Quantification of carotid plaque lipid content with magnetic resonance T2 mapping in patients undergoing carotid endarterectomy

<div><p>Background and purpose</p><p>Techniques to stratify subgroups of patients with asymptomatic carotid artery disease are urgently needed to guide decisions on optimal treatment. Reliance on estimates of % luminal stenosis has not been effective, perhaps because that approach entirely disregards potentially important information on the pathological process in the <i>wall</i> of the artery.</p><p>Methods</p><p>Since plaque lipid is a key determinant of plaque behaviour we used a newly validated, high-sensitivity T2-mapping MR technique for a systematic survey of the quantity and distribution of plaque lipid in patients undergoing endarterectomy. Lipid percentage was quantified in 50 carotid endarterectomy patients. Lipid distribution was tested, using two imaging indices (contribution of the largest lipid deposit towards total lipid (LLD %) and a newly-developed LAI ‘lipid aggregation index’).</p><p>Results</p><p>The bifurcation contained maximal lipid volume. Lipid percentage was higher in symptomatic <i>vs</i>. asymptomatic patients with degree of stenosis (DS ≥ 50%) and in the total cohort (P = 0.013 and P = 0.005, respectively). Both LLD % and LAI was higher in symptomatic patients (P = 0.028 and P = 0.018, respectively), suggesting that for a given plaque lipid volume, coalesced deposits were more likely to be associated with symptomatic events. There was no correlation between plaque volume or lipid content and degree of luminal stenosis measured on ultrasound duplex (r = -0.09, P = 0.53 and r = -0.05, P = 0.75), respectively. However, there was a strong correlation in lipid between left and right carotid arteries (r = 0.5, P <0.0001, respectively).</p><p>Conclusions</p><p>Plaque lipid content and distribution is associated with symptomatic status of the carotid plaque. Importantly, plaque lipid content was not related to the degree of luminal stenosis assessed by ultrasound. Determination of plaque lipid content may prove useful for stratification of asymptomatic patients, including selection of optimal invasive treatments.</p></div

Spearman’s rank correlation between left and right carotid plaque and lipid volume.

<p>(A) Scatter plot graph demonstrating statistically significant correlation between plaque burden (total plaque volume) between left and right carotid arteries. (B) Scatter plot graph showing statistically significant correlation between lipid volumes of the right and left carotid arteries quantified on T2 map (panel B).</p

Difference in lipid percentage between symptomatic and asymptomatic patients.

<p>(A) Using slice with maximal lipid content, symptomatic patients are more likely to have lipid in patients with degree of stenosis of more than 50%. (B) Similarly but using averaged 10 slices, symptomatic patients have larger lipid percentage than asymptomatic ones in the total 100 carotid arteries.</p

Assessment of lipid distribution using T2 mapping technique.

<p>(A) Cross sectional T1-weighted image of bilateral carotid arteries stenoses in the same patient. Segmented T2 map of the symptomatic right vessel of two weeks old history of transient ischaemic event (left sided facial weakness)- showing LAI of 40.48 suggestive of coalesced lipid compared to the left asymptomatic side with LAI of 2.41 (panel A). (B) Median LDD % is statistically higher in symptomatic patients compared to asymptomatic ones. (C) Similarly, median lipid aggregation index is statistically higher in symptomatic patients compared to asymptomatic ones. Notably two outlier vessels were identified with extremely high LDD % and LAI at the time of MRI where the corresponding plaque was yet still silent.</p

Baseline characteristics of recruited patients.

<p>Baseline characteristics of recruited patients.</p

T1 images, inverse SNR and inverse CNR metrics across four sites.

A) Representative T1 images of the same subject scanned at each of 4 sites in the travelling heads study. B) left panel, plots of inverse signal-to-noise ratio (iSNR) for 8 subjects (coloured lines) scanned at each of 4 sites (x-axis labels); right panel, plots of inverse contrast-to-noise ratio (iCNR) for the same subjects and sites. The grey violin plots in both panels indicate the equivalent distributions of T1 iSNR and iCNR, respectively, in the UK Biobank reference dataset, using matched random sampling of N = 8 participants. Box and whiskers represent inter-quartile range and 95% confidence intervals respectively. The iSNR and iCNR metrics are comparable across Siemens sites (CAM = Cambridge, OXF = Oxford, LIV = Liverpool) and aligned with the UKB benchmark distribution. Both iSNR and iCNR are higher for the GE site (KCL = Kings College London) (P < 0.05), indicating lower SNR and CNR.</p

Statistical results for SWI-derived IDPs.

In the top two panels, the left column shows data for 14 IDPs derived from T2* data and the right column shows data for 14 IDPs derived from QSM data. A) Distribution of log-transformed P-values from repeated measures ANOVA testing for a site effect on the mean value of individual IDPs in each class; the solid horizontal line represents the P-value equivalent to FDR = 5%. Green dots represent IDPs fitted to the ANOVA model including data from all four sites; orange dots represent P-values for each IDP fitted to the ANOVA including only data from the three Siemens sites (Cambridge, Oxford, Liverpool). There were more significant between-site differences in mean IDPs when the GE data from KCL were included in the analysis B) Swarm plots showing distribution of intra-class correlation coefficients (ICCs) for the same IDPs, estimated for each pair of all 4 sites (green points), and for each pair of the three Siemens sites (orange points). C) Each column represents finer-grained results for representative IDPs from each class of IDP: from left to right, T2* right pallidum, QSM right pallidum. Top row, plots of each IDP for 8 subjects (coloured lines) scanned at each of 4 sites (x-axis labels). Bottom row, correlations between each pair of sites for each IDP: upper triangle, Pearson’s correlations; lower triangle, Spearman’s correlations.</p

Comparison of ANOVA and Friedman tests.

Comparison of FDR-corrected P-values for site effects derived using repeated measures ANOVA (orange) and non-parametric Friedman (green) tests. (TIF)</p

ASL data IDP summaries.

A) Grey matter mean CBF perfusion (ml/100g/min) measurements for the single post-label delay (PLD) sequence used across all sites. B) Grey matter mean CBF perfusion measurements for the multi-PLD sequence available only on the Siemens sites. Raw data is plotted to the left; the cross-site correlation matrices to the right (upper triangle, Pearson’s correlation; lower triangle, Spearman’s correlation).</p

Covid-19 Clinical Neuroscience Study (COVID-CNS) consortium membership and affiliation.

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