalively ooi conliasl iesolulion, lleii use ol
ionizing iadialion, and lleii inaLilily lo deicl lysiologic lunclion. Alleinale imaging
iinciles lave Leen alied lo inciease conliasl iesolulion, lo eliminale exosuie lo
X-iay iadialion, and so on. !oi examle, in nucleai-medicine imaging, a radioactive iso-
tope is clemically allacled lo a Liologically aclive comound (sucl as iodine) and llen
is injecled inlo lle alienls eiileial ciiculalion. Tle comound collecls in lle secilic
Lody comailmenls oi oigans (sucl as lle llyioid), wleie il is sloied oi iocessed Ly lle
Lody. Tle isoloe emils iadialion locally, and lle iadialion is measuied using a secial
delecloi. Tle iesullanl nucleai-medicine image deicls lle level ol iadioaclivily llal was
measuied al eacl oinl. Because lle counls aie inleienlly digilal, comuleis lave Leen
used lo iecoid llem. Mullile images also can Le iocessed lo oLlain dynamic inloima-
lion, sucl as lle iale ol aiiival oi ol disaeaiance ol isoloe al ailiculai Lody siles.
Iltrasound
Anollei common eneigy souice is ultrasound (eclosonogialy), wlicl develoed oul
ol ieseaicl eiloimed Ly lle avy duiing Woild Wai !!. Iltrasonography uses ulses
ol ligl-liequency sound waves iallei llan ionizing iadialion lo image Lody sliucluies.
As eacl sound wave encounleis lissues in a alienls Lody, a oilion ol lle wave is
iellecled and a oilion conlinues. Tle lime iequiied loi lle eclo lo ieluin is iooi-
lional lo lle dislance inlo lle Lody al wlicl il is iellecled; lle amlilude (inlensily) ol
a ieluining eclo deends on lle acouslical ioeilies ol lle lissues encounleied and is
ieiesenled in lle image as Liigllness. Tle syslem consliucls lwo-dimensional images
Ly dislaying lle ecloes liom ulses ol mullile adjacenl one-dimensional alls. Sucl
images can Le sloied in digilal memoiies oi iecoided on videolae and llen dislayed
as lelevision (iaslei-dislay) images.
Nuclear Magnetic Resonance
Ciealion ol images liom magnetism giew oul ol nuclear magnetic resonance (NMR)
spectroscopy, a leclnique llal las long Leen used in clemisliy lo claiacleiize clemical
comounds. Many alomic nuclei willin lle Lody lave a nel magnelic momenl, so lley
acl lile liny magnels. Wlen a small clemical samle is laced in an inlense, uniloim
magnelic lield, llese nuclei line u in lle diieclion ol lle lield, sinning aiound lle axis
ol lle lield will a liequency deendenl on lle lye ol nucleus, on lle suiiounding
enviionmenl, and on lle sliengll ol lle magnelic lield.
!l a iadio ulse ol a ailiculai liequency is alied al iigll angles lo lle slalionaiy
magnelic lield, llose nuclei will iolalion liequency equal lo llal ol lle iadioliequency
ulse iesonale will lle ulse and aLsoiL eneigy. Tle liglei eneigy slale causes lle
nuclei lo clange lleii oiienlalion will iesecl lo lle lixed magnelic lield. Wlen lle
iadioliequency ulse is iemoved, lle nuclei ieluin lo lleii oiiginal aligned slale,
emilling a deleclaLle iadioliequency signal as lley do so. Claiacleiislic aiameleis ol
llis signalsucl as inlensily, duialion, and liequency slill away liom lle oiiginal
ulseaie deendenl on lle densily and enviionmenl ol lle nuclei.
!n lle case ol liadilional MR seclioscoy, dilleienl moleculai enviionmenls cause
dilleienl liequency slills (called clemical slills), wlicl we can use lo idenlily lle ai-
liculai comounds in a samle. !n lle oiiginal MR mellod, lowevei, lle signal is nol
localized lo a secilic iegion ol lle samle, so il is nol ossiLle lo cieale an image.
Ciealion ol images liom MR signals lnown as MR! lad lo awail lle develomenl ol
comulei-Lased ieconsliuclion leclniques, wlicl ieiesenl one ol lle mosl seclaculai
alicalions ol comuleis in medicine.
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Reconsliuclion leclniques weie liisl alied lo X-iay images aimed al addiessing lle
ioLlem ol sueiosilion ol sliucluies in slandaid iojeclion imaging. An X-iay image
al a given oinl ieiesenls lle lolal allenualion due lo all lle oveilaid sliucluies
liaveised Ly a Leam as llal Leam asses lliougl lle Lody; sladows casl Ly suiiound-
ing sliucluies may oLscuie lle oLjecl llal lle clinician wisles lo visualize. Contrast
radiographylle use ol iadioaque conliasl maleiial lo liglligll lle aieas ol inleiesl
(e.g., slomacl, colon, uiinaiy liacl)was used as eaily as 1902 lo addiess llis ioLlem.
Tle liisl clinical exeiimenls will angiographyimaging ol Llood vessels eiloimed Ly
lle injeclion ol oacilying agenls inlo lle Lloodslieamweie conducled in 1923.
Tle desiie lo seaiale sueiimosed sliucluies also led lo lle develomenl ol a
vaiiely ol analog lomogialic leclniques. !n llese mellods, lle X-iay souice and
delecloi weie moved in oosile aics, lleieLy causing a llin lomogialic (lanai) sec-
lion lo iemain in locus wlile ollei lanes weie Lluiied. Tlis mellod, lowevei, exoses
lle alienl lo a ielalively ligl X-iay dose Lecause lle Lluiied aieas aie exosed
conlinuously.
Mallemalical mellods loi ieconsliucling images liom iojeclions weie liisl devel-
oed Ly Radon in 1917 and lalei weie imioved Ly ollei ieseaicleis. Tlese mellods
weie used in lle 1950s and 1960s lo solve scienlilic ioLlems in many lields, including
iadio aslionomy and eleclion micioscoy. !n lle lale 1960s, Coimacl used lle lecl-
niques lo ieconsliucl lanloms (oLjecls will lnown slae) using X-iays. !n lle eaily
1970s, Hounslield led a leam al lle Iondon-Lased LM! Coioialion, wlicl develoed
lle liisl commeicially viaLle comuled lomogialy (CT) scannei.
!nslead ol deicling a diieclly measuiaLle aiamelei (lle aLsoilion ol X-iay
Leams as lley ass lliougl lle Lody), CT mallemalically ieconsliucls an image liom
X-iay-allenualion values llal lave Leen measuied liom mullile angles. As a iesull, il
is ossiLle lo view cioss-seclional slices lliougl lle Lody iallei llan lwo-dimensional
iojeclions ol sueiimosed sliucluies. Tlus, CT images iovide a iecise maing ol
lle inleinal sliucluies ol lle Lody in lliee-dimensional sacea lunclion nol iovided
Ly slandaid X-iay images. Tley also gieally imiove conliasl iesolulion.
!n lle Lasic CT imaging leclnique, lle alienl is laced Lelween an X-iay-sensilive
delecloi and an X-iay souice llal ioduces a collimaled (encil-lile) Leam. Tle meas-
uied dilleience Lelween lle souice and delecloi X-iay inlensilies ieiesenls lle amounl
ol X-iay allenualion due lo lle lissues liaveised Ly lle Leam; llis measuied allenualion
is a sueiosilion, oi projection, ol lle allenualions ol all lle individual lissue elemenls
liaveised Ly lle Leam. !n lle simlesl ieconsliuclion mellod, called back-projection,
lle measuied inlensily is disliiLuled uniloimly ovei all lle ixels liaveised Ly lle Leam.
!oi examle, il lle measuied allenualion is 20, and 10 ixels weie liaveised, llen lle
CT numLei ol eacl ol lle 10 ixels is inciemenled Ly 2 unils.
Tle allenualion measuied liom a single iojeclion is nol sullicienl lo ieconsliucl an
image. Tle same Lacl-iojeclion comulalion, lowevei, can Le alied lo lle allenua-
lions measuied liom mullile iojeclions. Tle souice and delecloi aie iolaled aLoul lle
alienl, and lle X-iay allenualion is measuied along eacl all. Because eacl ixel is
liaveised Ly mullile iojeclion alls, ils comuled allenualion is lle sum ol lle
conliiLulions liom eacl all. Tle lolal sum iovides a ieasonaLle liisl aioximalion
ol lle X-iay allenualion ol lle individual ixel. Tle image is luillei ielined using a
mallemalical edge-enlancemenl leclnique called convolution. !n ellecl, convolulion
iemoves sladows llal iesull liom lle Lacl iojeclion, llus slaiening lle Lluiiy
image.
Tle develomenl ol lle CT scannei diamalically imioved oui aLilily lo visualize
adjacenl sliucluies; loi lle liisl lime, lysicians weie aLle lo see inside a living luman
Leing cleaily, Lul noninvasively. Tlis aLilily led lo a ievolulion in medicine almosl as
gieal as lle one occasioned Ly lle invenlion ol X-iay imaging. As a iesull, Coimacl
and Hounslield weie awaided lle 1979 oLel Piize in Medicine.
Allei lle invenlion ol lle CT scannei, llis Lasic mellod ol ieconsliuclion liom io-
jeclions was alied lo ollei eneigy souices, including magnelism (MR!), ulliasound
(ulliasound-liansmission lomogialy), and vaiianls ol nucleai-medicine imaging
called positron-emission tomography (PET) and single-lolon-emission comuled
lomogialy (SPLCT).
Tle mosl diamalic examle ol ieconsliuclion liom iojeclions ollei llan CT is
MR!, wlicl is Lased on MR (Oldendoil, 1991). As desciiLed in lle ievious seclion,
MR lales advanlage ol magnelic ioeilies ol nuclei lo claiacleiize lle disliiLulion
and clemical enviionmenl ol nuclei willin a clemical samle. To cieale an image using
llese aiameleis, we need a way lo iesliicl llis samle lo a small volume willin a laigei
lissue. Will llis iesliiclion, lle aiameleis ol lle MR signal liom eacl small lissue
volume can Le maed lo voxel inlensilies deicling dilleienl lissue claiacleiislics.
Tle iesliiclion lo a small samle volume is accomlisled Ly laling advanlage ol lle
lacl llal lle iesonanl liequency ol alomic nuclei vaiies will lle magnelic lield. !l lle
lield can Le made dilleienl loi eacl small lissue volume, llen a iadioliequency ulse
will a given liequency will excile only llose nuclei in lle small volume llal lave lle
iesonanl liequency ol llal ulse. Tle Lasic mellod uses elecliomagnelic coils lo
sueiimose a vaiying magnelic lield on a laige lixed magnelic lield, lleieLy selling u
a giadienl in lle magnelic lield.
Tlis giadienl is clanged eleclionically, selling lle localion ol lle samle volume. !oi
examle, we use one giadienl lo sel lle lane ol seclion (lle z diieclion, alllougl lle
oiienlalion ol llis seclion may Le aiLiliaiy will iesecl lo lle alienl), and a second
giadienl sels a line willin a single seclion (lle x,y lane). As in CT, lle signal delecled
along llis line is a summalion ol lle signals liom all voxels along lle line. Tleieloie,
lle x,y giadienl is eleclionically iolaled, iolaling lle lane ol seclion and geneialing
addilional lines willin a given lane. Tle same ieconsliuclion leclniques develoed loi
CT llen ieconsliucl lle values loi lle individual voxels willin lle given lane. Because
lleie aie many dilleienl aiameleis llal can Le measuied loi eacl samled voxel, many
dilleienl lyes ol images can Le consliucled, many ol wlicl aie slill Leing develoed.
-
Mosl iouline images in iadiology aie slill lwo-dimensional. Because lle Lody is a lliee-
dimensional oLjecl llal clanges ovei lime, lowevei, lleie will always Le a diive lo cieale
lliee-dimensional lime-vaiying images. !n iecenl yeais, advances in digilal laidwaie
lave iovided lle sloiage and lliouglul lo manage laige lime-vaiying voxel-Lased
dala sels. Reconsliuclion modaliliessucl as CT, PLT, and MR!all aie eillei inlei-
enlly lliee-dimensional oi can Le made lliee-dimensional Ly acquisilion ol a seiies ol
closely saced aiallel slices (see Seclion 9.5). Tlus, lle only diawLacls ol llese lecl-
niques aie lle lime and exense iequiied lo acquiie a seiies ol aiallel slices, Loll ol
wlicl aie Lecoming smallei.
