Photon-Counting Detector CT Reduces Calcium Overestimation Compared With Energy-Integrating Detector CT
Micro-CT Validation in Cadaveric Arteries
Doosup Shin, MD; Lionel Chong, BS; Matthew Cannata, BSC; Eric Wolff, BS; Adil Ansari, BS; Christian Calistro, BA; Roosha Parikh, MD; Jonathan Weber, MPH; Jaffar M. Khan, MD, PHD; Carlos Collet, MD, PHD; Richard A. Shlofmitz, MD; Evan Shlofmitz, DO; Allen Jeremias, MD, MSC; Javier Jas Garcia, MS; Omar K. Khalique, MD; Brian L. Beatty, PHD; Ziad A. Ali, MD, DPHIL

Table of Contents
Abstract and Introduction
Beyond luminal stenosis assessment, contemporary coronary computed tomography angiography has evolved into a comprehensive tool for plaque characterization.[1,2] Coronary calcification is of particular clinical importance, as it can adversely affect the diagnostic performance of coronary computed tomography angiography through blooming artifacts related to partial volume aver-aging, beam hardening, and motion artifact, leading to systematic overestimation of coronary calcium and stenosis severity.[3]
Photon-counting detector computed tomography(PCD-CT) represents a fundamental technological advance over conventional energy-integrating detector computed tomography (EID-CT), offering higher spatial resolution and reduced blooming artifacts,[4] enhancing visualization of coronary anatomy and plaque characteristics, particularly calcified plaques.[5,6,7,8] A prior study suggested less overestimation of calcium volume with PCD-CT compared with EID-CT[9]; however, quantitative assessment of multiple calcium metrics and measurement behavior across both modalities has not been rigorously validated.
Accordingly, using human cadaveric coronary arteries, we sought to evaluate and directly compare scanner-related bias and measurement error in coronary calcium assessment between PCD-CT and EID-CT using micro–computed tomography (micro-CT) as the near-histologic resolution reference standard.
Methods
Native coronary arteries from 10 cadavers were harvested after fixation. Specimens were scanned using EID-CT (Revolution Apex 256, GE Healthcare; tube voltage 140 kVp; voxel size 0.488 × 0.488 × 0.625 mm;medium smooth kernel), PCD-CT (Naeotom Alpha, Siemens Healthineers; ultra-high-resolution mode;140 kVp; 0.265 × 0.265 × 0.2 mm; Bv68 kernel), and micro-CT (SkyScan, Bruker; 130 kVp; 0.008 × 0.008 ×0.008 mm). Matrix size was 512 × 512 for both clinical CTs and 2,240 × 2,240 for micro-CT
CT images were analyzed using Dragonfly 3DWorld (Comet Technologies Canada Inc) by 2 blinded investigators. Cross-sections were coregistered across modalities using anatomic landmarks and visual cues, and maximum thickness and area were measured manually. Calcium volume was quantified using semiautomated segmentation, with thresholds derived from manual delineation of calcified plaque. Mean attenuation (Hounsfield units [HU]) was measured within the segmented calcium regions.
Correlation and agreement with micro-CT were assessed using Pearson correlation and Lin’s concordance correlation coefficient. Relative error was calculated as (clinical CT error with PCD-CT compared with EID-CT. Agreement and bias were further evaluated using Bland-Altman analysis, with proportional bias assessed by regression of the differences on the mean. Generalized additive models with thin-plate splines were used to model measurement error as a function of mean HU, and the effective degrees of freedom were reported.
This study did not include living human subjects; therefore, institutional review board approval was not required.
Results
Fifteen coronary arteries with 45 calcified lesions were analyzed, yielding 309 coregistered cross-sections. Interobserver agreement was excellent for all measurements (intraclass correlation coefficients >0.9).
Both clinical CT modalities demonstrated strong correlation with micro-CT (Figure 1A); however, concordance was consistently higher for PCD-CT compared with EID-CT for maximum thickness(0.79 vs 0.63), area (0.88 vs 0.63), and volume (0.91vs 0.67) (all P < 0.001).
Both modalities overestimated calcium measurements relative to micro-CT; however, the magnitude of overestimation and relative error were consistently lower with PCD-CT (all P < 0.001)(Figure 1B), corresponding to median relative error reductions of 52.9% (IQR: 31.0%-73.1%) for maximum thickness, 66.7% (IQR: 43.0%-84.4%) for area, and 66.9% (IQR: 51.6%-84.9%) for volume. Bland-Altman analysis further demonstrated lower systematic bias and narrower limits of agreement with PCD-CT (Figure 1A).
Measurement error increased with calcium size for both modalities (proportional bias coefficients [ß]>0 for all measures; P < 0.001). This size-dependent bias was attenuated with PCD-CT compared with EID-CT, particularly for area (ß: 0.32 vs 0.56; P < 0.001)and volume (ß: 0.35 vs 0.75; P < 0.001).
PCD-CT demonstrated lower calcium attenuation compared with EID-CT (Figure 1C). Measurement error increased with calcium density for both scanners; however, the error-HU relationship differed significantly between scanners (P-interaction < 0.001)and PCD-CT exhibited a more linear and predictable relationship, whereas EID-CT showed more pronounced nonlinearity, reflected by higher effective degrees of freedom (Figure 1D).

