REVIEWS AND COMMENTARY • REVIEW

Guidelines for Acquisition, Interpretation, and

Reporting of Whole-Body MRI in Myeloma:
Myeloma Response Assessment and Diagnosis System
(MY-RADS)
Christina Messiou, MD • Jens Hillengass, MD • Stefan Delorme, MD • Frédéric E. Lecouvet, MD • Lia A. Moulopoulos, MD •
David J. Collins, BA • Matthew D. Blackledge, PhD • Niels Abildgaard, MD • Brian Østergaard, MD •
Heinz-Peter Schlemmer, MD • Ola Landgren, MD • Jon Thor Asmussen, MD • Martin F. Kaiser, MD •
Anwar Padhani, MD
From the Department of Radiology, Royal Marsden Hospital and Institute of Cancer Research, Downs Rd, Sutton SM2 5PT, England (C.M., M.D.B., M.F.K.); Roswell
Park Comprehensive Cancer Center, Buffalo, NY (J.H.); Department of Radiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany (S.D., H.P.S.);
Department of Radiology, Cancer Center and Institute of Experimental and Clinical Research, Brussels, Belgium (F.E.L.); Department of Radiology, National and Kapo-
distrian University of Athens, Athens, Greece (L.I.A.); The Royal Marsden Hospital, London, England (D.J.C.); Odense University Hospital, Odense, Denmark (N.A.,
J.T.A.); Vejle Hospital, Vejle, Denmark (B.Ø.); Memorial Sloan-Kettering Cancer Center, New York, NY (O.L.); and Paul Strickland Scanner Centre, Mount Vernon
Hospital, Northwood, England (A.P.). Received August 30, 2018; revision requested October 10; final revision received October 26; accepted October 30. Address cor-
respondence to C.M. (e-mail: [email protected]).
Study supported by National Health Service funding to the National Institute for Health Research Biomedical Research Centre, Clinical Research Facility in Imaging
at The Royal Marsden Hospital, and the Cancer Research Network. This report is independent research funded by the National Institute for Health Research. The
views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, or the
Department of Health.
Conflicts of interest are listed at the end of this article.

Radiology 2019; 291:5–13 • https://doi.org/10.1148/radiol.2019181949 • Content code:

Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary,
international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in
myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging meth-
ods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in
the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are
designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI
in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended
protocol for advanced assessments.
Published under a CC BY 4.0 license.

Online supplemental material is available for this article.

Online SA-CME • See www.rsna.org/learning-center-ry

Learning Objectives:
After reading the article and taking the test, the reader will be able to:
n Describe different patterns of myeloma infiltration on whole-body MR images
n List the components of the whole-body MRI protocol
n Describe how whole-body MRI should be used to assess response to treatment
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disclosures are listed at the end of this article.

Lrect treatment decisions in multiple myeloma (1) and

aboratory assessments of myeloma disease activity di- predominantly help to detect the destructive effects of
myeloma disease on trabecular and cortical bone rather
contribute to clinical risk stratification systems such as the than disease within the bone marrow space, sensitiv-
Revised International Staging System for Multiple My- ity and capability as a restaging tool are inherently lim-
eloma and gene expression profiling classifiers (2,3). ited (5,6) (although imaging of bone destruction may be
Conversely, skeletal survey, which has been in widespread helpful for surgical planning). Myeloma infiltrates within
use for decades, only offers a crude assessment of bone bone marrow can be depicted with CT if they lie within
involvement as a myeloma-defining event. More recently, the marrow spaces of long bones where they stand out
some centers have escalated imaging by replacing skeletal against fatty bone marrow (7). However, in trabecular
survey with low-dose whole-body CT, which has greater bone such as in the vertebral bodies, myeloma infiltrates
sensitivity (4). However, because skeletal survey and CT are difficult to assess due to the trabeculae themselves and
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Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma

