492 patients from 3 centers performing hybrid PET/CT or SPECT/CT were studied. Institutional review board approval or waiver was obtained at each site. Each patient had received both an MPI study with CTAC and a separate CAC scan performed on the same day. Each CTAC scan was visually assessed by two independent readers at each site and graded on a six point scale, to estimate the extent of CAC. AS was determined for each CAC scan and reclassified on the same scale. Agreement between visually-estimated coronary artery calcium (VECAC) scores and Agatston scores was determined using weighted kappa statistics and percentage agreements, as was inter-reader reproducibility of VECAC scores.
PET/CT and SPECT/CT scanning
At Columbia University Medical Center (116 women, 81 men), each patient was scanned using a Philips Precedence 16P SPECT/CT scanner. CTAC scans were performed free breathing without ECG-gating, in spiral mode with pitch 0.94, collimation 16×1.5 mm, scan length 14 mm, tube voltage 120 kVp, and effective mAs 50, adjusted by the technologist according to patient habitus. Typical dose-length-product was 75 mGy·cm, corresponding to estimated effective dose of 1.3 mSv.(2
) CAC scans were performed using an end-inspiratory breath hold with ECG-gating, axial mode, collimation 8×3.0 mm, scan length 14 cm, tube voltage 120 kVp, and effective mAs 70, on rare occasions increased by the technologist to reflect patient body habitus. Typical dose-length-product was 58 mGy·cm, corresponding to estimated effective dose of 1.0 mSv.
At Mid America Heart (111 women, 75 men), each patient was scanned using a Siemens Biograph 16 PET/CT scanner. Post-stress CTAC scans were performed using a light end-expiratory breath hold without ECG-gating, spiral mode with pitch 2, collimation 16×0.75 mm, tube voltage 120 kVp, effective mAs 9, and typical dose-length-product 15 mGy·cm, corresponding to estimated effective dose 0.3 mSv. CAC scans were performed using an extended craniocaudal scan also used for rest attenuation correction. This used an end-expiratory breath hold with ECG-gating, spiral mode with pitch 0.28, collimation 16×1.5 mm, tube voltage 120 kVp, effective mAs ~220 mAs adjusted by the technologist to reflect patient habitus, and typical dose-length-product 278 mGy·cm, corresponding to estimated effective dose 4.7 mSv.
At Cedars-Sinai (50 women, 59 men), each patient was scanned using a Siemens Biograph 64 PET/CT scanner. CTAC scans were performed free breathing without ECG-gating, spiral mode with pitch 1.5, collimation 24×1.2 mm, tube voltage 120 kVp, effective mAs 11, and typical dose-length product 16 mGy·cm, corresponding to estimated effective dose 0.3 mSv. CAC scans were performed using an end-inspiratory breath hold with prospective ECG-gating, collimation 30×0.6 mm, tube voltage 120 kVp, effective mAs 150, and typical dose-length-product 173 mGy·cm, corresponding to estimated effective dose 2.9 mSv.
Analysis of CT Scans
At each site, AS was determined using standard methodology on a dedicated workstation. At each site, two experienced readers blinded to the AS independently reviewed CTAC images and visually estimated CAC on a six level scale, classifying patients as having estimated AS of 0, 1-9, 10-99, 100-300, 400-999, or ≥1000. In addition, a single reader from the Mid America Heart and Cedars-Sinai sites each blindedly visually estimated CAC on 99 scans from Columbia University Medical Center. For the first 20 cases, readers were given post hoc feedback as to the correct classification based on the AS. Each reader also visually evaluated each CTAC scan for the presence or absence of calcium in each of the major coronary arteries (left main, left anterior descending (LAD), circumflex, and right coronary artery).
Since systematically missing a proximal LAD lesion may have important clinical implications, a subsequent analysis was performed in one center (Columbia) of cases with a discrepancy between visual assessment of LAD calcium on CTAC images, by either reader, and its measurement (0 or >0) on the CAC images, to determine the location in the vessel of the erroneous visual estimation. This was performed by a single reader who visually inspected the LAD of discrepant cases and classified calcium as being present or absent in the proximal, mid, and/or distal vessel. Analysis was performed on separate days for the CTAC and CAC images, with images being presented in random order on each day and the reader blinded to classifications from previous reading sessions.
Effect on Interpretation of Borderline MPI Scans
One use of the AS in hybrid imaging can be to provide an additional source of information to assist in interpretation of borderline MPI scans. For example, for a borderline, nonextensive perfusion defect, some readers will call the MPI study “probably normal” in the absence of coronary calcium, but report the perfusion defect in the presence of coronary calcium. Thus, inaccuracy of VECAC in estimating the AS could potentially lead not only to inaccurate characterization of coronary calcium, but also to inaccurate characterization of myocardial perfusion. To assess the effect of VECAC on MPI interpretation in such borderline scans, in one center (Columbia), we reassessed MPI in all scans which had been read as having a rest or stress perfusion defect in 1-3 segments of the AHA 17-segment model, none of which were described as a “severe” defect. MPI scans were read independently by each reader on 3 separate days, presented in random order on each occasion. On the first day, each reader read the MPI scan, using the 17-segment model. On the second day, each reader was presented with the MPI images, their original interpretation of these images, and the CAC scan images, and asked to reinterpret the MPI images in this context. The third reading day was analogous to the second day, except that CTAC scan images were presented rather than CAC scan images.
Agreement between VECAC on the CTAC scan and AS, measured on the standard CAC scan and converted to the same six-level scale, was determined using quadratic-weighted kappa statistics, with 95% confidence intervals (CIs) estimated using bootstrap with 1000 replications. Agreement between readers in VECAC was similarly assessed using quadratic weighted kappa statistics. Vessel-based analysis was performed by evaluating the proportion of segments with correct identification of calcium on the CTAC scan and associated standard kappa scores. Statistical analysis was performed using Stata 10.1 (StataCorp, College Station, TX).