Spins in motion. new methods for the visualization of intracranial flow

New methods for the visualization

of intraranial ow

Inauguraldissertation

zur Erlangung der Würde eines Doktors der Philosophie

vorgelegt der

Philosophish-Naturwissenshaftlihen Fakultät

der Universität Basel

von

Franeso Santini

aus Florenz, Italien

Basel, 2009

aufAntragvon:

Prof. Dr. Klaus Sheer

Referent

Prof. Dr. Jürgen Hennig

Korreferent

Basel,den 23.6.2009

Prof. Dr. EberhardParlow

Dekan

Magnetiresonaneimaginghasbeomeawidelyusedimagingtehniquefordiagnosti

purposes, with appliations in the whole human body. For many pathologies of the

entralnervoussystem,itisinfatthemethodofhoie,duetohighsofttissueontrast

and the possibilities of generating images related to organ funtion rather than pure

morphology.

Inthisthesis,thefouswillbeonmethodsdesignedtodealwithaspeiaspetof

theentral nervous system, whih is the irulation of uids (blood and erebrospinal

uid) inside the skull. These two uidompartments interat with eah other, and a

diseaseaeting onehasgood hanes ofaeting theother aswell. Thisisthereason

why the thesis is divided in two parts: the rst part, titled angiography, is mainly

related to the visualization of arteries and veins by means of angiographi sequenes,

and to the presentation of a novel method to enhane the visualization of datasets,

by inluding the funtional information deriving from time-resolved angiography into

a singleolor-oded set ofimages. The seond part, titledFlow quantifiation, is

presenting anewbSSFP-basedmethodfor3Dtime-resolved aquisitionofquantitative

ow information. This tehnique an be used for blood ow assessment, but it is

espeially suited for the measurement of erebrospinal uid. In the end, preliminary

linial results from a linial study that applies this quantiation tehnique to ow

insidethe erebral ventriles are presented.

Journal papers

ˆ Santini F, Patil S, Mekel S, Sheer K, Wetzel SG. Double-referene ross-

orrelation algorithm for separation of the arteries andveinsfrom 3DMRAtime

series. Journalof Magneti Resonane Imaging. 2008 ;28(3):646-654.

ˆ MekelS,Stalder A,Santini F,Radü EW,Rüfenaht DA,Markl M,Wetzel SG,

In-vivo Visualization and Analysis of 3D Hemodynamis in Cerebral Aneurysms

withFlow-sensitized 4DMR Imaging at3T, Neuroradiology. 2008 Jun;50(6):473-

84.

ˆ SantiniF,WetzelSG,BokJ,MarklM,SheerK.Time-resolvedthree-dimensional

phase-ontrast balaned SSFP, Magneti Resonane inMediine,in press.

ˆ SantiniF,ShubertT,PatilS,MekelS,WetzelSG,SheerK,Automatirefer-

eneseletionforartery/veinseparationfromtime-resolved3Dontrast-enhaned

MRAdatasets, Journal of Magneti ResonaneImaging, submitted.

Conferene proeedings

ˆ Santini F, Patil S, Mekel S, Wetzel S G, .Sheer K, Double-referene orre-

lation algorithm for artery and vein separation in ontrast-enhaned MR angiog-

raphy, Proeedings of the 23rd annual sienti meeting of ESMRMB, Warsaw,

Poland, 2006, pp. 47-48.

ˆ SantiniF,Patil S,MekelS,SheerK,WetzelSG,Artery/veinseparation and

stula detetion in MR angiographythroughdouble-referene orrelation analysis,

Proeedingsofthe 31stCongress ofESNR, Geneva, Switzerland, 2006.

ˆ Santini F, Wetzel S G, Sheer K, Automati Referene Seletion Method for

Unsupervised Artery/VeinSeparation in Time-Resolved Contrast-Enhaned Mag-

neti Resonane Angiography,Proeedingsof theJoint Annual MeetingISMRM-

ESMRMB 2007.

ˆ Santini F, Sheer K, Assessment of Respiration- and Cardia-Related Flow

Patterns of Cerebro-Spinal Fluid Using Balaned Steady-State Free Preession

ˆ Santini F, Wetzel SG, Sheer K, TrueFISP for 7D ow quantiation: a so-

lution to saturation-indued signal loss, Proeedings of the 19th Annual Inter-

national Conferene on Magneti Resonane Angiography, Istanbul, Turkey, 3-5

Otober2007.

ˆ Mekel S, Santini F, Stalder A, Markl M, Sheer K, Wetzel SG, In vivo vi-

sualization of ow in intraranial aneurysms, Proeedings of the 19th Annual

International Conferene on Magneti Resonane Angiography,Istanbul, Turkey,

3-5 Otober2007.

ˆ Santini F, BieriO, Sheer K, Flow ompensation in non-balaned SSFP, Pro-

eedings oftheAnnualMeeting ISMRM2008.

ˆ Santini F, Wetzel SG, Sheer K, Three-dimensional time-resolved ow quan-

tiation withbalaned SSFP, Proeedings oftheAnnualMeeting ISMRM2008.

ˆ Mekel S,Stalder A,Santini F, Markl M, Sheer K, Wetzel SG, In-vivo visu-

alization andanalysisof 3Dhemodynamis inerebral aneurysms,Proeedingsof

the AnnualMeeting ISMRM2008.

ˆ Santini F, Shubert T, Sheer K, Wetzel SG, In vivo assessment of CSF ow

patternsthrough4Dow-sensitivebSSFPsequene,Proeedingsofthe25thannual

meeting ofESMRMB, Valenia,Spain, 2008.

ˆ Santini F, Shubert T, Sheer K, Wetzel SG,In vivo 4D visualization of CSF

ow: healthy volunteers and hydroephalus, Proeedings of the Annual Meeting

ISMRM 2009.

ˆ SantiniF,MarklM,SheerK,Onoptimalenodingof owinthree-diretional

phase-ontrast sequenes, Proeedingsofthe AnnualMeeting ISMRM2009.

1 Introdution 11

1.1 MRIfor funtionalimaging . . . 12

1.2 Flow inthe entralnervoussystem . . . 13

1.3 Angiography . . . 14

1.3.1 NonenhanedMRA tehniques . . . 14

1.3.1.1 Time-of-ight angiography . . . 15

1.3.1.2 Phase-ontrast angiography . . . 15

1.3.1.3 ECG-gated fastspin-eho . . . 16

1.3.1.4 Balaned-SSFP-based methods . . . 16

1.3.2 Contrast-enhaned MRAtehniques . . . 18

1.3.2.1 Standard ontrast-enhanedMR angiography . . . 18

1.3.2.2 Time-resolved angiography . . . 19

1.4 Flow quantiation . . . 20

1.4.1 Phaseand motion . . . 20

1.4.1.1 Phase ontrast . . . 21

1.4.2 Three-diretional, three-dimensional,time-resolved . . . 22

1.5 Aimof thethesis . . . 25

1.6 Outlineof thethesis . . . 25

Referenes . . . 27

I Angiography 31 2 Artery/vein separation in CE-MRA 33 2.1 Introdution . . . 34

2.2 Theory. . . 35

2.2.1 Cross-orrelation . . . 35

2.2.2 Double-referene ross-orrelation . . . 35

2.2.3 RGB Enoding . . . 37

2.3 Implementation . . . 38

2.4 Experiments. . . 38

2.4.1 MRIimage aquisition . . . 40

2.4.2 Dataanalysisand quality assessment . . . 41

2.5 Results. . . 41

2.5.1 Visual assessment ofthevessels . . . 41

2.5.2 Quantitative assessment . . . 45

2.6 Disussion . . . 46

Referenes . . . 48

3 Automati referene seletion 51 3.1 Introdution . . . 52

3.2 The lusteringalgorithm . . . 52

3.3 Aquisition and analysis . . . 53

3.4 Results. . . 54

3.5 Disussion . . . 54

Referenes . . . 58

II Flow quantiation 59 4 Quantitative 4D ow measurements with bSSFP 61 4.1 Introdution . . . 62