\lliasound images, on lle ollei land, cannol Le acquiied as aiallel slices Lecause
sound does nol ass lliougl Lone oi aii. !oi llis ieason, we usually oLlain lliee-
dimensional ulliasound inloimalion Ly allacling a lliee-dimensional localing device lo
lle liansducei. Tle localoi gives lle osilion and oiienlalion ol lle slice lane in sace.
Beloie lle availaLilily ol laidwaie llal could sloie laige numLeis ol volume dala, lle
ulliasound images weie liisl iocessed in lwo dimensions lo exliacl ielevanl analomy
as lwo-dimensional conlouis oi iegions; lle lwo-dimensional conlouis weie conveiled
lo lliee-dimensional conlouis Lased on lle localion inloimalion and llen weie
dislayed will vecloi gialics (Biinlley el al., 1978). Sucl an aioacl was uselul loi
quanlilalion, Lul did nol iovide a iealislic lliee-dimensional view ol lle oLjecl.
- -
As noled aLove, one ol lle majoi molivalois loi develomenl ol new imaging modali-
lies is lle desiie lo inciease conliasl iesolulion. We lave alieady discussed lle use ol
iadiologic conliasl agenls and ieconsliuclion leclniques as examles ol liglly success-
lul allemls lo inciease conliasl iesolulion among lle dilleienl eneigy souices. !n addi-
lion, lislologic slaining agenls sucl as lemaloxylin and eosin (H&L) lave Leen used loi
yeais lo enlance conliasl in lissue seclions, and magnelic conliasl agenls sucl as
gadolinium lave Leen inlioduced lo enlance conliasl in MR images.
Alllougl llese mellods lave Leen veiy successlul, lley geneially aie somewlal
nonsecilic. !n iecenl yeais, advances in moleculai Liology lave led lo lle aLilily lo
design conliasl agenls llal aie liglly secilic loi individual molecules. !n addilion lo
iadioaclively lagged molecules used in nucleai medicine, molecules aie lagged loi
imaging Ly magnelic iesonance and olical eneigy souices. Tagged molecules aie
imaged in lwo dimensions oi lliee dimensions, ollen Ly alicalion ol ieconsliuclion
leclniques develoed loi clinical imaging. Tagged molecules lave Leen used loi
seveial yeais Ly sucl leclniques as immunocyloclemisliy (Linding ol lagged
anliLodies lo anligen) (Van ooiden, 2002) and - lyLiidizalion (Linding ol
lagged nucleolide sequences lo DA oi RA) (King el al., 2000). Moie iecenlly,
mellods lave Leen develoed lo image llese molecules in lle living oiganism, lleieLy
oening u enliiely new avenues loi undeislanding lle lunclioning ol lle Lody al lle
moleculai level.
-
Many new imaging leclniques lave Leen develoed in iecenl yeais. Mosl ol llese lecl-
niques can Le seen as a comLinalion ol an eneigy souice, a comulei-Lased iocessing
oi ieconsliuclion leclnique, incieased dimensionalily due lo advances in digilal
laidwaie, and, incieasingly, use ol moleculai conliasl agenls. Tle iemaindei ol llis
seclion desciiLes a lew examles ol llese leclniques.
Al lle gioss analomic level, charge-coupled device (CCD) cameras can Le used lo con-
veil exisling lilm-Lased equimenl lo unils llal can ioduce images in digilal loim.
Sloiage losloi, oi CR, syslems ielace lilm Ly suLsliluling a ieusaLle losloi lale
in a slandaid lilm casselle. Tle exosed lale is iocessed Ly a ieadei syslem llal scans
lle image inlo digilal loim, eiases lle lale, and aclages lle casselle loi ieuse. An
imoilanl advanlage ol CR syslems is llal lle casselles aie ol slandaid size, so lley
can Le used in any equimenl llal lolds lilm-Lased casselles (Hoiii, 1996). Moie
iecenlly, CR uses CCD aiiays lo caluie lle image diieclly.
Many new modalilies aie Leing develoed Lased on magnelic iesonance. !oi exam-
le, - (MRA) and -
(MRV) image Llood llow (Iee, 2003), and - - (DT!) is incieasingly
Leing used lo image wlile mallei liLei liacls in lle Liain (!iguie 9.1) (Ie Bilan el al.,
2001).
Figure 9.1. Dillusion lensoi image (DT!) ol lle mouse sinal coid. Al eacl ixel lle DT! lecl-
nique oululs a 3 I 3 dillusion lensoi desciiLing lle measuied dillusion ol walei in eacl ol lle
six iincile diieclions in lliee-dimensional sace. !n giay mallei, lle dillusion is geneially uni-
loim (isolioic) in all diieclions, Lul in wlile mallei dillusion is ieduced in lle diieclion eien-
diculai lo lle liLeis. Tlus, DT! is used lo visualize wlile mallei liLei liacls. Since eacl ixel (oi
voxel in lliee-dimensions) is desciiLed Ly a 3 I 3 maliix, visualizalion leclniques liom comulei
gialics aie needed in oidei lo ieiesenl lle inloimalion al eacl ixel. !n llis liguie, lle dillu-
sion lensois aie ieiesenled Ly ellisoids will axes along lle iincile diieclions ol lle dillusion
lensoi. Plologial couilesy ol David Iaidlaw (Aliens el al., 1998), lll://www.gg.callecl.edu/
~dll/images.llml.
\lliasound maclines lave essenlially Lecome secialized comuleis will allacled
eiileials, will aclive develomenl ol lliee-dimensional imaging. Tle ulliasound
liansducei now ollen swees oul a lliee-dimensional volume iallei llan a lwo-
dimensional lane, and lle dala aie wiillen diieclly inlo a lliee-dimensional aiiay
memoiy, wlicl is dislayed using volume oi surface-based rendering leclniques
(!iguie 9.2) (Rilclie el al., 1996).
Al lle micioscoic level, lle - uses eleclionic locusing lo move a
lwo-dimensional slice lane lliougl a lliee-dimensional lissue slice laced in a micio-
scoe. Tle iesull is a lliee-dimensional voxel aiiay ol a micioscoic, oi even suLmi-
cioscoic, secimen (Wilson, 1990; Paddocl, 1994). Al lle eleclion micioscoic
level geneiales lliee-dimensional images liom llicl eleclion-
micioscoic seclions using leclniques similai lo llose used in CT (Peilins el al., 1997).
Al lle moleculai level lagged molecules aie incieasingly inlioduced inlo lle living
oiganism, and imaged will olical, iadioaclive oi magnelic eneigy souices, ollen using
ieconsliuclion leclniques and ollen in lliee dimensions. Tle comLinalion ol llese vai-
ious mellods will liglly secilic lagged molecules las given iise lo lle lield ol molec-
ular imaging (Weissledei and Malmood, 2001; Massoud and GamLlii, 2003), wlicl in
addilion lo lunclional Liain imaging (Seclion 9.6) ieiesenls some ol lle mosl exciling
new develomenls in Liomedical imaging. !l is now Lecoming ossiLle lo comLine gene
sequence inloimalion, gene exiession aiiay dala, and moleculai imaging lo deleimine
nol only wlicl genes aie exiessed Lul also wleie lley aie exiessed in lle oiganism.
Tlese caaLililies will Lecome incieasingly imoilanl in lle post-genomic era loi delei-
mining exaclly low genes geneiale Loll lle sliucluie and lunclion ol lle oiganism.
9.4 Two-Dimensional Image Processing
Tle iaidly incieasing numLei and lyes ol digilal images las ciealed many ooilu-
nilies loi image iocessing, since one ol lle gieal advanlages ol digilal images is llal
Figure 9.2. Tliee-dimensional ullia-
sound image ol a lelus, . Tle
ulliasound ioLe swees oul a lliee-
dimensional volume iallei llan lle con-
venlional lwo-dimensional lane. Tle
volume can Le iendeied diieclly using
volume-iendeiing leclniques, oi as in
llis case, lelal suilaces can Le exliacled
and iendeied using suilace-iendeiing
leclniques. Plologial couilesy ol Pei
Peim, GL Healllcaie, lll://www.
gemedicalsyslems.com/iad/us/educalion/
msucme3d.llml.
lley can Le maniulaled jusl lile any ollei lind ol dala. Tlis advanlage was evidenl
liom lle eaily days ol comuleis, and success in iocessing salellile and saceciall
images geneialed consideiaLle inleiesl in Liomedical image iocessing, including aulo-
maled image analysis loi inleiielalion. Beginning in lle 1960s, ieseaicleis devoled a
laige amounl ol woil lo llis end, will lle loe llal evenlually mucl ol iadiogialic
image analysis could Le aulomaled.
One ol lle liisl aieas lo ieceive allenlion was aulomaled inleiielalion ol clesl
X-iay images, Lecause, ieviously, mosl alienls admilled lo a losilal weie suLjecled
lo iouline clesl X-iay examinalions. (Tlis iaclice is no longei consideied cosl elleclive
excel loi selecled suLgious ol alienls.) SuLsequenl ieseaicl, lowevei, conliimed lle
dillicully ol comlelely aulomaling iadiogialic image inleiielalion, and mucl ol lle
inilial enllusiasm las long ago woin oll. Cuiienlly, lleie is less emlasis on comlelely
aulomalic inleiielalion and moie on syslems llal aid lle usei, excel in secialized
aieas sucl as Liain imaging.
- - - --
Digilal image maniulalion, oi image processing, geneially involves lle liansloimalion
ol one oi moie inul images eillei inlo one oi moie oulul images oi inlo some
aLsliacl ieiesenlalion ol lle conlenls ol lle inul images. !oi examle, lle inlensily
values can Le modilied lo imiove conliasl iesolulion, oi a sel ol leims (
- ) can Le allacled lo secilic iegions ol inleiesl.
!mages can Le enlanced lo eimil luman viewing, lo slow views nol iesenl in lle
oiiginal images, lo llag susicious aieas loi closei examinalion Ly lle clinician, lo quan-
lily lle size and slae ol an oigan, and lo ieaie lle images loi inlegialion will ollei
inloimalion. Mosl ol llese alicalions iequiie one oi moie ol lle loui Lasic image-
iocessing sles: gloLal iocessing, segmenlalion, lealuie deleclion, and classilicalion.
Tlese sles aie geneially eiloimed in oidei, alllougl lalei sles may leed Lacl lo eai-
liei ones, and nol all sles aie iequiied loi eacl alicalion. Mosl sles geneialize liom
lwo-dimensional lo lliee-dimensional images, Lul lliee-dimensional images give iise lo
addilional image-iocessing ooilunilies and clallenges llal aie discussed in Seclion 9.5.
Global processing involves comulalions on lle enliie image, willoul iegaid lo se-
cilic local conlenl. Tle uiose is lo enlance an image loi luman visualizalion oi loi
luillei analysis Ly lle comulei. A simle Lul imoilanl examle is -
ol CT images. Tle CT scannei geneiales ixel values (Hounslield numLeis, oi
CT numLeis) in lle iange ol 1,000 lo 3,000. Humans, lowevei, cannol dislinguisl
moie llan aLoul 100 slades ol giay. To aieciale lle lull iecision availaLle will a CT
image, lle oeialoi can adjusl lle midoinl and lle iange ol lle dislayed CT values.
By clanging lle level and widll (i.e., inleicel and sloe ol lle maing Lelween ixel
value and dislayed giay scale oi, iouglly, lle Liigllness and conliasl) ol lle dislay,
iadiologisls enlance lleii aLilily lo eiceive small clanges in conliasl iesolulion willin
a suLiegion ol inleiesl.
