MYRADS
MYRADS
MYRADS
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.
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
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).
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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