REVIEW ARTICLE

Standardizing Magnetic Resonance Imaging Protocols,

Requisitions, and Reports in Multiple Sclerosis: An Update for
Radiologist Based on 2017 Magnetic Resonance Imaging in
Multiple Sclerosis and 2018 Consortium of Multiple Sclerosis
Centers Consensus Guidelines
Octavio Arevalo, MD,* Roy Riascos, MD,* Pejman Rabiei, MD,* Arash Kamali, MD,* and Flavia Nelson, MD†
surrogate marker of response to therapy and disease activity in
Abstract: The advent of magnetic resonance imaging has improved our clinical practice. Most importantly, MRI has allowed early diagno-
understanding of the pathophysiology and natural course of multiple sclero- sis of MS as well as confidence in the accuracy of the diagnosis.6,7
sis (MS). The ability of magnetic resonance imaging to show the evolution The supportive evidence of lesion activity on MRI as a surrogate
of MS lesions on sequential scans has brought it to be one of the endpoints
Downloaded from http://journals.lww.com/jcat by BhDMf5ePHKbH4TTImqenVHsCMLYwnrnSxvyCxbRYMD+3Vkt83l+1ONuXoQ+4z2gV on 02/06/2019

marker of disease progression in MS has been confirmed in many

in clinical trials for disease-modifying therapies. Based on the most updated
consensus guidelines from the American (Consortium of MS Centers) and
European (Magnetic Resonance Imaging in MS) boards of experts in MS,
this document shows the most relevant landmarks related to imaging find-
ings, diagnostic criteria, indications to obtain a magnetic resonance, scan
protocols and sequence options for patients with MS. Although incorporat-
ing the knowledge derived from the research arena into the daily clinical
practice is always challenging, in this article, the authors provide useful rec-
ommendations to improve the information contained in the magnetic reso-
nance report oriented to facilitate communication between radiologists and
specialized medical teams involved in MS patients' multidisciplinary care.
Key Words: multiple sclerosis, magnetic resonance imaging,
imaging protocol
(J Comput Assist Tomogr 2019;43: 1–12)
M ultiple sclerosis (MS) is an autoimmune inflammatory cen-
tral nervous system (CNS) disease, characterized by episodes
of focal lymphocytic infiltration of the neural tissue that cause
myelin and axonal destruction, followed by a remyelination phase.
Persistence of the inflammatory process, widespread microglial
activation, and progressive accumulation of lesions may convey
to neurodegeneration and accumulation of neurological disabil-
ity.1,2 Clinical manifestations of this pathologic process are epi-
sodes of focal neurologic deficits of at least 24 hours of duration
that recover partially or entirely and are called relapses; these of-
ten correspond to the presence of an enhancing lesion on mag-
netic resonance imaging (MRI). Not all enhancing lesions will
cause symptomatology during their active (enhancing) phase,
which may last from 2 to 6 weeks3–5; in fact, most lesions are clin-
ically silent. This makes MRI a more accurate biomarker of dis-
ease activity as opposed to relying on evidence of clinical relapses
and/or disability worsening in the absence of relapses. The advent
of MRI has significantly advanced our understanding of the path-
ophysiology of MS, allowing lesion evolvement on sequential
brain MR imaging, to become an endpoint in clinical trials for
new disease-modifying therapies (DMTs), therefore becoming a
From the *Department of Diagnostic and Interventional Imaging, The Univer-
sity of Texas Health Science Center, Houston, TX; and †Department of Neurol-
ogy, University of Minnesota Twin Cities, Minneapolis,MN.
Received for publication April 13, 2018; accepted April 16, 2018.
Correspondence to: Roy Riascos, MD, Department of Diagnostic and
Interventional Imaging, The University of Texas Health Science Center,
6431 Fannin, MSB 2.130B, Houston, TX 77030-1503 (e‐mail:
roy.f.riascoscastaneda@uth.tmc.edu).
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/RCT.0000000000000767
studies,8–10 and current guidelines in North America and Europe
recommend the best sequences shown to detect white matter (WM)
and gray matter (GM) lesions6,7,11,12 and capture disease activity,
providing clinicians with the best information available to make
decisions regarding diagnosis, response to therapy, and evidence
of disease progression.8
Despite the availability of these guidelines, which are often
followed closely by neurologists, experts in the field of MS, and
neuroradiologists, most neurologists taking care of MS patients
work in a non–MS-specialized practice and may not have access
to an MS MRI protocol and standardized radiology reports. In
routine clinical practice, neurologists do rely on the MRI reports
to monitor disease activity in the absence of clinical activity; how-
ever, not infrequently and especially in nonacademic institutions,
reports may be brief summaries of findings that mostly focus on
confirming the diagnosis and detecting lesion enhancement,
which may not be sufficient information for a clinician attempting
to make decisions on disease management, based on MRI activity.
This decoupling focus might be largely due to a lack of communi-
cation between clinicians managing MS patients and radiologists.
Issues of scan technique, the time between scans, and information
about lesion evolution such as increase in number of lesions and
increase in size (when feasible) may play an essential role in the
decision-making process, for both evaluation of response to ther-
apy and determination of disease progression.7,11,13 This article
summarizes the most relevant recommendations related to key im-
aging findings in MS, including revised diagnostic criteria, indica-
tions to obtaining an MRI, protocol, and sequence options, and
specifically provides useful recommendations for standardizing
the radiology report. Standardized reports will help clinicians with
the decision-making process in the treatment of the often unpre-
dictable course of MS. The present article is all based on the most
updated available consensus guidelines.6,7,11,14
Outcome Measurements
The most common endpoints used in clinical trials can be clas-
sified into 2 groups, namely, primary and secondary outcomes.15
Primary outcomes refer to data regarding the clinical evaluation
of patients; the most common outcomes used are the annualized
relapse rate16 and evaluation of accumulation of neurological dis-
ability by standardized measurements such as the Expanded Dis-
ability Status Scale (EDSS).15 Secondary outcomes include the
increase in number and volume (size) of the WM T2-weighted
(T2w) hyperintense lesion load, the presence of new T1-weighted
(T1w) contrast-enhancing lesions (CELs), and measures of whole
brain atrophy by MRI.10,15,17–19 Another important activity measure