4.2 Optimized gradient waveforms. . . 63

4.3 Sequene design . . . 64

4.3.1 Enoding sheme . . . 67

4.3.2 Eddy urrent ompensation . . . 67

4.3.3 Triggering . . . 67

4.4 Aquisitions . . . 67

4.4.1 Phantom studies . . . 67

4.4.1.1 Stati phantom . . . 68

4.4.1.2 Flowphantom . . . 68

4.4.1.3 Data reonstrutionand analysis . . . 69

4.4.2 In vivo studies . . . 69

4.4.2.1 Blood ow . . . 69

4.4.2.2 CSF ow . . . 69

4.4.2.3 Postproessing and visualization . . . 70

4.5 Results. . . 70

4.5.1 Image quality andeddyurrents . . . 70

4.5.2 Flow phantom experiment . . . 70

4.5.3 In vivo owharateristis. . . 70

4.6 Disussion . . . 73

Referenes . . . 76

5 On optimal ow enoding 79 5.1 Introdution . . . 80

5.2 Theory . . . 80

5.3 Aquisitions . . . 83

5.4 Results. . . 83

5.5 Disussion . . . 83

Referenes . . . 85

6 Cerebrospinal uidow 87 6.1 Introdution . . . 88

6.2 Materials andmethods . . . 88

6.2.1 MRIaquisitions . . . 88

6.2.2 Imagepreproessing . . . 89

6.2.3 Datavisualization . . . 89

6.3 Results. . . 89

6.3.1 Healthyvolunteers . . . 89

6.3.2 Patient . . . 90

6.4 Disussion . . . 91

Referenes . . . 92

7 Summary and onlusion 93 7.1 Bloodow . . . 94

7.2 CSFow . . . 95

7.3 Outlook . . . 96

Referenes . . . 98

Introdution

Magneti resonane imaging is a relatively new diagnosti imaging method, being

hypothesized by Raymond Damadian in 1971 [1℄ as a possible method for tumor de-

tetion, and introdued inlinial routine only inthe 1980s when therst ommerial

MRIsanners beame available. However, the suess of this tehnique has inreased

steadilyduring the years,and nowadays there is an ative sienti ommunity devel-

oping new methods and onepts. The biggest international onferene in the elds

of MRI, promoted by the International Soiety of Magneti Resonane in Mediine

(ISMRM),ountsthousands of originalontributions eah year.

Thereasons for the suessof MRIfor diagnosti imaging aremultiple: rst ofall,

the image formation does not relyon theusage of ionizing radiations, and up to date

thereisnosientiproofofharmfulbiologialeetsduetotheuseoflinialsanners.

Seondly,MRIoersavastrangeofpossibilitiesfortheimagingofsofttissues,enabling

thedierentiationofstruturesandtheidentiation ofawiderangeoflesions. Lastly,

theeldofappliationofMRIspansbeyondthestandardmorphologialimagingoered

byotherradiation-basedmethods,andanprovideusefulfuntionalinformation about

the organs.

Inneuroradiology,MRIisoftenthetoolofhoieforthediagnosis,asitanbeused

toeasilydierentiategrayandwhitematter,andtehniquesfor multimodalimagingof

the brainareavailable.

1.1 MRI for funtional imaging

Whileothertehniqueslike omputedtomography(CT)ofX-rayuorosopyoerhigh

spatialresolutionimagingoftheentralnervoussystem,thehoieofmethodsproviding

funtional information is rather limited, and often requires the usage of speialized

equipment. For example, digital subtration angiography is the method of hoie for

thediagnosisofneurovasularpathologies,butitrequiresadediatedmahine,ionizing

radiation, and theinsertion of an intraarterial atheter; positron emissiontomography

(PET)isanulear mediinetehniqueabletovisualizetissueperfusion,butwithalak

ofmorphologial refereneinformation and theneed for aradioative traer.

MRI oersa wide range of possibilitiesto obtain funtional information, available

on most ommerial sanners, often only requiring the seletion of an appropriate a-

quisitionmethod(pulsesequene),oratmosttheintravenousinjetionofagadolinium-

oriron-based ontrast agent.

AlthoughthetermfuntionalMRI (fMRI)ommonlyreferstoMRimagingofneu-

ralativation, possiblymeasured through thehemodynami response indiated bythe

BOLDeet (hangeinmagnetipropertiesofoxygenated/deoxygenated hemoglobin),

funtionalimaging isa moregeneri term,relating to all methods that give informa-

tionabout an organ that go beyond themorphologial harateristis and explorethe

atualphysiology.

ExamplesoffuntionalimagingavailablethroughMRIareperfusionmeasurements,

time-resolved or ardia-gated aquisitions of moving organs, hemial shift imaging,

diusionimaging, angiographyand owmeasurements.

Figure1.1: Ventriular systemofa normal subjet.

1.2 Flow in the entral nervous system

The entral nervous systemontains two important ompartments thatare omposed

of uids: the neurovasular system, in whih blood irulates, and the erebrospinal

uid(CSF)ompartment, whihprovides mehanial supportand protetion.

These two ompartments are linked together, as CSF is produed by blood ltra-

tioninsidethe horoid plexusintheventriular system(seeg. 1.1), andsubsequently

reabsorbedinthe venoussystem. CSFmovement isalsomainlydriven bybloodpulsa-

tion, thatexpands the brain vessels andtherefore redues theventriular spaeduring

systole,pushing theCSF outsidetheventriular spae.

An important pathology, the normal pressure hydroephalus (NPH) is believed to

be a onsequene of the driving eet of blood over CSF pulsation. [2,3℄. In normal

subjets, the ompliane ofthe brain parenhyma atsas a damper for the bloodpul-

sation, thereforereduing the CSF pulsatility. Ifthe brain tissuebeomesstier, CSF

pulsatility isfored toinrease, whih leads to enlargement of theventriular spae.

DespitetheneedforgoodimagingofCSFow, inorderto orretlydenethiskind

ofpathologies,therelaxationharateristisofCSF,whihshowsverylonglongitudinal

andtransversalrelaxationtimes,makeitverydiulttomeasurewithonventionalfast

T ₁

^{-weightedsequenes. Forthisreason,eitherlongrepetitiontimesarerequired(inthe}

orderofseonds), ornon-spoiledsteady-state sequenes (likethebalaned steady-state

freepreession [bSSFP℄sequene) need to be used.

