Index terms: Computed tomography Magnetic resonance sequence optimization Multiple sclerosis

The

evaluation of multiple sclerosis by magnetic resonance imaging

M. Runge, C. Price, M.D.*1 M.D.*

Val 4, Ann

Howard Joseph
+
C.

S. Kirshner, H. Allen,

M.D.t

M.D.* M.D., Ph.D.* Jr., M.D., J.D.*

Leon Partain, James,

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A. Evereffe

THIS EXHIBIT. A SELECTION AND

OF THE MRI NEURORADIOLOGY PANELS. WAS DISPLAYED AT THE 70TH SCIEN11FIC ASSEMBLYANDANNUAL MEETING OF THE RADIOLOGICAL SOCIE1Y OF NORTH AMERICA NOVEMBER 2530, 1984. WASHINGTON. D.C.

MRI superbly demonstrates the intracerebral of disease In multiple sclerosis.

component

Introduction
In clinical medicine, the diagnosis of multiple sclerosis (MS) continues to be a challenge, despite the wide range ofavailable tests. The development of magnetic resonance imaging (MRI) may provide an avenue for improved diagnosis, to be contrasted with that available using evoked

From the Department of Radiology and Radiological Sciences(), and the Department of Neurology(t), Vanderbilt Universily Medical Center, Nashville. tPresently at Division of Magnetic Resonance, Department of Radiology. New England Medical Center Hospitals, Boston. Address reprint requests to Val M. Runge, M.D., Division of Magnetic Resonance, Department of Radiology, New England Medical Center Hospitals. I 7 1 Harrison Avenue. Boston. MA 02111.

potentials,
Previous
-

cerebrospinal
clinical trials

fluid analysis,
have established

and computed
that when

tomography.
compared with

x-ray CT, MRI displays

improved

sensitivity

to the presence

of this disease.

The specificity of this new imaging modality, however, remains to be evaluated. Multiple sclerosis must be differentiated from other diseases of white matter that may present in a similar pattern on MRI. Also yet to be investigated is the true sensitivity of MRI to disease when compared with the lesions detected on post-mortem examination. Previous autopsy studies have revealed many more lesions than were detected with x-ray CT or suggested by clinical examination. Clinical investigation is being pursued in the areas of pulse sequence optimization (for visualization sclerosis and have of disease), been application of contrast media

(such as gadolinium
sions of multiple (in both severity
.

DTPA), and detection

distribution), however,

of spinal cord disease.

by MRI to change much research remains

The lewith time to be

observed

done to explore the correlation ogy and the definition of active

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Figure 1
Depending upon the exact pulse sequence utilized, intracranial disease in multiple sclerosis may appear as either high signal intensity or low signal intensity lesions when compared to normal brain tissue. On T2 weighted images (A), multiple sclerosis plaques appear as areas of high signal intensity (arrow), contrasting with surrounding normal white matter. On TI weighted images (B). the lesions are dark or black (low signal intensity) (arrow). This situation occurs because ofthe long TI and T2 values of MS plaques. Magnetic resonance imaging has proved to be significantly more sensitive to intracranial disease in MS than x-ray CT. In addition, MRI utilizes non-ionizing radiation and is capable of direct acquisition of sagittal and coronal images (as well as any oblique plane desired).

Figure 2
A wide spectrum of disease severity is seen on MRI in multiple sclerosis. In a study of42 patients (3). the disease was graded on a scale of -IV by the size, number, and definition of lesions, Only a few small punctate lesions are noted in grade I disease, while there is extensive, almost confluent, involvement ofthe white matter in grade IV. Figure 2 illustrates grade Il-Ill involvement in the supraventricular region.

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Figure 3 A typical case of MS imaged using multiecho-multislice technique (A-D). Spin echo 3000/32 (A&B) and 3000/64 (C&D) pulse sequences were utilized (TR/TE is given). High signal intensity (white) lesions contrast with normal surrounding white and gray maffer. More heavily T2 weighted images (C&D) (TE = #{243}4msec vs = 32msec) give a greater contrastbetween MS plaques and surrounding normaltissue. In more severe disease, lesions maytend to be confluentas opposed to the discrete punctate areas of involvement illustrated here. Note the lesion in the posterior limb of the right internal capsule (Figures 3B&D).

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uOO/45 identified by CT. This also illustrates the visual presentation of lesions suggesting the term lumpy-bumpy to describe confluent irregular involvement adjacent to the body of the lateral
ventricles. This pattern may also be recognized in severe cases

Figure 4
High resolution x-ray CT was diagnostic (for multiple sclerosis) in only 15 of 33 patients (45%) while MRI was diagnostic in all patients (3). The CT in each case was obtained within 2 weeks ofthe MRI examination. Less severe disease, grades I and II, were usually not visualized by CT. A typical case is presented (A&B) in which the lesions were almost confluent in the periventricular region on MRI, yet poorly

on x-ray CT.

Figure 5
Inversion recovery (lR) sequences may also be used to identify MS plaques. Some lesions (such as that illustrated on a TR/Tl/TE 1600/400/32 sequence) may demonstrate remarkably sharp borders. Previous work suggested the superiority of IF? techniques in the detection of brainstem and internal capsule lesions. This result may be primarily due to the higher signal-tonoise ratio available with such techniques (when compared with T2 weighted images) as utilized in this early research. IF? imagestend, however, to be difficultto interpret in the supraventricular region. Partial volume averaging with cortical sulci may mimic disease in such instances. Several studies have been pursuedto establish the relative efficacy of different pulse techniques. In general, lesions are well demonstrated on mildly T2 weighted sequences (for example SE2000/64). On more heavilyT2 weighted sequences, periventricular lesions may be lost in the high signal intensity of the cerebrospinalfluid. With shorter spin echo sequences (such as SE500/30), the contrast between normal and abnormal white maffer may be reduced or lost.