J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019 www.jcat.org 1

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Arevalo et al J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019
is the number of unique active lesions (gadolinium-enhancing
lesions plus unenhanced new and substantially enlarged T2-
hyperintense lesions) identified on sequential imaging. Measures
of unique active lesions correlate with clinical relapse rates; con-
sequently, the effects of DMTs on lesion activity correlate with
their effects on clinical relapses and accumulated disability, within
the context of clinical trials.20 Other MRI markers that have been
used as exploratory outcome measures are persistent black holes
(BHs), volumetric measures of specific brain structures, and ad-
vanced MRI techniques such as magnetization transfer ratio,
MR spectroscopy, and diffusion tensor imaging for brain tissue in-
tegrity.15,21 Nonetheless, the extent of the disease based on imag-
ing often does not correlate with the overall clinical disability, that
incongruence has been called the clinicoradiological paradox. It is
thought to be explained by many variables including underestima-
tion of the involvement of normal-appearing WM and GM, residual
brain volume, spinal cord lesions, and brain functional plasticity.22–24
In the last years, the clinicoradiological paradox has been fertile
ground for many studies in advanced techniques and also in the de-
velopment of novel MRI protocols headed to find more reliable im-
aging biomarkers.4,9,23,25–27 These techniques are currently far from
application in clinical practice and will not be part of this discussion.
Based on what we have learned from clinical trials, the MRI
measures most regularly used in clinical practice for diagnosis and
follow-up monitoring of MS patients are as follows:
1. Presence of T1w CEL (number, location, and enhancement
characteristics)
2. Increase in the number and size of T2w lesions, in reference to
a previous scan (when available)
3. Increase in T1w-hypointensities known as persistent black-holes,
4. Atrophy estimation (where available)
5. The presence of cortical lesions (in specialized MS centers)
Most MS-related T1w hypointensities are reversible; those
that persist for more than 6 months are designated as persistent
BHs and may represent irreversible structural damage.4,28,29 Other
useful measures are spinal cord lesions, the central vein sign
(CVS), iron deposition measures, and quantification of WM and
GM atrophy, but their use is not widespread yet.26,30–32
MS Diagnosis
Some clinic-pathological variants of MS have been described
in the literature including tumefactive MS, Schilder's disease, and
Balo concentric sclerosis.33,34 However, this revision will be mostly
focused on the relapsing and progressive forms. Diagnosis of MS is
based on the McDonald criteria and relies on demonstration of dis-
semination of demyelinating lesions in time and space. Albeit diag-
nosis might be made only on clinical grounds, MRI evaluation of
patients suspected to have a demyelinating CNS disease is a corner-
stone for supporting the diagnosis and to rule out other similar
disorders.10,13,35–38 By the 2010 revision of McDonald criteria,
which is the current framework for MS diagnosis, MRI findings
in a single scan may prove dissemination in space (DIS) or dissem-
ination in time (DIT).35 Dissemination in space consists of the pres-
ence of at least 1 typical T2w-hyperintense lesion in at least 2 of 4
locations characteristic for MS (juxtacortical, periventricular,
infratentorial, and spinal cord).35 Moreover, the presence of at least
1 new T2w-hyperintense or T1w-CEL in a follow-up MRI exami-
nation compared with the baseline scan or the simultaneous pres-
ence of asymptomatic T1w-CEL and T1w-hypointense lesions in
the same study will support DIT.35 The recently presented 2017 re-
vision adds cortical lesions as one of the characteristic locations.39
The Magnetic Resonance Imaging in MS (MAGNIMS)
steering committee11,12 has proposed some updates to the widely
2 www.jcat.org
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
used 2010 McDonald guidelines.35 Recommendations regard-
ing DIS criteria include changing the juxtacortical to cortical/
juxtacortical location, to consider optic nerve lesions as the typical
fifth area of MS lesions, and the requirement of at least 3 lesions in
the periventricular WM to consider that area affected. On the other
hand, MAGNIMS guidelines state that the differentiation between
symptomatic and asymptomatic lesions based on clinical findings
is not always accurate; thus, that discrimination might not be con-
venient.12 The MAGNIMS experts argue that following these rec-
ommendations will improve the specificity for MS diagnosis.12
Indications and protocols are summarized in Table 1.
MRI Protocols
Brain MRI is the most helpful tool in the diagnosis and mon-
itoring of MS patients. However, image acquisition parameters
should be standardized aiming to decrease technically related mis-
interpretations potentially resulting in inadequate patient care.7
One of the most critical issues is correct positioning, as some stud-
ies have shown that suboptimal positioning may result in errors
when measuring lesion size.40,41 The current standard is that the
axial plane must be oriented on a line drawn from the inferior sur-
face of the genu to the inferior border of the splenium of the cor-
pus callosum6 (Fig. 1). In addition, MRI scans of MS patients
should be done in high-field magnets of at least 1.5 T, but lesions
are better evaluated on a 3.0 T scan.6,11,27,42 Another item in im-
age quality assurance is that the spatial resolution of axial planes
should be at least 1  1 mm pixels, with nongapped section thick-
ness no wider than 3 mm, as long as volumetric acquisition does
not exceed 1  1  1 mm voxels.6 It is noteworthy that follow-up
scans should be done, if possible, using the same equipment and fol-
lowing the same positioning rules aiming to facilitate comparison.7,11
Studies have shown that the use of 3 T and 7 T scanners enables the
detection of more lesions compared with those of lower magnetic
fields, improves the definition of plaques and its relationships with
vascular structures, and better demonstrates DIS32,43,44; however, it
does not seem to be useful for earlier diagnosis.12
Administration of gadolinium-based contrast agents (GBCAs)
is deemed essential in the imaging workup of patients with demye-
linating diseases; notwithstanding, there has been a growing con-
cern about their safety profile. Gadolinium-based contrast agents
had been considered drugs with a high safety profile for a long
time45; however, more recent studies have proven the association
between GBCA administration and significant adverse effects such
as the nephrogenic systemic fibrosis in patients with chronic kidney
disease,46–48 and the gadolinium ion deposition in brain structures
(dentate nuclei and globus pallidus), bone, skin, and elsewhere
in the body.49–51 Based on the chemical structure of its chelating
ligands, GBCAs can be classified into 2 groups, macrocyclic
and linear, and each group can be further subdivided into ionic
and nonionic. Macrocyclic-ionic is the GBCAs subset with the
highest structural stability; consequently, it is the least prone to re-
lease the gadolinium ion to be impregnated on neural tissue.52
Health effects of gadolinium deposition in the brain are still un-
clear, so the need for contrast-enhanced studies must be clearly in-
dicated. The current tendency regarding contrast media is to use
macrocyclic GBCAs owing to its apparent safer pharmacological
profile,49,53 at a standard dose of 0.1 mmol/kg and with a delay of
5 minutes before the T1w acquisition.6
Comparing MAGNIMS and CMSC
Protocol Guidelines
Currently, there are 2 guidelines: one developed by the Con-
sortium of MS Centers (CMSC)6 (North America) and the other
by MAGNIMS11 (Europe), regarding brain MRI protocols. Those
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019 MRI Protocols, Requisitions, and Reports in MS

TABLE 1. MRI Protocols and Indications6,7,26

Scenario Indication CMSC MAGNIMS

Baseline evaluation – First clinical episode suggestive Mandatory Mandatory
of demyelinating disease – 3D inversion recovery–prepared – Axial PD and/or
– CDMS without an adequate T1 gradient echo T2w-FLAIR and/or T2-w
baseline scan – 3D sagittal T2w-FLAIR – Sagittal 2D/3D T2-FLAIR
– 3D T2w – 2D/3D T1w post-Gd
– 2D axial DWI Optional
– 3D FLASH post-Gd – Unenhanced 2D/3D T1w
Optional – 2D/3D DIR
– Axial PA – 2D axial DWI
– pre- or post-Gd
– Axial T1 spin-echo
– SWI
Follow-up – Yearly if clinically stable The same protocol as for Mandatory
– 6 mo after start DMT baseline evaluation – Axial PD and/or T2w-FLAIR
and/or T2-w
– 2D/3D T1w post-Gd
Optional
– Unenhanced 2D/3D T1w
– 2D/3D DIR
– 2D axial DWI
PML surveillance Every 3 mo in high-risk patients* – 3D sagittal T2w-FLAIR Not specified
– 2D axial DWI
Sudden clinical deterioration ASAP Tailored to clinical suspicion Tailored to clinical suspicion
Spinal MRI – Clinical history suspicious of Mandatory Mandatory
spinal cord involvement – Sagittal T2w Sagittal T2w and (dual-echo
– High suspicion of demyelinating – Sagittal PA or sagittal STIR or PD or STIR)
disease with nonconclusive PST1-IR Sagittal T1w post-Gd (only if
brain MRI – Axial T2w through demyelinating lesions T2w lesions)
Optional Optional
– Axial T2w images through the – Axial 2D/3D T2w
whole cervical cord – Sagittal PST1-IR
– Sagittal T1w post-Gd
*More than 18 months on natalizumab, positive John Cunningham virus antibodies.6
ASAP indicates as soon as possible; CDMS, clinically definite multiple sclerosis; FLASH, fast low angle shot magnetic; Gd, gadolinium; PA, proton
attenuation; PST1-IR, phase-sensitive T1 inversion recovery; STIR, short tau inversion recovery.