In orderto study the ow dynamis of theCNS, it isthereforeimportant to study

both the vasular ompartment, through angiography and blood ow quantiation,

and the CSF ompartment, whose geometry is simpler, but whih requires dediated

tehnique to be suessfullyevaluated.

1.3 Angiography

Angiographyistraditionally dened asthe radiographi visualization of the blood ves-

sels after injetion of a radiopaque substane [4℄. By extension, Magneti Resonane

Angiography(MRA) refersto magneti resonane imaging used tovisualize noninva-

sivelytheheart,blood vessels, orbloodowin theirulatory system [5℄,whihmayor

maynot involve the useofan exogenousontrast agent.

Even though,stritly speaking, angiography belongs to morphologial imaging,the

depition of the vessels generally relies on the eets generated by the blood owing

insidethemrather than theatual vasularmorphology.

Thisisoftendesirable,asthemainlinialinterestistostudythebloodowitself,in

ordertoevaluatewhetherthebloodsupplytoareasofthebodyisadequate,insuient,

laking,or present but abnormal.

Examples of auses of insuient or absent blood supply to tissues arethrombosis

and stenoses, whereas arteriovenous stulas are possible examples of abnormal blood

supply to body regions. In this latter ase, arterial (oxygenated) and venous (deoxy-

genated) blood get mixed beause of a pathologial shunt between an artery and a

vein. This results in a redued oxygen supply to the region downstream of the inter-

ested artery, and risk of rupture beause of an inreased blood pressure in thevenous

system[6 8℄.

MRI oers various alternatives for obtaining angiographi datasets: some exploit

theblood ow veloity to disriminate between uid and stati tissues; others rely on

the injetion of an intravasular ontrast agent that signiantly hanges the relax-

ation harateristis of blood, so that it an be easily identied using sequenes with

onventional weighting.

1.3.1 Nonenhaned MRA tehniques

Angiographysequenesthatdonotneedanyontrastagentinjetionrelyoneetsthat

generallygobeyondthelassialrelaxationharateristisoftissues. Asageneral prin-

iple,blood and uids move inside thebody,therefore they experiene radiofrequeny

pulsesand magnetield gradients ina dierent manner withrespetto statitissues.

This an be exploited to enhane the ontrast between blood and surrounding tis-

sues.

Figure 1.2: Time-of-ight angiography of the brain vessels. Left: oronal maximum

intensityprojetion (MIP);right: transversalMIP.

1.3.1.1 Time-of-ight angiography

The rst sequene for angiographi imaging to be introdued was the time-of-ight

(TOF)tehnique[9,10℄. Itisa

T ₁

^{-weightedsequenewitha}two-dimensionalaquisition, or thin-slab three-dimensional aquisition, with slie orientation perpendiular to the

main ow diretion. Short repetition times produe very low signal from all tissues

beause of saturation eets. Blood, on the other hand, benets from the so-alled

inow eet, whih means that at every TR the exited volume of blood leaves the

imaging slie, and a new volume enters. The next radiofrequeny pulse will therefore

exite non-saturated blood, thus resulting in maximum available signal (see g. 1.2).

Sometimes o-resonane saturation pulses are played before the atual exitation to

exploitmagnetization transfereets thatontribute to thesaturationof statitissues

[1113℄.

This sequene is oneptually simple and easily implemented, and also gives good

results inregions were blood ow is mainly direted along a singleaxis. On theother

hand, in regions were vessels bend signiantly (see g. 1.3), a portion of the vessel

might fallinsideone singleslie, ausingthe inoweettoease. Inthisase, asignal

drop isobserved and itmight be mistaken fora vesselpathology like astenosis.

1.3.1.2 Phase-ontrast angiography

Phase-ontrastisamethodforveloityquantiation, andwillbepresentedindetailin

setion1.4. However,itanalsobeusedasamethodforthedepitionofvesselstruture.

To ahieve this,time-averaged veloity is measured along one or more diretions, and

then to every voxel in the dataset a gray level value proportional to the measured

Figure 1.3: In-plane saturation in anterior tibial artery mimiking stenosis in TOF

aquisition (left),not seenon Gd-enhaned MRangiogram(right). (Soure:[14℄)

veloity is assigned. In ase of multiple diretion enoding, a sum of squares of the

veloities in the measured diretions is onsidered [15,16℄. This angiography method

is more aurate than TOF when more than one enoding diretion is implemented,

but this results in longer san times, the duration of the aquisition being (roughly)

proportionalto the numberof diretionsenoded.

1.3.1.3 ECG-gated fast spin-eho

Introdued as a onept in 1985 [17℄, angiography based on ECG-gated spin eho is

now beoming linially feasible in aeptable san times thanks to the development

of single-shot partial-Fourier fast spin-eho aquisitions [18,19℄. The priniple of this

tehnique relies on aquiring two datasets at dierent instantsof theardia yle. In

thedatasetaquired duringsystole, thefastowinthearteries generatesowvoids in

thevessels,whihappearblak. Inthediastoliphase, theow isslower andtherefore

thesignalfrom the artery appears bright. The bakground and venous signals appear

unhanged inthe twodatasetsdueto thelowveloities ofvenousow. Subtratingthe

systolidataset from thediastolione resultsinto a purearteriogram (seeg. 1.4).

Thistehnique hasbeen suessfullyapplied to thoraivessels[20℄ and promising

preliminaryresults have beenobtained withperipheral angiography [14,21℄.

1.3.1.4 Balaned-SSFP-based methods

balaned steady-state free preession (bSSFP) is a fast sequene haraterized by a

T ₂ /T ₁

^{ontrast. Thisweightinggivesveryhighsignalfromuids,thusmakingbSSFPan}

idealhoieforthedepitionofvessels,asshownalsoinhapter4. Thissequene,maybe

in onjuntion with

T ₂

preparation an be diretly used for the depition of vessels, for example in the imaging of oronary arteries [22,23℄. In alternative, an inversion

pulse an be used for bakground suppression and vessel seletion. This tehnique is

termed arterial spin labeling, and onsists of applying a non-seletive inversion pulse

Figure 1.4: Three-dimensional partial-Fourier FSE imaging withsystoli and diastoli

aquisition. Eah setion (S1,S2, ... Sn) is imaged inone single-shot aquisition. One

triggerdelay(d1)istimedforsystoleforone3Daquisition,whileaseonddelay(d2)is

timedfor diastole. Aquisitionsare performedeveryother or every third heartbeat. A

shorttauinversion-reovery(STIR)pulsean beusedforimprovedfat suppression. To

generate a bright-blood angiogram, systoli images (where arterial ow appears dark)

are subtrated from diastoli images. A = arteries, RF = radiofrequeny, V =veins.

(Soure:[14℄)

immediately followed by a slie-seletive inversion. The seond pulse is targeted to a

speiartery. AfteraninversiontimeTIthatwouldnullthebakgroundsignal,afast

bSSFPaquisition isperformeddownstreamtothetaggingpoint[24,25℄. Theresultof

thisaquisition will bea high-ontrast arteriogram.

