Whole-Body Magnetic Resonance Imaging: Technique, Guidelines and Key Applications

Whole-body magnetic resonance imaging: technique, guidelines and key applications

Paul Summers1, Giulia Saia1,2, Alberto Colombo1, Paola Pricolo1, Fabio Zugni1, Sarah Alessi1, Giulia Marvaso3,4, Barbara Alicja Jereczek-Fossa3,4, Massimo Bellomi1,4 and Giuseppe Petralia4,5

1Division of Radiology, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy 2Advanced Screening Centers, ASC Italia, 24060 Castelli Calepio, Bergamo, Italy 3Division of Radiotherapy, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy 4Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy 5Precision Imaging and Research Unit, Department of Medical Imaging and Radiation Sciences, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy

Abstract

Whole-body magnetic resonance imaging (WB-MRI) is an imaging method without ionising radiation that can provide WB coverage with a core protocol of essential imaging contrasts in less than 40 minutes, and it can be complemented with sequences to evaluate specific body regions as needed. In many cases, WB-MRI surpasses bone scintigra-

phy and computed tomography in detecting and characterising lesions, evaluating their Review response to therapy and in screening of high-risk patients. Consequently, international guidelines now recommend the use of WB-MRI in the management of patients with multiple myeloma, prostate cancer, melanoma and individuals with certain cancer predisposition syndromes. The use of WB-MRI is also growing for metastatic breast cancer, ovarian cancer and lymphoma as well as for cancer screening amongst the general population. In light of the increasing interest from clinicians and patients in WB-MRI as a radiation-free technique for guiding the management of cancer and for cancer screening, we review its technical basis, current international guidelines for its use and key applications.

Keywords: magnetic resonance imaging, whole-body, diffusion-weighted imaging, oncology

Background Correspondence to: Paul Summers The introduction of multiple receiver coils and table movement for multi-station scanning Email: [email protected] in the late 1990s transformed magnetic resonance imaging (MRI) from a segmental to a ecancer 2021, 15:1164 whole-body (WB) imaging modality [1–3]. Progressive improvements in scanner homo- https://doi.org/10.3332/ecancer.2021.1164 geneity and gradient systems facilitated the introduction of diffusion-weighted imaging Published: 07/01/2021 (DWI) [4] WB examinations by Takahara et al [5]. Evidence that DWI provides good diag- Received: 04/05/2020 nostic performance in the detection, characterisation and monitoring of therapy of many Copyright: © the authors; licensee cancers, consolidated in a first consensus meeting of experts in 2009 [6], has led to DWI ecancermedicalscience. This is an Open Access having a central role in WB-MRI. Further developments, including accelerated imaging and article distributed under the terms of the improved sequence design, have brought improvements in image quality and rendered Creative Commons Attribution License (http:// WB-MRI feasible in a clinically acceptable scan-time of under 40 minutes, opening further creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and opportunities for clinical use [7–9]. In the course of this progression, WB-MRI has become reproduction in any medium, provided the original an established part of the management of several cancer histotypes [10–15]. In light of the work is properly cited.