guidelines recommend particular approaches for the baseline recommend the inclusion of additional sequences on a case by case
and follow-up scans, but most of the mandatory and optional se- basis, considering specific patient needs and to rule out other differ-
quences overlap. In the CMSC guidelines, baseline and follow-up ential diagnoses6,11 (Table 1).
brain MRI protocols are the same and consist of 3-dimensional
(3D) inversion recovery–prepared T1 gradient echo, 3D sagittal
T2w fluid attenuation inversion recovery (FLAIR), 3D T2w,
2-dimensional (2D) axial diffusion-weighted imaging (DWI),
and 3D fast low angle shot magnetic postgadolinium as manda-
tory sequences. Moreover, optional sequences include axial proton
attenuation, pregadolinium or postgadolinium axial T1 spin-echo,
and susceptibility weighted image (SWI) for identification of
central vein within T2 lesions.6 The CMSC group suggests an
abbreviated protocol for progressive multifocal leukoencepha-
lopathy (PML) surveillance composed by 3D sagittal T2w-FLAIR
and 2D axial DWI acquisitions.6
The MAGNIMS guidelines discriminate between baseline
and follow-up scan protocols, without any specific comment on
PML surveillance.11 According to MAGNIMS, baseline MRI scans
must have (a) axial proton density (PD) and/or T2w-FLAIR or T2-
w, (b) sagittal 2D/3D T2-FLAIR, and (c) 2D/3D contrast-enhanced
T1w as mandatory sequences.11 Optional sequences for the baseline
study are unenhanced 2D/3D T1w, 2D/3D dual inversion recovery FIGURE 1. Correct orientation of the axial plane. Midline sagittal
(DIR), and 2D axial DWI.11 With respect to follow-up examinations, T1w image of the brain. The white line exemplifies the standard
MAGNIMS mandatory sequences are axial PD and/or T2w-FLAIR plane for the axial images, which must be oriented on a line drawn
or T2-w and 2D/3D contrast-enhanced T1w, with the same optional from the inferior surface of the genu to the inferior border of the
sequences as the baseline protocol.11 Both CMSC and MAGNIMS splenium of the corpus callosum.

© 2018 Wolters Kluwer Health, Inc. All rights reserved. www.jcat.org 3

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Arevalo et al J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019

Spine MRI Protocols Addressing MS Lesions by MRI

More than 90% of MS patients present spinal cord involve-
ment11; however, MRI evaluation of the spinal cord is much more
technically challenging owing to breathing and blood pulsations,
which lead to a noticeable increment in ghosting and truncation
artifacts.54 Considering technical challenges, spine MR protocols
should be standardized pursuing images of enough quality for
accurate diagnosis and surveillance; based on this, the CMSC
and MAGNIMS have published guidelines addressing the best
spinal MRI techniques.6,11 Indications and protocols are outlined
in Table 1.
Multiple sclerosis lesions are represented as plaques, which
are defined as foci of inflammatory demyelination when active
and of gliosis when chronic, usually seen on an MRI as oval-shaped
lesions, larger than 3 mm in diameter, often with well-defined bor-
ders. Typical plaque locations are the subcortical WM (U fibers),
periventricular WM, and posterior fossa (Fig. 2). Dawson's fin-
gers correspond to demyelinating periventricular plaques through
corpus callosum aligned with the medullary veins. In the spinal
cord, demyelinating plaques are commonly wedge-shaped and
its classic location is in the lateral or posterior margin of the spinal

FIGURE 2. Four typical locations of MS lesions. Magnetic resonance imaging of the brain with images in (A) axial FLAIR, (B) axial FLAIR
close-up, and (C) sagittal T2w; image in (D) corresponds to a sagittal short tau inversion recovery image of the cervical spine. Oval-shaped
hyperintense plaques, with well-defined borders are seen in the periventricular WM (arrows in A), in the subcortical WM (arrow in B), and in the
inferior aspect of the medulla oblongata (arrow in C). Focal hyperintensity of the posterior aspect of the spinal cord at C5-C6 level (arrows in
D) consistent with a MS plaque.

4 www.jcat.org © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019 MRI Protocols, Requisitions, and Reports in MS

cord involving less than a third of the cord cross section without
extending for more than three segments.1,30 One of the major bene-
fits of MRI is to serve as a tool for the assessment of disease activity,
defined as the detection of new T2w hyperintense or gadolinium-
enhancing lesions, or the unequivocal enlargement of a known
T2w lesion.9,10 The following is a point by point review of the most
pertinent landmarks of the MRI semiology of MS, with the purpose
of normalizing concepts in reporting MRI scans.
T2w Hyperintense Lesions
The increase in the signal intensity in T2w images is the rep-
resentation of the increment of tissue water content in that partic-
ular pixel. Hence, edema derived of the blood-brain barrier (BBB)
breakdown in acute demyelinating lesions, axonal loss, and gliosis
in chronic plaques and a combination of those patterns in subacute
lesions may lead to an unspecific elevation of the T2w signal in-
tensity in MRI.1 Because of that ambiguity, the most significant
variable to determine in regard T2w lesions is the lesion load in
terms of change in number, volume, or area of the lesions as a sur-
rogate of disease progression/activity.9,15,18,19
For clinicians who monitor MS patients, it is important that
the radiologist report includes the T2w lesion load on the base-
line MRI and its change in follow-up studies compared with the
initial scan (when available) (Table 2). Counting T2w lesions,
discriminating them in each of the 4 typical locations defined
in the 2010 McDonalds criteria (juxtacortical, periventricular,
infratentorial, and spinal cord),7,19,35 and the description of var-
iations in T2w lesion size in follow-up scans are semiquantita-
tively approaches to asses T2w lesion load (Fig. 3). A detailed
description of T2w lesion size variation would be crucial given
the enormous value of enlarging lesions as a marker of disease pro-
gression and treatment effectiveness.6,7,9,11,35 Notwithstanding, ac-
curate evolutionary T2w lesion load appraisal requires comparable
high-quality MRI scans following parameters aforementioned.40,41
Advanced MRI techniques such as using subtraction software have
shown to be helpful for accurate and consistent measurement of
T2w lesion load, but this resource is not widely available in daily
clinical practice.18,19
Contrast-Enhancing Lesions
The inflammatory process behind active MS plaques causes
focal disruption of the BBB allowing extravasation of the GBCA
into the extracellular space.1,13 The leakage of the GBCA through
permeable capillaries causes T1w shortening that is the basis for
the lesion enhancement seen in postcontrast T1w images and its
use as a clinical marker of currently active inflammation and
BBB disruption4,5,29,55(Fig. 4). Furthermore, On T1w series with-
out contrast, CELs may display similar or lower signal intensity
compared with surrounding normal-appearing WM.29
New inflammatory plaques usually show contrast enhance-
ment for 2 to 6 weeks with an average of 3 weeks and rarely for
more than 3 months.4,6,7,30,55 Noteworthy, CELs whose enhancing

TABLE 2. Recommendations for MRI Requisition and Report Based on MAGNIMS and CMSC Guidelines

Section Description
Requisition – Clinically suspected CNS location of the lesion
– Symptoms duration (≥24 h)
– Current therapy
MRI technique – Field strength of the MRI scan
– Sequences utilized
– Slice thickness
– Type and dose of contrast agent
– Anatomical area covered
Findings in reference to a previous scan when available T2w hyperintense lesions
– Semiquantitative assessment of lesions; discrimination in the 4 typical
locations (juxtacortical, periventricular, infratentorial, and spinal cord)
– Variations in T2w lesion size
CELs
– Number (if countable), size, location, interval changes, enhancement pattern
BHs
– Number (if countable), size, location, interval changes in number (estimate)
Atrophy (optional)
– Global qualitative assessment
– Optional: third ventricle width and/or callosal area
Cortical lesions (optional)
– Number (if countable), size, location, interval changes in number and volume
(estimate)
SWI (optional)
– Vein running through an MS plaque in at least 2 perpendicular planes.
– Abnormal pattern of iron deposition in deep GM on SWI
– Hypointense rim sign
Spinal cord lesions
– Number, size, location (axial and longitudinal), enhancement, interval changes
Conclusion – Highlight items that favor MS (DIS and DIT) or another differential diagnosis
– Solve the original inquiry
– Give a recommendation

© 2018 Wolters Kluwer Health, Inc. All rights reserved. www.jcat.org 5

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Arevalo et al J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019

FIGURE 3. New T2-hyperintense lesion. Brain MRI from a 26-year-old patient with images in axial T2-FLAIR. The baseline study is shown on
panel (A), and the follow-up image is displayed on panel (B). Notice the new T2-hyperintense lesion (arrow in B) without any significant
interval change of the baseline plaques (arrowheads).

