MRI has revolutionized the evaluation of demyelinating disease. The finding of subcallosal striations on sagittal thin slice FLAIR images is the earliest imaging manifestation of multiple sclerosis. Gadolinium-enhanced T1-weighted images are currently the most sensitive imaging technique for following multiple sclerosis, particularly for patients on the new immunotherapies. This issue of Applied Imaging discusses not only these generally accepted uses for MRI, but also new MR techniques that may be available in the near future.
MRI has revolutionized the evaluation of demyelinating disease.
The finding of subcallosal striations on sagittal thin slice FLAIR
images is the earliest imaging manifestation of multiple sclerosis.
-weighted images are currently the most sensitive imaging technique
for following multiple sclerosis, particularly for patients on the
new immunotherapies. This issue of Applied Imaging discusses not
only these generally accepted uses for MRI, but also new MR
techniques that may be available in the near future.--William G.
Bradley, Jr., MD, PhD, FACR
Detection of demyelinating disease was one of the earliest
applications in which MRI demonstrated superiority over CT.
Multiple sclerosis (MS) and its monophasic counterpart acute
disseminated encephalomyelitis (ADEM) are quite common in northern
latitudes, with an incidence of 80 per 100,000.
Since the disease has a variety of clinical presentations, it is
often included in the differential diagnosis when there are
positive neurologic findings, particularly in young adults. Despite
its being considered a disease of young women, the female:male
ratio is only 2:1, and 10% of the patients present after age 50.
In order to make a "definite" diagnosis of MS, there must be
multiple neurologic lesions in space and time, i.e., involvement of
at least two different parts of the central nervous system
separated in time by at least 24 hours. "Probable" MS is defined as
multiple lesions in the CNS occurring at a single time or a single
lesion coming and going over a period of time. "Possible" MS is a
single lesion at one time.
ADEM is an autoimmune, postviral leukoencephalopathy.
Classically, it occurs several weeks following an exanthemous viral
infection during which time the patient's immune system is directed
against his/her own white matter. Clinically, the patient may be
comatose or present with seizures--features that may be
indistinguishable from an acute encephalitis. Fortunately, ADEM has
a totally different appearance from viral encephalitis on MRI. ADEM
involves the white matter first with centrifugal spread to the
cortex, whereas a viral meningoencephalitis starts peripherally and
spreads centripetally from the gray matter into the white matter.
Distinguishing these two entities is important clinically as they
have different treatments. Viral encephalitis may be treated with
antiviral agents, such as acyclovir; whereas ADEM is treated with
steroids or plasmapheresis, if it is treated at all.
It may be impossible to distinguish possible or probable MS from
ADEM. They have the same CSF abnormalities (myelin basic protein
and oligoclonal bands) and they have a similar (if not identical)
MR appearance. While the plaques of ADEM are supposed to be larger
than those of MS, this is probably not true for the acute
tumefactive form of MS. The classic MR imaging findings in MS
include focal areas of hyperintensity on proton density or T
-weighted or FLAIR images. Classically, these lesions have an ovoid
appearance with the long axis pointing toward the ventricular
(Figure 1). This reflects the fact that MS is a perivenular disease
and that the subependymal veins course perpendicular to the
ependymal surface. Under the microscope, collections of
inflammatory cells are noted, called "Dawson's fingers" after the
Scottish pathologist who first described this appearance at the end
of the nineteenth century.
For patients in the 40- to 60-year age range, MS has the
potential of being confused with small vessel ischemic change both
in the deep white matter and in the brain stem. There are several
imaging features that help to distinguish these two entities. MS
plaques tend to be rounded, i.e., outwardly convex, while small
vessel ischemia tends to be outwardly concave. In the brain stem,
MS tends to be peripheral, abutting the CSF spaces, while small
vessel ischemia tends to be central (Figure 2). While involvement
of the basal ganglia can occur as frequently with MS as with small
vessel arteriosclerosis (i.e., lacunar infarction), the latter
tends to cavitate while the former does not. Involvement of the
cord is much more frequently seen in demyelinating disease than in
While the usual 5-mm thick T
-weighted axial images may detect the majority of cases of advanced
MS, we have found thin-slice (2 mm), sagittal FLAIR images (Figure
3) to be even better.
In one study, 42% of the patients being evaluated for possible MS
had positive findings on the 2-mm sagittal FLAIR images in the face
of normal conventional images.
The earliest MR findings in MS are 1-mm thick "subcallosal
striations" oriented perpendicular to the ependyma, like a stack of
These findings are undoubtedly an earlier manifestation of the same
perivenular disease that produces the ovoid lesion on conventional
The rationale behind the thin-slice, sagittal FLAIR technique is
simple: thinner slices minimize partial volume averaging of small
lesions, fast FLAIR improves contrast, and the sagittal plane
optimizes viewing the undersurface of the corpus callosum. It is
important to use the thinnest possible slices to minimize partial
volume averaging. While MRI is perfectly capable of detecting 2-mm
MS plaques on 2-mm thick slices, such lesions would not be
detectable using 5-mm slices with otherwise comparable techniques.