Segmentation involves lle exliaclion ol iegions ol inleiesl (RO!s) liom lle oveiall
image. Tle RO!s usually coiiesond lo analomically meaninglul sliucluies, sucl as
oigans oi ails ol oigans. Tle sliucluies may Le delinealed Ly lleii Loideis, in wlicl
case edge-detection techniques (sucl as edge-lollowing algoiillms) aie used, oi Ly lleii
comosilion on lle image, in wlicl case region-detection techniques (sucl as lexluie
analysis) aie used (Haialicl and Slaiio, 1992). eillei ol llese leclniques las Leen
comlelely successlul; iegions ollen lave disconlinuous Loideis oi nondislinclive inlei-
nal comosilion. !uilleimoie, conliguous iegions ollen oveila. Tlese and ollei com-
licalions male segmenlalion lle mosl dillicull suLlasl ol lle medical image-analysis
ioLlem. Because segmenlalion is dillicull loi a comulei, il is ollen eiloimed
manually Ly a luman oeialoi oi lliougl a comLinalion ol aulomaled and oeialoi-
inleiaclive aioacles. !l lleieloie iemains a majoi Lolllenecl llal ievenls moie
widesiead alicalion ol image-iocessing leclniques.
Feature detection is lle iocess ol exliacling uselul aiameleis liom lle segmenled
iegions. Tlese aiameleis may llemselves Le inloimaliveloi examle, lle volume ol
lle leail oi lle size ol lle lelus. Tley also may Le used as inul inlo an aulomaled clas-
sification ioceduie, wlicl deleimines lle lye ol oLjecl lound. !oi examle, small
iound iegions on clesl X-iay images migll Le classilied as lumois, deending on sucl
lealuies as inlensily, eiimelei, and aiea.
Mallemalical models ollen aie used lo aid in lle eiloimance ol image-analysis suL-
lasls. !n classic allein-iecognilion alicalions, lle suLlasls ol gloLal iocessing, seg-
menlalion, lealuie deleclion, and classilicalion usually aie eiloimed sequenlially.
Peole, lowevei, aeai lo eiloim allein-iecognilion ileialively. !oi examle, iadiol-
ogisls can eiceive lainl images and can liace disconlinuous Loideis, in ail Lecause
lley lnow wlicl lealuies lley aie seaicling loi. Many ieseaicleis lave alied ailili-
cial inlelligence leclniques lo imilale sucl inleiaclion among suLlasls. Tle comulei is
iogiammed will some ol lle liglei-level analomic lnowledge llal iadiologisls use
wlen lley inleiiel images. Tlus, ligl-level oigan models iovide leedLacl lo guide
lle lowei-level iocess ol segmenlalion.
Tle naluie ol lle alicalion deleimines wlicl ol llese suLlasls is eiloimed, lle
cloice ol leclnique loi eacl suLlasl, and lle ielalive oidei ol lle suLlasls. Because
image undeislanding is an unsolved ioLlem, and Lecause many alicalions aie
ossiLle, lleie is a wealll ol image-iocessing leclniques llal can Le alied lo digilal
images.
- - --
Alllougl comlelely aulomaled image-analysis syslems aie slill in lle luluie, lle wide-
siead availaLilily ol digilal images, comLined will image managemenl syslems sucl as
icluie aicliving and communicalion syslems (PACS; Clalei 18) and oweilul woil-
slalions, las led lo many alicalions ol image-iocessing leclniques. !n geneial, iou-
line leclniques aie availaLle on lle manulacluieis woilslalions (e.g., an MR console
oi an ulliasound macline), wleieas moie advanced image-iocessing algoiillms aie
availaLle as sollwaie aclages llal iun on indeendenl woilslalions.
Tle iimaiy uses ol lwo-dimensional image iocessing in lle clinical enviionmenl
aie loi image enlancemenl, scieening, and quanlilalion. Sollwaie loi sucl image io-
cessing is iimaiily develoed loi use on indeendenl woilslalions. Seveial jouinals
aie devoled lo medical image iocessing (e.g., --
), and lle numLei ol jouinal ailicles is iaidly
incieasing as digilal images Lecome moie widely availaLle. We desciiLe jusl a lew
examles ol image-iocessing leclniques in lle iemaindei ol llis seclion.
Image enhancement uses gloLal iocessing lo imiove lle aeaiance ol lle image
eillei loi luman use oi loi suLsequenl iocessing Ly comulei. All manulacluieis con-
soles and indeendenl image-iocessing woilslalions iovide some loim ol image
enlancemenl. We lave alieady menlioned CT windowing. Anollei leclnique is unsharp
masking, in wlicl a Lluiied image is suLliacled liom lle oiiginal image lo inciease local
conliasl and lo enlance lle visiLilily ol line-delail (ligl-liequency) sliucluies.
Histogram equalization sieads lle image giay levels lliougloul lle visiLle iange lo
maximize lle visiLilily ol llose giay levels llal aie used liequenlly. Temporal subtrac-
tion suLliacls a ieleience image liom lalei images llal aie iegisleied lo lle liisl. A com-
mon use ol lemoial suLliaclion is digilal-suLliaclion angiogialy (DSA) in wlicl a
Laclgiound image is suLliacled liom an image lalen allei lle injeclion ol conliasl
maleiial.
Screening uses gloLal iocessing, segmenlalion, lealuie deleclion, and classilicalion
lo deleimine wlellei an image slould Le llagged loi caielul ieview Ly a iadiologisl oi
allologisl. !n sucl an aioacl, lle comulei is allowed lo llag a ieasonaLle numLei
ol noimal images (lalse osilives) as long as il misses veiy lew aLnoimal images (lalse
negalives). !l lle numLei ol llagged images is small comaied will lle lolal numLei ol
images, llen aulomaled scieening ioceduies can Le economically viaLle. Scieening
leclniques lave Leen alied successlully lo mammogialy images loi idenlilying mass
lesions and clusleis ol miciocalcilicalions, lo clesl X-iays loi small canceious nodules,
and lo Paanicolaou (Pa) smeais loi canceious oi iecanceious cells (Gigei and
MacMalon, 1996), as well as lo many ollei images (!iguie 9.3; see also Coloi Plale !).
Quantitation uses gloLal iocessing and segmenlalion lo claiacleiize meaninglul
iegions ol inleiesl. !oi examle, leail size, slae, and molion aie suLlle indicalois ol
leail lunclion and ol lle iesonse ol lle leail lo lleiay (Claiysse el al., 1997).
Similaily, lelal lead size and lemui lengll, as measuied on ulliasound images, aie valu-
aLle indicalois ol lelal well-Leing (Biinlley, 1993L). Alllougl lle lileialuie desciiLes a
wealll ol aulomalic oi semiaulomalic leclniques loi segmenling images ol lle leail oi
ol lle lelus, lle mosl common clinical scenaiio conlinues lo Le manual oullining Ly
liained leclnicians. Tlis silualion slould clange, lowevei, as semiaulomalic leclniques
(llose llal lel lle usei coiiecl segmenlalion eiiois Ly lle comulei) Lecome widely avail-
aLle on indeendenl woilslalions llal aie cuslom-lailoied loi ailiculai alicalions.
9.5 Three-Dimensional Image Processing
Tle giowing availaLilily ol lliee-dimensional and liglei dimensionalily sliucluial and
lunclional images (Seclion 9.3.3) leads lo exciling ooilunilies loi iealislically oLseiv-
ing lle sliucluie and lunclion ol lle Lody. owleie lave llese ooilunilies Leen moie
widely exloiled llan in Liain imaging. Tleieloie, llis seclion concenliales on lliee-
dimensional Liain imaging, will lle iecognilion llal many ol lle mellods develoed
loi lle Liain lave Leen oi will Le alied lo ollei aieas as well.
Tle Lasic lwo-dimensional image-iocessing oeialions ol gloLal iocessing, seg-
menlalion, lealuie deleclion, and classilicalion geneialize lo liglei dimensions, and aie
usually ail ol any image-iocessing alicalion. Howevei, lliee-dimensional and
liglei dimensionalily images give iise lo addilional inloimalics issues, wlicl include
Figure 9.3. Aulomaled scieening ol Paanicolaou (PAP) smeais. Since laige numLeis ol PAP
smeais aie acquiied ioulinely, lleie is a need lo ieduce lle cosl and olenlial eiiois associaled
will uiely manual inleiielalion. (A) Raw micioscoic image ol ceivical cells. (B) Segmenled
image. Tle iogiam las segmenled lle cells and nuclei liom lle iaw image, iioi lo lealuie delec-
lion and classilicalion Lased on lle lealuies. ALnoimally classilied cells aie llagged loi ieview Ly
lle luman oeialoi. Plologial couilesy ol Pelei Iocll, VisiLle Diagnoslics, lll://www.
imm.dlu.dl/visiondag/VD03/medicinsl/l.dl.
image registration (wlicl also occuis lo a lessei exlenl in lwo dimensions), - ie-
iesenlalion ol analomy, - ieiesenlalion ol analomy, inlegialion ol salial and
symLolic analomic ieiesenlalions in --, analomic , and
ol analomy. All Lul lle liisl ol llese issues deal iimaiily will analomic sliucluie, and
lleieloie could Le consideied ail ol lle lield ol sliucluial inloimalics. Tley could also
Le llougll ol as Leing ail ol imaging inloimalics and neuioinloimalics.
Tle lollowing seclions discuss llese addilional inloimalics issues.
-
As noled ieviously, lliee-dimensional image volume dala aie ieiesenled in lle com-
ulei Ly a lliee-dimensional volume aiiay, in wlicl eacl (volume elemenl, anal-
ogous lo lle ixel in lwo dimensions) ieiesenls lle image inlensily in a small volume
ol sace. !n oidei lo accuialely deicl analomy, lle voxels musl Le accuialely iegisleied
(oi localed) in lle lliee-dimensional volume ( -), and seaialely
acquiied image volumes liom lle same suLjecl musl Le iegisleied will eacl ollei (
-).
Voxel Registration
Teclnologies sucl as CT, MR!, MRV, MRA, and conlocal micioscoy (Seclion 9.3) aie
inleienlly lliee-dimensional; lle scannei geneially oululs a seiies ol image slices llal
can easily Le ieloimalled as a lliee-dimensional volume aiiay, ollen lollowing align-
menl algoiillms llal comensale loi any alienl molion duiing lle scanning ioceduie.
!oi llis ieason, almosl all CT and MR manulacluieis consoles conlain some loim ol
lliee-dimensional ieconsliuclion and visualizalion caaLililies.
As noled in Seclion 9.3.3, lwo-dimensional images can Le conveiled lo lliee-dimen-
sional volumes Ly acquiiing a sel ol closely saced aiallel seclions lliougl a lissue oi
wlole secimen. !n llis case lle ioLlem is low lo align lle seclions will eacl ollei.
!oi wlole seclions (eillei liozen oi lixed), lle slandaid mellod is lo emLed a sel ol llin
iods oi sliings in lle lissue iioi lo seclioning, lo manually indicale lle localion ol
llese - on eacl seclion, llen lo lineaily liansloim eacl slice so llal lle coiie-
sonding liducials line u in lliee dimensions (Piolleio and Piolleio, 1986). A ou-
lai cuiienl examle ol llis leclnique is lle VisiLle Human, in wlicl a seiies ol
liansveise slices weie acquiied, llen ieconsliucled lo give a lull lliee-dimensional vol-
ume (Silzei and Wlillocl, 1998).
!l is dillicull lo emLed liducial maileis al lle micioscoic level, so inliinsic lissue
landmails aie ollen used as liducials, Lul lle Lasic iincile is similai. Howevei, in llis
case lissue disloilion may Le a ioLlem, so nonlineai liansloimalions may Le iequiied.
!oi examle, !iala and Haiiis (2001) lave develoed an inleilace llal allows lle usei
lo indicale, on eleclion-micioscoy seclions, coiiesonding cenleis ol small oiganelles
sucl as miloclondiia. A nonlineai liansloimalion (wai) is llen comuled lo Liing lle
landmails inlo iegislialion.
An aioacl Leing uisued (among ollei aioacles) Ly lle alional Cenlei loi
Micioscoy and !maging Reseaicl (lll://ncmii.ucsd.edu/) comLines ieconsliuclion
liom llicl seiial seclions will eleclion lomogialy (Solo el al., 1994). !n llis case lle
lomogialic leclnique is alied lo eacl llicl seclion lo geneiale a lliee-dimensional
digilal slaL, allei wlicl lle slaLs aie aligned will eacl ollei lo geneiale a lliee-
dimensional volume. Tle advanlages ol llis aioacl ovei lle slandaid seiial seclion
mellod aie llal lle seclions do nol need lo Le as llin, and lewei ol llem need Le acquiied.
