Uncovering and Characterizing Multiple Sclerosis Lesions: The Aid of Fluid‐Attenuated Inversion Recovery Images in the Presence of Gadolinium Contrast Agent

Abstract

Multiple sclerosis (MS) is a chronic illness affecting the central nervous system (CNS) of young adults, with an increasing disease burden over time. Classically regarded as an autoimmune disease sustained by a T-helper mediated inflammatory pathway of demyelination, it is now apparent that a more insidious degenerative process, in which axonal damage and neuronal death play a central role, may also be present. 1 Among patients and within patients over time, the combination of these pathological mechanisms promotes and sustains the progression of irreversible physical and cognitive disability.Magnetic resonance imaging (MRI) provides a sensitive tool for noninvasively studying pathological mechanisms in diseased brains. In the clinical setting, MS imaging is performed as a multisequence protocol. Pre-and post-contrast T1 weighted spin echo (SE) images as well as T2 weighted SE images and T2 fluid-attenuated inversion recovery (FLAIR) images are routinely used. These imaging sequences, commonly defined as conventional MRI techniques, allow identification of the distinctive multiple lesions.However, the gathered MRI-derived indices of disease poorly reflect the extent of patients' disability as quantified by clinical measures. Researchers use the term "clinical-MRI" paradox to describe such a disconnection 2 and ascribe several factors to its existence. Among them is the limited pathological specificity of MRI, ie, visible lesions do not mirror the heterogeneity of the biological mechanisms sustaining their pathology. Conversely, visualizing and characterizing the heterogeneity of brain parenchymal lesions in vivo is a fundamental prerequisite for following the disease's natural evolution over time, monitoring the effect of the administered drugs and developing new therapeutic strategies. An additional limitation of conventional MRI sequences is their inability to identify the effects of MS worsening beyond visible lesions or detecting pre-lesion formation in CNS tissue appearing as normal. For many years, using non-conventional quantitative MRI techniques 3 greatly aided in uncovering and quantifying pathology of normal-appearing CNS tissue. Non-conventional MRI techniques, however, may be labor-intensive, thus often difficult to use in daily clinical practice.In an attempt to overcome those MRI limitations, in the present paper Kataoka et al 4 propose using post-contrast, ie, gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA), FLAIR to identify and characterize, in greater detail, active lesions of MS patients. As opposed to non-conventional MRI techniques, the combination of FLAIR and Gd can be easily implemented. Thus, although the work reports a small cohort of patients and the findings do not allow any definite conclusion, the proposal of the authors to consider post-contrast FLAIR image as part of the MS imaging protocol is intriguing and worth of further larger investigations.By consensus, active lesions are regarded as the first in vivo recognizable event of MS and represent foci of inflammatory act...

Predicting Breakdown of the Blood-Brain Barrier in Multiple Sclerosis without Contrast Agents

“…On the basis of our experience and on published reports, 10,11 we believe that the presence of gadolinium does not substantially alter this identification because lesions only become more hyperintense when they enhance. Unfortunately, precontrast T2-weighted FLAIR scans were not available for analysis so that direct verification of this observation on the current dataset is not possible.…”

“…Postcontrast T2-weighted FLAIR scans allow detection of contrast-enhancing lesions without affecting the signal intensity of nonen-hancing lesions so that signal intensity within lesions on postcontrast scans is at least as great as that on precontrast scans. 10,11 …”

“…Note that the FLAIR data used for this study scan were acquired after contrast injection to aid in the clinical detection of enhancing lesions. 10,11 However, because both enhancing and nonenhancing lesions are hyperintense on postcontrast FLAIR scans, our threshold, which fell below the intensities of nonenhancing lesions (On-line Fig 1), ensured that both groups were included and that enhancement information in the postcontrast FLAIR data were not used for the enhancement prediction. Thus, voxels that met the intensity threshold criterion, regardless of whether they were enhancing or nonenhancing, were treated equally in subsequent analysis.…”

Use of Magnetic Resonance Imaging to Visualize Leptomeningeal Inflammation in Patients With Multiple Sclerosis

“…However, a recent and exciting MRI discovery with the advent of 3-T imaging has been the ability to detect LME adjacent to the cerebral cortex in patients with MS. [26][27][28] The preferred technique is highresolution postcontrast T2 FLAIR MRI with delayed image acquisition (at least 10 minutes after the intravenous administration of gadolinium). [26][27][28]63,64 In routine neurologic care, postcontrast T2 FLAIR MRI was shown to be significantly better than conventional T1-weighted imaging, providing as much as 10-fold increased sensitivity in the detection of low concentrations of contrast in the subarachnoid space. 63 Postcontrast T2 FLAIR MRI has shown utility in the detection of LME that is missed by conventional T1-weighted imaging in a range of neurologic illness, including reperfusion injury, 65 ischemia, 66 vasculitis, 67 and tumors.…”

Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis

“…[13][14][15][16][17][18] In MS, postcontrast T2-FLAIR offers outstanding detection of contrast enhancement within white matter lesions, 19,20 but leptomeningeal contrast enhancement has not been investigated. We therefore prospectively acquired these data on all eligible patients seen at our center from late 2009.…”