Meningeal contrast enhancement in multiple sclerosis: Assessment of field strength, acquisition delay, and clinical relevance.

BACKGROUND/PURPOSE: Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report an assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE). METHODS: This was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR). RESULTS: LME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non-significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008). CONCLUSION: 7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS.

Meningeal contrast enhancement in multiple sclerosis: assessment of field strength, acquisition delay, and clinical relevance.

Background/Purpose: Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report a comprehensive assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE). Methods: This was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR). Results: LME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non-significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008). Conclusion: 7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS.

A pilot trial of ocrelizumab for modulation of meningeal enhancement in multiple sclerosis.

BACKGROUND: Autopsy data suggests that meningeal inflammation in multiple sclerosis (MS) is driven by CD20+ B-cells. Ocrelizumab is an anti-CD20 monoclonal antibody, and thus could potentially ameliorate meningeal inflammation in MS. Leptomeningeal enhancement (LME) on MRI is suggested as a surrogate biomarker of meningeal inflammation in MS, and thus may be a way of monitoring for this treatment effect. OBJECTIVES: To determine if ocrelizumab impacts meningeal enhancement (ME) on 7T MRI in MS. METHODS: Twenty-two patients with MS started on ocrelizumab by their treating physician were enrolled into this single-center, open-label, prospective trial. Participants underwent 7T MRI of the brain prior to first infusion, with screening for the presence of LME. Fourteen patients (48 ± 11 years; 11 women) had LME on the baseline scan and were invited to return for an additional 7T MRI after 1 year of treatment. Fourteen MS patients (49 ± 10 years; 11 women) on non-CD20 treatment from a separate observational cohort of annual 7T MRIs were used for comparison - matched for LME at baseline, age, and sex. Post-contrast FLAIR and subtraction images were reviewed for LME and paravascular and dural enhancement (PDE). RESULTS: All subjects in the ocrelizumab and comparison groups had LME and PDE on their baseline scan. At the beginning of the study the mean number of foci of LME and PDE in the study group were 2.3 ± 1.7 and 6.6 ± 3.9 respectively. Mean LME and PDE count for the comparison group were 1.7 ± 1.5 and 7.8 ± 5.5. Mean volume of LME in the study group was 50.5 mm3 ± 65.0 mm3 and that of the PDE was 866 mm3 ± 937.9. Mean volume of LME and PDE for comparison group were 28.4 mm3 ± 36.0 and 885 mm3 ± 947.7 respectively. At follow-up, the number of patients with LME decreased to 8 (57 %) in both groups, whereas the proportion of patients with PDE was unchanged. Minimal mean change in the number of LME after 1 year were seen in both the study group (0.07 ± 2.9, p = 0.97) and comparison group (-0.71 ± 1.5, p = 0.08). Minimal mean change was seen in the volume of LME in both the study group (-21.91 mm3 ± 77.66, p = 0.27) and comparison group (3.4 mm3 ± 32.11, p = 0.77). There was minimal change in the mean number of foci of PDE after 1 year in both the study group (-0.71 ± 2.36, p = 0.32) and in the comparison group (-0.17 ± 3.89, p = 0.15). Mean change in volume of PDE was measurable, but not significant in both the study group (-397.1 mm3 ±959.6, p = 0.80) and in the comparison group (-417.0 mm3 ± 922.7) (p = 0.80). Comparisons between the changes in foci count and volume for both LME and PDE in the study versus comparison groups showed no significant differences. CONCLUSION: In this small pilot trial, ocrelizumab did not significantly reduce the number or volume of foci of LME or PDE in MS patients.

Components of carotid atherosclerotic plaque in spectral photon-counting CT with histopathologic comparison.

OBJECTIVES: This study aimed to demonstrate the effectiveness of spectral photon-counting CT (SPCCT) in quantifying fibrous cap (FC) thickness, FC area, and lipid-rich necrotic core (LRNC) area, in excised carotid atherosclerotic plaques by comparing it with histopathological measurements. METHODS: This is a single-center ex vivo cross-sectional observational study. Excised plaques of 20 patients (71 +/- 6 years; 13 men), obtained from carotid endarterectomy were scanned with SPCCT using standardized acquisition settings (120k Vp/19 µA; 7-18 keV, 18-30 keV, 30-45 keV, 45-75 keV, and 75-118 keV). FC thickness, FC area, and LRNC area were quantified and compared between high-resolution 3D multi-energy CT images and histopathology using the Wilcoxon signed-ranks test and Bland-Altman analysis. Images were interpreted twice by two radiologists separately, blinded to the histopathology; inter- and intra-rater reliability were assessed with the intra-class correlation coefficients (ICC). RESULTS: FC thickness and FC area did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements (p value range 0.15-0.51 for FC thickness and 0.053-0.30 for FC area). For the LRNC area, the p value was statistically non-significant for reader 1 (range 0.36-0.81). The Bland-Altman analysis showed mean difference and 95% confidence interval for FC thickness, FC area, and LRNC area, 0.04 (-0.36 to 0.12) square root mm, -0.18 (-0.34 to -0.02) log10 mm2 and 0.10 (-0.088. to 0.009) log10 mm2 respectively. CONCLUSION: The result demonstrated a viable technique for quantifying FC thickness, FC area, and LRNC area due to the combined effect of high spatial and energy resolution of SPCCT. KEY POINTS: • SPCCT can identify and quantify different components of carotid atherosclerotic plaque in ex vivo study. • Components of atherosclerotic plaque did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements.