Diffusion weighted imaging and diffusion tensor imaging in the evaluation of transplanted kidneys

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Availableonlineatwww.sciencedirect.com

ScienceDirect

EuropeanJournalofRadiologyOpen2(2015)71–80

Diffusion

weighted

imaging

and

diffusion

tensor

imaging

in

the

evaluation

of

transplanted

kidneys

Stefano

Palmucci

a,∗

,

Giuseppina

Cappello

a

,

Giancarlo

Attinà

a

,

Pietro

Valerio

Foti

a

,

Rita

Olivia

Anna

Siverino

a

,

Federica

Roccasalva

a

,

Marina

Piccoli

a

,

Nunziata

Sinagra

b

,

Pietro

Milone

a

,

Massimiliano

Veroux

b

,

Giovanni

Carlo

Ettorre

a

a_{Radiodiagnostic}_and_Radiotherapy_Unit,_University_Hospital_{“Policlinico-Vittorio}_Emanuele”,_Via_Santa_Soﬁa_78,₉₅₁₂₃_Catania,_Italy b_Vascular_Surgery_and_Organ_Transplant_Unit,_Department_of_Surgery,_{Transplantation}_and_Advanced_{Technologies,}_University_Hospital_{“Policlinico-Vittorio}

Emanuele”,ViaSantaSoﬁa78,95123Catania,Italy Received12March2015;accepted4May2015

Availableonline16May2015

Abstract

Objective: TheaimofthisstudyistoinvestigatetherelationbetweenrenalindexesandfunctionalMRIinapopulationofkidneytransplant recipientswhounderwentMRwithdiffusion-weightedimaging(DWI)anddiffusiontensorimaging(DTI)ofthetransplantedgraft.

Method: Studypopulationincluded40patientswithsinglekidneytransplant.Thepatientsweredividedinto3groups,onthebasisofcreatinine clearance(CrCl)valuescalculatedusingCockcroft-Gaultformula:groupA,includingpatientswithnormalrenalfunction(CrCl≥60mL/min); groupB,whichreferstopatientswithmoderaterenalimpairment(CrCl>30but<60mL/min);and,finally,groupC,whichmeanssevererenal deterioration(CrCl≤30mL/min).Allpatientswereinvestigatedwitha1.5TeslaMRIscanner,acquiringDWIandDTIsequences.AMann–Whitney Utestwasadoptedtocompareapparentdiffusioncoefficients(ADCs)andfractionalanisotropy(FA)measurementsbetweengroups.Receiver operatingcharacteristic(ROC)curveswerecreatedforpredictionofnormalrenalfunction(groupA)andrenalfailure(groupC).Pearsoncorrelation wasperformedbetweenrenalclearanceandfunctionalimagingparameter(ADCandFA),obtainedforcorticalandmedullarregions.

Results: Mann–WhitneyUtestrevealedahighlysignificantdifference(p<0.01)betweenpatientswithlowCrCl(groupC)andnormalCrCl (groupA)consideringbothmedullarADCandFAandcorticalADC.Regardingcontiguousgroups,thedifferencebetweengroupBandCwas highlysignificant(p<0.01)formedullarADCandsignificant(p<0.05)forcorticalADCandmedullarFA.Nodifferencebetweenthesegroups wasfoundconsideringcorticalFA.AnalyzinggroupsAandB,wefoundasignificantdifference(p<0.05)formedullarbothADCandFA,while nodifferencewasfoundforcorticalADCandFA.

StrongestPearsoncorrelation wasfound betweenCrCland medullarADC (r=0.65). Forpredictingnormalrenalfunctionorsevererenal impairment,highestvaluesofAUCwereobservedusingmedullarADCcut-offvalues(respectively0.885and0.871);medullarFAshowedalso highaccuracy(respectively0.831and0.853).

Conclusions: DWIandDTIarepromisingtoolsfornon-invasivemonitoringofrenalfunction;medullarADCprovedtobethebestparameterfor renalfunctionassessment.

Keywords:Magneticresonanceimaging;DiffusionweightedMRI;Diffusiontensorimaging;Kidneytransplantation

Abbreviations:DWI,diffusionweightedimaging;ADC,apparentdiffusion coefficient;DTI,diffusiontensorimaging;FA,fractionalanisotropy;CrCl, cre-atinineclearance;ROI,regionofinterest;ROC,receiveroperatingcharacteristic curve;AUC,areaunderthecurve.