Whole-body MRI as currently used includes DW MRI se-

Abbreviations quences that are sensitive to cellular density and viability and
ADC = apparent diffusion coefficient, DW = diffusion weighted, FDG = are important for disease detection, monitoring, and therapy
fluorodeoxyglucose, MY-RADS = Myeloma Response Assessment and
Diagnosis System response assessments. Inclusion of DW MRI allows highly sensi-
tive and quantitative evaluation of soft tissue and bone marrow,
Summary which is widely available and quick to perform and interpret.
This Myeloma Response Assessment and Diagnosis System, or MY- The relationship of apparent diffusion coefficient (ADC) (in
RADS, consensus on whole-body MRI in myeloma proposes a core square micrometers per second) values with cell density permits
clinical protocol for whole-body MRI and an extended protocol for
advanced assessments. response assessments ahead of changes in lesion size, in addition
to assessments of response heterogeneity (8,30–32).
Essentials Whole-body MRI including DW MRI has become estab-
nn Whole-body MRI is now incorporated into international stan- lished as the most sensitive technique for bone marrow imaging
dards for imaging patients with myeloma.
(23–25) with additional benefits of speed, coverage, and quanti-
nn Core clinical and comprehensive protocols for whole-body MRI
include anatomic and functional imaging and can be completed in
fication in comparison with traditional MRI, obviating intrave-
30 minutes and 50 minutes, respectively. nous injections and radiation exposure. Wide anatomic coverage
nn Standardized acquisition protocols and structured reporting will is essential because 50% of lesions would be missed by imaging
support clinical deployment, training, and research in imaging of the spine alone (33). Avoidance of ionizing radiation is likely to
myeloma. become increasingly relevant as surveillance imaging of high-risk
patients with monoclonal gammopathy of undetermined signifi-
the copresence of degenerative changes, benign lesions, and os- cance and of those with smoldering disease gains momentum.
teoporosis in the population at risk. Whole-body MRI is a generally well-tolerated technique (24)
The excellent soft-tissue contrast of MRI allows direct imaging that offers the additional benefits of assessing skeletal complica-
of the bone marrow, providing high sensitivity (8–11). Perhaps tions, such as spinal canal and/or nerve root compression, and is
the clearest benefit of using MRI is the early detection of focal my- the most accurate method for differentiating benign from malig-
eloma disease. It is well established that patients with unequivo- nant vertebral compression fractures (34).
cal focal lesions at MRI have poorer outcomes. If disease can be Although the International Myeloma Working Group has
detected early, and patients are stratified and treated according to taken a pragmatic approach in recommending a range of pos-
clinical risk, then survival advantages are conferred (12–19). Fur- sible imaging investigations (including low-dose CT, FDG
thermore, most patients with apparently solitary plasmacytoma at PET/CT, and MRI) for patients with a new potential diag-
skeletal surveys are upstaged with MRI, which profoundly influ- nosis of myeloma, the high sensitivity of whole-body MRI is
ences treatment strategies (11,12). The number and sizes of focal explicitly acknowledged (6,35) and it is now recommended as
lesions at MRI have also been shown to predict outcome (20,21). first-line imaging for all patients with a suspected diagnosis of
Fluorodeoxyglucose (FDG) PET/CT can also be used for diag- asymptomatic myeloma or solitary bone plasmacytoma. In the
nosis of focal bone lesions; however, MRI is more sensitive for United Kingdom, whole-body MRI is recommended as first-
diagnosis and contemporary MRI techniques have increased the line imaging for all patients with a suspected new diagnosis
advantage (22–25) (sensitivity of diffusion-weighted [DW] imag- of myeloma (26). Recently, the British Society for Haematol-
ing has been reported as 77% compared with 47% for FDG PET/ ogy additionally recommended the use of whole-body MRI for
CT) (23). Gene expression profiling has revealed lower expression monitoring response of nonsecretory myeloma, oligosecretory
of hexokinase 2, which is involved in the glycolysis pathway, in myeloma (which can occur at relapse in patients with previ-
lesions that are negative at FDG PET and positive at MRI. The ous secretory disease), and for those patients with extramedul-
prognostic significance of lesions that are discrepant between MRI lary disease (36). The uses of whole-body MRI in myeloma are
and FDG PET/CT is not yet known (25). However, whole-body summarized in Figure 1.
MRI does result in the largest rise in quality-adjusted life years Acknowledging the increasingly important role of whole-body
compared with CT or FDG PET/CT (26). MRI for directing patient care in myeloma, a multidisciplinary,
Although whole-body DW MRI has emerged as one of the international, and expert panel of radiologists, medical physicists,
most sensitive tools for imaging bone marrow with increased lesion and hematologists with experience in whole-body MRI in my-
conspicuity compared with conventional MRI sequences (27–29), eloma convened to discuss the performance standards, merits, and
some debate remains as to its specificity. There are few studies re- limitations of currently available imaging methods. The recently
lating to myeloma. Although Lecouvet et al (28) presented data published Metastasis Reporting and Data System for Prostate
to suggest high specificity for detection of metastatic bone disease Cancer, or MET-RADS, guidelines on the use of whole-body
(98%–100%), a recent meta-analysis showed a pooled specificity MRI for metastasis evaluations (37) were used as a model to for-
of 86.1% (29). The paucity of myeloma-specific prospective stud- mulate the performance standards for whole-body MRI use in the
ies and marked heterogeneity in reference standards make current assessment of involvement by myeloma. The Myeloma Response
judgments on specificity challenging, and biopsy of all lesions is Assessment and Diagnosis System (MY-RADS) imaging recom-
not feasible. The approach offered by the International Myeloma mendations are designed to promote standardization and dimin-
Working Group of 3–6-month follow-up of equivocal solitary ish variations in the acquisition, interpretation, and reporting of
small lesions is a pragmatic solution (6). whole-body MRI in myeloma. The system also provides a means