An alleinalive aioacl lo lliee-dimensional voxel iegislialion liom lwo-
dimensional images is sleieo-malcling, a leclnique develoed in comulei vision llal
acquiies mullile lwo-dimensional images liom lnown angles, wlicl linds coiieson-
ding oinls on lle images, and uses lle coiiesondences and lnown cameia angles lo
comule lliee-dimensional cooidinales ol ixels in lle malcled images. Tle leclnique
is Leing alied lo lle ieconsliuclion ol synases liom eleclion miciogials Ly a HBP
collaLoialion Lelween comulei scienlisls and Liologisls al lle \niveisily ol Maiyland
(Agiawal el al., 2000).
Volume Registration
A ielaled ioLlem lo llal ol aligning individual seclions is lle ioLlem ol aligning se-
aiale image volumes liom lle same suLjecl, i.e., - alignmenl. Because dillei-
enl image modalilies iovide comlemenlaiy inloimalion, il is common lo acquiie
moie llan one lind ol image volume on lle same individual. Tlis aioacl las Leen
ailiculaily uselul loi Liain imaging Lecause eacl modalily iovides dilleienl inloima-
lion. !oi examle, PLT (Seclion 9.3.2) iovides uselul inloimalion aLoul lunclion, Lul
does nol iovide good localizalion will iesecl lo analomy. Similaily, MRV and MRA
(Seclion 9.3.5) slow Llood llow Lul do nol iovide lle delailed analomy visiLle will
slandaid MR!. By comLining images liom llese modalilies will MR!, we can slow
lunclional images in leims ol lle undeilying analomy, lleieLy ioviding a common
neuioanalomic liamewoil.
!n oui own (1B) HBP woil, we acquiie an MR! volume dalasel deicling coilical
analomy, an MRV volume deicling veins, and an MRA volume deicling aileiies
(Modayui el al., 1997; Hinslaw el al., 2002). By lusing llese seaiale modalilies inlo a
single common liame ol ieleience (analomy, as given Ly lle MR! dalasel), il is ossiLle
lo gain inloimalion llal is nol aaienl liom one ol lle modalilies alone. !n oui case lle
lused dalasels aie used lo geneiale a visualizalion ol lle Liain suilace as il aeais al
neuiosuigeiy, in wlicl lle veins and aileiies iovide iominenl landmails (!iguie 9.9).
Tle iimaiy ioLlem lo solve in multimodality image fusion is volume iegislialion
llal is, lle alignmenl ol seaialely acquiied image volumes. !n lle simlesl case, sea-
iale image volumes aie acquiied duiing a single silling. Tle alienls lead may Le
immoLilized, and lle inloimalion in lle image leadeis may Le used lo iolale and
iesamle lle image volumes unlil all lle voxels coiiesond.
Howevei, il lle alienl moves, oi il examinalions aie acquiied al dilleienl limes,
ollei iegislialion mellods aie needed. Wlen inlensily values aie similai acioss modal-
ilies, iegislialion can Le eiloimed aulomalically Ly inlensily-Lased olimizalion
mellods (Woods el al., 1992; Collins el al., 1994). Wlen inlensily values aie nol similai
(as is lle case will MRA, MRV, and MR!), images can Le aligned lo lemlales ol lle
same modalilies llal aie alieady aligned (Woods el al., 1993; AslLuinei and !iislon,
1997). Alleinalively, landmail-Lased mellods can Le used. Tle landmail-Lased mell-
ods aie similai lo llose used lo align seiial seclions, Lul in llis case lle landmails aie
lliee-dimensional oinls. Tle Monlieal Regislei Piogiam (MacDonald, 1993) (wlicl
can also do nonlineai iegislialion, as discussed in Seclion 9.5.5) is an examle ol sucl
a iogiam.
-
Tle ieconsliucled and iegisleied lliee-dimensional image volumes can Le visualized
diieclly using volume rendering leclniques (!oley el al., 1990; IicllenLell el al., 1998)
(!iguie 9.2) wlicl iojecl a lwo-dimensional image diieclly liom a lliee-dimensional
voxel aiiay Ly casling iays liom lle eye ol lle oLseivei lliougl lle volume aiiay lo lle
image lane. Because eacl iay asses lliougl many voxels, some loim ol segmenlalion
(usually simle llieslolding) ollen is used lo iemove oLscuiing sliucluies. As woilsla-
lion memoiy and iocessing owei lave advanced, volume iendeiing las Lecome
widely used lo dislay all soils ol lliee-dimensional voxel dalaianging liom cell
images ioduced Ly conlocal micioscoy lo lliee-dimensional ulliasound images, oi lo
Liain images ciealed liom MR! oi PLT.
Volume images can also Le given as inul lo image-Lased leclniques loi waiing lle
image volume ol one sliucluie lo ollei, as desciiLed in Seclion 9.5.5. Howevei, moie
commonly lle image volume is iocessed in oidei lo exliacl an exlicil - (oi quan-
lilalive) ieiesenlalion ol analomy. Sucl an exlicil ieiesenlalion eimils imioved
visualizalion, quanlilalive analysis ol sliucluie, comaiison ol analomy acioss a
oulalion, and maing ol lunclional dala. !l is llus a comonenl ol mosl ieseaicl
involving lliee-dimensional image iocessing.
Lxliaclion ol salial ieiesenlalions ol analomy, in lle loim ol lliee-dimensional sui-
laces oi volume iegions, is accomlisled Ly a lliee-dimensional geneializalion ol lle seg-
menlalion leclniques discussed in Seclion 9.4.1. As in lle lwo-dimensional case, lully
aulomaled segmenlalion is an unsolved ioLlem, as allesled lo Ly lle numLei ol aeis
aLoul llis suLjecl in -- . Howevei, Lecause ol lle
ligl qualily ol MR! Liain images, a gieal deal ol iogiess las Leen made in iecenl yeais
loi Liain imaging in ailiculai; in lacl, seveial sollwaie aclages do a ciediLle joL ol
aulomalic segmenlalion, ailiculaily loi noimal macioscoic Liain analomy in coilical
and suLcoilical iegions (Collins el al., 1995; !iislon el al., 1995; SuLiamaniam el al.,
1997; Dale el al., 1999; MacDonald el al., 2000; Biain !nnovalion B.V., 2001; !MR!DB
!mage Analysis Giou, 2001; Van Lssen el al., 2001; Hinslaw el al., 2002). Tle
HBP-lunded !nleinel Biain Segmenlalion Reosiloiy (Kennedy, 2001) is develoing a
ieosiloiy ol segmenled Liain images lo use in comaiing llese dilleienl mellods.
Poulai segmenlalion and ieconsliuclion leclniques include ieconsliuclion liom
seiial seclions, iegion-Lased mellods, edge-Lased mellods, model- oi lnowledge-Lased
mellods, and comLined mellods.
Reconstruction from Serial Sections
Tle classic aioacl lo exliacling analomy is lo manually oi semiaulomalically liace
lle conlouis ol sliucluies ol inleiesl on eacl ol a seiies ol aligned image slices, llen lo
tile a suilace ovei lle conlouis (Piolleio and Piolleio, 1982). Tle liled suilace usually
consisls ol an aiiay ol lliee-dimensional oinls connecled lo eacl ollei Ly edges lo
loim liiangulai lacels. Tle iesulling lliee-dimensional - - is llen in a loim
wleie il can Le luillei analyzed oi dislayed using slandaid lliee-dimensional suilace
iendeiing leclniques sucl as llose alied in lle comulei-geneialed lilm indusliy
(!oley, 2001).
eillei lully aulomalic conloui liacing noi lully aulomalic liling las Leen salislac-
loiily demonslialed in lle geneial case. Tlus, semiaulomalic conloui liacing lollowed
Ly semiaulomalic liling iemains lle mosl common mellod loi ieconsliuclion
liom seiial seclions, and ieconsliuclion liom seiial seclions ilsell iemains lle mellod
ol cloice loi exliacling micioscoic lliee-dimensional Liain analomy (!iala and
Haiiis, 2001).
Region-Based and Edge-Based Segmentation
Tlis and lle lollowing seclions iimaiily concenliale on segmenlalion al lle macio-
scoic level.
!n iegion-Lased segmenlalion, voxels aie gioued inlo conliguous iegions Lased on
claiacleiislics sucl as inlensily ianges and similaiily lo neiglLoiing voxels (Slaiio
and Sloclman, 2001). A common inilial aioacl lo iegion-Lased segmenlalion is lo
liisl classily voxels inlo a small numLei ol lissue classes sucl as giay mallei, wlile mal-
lei, ceieLiosinal lluid, and Laclgiound, llen lo use llese classilicalions as a Lasis loi
luillei segmenlalion (Cloi el al., 1991; ZijdenLos el al., 1996). Anollei iegion-Lased
aioacl is called iegion giowing, in wlicl iegions aie giown liom seed voxels manu-
ally oi aulomalically laced willin candidale iegions (Davalzilos and Biyan, 1996;
Modayui el al., 1997). Tle iegions lound Ly any ol llese aioacles aie ollen luillei
iocessed Ly mallemalical moilology oeialois (Haialicl, 1988) lo iemove unwanled
conneclions and loles (Sandoi and Iealy, 1997).
Ldge-Lased segmenlalion is lle comlemenl lo iegion-Lased segmenlalion; inlensily
giadienls aie used lo seaicl loi and linl oigan Loundaiies. !n lle lwo-dimensional case,
conloui-lollowing mellods connecls adjacenl oinls on lle Loundaiy. !n lle lliee-
dimensional case, isosuilace-lollowing oi maicling-cuLes (Ioiensen and Cline, 1987)
mellods connecl Loidei voxels in a iegion inlo a lliee-dimensional suilace mesl.
Boll iegion-Lased and edge-Lased segmenlalion aie essenlially low-level leclniques
llal only lool al local iegions in lle image dala.
Model- and Knowledge-Based Segmentation
Tle mosl oulai cuiienl mellod loi medical image segmenlalion, loi lle Liain as well
as ollei Liological sliucluies, is lle use ol deformable models. Based on ioneeiing
woil called Snales Ly Kass el al. (1987), deloimaLle models lave Leen develoed loi
Loll lwo dimensions and lliee dimensions. !n lle lwo-dimensional case lle deloimaLle
model is a conloui, ollen ieiesenled as a simle sel ol lineai segmenls oi a -,
wlicl is inilialized lo aioximale lle conloui on lle image. Tle conloui is llen
deloimed accoiding lo a cosl lunclion llal includes Loll inliinsic leims limiling low
mucl lle conloui can disloil, and exliinsic leims llal iewaid closeness lo image
Loideis. !n lle lliee-dimensional case, a lliee-dimensional suilace (ollen a liiangulai
mesl) is deloimed in a similai mannei. Tleie aie seveial examles ol HBP-lunded woil
llal use deloimaLle models loi Liain segmenlalion (Davalzilos and Biyan, 1996; Dale
el al., 1999; MacDonald el al., 2000; Van Lssen el al., 2001).
An advanlage ol deloimaLle models is llal lle cosl lunclion can include lnowledge
ol lle execled analomy ol lle Liain. !oi examle, lle cosl lunclion emloyed in lle
mellod develoed Ly MacDonald (MacDonald el al., 2000) includes a leim loi lle
execled lliclness ol lle Liain coilex. Tlus, llese mellods can Lecome somewlal
lnowledge-Lased, wleie lnowledge ol analomy is encoded in lle cosl lunclion.
An alleinalive lnowledge-Lased aioacl exlicilly iecoids slae inloimalion in a
geomeliic consliainl nelwoil (GC) (Biinlley, 1992), wlicl encodes local slae vaii-
alion Lased on a liaining sel. Tle slae consliainls deline seaicl iegions on lle image
in wlicl lo seaicl loi edges. !ound edges aie llen comLined will lle slae consliainls
lo deloim lle model and ieduce lle size ol seaicl iegions loi addilional edges
(Biinlley, 1985, 1993a). One olenlial advanlage ol llis soil ol model ovei a uie
deloimaLle model is llal lnowledge is exlicilly ieiesenled in lle model, iallei llan
imlicilly ieiesenled in lle cosl lunclion.
