eMedicine Specialties > Radiology > Brain/Spine

Brain, Multiple Sclerosis: Imaging

Author: James A Wilson, MD, MSc, FRCPC, BSc(H), Neurologist and Clinical Neurophysiologist, Oconee Neurology Services
Coauthor(s): Omar Islam, MD, FRCP(C), Assistant Professor of Diagnostic Radiology, Queen's University; Consulting Staff, Department of Diagnostic Radiology, Division of Neuroradiology, Kingston General Hospital
Contributor Information and Disclosures

Updated: Jan 24, 2007

Radiography

Findings

Plain radiographic studies have no positive predictive value in the diagnosis of MS. Occasionally, plain radiographs may be used to exclude mechanical bony lesions.

Degree of Confidence

Plain images cannot demonstrate MS-specific lesions.

Computed Tomography

Findings

Similar to radiography, CT has had a limited role in the diagnosis of MS and in the treatment of patients since the advent of MRI. CT scans may be used to exclude other causes for neurologic impairment, but they have a low positive predictive value in the diagnosis of MS.

Prior to MRI, CT was used in an attempt to identify active MS lesions with the injection of double or triple doses of intravenous contrast material. However, the scans were insensitive for the detection of chronic lesions. CT scans can help in assessing the degree of cerebral atrophy associated with advanced MS, but given the plethora of additional information provided by MRI, CT is no longer used for this purpose.

Degree of Confidence

CT has a low positive predictive value in the diagnosis of MS.

In a cohort of 200 patients, Paty et al found that of the 19 who went on to develop clinically definite MS (CDMS), abnormal CT findings were demonstrated in only 9 (47%). In contrast, abnormal MRI findings were demonstrated in 18 (95%). All of the abnormal CT findings were also demonstrated on MRIs.

False Positives/Negatives

CT imaging in MS is nonspecific and insensitive; thus, the false-negative rate is high. An acute MS lesion may enhance and appear simply as an enhancing white matter lesion on CT scans, but the appearance is highly nonspecific. When a highly active MS lesion is observed to enhance and possibly exerts mass effect, it can be termed tumefactive due to the potential for misidentification as a tumor. Because CT scans typically do not help identify the more chronic lesions, the tumefactive MS lesion may appear as a solitary enhancing mass, which leads to neurosurgical intervention. Fortunately, this situation is relatively uncommon.

Magnetic Resonance Imaging

Findings

The advent of MRI has revolutionized the diagnosis and monitoring of MS.

Typical findings and pulse sequences

Because of the inflammation and breakdown of the blood-brain barrier in MS lesions, the presence of extravascular fluid leads to hyperintensity on T2-weighted images. Thus, in a patient with MS, MRIs typically demonstrate more than 1 hyperintense white matter lesion.

Lesions may be observed anywhere in the CNS white matter, including the supratentorium, infratentorium, and spinal cord; however, more typical locations for MS lesions include the periventricular white matter, brainstem, cerebellum, and spinal cord.

Ovoid lesions perpendicular to the ventricles are common in MS and occasionally are called Dawson bars or fingers, which occur along the path of the deep medullary veins.

Perhaps the most specific lesions in MS are noted in the corpus callosum at the interface with the septum pellucidum (Gean-Marton, 1991).

Proton density (PD)–weighted MRI has an advantage over standard T2 imaging because, on PD series, MS lesions remain hyperintense while CSF signal is suppressed. Therefore, the lesions are easily identified. Depending on the PD technique, CSF signal is suppressed to a variable degree, rendering it isointense to hypointense relative to the brain parenchyma. This sequence results in substantial suppression of Virchow-Robin spaces, which are perivascular CSF spaces that may penetrate to the subcortical white matter. These spaces may appear as hyperintense spots on standard T2-weighted MRIs.

Compared with other techniques, nonenhanced T1-weighted MRI is far less sensitive in detecting MS lesions. Acute lesions usually are not depicted at all. With T1-weighted MRI, the clinician can gain a general appreciation of the global cerebral atrophy that occurs with advanced chronic MS. Global atrophy has been suggested to have the strongest imaging correlation with disability.

Chronic MS lesions usually result in localized leukomalacia, and they may appear as hypointense lesions that represent loss of tissue.

Gadolinium-enhanced T1-weighted MRIs can depict acute active MS lesions. These appear as enhancing white matter lesions, and the presence of an enhancing lesion has been shown to increase the specificity for MS (Barkhof, 1997; Tintoré, 2000).

Newer pulse sequences and techniques

Newer MRI pulse sequences and techniques have emerged, and these are potentially useful in the evaluation of patients with MS.

Fluid-attenuated inversion recovery (FLAIR) MRI is a heavily T2-weighted technique that dampens ventricular (ie, free water) CSF signal. Thus, the highest signals on the sequence are from certain brain parenchymal abnormalities, such as MS lesions, while the CSF appears black. This appearance is different from that on PD-weighted MRIs, on which periventricular MS lesions may appear nearly isointense to the adjacent CSF. The greater relative suppression of CSF on FLAIR images compared with PD-weighted series increases the contrast between periventricular lesions and CSF, enhancing their detection. FLAIR has been shown to be superior to PD-weighted sequences in the detection of MS lesions in the cerebral hemispheres. However, PD-weighted imaging remains the investigation of choice for infratentorial lesions (Hashemi, 1995).