∗_{Corresponding}_author._Tel.:_{+390953782360;}_fax:_{+390953782368.}

E-mailaddress:[email protected](S.Palmucci).

1. Introduction

Renal graft function is monitored using clinical parame-ters – such as serum creatinine, creatinine clearance – and imagingmodalities,mainlyrepresentedbyultrasound, ecocolor-doppler and scintigraphy; however, the assessment of renal diseaserequiresparenchymalbiopsytomakeacorrect diagno-sis,gradingalsothelevelofdamage.Renalbiopsyisaninvasive http://dx.doi.org/10.1016/j.ejro.2015.05.001

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offunctionalMRIintheevaluationofkidneydiseases[4].DWI hasbeenusedtocharacterizefocalrenallesions[5],andto inves-tigaterenalfunction,eitherinnormalkidneys[6]orrenalgraft also[7].

Allrenalfunctions,suchasglomerularfiltration,tubular reab-sorptionand secretion,arebased onwater transportation[8]. Thus,quantification of Brownian motions measuredby DWI mayprovideafunctionalassessmentofrenalparenchyma. Dif-fusionandperfusioneffectsareexpressedbyanumericalvalue, namedADC, whichdecreases withrestrictionofdiffusionof watermolecules.ADCisdefinedas“anaverageindexofhow freelywatercanmovewithinavoxel(i.e.averagedacross all tissuestructuresandcompartmentswithinthevoxel)andhence thetermapparent”[9].

However,molecularmotilitymaynotbethesameinall direc-tions,leadingtoacertainanisotropy.Itcanbedueforexample toanobstaclelimitingmolecularmovementsortotheanatomic orientationofthestructuresofthetissue.DTIisabletoevaluate diffusionanisotropymeasuringdiffusionofwatermoleculesfor eachsingledirection ofthegradient pulses.DTIallowsusto obtaininvivoinformationaboutorientedtissues,suchasbrain whitematter,musclesandmyocardium[10].Itsrolehasbeen emphasizedinbrainstudy, particularly inpatients withbrain tumorstoevaluatedisplacementorinterruptionofwhitematter pathways,andindemyelinatingdiseasetodetectsubtlechanges inmyelinfibersintegrity [11].Asinbrainwhite matter,also inrenalmedulla thereis anintrinsic orientationof the struc-turesbecauseit isassembledintubuliandductiwithparallel coarse.Thus,severalstudieshavepointedoutthatnormalrenal architecturesuggestadifferentevaluationofdiffusiondirection usingDTI,thatcouldbeabletoevaluatethedegreeofmedullary anisotropy[12].

Thepurposeofourstudy wastoevaluatetheusefulnessof DWI and DTI in assessing allograft dysfunction correlating ADC and FA values with laboratory data; diagnostic accu-racy of ADC and FA is calculated, in order to investigate whichisthemostusefulparameterfortheevaluationofrenal function.

2. Materialandmethods

2.1. Studypopulation

PatientswereenrolledbetweenSeptember2014andJanuary 2015.Thisstudywasapprovedbyourinternalethicscommittee

period. MRI examinations were performed at a mean post-transplant time of 3.8 years (range, 8 days-22.8 years). No patientswereexcludedfromthisstudy.

Kidneytransplantations,clinicalmanagementandfollow-up were performed by the same surgical team. All transplanted kidneyswereplacedintherightiliacfossawithvascular anas-tomosestothecommonorexternaliliacvessels.The patients weredividedinto3groups,onthebasisofCrClvaluescalculated usingCockcroft-Gaultformula:

- groupA,patientswithCrCl≥60mL/min; - groupB,patientswithCrCl>30but<60mL/min; - groupC,patientswithCrCl≤30mL/min.

2.2. MRIprotocol

Allexaminationswereperformedusinga1.5Teslascanner (SignaHDxt,GeneralElectric).Imageswereacquired withan 8-channels array coil (8 channel bodycoil), using the lower configuration;sequenceswerenotrespiratory-triggered,sothat no“respiratory”beltwasused.