ecancer 2021, 15:1164; www.ecancer.org; DOI: https://doi.org/10.3332/ecancer.2021.1164 1 screening, we review itstechnical basis,current international guidelinesfor itsuseandkey applications. increasing interest from cliniciansandpatients in WB-MRI asaradiation-free technique for guidingthemanagement of cancer andfor cancer ecancer 2021, 15:1164; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1164 lowest to calculate the corresponding apparentcoefficient diffusion (ADC) map for image interpretation and disease response assessment [22]. The during free-breathing isrecommendedin order to reduce motion artefacts andincrease [21]. SNR At leasttwo b-values are neededinorder central to due to itsabilityWB-MRI to detectmalignant lesions characterised by highcellularity. Acquiring multipleaverages of theDWI data The finalessential component of a protocolWB-MRI isasingle-shot diffusion-weighted echo-planar imagingsequence. DWI hasbecome detection of vertebral metastases, fractures andspinalcord compression [11,13]. Sagittal T1-weighted TSEand fat-saturated (shortinversiontau recovery—STIR) T2-weighted TSE images of the whole spineare usedfor the can behelpful inconfirming thepresence of spinalcord compression [20]. for theevaluation of diseaseinorgans other thanbone[18] a goodwith trade-off between duration andsignalto noiseratio (SNR) T2-weighted images, acquired usingsingle-shotor half-acquisitionturbo spinecho(HASTE)sequences fatwithout suppression, canbeused foregoes thediscrimination of water andfat components. alternative, a T1-weighted(TSE)echo sequencespin turbo 3D couldbe performed thistypically [17],but results inalonger acquisition and of fat-only and water-only images. These are useful in the detection, characterisation and response assessment of bone metastases. As an are usually obtained gradient-echowith (GRE) Dixon acquisitions [16],producing images in-andopposed-phase that allow thecalculation imaging protocolsWB-MRI generallymorphological include and T1- T2-weighted sequences along with DWI (Tableimages 1 ). T1-weighted Sequences andimage acquisition Technical considerations mendations are for theuseof contiguous slices with athickness between 5and7mm[11,13]. to allow efficient image comparison and improve the readability of the examination. The choice of SLT remains somewhat variable; recom- conventionalthe cross-sectional anatomy of otherSlice modalities. thickness(SLT)remain should consistent across thedifferent sequences of view (FOV) andnumber of slices [32]. Axial acquisitionhas afurther advantage inproviding images that canbedirectly correlated with reducetions andthus Coronal scantime. DWI scansare more likely, however, to suffer from distortion thanaxialDWI with the samefield Both coronal andaxialacquisitionshave beenusedin WB-MRI affected by multiplemyeloma should,instead, spanfrom vertex to knees[11]. surveillance incancer predispositionsyndromes that favour soft-tissue tumours,asLFS such [31]. The acquisition of inpatientsWB-MRI extended to thefeet performedwhen for diseasesthatfrequently involve theextremities, asneurofibromatosis such [30],or aspartof fromspan the vertex to mid-thigh. Ais that distinction patientthe with thearmsremain lyingsupine, adducted. The acquisition should be Following well-establishedpractices for positronWB emissiontomography (PET)andcomputed tomography (CT), WB-MRI acquisitions sequences targeted to theprostate canbeaddedto provide anall-in-oneprostate cancer (PC)stagingexamination [17,29]. example, apost-contrast T1-weighted brain scanisrecommended inLi–Fraumeni syndrome (LFS) [28].For men, axial T2-weighted andDWI disease or brain oedema. While contrast mediaisnot routinely usedin studies,itmayWB-MRI be useful for detecting brain metastases or meningeal sequence for evaluation of lungparenchyma [26], and a fluid-attenuated inversion recovery TSE sequence for detection of focal brain lesions Coverage of thelungandbrain canbeincorporated less than 2minuteswith of scanningby usingasinglebreath-hold, shortecho-timeGRE Obtaining fewer averages of thelow b-value images, that have intrinsically higher isonemeasure SNR, for minimising acquisition times. usually of secondary importance for examinations.WB-MRI DWIWB requires arelatively long(10–15minutes) acquisition time[24,25]. in tissues that have anisotropic(kidneys, diffusion and white matter) may, however, be biased with diffusion such encoding, though this is acquired encodeddiffusion multiple with directionsthat are prone to different eddy currentof inducedvaluesThe distortions [23]. ADC all three axes canprovide higherby SNR reducingItecho times. may alsoreduce theblurringthat canarise when averaging across images 1,000 s/mm b-valuebe atshould 50 s/mmleast [27]. Depending on clinical context, sequences to evaluate specific body regions can be added to a basic protocolWB-MRI 2 isrecommended [13, 21,22]. Theof use encoding asinglediffusion direction with simultaneousapplication of gradients from 2 inorder to reduce perfusion-related signals, while ahighb-value intherange between 800and [11, 17,18]. The coronal orientation may permittheacquisition of fewer sta- [19], and [13]. For 2