Combined Methods
Mosl Liain segmenlalion aclages use a comLinalion ol mellods in a sequenlial
ieline. !oi examle, in oui own iecenl woil (1B) we liisl use a GC model lo ie-
iesenl lle oveiall coilical enveloe, excluding lle delailed gyii and sulci (Hinslaw
el al., 2002). Tle model is semiaulomalically deloimed lo lil lle coilex, llen used as
a masl lo iemove noncoilex sucl as lle slull. !sosuilace lollowing is llen alied lo
lle masled iegion lo geneiale lle delailed coilical suilace. Tle model is also used on
aligned MRA and MRV images lo masl oul noncoilical veins and aileiies iioi lo
isosuilace lollowing. Tle exliacled coilical, vein, and aileiy suilaces aie llen ien-
deied lo ioduce a comosile visualizalion ol lle Liain as seen al neuiosuigeiy
(!iguie 9.9).
MacDonald el al. (2000) desciiLe an aulomalic mulliiesolulion suilace deloima-
lion leclnique called analomic segmenlalion using ioximilies (ASP), in wlicl an
innei and oulei suilace aie iogiessively deloimed lo lil lle image, wleie lle cosl
lunclion includes image leims, model-Lased leims, and ioximily leims. Dale el al.
(1999) desciiLe an aulomaled aioacl llal is imlemenled in lle !ieeSuilei io-
giam (!iscll el al., 1999). Tlis mellod inilially linds lle giay-wlile Loundaiy, llen
lils smooll giay-wlile (innei) and wlile-CS! (oulei) suilaces using deloimaLle mod-
els. Van Lssen el al. (2001) desciiLe lle Suie!il iogiam, wlicl linds lle coilical
suilace midway Lelween lle giay-wlile Loundaiy and lle giay-CS! Loundaiy. Tlis
mid-level suilace is ciealed liom ioLaLilislic ieiesenlalions ol Loll innei and
oulei Loundaiies llal aie deleimined using image inlensily, inlensily giadienls, and
lnowledge ol coilical loogialy. Ollei sollwaie aclages also comLine vaiious
mellods loi segmenlalion (Davalzilos and Biyan, 1996; Biain !nnovalion B.V., 2001;
!MR!DB !mage Analysis Giou, 2001; Sensoi Syslems !nc., 2001; Wellcome
Deailmenl ol Cognilive euiology, 2001).
-
Given segmenled analomic sliucluies, wlellei al lle macioscoic oi micioscoic level,
and wlellei ieiesenled as lliee-dimensional suilace mesles oi exliacled lliee-dimen-
sional iegions, il is ollen desiiaLle lo allacl laLels (names) lo lle sliucluies. !l lle
names aie diawn liom a conliolled leiminology lley can Le used as an index inlo a
dalaLase ol segmenled sliucluies, lleieLy ioviding a qualilalive means loi comaiing
sliucluies liom mullile suLjecls.
!l lle leims in lle vocaLulaiy aie oiganized inlo symLolic qualilalive models (ontolo-
gies) ol analomic concels and ielalionslis, lley can suoil syslems llal maniulale
and ieliieve segmenled sliucluies in inlelligenl ways. !l lle analomic onlologies aie
linled lo ollei onlologies ol lysiology and allology, lley can iovide incieasingly
solislicaled lnowledge aLoul lle ol lle vaiious images and ollei dala llal
aie incieasingly Lecoming availaLle in online dalaLases. !l is oui Leliel llal llis lind ol
lnowledge (Ly lle comulei, as oosed lo lle scienlisl) will Le iequiied in oidei lo
aclieve lle seamless inlegialion ol all loims ol imaging and nonimaging dala.
Al lle mosl lundamenlal level, (!nleinalional Analomical
omenclaluie Commillee, 1989) and ils successoi, (!edeialive
Commillee on Analomical Teiminology, 1998) iovide a classilicalion ol ollicially
sanclioned leims llal aie associaled will macioscoic and micioscoic analomical
sliucluies. Tlis canonical leim lisl, lowevei, las Leen suLslanlially exanded Ly syn-
onyms llal aie cuiienl in vaiious lields, and las also Leen augmenled Ly a laige num-
Lei ol new leims llal designale sliucluies omilled liom . Many
ol llese addilions aie iesenl in vaiious conliolled leiminologies (e.g., MeSH (alional
IiLiaiy ol Medicine, 1999), SOMLD (Saclman el al., 1997), Read Codes (Sclullz
el al., 1997), GAIL (Recloi el al., 1993)). \nlile llese vocaLulaiies aie
enliiely comulei-Lased, and lleieloie lend llemselves loi incoioialion in comulei-
Lased alicalions.
Tle mosl comlele iimale leiminology is -, develoed
Ly Bowden and Mailin al lle \niveisily ol Waslinglon (Bowden and Mailin, 1995).
-, wlicl is included as a lnowledge souice in lle alional IiLiaiy ol
Medicines \nilied Medical Ianguage Syslem (\MIS; see Clalei 7) (IindLeig el al.,
1993), is iimaiily oiganized as a ail-ol lieiaicly ol nesled sliucluies, will linls lo a
laige sel ol ancillaiy leims llal do nol lil inlo lle sliicl ail-ol lieiaicly. Ollei neu-
ioanalomical leiminologies lave also Leen develoed (Paxinos and Walson, 1986;
Swanson, 1992; Bloom and Young, 1993; !ianllin and Paxinos, 1997). A clallenge loi
Liomedical inloimalics is eillei lo come u will a single consensus leiminology oi lo
develo !nleinel lools llal allow liansaienl inlegialion ol disliiLuled Lul commonly
agieed-on leiminology, will local modilicalions.
Classilicalion and onlology iojecls lo dale lave locused iimaiily on aiianging lle
leims ol a ailiculai domain in lieiaiclies. As we noled will iesecl lo lle evalualion
ol (Rosse, 2000), insullicienl allenlion las Leen aid lo lle
ielalionslis Lelween llese leims. , as well as analomy seclions ol lle
conliolled medical leiminologies, mix -- - and - -ielalionslis in lle analomy
segmenls ol lleii lieiaiclies. Alllougl sucl leleiogeneily does nol inleileie will using
llese leim lisls loi leywoid-Lased ieliieval, llese iogiams will lail lo suoil liglei-
level lnowledge (ieasoning) iequiied loi lnowledge-Lased alicalions.
!n oui own Sliucluial !nloimalics Giou al lle \niveisily ol Waslinglon we (1B and
co-woileis) aie addiessing llis deliciency Ly develoing a
(!MA), (!iguie 9.4) wlicl we deline as a comielensive symLolic desciilion
ol lle sliucluial oiganizalion ol lle Lody, including analomical concels, lleii ie-
leiied names and synonyms, delinilions, alliiLules, and ielalionslis (Rosse el al., 1998;
Rosse and Mejino, 2003).
Tle !MA is Leing imlemenled in Piolege-2000, a liame-Lased lnowledge acquisilion
syslem develoed al Slanloid (Musen, 1998; Mejino el al., 2001). !n Piolege analomical
concels aie aiianged in classsuLclass lieiaiclies, will inleiilance ol delining alliiL-
ules along lle - linl, and ollei ielalionslis (e.g., ails, Liancles, salial
adjacencies) ieiesenled as addilional slols in lle liame. Tle !MA cuiienlly consisls
ol ovei 70,000 concels, ieiesenled Ly aLoul 100,000 leims, and aiianged in ovei
1.2 million linls using 110 lyes ol ielalionslis. Tlese concels ieiesenl sliucluies al
all levels: macioscoic (lo 1 mm iesolulion) cellulai, and maciomoleculai. Biain
Figure 9.4. Tle !oundalional Model Lxloiei, a WeL viewei loi lle liame-Lased \niveisily ol
Waslinglon !oundalional Model ol Analomy (!MA). Tle lell anel slows a lieiaiclical view
along lle ail ol linl. Hieiaiclies along ollei linls, sucl as is-a, Liancl-ol, liiLulaiy-ol, can also
Le viewed in llis anel. Tle iigll land anel slows lle delailed local and inleiiled alliiLules
(slols) associaled will a selecled sliucluie, in llis case lle lloiacic veileLial column. See also
!iguie 9.5. Plologial couilesy ol lle Sliucluial !nloimalics Giou, \niveisily ol Waslinglon.
sliucluies lave Leen added Ly inlegialing - will lle !MA as a
(!MA) (Mailin el al., 2001).
Oui Leliel is llal lle !MA will iove uselul loi symLolically oiganizing and inle-
gialing Liomedical inloimalion, ailiculaily llal oLlained liom images. Bul in oidei lo
answei nonliivial queiies in neuioscience and ollei Lasic science aieas, and lo develo
smail lools llal iely on dee lnowledge, addilional onlologies musl also Le devel-
oed, among ollei llings, loi lysiologic lunclions medialed Ly neuioliansmilleis, and
allologic iocesses and lleii clinical manileslalions, as well as loi lle iadiologic
aeaiances will wlicl lley coiielale. Tle ielalionslis llal exisl Lelween llese con-
cels and analomical ails ol lle Lody musl also Le exlicilly modeled. exl-geneia-
lion inloimalics elloils llal linl lle !MA and ollei analomical onlologies will
seaialely develoed lunclional onlologies will Le needed in oidei lo accomlisl llis
lye ol inlegialion.
--
Salial ieiesenlalions ol analomy, in lle loim ol segmenled iegions on lwo-dimen-
sional oi lliee-dimensional images, oi lliee-dimensional suilaces exliacled liom image
volumes, aie ollen comLined will symLolic ieiesenlalions lo loim digilal allases. A
digilal allas (wlicl loi llis clalei ieleis lo an allas ciealed liom lliee-dimensional
image dala lalen liom ieal suLjecls, as oosed lo ailisls illuslialions) is geneially cie-
aled liom a single individual, wlicl lleieloie seives as a canonical inslance ol lle
secies. Tiadilionally, allases lave Leen iimaiily used loi educalion, and mosl digilal
allases aie used lle same way.
As an examle in lwo dimensions, lle Digilal Analomisl !nleiaclive Allases (Sundslen
el al., 2000) weie ciealed Ly oullining RO!s on lwo-dimensional images (many ol wlicl
aie snaslols ol lliee-dimensional scenes geneialed Ly ieconsliuclion liom seiial sec-
lions) and laLeling lle iegions will leiminology liom lle !MA. Tle allases, wlicl aie
availaLle on lle WeL, eimil inleiaclive Liowsing wleie lle names ol sliucluies aie given
in iesonse lo mouse clicls; dynamic ciealion ol in diagiams, in wlicl selecled laLels
aie allacled lo iegions on lle images; and dynamically geneialed quizzes, in wlicl lle
usei is asled lo oinl lo sliucluies on lle image (Biinlley el al., 1997).
As an examle in lliee dimensions, lle Digilal Analomisl Dynamic Scene Geneialoi
(DSG, !iguie 9.5; see also Coloi Plale !!) cieales inleiaclive lliee-dimensional allases
on-lle-lly loi viewing and maniulalion ovei lle WeL (Biinlley el al., 1999; Wong
el al., 1999). !n llis case lle lliee-dimensional scenes geneialed Ly ieconsliuclion liom
seiial seclions aie Liolen down inlo lliee-dimensional iimilive mesles, eacl ol
wlicl coiiesonds lo an individual ail in lle !MA. !n iesonse lo commands sucl as
dislay lle Liancles ol lle coionaiy aileiies lle DSG lools u lle Liancles in lle
!MA, ieliieves lle lliee-dimensional model iimilives associaled will llose Liancles,
deleimines lle coloi loi eacl iimilive Lased on ils lye in lle !MA is-a lieiaicly,
iendeis lle assemLled scene as a lwo-dimensional snaslol, llen sends il lo a WeL-
Liowsei, wleie lle usei may clange lle cameia aiameleis, add new sliucluies, oi
selecl and liglligll sliucluies. Tle comlele scene may also Le downloaded loi viewing
in a VRMI Liowsei.
An examle ol a lliee-dimensional Liain allas ciealed liom lle VisiLle Human is
Voxelman (Holne el al., 1995), in wlicl eacl voxel in lle VisiLle Human lead is laLeled
will lle name ol an analomic sliucluie in a geneialized voxel model (Holne el al.,
1990), and liglly delailed lliee-dimensional scenes aie dynamically geneialed. Seveial
ollei Liain allases lave also Leen develoed iimaiily loi educalional use (1olnson and
Beclei, 2001; Slensaas and Milllouse, 2001).