UnenhancedT1andT2-weightedsequenceswereperformed before DTIin order toobtain a morphological evaluation of transplanted kidneys. Axial sequences were positioned per-pendicularly to the major axis of the kidney (Fig. 1). No intravenoushypotonicagentwasadministrated.Protocol exam-inationincluded:

- Axial T2-weighted Fast Recovery Fast Spin Echo

sequence, obtained with a TR=3200ms, TE=110ms, thickness=5mm, gap interval=0.5mm, Number of Excitations=4,matrix=320×224,FieldofView=36–40; - Coronal T2-weighted Fast Recovery Fast Spin Echo

sequence, obtained with a TR=3100ms, TE=103ms, thickness=3mm,gapinterval=0.3mm,Numberof Excita-tions=4,matrix=320×224;

- Diffusion-weighted sequences, obtained by Single Shot Echo Planar Imaging technique, using a b value of 500. Namely, acquisition parameters were the following: TR=3000ms; TE=40–79ms; Number of Excitations=2; acceleration factor=2; EPI factor=80; thickness=5mm; spacing=1mm; FieldofView=34–42;matrix=128×128, acquisitiontime=1min42s.

- DTIwasacquiredusinga“free-breathing”SingleShotEcho PlanarImagingtechnique,withdiffusiongradientactivefor 6 directions. Acquisition parameters were: TR=7500ms;

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S.Palmuccietal./EuropeanJournalofRadiologyOpen2(2015)71–80 73

Fig.1.Axialb=0(a),ADCmap(b)andFAmap(c)imagesofa52-yearoldwomanwithgoodrenalfunction(CrCl=104mL/min).FAmapshowsgoodvisual differentiationbetweencorticalandmedullarparenchyma.

TE=86ms; Number of Excitations=4; acceleration fac-tor=2; EPI factor=80; thickness=6mm; spacing=1mm; Field of View=34–42cm; matrix=128×128, acquisition time=3min38s.

2.3. Imageanalysis

Morphological evaluation of the transplanted kidney was performed using axial and coronal T2-weighted sequences. Weinvestigatedbothvascularandnonvascularcomplications thatmay affecttransplantedkidneys,such as focalor diffuse parenchymalsignalalterations,perirenalfluidcollections, lym-phoceles,arterial,venousandcollectingsystemabnormalities. Theseconditions,whichcanoccurbothintheearly postopera-tiveperiodandinthelong-term,mustberecognizedbecause theyinfluencethetransplantedpatients’outcome.ADCandFA werecalculatedbyplacingacircularROIbothinthecortical andinthemedullaforeachtransplantedkidneyinthreedifferent levels:upper,middleandlowerthird.Forpositioningofcortical andmedullarROIs,anatomicalT2-weighted acquisitions and b=0imageswereused.

TheROIs were alwaysplaced avoidingall possible inclu-sionsofvesselsandfocallesions.Ameanscorewasobtained for bothcorticalandmedullarADCvalues andfor both cor-ticalandmedullar FAvalues.Post-processingwasperformed using the General Electric Functool software package (GE Healthcare®).

2.4. Statisticalanalysis

StatisticalanalysiswasperformedusingWin-StatSoftware andaMedCalcprogram(MedCalcversion11.4.4.0,MedCalc Softwarebvba,Mariakerke,Belgium).

CorticalandmedullarADCandFAmeanvalueswere com-paredamongthethreedifferentgroupsusingtheMann–Whitney

Utest;p<0.05wasconsideredstatisticallysignificant.Both cor-ticalandmedullarADCandFAwerecorrelatedtoCrClusing Pearsonlinearregression.

Lastly, optimal ADC and FA threshold values for group membershipweredeterminedbyROCanalysis,calculating cor-respondingsensitivities,specificitiesanddiagnosticaccuracies.

3. Results

3.1. Qualitativeanalysis

Morphologicimagingshowedabsenceofrenaldiseasein23 patients.Novascularcomplications–suchasrenalartery steno-sisorpartialveinthrombosis–werefound.MRIdemonstrated 5fluidcollectionsand6lymphoceleslocatedinrenalgraftarea, behindtheiliacvesselsorneartheinguinalregion.Arenalmass wasfoundin1patient.In2patientsrenalpelvisdilatationwas demonstrated.3casesofpyelonephritiswerealsofound.

3.2. Quantitativeanalysis

Thepatients’distributioninto3groups,onthebasisofCrCl, wasasfollow(Table1):10patientsingroupA(4malesand6 females,withameanageof51.2years);12patientsingroup B(8malesand4females,withameanageof48.7years);18 patientsingroupC(12malesand6females,withameanage of51.6years).

ComparingmeanvaluesofcorticalADC(Fig.2),wedidnot observeasignificantdifference(p=0.06)betweengroupsAand B,whereaswefoundahighlysignificantdifference(p<0.01) inthecomparisonbetweengroupsAandC,andastatistically significantdifferencebetweengroupsBandC(p=0.02).