Review ecancer 2021, 15:1164; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1164 tion, andisto berecommended where available. coverage of eachstation [33]have largely been inadequate. Slice specific shimming[34], on the other hand, has provided consistent reduc this problem by notthe different shimming stations, bythe samecentre applying frequency to allstations or by limitingthesuperior-inferior cent to eachother ashappens when viewing theimages inanatomic order or intensity inmaximum projection (MIP). Attempting to deal with Theof impact magneticinhomogeneityfield isparticularly evident where thesuperior andinferior limitsof successive stations are seenadja- saturation leadingto a variable SNRinDWI, andincreases theriskof ‘phase-wrapping’ inDIXON scans[33]. theses. An advantage of 3 T scanners isseeninhigherthe lowerbut SNR, homogeneity of thestatic fieldcanreduce theeffectiveness of fat be performedcan WB-MRI on both 1.5 T and3 T scanners,1.5 but T may bepreferred when patients have non-removable metallic pros- sis Reporting andData System for Prostate Cancer, MET-RADS-P; Myeloma Response Assessment andDiagnosis System, MY-RADS; PC,Prostate Cancer Slice thickness;STIR,Short tauinversion recovery; TE, Echo time; TSE, Turbo spinecho; W, Weighted; 3D, Three-dimensional; BC,Breast Cancer; METasta- ADC, Apparent diffusioncoefficient; CA,Comprehensive assessment; FOV, Field of view; GRE,Gradient echo;MIP, Maximum intensity projection; SLT, g f e d c b a Table 1.Sequence components for WB-MRI examinations. b800–1,000 s/mm Alternatively, a3D T1W TSE allowing multiplanar reformatting may beperformed Coronal acquisition accepted under MY-RADS 3D MIP images, displayed rotating around cranio-caudal axis,usinganinverted greyscale Add b500–600s/mm Suggest axial with common SLT across WB images to facilitate image review Coronal acquisition with 2mmSLT accepted under MET-RADS-P 1 3 2 7 6 5 4 Whole spine—sagittal, T1Wspine—sagittal, TSE Whole WB—axial, T1W GREDixon (preferred) or fat suppressed, 4–5mmSLT STIR T2Wspine—sagittal TSE Whole SLT b50–100 s/mm ,Regional assessments—if clinically needed short TE (<1.5ms) breath-hold examination <3mmSLT, with Lung: 3D T1W GRE volume interpolated suppression, 5mmSLT fat- T2WWB—axial, without TSE ֘ ֘ ֘ 5–7 mmSLT WB—axial, diffusion weighted STIR image reconstructions mandatory value images 3D-MIP reconstructions of highestb- Coronal b800–1,000reconstruction data fitting ADC calculation by mono-exponential Sequence description d

2 DWI images from all stations grouped andreconstructed as5mmcontiguous, two-dimensional coronal slices 2 g andb800–1,000s/mm 2 for CA d c , 5mmSLT c , 4–5mm

f d 2e Fat Fat Core Core standard FOV outside or known sites Symptomatic knees vertex to CA. knees vertex to Core knees vertex to Core myeloma (MY-RADS) Multiple a

[11]

Core Core mid-thighs vertex to No mid-thighs vertex to CA mid-thighs skull baseto Core Core (MET-RADS-P) cancer Metastatic prostate b

[13] Yes Yes mid-thighs vertex to Yes T1W GREat 0.6mm nal, post-contrast 3D T2W axial, T2W coro- T1W axial, Brain: Yes mid-thighs vertex to Yes thighs skull baseto mid- Yes Breast cancer a Suggested protocols Yes Yes mid-thighs vertex to Yes mm fat-suppression 5 coronal without Abdomen: T2W Yes thighs vertex to mid- Yes mid-thighs skull baseto Yes Ovarian cancer a contiguous Yes No mid-thighs vertex to Yes Yes mid-thighs vertex to Yes thighs to mid- skull base Yes Lymphoma Yes No mid-thighs vertex to Yes Yes mid-thighs vertex to Yes thighs to mid- skull base Yes Screening 3 -