lasts for more than 1 month have the higher risk to be part of that
14% to 41% of CEL that evolves into persistent BH.4 Some au-
thors have described the lesion pattern of enhancement as a tool
for plaque's age calculation29,55; in this way, nodular enhancement
accounts for around 65% of plaques, and it is consistently seen in
the first 29 days from onset.55 Otherwise, ring enhancement is
present in 23% of plaques and corresponds to the late appearance
of aggressive nodular enhancing lesions that last more than
1 month. Ring enhancement pattern is thought to stand for more
destructive lesions inferred by the fact that 75% of them will cul-
minate as persistent BH.29,55
Studies have found a correlation between the number of
new CEL and the likelihood of treatment failure17; however,
its use as a surrogate for MS relapses has been a focus of debate
and research owing to its weak association with neurological
signs and symptoms.5,13,15,24 Radiologists are encouraged to re-
port changes in number, size, and enhancing pattern of CEL in
both baseline and follow-up scans, paying particular attention to
those becoming persistent BH (Table 2).
Black Holes
A BH is defined as a focal hypointense area in T1w images
that coincides with a hyperintense lesion in T2w images.4,56 Even
though most MS-related T1w hypointensities are reversible, those
that persist for more than 6 months are designated persistent BHs
and may represent irreversible structural damage4,28,29(Fig. 5).
Histologically, persistent BHs demonstrate gliosis with reactive
astrocytes, an absence of myelinated axons, and hypocellularity as
the vestige of a previous destructive inflammatory process.4,11,29,56
Consequently, T1w lesion load and BHs accumulation directly

FIGURE 4. Contrast-enhancing lesion. Brain MRI from a 26-year-old patient with images in axial T1w before (A) and after (B) gadolinium
administration. A hypointense and well-circumscribed lesion is seen in the deep WM of the left parietal lobe (arrow in A), which shows ring
enhancement after contrast administration (arrow in B), concerning for an acute demyelinating plaque.

6 www.jcat.org © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019 MRI Protocols, Requisitions, and Reports in MS

FIGURE 5. Black holes. Brain MRI from a 38-year-old patient with images in (A) axial T1w, (B) axial T2, and (C) axial T1w after gadolinium
administration. Arrows indicate some of multiple oval-shaped, well-circumscribed lesions located in the periventricular with matter
bilaterally. Lesions are hypointense in T1w and hyperintense in T2w and do not show enhancement after gadolinium injection. Persistent
BHs are those that last more than 6 months.

correlate with disability progression calculated by clinical scales
such as the EDSS.7,15,21,57 Because quantitative assessment of BHs
number and size is challenging, some researchers have designed
dedicated automated software with promising results in regards with
its correlation with disability and prognosis28,58,59 (Table 2).
Atrophy Estimation
Brain volume loss seen in MS may be multifactorial, and its
causes can be organized into 3 categories as follows: disease in-
herent, related to the treatment, and others. Brain atrophy inherent
to MS is the portrayal of the subjacent irreversible demyelination
and axonal loss; moreover, brain shrinkage may be secondary to
the MS treatment owing to inflammation and edema resolution
or corticosteroid administration (pseudoatrophy). Other causes
of brain volume loss found in MS patients not related to demyelin-
ating disease are hypertension, alcohol intake, smoking, and dehy-
dration, among others.7 This diversity of subjacent causes makes
atrophy an unreliable disease diagnostic criterion or disease pro-
gression marker.7,11,15,60 Nevertheless, some studies have shown
that volume loss rate is higher in MS patients (0.5%–1.0% per
year) compared with healthy age-matched controls (0.1%–0.3%
per year)60–63 and that this fact predicts cognitive impairment
and disability progression over time.64–67
Brain volume loss quantification in MS poses a technical chal-
lenge, and automated software tools have been developed to do it
precisely, but they are not broadly available in daily clinical prac-
tice.60,62,68,69 The use of specialized segmentation software in the re-
search setting has allowed the quantification of specific atrophy rates
for GM and WM separately.70–72 Respecting to GM atrophy, re-
searchers have found that its volume reduction is less likely affected
by confounding conditions such as inflammation, edema, or gliosis
and that it better correlates with clinical outcomes and disability
progression compared with global atrophy measurements.70,71,73,74
On the other hand, the clinical significance of exact automated WM
atrophy quantification is hampered owing to that its variability par-
tially lies on those extrinsic factors aforementioned.71
The inclusion of qualitative or semiquantitative atrophy char-
acterization in the radiology report is generally well received. Two
of the most popular measurements for easy semiquantitative cal-
culation of atrophy are (a) callosal area in a midline sagittal T1w
image and (b) third ventricle width in millimeters.15,75–77 Albeit
those 2 measurements have proven to be useful in tracing atrophy
progression in MS patients, its inclusion in the radiology report is
optional (Table 2). Spinal atrophy is also associated with long-
term disability,78 but its objective evaluation and applicability in
the clinical setting are still controversial.