Comparing mean values of medullar ADC (Fig. 3) we observedasignificantdifference(p=0.02)betweengroupsA andB; ahighly significantdifference (p<0.01)was reported betweengroupsAandC,andbetweengroupsBandC.

Comparingmean valuesof corticalFA(Fig.4)we didnot observe a significant difference comparing groups A and B (p=0.74), groups A and C (p=0.63), and groups B and C (p=0.98).

Comparing mean values of medullar FA (Fig. 5) between groupsAandB,weobservedasignificantdifference(p=0.03). InthecomparisonbetweengroupsAandC,weobservedahighly significantdifference(p<0.01).FormedullarFA,thedifference reportedbetweengroupsBandC,wasalsosignificant(p=0.02). Pearsoncorrelationtestshowedastrongpositivecorrelation betweenCrClandmedullarFA(Fig.6a),withacoefficientof 0.62whilecorticalFAshowednocorrelationwithrvalue<0.1. For ADC values a positive correlation was found between

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P almucci et al. / Eur opean Journal of Radiolo gy Open 2 (2015) 71–80

GroupA GroupB GroupC

CrCl≥60mL/min CrCl>30<60mL/min CrCl≤30mL/min

PT ClCr ADCcort ADCmed FAcort FAmed PT ClCr ADCcort ADCmed FAcort FAmed PT ClCr ADCcort ADCmed FAcort FAmed 2 67 2.31 2.36 0.265 0.233 3 45 1.75 2.17 0.278 0.230 1 17 2.63 2.30 0.213 0.149 4 94 2.57 2.41 0.288 0.347 6 55 2.36 2.09 0.203 0.154 5 21 2.19 2.40 0.264 0.139 7 71 2.39 2.54 0.315 0.231 10 42 2.14 2.36 0.179 0.202 9 4 2.23 1.82 0.203 0.156 8 104 2.56 2.18 0.187 0.311 11 36 2.63 1.93 0.232 0.263 12 15 1.62 1.75 0.245 0.172 13 72 2.19 2.48 0.217 0.340 17 34 2.13 1.90 0.229 0.204 14 7 1.97 1.83 0.319 0.177 15 116 2.90 2.55 0.193 0.267 20 50 2.10 2.16 0.074 0.261 16 28 1.62 1.79 0.280 0.100 19 92 2.48 2.55 0.204 0.262 22 32 1.99 2.03 0.171 0.142 18 30 2.16 2.36 0.224 0.284 27 99 2.26 2.40 0.267 0.197 25 44 2.04 2.61 0.289 0.190 21 26 1.83 1.95 0.176 0.225 31 74 2.20 2.46 0.183 0.474 29 34 2.13 2.30 0.223 0.222 23 18 1.88 2.08 0.238 0.213 34 93 1.89 1.96 0.188 0.213 33 51 2.54 2.39 0.318 0.260 24 10 2.14 1.66 0.201 0.103 36 57 2.36 2.23 0.246 0.328 26 20 1.86 1.92 0.152 0.156 39 52 1.88 2.04 0.151 0.225 28 9 1.96 1.91 0.166 0.118 30 15 1.87 1.79 0.120 0.111 32 11 1.91 1.71 0.193 0.103 35 30 1.80 1.98 0.294 0.191 37 24 1.75 1.94 0.178 0.197 38 29 1.70 1.84 0.202 0.275 40 19 1.50 1.64 0.305 0.190

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Fig.2.Box-and-whiskerplotforcorticalADCvalues(a–c):consideringcorticalADCmeasurement,wefoundasignificantstatisticaldifferenceonlycomparing groupsBandC(b)andgroupsAandC(c).NodifferencewasobservedforcorticalADCmeasurementsbetweengroupAandB(a).

Fig.3. Box-and-whiskerplotformedullarADCmeasurements(a–c):comparingmeanvaluesbetweengroupsAandB(a)weobservedasignificantdifference (p=0.02).ComparinggroupsBandC(b),thedifferencewashighlysignificant,withap<0.01.Highlysignificantdifference(p<0.01)wasreportedinthecomparison betweengroupsAandC(c).

medullarADCandCrCl,withrcoefficientof 0.66(Fig.6b). Amoderatepositivecorrelationwasreportedbetweencortical ADCandCrCl,withrcoefficientof0.57.