1.3.2 Contrast-enhaned MRA tehniques

Theusageofintravasularontrastagentsishighlybeneialfromatehniquepointof

view. Theontrastmediathatarenormallyusedforangiographyaregadolinium-based,

andthey redue the longitudinal relaxation time

T 1

^{. This allows theaquisition to be}

performed without exploiting veloity-indued eets, but with standard

T ₁

^-weighted

sequenes,whiharewell-suited for fastimaging[26℄. Withthis method,thedepition

of the vessels is not related to ow diretion. Contrast-enhaned angiography (CE-

MRA) has been widely used, when no ontraindiation to the use of ontrast agent

persists[14,27,28℄.

1.3.2.1 Standard ontrast-enhaned MR angiography

Standard ontrast-enhaned angiography is performed by intravenous injetion of a

bolus of ontrast agent, followed by a radiofrequeny-spoiled gradient realled eho

(RF-spoiledGRE)aquisition[26,29℄. Withonventionalextraellular ontrastagents

(moleulesthatdiusefromthebloodvesselstotheextraellularspae),theaquisition

isnormallylimitedasrstpass oftheontrast agentbolus,asimaginginthesteady-

state angiography is not useful beause of rapid extravasation of suh extraellular

ontrastmediaresultingindereasingvasularandinreasingbakgroundsignal[26,27℄.

More reently [27℄, a new lass of ontrast agents, named blood pool ontrast agents,

has been introdued. Moleules of this family are bound to maromoleules that do

notdiuseinthe extravasularspae(albumin, dextran,polylisine,et.[30,31℄). These

ontrastagentsallowaquisitionofanarteriovenousangiogramduringupto42minutes

afterinjetion[27℄.

With a standard rst-pass angiography aquisition, one three-dimensional dataset

is aquired. The sequene timing is adjusted in order to have the enter of the k-

spaeaquiredeitherduringthearterialphase(all arteriesareenhanedbutnovenous

enhanement isvisibleyet), or during alater phasewhen all thevesselsareenhaned.

The ritial point in this kind of aquisition is to time the sequene orretly in

orderto haveallthedesiredvesselsproperlyenhaned. Earlyaquisitionofthek-spae

enter an result in ringing artifats at thevessel boundaries (see g. 1.5), whereas

lateaquisition resultsindereasedarterial signaland venousontamination [29℄. The

most used timing tehnique is the injetion of a low-dose test bolus, imaged with a

time-resolved sequene,inorderto alulatethetimeneededfor thebolusto reahthe

region of interest. This timeis then introdued as a delay for the seond aquisition.

withtheatualontrast agent bolus.

In order to avoid dealing with bolus timing, or to image areas where arterial en-

hanement an our at dierent time points, a omplete time-resolved approah an

Figure 1.5: Ringing artifat due to early aquisition of k-spae enter in CE-MRA

(Soure:[29℄)

be used.

1.3.2.2 Time-resolved angiography

Time-resolved aquisition protools have been available sine 1996 [32℄, and are get-

ting more and more used as newer aquisition aeleration tehniques implemented

on ommerial MRI sanners. Most of these tehniques rely on view sharing (Time-

Resolved imaging of Contrast KinetiS [TRICKS℄ [32℄, Time-Resolved Eho-shared

Angiographi Tehnique [TREATS℄ [33,34℄, Time-resolved imaging With Stohasti

Trajetories [TWIST℄ [21℄, 4-Dimensional Time-Resolved Angiography using Keyhole

[4D-TRAK℄[35℄).

Theaquisitionisstillathree-dimensional

T ₁

^{-weightedsequene,butseveraldatasets}

areaquired subsequently, eah withan aquisition timeranging fromone to few se-

onds.

The aquired datasets are normally reonstruted separately, providing hemody-

nami ow information. With time-resolved MRA it is possible to depit phenomena

withshort arterial-to-venous transit times, distinguish arterial from venous strutures

and determinediretion of ow.

Withthisaquisitionmethod,multipledatasetsofarterialandarteriovenousphases

are obtained. In order to obtain a pure arteriogram or venogram, a postproessing

algorithm for artery/vein separation is needed. The existing algorithms are semiau-

tomati, needing a ertain degree of user interation for seletion of referene points

or images [3638℄. A novel method for ompletely automati artery/veinseparation is

presentedinhapter 2.

1.4 Flow quantiation

MRI allows for another method of assessment and visualization of the harateristis

of ow inside vessels and organs. By using the harateristis of the MR signal, it is

possible to enode the atual veloity of a moving set of protons (isohromat) in the

phase omponent of the reonstruted image. This is useful, for example, in ardi-

ology to alulate theventriular stroke volume, valve regurgitation, et. [39,40℄ or in

neuroradiologytoassesstheowharateristisoftheerebrospinaluidinpathologies

likehydroephalus andChiari malformation [41,42℄.

Reently,the studyofthree-dimensionalowpatternsallowed forthestudyofother

ow-related parameters like wall shear stress and vortiity, that arebelieved to orre-

latewith the severityor the prognosis of vasularpathologies like plaque formation or

aneurysmdevelopment [43,44℄.

1.4.1 Phase and motion

Movingisohromatsinteratwiththeimaginggradientsinadierent waywithrespet

to stationary spins. The standard imaging onepts assume that every isohromat

experienesa magnetield generated bygradientswhose intensity isonly determined

by thespin's spatial position. This results ina phase evolution of the signal given by

the isohromat that is diretly proportional to the spatial position and to the zeroth

moment of the applied gradient.

Ingeneral, thephaseevolutionisgivenby:

φ(t) = ˆ t

0

ω L (τ )dτ = γ ˆ t

0

B (τ )dτ = γ ˆ t

0

G x (τ )x(τ )dτ,

^(1.1)

where

ω L

^{is the loal Larmor pulsation,}

γ

^{is the} gyromagneti ratio,

B(t)

^{is the lo-}

al magneti eld,

G x (t)

^{is the gradient amplitude,}

x(t)

^{is the spatial position of the}

isohromat alongthe gradient axis. Assuming a onstant positionovertime

x(t) = x ₀

^:

φ(t) = γ

ˆ t 0

G x (τ )dτ

x ₀ = γM ₀ x ₀ ,

^(1.2)

where

M 0 = ´ t

0 G x (τ )dτ

^{isnamed zerothmoment of thegradient.}

If the spatial position is not onstant, but the isohromat is moving a onstant

veloity,i.e.

x(t) = x ₀ + v _x t

^{,eq. (1.1) beomes:}

φ(t) = γ ˆ t

0

G x (τ ) (x ₀ + v x τ ) dτ

= γ ˆ _t

0

G x (τ )dτ

x ₀ + γ ˆ _t

0

G x (τ )τ dτ

v x

^(1.3)

= γM ₀ x ₀ + γM ₁ v _x ,

where

M ₁ = ´ t

0 G x (τ )τ dτ

^{isnamed rstmoment of thegradient.}

Figure1.6: Flowvoid(arrow)due tointra-voxel dephasingrelatedto owintheAque-

dutofSylvius.