© 2018 Wolters Kluwer Health, Inc. All rights reserved. www.jcat.org 7

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Arevalo et al J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019
Cortical Lesions
Detection and quantification of cortical involvement in MS
using MRI persist challenging by the fact that little myelin is pres-
ent in the cortex and the partial volume effects with CSF in sulci
using T2w-based sequences; for that reason, MRI sensitivity com-
pared with the histological analysis is still inadequate.70,79,80 From
the histologic point of view, the cortical damage in MS has some
differences compared with WM lesions such as the milder glial reac-
tion, the paucity of lymphocytic infiltration, and the integrity of the
BBB, leading to not substantial or quickly resolving enhancement.1,30
Studies have classified cortical lesions in MS into 4 catego-
ries based on its extension with respect to cortical width.80–83 Type
1 lesions are those extending across both WM and GM, believed
to contribute at least to some of the currently called juxtacortical
plaques.12,84 Type 2 lesions are those confined to a fraction of
the cortex width without extension neither to the WM nor the
brain surface.82 Moreover, demyelinating lesions affecting only
the subpial portion of the cortex are designated as type 3 and ac-
count for around 65% of all cortical lesions.82 Type 4 lesions af-
fect the cortex without extension beyond its boundaries, but in
contrast to type 2, type 4 lesions involve the whole cortex width.82
Purely intracortical lesions (types 2, 3, and 4) account for the 85%
of all cortical lesions; nevertheless, MRI scans including advanced
dedicated sequences such as DIR cannot detect the vast majority of
them either in vivo or on retrospective postmortem analysis.70,83,85
Dual inversion recovery is an MRI pulse sequence usually done in
3 T magnets that enhances the conspicuity of MS plaques and cor-
tical lesions by suppressing WM and CSF signal79,83,86; it is partic-
ularly useful for the detection of cortical involvement in MS
patients, but its statistical and clinical significance is now under
study. In 2011, a consensus guideline for cortical lesion detection
was reported by Geurts et al81; the authors concluded that the
interrater agreement on detection was not adequate enough and
more studies were needed to make better recommendations.
The standardized definition for cortical lesion in DIR se-
quence is a focal cortical based hyperintensity of at least 3 pixels
in size (resolution of 1 mm2 or higher).81 Information concerning
cortical lesion burden is of paramount importance owing to its
correlation with cognitive decline and future disability.12,70,86,87
Although DIR is becoming more widely available, it is not often
part of an MS imaging protocol, outside academic centers (Table 2).
A practical approach to classifying cortical lesions by DIR is
intracortical, mixed (mostly ~75% intracortical with some ex-
tension into the subcortical WM), and juxtacortical (mostly
~75% subcortical with some extension into the cortex).88
Susceptibility Weighted Images in MS
The interaction between antigen-presenting and other im-
mune cells that takes place in the perivenular space is thought to
be the genesis of the abnormal immune response against myelin
components in MS; therefore, it is the currently accepted explan-
atory theory for the most typical location of MS plaques that is
surrounding a central venous structure.31 Susceptibility weighted
image is an MRI sequence that uses the difference in the magnetic
susceptibility of tissues based on its iron content as an endogenous
intrinsic source of image contrast.89 The proposed pathophysi-
ologic model is that higher tissue oxygen extraction rate due to
the ongoing inflammatory process in MS plaques increases the
deoxyhemoglobin concentration in the corresponding draining veins,
making those veins more conspicuous in SWI examinations.13,31
Researchers found that around 78% of MS plaques displayed
a central vessel in SWI and named it the CVS.31,90,91 Central vein
sign is more consistently observed in the periventricular WM
(94% of MS plaques) noting that the closer to the cortex, the less
8 www.jcat.org
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
prevalent it is; for instance, CVS is present in 84% of plaques lo-
cated in deep WM and only in 66% of juxtacortical ones. Central
veins have also been described in the thalamus, cerebellum, and
brainstem in MS patients.31
To be considered as a positive CVS, the vein must be visual-
ized as a centrally located thin dark line/dot running through the
(almost) entire lesion, in at least 2 perpendicular planes.31 Lesions
smaller than 3 mm in diameter in any axis, confluent lesions,
plaques with multiple distinct veins, or those poorly visible owing
to artifacts may not be considered suitable for CVS.31 Even
though positive CVS is strongly related to MS lesions, it is not
100% specific; in consequence, a recently published expert con-
sensus has set thresholds to use the CVS as a discriminating tool
for differentiating MS from other WM processes.31 Facing WM
T2w hyperintense lesions on an MRI scan, at least 1 of the follow-
ing 3 criteria must be met to consider MS: (a) 40% or more of
WM lesions have positive CVS, (b) 6 or more positive CVS le-
sions, or (c), if total lesion number is less than 6, positive CVS le-
sions must outnumber negative CVS (Table 2).
Researchers have described at least 2 patterns of brain iron
deposition in MS patients using MRI: related to deep GM and that
associated with WM demyelinating plaques. Abnormal T2w hy-
pointensity of the thalamus, caudate nucleus, globus pallidus, den-
tate nucleus, and rolandic cortex seen in some MS patients is the
reflection of the subjacent pathologic iron deposition, and it has
been correlated with disease severity and disability.92–94 Regard-
ing WM lesions, different patterns of iron deposition have been
described in SWI such as uniform darkening and central darken-
ing, but apparently, the most significant pattern may be the hypo-
intense rim surrounding MS plaques.95 The hypointense rim
corresponds to deposition of iron derived from the ongoing in-
flammatory process on the plaque boundaries, and it matches with
the ring-enhancing portion of late acute MS plaques.13,32,44 Once
the limited enhancement period expires in early chronic plaques
(BBB reconstitution), the persistence of the hypointense rim in
SWI is a marker of persistent inflammation, allowing the recogni-
tion of chronic active demyelinating plaques.13,44,96 (Table 2).
Spinal Cord Lesions
Spinal cord examination in MS patients is particularly chal-
lenging owing to its technical difficulties as previously discussed.6
Nevertheless, spinal cord lesions have a prominent role in diagno-
sis and prognosis estimation, particularly in patients coming-up
with clinically isolated syndrome and in patients with nonconclusive
brain WM lesions.54,97,98 Classically, spinal cord MS lesions have
been described as wedge-shaped T2w hyperintensities, most com-
monly located at the posterior/lateral aspect of the cord, involving
both GM and WM, and extending less than 3 segments.30,54,97 The
cervical spinal cord is the most affected segment, followed by the
thoracic segment, but MS plaques can be observed at any level,
and most of the enhancing lesions dwell in the cervical segment.30
In regards to spinal cord atrophy estimation, some semiquantitative
approaches have demonstrated to have a moderate correlation with
disability associated with MS assessed by EDSS; however, it is not
consistently used in daily clinical practice.78,99,100
Radiology Report
Standardized radiology reports allow smooth communication
between clinicians taking care of MS patients and radiologists.
Some academic reference institutions have set-up guidelines ruling
appropriate and relevant reports applicable to the most common
clinical settings101–104; however, this document aims to bring to-
gether and summarize those general recommendations along with
the specific terminology used in the current diagnostic criteria,
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019
and the nomenclature used in the research environment.6,7,11,12,35
The aforementioned is to allow effective communication between
different teams involved in the multidisciplinary care of MS patients,
particularly in regards to MRI scans interpretation and reporting.
Radiologists should encourage clinicians in their team to in-
clude specific and relevant data from the history of present illness