ROCanalysisfor predictionof normalclearance valuesor advancedrenal impairmentusing ADCandFA mean values, areshowninFigs.7and8respectively.

In the prediction of renal low clearance values (patients of group C), using a threshold cortical ADC value ≤1.97×10−3mm2/s,theROCcurveshowedanAUCof0.814, a 95% Confidence Interval (CI) for the area=0.660–0.919, with sensitivity of 72.2% and specificity of 86.4%; for pre-dictionof normalrenalfunction(groupA),usingathreshold

Fig.4.Box-and-whiskerplotforcorticalFAvalues(a–c):nodifferencewasobservedcomparingmeanvaluesbetweengroupsAandB(a),betweengroupsBand C(b)andbetweengroupsAandC(c).

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Fig.5.Box-and-whiskerplotformedullarFAmeasurements(a–c):comparingmeanvaluesbetweengroupsAandB(a),weobservedasignificantdifference (p=0.03).IncomparinggroupsBandC(b),thedifferencewasalsosignificant(p=0.02).InthecomparisonbetweengroupsAandC(c),weobservedahighly significantdifference(p<0.01).

cortical ADC value >2.16×10−3mm2/s, the ROC curve showedan AUCof 0.832, 95%CI=0.680–0.931, with sensi-tivityof90%andspecificityof76.7%.

In the predictionof renallow clearance values(group C), using a thresholdmedullar ADC value≤1.98×10−3mm2/s, 95%CI=0.727–0.956,theROCcurveshowedanAUCof0.871, withsensitivityof77.8%andspecificityof86.4%.Forthe pre-dictionofrenalnormalclearancevalues(patientsofgroupA) usingathresholdmedullarADCvalue>2.3×10−3mm2/s,95% CI=0.744–0.964,theROCcurveshowedanAUCof0.885,with sensitivityof80%andspecificityof83.3%.

In the prediction of renal low clearance values (patients of group C) using a threshold cortical FA value ≤0.178×10−3mm2/s,95%CI=0.363–0.686,theROCcurve showed an AUC of 0.527, with sensitivity of 27.8% and specificityof86.4%. Forpredictionofrenalnormalclearance values (patients of group A) using a threshold cortical FA value>0.179×10−3mm2/s,95% CI=0.385–0.707, theROC curveshowedanAUCof0.550,withsensitivityof100%and specificityof30%.

In the prediction of renal low clearance values (patients

of group C) using a threshold medullar FA value

≤0.197×10−3mm2/s, 95% CI=0.679–0.930, the ROC curve showed an AUC of 0.831, with sensitivity of 77.8% and specificity of 81.8%. For prediction of renal normal clearance values (group A), using a threshold medullar FA value >0.23×10−3mm2/s, the ROC curve showed an AUC of 0.853, 95% CI=0.706–0.945, withsensitivity of 80%and specificityof80%.

4. Discussion

Several authorshaveinvestigatedtherole ofDTIfor eval-uation ofnormalandinjuredkidneys.Gursesetal.andWang etal.showed thefeasibilityof renaldiffusiontensorimaging and repeatabilityof FAmeasurements [13,14].Other authors triedtocorrelateDTIparametersmeasurementstorenalfunction in patients withchronic kidney diseases [15–17]. In particu-lar,alltheseauthorsagreethatdecreaseofFAvaluesofrenal parenchymareflectsseverityofrenaldamage.Liuetal.founda

Fig.6.ScatterdiagramsofPearsoncorrelationbetweenmedullarFAandClCr(a),andmedullarADCandCrCl(b),bothshowingastrongcorrelation(respectively r=0.62andr=0.66).

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Fig.7.ROCcurvesinpredictionofgroupA:theROCcurve(a)showsanAUCof0.871,withasensitivityof77.8%andspecificityof86.4%inthepredictionoflow creatinineclearancevalues(groupC)usingathresholdmedullarADCvalue≤1.98×10−3mm2_/s._AUC_of_0.814_(b),_with_a_sensitivity_of_72.2%_and_specificity_of

86.4%wasfoundusingathresholdcorticalADCvalue≤1.97×10−3mm2_/s._The_ROC_curve_(c)_shows_an_AUC_of_0.831,_with_a_sensitivity_of_77.8%_and_specificity

of81.8%usingathresholdmedullarFAvalue≤0.197×10−3mm2_/s._Finally_(d)_an_AUC_value_of_0.527,_with_a_sensitivity_of_27.8%_and_specificity_of_86.4%,_was

reportedusingathresholdcorticalFAvalue≤0.178×10−3mm2_/s.