Review where S hear theinstructionsclearly andcommunications shouldbemaintained between scansto ensure they are awake when theinstructionsare given. The patient shouldbeinformed before theexamination of theinstructionsandbreath-hold duration. During theexamination, they mustbeableto Image quality of theDixon T1- andHASTE T2-weighted images may beimproved if thechestandabdomenstations are obtained inbreath-hold. encouraging themto void their bladder prior to entering thescanner. provision of accurate information abouttheexamination, having the patient change into asingle-usegown to avoid hiddenmetal objects and important to ensure they are comfortable andfully prepared to remain stillfor theduration of theexamination. Preparation shouldinclude be positionedandconnected for theduration of theprocedure. Because thiseffectively thepatient sandwiches between arrays of coils, itis should beaddedinorder to maintainon the entire ahighSNR body [35]. To avoid timebeinglostonchangeovers of the coils, allcoils should body coil array(s) are necessary to coverabdomen andpelvis.Ifchest, the theexamination isto beextended to thefeet, alower limbcoil fixed head-coilpatientthe position, is generally headfirst positioned headandneckarray inthe coil. In addition,aspinearray coil andanterior Achieving coverageWB optimisingwhile requiresSNR ofuse the alarge number of receiver coils. Given thatmodern systems most provide a ecancer 2021, 15:1164; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1164 the signalintensities inthedifferent b-value DWI images: aremaps ADC usefulfor and responsefindings classifying to therapy [11,13]. is usuallyADC calculated with amonoexponential fittingto only (W)images: substitution rF%providecan aquantitative assessmentof ofdistribution the fat within thebody, andof oncological relevance, describebonemarrow Relative fat fraction (rF%)havemaps emerged asanobjective image-based biomarker of disease[36].Obtained from T1 GREDixon images, providing anappearance similar to that of PET. axis, allow an‘at-a-glance’ overview for diseaseassessmentand lesiondetection. Typically, theseare displayed ininverse grey scale,thus sequence intoof single-stack images with coverage.WB A seriesof MIPs of thehighb-value DW images, rotating around thecranio-caudal and reduceMRI thescope for operator errors. To facilitate image reading andreporting, we canunify (compose) thedifferent stations of each Where possible,‘set-upand go’ acquisition andpost-processing shouldbeusedto simplify andaccelerate theoperational workflow for WB- Post-processing andquantitative analysis advanced shimming techniques [43], these canbe addressed to someextent, though the shimming may add notably to the examination dura- is otherwisewhich favourable to reducingnumberthe of averages necessary (and thusscantime) or pursuing higher spatial resolution. With signal intensity indeep structures or between imagingstations. Both theseissuesbecome more pronounced onmoving from 1.5T to 3.0T, ciated use ofwith the large numbers of smallcoils as well of asbeingafunction patient size andcomposition that canleadto inhomogeneous artefactbetween stations onDWI scans,andproducing water-fat swaps intheDixon technique. Radio-frequency inhomogeneities are asso- station,a singlescanning staticthe inhomogeneityfield can distortionsyield thatcan disrupt anatomy, for example, creating a‘broken spine’ staticthe and radiofrequency magnetichomogeneitiesfield that are available [33]. When attempting to obtain large anatomical coverage in Despite considerable progress, facesstill WB-MRI anumber of technical andpractical challenges. Several of theseare tiedto thequality of shown very good repeatability [41,42] suggesting utility practice. inclinical relatively efficientsegmentation of adistributed lesionload(Figure 1).In evaluation of bonemarrow andof bonemetastases [22, 40]ithas ings automaticsegmentation techniques have beendeveloped to assistindistinguishingmalignant lesionsfrom healthy tissueandbenignfind- and ADC maps. This necessitates considerablefor time reading andreporting, andcanincrease theriskof misinterpretations. Several semi- The large number of images produced in each examinationWB-MRI complicates extracting thequantitative information provided via rF% [37, 39]. A recently proposed tool for DWIWB segmentation combines application of thresholds andmanualeditingto provide a high and S [37]. The rF%aremaps obtainedby signal intensity dividingthe of thefat-only imagesby (F) of thesum thefat-only and water- low are thesignalintensities inthehighandlow b-value images (b AD Cl rF = − % n = () 100 bb FW high    + S × S − high low F    low high , andb low ), respectively [38]. 4

