About Multiple Sclerosis
Multiple Sclerosis (MS) is a chronic, immune-mediated, inflammatory disease of the Central Nervous System (CNS) that causes demyelination of axonal myelin sheaths and neurodegeneration. The peak onset is between age 20 and 40 years and women are affected approximately twice as often as men. Patients with MS suffer from a variety of neurological symptoms.
Four disease courses have been identified in multiple sclerosis:
clinically isolated syndrome (CIS)
relapsing-remitting MS (RRMS)
primary progressive MS (PPMS)
secondary progressive MS (SPMS)
Although multiple sclerosis is primarily a white matter disease, grey matter can also be affected.
Magnetic Resonance Imaging (MRI) is a valuable diagnostic tool that is capable of showing demyelinating lesions in the brain and monitoring their evolution (fig. 1).
Fig. 1 MRI is very useful at the follow-up step, in patients with established MS. Upper row shows 3D FLAIR in sagittal (A), coronal (B) and axial (C) plane. Lower row shows 3D FLAIR in sagittal (D), coronal (E) and axial (F) plane. Lower row MR images (D, E, F) have been obtained six (6) months later compared to upper row's. Disease progression can clearly be seen in the form of new lesions in pons. Image courtesy of Bac Nguyen.
There are a lot of pulse sequences that can be used in MRI of multiple sclerosis, each offering different aspects of disease’s complex pathophysiology. The analysis of advanced and quantitative MR Imaging techniques (e.g. PWI, DWI, DTI, in-vivo MRS) is outside the scope of this review.
Fluid Attenuated Inversion Recovery (FLAIR):
FLAIR is one of the most important sequences for MS detection and evaluation, because of its high sensitivity. FLAIR pulse sequence uses an inversion recovery pulse (180°) to selectively suppress the signal from the cerebrospinal fluid (CSF) (fig. 2). Inversion time (TI) should be selected in the range of 1700-2500 msec (TI selection depends on the field strength and manufacturer). White matter lesions ("T2 lesions") are depicted as focal areas of hyperintensity ("bright spots"), reflecting different levels of myelin loss, inflammatory activity and gliosis (fig. 3). FLAIR imaging provides very high sensitivity in the depiction of hyperintense T2 lesions close to the CSF, such as the juxtacortical and the periventricular white matter, but is less sensitive in the posterior fossa, cortex and grey matter (fig. 4).
Fig. 2 FLAIR sequence timing diagram. FLAIR pulse sequence uses an inversion recovery pulse (180°) to selectively suppress the signal from the CSF. Inversion time (TI) should be selected in the range of 1700-2500 msec, depending on the field strength and vendor.
Fig. 3 3D sagittal FLAIR (A), multiplanar reconstruction in coronal plane (B) and axial 2D FLAIR (C). MS lesions are depicted as focal areas of hyperintensity ("T2 lesions").
Fig. 4 3D sagittal FLAIR (A) and multiplanar reconstruction in coronal (B) and axial (C) plane. 3D sagittal DIR (D) and multiplanar reconstruction in coronal (E) and axial (F) plane. DIR sequence is very useful in depicting cortical grey matter lesions (red circle), which are not well visible on FLAIR sequence. Image courtesy of Bac Nguyen.
Double Inversion Recovery (DIR):
DIR is a recent sequence, which attenuates the CSF as well as the white matter, providing a superior delineation between grey and white matter and enhancing any inflammatory lesion. Two inversion recovery pulses are required to obtain DIR sequence. TI1is used for the suppression of the CSF and TI2is used for the suppression of the white matter.
TI1 should be obtained at 1700-3500 msec, while TI2at 320-450 msec (the selection of the inversion times basically relies on the field strength and the vendor). DIR provides higher sensitivity than FLAIR (fig. 5), because it suppresses both the signal of the white matter and the CSF. Moreover, the sequence is very useful in depicting infratentorial and cortical grey matter lesions, which are not well visible on FLAIR sequence (fig. 4).
On the other hand, DIR imaging is more time consuming than FLAIR because it uses two (2) inversion recovery pulses (fig. 5). Therefore, DIR is acquired with lower spatial resolution, in order to be acceptable in daily clinical practice, and small MS plaques may not be shown well (fig. 6).