Magnetic resonance (MR) spectroscopy uses the characteristic spectra of specific biochemical markers to quantitate organic compounds in vivo. N -acetylaspartate (NAA) is a relatively specific neuronal marker that is in sufficient concentrations in the brain to be revealed on MR spectroscopic images. By comparing the spectral signal of NAA with that of creatinine (Cr), MR spectroscopic can be useful in assessing neuronal and axonal loss.

Arnold et al noted that the CNS NAA-Cr ratio was decreased in moderate-to-advanced MS. In addition, white matter that appeared normal on T1- and T2-weighted images also demonstrated the reduction (Arnold, 1990). In addition, a normal ratio was noted in the area of a recently active lesion associated with clinical deficits that subsequently resolved. The findings led the authors to propose that MRS findings may be able to help identify irreversible axonal damage.

In a study involving 88 patients with MS, De Stefano et al found a strong correlation between disability scores and NAA-Cr ratios (De Stefano, 2001). The ratio exhibited a stronger correlation in MS patients with milder disability scores. Because MR spectroscopy appears to be capable of depicting changes in white matter that are not detected with routine pulse sequences and because the findings are correlated with disability scores, the use of MR spectroscopy may prove valuable in monitoring patients after treatment and in formulating their prognosis.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA.

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

In patients with CDMS, MRI demonstrates a high rate of abnormal findings compatible with the diagnosis. In a study by Lukes et al, lesions were demonstrated in 10 patients with CDMS (Lukes, 1983). In a larger study by Robertson et al, MRI findings were abnormal in 124 of 133 patients with CDMS (Robertson, 1985). Ormerod et al found that 112 of 114 patients with CDMS had abnormal MRI findings and that 102 of 114 had discrete white matter lesions (Ormerod, 1987).

MRI is well established as the preferred imaging modality for depicting MS lesions. Another major use of MRI has been the evaluation of patients who have had only one episode of neurologic impairment and who do not meet the clinical criteria for the diagnosis. The overall risk of developing MS after a single episode of neurologic impairment is estimated to be as low as 12% (2-y follow-up study by Beck et al in 1993) to as high as 45% (12.9-y follow-up study by Sandberg-Wollheim et al in 1990) or 58% (14.9-y follow-up study by Rizzo et al in 1988).

MRI has been proven to be the most useful investigation for predicting the progression to MS. In a 10-year follow-up study of patients with a clinically isolated event, 45 (83%) of 54 patients with abnormal MRI findings went on to develop clinical MS, whereas only 3 of 27 with normal MRI findings developed MS (O'Riordan, 1998).

Tintoré et al followed up 70 patients for an average of 28.3 months after an isolated neurologic event and compared various MRI criteria for the diagnosis MS, as defined by Paty et al, Fazekas et al, and Barkhof et al (Tintoré, 2000; Paty, 1988; Fazekas, 1985; Barkhof, 1997). With the method of Paty et al, which requires 3 or 4 lesions (1 of which is periventricular), the authors reported a sensitivity of 86% but a specificity of only 54%.

The criteria of Fazekas et al resulted in the same sensitivity and specificity. These criteria require 3 lesions with 2 of the 3 following characteristics: infratentorial location, periventricular location, and lesion greater than 6 mm. The criteria of Barkof require 1 infratentorial lesion, 1 juxtacortical lesion, 3 periventricular lesions, and either 1 gadolinium-enhanced lesion or more than 9 lesions on T2-weighted MRIs. These criteria resulted in a sensitivity of 73% and a specificity of 73%. Thus, as the MRI criteria become more stringent in the diagnosis of MS, specificity increases at the expense of decreasing sensitivity.

False Positives/Negatives

In virtually all patients with clinically well-established MS, MRIs demonstrate the corresponding changes. False-negative findings occur more frequently in patients with early MS and a minimal clinical history of neurologic impairment than in other patients.

O'Riordan et al prospectively found that, in 3 of 27 patients with normal MRI findings, MS subsequently developed (O'Riordan, 1998). The patients with normal MRI findings all developed lesions detectable on MRIs when the disease became established. Similarly, as patients are followed for longer periods, the rate of false-positive findings decreases because, in many patients with abnormal MRI findings after a single neurologic event, the clinical criteria for MS eventually develop.

Ultrasonography

Findings

Ultrasonography is not currently used in the investigation of MS. Recently, however, Berg et al used transcranial sonography to determine the size of the ventricles in patients with MS (Berg, 2000). The authors found that an increasing size is correlated with the MRI-determined brain volume, as well as cognitive dysfunction and clinical disability. Further studies may establish a role for ultrasonography in the prognosis and treatment of patients with MS.

Nuclear Imaging

Findings

Nuclear medicine studies are not used in the diagnosis or management of MS.

Angiography

Findings

Angiography has a limited role in the diagnosis and management of MS. Occasionally, when CNS vasculitis is considered in a patient with undifferentiated findings, angiography may be considered.

Degree of Confidence

No positive angiographic findings are specific to MS.

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