Review has returned to theactive disease range (red band)andthePSA having increased, is compatible witha predominance of active metastatic disease. response, buttheleft-hand peakindicates a residual component of diseaseisstillactive. Atthe second follow-up (yellow histogram), (e):thedistribution range (yellow band)indicating according to theMET-RADS-P guidelines[13], together with areduction inPSA, this could suggest apositive therapeutic the active disease range (red band), whilethe (orange) histogram at first follow-up shows two peaks. Theright-most fallinginthelikely-response peak, backdrop to comparisons of ADC histograms between successive examinations in (d) and (e). (d): The peak of the(blue) histogram falls in at baseline ecancer 2021, 15:1164; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1164 [13], theuser-defined thresholds (1,000and 1,400 µm inverted grey-scale MIPs from b-900diffusion weighted images are colours representing three ranges of ADC values. BasedonMET-RADS-P guidelines sensitive metastatic PCseen at (a): baseline, (b): 4month follow-up and (c): 8month follow-up examinations duringhormonaltherapy. Overlaidon here https://ecancer.org/journal/14/1064-whole-body-magnetic-resonance-imaging-technique-guidelines-and-key-applications Figure/Video 1. measurements for advanced assessment, astructured reporting template andguidance ondefining response assessment categories that incorporates ADC and reduce variation inacquisition, interpretation andreporting of WB-MRI. MY-RADS describesacore clinicalimagingprotocol with extension therapy monitoring, the Myeloma Response Assessment and Diagnosis System (MY-RADS) was published in 2019 to promote standardisation British Society for Haematology recommends WB-MRI for therapy monitoring inmultiplemyeloma patients [46].Reflecting theapplication to [45]. The Oxford Centre of Evidence-based Medicine similarly recommends WB-MRI for stagingallforms of multiplemyelomathe [10]while include italong with fluorodeoxyglucose (FDG)-PET/CT andspineMRIfor monitoring incaseof serological relapse or diseaseprogression Britain’s National Institute for Health andCare Excellence guidance recommends WB-MRI asfirst-line imagingfor suspected myeloma and Multiple myeloma tracer to achieve adequate biodistributionfor imaging. tendtimes to belonger thanthoseof PET,the examination but doesnot necessitate injectionof aradioactive tracer, nor the wait for the cellularity orcontent, chemical and altered pathway metabolismchemical in the targeted by PET thespecific tracer. WB-MRI examination radioactive tracer. Consequently, differences insensitivity between WB-MRI andPET are typically attributed to mismatches between hyper T2-weightings that largely reflectfat and water andfat content, while PET contrast derives from metabolic activity of theadministered cal images are produced a choicewith of contrasts beingavailable, includingDWI associated with changes inthecell density, and T1- and has enteredWB-MRI a clinical domaindominated by bone scan (BS), (CT), PET and the combination—PET/CT. In morphologiWB-MRI, - Clinical Applications and seeitfavourably incomparison to other imagingprocedures [44]. a long,noisywith examination. Nonetheless, when informed well, patients appear to appreciate asaneffectiveWB-MRI imagingtechnique tion. Practicala greaterissues include senseof beinginaclosespace becauseof thecoverage of thepatient with coils, andtheneedto cope lesion (yellow) <1,400µm Illustration of thequantitative analysis of ADC viasemi-automated segmentation in a patient with metastatic PC. To view thisvideo,click [11]. 2 /s