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 Messiou et al

for response assessment and standardized protocols

to facilitate data sharing for future developments.

Whole-Body MRI Data Acquisition

and Analysis
The core clinical protocol for whole-body MRI
when used alone is designed for myeloma detection
in bone marrow but can also image extramedullary
disease and should be completed within 30 minutes
of imaging time (Table 1). More comprehensive as-
sessments can be performed within 45–50 minutes
of imaging time (Table 1). Details of machine setup,
sequence specification, quality assurance procedures,
and quality control and radiographic aspects can be
found in Table E3 (Appendix E1 [online]).
The core protocol for whole-body MRI is ad-
equate for the detection of disease at diagnosis.
Comprehensive assessments are recommended for
assessment of soft tissue, extramedullary disease, or
for those patients in whom serial tumor response
assessments (including clinical trials) are planned.

Clinical Information
The following information should ideally be
available to radiologists at the time of reporting
(and increasing use of electronic patient records
increases the feasibility of this): time of initial di-
agnosis or suspected diagnosis, serum paraprotein
levels and light chain levels and trephine status Figure 1: Image shows current guidelines on imaging from International Myeloma
(if performed, including site), symptomatic sites Working Group (IMWG), National Institute for Clinical Excellence, and British Soci-
including any clinical indication of cord or nerve ety of Haematology. Source.—References 6, 26, 36. FDG = fluorodeoxyglucose.
root compression, first line or relapse state, cur-
rent treatment, history of autograft or allograft transplant, window level to a normal tissue such as muscle or subcutane-
details of previous radiation therapy or surgical interventions ous fat for each time point.
including vertebroplasty, granulocyte colony–stimulating factor The evaluation of source images obtained with DW MRI se-
or steroid administration, and minimal residual disease status quences at b values of 800–900 sec/mm2 is based on comparing
(if performed). high b-value image intensity to adjacent muscle signal intensity,
but assessments of ADC maps are numeric (unit, 31023 mm2/
Assessing Images from Whole-Body MRI sec or 31026 mm2/sec [µm2/sec]).
Multisequence evaluations should be performed by using all im- The definitions for hypointense and hyperintense signal on im-
ages from DW MRI (low, intermediate [if obtained], and high ages at b values of 800–900 sec/mm2 remain subjective but can
b values and ADC maps) in conjunction with the anatomic and be gauged by using adjacent muscle as the reference background
fat fraction images by using image linking and scrolling worksta- tissue (39–41).
tion facilities and coregistration tools as diagnostic aids. Not all hyperintense bone lesions on high b-value images are
Maximum intensity projections of high b-value images malignant in nature. Causes for apparent high b-value focal bone
displayed by using the inverted gray scale are useful for global lesions that are false-positive for cancer include bone marrow
tumor volume assessments and for localizing regional tumor edema caused by fractures, osteoarthritis, infection, bone infarcts,
distribution. These images are able to display disease (eg, for vertebral hemangiomas, chondromas, cysts, focal fat-poor bone
referring clinicians in multidisciplinary meetings or in dis- marrow, and artifacts around metal implants (42,43). Further-
cussion with patients), but maximum intensity projection more, successfully treated focal lesions may undergo liquid trans-
images should not be used alone for reading because appar- formation and can stand out on DW images due to the T2 shine-
ent false-positive and false-negative disease assessments can through phenomenon.
occur (eg, due to T2 shine-through, respiratory motion sig- The presence of focal bone lesions can also be obscured when
nal dephasing, sparse disease pattern) (37,38). Serial volume background bone marrow hyperplasia occurs as the result of ane-
maximum intensity projection image comparisons can be mia, as a rebound after high-dose therapy, or due to use of bone
facilitated by using windowing techniques; for example, by marrow growth factors. This is commonly encountered after
maintaining window width between studies but adjusting the allogenic stem cell transplantation. The detection of skeletal