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Periventricular lesions were the most numerous, being seen in all 42 patients studied (3). These were best visualized with T2 weightedtechniques. Although large discrete lesions do occur (A&B), with especial predilection for the frontal horns, the observations of many small punctafe lesions adjacenttothe body ofthe ventricles (forming a lumpy-bumpy paffern) was more

common (see Figure 4). Supraventricular lesions were encountered in 84% of the patients in a study of anatomical distribution of disease by MRI (3). These were best identified using a T2 weighted sequence. In severe disease, plaques tended to become confluent.

A Figure 7

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Lesions could be noted in several instances in the internal capsule. This is illustrated in A and B. External capsule lesions were also detected in some patients.

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Figure 8
Multiecho-multislice techniques are now available, allowing simultaneous acquisition of multiple adjacent sections with different T2 weighting. Use of these techniques allows improved lesion recognition. Multiecho-multislice images are compared with those produced by inversion recovery technique in the same patient with multiple sclerosis. (A&B) SE3000/32; (C&D) 3000/64; (E&F) IF?1800/400/32

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Figure 9
TI and T2 measurements can also be made. Illustrated in the same patient are (A) a ratio image in which the displayed signal intensity is that of an inversion recovery scan divided by that of a spin echo scan with the same TR; (B) a calculated TI image, and (C) a calculated spin density image. On the calculated TI image, the gray scale is so defined that a reduction in TI results in a lower signal intensity. Thus the lesions of multiple sclerosis are seen in general as high signal intensity (long TI)
-

when compared with surrounding normal cerebral tissue. It should also be noted that the TI of cerebrospinal fluid is very long (exceeding that of disease plaques). The potential use of calculated TI, T2, and spin density images in establishing the activity of disease is yet to be investigated. The water content as depicted by spin density images may be of particular interest.

A Figure 10

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Many elderly patients, some with a history of hypertension ortransient ischemic attacks manifest a disease of white matter that has been termed deep white matter infarction. This is well seen by MRI and should not be confused with MS. lnvolvementtends to be symmetrical and confluent, with disease extending to the gray matter-white matterjunction. Large ventricles and subcortical infarcts are common associated findings. Two cases ofthis disease (A&B) are illustrated.

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Figure 11
Lesions in the gray matter with long TI and T2 values which, therefore, appear as white areas of high signal intensity on T2 weighted sequences, and which conform to an arterial distribution, should not be confused with multiple sclerosis, either. These are readily identified as cerebral infarcts. The distribution of disease, notthe elevation in relaxation rates, is diagnostic. An infarct in the left parietal region is illustrated (A-D).

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(A) The use of MRI has identified the relatively common, although previously unsuspected, occurrence of nonfatal brainstem infarcts (arrow). Lesions in the brainstem should be correlated with clinical history to enable a correct diagnosis. There are other instances in which, in MRI images, relatively common dinical entities may on superficial view resemble multiple sclerosis. (B&C) Obstructive hydrocephalus with transependymal flow of cerebrospinal fluid (arrow), presents a characteristic appearance on MRI which is notto be confused with MS. In this second patient (D), a cerebellar neoplasm (open arrow) was the cause of obstruction.

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Conclusions
Brainstem lesions were seen on MRI in I 2 of 42 patients with multiple sclerosis (3). This demands close attention to this area in routine imaging. None of these lesions was seen by CT. Ten patients with multiple sclerosis were scanned Iwice with a six month interval beIween scans. In this population, significant changes were observed that only partially corresponded to the clinical course of the disease. Both apparent progression and regression were observed. MRI is extremely sensitive to the presence of intracerebral disease in multiple sclerosis. Future imaging advances should make possible the visualization of cord involvement, the major region of involvement in a substantial number of patients. In multiple sclerosis, a wide spectrum of disease severity and rapid significant temporal changes in extent of involvement can be documented with MRI. In MS. disease involvement is classically asymmetric. Plaques occur in a characteristic anatomical distribution and typically appear, early, as discrete punctate lesions; the lesions may tend to become more confluent in advanced disease. This pattern is distinct and should not be confused with other diseases of the gray and white matter. Further research is needed to investigate the correlation beIween tissue histol-

ogy and the changes

observed

on MRI. The pomedia

tential application of intravenous contrast in MR imaging also is yet to be explored.

Readings
Lukes SA Crooks LE,Aminoff MJ, ef al. Nuclear magnetic resonance imaging in multiple sclerosis. Ann Neurol 1983; 13:592-601. 2. Young IR, Hall AS, Pallis CA, et al. Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet 1981; 2:1063-lO#{243}#{243}. 3. Runge VM, Price AC, Kirshner HS, et al. Magnetic resonance imaging of multiple sclerosis: A study of pulse-technique
.

4, Maravilla onance
cervical

KR, Weinreb demonstration

efficacy.

MR

I 984;

143:1015-1026.

5, Johnson imaging: 5:495. o. Jackson JA, Leake DR. Schneiders NJ, et al. Magnetic resonance imaging in multiple sclerosis: Results in 32 cases. AJNR 1985; 6:171.

JC. of cord. AJNR I 985; MA, Li DKB, Bryant Serial observations

Suss R, Nunnally RL. Magnetic resmultiple sclerosis plaques in the 5:685-689. DJ. et al. Magnetic resonance in multiple sclerosis. AJNR I 984;

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