As shown in the formula, a moving isohromat aquires a phase that is normally

unwanted,andthisanbeaauseofartifats,likesignallossduetointra-voxeldephas-

ing(givenbydierentphasesaumulated byspins insideonevoxelmovingatdierent

speeds, seeg. 1.6),or shiftingof anatomial strutures[45℄.

1.4.1.1 Phase ontrast

In theapproximation ofonstant ow veloity,the phaseof the isohromat assumes a

valuethat is proportional to the rst moment of the gradient along the ow diretion

and to the veloity itself. If the imaging sequene is designed in a way that the rst

momentofthe gradientsiskeptonstantthroughout thewholek-spae,thenthisphase

shiftdoesnot auseanyartifat butwill be enodedinthereonstrutedphaseimage,

and anbeused toobtain diretinformation about ow veloity.

However, phaseimagesmayhave spuriouserrorsdue toeldinhomogeneitiesorra-

diofrequenypenetration eets[45℄, thatwouldinterfere withthepossibilityof quan-

tifying veloity from a single san. These bakground phases are independent of the

gradientpulsesandan beeliminatediftwophaseimagesareolleted andsubtrated.

If the rst moment of the gradients is hanged between two suh sans, there will be

veloitydependent phase information inthe subtrated image. Thismethod isnamed

phase ontrast and wasintrodued in1960 byHahn [46℄.

The pratial realization of a phase ontrast sequene, inthe most lassial form,

onsists of a standard imaging sequene, normally based on gradient-eho in order to

ahieve short aquisition times[47℄,inwhih abipolar gradient pulseisadded (on any

axis) before signal aquisition (see g. 1.7). Thisbipolar pulse has

M ₀ = 0

^{, therefore}

it does not ontribute to the spatial enoding, and has a

M ₁

^{that depends on the}

Figure1.7: a) Bipolar gradient pulse;b) Typialpulse sequene withowenoding in

thethrough-planediretion.

parameters ofthe gradient pulse (seeg. 1.7a for symbolreferene):

M ₁ = A(w + r)(w + 2r).

^(1.4)

The seond aquisition is either performed without the ow-sensitizing gradient

(refereneaquisition), or withinverted polarity,and therefore opposite

M ₁

^(balaned

aquisition).

The

M ₁

^{valuealsoposesalimitonthemaximumveloitythatanbeenodedbythe}

sequene,asthephaseanonly assumevaluesbetween

−π

^and

+π

^{. Thisveloitylimit}

is alled Ven (sometimes referred to veloity anti-aliasing limit), and is the veloity

value thatgivesaphase shiftof

π

^{,andan beobtained withthefollowing formula:}

v enc = ^π / γ∆M 1 ,

^(1.5)

where

γ

^isthegyromagnetiratioand

∆M ₁

^{isthediereneoftherstmomentsofthe}

ow-sensitizing gradients of the two sans. It is important to orretly hoose a Ven

not lowerthan the maximum expeted veloity,otherwise phasewrapping ours,and

nottoo muhhigher, otherwisethe signal-to-noise ratio deays.

The veloity an be extrated from the phase ontrast image by simple saling of

the phasevalueoftheimage resulting from the subtration ofthephase images:

v = ^φ / γ∆M 1 ,

^(1.6)

where

φ

^{is the measured phase. An example of phase ontrast data from the head}

vesselsis showningure1.8.

1.4.2 Three-diretional, three-dimensional, time-resolved

Sine the beginning of the 1990s, the phase ontrast method was extended in order

to enode ow in multiple diretions in a single aquisition session [47 49℄. All the

Figure1.8: Two-dimensional phaseontrast dataoftheinternal arotidarteries andof

thebasilar artery. a) Magnitude image. b-f) Phaseontrast images of thehighlighted

region,at ve dierent ardia phases. The arteries lookbrighterin thesystoli phase

due to higher veloities. g) Veloity time ourse in the right internal arotid artery

extrated fromthephaseontrast images.

x y z

1 0 0 0

2 + 0 0

3 0 + 0

4 0 0 +

x y z

1 - - -

2 + + -

3 + - +

4 - + +

Table 1.1: Tables representing thesigns of the enoding moments in three-diretional

ow assessment. Rows areenodingsteps, olumnsareenodingdiretion. A + sign

represents positive enoding moment;a - sign representsnegative enodingmoment;

a0 signmeans noenoding. Ontheleft,four-point referenedaquisitionsheme; on

theright, four-point balaned aquisition sheme.

Figure1.9: Three-dimensional,three-diretional,time-resolvedowmeasurementofthe

erebralvessels. top: streamlinesin the irleof Willis ofa healthyvolunteer. bottom:

streamlinesin a large, wide-neked, oval-shaped parophthalmi aneurysm of the right

internal erebralartery (adaptedfrom [43℄).

presented methods rely on aquiring four steps, with dierent ow sensitivities (see

table1.1).

In 2003, Markl et al [50℄ demonstrated the feasibility of a time-resolved three-

dimensionaltehniqueforowaquisition,basedonRF-spoiled gradient eho,together

with a visualization proedure able to depit ow patterns inthree dimensions. This

approahallowsamoreexibledenitionofareasofinterestinsidetheaquireddataset,

andthepossibilityofextrating indiretow-relatedparameters likewall shear stress.

Two examplesofthree-diretional,three-dimensional, time-resolved owquantia-

tionofthe brainvessels isshown ingure1.9.

1.5 Aim of the thesis

Asmentionedabove,MRIisamajortoolforthediagnosisofbraindiseases,andinfat

averysigniantportionofresearheortsfromtheinternationalommunityisfoused

onheadimaging. BOLDfMRI,perfusionMRIwereprimarilydevelopedfor monitoring

theativityandviabilityof theentral nervoussystem. However, mostofthemethods

still holdroomfor improvement. One major issueis theinrease ofsignal-to-noise, for

multiplereasons: apartfromtheobviousinrease inimage quality,signalgainanalso

be traded for higher resolutions and for faster aquisitions. Therefore thegeneral goal

ofmethoddevelopment isto obtainbetter,moredetailed images,and faster. However,

signal-to-noisedoesnot neessarilymeanhigherdiagnosti potential. Theotherruial

aspet derives from image ontrast. An optimal sequene will have a high ontrast

betweenthe desiredtarget ofthe imaging(alesion, avessel, et.) andthebakground.

Inthis thesis, newmethodsarepresentedthataim toenhane imagequalityinthe

visualizationofintraranialow. Theaimofthemethodsherebypresentedistoahieve

ahigherdiagnostipotentialbyenhaningsignalharateristisandimageontrastwith

respetto unwantedbakground.

Forangiographiaquisition,thisisahievedbyintroduingapostproessingmethod

for time-resolved ontrast-enhaned MRangiographydatasetswhihenables, inan op-

erator-independent way, the suppression of unwanted bakground strutures and the

enhanement of potential pathologial onditions.