positivecorrelationbetweenFAandeGFR(estimated glomeru-larfiltrationrate):r=0.689forcortexandr=0.696formedulla

[15].Wangetal.demonstratedthatcorticalandmedullarADC andFAvaluesweresignificantlylowerinpatientswithchronic kidney diseasethan thoseof healthyvolunteers: thesevalues showed negativecorrelationwithserum creatinineandblood ureanitrogen[16].Gaudianoetal.investigatedtheroleofFA valuesinawidespectrumofchronickidneydiseases,showing that onlymedullaryFAcould beamarker of renalstructural integrityalterations[17].

Inaddition,Luetal.studiedearlychangesofDTparameters indiabeticnephropathyfindinglowermeanmedullaryFAand ADCvaluesamongdiabeticswithrelativelyintactrenal func-tion(eGFR≥60ml/min/1.73m2₎_compared_to_healthy_controls.

ThesefindingssuggestthatmedullarybothFAandADCmay identifyearlychangesindiabetics[18].

DiffusionMRIhasbeenusedalsotoevaluaterenalallograft function [19–21]. Palmucci et al.evaluated the role of ADC measurementsintransplantedkidneyfindinganADCthreshold ≥2.08×10−3mm2/stopredictanormalclearance,althougha certainoverlapbetweengroups[19].

Hueperetal.studiedDTIasnon-invasivetoolfordetectionof allograftdysfunctionsfindingasignificantreductionofmedullar FAintransplantedkidneyscomparedtohealthyvolunteers.They alsofoundastrongcorrelationbetweenmeanFAinthemedulla andeGFR(r=0.72)[20].

In a recent work by Lanzman et al. [21], the relation-ship between FA, ADC and renal function was analyzed.

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Fig.8.ROCcurvesinpredictionofgroupC:theROCcurve(a)showsanAUCof0.885,withasensitivityof80%andspecificityof83.3%inthepredictionof normalcreatinineclearancevalues(groupA)usingathresholdmedullarADCvalue>2.3×10−3mm2_/s._AUC_of_0.832_(b),_with_a_sensitivity_of_90%_and_specificity

of76.7%wasfoundusingathresholdcorticalADCvalue>2.16×10−3mm2_/s._The_ROC_curve_(c)_shows_an_AUC_of_0.853,_with_a_sensitivity_of_80%_and_specificity

of80%usingathresholdmedullarFAvalue>0.23×10−3mm2/s.Finally(d),anAUCvalueof0.550,withasensitivityof100%andspecificityof30%,wasreported usingathresholdcorticalFAvalue>0.179×10−3mm2/s.

They divided patients into two groups according to eGFR: group A (eGFR>30mL/min/1.73m2) and group B (eGFR≤30mL/min/1.73m2). Cortex and medulla ADC val-uesshowedhighervaluesinpatientsofgroupA,comparedwith patientswithimpairedfunction[21].MeanFAvaluesforcortex andmedullaweresignificantlyhigheringroupA(0.39±0.06 and0.17±0.4),incomparisonwithgroupB(0.27±0.05and 0.14±0.03) [21]. There was significant correlation between eGFRandmedullaryFA,witharvalueof0.65(p<0.01)[21]. Severaltheorieshavebeenproposedtoexplainwater diffu-sionreductioninrenaldiseases.

Incasesofrenaldysfunction,filtrationrateislowandwater transport processes decrease [22]. All pathogenetic features of graftrejection, such as inflammation,edema, necrosisand

fibrosis[23],decreaserenalwatercontent,perfusionand inter-stitialspacesreducingmolecularextracellularfreediffusionand resultinginadecreaseofADC[7].

Namely,ininterstitialfibrosis,collagendepositionnarrows spaces betweentubuli, andwaterdiffusionbecomes reduced. Recent experience byTogaoetal.hasalready confirmedthis fact:theseresearchersstoppedureteralexcretioninratsto evalu-ateADCbehaviorinrenalfibrosis.TheyfoundanADCdecrease relatedtoan increasednumberof cells,including fibroblasts, concludingthat“ADChasthepotentialtoserveasasensitive noninvasivebiomarkerofrenalfibrosis”[24].AlsoZhaoetal.,in arecentstudy,correlatedpathologicalfibrosisscorewithADC decreaseinpatientswithchronicrenaldiseases,findingagood correlation[25].

