The Use of Noncontrast Quantitative MRI to Detect Gadolinium-Enhancing Multiple Sclerosis Brain Lesions: A Systematic Review and Meta-Analysis

Abstract

Background Concerns have arisen about the long-term health effects of repeated gadolinium injections in multiple sclerosis (MS) patients and the incomplete characterization of MS lesion pathophysiology that results from relying on enhancement characteristics alone. Purpose To perform a systematic review and meta-analysis analyzing whether non-contrast MRI biomarkers can distinguish between enhancing and non-enhancing brain MS lesions. Data Sources Ovid MEDLINE, Ovid Embase, and the Cochrane Database from inception to August 2016. Study Selection We included 37 journal articles on 985 MS patients who had MRI in which T1-weighted post-contrast sequences were compared to non-contrast sequences obtained during the same MRI examination using ROI analysis of individual MS lesions. Data Analysis We performed random-effects meta-analyses comparing the standard mean difference of each MRI metric taken from enhancing versus non-enhancing lesions. Data Synthesis DTI-based FA values are significantly different between enhancing and non-enhancing lesions (P=0.02), with enhancing lesions showing decreased FA compared to non-enhancing lesions. Of the other most frequently studied MRI biomarkers (MD, MTR, or ADC) none were significantly different (P-values of 0.30, 0.47, and 0.19. respectively) between enhancing and non-enhancing lesions. Of the limited studies providing diagnostic accuracy measures, gradient echo-based QSM had the best performance in discriminating between enhancing and non-enhancing MS lesions. Limitations MRI techniques and patient characteristics were variable across studies. Most studies did not provide diagnostic accuracy measures. All imaging metrics were not studied in all 37 studies. Conclusions Non-contrast MRI techniques, such as DTI-based FA, can assess MS lesion acuity without gadolinium.

Clinical Integration of Automated Processing for Brain Quantitative Susceptibility Mapping: Multi‐Site Reproducibility and Single‐Site Robustness

“…The arrow points to a lesion that is hyperintense on QSM but nonenhancing on the contrast enhanced T1‐weighted image. Recent efforts indicate that enhancement or lack thereof on QSM of lesions seen on T2 can predict T1 enhancement . Figure shows an intracranial hemorrhage.…”

Histogram analysis of apparent diffusion coefficient and fluid-attenuated inversion recovery in discriminating between enhancing and nonenhancing lesions in multiple sclerosis

“…Given the unclear long-term consequences of repeated Gd exposure [2,3], many studies have since investigated the performance of qualitative and quantitative MRI markers that do not rely on contrast agents in predicting Gd-enhancing MS lesions. However, as recently summarized in a meta-analysis by Gupta et al, only 3 studies have provided diagnostic performance in the form of AUC for differentiating new ELs and NELs [4]. Moreover, to our knowledge, all noncontrast MRI biomarker MS studies utilizing within-subject multiple lesions do not account for potential clustering bias [6][7][8][9][10][11][12][13][14][15][16][17], which may result in overestimation of statistical significance [18][19][20].…”

“…However, no significant differences were noted with mean diffusivity, magnetization transfer ratio, or apparent diffusion coefficient (ADC) values between ELs and NELs [4]. Moreover, only a minority of the studies included within the meta-analysis provided diagnostic performance measures in the form of area under the curve (AUC) [4]. Most importantly, to our knowledge, all MS studies that have previously investigated noncontrast MRI measures using multiple lesions within the same MS patient did not account for clustering bias [6][7][8][9][10][11][12][13][14][15][16][17].…”

“…In a recent meta-analysis by Gupta et al, fractional anisotropy of enhancing lesions (ELs) were significantly lower than nonenhancing lesions (NELs). However, no significant differences were noted with mean diffusivity, magnetization transfer ratio, or apparent diffusion coefficient (ADC) values between ELs and NELs [4]. Moreover, only a minority of the studies included within the meta-analysis provided diagnostic performance measures in the form of area under the curve (AUC) [4].…”

“…allergic reaction or renal insufficiency). Furthermore, investigation of noncontrast MRI techniques may complement the information provided by Gd enhancement and provide added value in further understanding the pathophysiology of MS lesions [4].…”