!n leeing will lle lleme ol analomy as an oiganizing liamewoil, allases lave also
Leen develoed loi inlegialing lunclional dala liom mullile sludies (Bloom and
Young, 1993; Toga el al., 1994, 1995; Swanson, 1999; !ougeiousse el al., 2000; Rosen
el al., 2000; Mailin and Bowden, 2001). !n lleii oiiginal uLlisled loim llese allases
eimil manual diawing ol lunclional dala, sucl as neuioliansmillei disliiLulions, onlo
laid-coy iinlouls ol Liain seclions. Many ol llese allases lave Leen oi aie in lle
iocess ol Leing conveiled lo digilal loim. Tle IaLoialoiy ol euioimaging (IO!)
Figure 9.5. Tle Digilal Analomisl Dynamic Scene Geneialoi (see lexl). Tlis-scene was ciealed
Ly iequesling lle lollowing sliucluies liom lle scene geneialoi seivei: lle ails ol lle aoila, lle
Liancles ol lle ascending aoila, lle liiLulaiies ol lle iigll aliium, lle Liancles ol lle liacleo-
Lionclial liee, and lle ails ol lle lloiacic veileLial column. Tle seivei was llen iequesled lo
iolale lle cameia 45 degiees, and lo iovide lle name ol a sliucluie selecled will lle mouse, in
llis case lle lliid lloiacic veileLia. Tle selecled sliucluie was llen lidden (nole lle ga indi-
caled Ly lle aiiow). Tle lell liame slows a ailial view ol lle !MA ail ol lieiaicly loi lle llo-
iacic veileLial column. Clecled sliucluies aie associaled will lliee-dimensional iimilive
mesles llal weie loaded inlo lle scene. Plologial couilesy ol lle Sliucluial !nloimalics
Giou, \niveisily ol Waslinglon.
al \CIA las Leen ailiculaily aclive in lle develomenl and analysis ol digilal allases
(Toga, 2001L), and lle Callecl HBP las ieleased a WeL-accessiLle lliee-dimensional
mouse allas acquiied will micio-MR imaging (Dlenain el al., 2001).
Tle mosl widely used luman Liain allas is lle Talaiiacl allas, Lased on oslmoilem
seclions liom a 60-yeai-old woman (Talaiiacl and Touinoux, 1988). Tlis allas inlio-
duced a iooilional cooidinale syslem (ollen called Talaiiacl sace) wlicl consisls
ol 12 ieclangulai iegions ol lle laigel Liain llal aie iecewise alline liansloimed lo
coiiesonding iegions in lle allas. \sing llese liansloims (oi a simlilied single alline
liansloim Lased on lle anleiioi and osleiioi commissuies), a oinl in lle laigel Liain
can Le exiessed in Talaiiacl cooidinales, and lleieLy ielaled lo similaily liansloimed
oinls liom ollei Liains. Ollei luman Liain allases lave also Leen develoed (Holne
el al., 1992; Caviness el al., 1996; Diuiy and Van Lssen, 1997; SclallenLiand and
Waiien, 1977; Van Lssen and Diuiy, 1997).

Biain inloimalion syslems ollen use allases as a Lasis loi maing lunclional dala onlo
a common liamewoil, mucl lile geogialic inloimalion syslems (G!Ss) use lle eaill
as lle Lasis loi comLining dala. Howevei, unlile G!Ss, Liain inloimalion syslems musl
deal will lle lacl llal no lwo Liains aie exaclly alile, esecially in lle liglly lolded
luman ceieLial coilex. Tlus, nol only do Liain-imaging ieseaicleis lave lo develo
mellods loi ieiesenling individual Liain analomy, lley musl also develo mellods loi
ielaling lle analomy ol mullile Liains. Only Ly develoing mellods loi ielaling mul-
lile Liains will il Le ossiLle lo geneiale a common analomic liame ol ieleience loi
oiganizing neuioscience dala. Solving llis ioLlem is cuiienlly a majoi locus ol woil
in lle HBP and in imaging inloimalics in geneial.
Two geneial aioacles loi quanlilalively dealing will analomic vaiialion can Le
delined: (1) waiing lo a template atlas, and (2) population-based atlases. Vaiialion can
also Le exiessed in a qualilalive mannei, as desciiLed in lle seclion on qualilalive
classilicalion.
Warping to a Template Atlas
Tle mosl oulai cuiienl quanlilalive mellod loi dealing will analomic vaiialion is lo
deloim oi wai an individual laigel Liain lo a single Liain closen as a lemlale. !l lle
lemlale Liain las Leen segmenled and laLeled as an allas (Seclion 9.5.4), and il lle ieg-
islialion ol lle laigel Liain lo lle lemlale is exacl, llen lle laigel Liain will Le aulo-
malically segmenled, and any dala liom ollei sludies llal aie associaled will lle
lemlale Liain can Le aulomalically iegisleied will lle laigel Liain Ly inveiling lle
wai (Cliislensen el al., 1996; Toga and Tlomson, 2001). Sucl a ioceduie could Le
veiy uselul loi suigical lanning, loi examle, since lunclional aieas liom alienls
wlose demogialics malcl llal ol lle suigical alienl could Le sueiimosed on lle
alienls analomy (Kilinis el al., 1996).
Tle ioLlem, ol couise, comes will lle woid exacl. Since no lwo Liains aie even
loologically alile (sulci and gyii aie iesenl in one Liain llal aie nol iesenl in
anollei), il is imossiLle lo comlelely iegislei one Liain lo anollei. Tlus, lle ieseaicl
ioLlem, wlicl is veiy aclively Leing uisued Ly many HBP ieseaicleis (Toga and
Tlomson, 2001), is low lo iegislei lwo Liains as closely as ossiLle. Mellods loi doing
llis can Le divided inlo volume-Lased waiing and suilace-Lased waiing.
Volume-based warping. Puie volume-Lased iegislialion diieclly iegisleis lwo image
volumes, willoul lle ieiocessing segmenlalion sle. Wleieas inlia (single)-alienl
iegislialion (see Seclion 9.5.1) eslaLlisles a lineai liansloimalion Lelween lwo dalasels,
inlei (mullile)-alienl iegislialion eslaLlisles a nonlineai liansloimalion (wai) llal
ielales voxels in one volume lo coiiesonding voxels in lle ollei volume. Because ol lle
gieal vaiiaLilily ol lle ceieLial coilex uie volume-Lased iegislialion is Lesl suiled loi
suLcoilical sliucluies iallei llan lle coilex. As in lle lineai case lleie aie lwo Lasic
aioacles lo nonlineai volume iegislialion: -- and -, Loll
ol wlicl geneially use eillei lysically Lased aioacles oi minimizalion ol a cosl
lunclion lo aclieve lle olimal wai.
-- aioacl uses claiacleiislics ol lle voxels llemselves, geneially
willoul lle segmenlalion sle, lo nonlineaily align lwo image volumes (Gee el al.,
1993; Collins el al., 1995; Cliislensen el al., 1996; Kjems el al., 1999). Mosl slail Ly
iemoving lle slull, wlicl ollen musl Le done manually.
Tle - aioacl is analogous lo lle lwo-dimensional case; lle usei
manually indicales coiiesonding oinls in lle lwo dalasels (usually will lle aid ol
lliee oillogonal views ol lle image volumes). Tle iogiam llen Liings lle coiieson-
ding oinls inlo iegislialion wlile caiiying along lle inleivening voxel dala. Tle
Monlieal Regislei iogiam (MacDonald, 1993) can do nonlineai lliee-dimensional
wais, as can lle 3-D Ldgewai iogiam (Boolslein and Gieen, 2001), wlicl is a gen-
eializalion ol lle 2-D Ldgewai iogiam develoed Ly Boolslein (1989).
A vaiialion ol landmail-Lased waiing malcles cuives oi suilaces iallei llan
oinls, llen uses lle suilace wais as a Lasis loi inleiolaling lle wai loi inleivening
voxels (Tlomson and Toga, 1996; Davalzilos, 1997).
Surface-based warping. Suilace-Lased iegislialion is iimaiily used lo iegislei lwo
coilical suilaces. Tle suilace is liisl exliacled using leclniques desciiLed in Seclion
9.5.2, llen image-Lased oi ollei lunclional dala aie ainled on lle exliacled suilace
wleie lley aie caiiied along will wlalevei deloimalion is alied lo lle suilace. Since
lle coilical suilace is lle mosl vaiiaLle ail ol lle Liain, yel lle mosl inleiesling loi
many lunclional sludies, consideiaLle ieseaicl is cuiienlly Leing done in lle aiea ol
suilace-Lased iegislialion (Van Lssen el al., 1998).
!l is veiy dillicull il nol imossiLle lo malcl lwo suilaces in lleii lolded u slale, oi
lo visualize all lleii aclivily. (Tle ceieLial coilex giay mallei can Le llougll ol as a
lwo-dimensional sleel llal is essenlially ciumled u lo lil inside lle slull). Tleieloie,
mucl elloil las Leen devoled lo ieconliguiing (Van Lssen el al., 2001) lle coilex so
llal il is easiei lo visualize and iegislei (!iguie 9.6). A ieiequisile loi llese leclniques
is llal lle segmenled coilex musl Le loologically coiiecl. Tle iogiams !ieeSuilei
(Dale el al., 1999), Suielil (Van Lssen el al., 2001), ASP (MacDonald el al., 2000), and
olleis all ioduce suilaces suilaLle loi ieconliguialion.
Common ieconliguialion mellods include , - -, and
. unciumles lle delailed gyii and sulci ol lle lolded suilace Ly ailially
Llowing lle suilace u lile a Lalloon (!iscll el al., 1999; Biain !nnovalion B.V., 2001;
Van Lssen el al., 2001). Tle iesulling suilace lools lile a lissencelalic (smooll) Liain,
in wlicl only lle majoi loLes aie visiLle, and lle oiiginal sulci aie ainled on lle sui-
lace as dailei inlensily cuives. Tlese mails, along will any lunclional dala, aie caiiied
along in lle ollei ieconliguialion mellods as well.
- - luillei exands lle inllaled Liain lo a sleie, again will
ainled lines ieiesenling lle oiiginal gyii and sulci. Al llis oinl il is simle lo deline
a suilace-Lased cooidinale syslem as a seiies ol longiludelalilude lines ieleiied lo a
common oiigin. Tlis sleiical cooidinale syslem eimils moie iecise quanlilalive
comaiison ol dilleienl Liains llan lliee-dimensional Talaiiacl cooidinales Lecause il
iesecls lle loology ol lle coilical suilace. Tle suilace is also in a loim wleie essen-
lially lwo-dimensional waiing leclniques can Le alied lo deloim lle gyii and sulci
mailed on lle sleie lo a lemlale sleiical Liain.
Tle lliid aioacl is lo lle suilace Ly maling aililicial culs on lle inllaled
Liain suilace, llen sieading oul lle cul suilace on al lwo-dimensional lane
wlile minimizing disloilion (!iscll el al., 1999; Huidal el al., 2000; Van Lssen el al.,
2001). Since il is imossiLle lo eliminale disloilion wlen iojecling a sleie lo a lane,
Figure 9.6. Biain suilace ieconliguialion using lle Caiel sollwaie suile develoed Ly lle David
Van Lssen laLoialoiy al Waslinglon \niveisily (Van Lssen el al., 2001). Tle Liain suilace is liisl
segmenled (A), llen inllaled (B), exanded lo a sleie (C), and llallened (D). Al all slages any
sliucluial oi lunclional dala ainled on lle suilace aie caiiied along will lle ieconliguialion. !n
llis case lle Liain sulci aie ainled onlo lle suilace. Tle aiiows oinl lo lle sueiioi lemoial
sulcus in eacl conliguialion. Plologial couilesy ol lle S\MS dalaLase al Waslinglon
\niveisily (Van Lssen, 2002), lll://Liainma.wusll.edu:8081/sums/diiecloiy.do'dii_id=636032.
mullile mellods ol iojeclion lave Leen devised, jusl as lleie aie mullile mellods
loi iojecling lle eaills suilace (Toga and Tlomson, 2001). !n all cases, lle iesulling
llal ma, lile a lwo-dimensional allas ol lle eaill, is easiei lo visualize llan a lliee-
dimensional ieiesenlalion since lle enliie coilex is seen al once. Teclniques loi wai-
ing one coilex lo anollei aie alicaLle lo llal mas as well as sleiical mas, and lle
wais can Le inveiled lo ma ooled dala on lle individual exliacled coilical suilace.