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S.Palmuccietal./EuropeanJournalofRadiologyOpen2(2015)71–80 79 In our study, the Mann–WhitneyU test revealed ahighly

significantdifference(p<0.01)betweenpatientswithlowCrCl (groupC)andnormalCrCl(groupA)consideringbothmedullar ADCandFAandcorticalADC.Regardingcontiguousgroups, differencebetweenpatientswithintermediatecreatinine clear-ance(groupB)andpatientsofgroupCwashighlysignificant (p<0.01)formedullarADCandsignificant(p<0.05)for corti-calADCandmedullarFA.Nodifferencebetweenthesegroups wasfoundconsideringcorticalFA.AnalyzinggroupsAandB, wefoundasignificantdifference (p<0.05)formedullar both ADCandFA,whilenodifferencewasfoundforcorticalADC andFA.

Wefoundagoodcorrelationbetween creatinineclearance andmedullarADC(r=0.65),andbetweencreatinineclearance andmedullarFA(r=0.62).Amoderatecorrelationwasobserved betweencreatinineclearanceandcorticalADC(r=0.56),while corticalFAdidshownocorrelation. Incontrastwithprevious studyofLanzmanetal.[21],corticalFAvalueswerenot signifi-cantlydifferentinourMann–Whitneyanalysis;acertaindegree of overlap wasobserved, with mediansof 0.211ingroup A, 0.226ingroupBand0.208ingroupC.Probably,different repar-titionofpatientscouldexplainthisdegreeofoverlap;however, ithastobenotedthatcorticalFAdidnotshowcorrelationalso inthepreviouslymentionedstudybyLanzman[21].

InbothpredictionofgroupCandgroupA,medullarADC revealedthebestaccuracy,showinganAUCof0.871,with sen-sitivityof77.8%andspecificityof86.4%,butalsomedullarFA showedahighaccuracy.

Limitationsofthisstudywerethesmallnumberofpatients enrolled,aswellastheabsenceofhistopathologiccorrelation.In addition,ahighermagneticfieldstrengthwouldhaveprovided abetter signal-to-noise ratio, higher values of FA andbetter imagesquality[26–28].

AcertaindegreeofoverlapforADCandFAvaluesamong thethreedifferentclassesstudiedrepresentsalimit.

Anotherlimitationisthatweusedonlysixencoding direc-tions: as demonstrated in a study by Chuck et al., a higher number of encoding directions results in better image qual-ityandimprovedcortico-medullarydiscrimination,althoughit doesnotinfluenceFAvalues.Althoughthelongeracquisition time, “the increase in image quality allows for a more pre-cisedataevaluationwhenplacingROIsforFAmeasurements”

[29].

5. Conclusion

TheseresultsemphasizedtheroleofDWI inevaluationof transplantedkidney:medullarADCresultedthebestparameter forrenalassessment,distinguishingbetweenpatientswithgood, moderateorimpairedrenalfunction.AmedullarADCvalueof 2.3maybeusedasathresholdforpredictinganormalclearance level.Inourstudy,alsomedullarFAvaluesgoodcorrelatedwith renalfunctionality,althoughinaslightlylowerdegree.However, acertaindegreeofoverlapbetweenADCandFAvalues,among thethreedifferentclasses,seemstolimituseoffunctionalMR indailyclinicalpractice.

References

[1]Franke M,KramarczykA,TaylanC, MaintzD,HoppeB,KoerberF. Ecoguidatabiopsiarenalepercutaneain295bambinieadolescenti:ilruolo dellaecografiaeanalisidellecomplicanze.PLOSONE2014;9(dicembre (12)):e114737.

[2]Perez-Rodriguez J,LaiS,EhstBD,FineDM, BluemkeDA. Nephro-genicsystemicfibrosis:incidence,associationsandeffectofriskfactor assessment–reportof33cases.Radiology2009;250(February(2)):371–7. [3]Canga A, KislikovaM, Martìnez-GalvezM,Arias M,Fraga-RivasP, Poyatos C, et al. Renal function, nephrogenic systemic fibrosis and otheradversereactionsassociatedwithgadolinium-basedcontrastmedia. Nefrologia2014;34(4):428–38.

[4]GiletAG,KangSK,KimD,ChandaranaH.Advancedrenalmassimaging: diffusionandperfusionMRI.CurrUrolRep2012;13:93–8.