in the requisition order such as the clinically suspected CNS loca-
tion of the lesion based on symptoms and physical examination; it
is useful to determine if a specific lesion may be deemed as symp-
tomatic or not as part of the diagnostic criteria of DIT. Other valuable
information from the history is the symptoms duration (≥24 hours)
and current therapy including corticosteroids and DMT.6 The report
should include the MRI scan field strength, sequences used, the
slice thickness, and the anatomical area covered as well. Bearing
in mind the current concerns about GBCAs safety profiles, radi-
ologists are encouraged to include the type and dose of contrast
agent administered.6
The radiology report must include relevant information for
the MS diagnosis and classification, all of this oriented to fulfill
DIS and DIT criteria. A careful and detailed description of the
items as mentioned previously includes size of lesions, special dis-
tribution, shape, presence, and pattern of enhancement, and inter-
val size changes6 (when present). Findings that favor diagnoses
other than MS must also be highlighted. At the end of the report,
the conclusion will show a concise interpretation of the constella-
tion of findings described previously, highlighting items that favor
either the diagnosis of MS (DIS and DIT) or another differential
diagnosis.6 At this point, the MRI reader should address and try
to solve the original inquiry presented by the clinician in the req-
uisition form101,103 (Table 2).
Incorporating the knowledge obtained from the research arena
into the daily clinical practice is always challenging owing to many
variables. Manual lesion count is by far more time-consuming and
is not often feasible owing to tight work schedules; moreover, the
inherent interrater and intrarater variability could also hamper the
reliability and significance of those measurements. On the other
hand, specialized software and hardware with volumetry and seg-
mentation capabilities are costly and not widespread available. Nev-
ertheless, a semiquantitative approach to persistent BH and T2w
hyperintense lesion reporting in routine clinical practice is usually
well received; it includes reporting the presence of new lesions or
lesion count (when achievable), but perhaps more importantly, the
description of indirect markers of volume changes such as varia-
tions in plaques diameters. Ancillary findings such as some patterns
of iron deposition and the CVS could enrich the MRI interpretation
and help radiologists in making a decision in complicated cases as
previously reviewed. Bearing that in mind, we encourage radiologist
to pursue agreements with the neurology team at their institution
aimed to standardize MRI protocols and reports based on the cur-
rent guidelines and adjusted to the available in-home resources.
CONCLUSIONS
Magnetic resonance imaging is a cornerstone in the diagno-
sis and surveillance of patients with MS; it allows observing in
vivo many pathologic processes occurring at the cellular level
such as the integrity of the BBB, demyelination, iron deposition,
and the spatial relationship between vascular structures and demy-
elinating plaques. Nevertheless, some limitations regarding tech-
nical issues remain, and clinical significance of certain findings
is still pending confirmation and under study. Current American6
and European7,11 MS guidelines gather the most updated recom-
mendations regarding MRI scan protocols, nomenclature, the clin-
ical significance of MRI findings, follow-up protocols, and a
tailored radiology report. Despite these guidelines, there have
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
MRI Protocols, Requisitions, and Reports in MS
been some discrepancies between radiology report and clinician's
expectation, more often in nonspecialized MS centers. This docu-
ment not only reviews the current MRI protocols, revised diag-
nostic criteria, lesion description and its clinical significance,
and more recent MRI measures in MS but also provides important
details that would allow an ideal radiology report, which has be-
come essential for optimal monitoring of disease activity and in
the decision-making process for evaluating response to therapy
in MS, all with the goal to harmonize the communication between
radiologists and clinicians involved in MS patients' multidisciplin-
ary care and ultimately improve patient's outcomes.
REFERENCES
1. Matthews PM, Roncaroli F, Waldman A, et al. A practical review of the
neuropathology and neuroimaging of multiple sclerosis. Pract Neurol.
2016;16:279–287. doi: 10.1136/practneurol-2016-001381.
2. Stys PK, Zamponi GW, van Minnen J, et al. Will the real multiple sclerosis
please stand up? Nat Rev Neurosci. 2012;13:507–514. doi: 10.1038/nrn3275.
3. Davis M, Auh S, Riva M, et al. Ring and nodular multiple sclerosis
lesions: a retrospective natural history study. Neurology. 2010;74:
851–856. doi: 10.1212/WNL.0b013e3181d31df5.
4. Sahraian MA, Radue EW, Haller S, et al. Black holes in multiple sclerosis:
definition, evolution, and clinical correlations. Acta Neurol Scand. 2010;
122:1–8. doi: 10.1111/j.1600-0404.2009.01221.x.
5. Petkau J, Reingold SC, Held U, et al. Magnetic resonance imaging as a
surrogate outcome for multiple sclerosis relapses. Mult Scler. 2008;14:
770–778. doi: 10.1177/1352458507088104.
6. Traboulsee A, Simon JH, Stone L, et al. Revised recommendations of the
consortium of MS centers task force for a standardized MRI protocol and
clinical guidelines for the diagnosis and follow-up of multiple sclerosis.
AJNR Am J Neuroradiol. 2016;37:394–401. doi: 10.3174/ajnr.A4539.
7. Wattjes MP, Rovira À, Miller D, et al. Evidence-based guidelines:
MAGNIMS consensus guidelines on the use of MRI in multiple
sclerosis—establishing disease prognosis and monitoring patients.
Nat Rev Neurol. 2015;11:597–606. doi: 10.1038/nrneurol.2015.157.
8. Sormani MP, Bruzzi P. MRI lesions as a surrogate for relapses in multiple
sclerosis: a meta-analysis of randomised trials. Lancet Neurol. 2013;12:
669–676. doi: 10.1016/S1474-4422(13)70103-0.
9. Sormani MP, Stubinski B, Cornelisse P, et al. Magnetic resonance active
lesions as individual-level surrogate for relapses in multiple sclerosis.
Mult Scler. 2011;17:541–549. doi: 10.1177/1352458510391837.
10. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course
of multiple sclerosis: the 2013 revisions. Neurology. 2014;83:278–286.
doi: 10.1212/WNL.0000000000000560.
11. Rovira À, Wattjes MP, Tintoré M, et al. Evidence-based guidelines:
MAGNIMS consensus guidelines on the use of MRI in multiple
sclerosis-clinical implementation in the diagnostic process. Nat Rev
Neurol. 2015;11:471–482. doi: 10.1038/nrneurol.2015.106.
12. Filippi M, Rocca MA, Ciccarelli O, et al. MRI criteria for the diagnosis
of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol.
2016;15:292–303. doi: 10.1016/S1474-4422(15)00393-2.
13. Tommasin S, Giannì C, De Giglio L, et al. Neuroimaging techniques to
assess inflammation in Multiple Sclerosis. Neuroscience. 2017. doi:
10.1016/j.neuroscience.2017.07.055.
14. Consortium of Multiple Sclerosis Centers (CMSC). Consortium of MS
Centers MRI Protocol and Clinical Guidelines for the Diagnosis and
Follow-up of MS. Available at: http://c.ymcdn.com/sites/www.mscare.
org/resource/collection/9C5F19B9-3489-48B0-A54B-623A1ECEE07B/
2018MRIGuidelines_booklet_final.pdf. Accessed April 10, 2018.
15. van Munster CE, Uitdehaag BM. Outcome measures in clinical trials
for multiple sclerosis. CNS Drugs. 2017;31:217–236.
doi: 10.1007/s40263-017-0412-5.
www.jcat.org 9
Arevalo et al
16. Lavery AM, Verhey LH, Waldman AT. Outcome measures in
relapsing-remitting multiple sclerosis: capturing disability and disease
progression in clinical trials. Mult Scler Int. 2014;2014:262350. doi:
10.1155/2014/262350.
17. Bermel RA, You X, Foulds P, et al. Predictors of long-term outcome in
multiple sclerosis patients treated with interferon β. Ann Neurol. 2013;73:
95–103. doi: 10.1002/ana.23758.
18. Fisniku LK, Brex PA, Altmann DR, et al. Disability and T2 MRI lesions: a
20-year follow-up of patients with relapse onset of multiple sclerosis.
Brain. 2008;131(pt 3):808–817. doi: 10.1093/brain/awm329.
19. Tintore M, Rovira À, Río J, et al. Defining high, medium and low
impact prognostic factors for developing multiple sclerosis. Brain. 2015;
138(pt 7):1863–1874. doi: 10.1093/brain/awv105.
20. Wolinsky JS, Narayana PA, Nelson F, et al. Magnetic resonance imaging
outcomes from a phase III trial of teriflunomide. Mult Scler. 2013;19:
1310–1319. doi: 10.1177/1352458513475723.
21. Truyen L, van Waesberghe JH, van Walderveen MA, et al. Accumulation