Review APC isableto better reflect theheterogeneity of disease[13]. as theclinicalsignificance of thesub-centimetre nodesthat are poorly seen with remainsWB-MRI to beestablished.Moreover, WB-MRI in less inlightof theabove-mentionedperformance for bonemetastases, remainsWB-MRI attractive aloneor incombination PSMAwith PET reportssuggest that PET/CT tracers(PSMA)-based some with may permitgreater sensitivity sacrificing specificitywithout [62,63].Nonethe- ecancer 2021, 15:1164; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1164 with metastatic castration resistant PC,there isaradiographic progression without clinical/prostate-specific antigen (PSA) and hasclear value inthedetection of skeletal related events suchasspinalcord compression andfractures. Moreover, for upto 30%of patients that theflare phenomenoncaninterfere with thetherapy response assessment [55,56].Notably, WB-MRI isnot affected by thisphenomenon stances PET for both local and distant disease in staging (e.g. [53]),a2018review of the literature suggests it does not perform so well in allcircum - [52], but bears a significant radiation exposure compared to WB-MRI. Although some studies have shown very good performance of Choline PET/CT may not inform ontumour viability androgen during receptor inhibition[51],theoption of pairingit with FDG-PET hasbeensuggested For APC, the ASCO guidelines consider WB-MRI, PET/CT and PET/MRI as alternatives study isattractive for localandsystemic staging metastases imaging isnegative or equivocal [47].Multiplehavestudies recognised that MRIismore sensitive thanCT andBSfor thedetection of bone entered therecent AmericanSociety of ClinicalOncology (ASCO) guidelines, where they are indicated for screening where conventional Network (NCCN) guidelinesrecommendsystemic staging CTwith andBSfor patients with advanced PC(APC). andPETWB-MRI have guidelines recommend at leastcross-sectionalimaging andaBS[12].Similarly,abdominopelvic EAU andNational Comprehensive Cancer Atforstaging initial unfavourable intermediate risk(Gleason Score 4+3)andhigh-riskPCpatients, European Association of Urology (EAU) Prostate cancer mance indetection of metastatic nodaldetection assessment. and MRI CT, dependent on morphological assessment of nodal disease, have similar unfortunatelybut limited levels of perfor recommendedfor externalradiation beam therapy or extended noderesection, lymph illustrating theimportance of whole-body lymphnode etLarbi al [60],only one-third of enlargednodes seenon lymph inmetastaticWB-MRI prostate cancer patients were theregionswithin Lymphnodes are another common site of PCmetastasisand are thusaconcern both instagingandoligoprogression. In a2016study by shows that thestereotactic ablative radiotherapy isassociated with animprovement inoverall survival inpatients with oligometastatic PC[59]. of oligometastatic disease(one to five oligometastatic lesions), are potentially candidates for localtherapy [58].Evidence from arandomised trial Instead, WB-MRI isincreasingly usedfor APC therapy monitoring (Figure 2 ) andfor patients experiencing biochemicalrecurrence that, incase ( 11 C)choline and( W, Weighted; TSE, Turbo spinecho;GRE,Gradient echo;DWI, Diffusion weighted imaging;FOV, Field of view a Table 2.‘All-in-one’ protocol with WB-MRI for PCstaging. slice thickness [54]. The Advanced Prostate Cancer Consensus Conference recognises thelimitations of BSandCT for boneassessment, andhighlights T1W TSE DWI T2W TSE DWI T1W GREDixon [48, 49].Forreason, this an‘all-in-one’ approach(Table 2 ) thatcombines multiparametricof MRI theprostate a with WB-MRI Sequence 18 F)choline haveF)choline beenfound to perform comparably or worse thanMRIandCT for recent nodaldisease,but preliminary Sagittal whole-spine Axial prostate prostate Axial andsagittal Axial WB Axial WB Plane andcoverage [13, 50]. [61]. Several PET tracers, including2-deoxy-2-( 4–5 mm low: 50–100s/mm 2 b-values: small FOV 3 mm small FOV 3 mm high: 800–1,000s/mm 5–7mm 5 mm a a a

a a

Parameters 2

2 [47]. As prostate membrane specific antigen (PSMA) Prostate Prostate Bone andlymphnodesmetastases Bone andlymphnodesmetastases Bone metastases 18 F)fluoro-D-glucose, ( sodium Assessment progression 18 F)fluoride, [57]. 6 -

