magnetic resonance imaging characterization of microbial infections

great potential for this purpose, since red fluorescent dyes increase2.. ClassicalMRImodalities.ACoronalturbospinechoRAREimagesofthemousebrainshowingprotondensity-,T2-andT1-weightedMRcont

Contents lists available at ScienceDirect

Verena Hoerr ∗ , Cornelius Faber

DepartmentofClinicalRadiology,UniversityHospitalofMuenster,48149Muenster,Germany

a r t i c l e i n f o

Articlehistory:

Received11June2013

Receivedinrevisedform19October2013

Accepted23October2013

Availableonline7November2013

Keywords:

Microbialinfections

MRImodalities

Molecularimaging

Contrastagents

a b s t r a c t

Theinvestigationofmicrobialinfectionsreliestoalargepartonanimalmodelsofinfection,ifhost pathogeninteractionsorthehostresponseareconsidered.Especiallyfortheassessmentofnovel ther-apeuticagents,animalmodelsarerequired.Non-invasiveimagingmethodstostudysuchmodelshave gainedincreasingimportanceovertherecentyears.Inparticular,magneticresonanceimaging(MRI) affordsavarietyofdiagnosticoptions,andcanbeusedforlongitudinalstudies.Inthisreview,we intro-ducethemostimportantMRImodalitiesthatshowhowMRIhasbeenusedfortheinvestigationofanimal modelsofinfectionpreviouslyandhowitmaybeappliedinthefuture

©2013TheAuthors.PublishedbyElsevierB.V.Allrightsreserved

1 Introduction

夽 Thisisanopen-accessarticledistributedunderthetermsoftheCreative

Com-monsAttribution-NonCommercial-NoDerivativeWorksLicense,whichpermits

non-commercialuse,distribution,andreproductioninanymedium,providedthe

originalauthorandsourcearecredited

∗ Correspondingauthorat:Albert-Schweitzer-Campus1,BuildingA16,48149

Muenster,Germany.Tel.:+492518352418

E-mailaddress:vhoerr@uni-muenster.de(V.Hoerr)

0731-7085/$–seefrontmatter©2013TheAuthors.PublishedbyElsevierB.V.Allrightsreserved

great potential for this purpose, since red fluorescent dyes increase

2 Endogenous MRI contrast

Fig 1. ClassicalMRImodalities.(A)Coronalturbospinecho(RARE)imagesofthemousebrainshowingprotondensity-,T2-andT1-weightedMRcontrast.(AI)protondensity (TE:9.8ms,TR:3000ms),(AII)T2(TE:69ms,TR:3000ms)and(AIII)T1(TE:9.8ms,TR:400ms)weightedimageswereacquiredat9.4Twiththefollowingparameters(slice thickness:1mm,fieldofview:2cm×2cm,matrixsize:206×206,numberofaverages:4).(B)Coronaldiffusiontensorimaging(DTI)ofthemousebrainshowing(BI)the fractionalanisotropy(FA),(BII)preferreddiffusiondirectionsencodedbytheindicatedcolorsphere,and(BIII)thelocalapparentdiffusioncoefficient(ADC),depictedas ADCmap.HighADCvaluesappearbrightonthemapandindicatelesstightlyorganizedtissue.Imageswereacquiredat9.4Twiththefollowingparameters(TE:35ms,TR:

2250ms,slicethickness:1mm,30gradientdirections,Bvalue1000s/mm2,fieldofview:2cm×2cm,matrixsize:128×128)

Fig 2.CerebralinflammationinducedbyHerpessimplexvirus-1.CoronalT2weightedturbospinecho(RARE)imagesofthemousebrain.(A)Brainofahealthymouse (B)Day7ofanherpessimplexvirus-1infectedmouseshowingexpandedlesionsfromtheBulbusolfactoriustotheCortexcerebri(yellowarrowsinthelateralareasofthe brain).Imageswereacquiredona9.4TBiospec94/20smallanimalscannerwiththefollowingparameters(TE:40ms,TR:4500ms,slicethickness:0.6mm,fieldofview:

2cm×2cm,matrixsize:256×256,numberofaverages:4).(Forinterpretationofthereferencestocolorinthisfigurelegend,thereaderisreferredtothewebversionof thisarticle.)