of hypointense lesions (“black holes”) on T1 spin-echo MRI correlates
with disease progression in multiple sclerosis. Neurology. 1996;47:
1469–1476.
22. Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited.
Curr Opin Neurol. 2002;15:239–245.
23. Hackmack K, Weygandt M, Wuerfel J, et al. Can we overcome the
“clinico-radiological paradox” in multiple sclerosis? J Neurol. 2012;259:
2151–2160. doi: 10.1007/s00415-012-6475-9.
24. Daumer M, Neuhaus A, Morrissey S, et al. MRI as an outcome in
multiple sclerosis clinical trials. Neurology. 2009;72:705–711.
doi: 10.1212/01.wnl.0000336916.38629.43.
25. Mollison D, Sellar R, Bastin M, et al. The clinico-radiological paradox of
cognitive function and MRI burden of white matter lesions in people with
multiple sclerosis: a systematic review and meta-analysis. PLoS One.
2017;12:e0177727. doi: 10.1371/journal.pone.0177727.
26. Wattjes MP, Steenwijk MD, Stangel M. MRI in the diagnosis and
monitoring of multiple sclerosis: an update. Clin Neuroradiol.
2015;25(suppl 2):157–165. doi: 10.1007/s00062-015-0430-y.
27. Wattjes MP, Harzheim M, Lutterbey GG, et al. Does high field MRI
allow an earlier diagnosis of multiple sclerosis? J Neurol. 2008;255:
1159–1163. doi: 10.1007/s00415-008-0861-3.
28. Andermatt S, Papadopoulou A, Radue E-W, et al. Tracking the evolution
of cerebral gadolinium-enhancing lesions to persistent T1 black holes in
multiple sclerosis: validation of a semiautomated pipeline.
J Neuroimaging. 2017;27:469–475. doi: 10.1111/jon.12439.
29. van Waesberghe JH, van Walderveen MA, Castelijns JA, et al. Patterns of
lesion development in multiple sclerosis: longitudinal observations with
T1-weighted spin-echo and magnetization transfer MR. AJNR Am J
Neuroradiol. 1998;19:675–683.
30. Dekker I, Wattjes MP. Brain and spinal cord MR imaging features in
multiple sclerosis and variants. Neuroimaging Clin N Am. 2017;27:
205–227. doi: 10.1016/j.nic.2016.12.002.
31. Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical
evaluation for the diagnosis of multiple sclerosis: a consensus statement
from the North American Imaging in Multiple Sclerosis Cooperative.
Nat Rev Neurol. 2016;12:714–722. doi: 10.1038/nrneurol.2016.166.
32. Bagnato F, Hametner S, Yao B, et al. Tracking iron in multiple sclerosis: a
combined imaging and histopathological study at 7 Tesla. Brain. 2011;
134(pt 12):3602–3615. doi: 10.1093/brain/awr278.
33. Ashrafi MR, Tavasoli AR, Alizadeh H, et al. Tumefactive multiple
sclerosis variants: report of two cases of Schilder and Balo diseases.
Iran J Child Neurol. 2017;11:69–77.
34. Popescu BF, Pirko I, Lucchinetti CF. Pathology of multiple sclerosis: where
do we stand? Contin Lifelong Learn Neurol. 2013;19(4 Multiple Sclerosis):
901–921. doi: 10.1212/01.CON.0000433291.23091.65.
10 www.jcat.org
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019
35. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for
multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol.
2011;69:292–302. doi: 10.1002/ana.22366.
36. Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple
sclerosis: 2005 revisions to the “McDonald Criteria.” Ann Neurol. 2005;
58:840–846. doi: 10.1002/ana.20703.
37. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic
criteria for multiple sclerosis: guidelines from the International Panel on
the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–127.
38. Brownlee WJ, Hardy TA, Fazekas F, et al. Diagnosis of multiple
sclerosis: progress and challenges. Lancet. 2017;389:1336–1346.
doi: 10.1016/S0140-6736(16)30959-X.
39. Cohen J. 2017 Proposed Revisions to the McDonald Diagnostic Criteria
for Multiple Sclerosis. Oral Presentation Presented at the MS Paris
2017, 7th Joint ECTRIMS-ACTRIMS Meeting; October 26, 2017;
Paris, France. Available at: http://journals.sagepub.com/doi/pdf/10.1177/
1352458517731283. Accessed January 18, 2018.
40. Gawne-Cain ML, Webb S, Tofts P, et al. Lesion volume measurement
in multiple sclerosis: how important is accurate repositioning? J Magn
Reson Imaging. 1996;6:705–713.
41. Gallagher HL, MacManus DG, Webb SL, et al. A reproducible
repositioning method for serial magnetic resonance imaging studies of the
brain in treatment trials for multiple sclerosis. J Magn Reson Imaging.
1997;7:439–441.
42. Wattjes MP, Barkhof F. High field MRI in the diagnosis of multiple
sclerosis: high field-high yield? Neuroradiology. 2009;51:279–292.
doi: 10.1007/s00234-009-0512-0.
43. Mistry N, Tallantyre EC, Dixon JE, et al. Focal multiple sclerosis lesions
abound in “normal appearing white matter.” Mult Scler. 2011;17:
1313–1323. doi: 10.1177/1352458511415305.
44. Absinta M, Sati P, Gaitán MI, et al. Seven-Tesla phase imaging of acute
multiple sclerosis lesions: a new window into the inflammatory process.
Ann Neurol. 2013;74:669–678. doi: 10.1002/ana.23959.
45. Bleicher AG, Kanal E. Assessment of adverse reaction rates to a newly
approved MRI contrast agent: review of 23,553 administrations of
gadobenate dimeglumine. AJR Am J Roentgenol. 2008;191:
W307–W311. doi: 10.2214/AJR.07.3951.
46. Grobner T. Gadolinium—a specific trigger for the development of
nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis?
Nephrol Dial Transplant. 2006;21:1104–1108. doi: 10.1093/ndt/gfk062.
47. Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis:
suspected causative role of gadodiamide used for contrast-enhanced
magnetic resonance imaging. J Am Soc Nephrol. 2006;17:2359–2362.
doi: 10.1681/ASN.2006060601.
48. Sadowski EA, Bennett LK, Chan MR, et al. Nephrogenic systemic
fibrosis: risk factors and incidence estimation. Radiology. 2007;243:
148–157. doi: 10.1148/radiol.2431062144.
49. Kanda T, Nakai Y, Oba H, et al. Gadolinium deposition in the brain.
Magn Reson Imaging. 2016;34:1346–1350. doi: 10.1016/j.
mri.2016.08.024.
50. Stojanov D, Aracki-Trenkic A, Benedeto-Stojanov D. Gadolinium
deposition within the dentate nucleus and globus pallidus after repeated
administrations of gadolinium-based contrast agents-current status.
Neuroradiology. 2016;58:433–441. doi: 10.1007/s00234-016-1658-1.
51. Kanda T, Ishii K, Kawaguchi H, et al. High signal intensity in the dentate
nucleus and globus pallidus on unenhanced T1-weighted MR images:
relationship with increasing cumulative dose of a gadolinium-based
contrast material. Radiology. 2014;270:834–841. doi: 10.1148/
radiol.13131669.
52. Hao D, Ai T, Goerner F, et al. MRI contrast agents: basic chemistry
and safety. J Magn Reson Imaging. 2012;36:1060–1071.
doi: 10.1002/jmri.23725.
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019
53. Radbruch A. Are some agents less likely to deposit gadolinium in the brain?
Magn Reson Imaging. 2016;34:1351–1354. doi: 10.1016/j.mri.2016.09.001.
54. Lycklama G, Thompson A, Filippi M, et al. Spinal-cord MRI in multiple
sclerosis. Lancet Neurol. 2003;2:555–562.
55. He J, Grossman RI, Ge Y, et al. Enhancing patterns in multiple
sclerosis: evolution and persistence. AJNR Am J Neuroradiol. 2001;22:
664–669.
56. van Walderveen MA, Kamphorst W, Scheltens P, et al. Histopathologic
correlate of hypointense lesions on T1-weighted spin-echo MRI in
multiple sclerosis. Neurology. 1998;50:1282–1288.
57. van Walderveen MA, Barkhof F, Hommes OR, et al. Correlating MRI and
clinical disease activity in multiple sclerosis: relevance of hypointense
lesions on short-TR/short-TE (T1-weighted) spin-echo images.
Neurology. 1995;45:1684–1690.
58. Tam RC, Traboulsee A, Riddehough A, et al. Improving the clinical
correlation of multiple sclerosis black hole volume change by
paired-scan analysis. Neuroimage Clin. 2012;1:29–36.
doi: 10.1016/j.nicl.2012.08.004.
59. Tam RC, Traboulsee A, Riddehough A, et al. The impact of intensity
variations in T1-hypointense lesions on clinical correlations in multiple
sclerosis. Mult Scler. 2011;17:949–957. doi: 10.1177/1352458511402113.
60. De Stefano N, Airas L, Grigoriadis N, et al. Clinical relevance of brain
volume measures in multiple sclerosis. CNS Drugs. 2014;28:147–156.
doi: 10.1007/s40263-014-0140-z.
61. Miller DH, Barkhof F, Frank JA, et al. Measurement of atrophy in multiple
sclerosis: pathological basis, methodological aspects and clinical
relevance. Brain. 2002;125(pt 8):1676–1695.
62. Kalkers NF, Ameziane N, Bot JC, et al. Longitudinal brain volume
measurement in multiple sclerosis: rate of brain atrophy is independent
of the disease subtype. Arch Neurol. 2002;59:1572–1576.
63. Sormani MP, Arnold DL, De Stefano N. Treatment effect on brain atrophy
correlates with treatment effect on disability in multiple sclerosis.
Ann Neurol. 2014;75:43–49. doi: 10.1002/ana.24018.