Review the corresponding time-point. In the26patients whose progression involved bone,just13cases were considered inprogression onthebone sion duringthestudy, all were seen with atWB-MRI of time first appearance of progression, only but 11of these were evident ontheCT of metastatic BCusingbonescintigraphy, CT and atWB-MRI 12-week intervals. Amongst 33patients the who arrived at radiological progres- The recentResponse Evaluationof Cancer Therapeutics(RESPECT) CT (93%)consistent with previous bimodality comparisons ecancer 2021, 15:1164; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1164 computed tomography (SPECT)and SPECT-CT (91% versus74% and85%,respectively),62%, andnearly identical sensitivity to Trial conventional andultrasoundMRI being alternatives for abdominal imaging where appropriate [69–71].In adirect comparison, theSKELETA Medical Oncology (ESMO), Royal College of Radiologistsand North (UK) American NCCN recommendations for thecontexts they cover, with ing, recurrence)evaluation inthe of breastcancer patients (BC) (see [68]for asummary). CT, BSandFDG-PET dominate European Society for Currently, internationalareguidelines mixed asto the which imaging techniquesWB to apply andunder what conditions (staging, monitor Breast cancer sensitivity [67]. always created concerns for theabsence of contrast agent, isperformed DWIwith andallows detection, even of smallmetastases, goodwith [64], detectionof smaller lesionscanbeexpected; andif negative, low-dose CT of thelungsconsidered [26]. The study of liver, which has reported to perform well indemonstratingpulmonary lesionsgreater than5mm[66] . Taking advantage of techniques to improve resolution to studyis difficult conventionalthe with T1-, and diffusion-weightedT2- images. Breath-hold, GREimagesecho-time, short have been mance in the detection of extracranial metastases from and melanoma other tumours in multiple body regions in Swiss guidelinesfor the treatment and follow-upof melanoma cutaneous alternative to contrast-enhanced CT or PET/CT for follow-upof advanced melanoma (stage III or higher) andthisis also therecommendation The GermanDermatological Society Dermatologic andthe Cooperative Oncology Group Melanoma consider 14 anatomical regions inabaselinetemplate andresponse assessment criteria for following diseaseevolution infollow-up. definedMetastasisin the Reporting and Data System for Prostate Cancer (MET-RADS-P) Standards for image acquisition,interpretation andreportingfor clinicalcare andclinicaltrialsinvolving APC patients have recently been metastasis (c): anon-regional lymphnodemetastasis and(d): bonemarrow disease. In the‘at-a-glance’ diseaseassessment facilitated by theMIP, WB-MRI shows aclinicalpattern of typeN1M1b,involving (b): regional lymphnode grey-scale MIP of b-900diffusion-weighted images and(b–d):axialb-900diffusion-weighted images b-900images from WB-MRI performed for staging. Figure 2.Metastatic PCstaging with WB-MRI. A 70-year-old male withhigh-riskPC(PSA 28ng/mL, Gleason score (GS) [72] showed that providesWB-MRI higher sensitivity for bonemetastases arisingfrom breast andPCthanBS,singlephoton emission [73, 74]. study [75] monitored treatment response inacohort of 44 women with [14]. WB-MRI has demonstrated comparable diagnostic perfor [14, 15]suggest theuseof WB-MRI asa valid guidelines [13]. For reporting, theseguidelines 4+4)seenin(a): coronal inverted [64, 65]. Lung parenchyma 19 F-NaF PET- 7 - -

Review CT or BSfor stagingandtherapy monitoring inthesepatients. ration fortherapies. childbirth-based As a technique ionising radiationwithout andrequiring nocontrast agent, itis more appropriate than is alsoestablishinganimportantWB-MRI role inthecare of pregnant women with BC[25,80] where systemic stagingismandatory inprepa - is necessary. This useof WB-MRI isdriven by growing awareness of radiation induced risks,especially for thoseunder 35 years of age [79]. A subgroup of BC patients for whom is seeing increasingWB-MRI use, is that of young BC patients for whom serialtreatment monitoring imaging of liver metastases isDWI well-established asoutperforming both CT andPET [77,78]. sensitivitythe hasbeenseento exceedof those CT andFDG-PET [77] . Liver metastases are alsorelatively common inBCpatients. In the secondAs BCisthe common most ofcause brain metastases anticancer therapy. scintigraphy atof thetime radiological progression. This strongly suggests thesuitability of forWB-MRI response assessment insystemic ecancer 2021, 15:1164; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1164 could beof interest asaone-stop-shop for TNM stagingof rectal cancer ina single session. colon and rectal cancer patients canbe expected to expand. Moreover, combining WB-MRI systemic staging with rectal MRI for local staging ment for standard pathways instagingpatients colonwith cancer [93].Considering this,therole of inthemanagementWB-MRI of both a rectalforMRI rectalcancer staging[91,92]. The Streamline Cstudy, however, found that WB-MRI-based pathways are a viable replace- and NCCNESMO guidelinesboth recommend CTan abdomen-pelvis for colon cancer staging,andachest-abdomen-pelvisCT together with Colorectal cancer with WB-MRI toallow tumor-node-metastasis (TNM) pathways andrequire shorter stagingtime needed brain when NCCN guidelinesrecommendthe staging of lungcancer PET/CTwith and/or total body CT, with theadditionof anMRIexamination of the Lung cancer pregnancy in1,000)[88]to minimise exposure to ionisingradiation. [87] (Figure 3). Furthermore, use is emergingWB-MRI in young patients (<35 years) for detection lymphoma in patients with variable FDG (e.g. follicularand Hodgkin’s lymphoma lymphoma) toOwing itshighaccuracy, FDG-PET/CT istherecommendedimaging technique for thestagingandfollow-upof mostcommon lymphomas Lymphoma have arole inthemanagement of ovarian cancer patients. roperitoneal lymphadenopathy detection (respectively, 87%and versus 71%)[85]. These promising results suggest that couldWB-MRI staging of peritoneal lesions (91% versus 75%and 71% respectively), and both and FDG-PETWB-MRI to be more accurate than CT in ret- responseto advancedovarian epithelial cancer [84]. has alsobeenshownWB-MRI to bemore accurate thanboth CT andFDG-PET inthe [83]. Furthermore, quantitative analysis using ADC measurements hasproven robust to detect early microstructural changes occurring in of ovarian masses [82],as well asfor assessing the involvement of mesentery, para-aortic lymph nodes,large bowel and sigmoid-rectum CTchest-abdomen-pelvis [81].Evidence shows that has higherWB-MRI diagnosticaccuracy thanCT indetermining themalignant nature For stagingandfollow-upof ovarian cancer patients, theEuropean Society of Urogenital Radiology guidelinesrecommend contrast-enhanced Ovarian cancer [89]. The Streamline L study has shown that entirely pathwaysWB-MRI-based are viable in replacement for standard [90]. Incancer lung patients for whom abrain MRIisnecessary, integration of thisexamination [86]. It hasbeendemonstrated, however, that showsWB-MRI higher sensitivity (94%)

