Quantification of Aortic Valve Fibrotic and Calcific Tissue from CTA: Prospective Comparison with Histology

Abstract

Background Quantifying the fibrotic and calcific composition of the aortic valve at CT angiography (CTA) can be useful for assessing disease severity and outcomes of patients with aortic stenosis (AS); however, it has not yet been validated against quantitative histologic findings. Purpose To compare quantification of aortic valve fibrotic and calcific tissue composition at CTA versus histologic examination. Materials and Methods This prospective study included patients who underwent CTA before either surgical aortic valve replacement for AS or orthotopic heart transplant (controls) at two centers between January 2022 and April 2023. At CTA, fibrotic and calcific tissue composition were quantified using automated Gaussian mixture modeling applied to the density of aortic valve tissue components, calculated as [(volume/total tissue volume) × 100]. For histologic evaluation, explanted valve cusps were stained with Movat pentachrome as well as hematoxylin and eosin. For each cusp, three 5-µm slices were obtained. Fibrotic and calcific tissue composition were quantified using a validated artificial intelligence tool and averaged across the aortic valve. Correlations were assessed using the Spearman rank correlation coefficient. Intermodality and interobserver variability were measured using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results Twenty-nine participants (mean age, 63 years ± 10 [SD]; 23 male) were evaluated: 19 with severe AS, five with moderate AS, and five controls. Fibrocalcific tissue composition strongly correlated with histologic findings (r = 0.92; P < .001). The agreement between CTA and histologic findings for fibrocalcific tissue quantification was excellent (ICC, 0.94; P = .001), with underestimation of fibrotic composition at CTA (bias, -4.9%; 95% limits of agreement [LoA]: -18.5%, 8.7%). Finally, there was excellent interobserver repeatability for fibrotic (ICC, 0.99) and calcific (ICC, 0.99) aortic valve tissue volume measurements, with no evidence of a difference in measurements between readers (bias, -0.04 cm³ [95% LoA: -0.27 cm³, 0.19 cm³] and 0.02 cm³ [95% LoA: -0.14 cm³, 0.19 cm³], respectively). Conclusion In a direct comparison, standardized quantitative aortic valve tissue characterization at CTA showed excellent concordance with histologic findings and demonstrated interobserver reproducibility. Clinical trial registration no. NCT06136689 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almeida in this issue.

Graphical abstract

Figure 1:

Study flowchart. CTA = CT angiography.

Figure 2:

Example images show comparison of tissue quantification of the aortic valve from CT angiography (CTA) and histologic assessment with use of Movat pentachrome staining in a 75-year-old male participant with aortic stenosis. For CTA, a region of interest was defined between the lower coronary ostium and the virtual basal ring using coronal and axial planes; scan-specific thresholds were used for fibrotic (red) and calcific (yellow) tissues. For quantitative histologic assessment, every valve was evaluated using nine nonconsecutive slices (three per cusp), and the proportion of fibrotic (red) and calcific (yellow) tissues was averaged across the whole set. The bottom right CTA image is not supported by artificial intelligence.

Figure 3:

Scatterplot (left) and Bland-Altman plot (right) compare the quantification of fibrotic tissue composition of the aortic valve at CT angiography (CTA) and quantitative histologic findings. The Spearman rank correlation coefficient shows a strong correlation between CTA and quantitative histology (r = 0.92; P < .001). The Bland-Altman plot shows underestimation of fibrotic tissue composition measurement at CTA compared with quantitative histologic assessment (bias, −4.9%; 95% limits of agreement: −18.5%, 8.7%). Calcific tissue composition (percentage) is determined by subtracting the fibrotic tissue composition from 100%; the corresponding Bland-Altman plot is presented in Figure S7.

Figure 4:

Representative examples of Warren-Yong scores in hematoxylin and eosin (H&E) staining, Movat pentachrome staining, and CT angiography (CTA). On slides stained with hematoxylin and eosin and Movat pentachrome, calcification of aortic cusps was semiquantitatively assessed (1 = absence of calcification; 2 = mild valve thickening and early nodular calcification; 3 = moderate thickening with many calcified nodules; and 4 = severe thickening with many calcified nodules). On CTA images, fibrotic tissue is shown in red, and calcific tissue is shown in yellow. CTA images in the left column are not supported by artificial intelligence.

Figure 5:

Bar graph shows the number of participants with severe aortic stenosis (AS), moderate AS, and heart transplant in the respective Warren-Yong scores.

Figure 6:

Bland-Altman plots of interobserver repeatability between two readers for assessing fibrotic and calcific tissue volume measurements at CT angiography. No evidence of a difference in measurements was observed between the two readers for either fibrotic (bias, −0.04 cm³; 95% limits of agreement [LoA]: −0.27 cm³, 0.19 cm³) or calcific (bias, 0.02 cm³; 95% LoA: −0.14 cm³, 0.19 cm³) tissue volumes.