The sagittal plane is also used because there is less white matter
to cover from medial to lateral than from front to back or top to
bottom. While others have suggested a role for gadolinium for the
initial detection of early demyelinating disease, this author has
never seen a case where enhanced images were positive and
thin-slice, sagittal FLAIR was not. In fact, in one study, the
association of subcallosal striations with MS was quite significant
While gadolinium may be less sensitive than thin-slice sagittal
FLAIR techniques for the detection of early demyelinating disease,
it may add to the specificity of the diagnosis. If there has been
only a single clinical episode at the time of the initial
diagnosis, the highest possible clinical rating is "probable." If
at this time some lesions enhance and some do not,
gadolinium-enhanced MRI can be used as a "paraclinical" test to
suggest multiphasic disease and therefore a "definite"
Gadolinium is also useful to follow patients--particularly those
on the newer immunotherapies for MS.
Since these drugs produce flu-like symptoms, patients and
physicians need a more objective measure of efficacy than can be
provided by the clinical examination alone of a disease that tends
to wax and wane. Since active and healing disease both appear
bright on T
-weighted images, gadolinium is needed to demonstrate active
disease. We typically use interleaved 3-mm contiguous sections for
this semi-quantitative evaluation.
Gadolinium also has a role in the evaluation of tumefactive MS,
which might be confused with an abscess or tumor. In MS, there is
incomplete rim enhancement (Figure 4A) in contradistinction to
abscesses or metastases, which tend to have solid or complete rim
enhancement, or gliomas, which tend to enhance throughout (if they
enhance at all). On T
-weighted images, tumefactive MS produces a "fried egg" appearance,
the plaque being the yolk and the surrounding vasogenic edema the
white (Figure 4B). Tumefactive MS and ADEM also tend to be bright
on diffusion imaging
ADEM tends to involve the periventricular white matter, the
white matter of the thalami, and the middle cerebellar peduncle
(Figure 6). Like acute tumefactive MS, it enhances peripherally in
the zone of active demyelination. When involving the brachium
pontis, ADEM can be confused with another demyelinating disease,
progressive multifocal leukoencephalopathy (PML). The latter,
generally seen in AIDS patients, tends not to enhance, which helps
distinguish it from ADEM (which does enhance).
Acute demyelination should be included in the differential
diagnosis of any young person presenting with one or more masses in
Both acute tumefactive MS and ADEM can involve the spinal cord.
The resulting cord swelling may be impossible to differentiate from
viral myelitis or low-grade tumor. These three inflammatory
conditions generally present clinically with a "transverse
myelitis," i.e., a sensory level appearing over a matter of days.
This rapid onset distinguishes inflammation from neoplasms, which
are more indolent. Chronic MS produces plaques that are
longitudinally oriented and flame-shaped without mass effect
(Figure 7). These tend to be dorsolateral in position and are more
frequently found in the cervical than in the thoracic cord.
Longstanding MS can produce atrophy of the cord. These lesions are
evaluated best on T
-weighted fast spin echo images that minimize CSF pulsation
In addition to its current image-based evaluation of multiple
sclerosis, MR can also be used to interrogate other features of MS
on a microscopic level. Magnetization transfer (MT) is a technique
that can quantify the ratio of protein-bound water compared to free
water. Normally, most of the water in white matter is tightly bound
to myelin protein. With demyelination, some of this water is freed,
changing its magnetization transfer ratio (MTR). A number of
investigators have shown abnormal MTRs in normally appearing white
matter by conventional MRI. Future MS protocols are quite likely to
include quantitative assessment of the white mater by MTR.
In the newer class of echo planar imaging (EPI) MR systems, EPI
diffusion imaging has become routine, as the images can be acquired
in less than a minute. In 5 to 10 minutes, a diffusion tensor can
be acquired. This provides a position-independent quantitative
assessment of the apparent diffusion coefficient. Using such
techniques, the motion of water within a white matter voxel can be
assessed quantitatively. Since water tends to flow parallel to
axons rather than perpendicular to them, this measurement is
generally quite anisotropic. With demyelination, the "anisotropy
index" decreases, providing another microscopic measure of disease
activity using MRI.
1. Which of the following techniques is most sensitive for early
detection of MS: axial proton density, axial FLAIR, sagittal FLAIR,
, axial T
2. All patients with suspected MS should be given gadolinium.
True or false.
3. Patients being followed for MS by MRI should have T
-weighted images with gadolinium. True or false.
4. The thinnest possible slices should be used when evaluating
MS. True or false.
5. All patients with suspected MS should have an MRI study. True
1. Sagittal FLAIR, since it optimally visualizes the
undersurface of the corpus callosum and maximizes contrast against
2. False. Sagittal thin slice FLAIR is more sensitive than
gadolinium for detection of early MS; thus, gadolinium is not
3. True. Only with gadolinium can you distinguish acute
[enhancing] plaques from nonenhancing gliotic scars.
4. True. Thin slices minimize partial volume averaging and
enhance detection of disease.
5. False. Patients with cardiac pacemakers and ferromagnetic
intracranial aneurysm clips are precluded from having MRI