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Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma

Figure 2: MR images show patterns of myeloma dis-

ease. A, C, E, G, I, Axial diffusion-weighted MR images
(b value of 900 sec/mm2). B, D, F, H, J, Corresponding
apparent diffusion coefficient (ADC) maps. A, B, Images
show appearances of normal adult bone marrow. C, D,
Images demonstrate focal lesion (white arrows) greater
than 5 mm, which returns higher signal intensity at b
value of 900 sec/mm2 than does muscle and background
marrow, and which has ADC resembling soft tissue that
is higher than background marrow but lower than fluid,
as seen in bowel anteriorly (black arrow). E, F, Images
show marrow that has diffusely higher signal intensity
than does muscle and returns ADC that is similar to soft
tissues. G, H, Images demonstrate focal lesion (arrows)
that returns higher signal intensity than does muscle and
background marrow at b value of 900 sec/mm2. How-
ever, background marrow is also higher signal intensity
than muscle, suggesting background diffuse marrow hy-
percellularity that is confirmed on ADC map. I, J, Images
show widespread heterogeneity with tiny nodular areas
of altered diffusion signal (5 mm) with preserved normal
marrow between them. This variegated or micronodular
pattern is confirmed on, K, water-only Dixon and, L, sagit-
tal T1 images. M, Image shows paramedullary soft-tissue
disease that is in direct continuity with marrow disease,
as demonstrated around left femur in M (black arrow). In
contrast, N, extramedullary disease is soft-tissue disease
that is not in continuity with marrow disease, as demon-
strated in M and N (white arrows), which show ischiorec-
tal fossa and pancreatic disease, respectively.

lesions at whole-body DW imaging may also be im-

paired in areas of body movement such as the ribs
and occasionally in the sternum, but review of the
maximum intensity projections of high b-value im-
ages can be helpful. Evaluation of skull vault lesions
is best performed by evaluating the axial source
high b-value images and corresponding Dixon fat
fraction images. The visibility of skull base disease is
generally impaired because of susceptibility effects
and because of the adjacent high signal intensity of
the brain on high b-value images.
Strategies for mitigating false-positive results due
to DW imaging hyperintensities include direct cor-
relations with morphologic appearances, including
T1-weighted spin-echo and Dixon images (44,45)
and ADC values (ADC values of normal bone mar-
row are generally below 600–700 µm2/sec and viable
tumor lies between 700–1400 µm2/sec (46,47,48).
Tumor ADC values greater than or equal to 1400
µm2/sec are usually observed in treated or necrotic
disease. However, myeloma is a disease where there is
intermixing of myeloma cells, fat, and myeloid cells of b values of DW images used for calculations (hence, the
within the marrow space, the relative proportions of which can constraints on the recommended choices of b values). The
alter ADC values, which must also be considered (30,49). Every ADC values may also depend on the diffusion time achiev-
suspicious lesion on high b-value images should be evaluated with able with diffusion sequences (which is dependent on se-
other sequences, particularly Dixon fat fraction images by using quence waveforms and imager specifications). Aside from
coregistration tools. imaging parameters, ADC quantification is influenced by
The authors also recognize there are limitations of the additional factors, which are patient related caused by sus-
ADC cutoff values referred to previously, which are partly ceptibility effects (eg, implants, air-tissue interfaces) or mo-
related to the fact that ADC values depend on the choice tion and technique related caused by the specifications of

