Purpose: To assess the clinical feasibility of automated segmentation of the myocardial area at risk (MAAR) using coronary computed tomography angiography (CT-MAAR), as compared to stress magnetic resonance myocardial perfusion imaging (MR-MPI). Materials and Methods: Thirty patients who underwent coronary computed tomography angiography (CTA) and stress MR-MPI were retrospectively evaluated. The myocardial territory of the left ventricle (LV) distal to coronary artery stenosis (≥50% or ≥70% stenosis on coronary CTA) was three-dimensionally quantified using a Voronoi diagram. The ratio of all stenosis-related territories to the LV volume was defined as CT-MAAR (%-LV volume). The proportion of segments with perfusion defects in stress MR-MPI to the total of 16 segments (range: 0% - 100%; with a 6.3%-interval scale) was defined as the reference. Correlation was assessed using Spearman’s test. The capability of CT-MAAR to predict the ischemic burden was assessed. Results: Stress MR-MPI depicted a median ischemic burden of 25.2% (range: 18.9% - 44.1%) in 30 patients without myocardial infarction. When CTA stenosis criteria of ≥50% (n = 30) and ≥70% (n = 27) were applied to estimate CT-MAAR, the median CT-MAAR values were 48.2% (31.6% - 64.3%) and 32.5% (23.7% - 51.9%), respectively. The correlations between the CT-MAAR values and the MR-based ischemic burden were significant (0.73 and 0.97 for ≥50% and ≥70% stenosis, respectively). CT-MAAR predicted the MR-based ischemic burden within ±1 segment of %-LV (6.3%) in 40% (12/30) of patients with ≥50% stenosis, and in 81.5% (22/27) of patients with ≥70% stenosis. Conclusions: Comprehensive assessment of resting coronary CTA combined with Voronoi diagram-based myocardial segmentation may help predict the myocardial ischemic burden in patients with severe coronary CTA stenosis.
Coronary computed tomography angiography (CTA) is widely used in clinical practice for assessing obstructive coronary artery disease (CAD), because of its high sensitivity and negative predictive value [
Furthermore, the Voronoi diagram is a type of centerline method that divides space (i.e., volume) by seeded points or lines [
This retrospective observational study was approved by the local ethics committee (clinical research 1509002). The need for informed consent was waived because of the retrospective nature of the study. From June 2009 to March 2016, we retrospectively collected the records of 91 consecutive patients who underwent coronary CTA and stress MR-MPI within an interval of less than 6 months. All patient information was protected in compliance with the guidelines provided by the institutional review board. The flow chart for patient selection is shown in
We used a 256-slice (128 multi-detector row) CT (Brilliance iCT; Philips Healthcare, Cleveland, OH, USA) and an automatic dual-head injector (Stellant Dual Flow; Nihon MEDRAD K.K., Osaka, Japan). All patients received 1.2 mg (i.e., 2 puffs) of sublingual nitroglycerin (Myocor spray; Astellas Pharma, Tokyo, Japan). For patients with a resting heart rate of more than 60 beats/min, an intravenous beta-blocker (0.125 mg/kg of landiolol hydrochloride, Corebeta; Ono Pharmaceutical Co., Osaka, Japan) was administered 5 min before the timing-bolus scan, to reduce the heart rate. Coronary CTA was performed with iohexol (Omnipaque; 350 mg iodine/mL; Daiichi Sankyo, Tokyo, Japan) or with iopamidol (Iopamiron; 370 mg iodine/mL; Bayer Yakuhin, Osaka, Japan) at an injection rate of 5.0 - 5.5 mL/s for 10 s, followed by a saline chaser (20 mL, 5.0 - 5.5 mL/s). The scan parameters were as follows: retrospective electrocardiogram- gated mode (heart rate >60 beats/min) or prospective electrocardiogram-gated mode (heart rate ≤60 beats/min); tube voltage, 120 kV; effective tube current time-product, 800 - 1300 mAs/rotation with dose modulation; gantry rotation
time, 0.27 s/rotation; collimation, 2 × 128 × 0.625 mm with a dynamic z-focal spot; 250-mm display field of view; 0.8/0.4-mm slice thickness/overlap; and 512 × 512 image matrix. Image reconstruction was performed individually to reduce motion artifacts, with 0.8-mm slice thickness and 0.4-mm intervals using hybrid iterative reconstruction (iDose4 level 4; Philips Healthcare, Cleveland, OH, USA) and a medium-smooth cardiac kernel.