[5]PaudyalB,PaudyalP,TsushimaY,OriuchiN,AmanumaM,MiiyazakiM, etal.TheroleoftheADCvalueinthecharacterisationofrenalcarcinoma bydiffusion-weightedMRI.BrJRadiol2010;83(April(988)):336–43. [6]Faletti R,CassinisMC,FonioP,GrassoA,BattistiG,BergamascoL,

etal.Diffusion-weightedimagingandapparentdiffusioncoefficientvalues versuscontrast-enhancedMRimagingintheidentificationand character-isationofacutepyelonephritis.EurRadiol2013;23(12):3501–8. [7]PalmucciS,MauroLA,VerouxP,FaillaG,MiloneP,EttorreGC,etal.

Magneticresonancewithdiffusion-weightedimagingintheevaluationof transplantedkidneys:preliminaryfindings.TransplantProc2011;43(May (4)):960–6.

[8]Abou-El-GharME,El-DiastyTA,El-AssmyAM,RefaieHF,RefaieAF, Ghoneim MA. Roleof diffusion-weightedMRIin diagnosis of acute renalallograftdysfunction:aprospectivepreliminarystudy.BrJRadiol 2012;85(June(1014)):e206–11.

[9]VanAT,GranzieraC,BammerR.Anintroductiontomodel-independent diffusion magnetic resonance imaging. Top Magn Reson Imaging 2010;21(December(6)):339–54.

[10]LeBihanD,ManginJF,PouponC,ClarkCA,PappataS,MolkoN,etal. Diffusiontensorimaging:conceptsandapplications.JMagnReson Imag-ing2001;13(April(4)):534–46.

[11]PaganiE,BammerR,HorsfieldMA,RovarisM,GassA,CiccarelliO, etal.DiffusionMRimaginginmultiplesclerosis:technicalaspectsand challenges.AJNRAmJNeuroradiol2007;28(March(3)):411–20. [12]FukudaY,OhashiI,HanafusaK,NakagawaT,OhtaniS,AnnakaY,etal.

Anisotropicdiffusioninkidney:ApparentDiffusionCoefficient measure-mentsforclinicaluse.JMagnResonImaging2000;11:156–60. [13]Gürses B,Kilic¸kesmezO,Tasdelen N,FiratZ, GürmenN.Diffusion

tensor imaging of the kidney at 3Tesla MRI: normative values and repeatabilityofmeasurementsinhealthyvolunteers.DiagnIntervRadiol 2011;17(December(4)):317–22.

[14]WangWJ,PuiMH,GuoY,HuXS,WangHJ,YangD.MRdiffusiontensor imagingofnormalkidneys.JMagnResonImaging2014;40(November (5)):1099–102.

[15]LiuZ,XuY,ZhangJ,ZhenJ,WangR,CaiS,etal.Chronickidneydisease: pathologicalandfunctionalassessmentwithdiffusiontensorimagingat3T MR.EurRadiol2015;25(March(3)):652–60.

[16]WangWJ,PuiMH,GuoY,WangLQ,WangHJ,LiuM.3Tmagnetic reso-nancediffusiontensorimaginginchronickidneydisease.AbdomImaging 2014;39(August(4)):770–5.

[17]GaudianoC,ClementiV,BusatoF,CorcioniB,OrreiMG,FerramoscaE, etal.Diffusiontensorimagingandtractographyofthekidneys:assessment ofchronicparenchymaldiseases.EurRadiol2013;23(June(6)):1678–85. [18]LuL,SedorJR,GulaniV,SchellingJR,O’BrienA,FlaskCA,etal.Use ofdiffusiontensorMRItoidentifyearlychangesindiabeticnephropathy. AmJNephrol2011;34(5):476–82.

[19]PalmucciS,MauroLA,FaillaG,FotiPV,MiloneP,SinagraN,etal. Magnetic resonancewith diffusion-weightedimaging intheevaluation oftransplantedkidneys:updatingresultsin35patients.TransplantProc 2012;44(September(7)):1884–8.

[20]HueperK,GutberletM,RodtT,GwinnerW,LehnerF,WackerF,etal. Diffusiontensorimagingandtractographyforassessmentofrenalallograft dysfunction-initialresults.EurRadiol2011;21(November(11)):2427–33.

(10)

renalfibrosisinchronickidneydiseaseusingdiffusion-weightedMRI.Clin Radiol2014;69(November(11)):1117–22.

directionsonimagequalityanddiffusiontensorparameters.JClinImaging Sci2013;3(November):53.