For ow quantiation, a new tehnique for three-dimensional ow, based on bal-

aned-SSFP,ispresented. bSSFPisafastaquisitionsequenethatgivesoptimalsignal

fortheimagingofuids(andforthisreasonitanalsodiretlyusedforangiography,as

mentioned insetion 1.3.1.4). FromaSNR point ofview,ithasideal harateristis to

beusedasaowquantiationsequene. Thissequeneanbeusedtoexploretheblood

ow in intraranial vessels, and the ow of CSF in the ventriular and subarahnoid

spae.

Thegoalofthethesisistopresent thesenovel methods,andevaluate theirapplia-

bility ina reallinial environment. For this reasons, experiments on healthy subjets

and onpatientsareonsidered inthis work.

1.6 Outline of the thesis

Thisthesisisdividedintwoparts,eahfousingmainlyononeofthetwouidompart-

mentsoftheCNS:thebloodandtheCSF.Therstpart,titledAngiography,presents

anovelmethodforthestudyoftime-resolvedontrast-enhanedMRAdatasets. Froma

timeseriesof three-dimensional angiography datasets, aquiredduring therst passof

theontrast agentbolus,asingleolor-odeddataset isobtained,inwhih arteriesand

veins areseparatedandpathologies thatimpair thebloodow, like arteriovenous mal-

formations,arehighlighted. Inpartiular,inhapter 2thealgorithmdouble-referene

ross-orrelationthat performstheseparation and theolor-oding is presented, while

hapter 3 demonstrates a method for automati referene seletion to be used with

the previous algorithm in order to ahieve unsupervised analysis of the time-resolved

datasets. Themethodisbasedontheanalysisofthetimeoursesofthesignalintensity

of eah voxel in the dataset. These time ourses reet thebolus shape and timing at

eah anatomial loation. The omparison with two referene funtions, representing

thetime ourse of thesignal intensity inarteries and veins respetively, gives a prob-

ability index that the onsidered test voxel belongs to an artery, to a vein, or to the

bakground. The algorithm presented inthis thesisuses ross-orrelation assimilarity

test, henethe name of the method, but also introdues a way of taking into aount

themutual orrelationbetween referenes to ahieve a more aurate separation. This

isrealizedbyapplyinga red-green-blueolormapto theoutputdataset,whihhanges

itsharateristis depending onthe refereneorrelationvalue.

The identiation of the referene time ourses an be done manually, or with an

automatialgorithm. Theproposedautomatialgorithmforrefereneseletionisbased

onamodiedk-means lusteringtehniquethatperformsanapproximateunsupervised

separationon asubset oftheaquiredvoxels. Chapter 3introduesthis algorithm and

demonstratesthatthereisnostatistialdiereneinthequalityofthenalangiograms

In the seond part, termed Flow quantifiation, a novel method for time-

resolved three-dimensional, three-diretional ow quantiation ispresented. Thisme-

thodisbased onbSSFP,andis espeiallysuited for theinvestigation ofCSF owpat-

terns. Inhapter 4thesequeneisintrodued;inhapter 5areonstrutionmethod

able to enhane the temporal resolution of ow quantiation sequenes is presented.

BalanedSSFP,with a

T ₂ /T ₁

^{ontrast and short repetition times (inthe order of few}

milliseonds),isan ideal sequenefor fastaquisition of uids, whihpresent longlon-

gitudinalandtransversalrelaxationonstants,beauseattheendofTRthetransversal

magnetization is refoused and preserved ina steady-state. Flow quantiation based

onthissequeneanhavehighSNR,thusallowingthe usageofaelerationtehniques

for reduing the total aquisition times. However, the steady-state of bSSFP is very

sensitive to dephasing due to ow oreddy urrents, therefore speialmeasures need to

be taken in the sequene design in order to minimize the artifats arising from these

twophenomena. Inhapter4thetwomainmethods foreddyurrentompensationare

presented andompared, and the optimal implementation isidentied. Unfortunately,

thesemethodsintrodueapenaltyinthetemporalresolution. Thereonstrutionteh-

nique presented in hapter 5 is an eient reonstrution method to ompensate for

thispenalty.

Finallyhapter 6shows preliminaryresultsofthelinialappliation oftheafore-

mentioned owenodingsequene. This sequeneisused to imagetheventriular sys-

temofhealthyvolunteers, inorderto identifyphysiologiowpatternsoftheCSF,and

to image the CSF irulation ina patient sueringof three-ventriular hydroephalus,

beforeaventriulostomyoperationwasperformed,andaftersurgery,inordertoonrm

the diagnosisand to assessthe outome oftheoperation.

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Angiography

Artery/vein separation in

ontrast-enhaned MR angiography

Anadapted versionof thishapter ispublishedas: SantiniF,PatilS,Mekel S,SheerK,Wetzel

SG.Double-refereneross-orrelationalgorithmforseparationofthearteriesandveinsfrom3DMRA

timeseries. JournalofMagneti ResonaneImaging. 2008;28(3):646-654.

2.1 Introdution

Time-resolvedontrast-enhanedmagnetiresonaneangiography(CE-MRA)[13℄with

hightemporal resolution hasbeomea widelyusedtehnique to visualize thedynami

transit of a ontrast bolus from the arterial to the arteriovenous phase. To improve

thevisualization of vasular struture ompared to bakground, usually magnitude or

omplex subtration is performed [4℄. This method, either implemented as a 2D or

3Dsequene, hasbeen extensively used, for example,for thework-up ofneurovasular

disorders (e.g. arteriovenous stula) [511℄. However, there are important limitations

of thetehnique. First, due to the short arteriovenous transit time(e.g. 8 se for the

erebralvessels)and thesmalldiameter ofmany important vessels, thereisa trade-o

betweenthespatialandtemporalresolutionsofCE-MRAevenifaeleratedMRaqui-

sitions with parallel imaging tehniques are used. Seond, inontrast to intra-arterial

digitalsubtrationangiography(DSA),due tothe arterialoverlayinthevenousphase,

aseparationofthearterial andvenousphaseisnot possible,but merelytheseparation

of an arterial and an arteriovenous phase. A display of the venous phase without

superimposition of arteries is yet of interest for the evaluation of numerous vasular

disorders.

Dierentpostproessingstrategieshavebeenproposedtodealwiththistask[1219℄.

The most ommonly applied is the simple subtration of the arterial data sets from

venous datasets. However, the signal-to-noise ratio (SNR) in the resultant image is

redued by a fator of if noise properties of the two images are similar. A method

termed ross-orrelation [12℄ was shown to be superior ompared to the subtration

method both in terms of artery/vein separation and SNR. With this tehnique, the

signalintensitytimeourseof aregion-of-interest(ROI)plaed withinanartery (vein)

isross-orrelated withthetime oursesof allaquired datasets. Theross-orrelation

asan indexof similarityideally yieldsan arteriogram(venogram)only. Thistehnique

alsoleadstoaninreaseinSNRbyafatorofabouttwowithrespettothesubtration

tehnique. Theimpliitassumptionofthistehniqueisthatthetemporalbehaviorofthe

arterialphasedoesnotoverlapwiththetemporalbehaviorofvenousphasesigniantly.