(A) Scatter plots (left 2 columns) show the relationship between clinical CT and micro-CT calcium measurements, with regression lines (red) and the line of identity (gray, dotted). Bland-Altman plots (right 2 columns) display mean bias (red, dotted) and limits of agreement (blue, dotted). (B) Violin plots of relative error for clinical CT compared with micro-CT for maximum thickness, area, and volume. Data are presented as median (IQR); P values compare PCD-CT and EID-CT. (C) Differences in calcium attenuation (HU) between PCD-CT and EID-CT in coregistered cross-sections are shown using paired box plots. Boxes represent the median and IQR, with whiskers extending to 1.5 × IQR. (D) Generalized additive models with thin-plate splines showing the relationship between clinical CT measurement error (referenced to micro-CT) and calcium attenuation (HU). (E) Representative coregistered cross-sections across micro-CT, PCD-CT, and EID-CT are shown. Density maps (rainbow scale) depict attenuation gradients (green-yellow: 130-500 HU; orange-red: 500-1,000 HU; deep red: >1,000 HU). The first row illustrates eccentric fragmented calcification: micro-CT demonstrates 2 distinct fragments that are less clearly resolved on clinical CT, particularly EID-CT due to blooming, whereas a focal low-attenuation region is better appreciated on PCD-CT and density maps. The second row shows concentric calcification: PCD-CT reduces overestimation and reveals intraplaque heterogeneity, with density maps suggesting a less dense component, which is not apparent on EID-CT. The third row demonstrates thin, “eggshell” calcification: PCD-CT shows closer agreement with micro-CT, with improved delineation of low-attenuation regions, whereas EID-CT appears more confluent. CCC = concordance correlation coefficient; CT = computed tomography; EDF = effective degrees of freedom; EID-CT = energy-integrating detector computed tomography; HU = Hounsfield unit; micro-CT = micro–computed tomography; PCD-CT = photon-counting detector computed tomography.
Discussion
In this cadaveric validation study using micro-CT as anear-histologic reference, PCD-CT demonstrated superior quantitative accuracy for coronary calcium assessment compared with EID-CT. Although both modalities systematically overestimated calcium measurements, PCD-CT significantly reduced measurement error and improved agreement.
We also observed proportional bias, with increasing overestimation in larger and denser plaques, likely reflecting expansion of blooming arti-facts; this effect was attenuated with PCD-CT. In addition, PCD-CT demonstrated a more stable and predictable relationship between calcium density and measurement error. Lower mean attenuation values observed with PCD-CT may reflect improved photon energy resolution, reduced beam-hardening effects, and enhanced detection of mixed plaque composition (Figure 1E). Although these findings are hypothesis-generating, the observed differences in attenuation and measurement error behavior be-tween the 2 CT modalities highlight the need for further studies evaluating threshold-based classification for calcium scoring and plaque segmentation in the PCD-CT era.
Our results suggest that PCD-CT may enable more accurate characterization of calcified lesions(Figure 1E), particularly in complex plaques, with potential to improve prediction of lesion behavior during percutaneous coronary intervention and inform the need for advanced calcium modification techniques, while also enhancing assessment of stenosis severity and its downstream clinical implications.[10] Despite these advances, it could not fully resolve heterogeneous or fragmented calcium structures observed on micro-CT, underscoring inherent resolution constraints. Future work integrating spatial and density-based plaque characterization may provide additional insights beyond conventional calcium quantification.
Several limitations should be acknowledged. First, measurements may be influenced by operator-dependent segmentation and window settings, although interobserver agreement was excellent and standardized methods were applied. Second, imaging was performed without intraluminal contrast, as this is not feasible with micro-CT, limiting lumen assessment and evaluation of potential incremental benefits of PCD-CT in contrast-enhanced settings; however, this is less likely to materially affect comparative calcium measurements. Third, the ex vivo design does not account for in vivo factors such as motion, contrast dynamics, or surrounding tissues. Fourth, noncalcified plaque was not evaluated, and the impact of virtual monoenergetic image reconstruction at different energy levels warrants further study. Finally, the sample size was modest, particularly for volumetric analyses.
PCD-CT significantly reduces overestimation of coronary calcium compared with EID-CT, achieving approximately 60% lower measurement error relative to micro-CT. Although the observed attenuation of size-dependent proportional bias and the more stable measurement behavior across HU values with PCD-CT are hypothesis-generating, PCD-CT demonstrated greater accuracy, supporting its potential clinical advantage in evaluating heavily calcified coronary lesions.

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