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 Messiou et al

Table 1: Sequence Components for Whole-Body MRI Examinations

Comprehensive Assessments
No. Sequence Description Core Clinical Protocol for Research
1 Whole spine: sagittal, T1-weighted, fast spin-echo, Yes Yes
section thickness of 4–5 mm
2 Whole spine: sagittal, T2, STIR or fat-suppressed Yes Yes
T2-weighted, section thickness of 4–5 mm
3 Whole body (vertex to knees): T1-weighted, Axial or coronal (5 mm)* Axial and coronal
 gradient-echo Dixon technique. Fat and water image
reconstructions are mandatory and should be used to
generate fat fraction maps (FF = F/(F+W) 3 100%).
(A 3D fast spin-echo T1-weighted sequence offering
multiplanar capability may be performed as an alternative
to replace sequences 1 and 3.)
4 Whole body (vertex to knees): axial, diffusion- 2 b values (50–100 sec/mm2 3 b values
 weighted, STIR fat suppression, 5 mm contiguous and 800–900 sec/mm2) (additional 500–600 sec/mm2)
sectioning, multiple stations.
ADC calculations with monoexponential data fitting
3D MIP reconstructions of highest b-value images†
5 Whole body (vertex to knees): axial, T2-weighted, Optional Yes
 fast spin-echo without fat suppression, 5-mm contiguous
sectioning, multiple stations, preferably matching the
diffusion-weighted images
6 Regional assessments: for example, symptomatic or known sites Usually not Optional
 outside standard field of view, through sites of suspected
cord compression, nerve root involvement, extramedullary disease
Note.—ADC = apparent diffusion coefficient, MIP = maximum intensity projection, STIR = short inversion time inversion-recovery, 3D =
three-dimensional.
*
5-mm axial imaging may be chosen to match section thickness of diffusion-weighted imaging to facilitate image review.
†
Whole-body 3D MIP images displayed as a sequence of coronal or sagittal MIP images rotating in the axial plane (3 degrees of rotation
per frame) by using an inverted gray scale.

the MRI unit, including magnetic field strength, gradients, DW imaging. Otherwise, the ADC values can be erroneous,
and coils (39). Where there are deviations from the recom- reflecting the distribution of noise on the images.
mended b values due to machine, software, or technical Preferably, water signal should be detectable for the as-
factors, then institutions can determine their own muscle- sessed region on all b-value images. However, the absence of
normalized high b-value signal intensity and ADC cutoff tissue signal intensity on very high (b value of 800–900 sec/
values for normal marrow and for untreated bone marrow mm2) b-value images does not in and of itself invalidate a
lesions as described by Padhani et al (41). tissue from ADC measurements. Where applicable, if signal
intensity is detectable on low and intermediate b-value im-
Size measurements.—The International Myeloma Working ages, then ADC measurements should be performed. ADC is
Group stipulates 5 mm as the threshold for defining an un- generally considered to be a parameter with good reproduc-
equivocal focal active lesion (Fig 2). Therefore, lesions less than ibility, and the coefficient of variation in myeloma-involved
or equal to 5 mm should be documented for surveillance but bone marrow has been reported as low as 2.8% (31).
precise measurements not given due to limitations on image
resolution. Lesions greater than 5 mm but less than 1.0 cm Diffuse disease.—For patients with a suspected new diagnosis
with appropriate signal characteristics should be documented of myeloma, diffuse disease can be suspected from diffuse de-
as focal active disease, but once again, precise measurements creased signal on T1 fast spin-echo or Dixon in-phase and fat-
not given. only images, and diffuse increased signal throughout the marrow
In rare instances when there are unequivocal malignant relative to normal muscle on high b-value images (Fig 2) (48).
lesions less than 1.0 cm and entry to clinical trials mandates Suspicion for diffuse infiltration can be documented but must
the presence of measurable disease, a relaxation of the thresh- be confirmed with trephine biopsy, and imaging must be per-
old of greater than or equal to 1.0 cm may be applied in the formed to state whether posterior iliac crest sampling is likely
knowledge of the caveats on image resolution. to be representative. An ADC measurement using a region of
interest greater than 1 cm2 of representative involved bone mar-
Obtaining ADC values.—ADC measurements should only row can be measured particularly where diffuse infiltration is
be obtained from lesions or areas when water is detectable at suspected (50).