Table 1

TypicalTEandTRvaluesusedforspinechoandgradientechosequences

aRequiresbothshortTRandshortTE

bRequiresbothlongTRandlongTE

c RequiresshortTRandlongTE

d Dependsonmagneticfieldstrength.HigherB0fieldsrequirelongerTRandshorterTE

eTRdependsontheappliedflipangle

3 Functional parameterization

[41,53–62]

label-ing [69,70] TOF and phase-contrast MRA are the most commonly

4 Molecular MR imaging

5 Iron oxide particles

even single mammalian cell can be detected and tracked by MRI

( Fig 3 A) [98–104] , indicating the suitability of iron contrast as

6 Lanthanide chelates

[121–125]

Fig 3.Detectionofiron-labeledmacrophagesandiron-labeledbacteria.MRimagesofasubcutaneousS.aureusinfectionat24hpostinfection.(A)AxialT2*-weightedFLASH MRIofasubcutaneousinfectioninducedwithunlabeledbacteria,followingintravenousco-injectionof5-nmSPIOs2hand5hpostinfection.SPIOswerephagocytozedby macrophagesandweredetectedassignalvoids(yellowarrowheads)atthezoneofinfection(yellowellipsoid).(B)AxialT2*-weightedFLASHimagesofthemouseflank, revealinganulcerousabscess(yellowellipsoid)withbacterialcolonization(yellowarrow)wheniron-labeledbacteriawereusedtoinducetheinfection.Imageswereacquired

ona9.4TBiospec94/20smallanimalscannerwiththefollowingparameters(TE:6ms,TR:1500ms,flipangle:30◦,slicethickness:0.5mm,fieldofview:3.2cm×3.2cm, matrixsize:256×256,numberofaverages:2).(Forinterpretationofthereferencestocolorinthisfigurelegend,thereaderisreferredtothewebversionofthisarticle.)

7. 19F imaging

Fig 4. CerebrallesionsenhancedbyGd-contrast.SagittalT1-weightedFLASHimagesofthebrainofanEAE(experimentalautoimmuneencephalomyelitis)mouse(A) preand(B)postGd-administration.Inpre-contrastimages,inflammatorylesionswerenotdetected.Thelateralventricle(yellowarrowhead)appearedhypointense pre-contrast.AfterGdadministration,inflammatorylesionswithimpairedblood–brain-barrierweredetectedashyperintensities,inthecaudateputamen(yellowarrow).Images wereacquiredona9.4TBiospec94/20smallanimalscannerwiththefollowingparameters(TE:2.6ms,TR:30ms,flipangle:30◦,slicethickness:0.5mm,fieldofview: 1.5cm×1.5cm,matrixsize:128×128,numberofaverages:2).(Forinterpretationofthereferencestocolorinthisfigurelegend,thereaderisreferredtothewebversion

Fig 5.19FMRIofamurineS.aureusthighinfectionatday3postinfection.12hpostPFC(perfluorcarbon)administration,PFCphagocytozedbymacrophageswasdetected

atthesiteofinfectionandallowedforassessmentofantibiotictreatment.19FSSFP-CSIimagesoftheinfectedthighmuscletreatedwith(A)0.9%NaCl,(B)Vancomycinand (C)Linezolid

Reprintedwithpermissionfromreference[166]

MRI [136–139] 19F is a spin-½ isotope with a 100% natural

sig-nal [77,140] Its gyromagnetic ratio differs only 6% from that of a

[141,142]

[142,144] Compared to other fluorinated compounds whose

tracking.

[153,154] To achieve T1 weighted images these sequences are

[158] , making ultrafast sequences such as UTE or zero-echo-time

8 Novel approaches and challenges

applied to infectious diseases [172–176] Even though the

investi-gations.

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