Tle ioLlem ol waiing any ol llese ieconliguied suilaces lo a lemlale suilace is
slill an aclive aiea ol ieseaicl Lecause il is imossiLle lo comlelely malcl lwo coilical
suilaces. Tlus, mosl aioacles aie lieiaiclical, in wlicl laigei sulci sucl as lle laleial
and cenlial sulcus aie malcled liisl, lollowed Ly minoi sulci.
Population-Based Atlases
Tle main ioLlem will waiing lo a lemlale allas is deciding wlicl allas lo use as a
lemlale. Wlicl Liain slould Le consideied lle canonical Liain ieiesenling lle
oulalion' As noled ieviously, lle widely used Talaiiacl allas is Lased on a 60-yeai-
old woman. Tle VisiLle Human male was a 38-yeai-old convicl and lle lemale was an
oldei women. Wlal aLoul ollei oulalions sucl as dilleienl iacial gious' Tlese con-
sideialions lave iomled seveial gious lo woil on mellods loi develoing Liain
allases llal encode vaiialion among a oulalion, Le il lle enliie oulalion oi selecled
suLgious. Tle !nleinalional Consoilium loi Biain Maing (!CBM), a collaLoialion
among seveial Liain maing inslilulions seaileaded al \CIA (lll://www.
loni.ucla.edu/!CBM), is collecling laige numLeis ol noimal Liain-image volumes liom
collaLoialois aiound lle woild (Mazziolla el al., 2001). To dale seveial llousand Liain-
image volumes, many will DA samles loi lalei coiielalion ol analomy will genel-
ics, aie sloied on a massive lile seivei. As dala colleclion conlinues mellods aie undei
develomenl loi comLining llese dala inlo oulalion-Lased allases.
A good ligl-level desciilion ol llese mellods can Le lound in a ieview ailicle Ly Toga
and Tlomson (2001). !n llal ailicle lliee main mellods aie desciiLed loi develoing
oulalion-Lased allases: --, -, and - aioacles.
!n lle -- mellod, a sel ol Liains is liisl liansloimed lo Talaiiacl sace Ly
lineai iegislialion. Coiiesonding voxels aie llen aveiaged, yielding an aveiage Liain
llal ieseives lle majoi lealuies ol lle Liain Lul smoolles oul lle delailed sulci and
gyii (!iguie 9.7; see also Coloi Plale !!!). Tle Monlieal aveiage Liain, wlicl is an avei-
age ol 305 noimal Liains (Lvans el al., 1994), is consliucled in llis way. Alllougl nol
delailed enougl lo eimil iecise comaiisons ol analomic suilaces, il is neveilleless
uselul as a coaise means loi ielaling mullile lunclional siles. !oi examle, in oui own
woil (1B) we lave maed coilical language siles liom mullile alienls onlo lle avei-
age Liain, allowing a iougl comaiison ol lleii disliiLulion loi dilleienl alienl suL-
classes (Mailin el al., 2000).
!n lle - aioacl, a seiies ol Liains aie segmenled, and llen lineaily lians-
loimed lo Talaiiacl sace. A ioLaLilily ma is consliucled loi eacl segmenled sliuc-
luie, sucl llal al eacl voxel lle ioLaLilily can Le lound llal a given sliucluie is iesenl
al llal voxel localion. Tlis mellod las Leen imlemenled in lle Talaiiacl Demon, an
!nleinel seivei and 1ava clienl, develoed Ly !ox el al. as ail ol lle !CBM iojecl
(Iancaslei el al., 2000). A WeL usei inuls one oi moie sels ol Talaiiacl cooidinales,
and lle seivei ieluins a lisl ol sliucluie ioLaLililies loi llose cooidinales.
!n lle - mellod, lle slalislical ioeilies ol deloimalion lields io-
duced Ly nonlineai waiing leclniques (see Seclion 9.5.5) aie analyzed lo encode
analomic vaiialion in oulalion suLgious (Cliislensen el al., 1996; Tlomson
and Toga, 1997). Tlese allases can llen Le used lo delecl aLnoimal analomy in
vaiious diseases.

Tle main ieason loi linding ways lo ieiesenl analomy is lo examine lle ielalionsli
Lelween sliucluie and lunclion in Loll lealll and disease. !oi examle, low does lle
Liancling allein ol lle dendiilic liee inlluence lle lunclion ol lle dendiile' Does
lle allein ol coilical lolds inlluence lle disliiLulion ol language aieas in lle Liain'
Does lle slae ol lle coius callosum ielale lo a iedisosilion lo sclizolienia'
Figure 9.7. PioLaLilislic Liain allas, coional seclion. !ndividual MR! image volumes liom 53 suL-
jecls weie lineaily aligned, and eacl suLjecls loLes and dee nuclei weie manually delinealed.
Tlese delinealions weie aveiaged acioss lle suLjecls and used lo cieale ioLaLilily mas loi lle
lilelilood ol linding lle secilied loLe oi nuclei al a given voxel osilion. Lacl sliucluie is
deicled in a dilleienl coloi in lle coloi veision ol llis image. Tle inlensily ol lle coloi is io-
oilional lo lle ioLaLilily ol linding llal sliucluie al lle secilied localion. Plologial coui-
lesy ol Aillui Toga, IaLoialoiy loi euio !maging, \CIA. lll://www.loni.ucla.edu/CRR/
CRR.PioLaLilislic.llml.
Can suLlle clanges in Liain sliucluie Le used as a iedicloi loi lle onsel ol
Alzleimeis disease' Tlese linds ol queslions aie Lecoming incieasingly ossiLle lo
answei will lle availaLilily ol lle mellods desciiLed in lle ievious seclions.
Howevei, in oidei lo examine llese queslions, mellods musl Le lound loi claiaclei-
izing and classilying lle exliacled analomy. Boll qualilalive and quanlilalive
aioacles aie Leing develoed.
Qualitative Classification
Tle classical aioacl lo claiacleiizing analomy is loi lle luman Liologisl lo giou
individual sliucluies inlo vaiious classes Lased on eiceived alleins. Tlis aioacl is
slill widely used lliougloul science since lle comulei las yel lo malcl lle allein-
iecognilion aLililies ol lle luman Liain.
An examle classilicalion al lle cellulai level is lle 60 lo 80 moilologic cell lyes
llal loim lle Lasis loi undeislanding lle neuial ciicuiliy ol lle ielina (wlicl is an oul-
giowll ol lle Liain) (Dacey, 1999). Al lle macioscoic level, Ono las develoed an
allas ol ceieLial sulci llal can Le used lo claiacleiize an individual Liain Lased on
sulcal alleins (Ono el al., 1990).
!l llese and ollei classilicalions aie given syslemalic names and aie added lo lle
symLolic onlologies desciiLed in Seclion 9.5.3, lley can Le used loi inlelligenl index-
ing and ieliieval, allei wlicl quanlilalive mellods can Le used loi moie iecise clai-
acleiizalion ol sliucluielunclion ielalionslis.
Quantitative Classification
Quanlilalive claiacleiizalion ol analomy is ollen called - (Boolslein,
1997) oi (Ascioli, 1999). Quanlilalive claiacleiizalion
eimils moie suLlle classilicalion sclemes llan aie ossiLle will qualilalive mellods,
leading lo new insiglls inlo lle ielalion Lelween sliucluie and lunclion, and Lelween
sliucluie and disease (Toga, 2001a; Toga and Tlomson, 2001).
!oi examle, al lle ulliasliucluial level, -, wlicl is a slalislical mellod
loi eslimaling liom samled dala lle disliiLulion ol sliucluial comonenls in a
volume (WeiLel, 1979), is used lo eslimale lle densily ol oLjecls sucl as synases
in image volumes ieconsliucled liom seiial eleclion miciogials (!iala and Haiiis,
2001).
Al lle cellulai level Ascoli el al. aie engaged in lle I-neuion iojecl, wlicl allemls
lo model dendiilic moilology Ly a small sel ol aiameleiized geneialion iules, wleie
lle aiameleis aie samled liom disliiLulions deleimined liom exeiimenlal dala
(!iguie 9.8) (Ascioli, 1999). Tle iesulling dendiilic models caluie a laige sel ol den-
diilic moilologic classes liom only a small sel ol vaiiaLles. Lvenlually, lle loe is lo
geneiale viilual neuial ciicuils llal can simulale Liain lunclion.
Al lle macioscoic level landmail-Lased mellods lave slown clanges in lle slae
ol lle coius callosum associaled will sclizolienia llal aie nol oLvious liom visual
inseclion (DeQuaido el al., 1999). PioLaLilislic allas-Lased mellods aie Leing used lo
claiacleiize giowll alleins and disease-secilic sliucluial aLnoimalilies in diseases
sucl as Alzleimeis and sclizolienia (Tlomson el al., 2001). As llese leclniques
Lecome moie widely availaLle lo lle clinician, lley slould eimil eailiei diagnosis and
lence olenlial liealmenl loi llese deLililaling diseases.
9.6 Functional Imaging
Many imaging leclniques nol only slow lle sliucluie ol lle Lody Lul also lle lunclion.
!oi imaging uioses, lunclion can Le inleiied Ly oLseiving clanges ol sliucluie ovei
lime. !n iecenl yeais llis aLilily lo image lunclion las gieally acceleialed. !oi examle,
ulliasound and angiogialy aie widely used lo slow lle lunclioning ol lle leail Ly
deicling wall molion, and ulliasound dolei can image Loll noimal and disluiLed
Llood llow (Mella el al., 2000). Molecular imaging (Seclion 9.3.5) is incieasingly aLle lo
deicl lle exiession ol ailiculai genes sueiimosed on sliucluial images, and llus
can also Le seen as a loim ol lunclional imaging.
A ailiculaily iolound alicalion ol lunclional imaging is lle undeislanding ol
cognilive aclivily in lle Liain. !l is now ioulinely ossiLle lo ul a noimal suLjecl in a
scannei, lo give lle eison a cognilive lasl, sucl as counling oi oLjecl iecognilion, and
Figure 9.8. Tle I-neuion iojecl. Tle Liancling allein ol a given oulalion ol neuions is
modeled Ly a small sel ol aiameleis measuied liom exeiimenlal dala. Tlese aiameleis aie
used lo geneiale synllelic neuions (A lo D) llal lool veiy similai lo exeiimenlally ieconsliucled
neuions (L). Tle viilual cell dislayed in anels A lo D was ciealed will only 11 lines ol slo-
claslic iules lo iesemLle lle ieal 2107-comailmenl Puilinje cell slown in anel L. (A) !ionl
view; (B) side view; (C) delail on dendiilic Liancles; (D) delail on dendiilic sines. Plologial
couilesy ol Geoigio Ascioli, Geoige Mason \niveisily, lll://www.liasnow.gmu.edu/
ascoli/CG/index.llm. (Reiinled liom Ascoli, GA. Piogiess and Peiseclives in Comulalional
euioanalomy. Anal Rec. 257(6): 195-207. Coyiigll 1999, Wiley. Reiinled Ly Peimission ol
Wiley-Iiss !nc., A SuLsidiaiy ol 1oln Wiley & Sons, !nc.)
lo oLseive wlicl ails ol lle Liain ligll u. Tlis uniecedenled aLilily lo oLseive lle
lunclioning ol lle living Liain oens u enliiely new avenues loi exloiing low lle
Liain woils.
!unclional Liain-imaging modalilies can Le classilied as - oi
-. !n Loll cases il is lalen as axiomalic llal lle lunclional dala musl Le maed lo
lle individual suLjecls analomy, wleie lle analomy is exliacled liom sliucluial images
using leclniques desciiLed in lle ievious seclions. Once maed lo analomy, lle lunc-
lional dala can Le inlegialed will ollei lunclional dala liom lle same suLjecl, and will
lunclional dala liom ollei suLjecls wlose analomy las Leen ielaled lo a lemlale oi
ioLaLilislic allas. Teclniques loi geneialing, maing, and inlegialing lunclional dala
aie ail ol lle lield ol !unclional Biain Maing, wlicl las Lecome veiy aclive in lle
lasl lew yeais, will seveial conleiences (Oiganizalion loi Human Biain Maing, 2001)
and jouinals (!ox, 2001; Toga el al., 2001) devoled lo lle suLjecl.