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Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma

Table 2: Clinical Reporting Template

Clinical Reporting Template Notes

Indication
Technique Core or comprehensive protocol, additional sequences and deviations
Findings
Dates of previous examinations
Evaluation of bones Spine and then head to thighs in descending order
Measurements of up to five focal lesions and Normal, focal, focal on diffuse, diffuse, micronodular*
   document pattern of marrow infiltration
Paramedullary or extramedullary sites Measure size
Vertebral fractures Document presence and use a combination of morphologic and
 functional imaging to characterize as benign versus malignant.
Source.—Reference 52.
RAC for each anatomic region† Cervical spine, thoracic spine, lumbar spine, pelvis, long bones, skill, ribs or
other
   1: Highly likely to be responding
   2: Likely to be responding
  3: Stable
   4: Likely to be progressing
   5: Highly likely to be progressing
Posterior iliac crests Is trephine likely to be representative?
Incidental findings Incidental lesions including avascular necrosis, which may be a complication
of myeloma treatment. Source.—Reference 53.
Conclusion
Summary statement, RAC score, heterogeneity, State level of concern regarding incidental findings
  recommendations including for investigation
of equivocal findings
Note.—RAC = response assessment category.
*
See also Figure 2.
†
See also Table 3.

Although useful data are emerging to differentiate normal 5, highly likely to be progressing (Table 3). More detailed case
age-matched bone marrow from diffuse disease by using ADC report forms for research are included in Appendix E1 (online).
(47,48,49), whole-marrow quantitative measures of ADC are not
yet practical measures and therefore not part of the MY-RADS Clinical Trial Assessments
standard. However, marrow ADC values above 600–700 µm2/
Most clinical reports will be performed as outlined in the previous
sec in a nontreated and newly diagnosed patient with multiple
section. However, academic centers wishing to collect assess-
myeloma could be used to increase confidence for the diagnosis
ments of disease for clinical trials may require more sophis-
of diffuse marrow involvement (8). For patients who have been
ticated scoring systems. Detailed instructions for a proposed
treated, there is increased potential for false-positive appearances
clinical trials scoring system and an exemplar case study can
of diffuse infiltration due to rebound hypercellularity related to
be found in Table E2 and Figure E1 (Appendix E1 [online]).
treatment effects or granulocyte colony–stimulating factor (8).
Knowing that quantitative assessments such as ADC and fat
Therefore, when diffuse disease is suspected, administration of
fraction measurements can change over time (for example, re-
granulocyte colony–stimulating factor must be excluded and if
sponding myeloma may show an early increase in ADC values at
progression is suspected based on suspicion for diffuse infiltra-
4–6 weeks due to cell death, followed by a decrease in ADC with
tion alone, then this must be confirmed with serum biochemis-
return of normal fatty marrow [51]), it is difficult to be prescriptive
try and/or marrow sampling.
regarding the frequency of imaging follow-up. Therefore, for cor-
relation, we recommend that imaging should coincide with clini-
Structured Reporting
cal routines where serum and marrow assessments are performed.
Structured clinical reporting (Table 2) should be performed for
each examination. For response assessments, we recommend
that response assessment category, or RAC, be assigned accord- Conclusion
ing to anatomic regions. For each region, RAC can be assigned The Myeloma Response Assessment and Diagnosis System
by using the criteria given in Table 3. The RAC should use a (MY-RADS) system provides comprehensive characteriza-
five-point scale as follows: 1, highly likely to be responding; 2, tion of the myeloma state, both at diagnosis and the start of
likely to be responding; 3, stable; 4, likely to be progressing; treatment, as well as over time as the disease evolves during