staginginasinglesittingisanobvious step for efficiency. avidity subtypeslymphoma than FDG-PET/CT (61%) and contrast-enhanced CT (71%) [76], contrast-enhanced brain MRIshouldbeconsidered inthesepatients as [79] and pregnant women (lymphoma occurring in 1 8

Review white arrow inbandd)aniliaclesion(blackarrow inbande). Metastasis intheright iliacbone was confirmed by CT-guided biopsy (f). addition to the T10metastasis (white arrowhead inaand b), asternal metastasis (smaller white arrow inband c), asecond thoracic vertebral lesion(longer inverted grey scaleMIP of theb-900diffusion weighted images; with corresponding hyperintensities beingseenintheaxialsource images (c–e). In metastasis of the T10 vertebra (white arrowhead). At WB-MRI 1month later, oligometastatic disease withmultiplebonelesions was evident in (b): the ecancer 2021, 15:1164; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2021.1164 but further efforts to standardise acquisition andreporting are warranted to reduce the variation indiagnosticperformance. of in oncology.WB-MRI guidelines demonstrate Existing thecentral role of WB-MRI examinations with DWI insomeoncology applications, developments inimagingstrategyintelligence andartificial holdthepromise of further improvements andare likely to expand theuse cases a seemed impossible: examinationWB-MRI that provides a core clinical protocol for WB imaging in little more than half an hour. Continuing Thanks to aseriesof improvements inscanner hardware andimagingtechnique, itispossibleto achieve inclinicalroutine what 20 years ago Conclusions subjects to generate clinicalinterest inthetechnique and to motivate further research. and resultsof are thestudies too heterogeneousto draw unequivocal conclusions, enoughtumours have beendiagnosedinasymptomatic the use of in asymptomaticWB-MRI individuals[27, 97, 98–106], the largest of which includes30,000 subjects The applicationof to oncologicalWB-MRI screening general inthe population isstillamatter of debate. Several reports have demonstrated Consortium recommendedin aconsensus statement by Care the for Consortium CMMRD andtheInternational Biallelic Mismatch Repair Deficiency For constitutional mismatch repair deficiency (CMMR-D) syndrome, anannual examinationWB-MRI from theage of 6 years hasbeen with acontrast-enhanced brain MRIand,in women, with acontrast-enhanced breast MRIas well. ticipants,an annual is recommendedWB-MRI for patients LFSwith asascreening examination [28,31]. The exam shouldbecomplemented According to the American Association for Cancer Research (AACR), as well asamulticentre cohort review involving 13cohorts and578par emerged astheimagingtechnique of choice for cancer screening insubjects with cancer predisposition syndromes [28,31,95,96]. Dueto spatial its resolutionand highsensitivity, along non-invasiveits with nature andtheabsence of ionisingradiationhas [94],WB-MRI Cancer screening Figure 3.Bone lesionsinlymphoma. A 51-year-old male with follicular lymphoma(G1-G2). (a): [95]. For hereditary paraganglioma-pheochromocytoma, ontheother hand,the AACR hasrecommended biennial [96]. WB-MRI 18 FDG-PET for distant stagingto have asinglebone [107]. Although themethods 9 -

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