Fig. 5 3D sagittal FLAIR (A) and multiplanar reconstruction in coronal (B) and axial (C) plane. 3D sagittal DIR (D) and multiplanar reconstruction in coronal (E) and axial (F) plane. 3D DIR provides higher sensitivity, therefore the MS lesions are better highlighted. Nonetheless, 3D DIR was acquired with lower spatial resolution and was more time consuming than 3D FLAIR. Images courtesy of Bac Nguyen.
Fig. 6 3D sagittal FLAIR (A) and multiplanar reconstruction in coronal (B) and axial (C) plane. 3D sagittal DIR (D) and multiplanar reconstruction in coronal (E) and axial (F) plane. 3D FLAIR provides higher spatial resolution, therefore the small MS lesion in subcortical region (green cursor) is better highlighted. This lesion is very difficult to be depicted on DIR sequence. In addition, 3D FLAIR was less time consuming than 3D DIR, because it uses one (1) inversion recovery pulse instead of two (2). Images courtesy of Bac Nguyen.
Pre- and post-contrast T1-w:
Pre and post-contrast T1-w images are very useful in order to delineate which MS lesions are active. Old plaques are hyperintense on T2-w and FLAIR sequences and hypointense on T1-w images without gadolinium enhancement. On the contrary, active plaques show gadolinium enhancement (fig. 7). The latter correlates with inflammation and increased vascular permeability and disappears after treatment (or with time), when the integrity of the blood-brain-barrier (BBB) is restored. Moreover, the 3D high-resolution T1-w images, can be used for brain volumetry and for detecting the black holes, i.e. persistently dark lesions, associated with severe tissue damage (i.e., both demyelination and axonal loss).
Fig. 7 illustrates a patient with MS lesions on brain and cervical spine. Pre and post-contrast T1-w images are very useful in order to delineate which MS lesions are active. The old lesion is hyperintense on FLAIR imaging and hypointense on pre- and post-contrast T1-w images (red circle). On the contrary, the active lesion shows gadolinium enhancement (red arrow).
Nowadays, T2-w and PD-w are not the first determining sequences in MS, because the high signal from the CSF can obscure small lesions (fig. 8). However, they are particularly useful in the posterior fossa, where FLAIR images have limited sensitivity and are more prone to artifacts.
Fig. 8 2D axial T2-w (A) and 2D axial FLAIR (B). The MS lesion (red arrow) cannot easily be detected on T2-w imaging due to the high signal from the CSF.
Phase-sensitive inversion recovery (PSIR):
PSIR stands for Phase Sensitive Inversion Recovery and is typically used to improve the delineation of grey and white matter. In addition, the sequence provides high contrast-to-noise ratio (CNR) between MS lesions and normal tissue. TI value of PSIR sequence should be selected at 350-600 msec. While using this technique it is important to use the phase sensitive reconstruction (real). PSIR sequence is useful for depicting cortical grey matter lesions (common in MS), which are usually not well visible on the other series. PSIR images may be more sensitive than DIR images for the detection of cortical grey matter lesions. Moreover, PSIR sequence shows great potential in revealing MS lesions in the cervical spinal cord (fig. 9).
Fig. 9 T2-w (A) and PSIR (B) sequences. PSIR sequence can easily detect the MS lesion with high contrast. Image courtesy of Bac Nguyen.
Susceptibility-weighted imaging (SWI/SWAN):
SWI is a neuroimaging technique, which uses tissues magnetic susceptibility differences to generate a unique contrast, different from that of proton density (PD), T1, T2, and T2*. In clinical practice, SWI is mainly used to detect hemorrhage, microbleeding (diffuse axonal injury), hemorrhagic transformation and to identify iron and other mineral deposition. Although, many papers have establish its usefulness in MR diagnosis of neurodegenerative diseases, such as multiple sclerosis.
Multiple sclerosis is a potentially disabling disease of the brain and spinal cord (central nervous system). MRI is by far the most sensitive technique for detecting MS lesions and has proved to be a very important tool for diagnosing MS and monitoring clinical trials.
FLAIR, T2-w and pre- and post-contrast T1-w are well-established pulse sequences, which are used worldwide for the detection and evaluation of MS plaques in clinical practice.
DIR and PSIR techniques provide higher sensitivity in the depiction of MS lesions compared with the standard imaging (especially in the infratentorial and cortical region), but they are not widely available and (most of the time) are more time consuming.
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