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 Messiou et al

Table 3: MY-RADS Response Assessment Categories

RAC Descriptions*
RAC Descriptions *
For soft-tissue disease, RECIST version 1.1 criteria meeting
1: Highly likely to be responding    requirements for PD
Return of normal fat containing marrow in areas previously Note.— Multiple criteria determine response assessment cat-
   infiltrated by focal or diffuse myelomatous infiltration egory (RAC). For RAC 1 or 2, when diffusion-weighted imaging
Unequivocal decrease in number or size of focal lesions and morphology are discordant, consideration should be given
Conversion of a packed bone marrow infiltrate into to pitfalls such as T1 pseudoprogression and bone marrow fat
  discrete nodules, with unequivocal decrease in tumor reemergence (the latter two may not increase apparent diffusion
load in the respective bone marrow space coefficient [ADC] values). MY-RADS = Myeloma Response As-
Decreasing soft tissue associated with bone disease sessment and Diagnosis System, RECIST = Response Evaluation
Criteria in Solid Tumors.
Emergence of intra- or peritumoral fat within/around
   focal lesions (fat dot or halo signs)
*
RECIST version 1.1 categories for soft-tissue disease are as fol-
lows. Complete response (CR): Disappearance of all target lesions.
Previously evident lesion shows increase in ADC from Partial response (PR): At least a 30% decrease in the sum of the
  1400 µm2/sec to .1400 µm2/sec longest diameter (LD) of target lesions, taking as reference the
40% increase in ADC from baseline with corresponding baseline sum LD. Stable disease (SD): Neither sufficient shrinkage
  decrease in normalized high b-value signal intensity; to qualify for PR nor sufficient increase to qualify for PD, taking
morphologic findings consistent with stable or responding as reference the smallest sum LD since the treatment started. Pro-
disease gressive disease (PD): At least a 20% increase in the sum of the LD
For soft-tissue disease, RECIST version 1.1 criteria for PR/CR of target lesions, taking as reference the smallest sum LD recorded
since the treatment started or the appearance of one or more new
2: Likely to be responding
lesions. Progression of nodes: nodes less than 1.0 cm have to have
Evidence of improvement but not enough to fulfill grown by at least 5 mm in short axis from baseline or treatment
   criteria for RAC 1. For example: nadir and be greater than or equal to 1 cm to be considered to
   Slight decrease in number/size of focal lesions have progressed. Nodes that are 1.0–1.5 cm and have grown by at
   Previously evident lesions showing increases in ADC least 5 mm in short axis from baseline or treatment nadir and are
   from 1000 µm2/sec to ,1400 µm2/sec greater than or equal to 1.5 cm in short axis can be considered to
  .25% but ,40% increase in ADC from baseline with have progressed. For nodes greater than or equal to 1.5 cm in short
   corresponding decrease in high b-value signal intensity; axis, use RECIST version 1.1 progression criteria. Progression of
visceral disease: Use RECIST version 1.1 progression criteria above
morphologic findings consistent with stable or respond-
applied to soft-tissue disease. Source.—Reference 54.
ing disease
For soft-tissue disease, RECIST version 1.1 not meeting
   requirements for PR
3: No change therapy and follow-up. MY-RADS recommendations are likely
No observable change
to fulfill the need to promote standardization and diminish
4: Likely to be progressing
variations in the acquisition, interpretation, and reporting of
Evidence of worsening disease, but not enough to
whole-body MRI and allow better response assessments. This
   fulfill criteria for RAC 5
Equivocal appearance of new lesion(s)
system is designed for guiding patient care but has potential
No change in size but increasing signal intensity on high for incorporation into clinical trials when lesion measurements
    b-value images (with ADC values ,1400 µm2/sec) con- become more important. MY-RADS allows the categoriza-
sistent with possible disease progression tion of patients with specific patterns of disease for clinical
Relapsed disease: reemergence of lesion(s) that trial stratification. MY-RADS requires validation within clini-
   previously disappeared or enlargement of lesion(s) cal trials, including assessments of reproducibility. We suggest
   that had partially regressed/stabilized with prior treatments that MY-RADS be evaluated in studies that assess the effects
Soft tissue in spinal canal causing narrowing not associated of life-prolonging myeloma treatments, including novel treat-
   with neurologic findings and not requiring radiation therapy ment strategies such as immunotherapy. In these studies, MY-
For soft-tissue disease, RECIST version 1.1 criteria RADS assessments of the depth and heterogeneity of response
   not meeting requirements for PD should be compared with established myeloma response cri-
5: Highly likely to be progressing teria. Given the high rates of complete response seen in pa-
New critical fracture(s)/cord compression requiring radiation tients with multiple myeloma with new treatment approaches,
  therapy/surgical intervention; only if confirmed as malig-
new response categories need to be defined that can identify
nant with MRI signal characteristics
responses that are deeper than those conventionally defined as
Unequivocal new focal (.5 to 10 mm)/diffuse area(s)
   of infiltration in regions of previously normal marrow
complete response.
Unequivocal increase in number/size of focal lesions Correlations with quality-of-life measures, rates of skeletal
Evolution of focal lesions to diffuse neoplastic pattern events, and rates of progression-free survival are also needed. The
Appearance/increasing soft tissue associated with bone disease latter are prerequisites for the introduction of whole-body MRI
New lesions/regions of high signal intensity on high into longer term follow-up registry studies that prospectively
  b-value images with ADC value between 600–1000 µm2/sec collect appropriate meta-data, which would allow objective as-
sessments of whether whole-body MRI is effective in supporting