However, this assumption is not always fullled and an unwanted depition of venous

signalinthe arteriogramand vieversa an be observed.

Inthishapter, the theoryoftheross-orrelationmethodis revised,andanexten-

sionof thismethod,termeddouble-referene ross-orrelation, is introdued.

2.2 Theory

2.2.1 Cross-orrelation

Theross-orrelationbetween adisretetest funtion

T

^{anddisretereferenefuntion}

R

^{an be dened as:}

c(T, R) =

N −1

X

i=0

R(t i ) − R ¯

T (t i ) − T ¯ v

u u u t

N −1

X

i=0

R(t i ) − R ¯ 2

v u u t

N −1

X

i=0

T (t i ) − T ¯ 2

,

^(2.1)

where N is the number of measured 3D volume datasets and

R ¯

^,

T ¯

^{are means of the}

orrespondingseries. The oeient

c(T, R)

^ismaximalif

T = R

^.

The mean-detrended and normalized value ofa funtion

T

^{an be dened as:}

T (t ˆ _i ) = T (t _i ) − T ¯ v

u u t

N −1

X

i=0

T (t i ) − T ¯ 2

.

^(2.2)

Dening

R ˆ

^{ina similarway,we obtain:}

c(T, R) = ˆ T · R, ˆ

^(2.3)

whihisthesalarprodutbetweenthetwovetors

T ˆ

^and

R ˆ

^{. Theorrelationoeient}

c

^{isalwaysin theinterval}

[−1, 1]

^{, beingthesalarprodutbetween two vetorsofunit}

norm. In general, the orrelation oeients are the osine of the angle between the

refereneand test vetor in N-dimensionalspae ofthe disrete timeourses. Beause

of the normalization proedure of thetest vetor, the temporal behavior of thesignal

(for e.g. vasular struture) as well asbakground falls into thesame dynami range.

This is undesirable as it disards the atual signal strength information (gray level

valuein the original image) of thetest vetor. Hene, inorder not to lose SNR in the

resultant orrelation map, the salar produt between the normalized referene vetor

and non-normalizedtest vetor isomputed, ie

T ˜ (t i ) = T (t i ) − T ¯

^.

Thus, the formula fororrelation oeientsbeomes:

c(T, R) = ˜ T · R. ˆ

^(2.4)

2.2.2 Double-referene ross-orrelation

With the standard ross-orrelation tehnique, the ross-orrelated oeient an be

interpreted asthe length ofthe projetion of the timeourse of the test vetor on the

axisofthereferenevetor. Theorrelationmapsobtainedwithrespettoarterialrefer-

eneand venous referenearetreated asindependent of eah other. However, beause

Figure 2.1: a) Vetor representation of orrelation oeients in the standard ross-

orrelationtehnique. The orrelation oeientsare projetions of thetest vetor on

therefereneaxes. Thetestvetoromponentsthatarenotoplanarwiththereferenes

aredisardedintheprojetionproess. Theskewangle

θ

^{isalsoshown. b)Orthogonal}

transformation of referene system. From the projetion of test vetor on the arterial

and venous referene another oeient is alulated, orresponding to theprojetion

ofvetor onthe axisnormalto the arterial referene.

of signiant overlapping of arterial and venous phase, there is sometimes a mutual

dependeny between the twoorrelationmaps. Inthisase thearterial andvenousref-

erenetimeoursesbeomesimilartoeahother, andthereforetheresultingorrelation

mapswillshowlittledierene. Inthedouble-refereneross-orrelationtehnique this

dependeny isdeoupled by formulating the relation between theonsidered referene

vetors. Theaim ofthis approahis to lassifya voxel asarterial or venous asthe

resultof aomparisonbetween the measuresofsimilarityofthevoxeltimeoursewith

the arterialand venousreferenes, representedbythe standard ross-orrelationmaps.

Thelassieralsousesasoftmargin approahinsteadofahardthresholding inorder

to take into aount for voxels withmixed arterial and venoustime ourses. Thelas-

siation is obtained through a nonlinear transformation of the orrelation maps and

throughan appliation ofan RGB olor mapto thetransformed values.

Considera2-dimensionalsubspaeformedbytworeferenevetors,whihisalledas

vesselplane. Thetworeferenevetorsformonthisplaneanangle

θ = arccos(R artery , R vein )

thatisgivenbythearosineoftheorrelationoeientbetweenthereferenes,whih

we termedasskewangle (seeFig. 2.1a).

Thelength ofthe projetion vetorof timeourseofthetest vetoronto thisplane

gives the signal strength information. The diretion angle omparison with the skew

angleindiates whetheritisapartofanarteryoravein. Theoordinatesofprojetion

vetorinthisplanearetheross-orrelation oeients

c(T, R artery )

^and

c(T, R vein )

^of

thetimeourseofthetestvetorobtainedwithrespettoarterial refereneandvenous

referene,respetively.

Thus,thealulationoflengthanddiretionofanyvetorinthevesselplaneanbe

performedprovided itsross-orrelationoeientsareknown. Inordertosimplifythis

algebraimanipulation, thevesselplaneisonvertedintoan orthonormal(retangular)

oordinate system. Although any arbitrary orthonormal system an be hosen, for

simpliity an orthonormal system formed by

(R artery , R ^⊥ _artery )

^{is hosen (Fig. 2.1b).}

The oordinates of any vetor in the new orthonormal systeman be alulated from

theorrelationoeients usingtheoordinate transformation formula given by

"

T R artery

T _R ⊥ artery

#

=

1 0

− cot(θ) csc(θ)

c(T, R artery ) c(T, R _vein )

(2.5)

where

T _{R artery}

^and

T _R ⊥ artery

are oordinates of the test vetor inthe new orthonormal

referenesystem, and

θ

^{is the skew angle. The alulation of the length and diretion}

of any vetor in this retangular oordinate systemmay be done by onverting it into

apolaroordinate system. Theretangular topolaroordinate transformationisgiven

by:

r = q

(T R artery ) ² + (T _R ⊥

artery ) ² ,

^(2.6)

α =

^sign

(T _R ⊥

artey ) arccos

T R artery

r

,

^(2.7)

where

0 ≤ r < ∞

^and

− π < α ≤ π

^{. In order to form an image from length}

r

^and

diretion angle

α

^{,olormapenodingmay be used.}

2.2.3 RGB Enoding

Colormapshavemoredegreesoffreedomasomparedtogray-levelmaps. Forexample,

anRGBmapsynthetiallyrepresentsthreegray-levelmapsinoneimage. Inthepresent

ase, two salarvalues, thevetor length

r

^{and the diretion angle}

α

orresponding to eah voxel are enoded using RGB olormap. The RGB olormap enoding leads to

simultaneous visualization of both arteriogram (red) and venogram (blue); otherwise

impossible withgray-levelenoding.

The parameter

α

^{is an angle between a vetor and the arterial referene in an}

orthogonal system formed by arterial and venous referene. Hene, it indiates the

proximityofthat vetorwitheitherthearterial referene orthevenous referene. The

omparisonofthebisetorofskewanglebetweenarterialrefereneandvenousreferene

and

α

^{ategorizesthevetoraspartofan}arteriogram(red)oravenogram(blue). If

α

^is

muh higherthanthearterialorvenousreferenediretionangle, thevoxelisidentied

asnoiseandmappedasbakgroundsignal(blak). Parameter

r

^{representsthelengthof}

theprojetion ofthetest vetoronto the vesselplane. Therefore, itisdiretlymapped

asbrightness of the voxel.