-
!mage-Lased lunclional dala geneially come liom scanneis llal geneiale ielalively low-
iesolulion volume aiiays deicling salially localized aclivalion. !oi examle, PLT
(Heiss and Plels, 1983; Aine, 1995) and magnelic iesonance seclioscoy (MRS)
(Ross and Bluml, 2001) ieveal lle ulale ol vaiious melaLolic ioducls Ly lle lunc-
lioning Liain; and functional magnetic resonance imaging (fMRI) ieveals clanges in
Llood oxygenalion llal occui lollowing neuial aclivily (Aine, 1995). Tle iaw inlensily
values geneialed Ly llese leclniques musl Le iocessed Ly solislicaled slalislical algo-
iillms lo soil oul low mucl ol lle oLseived inlensily is due lo cognilive aclivily and
low mucl is due lo Laclgiound noise.
As an examle, one aioacl lo lMR! imaging is lle Loxcai aiadigm alied lo lan-
guage maing (Coiina el al., 2000). Tle suLjecl is laced in lle MR! scannei and lold
lo silenlly name oLjecls slown al 3-second inleivals on a lead-mounled dislay. Tle
aclual oLjecls (on slale) aie alleinaled will nonsense oLjecls (oll slale), and lle
lMR! signal is measuied duiing Loll lle on and lle oll slales. Lssenlially lle voxel val-
ues al lle oll (oi conliol) slale aie suLliacled liom llose al lle on slale. Tle dilleience
values aie lesled loi signilicanl dilleience liom nonaclivaled aieas, llen exiessed as
-values. Tle voxel aiiay ol -values can Le dislayed as an image.
A laige numLei ol alleinalive mellods lave Leen and aie Leing develoed loi acquii-
ing and analyzing lunclional dala (!iaclowial el al., 1997). Tle oulul ol mosl ol llese
leclniques is a low-iesolulion lliee-dimensional image volume in wlicl eacl voxel
value is a measuie ol lle amounl ol aclivalion loi a given lasl. Tle low-iesolulion vol-
ume is llen maed lo analomy Ly lineai iegislialion lo a ligl-iesolulion sliucluial
MR dalasel, using one ol lle lineai iegislialion leclniques desciiLed in Seclion 9.5.1.
Many ol llese and ollei leclniques aie imlemenled in lle SPM iogiam (!iislon
el al., 1995), lle A!! iogiam (Cox, 1996), lle IyngLy loollil (Hansen el al., 1999),
and seveial commeicial iogiams sucl as Medex (Sensoi Syslems !nc., 2001), and
BiainVoyagei (Biain !nnovalion B.V., 2001). Tle !isWidgels iojecl al lle \niveisily
ol PillsLuigl is develoing a sel ol 1ava wiaeis loi many ol llese iogiams llal allow
cuslomized ciealion ol gialical usei inleilaces in an inlegialed desllo enviionmenl
(Colen, 2001). A similai elloil (VoxBox) is undeiway al lle \niveisily ol Pennsylvania
(KimLoig and Aguiiie, 2002).
-
!n addilion lo lle image-Lased lunclional mellods lleie aie an incieasing numLei ol
leclniques llal do nol diieclly geneiale images. Tle dala liom llese leclniques aie gen-
eially maed lo analomy, and llen dislayed as lunclional oveilays on analomic
images.
!oi examle, coilical slimulalion maing (CSM) is a leclnique loi localizing lunc-
lional aieas on lle exosed coilex al lle lime ol neuiosuigeiy (!iguie 9.9; see also
Coloi Plale !V). !n oui own woil (1B) lle leclnique is used lo localize coilical language
aieas so llal lley can Le avoided duiing lle ieseclion ol a lumoi oi eilelic locus
(Ojemann el al., 1989). !ollowing iemoval ol a oilion ol lle slull (cianiolomy) lle
alienl is awalened and asled lo name common images slown on slides. Duiing llis
Figure 9.9. Remole visualizalion ol inlegialed sliucluial and lunclional Liain dala maed onlo
a single alienls Liain. MR!, MRV (veins), and MRA (aileiies) Liain-image volumes aie
acquiied and iegisleied, llen segmenled lo geneiale lle coilical suilace, aileiies, and Liains.
lMR! dala ieiesenling aieas ol language iocessing aie iegisleied lo lle sliucluial volumes,
llen iojecled lo lle suilace as lle ligll-coloied iegions. Coilical slimulalion maing (CSM)
dala (small sleies) acquiied duiing neuiosuigeiy aie also iegisleied lo lle alienls analomy.
Tle inlegialed dala aie iendeied on a visualizalion seivei, wlicl can Le accessed liom a weL
Liowsei using a simle 1ava alel. Plologial couilesy ol lle Sliucluial !nloimalics Giou,
\niveisily ol Waslinglon.
lime lle suigeon alies a small elecliical cuiienl lo eacl ol a sel ol numLeied lags
laced on lle coilical suilace. !l lle alienl is unaLle lo name lle oLjecl wlile lle cui-
ienl is alied lle sile is inleiieled as essenlial loi language and is avoided al suigeiy.
!n llis case, lle lunclional-maing ioLlem is low lo ielale llese slimulalion siles lo
lle alienls analomy as seen on an MR! scan.
Oui aioacl, wlicl we call visualizalion-Lased maing (Modayui el al., 1997;
Hinslaw el al., 2002), is lo acquiie image volumes ol Liain analomy (MR!), ceieLial
veins (MRV), and ceieLial aileiies (MRA) iioi lo suigeiy, lo segmenl lle analomy,
veins, and aileiies liom llese images, and lo geneiale a suilace-iendeied lliee-
dimensional model ol lle Liain and ils vessels llal malcles as closely as ossiLle lle
coilical suilace as seen al neuiosuigeiy. A visual-maing iogiam llen eimils lle
usei lo diag numLeied lags onlo lle iendeied suilace sucl llal lley malcl llose seen
on lle inliaoeialive lologial. Tle iogiam iojecls lle diagged lags onlo lle
ieconsliucled suilace, and iecoids lle x-y-z image-sace cooidinales ol lle iojeclions,
lleieLy comleling lle maing.
Tle ieal goal ol lunclional neuioimaging is lo oLseive lle aclual elecliical aclivily ol
lle neuions as lley eiloim vaiious cognilive lasls. lMR!, MRS, and PLT do nol
diieclly iecoid elecliical aclivily. Rallei, lley iecoid lle iesulls ol elecliical aclivily,
sucl as (in lle case ol lMR!) lle oxygenalion ol Llood sulying lle aclive neuions.
Tlus, lleie is a delay liom lle lime ol aclivily lo lle measuied iesonse. !n ollei woids
llese leclniques lave ielalively ooi lemoial iesolulion (Seclion 9.2.2).
Electroencephalography (EEG) oi magnetoencephalography (MEG), on lle ollei land,
aie moie diiecl measuies ol elecliical aclivily since lley measuie lle elecliomagnelic
lields geneialed Ly lle elecliical aclivily ol lle neuions. Cuiienl LLG and MLG mell-
ods involve lle use ol laige aiiays ol scal sensois, lle oulul ol wlicl aie iocessed
in a similai way lo CT in oidei lo localize lle souice ol lle elecliical aclivily inside lle
Liain. !n geneial llis souice-localizalion ioLlem is undei-consliained, so inloima-
lion aLoul Liain analomy oLlained liom MR! is used lo iovide luillei consliainls
(Geoige el al., 1995).
9.7 Conclusions
Tlis clalei locuses on mellods loi iocessing images in Liomedicine, will an emla-
sis on Liain imaging and lle exliaclion and claiacleiizalion ol analomic sliucluie,
Loll loi ils own sale, and as a suLsliale on wlicl lo ma lunclion. Ollei llan lle inlei-
esl and exeilise ol lle aullois, an imoilanl ieason lo concenliale on Liain imaging
is llal a laige ail ol lle mosl advanced image-iocessing woil is cuiienlly in llis aiea.
As llese leclniques develo, and as new imaging modalilies incieasingly Lecome avail-
aLle loi imaging ollei and moie delailed Lody iegions, lle leclniques will incieasingly
Le alied in all aieas ol Liomedicine. !oi examle, lle develomenl ol moleculai-
imaging mellods is analogous lo lunclional-Liain imaging, in llal lunclional dala, in
llis case liom gene exiession iallei llan cognilive aclivily, aie maed lo an analomic
suLsliale. Since lle same Lasic iinciles aly in Loll lunclional-Liain maing and
moleculai imaging, lle same leclniques aly: salial and symLolic ieiesenlalion ol
analomy, dealing will analomic vaiialion, claiacleiizalion ol analomy, visualizalion,
and mullimodalily image lusion.
Tlus, llese geneial mellods will incieasingly Le alied lo diveise aieas ol Liomed-
icine. As lley aie alied, and as imaging modalilies conlinue lo iolileiale, an incieas-
ing demand will Le laced on mellods loi managing lle images and loi sloiing and
accessing llem. Al lle same lime, imaging will conlinue lo lay an incieasing iole in
inlegialed Liomedical inloimalion syslems. Tlese lwo suLjecls, managemenl ol images,
and inlegialion in Liomedical alicalions, aie lle suLjecls ol Clalei 18.
Questions for Discussion
1. Wlal is lle geneial iincile llal undeilies comuled axial lomogialy (CT)' Wlal
aie lle advanlages ol CT images ovei convenlional X-iay images'
2. Lxlain lle geneial iincile undeilying magnelic iesonance imaging (MR!)' Wlal
aie lle advanlages ol llis mellod comaied lo oldei mellods ol imaging'
3. Lxlain lle dilleiences among conliasl, salial, and lemoial iesolulion.
4. DesciiLe lle loui slandaid image-iocessing sles, and suggesl low llese migll Le
alied Ly an image-analysis iogiam looling loi aLnoimal cells in a PAP smeai.
5. Wlal is lle segmenlalion sle in image analysis' Wly is il so dillicull lo eiloim' Give
lwo examles ol ways Ly wlicl cuiienl syslems avoid lle ioLlem ol aulomalic seg-
menlalion. Give an examle ol low lnowledge aLoul lle ioLlem lo Le solved (e.g.,
local analomy) could Le used in luluie syslems lo aid in aulomalic segmenlalion.
6. Wlal addilional inloimalics issues aiise wlen going liom lwo-dimensional lo lliee-
dimensional image iocessing' Wlal aie lle lliee-dimensional veisions ol lwo-
dimensional image-iocessing oeialions sucl as iegion giowing and edge linding'
7. Wlal is a lliee-dimensional Liain allas' Wlal aie lle mellods loi iegisleiing a
alienl image volume lo llal allas' Wlal is lle use ol a Liain allas'
8. Give some examle leclniques loi imaging lle lunclion ol lle Liain.
Suggested Readings
Biinlley 1.!. (1991). Sliucluial inloimalics and ils alicalions in medicine and Liology.
, 66(10):589591.
Sloil inlioduclion lo lle lield.
Biinlley 1.!., Rosse C. (2002). !maging and lle Human Biain Piojecl: A ieview. -
, 41:245260.
Review ol image iocessing woil ielaled lo lle Liain. Mucl ol lle Liain-ielaled maleiial loi llis
clalei was lalen liom llis ailicle.
Polclen L.1. (2000). Piosecls loi iogiess in diagnoslic imaging. ,
247(4):411424.
onleclnical desciilion ol newei imaging mellods sucl as caidiac MR!, dillusion lensoi imag-
ing, lMR!, and moleculai imaging. Cuiienl and olenlial use ol llese mellods loi diagnosis.
RoLL R.A. (2000). - --. ew Yoil: Wiley-Iiss.
Oveiview ol Liomedical imaging modalilies and iocessing leclniques.
Rosse C., Mejino 1.I.V. (2003). A ieleience onlology loi Lioinloimalics: Tle !oundalional Model
ol Analomy. -, 36(6):478500.
Desciilion and iinciles Lelind a laige symLolic onlology ol analomy.
Slaiio I.G., Sloclman G.C. (2001). -. \ei Saddle Rivei, 1: Pienlice-Hall.
Delailed desciilion ol many ol lle ieiesenlalions and mellods used in image iocessing. ol
secilic lo medicine, Lul mosl ol lle mellods aie alicaLle lo medical imaging.

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Imaging and Structural Informatics

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