Radiology: Volume 291: Number 1—April 2019 n radiology.rsna.org 11

Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma

patient care and drug development. It is anticipated that, as evi- 13. Merz M, Hielscher T, Wagner B, et al. Predictive value of longitudinal whole-
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we recommend that Myeloma Response Assessment and Diagno- abnormal free light chain ratio identifies patients with asymptomatic myeloma at
high risk for progression to symptomatic disease. Leukemia 2013;27(4):947–953.
sis System is now evaluated in clinical trials to assess its impact on 15. Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone
the clinical practice of myeloma. for high-risk smoldering multiple myeloma. N Engl J Med 2013;369(5):438–447.
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received payment for lectures including service on speakers bureaus from Janssen magnetic resonance imaging of bone marrow in previously untreated patients
and Takeda; received payment for development of educational presentations from with multiple myeloma. Ann Oncol 2005;16(11):1824–1828.
Amgen. Other relationships: disclosed no relevant relationships. J.H. Activities re- 18. Mariette X, Zagdanski AM, Guermazi A, et al. Prognostic value of vertebral le-
lated to the present article: institution received grant from Celgene. Activities not sions detected by magnetic resonance imaging in patients with stage I multiple
related to the present article: is a consultant for Amgen and Celgene; has grants/ myeloma. Br J Haematol 1999;104(4):723–729.
grants pending with Celgene and Sanofi; received payment for lectures including 19. Dhodapkar MV, Sexton R, Waheed S, et al. Clinical, genomic, and imaging
service on speakers bureaus and payment for travel/accommodations/meeting ex- predictors of myeloma progression from asymptomatic monoclonal gammopathies
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and Takeda. Other relationships: disclosed no relevant relationships. S.D. disclosed 20. Mai EK, Hielscher T, Kloth JK, et al. A magnetic resonance imaging-based
no relevant relationships. F.E.L. disclosed no relevant relationships. L.I.M. dis- prognostic scoring system to predict outcome in transplant-eligible patients with
closed no relevant relationships. D.J.C. disclosed no relevant relationships. M.D.B. multiple myeloma. Haematologica 2015;100(6):818–825.
disclosed no relevant relationships. N.A. disclosed no relevant relationships. B.Ø. 21. Rasche L, Angtuaco EJ, Alpe TL, et al. The presence of large focal lesions is a strong
disclosed no relevant relationships. H.P.S. Activities related to the present article: independent prognostic factor in multiple myeloma. Blood 2018;132(1):59–66.
disclosed no relevant relationships. Activities not related to the present article: is a 22. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Work-
consultant for Bayer and Curagita; received payment for lectures including service ing Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol
on speakers bureaus from Bayer and Siemens; received payment for travel/accom- 2014;15(12):e538–e548.
modations/meeting expenses unrelated to activities listed from Bayer, Curagita, and 23. Sachpekidis C, Mosebach J, Freitag MT, et al. Application of (18)F-FDG PET
Siemens. Other relationships: disclosed no relevant relationships. O.L. disclosed and diffusion weighted imaging (DWI) in multiple myeloma: comparison of
no relevant relationships. J.T.A. disclosed no relevant relationships. M.F.K. Activi- functional imaging modalities. Am J Nucl Med Mol Imaging 2015;5(5):479–492.
ties related to the present article: disclosed no relevant relationships. Activities not 24. Pawlyn C, Fowkes L, Otero S, et al. Whole-body diffusion-weighted MRI: a new
related to the present article: is a consultant for and received payment for lectures gold standard for assessing disease burden in patients with multiple myeloma?
including service on speakers bureaus from Amgen, Celgene, Janssen, and Takeda; Leukemia 2016;30(6):1446–1448.
has grants/grants pending with Celgene; received payment for travel/accommoda- 25. Rasche L, Angtuaco E, McDonald JE, et al. Low expression of hexokinase-2 is
tions/meeting expenses unrelated to activities listed from Takeda. Other relation- associated with false-negative FDG-positron emission tomography in multiple
ships: disclosed no relevant relationships. A.P. disclosed no relevant relationships. myeloma. Blood 2017;130(1):30–34.
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