Figure2.2showstheolorassignedtoeahvetorlyingonthevesselplaneusingthe

RGB olor map. The region inproximity to the bisetor of skew angle appears purple

inolor dueto mixed mappingof redand blueolors.

Figure2.2: RGB olor enoding of the vesselplane. The skew angle

θ

^{is indiated as}

the angle between the referene diretions. Four zones are identied in the plane, a

purearterialbloodzone(red),wherephaserangesfrom

− ^θ / 2

^to

θ / 4

^{;amixedbloodzone}

(purple), with range

θ / 4

^,

3 / 4 θ

^{; a pure venous blood zone (blue), with range}

³ / 4 θ

^,

³ / 2 θ

^;

anda no vessel zone(blak), rangingoutside theaforementionedones.

2.3 Implementation

Thedouble refereneross-orrelation algorithm wasimplemented asANSI Cplug-ins

forMatlab(TheMathworksIn.,Natik,MA).Allprogramswereimplementedona64-

bitpersonalomputerwith2 GB of RAMrunning GNU/Linux(kernel version2.6.12)

operatingsystem. Theeetiveomputationtimewiththis ongurationwaslessthan

aminuteforeahdataset. Inordertoimprove theworkowinalinialenvironment,a

userinterfaebasedonQtgraphilibraries(NokiaQtSoftware,Norway)wasspeially

developed, whih inluded a database interfae where DICOMinformation wasstored,

andan interfae to seletthedatasets to useforanalysis (seeg. 2.3).

Thealgorithm requirestheseletionofreferenetimeoursesfor arteriesandveins.

This an be done manually by a spei user interfae (g. 2.4), by seleting points

ineasily-identiable vessels (arotid artery and superior sagittal sinus), or byusing a

lusteringalgorithm (desribedinhapter3) thatautomatiallyidenties thereferene

timeourses.

2.4 Experiments

Toevaluatethedoublerefereneross-orrelationtehnique,tenrandomlyhosentime-

resolved 3D erebral CE-MRA datasets from patients in whom neurovasular disease

was ruled out by MR and MRA workup were inluded in this analysis. In addition,

Figure 2.3: Dataset seletion interfae, with previews. It also inlude some basi DI-

COMfuntionality (DICOMsend, save to disk,delete).

Figure2.4: Interfae for manualseletion of referenepoints.

twodatasetsfrompatientswithaerebralduralarteriovenousstulaasprovenbyDSA

wereinluded. Thisretrospetiveanalysisofthepatientdatawasapprovedbytheloal

ethisboard.

2.4.1 MRI image aquisition

Cerebral time-resolved 3D-MRA datasets used for this study were aquired using 3D

FLASH sequene implemented on a 1.5T MRI system (Magnetom Avanto, Siemens

MedialSolutions, Erlangen,Germany)asdesribed byMekeletal[6,7℄. Anin-plane

resolutionof2.0mmx2.0mmwithasliethiknessof2.2mmandatemporalresolution

of 1.5 se per 3D dataset were obtained. A single bolus of ontrast agent (0.5 molar

Gadolinium-DOTA) was administered using a power injetor(20 ml, 3 ml/s) followed

by a saline ush. In total, a series of 25 3D-datasets were aquired in 37.5 seonds,

where theaquisition of therstdataset was startedsimultaneouslywiththeinjetion

oftheontrast agent bolus.

Toevaluate theeetoftime resolutiononthe separationperformane,onedataset

was downsampled from the original time resolution (1.5s) to lower sampling periods

(3.0s, 4.5s, 6.0s and 7.5s) to mimi multiple aquisitions at dierent time resolutions.

The ross-orrelation and the double-referene orrelation algorithms were then inde-

pendently applied on allobtained datasets.

Inordertodiretlyomparetheresultsofthedouble-refereneorrelationalgorithm

withtheross-orrelationtehnique,graylevelmapswerealsoalulatedfromtheRGB

images. This was ahieved by alternatively seleting the red hannel and the blue

hannelinformationfordiretomparisonwiththestandardross-orrelationalgorithm

andquantitative analysis.

2.4.2 Data analysis and quality assessment

The results of the double-referene orrelation algorithm were presented to two ex-

periened radiologists for qualitative evaluation as red-green-blue maximum intensity

projetion images. Theywere asked to deide whether the artery/veinseparation was

orret, andto identify and desribe possible pathologies.

Quantitative assessment of the separation eieny was evaluated by alulating

theontrast between arteries and veins inthearterial and venousgraylevel maps. For

this purpose, the sagittal maximum intensity projetions (obtained with the double-

referene orrelation and with the ross-orrelation algorithms) were alulated, and

ROIs were seleted in the arteries of the irle of Willis and in the superior sagittal

sinus. Speial attention was taken so to selet areas where arteries and veins do not

overlapinthe projetion. The meanintensities ofthe ROIs werealulated intheal-

ulated arterial map and inthe alulated venous map. The ontrasts were alulated

as artery/vein intensity ratio between the values obtained from the arterial map, and

asvein/arteryintensityratio between thevalues obtained from thevenousmap. With

this method,four values were obtained for eah dataset, i.e.

AV DRC

^,

AV CC

^,

V A DRC

^,

V A _CC

^,respetively representingtheartery/veinontrast inthedouble-referene orre- lation arterial map, the artery/vein ontrast in the ross-orrelationarterial map, the

vein/arteryontrastinthedouble-refereneorrelationvenousmapandthevein/artery

ontrast in the ross-orrelation venous map. In ase of perfet separation, these in-

dies would all assume an innite value. The results were ompared by alulating

thedierenebetweentheontrast obtainedwithross-orrelationandtheontrast ob-

tainedwithdouble-refereneorrelation,dividedbytheontrastoftheross-orrelation

algorithm.

2.5 Results

2.5.1 Visual assessment of the vessels

The radiologists reported a orret visual separation of arteries and veins using the

double referene ross-orrelation algorithm on all datasets. Examples are shown in

gure 2.5 , representing arteriograms and venograms of ve datasets, and in gure

2.6,where theresultsobtainedwiththedoublerefereneross-orrelationalgorithmon

the dataset of a normal subjet are ompared to the results deriving from the ross-

orrelationtehnique.

The improvement on the separation of arteries and veins was visually pronouned

if the skew angle was low, indiating a high bolus dispersion, as shown in gure 2.7

. In both datasets from patients suering from dural erebral arteriovenous stulas,

the radiologists were able to identify, in aordane to the ndings from DSA, four

funtional typesof vessels,asshowningure2.8. Thearteries were depitedinred;

the veins with normal (late) venous outow in blue; the arterialized veins, i.e. the

veins with early lling with arterial blood due to the stula, and no normal venous

outow inred; veins that showed early llingwith arterial blood but also late venous