64. Popescu V, Agosta F, Hulst HE, et al. Brain atrophy and lesion load predict
long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry.
2013;84:1082–1091. doi: 10.1136/jnnp-2012-304094.
65. Fisher E, Rudick RA, Cutter G, et al. Relationship between brain atrophy
and disability: an 8-year follow-up study of multiple sclerosis patients.
Mult Scler. 2000;6:373–377. doi: 10.1177/135245850000600602.
66. Shiee N, Bazin PL, Zackowski KM, et al. Revisiting brain atrophy and its
relationship to disability in multiple sclerosis. PLoS One. 2012;7:e37049.
doi: 10.1371/journal.pone.0037049.
67. Jacobsen C, Hagemeier J, Myhr KM, et al. Brain atrophy and
disability progression in multiple sclerosis patients: a 10-year
follow-up study. J Neurol Neurosurg Psychiatry. 2014;85:1109–1115.
doi: 10.1136/jnnp-2013-306906.
68. Dwyer MG, Silva D, Bergsland N, et al. Neurological software tool for
reliable atrophy measurement (NeuroSTREAM) of the lateral ventricles
on clinical-quality T2-FLAIR MRI scans in multiple sclerosis.
Neuroimage Clin. 2017;15:769–779. doi: 10.1016/j.nicl.2017.06.022.
69. Anderson VM, Fox NC, Miller DH. Magnetic resonance imaging
measures of brain atrophy in multiple sclerosis. J Magn Reson Imaging.
2006;23:605–618. doi: 10.1002/jmri.20550.
70. Geurts JJ, Calabrese M, Fisher E, et al. Measurement and clinical effect of
grey matter pathology in multiple sclerosis. Lancet Neurol. 2012;11:
1082–1092. doi: 10.1016/S1474-4422(12)70230-2.
71. Furby J, Hayton T, Altmann D, et al. A longitudinal study of MRI-detected
atrophy in secondary progressive multiple sclerosis. J Neurol. 2010;257:
1508–1516. doi: 10.1007/s00415-010-5563-y.
72. Popescu V, Ran NC, Barkhof F, et al. Accurate GM atrophy quantification
in MS using lesion-filling with co-registered 2D lesion masks.
Neuroimage Clin. 2014;4:366–373. doi: 10.1016/j.nicl.2014.01.004.
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
MRI Protocols, Requisitions, and Reports in MS
73. Fisher E, Lee JC, Nakamura K, et al. Gray matter atrophy in multiple
sclerosis: a longitudinal study. Ann Neurol. 2008;64:255–265.
doi: 10.1002/ana.21436.
74. Rudick RA, Lee JC, Nakamura K, Fisher E. Gray matter atrophy
correlates with MS disability progression measured with MSFC but not
EDSS. J Neurol Sci. 2009;282:106–111. doi: 10.1016/j.jns.2008.11.018.
75. Simon JH, Jacobs LD, Campion MK, et al. A longitudinal study of brain
atrophy in relapsing multiple sclerosis. The Multiple Sclerosis
Collaborative Research Group (MSCRG). Neurology. 1999;53:139–148.
76. Odenthal C, Simpson S, Oughton J, et al. Midsagittal corpus callosum
area and conversion to multiple sclerosis after clinically isolated
syndrome: a multicentre Australian cohort study. J Med Imaging Radiat
Oncol. 2017;61:453–460. doi: 10.1111/1754-9485.12570.
77. Müller M, Esser R, Kötter K, et al. Width of 3. Ventricle: reference
values and clinical relevance in a cohort of patients with relapsing
remitting multiple sclerosis. Open Neurol J. 2013;7:11–16.
doi: 10.2174/1874205X01307010011.
78. Lukas C, Knol DL, Sombekke MH, et al. Cervical spinal cord volume
loss is related to clinical disability progression in multiple
sclerosis. J Neurol Neurosurg Psychiatry. 2015;86:410–418.
doi: 10.1136/jnnp-2014-308021.
79. Simon B, Schmidt S, Lukas C, et al. Improved in vivo detection of
cortical lesions in multiple sclerosis using double inversion recovery
MR imaging at 3 Tesla. Eur Radiol. 2010;20:1675–1683.
doi: 10.1007/s00330-009-1705-y.
80. Geurts JJ, Bö L, Pouwels PJ, et al. Cortical lesions in multiple sclerosis:
combined postmortem MR imaging and histopathology. AJNR Am J
Neuroradiol. 2005;26:572–577.
81. Geurts JJ, Roosendaal SD, Calabrese M, et al. Consensus recommendations
for MS cortical lesion scoring using double inversion recovery MRI.
Neurology. 2011;76:418–424. doi: 10.1212/WNL.0b013e31820a0cc4.
82. Bø L, Vedeler CA, Nyland HI, et al. Subpial demyelination in the cerebral
cortex of multiple sclerosis patients. J Neuropathol Exp Neurol. 2003;62:
723–732.
83. Geurts JJ, Pouwels PJ, Uitdehaag BM, et al. Intracortical lesions in
multiple sclerosis: improved detection with 3D double inversion-recovery
MR imaging. Radiology. 2005;236:254–260. doi: 10.1148/
radiol.2361040450.
84. Sethi V, Muhlert N, Ron M, et al. MS cortical lesions on DIR: not quite what
they seem? PLoS ONE. 2013;8.e78879. doi: 10.1371/journal.pone.0078879.
85. Seewann A, Kooi EJ, Roosendaal SD, et al. Postmortem verification of
MS cortical lesion detection with 3D DIR. Neurology. 2012;78:302–308.
doi: 10.1212/WNL.0b013e31824528a0.
86. Calabrese M, De Stefano N, Atzori M, et al. Detection of cortical
inflammatory lesions by double inversion recovery magnetic resonance
imaging in patients with multiple sclerosis. Arch Neurol. 2007;64:
1416–1422. doi: 10.1001/archneur.64.10.1416.
87. Calabrese M, Rocca MA, Atzori M, et al. A 3-year magnetic resonance
imaging study of cortical lesions in relapse-onset multiple sclerosis.
Ann Neurol. 2010;67:376–383. doi: 10.1002/ana.21906.
88. Nelson F, Poonawalla AH, Hou P, et al. Improved identification of
intracortical lesions in multiple sclerosis with phase-sensitive inversion
recovery in combination with fast double inversion recovery MR imaging.
Am J Neuroradiol. 2007;28:1645–1649. doi: 10.3174/ajnr.A0645.
89. Haacke EM, Xu Y, Cheng Y-CN, et al. Susceptibility weighted imaging
(SWI). Magn Reson Med. 2004;52:612–618. doi: 10.1002/mrm.20198.
90. Kau T, Taschwer M, Deutschmann H, et al. The “central vein sign”: is
there a place for susceptibility weighted imaging in possible multiple
sclerosis? Eur Radiol. 2013;23:1956–1962. doi: 10.1007/s00330-013-2791-4.
91. Campion T, Smith RJP, Altmann DR, et al. FLAIR* to visualize veins in
white matter lesions: a new tool for the diagnosis of multiple sclerosis?
Eur Radiol. 2017;27:4257–4263. doi: 10.1007/s00330-017-4822-z.
www.jcat.org 11
Arevalo et al
92. Bakshi R, Shaikh ZA, Janardhan V. MRI T2 shortening (‘black T2’) in
multiple sclerosis: frequency, location, and clinical correlation.
Neuroreport. 2000;11:15–21.
93. Bakshi R, Benedict RH, Bermel RA, et al. T2 hypointensity in the deep
gray matter of patients with multiple sclerosis: a quantitative magnetic
resonance imaging study. Arch Neurol. 2002;59:62–68.
94. Zhang Y, Zabad RK, Wei X, et al. Deep grey matter “black T2”
on 3 tesla magnetic resonance imaging correlates with disability in
multiple sclerosis. Mult Scler. 2007;13:880–883.
doi: 10.1177/1352458507076411.
95. Haacke EM, Makki M, Ge Y, et al. Characterizing iron deposition in
multiple sclerosis lesions using susceptibility weighted imaging. J Magn
Reson Imaging. 2009;29:537–544. doi: 10.1002/jmri.21676.
96. Enzinger C, Barkhof F, Ciccarelli O, et al. Nonconventional MRI and
microstructural cerebral changes in multiple sclerosis. Nat Rev Neurol.
2015;11:676–686. doi: 10.1038/nrneurol.2015.194.
97. Kearney H, Miller DH, Ciccarelli O. Spinal cord MRI in multiple
sclerosis—diagnostic, prognostic and clinical value. Nat Rev Neurol.
2015;11:327–338. doi: 10.1038/nrneurol.2015.80.
98. Sombekke MH, Wattjes MP, Balk LJ, et al. Spinal cord lesions in
patients with clinically isolated syndrome: a powerful tool in
12 www.jcat.org
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
J Comput Assist Tomogr • Volume 43, Number 1, January/February 2019
diagnosis and prognosis. Neurology. 2013;80:69–75.
doi: 10.1212/WNL.0b013e31827b1a67.
99. Lukas C, Sombekke MH, Bellenberg B, et al. Relevance of spinal cord
abnormalities to clinical disability in multiple sclerosis: MR imaging
findings in a large cohort of patients. Radiology. 2013;269:542–552.
doi: 10.1148/radiol.13122566.
100. Stankiewicz J, Neema M, Alsop D, et al. Spinal cord lesions and
clinical status in multiple sclerosis: a 1.5 T and 3 T MRI study. J Neurol
Sci. 2009;279:99–105. doi: 10.1016/j.jns.2008.11.009.
101. European Society of Radiology (ESR). Good practice for radiological
reporting. Guidelines from the European Society of Radiology (ESR).
Insights Imaging. 2011;2:93–96. doi: 10.1007/s13244-011-0066-7.
102. Kahn CE, Heilbrun ME, Applegate KE. From guidelines to practice:
how reporting templates promote the use of radiology practice guidelines.
J Am Coll Radiol. 2013;10:268–273. doi: 10.1016/j.jacr.2012.09.025.
103. Kahn CE, Langlotz CP, Burnside ES, et al. Toward best practices in
radiology reporting. Radiology. 2009;252:852–856. doi: 10.1148/
radiol.2523081992.
104. Kushner DC, Lucey LL. American College of Radiology. Diagnostic
radiology reporting and communication: the ACR guideline. J Am Coll
Radiol. 2005;2:15–21. doi: 10.1016/j.jacr.2004.08.005.
© 2018 Wolters Kluwer Health, Inc. All rights reserved.