We used a 3-T MR system (Achieva 3.0 T Quasar Dual; Philips Healthcare, Cleveland, OH, USA) equipped with a 32-element cardiac phased-array coil. Using an established comprehensive cardiac MR protocol [
ICA was performed following the standard institutional catheterization approach. Quantitative coronary analysis was performed by an independent cardi- ologist (T.U., 15 years of experience), who was blinded to other results, using commercially available software (CAAS5.9; Pie Medical Imaging, Maastricht, the Netherlands). Coronary artery stenosis ≥50% and ≥70% were considered as significant and obstructive CAD, respectively. When multiple stenoses were seen in two or more segments, the proximal stenosis was defined as the culprit stenosis. All coronary artery segments and stenotic lesions (≥50% stenosis) were classified by the main coronary vessels: the left anterior descend- ing artery (LAD), including diagonal branches, the left circumflex artery (LCX), including the high lateral branch and ramus intermedius, and the right coronary artery (RCA), based on the American Heart Association guidelines [
The 16-segment model, excluding the apex, was applied [
All CTA images were evaluated by two observers (Y.T. and T.Y., who had 4 years and 2 years of experience in cardiac CT, respectively) using a commercially available workstation (Aquarius intuition; TERARECON, Inc., Tokyo, Japan). First, an overall assessment of image quality was performed at the subject level to assess misalignment of the coronary arteries between the slabs and discontinuity of coronary vessels due to motion artifacts and arrhythmia. If any of the aforementioned requirements were unsuitable, the patient was excluded from the study. Using a single dataset of coronary CTA with sufficient image quality, stenosis severity per segment was semiquantitatively assessed using the standard guidelines for reporting coronary CTA [
The same two observers evaluated the coronary CTA-based myocardial territory using dedicated software (TVA; TERARECON Inc. Tokyo, Japan). Post- pro- cessing of Voronoi diagram-based myocardial segmentation using coronary CTA was shown in
For this study, the stenosis-related CT myocardial territory was quantified at both levels of stenosis (≥50% and ≥70% on coronary CTA). The discrepancies of the stenosis-related CT myocardial territories were individually reviewed and
solved by consensus. The two sums of all stenosis-related CT myocardial territories (i.e., the ratio of the LV volume at risk to the whole LV volume) were calculated using the two standards of the CTA stenosis (≥50% and ≥70%) as significant and obstructive CTA stenosis-based CT-MAAR, respectively.
Categorical variables were expressed as proportions and continuous variables were Altman plotting expressed as the mean ± the standard deviation or as the median (interquartile range), as appropriate. With regard to coronary CTA stenosis severity and the stenosis-related CT myocardial territory for stenotic lesions ≥50%, the intra- and inter-observer reproducibility of the two operators were assessed using Spearman’s test and Bland-Altman plotting.
Correlations between CTA-based MAAR and MR-based ischemic burden were evaluated with Spearman’s test. The ability of CTA-based MAAR to estimate the MR-based ischemic burden within ±6.3%, corresponding to a single segment of the LV (100/16 = 6.3) in the assessment of MR-based ischemia, was calculated. All analyses were performed using JMP version 11 (SAS Institute, Cary, NC, USA). For all analyses, p < 0.05 was significant.
Of the 50 patients, 20 were excluded for the following reasons: no ICA (n = 6), previous revascularization therapy (CABG, n = 1; PCI, n = 5), valvular heart disease (n = 3), cardiomyopathy (n = 2), total coronary artery occlusion (n = 2), and poor image quality on MR-MPI (n = 1) or on coronary CTA (n = 1). Thirty patients were finally analyzed (24 men and 6 women; mean age, 67.5 ± 7.9 years). The patient characteristics are listed in
A total of 438 segments were assessed. The intra- and inter-observer agreement for the semiquantitative assessment of stenotic severity on coronary CTA was 0.71 and 0.67, respectively. The by-consensus diagnosis per segment was as follows: non-CAD stenosis (n = 361), moderate stenosis (n = 30), severe stenosis (n = 28), occluded lesions (n = 3), and unassessable calcified segments (n = 16). When using the CTA stenosis criterion of ≥50%, 77 lesions in30 patients met the criteria for significant CTA-based MAAR. However, when using the CTA stenosis criterion of ≥70%, 47 lesions in 27 patients met the criteria for obstructive CTA-based MAAR.
Seventy-seven coronary CTA lesions with a stenosis of ≥50% were assessed. Voronoi-based segmentation was successfully performed for all lesions. The respesentati ve for Compute cases are shown in
N = 30 | |
---|---|
Male/female | 24 (80.0%)/6 (20.0%) |
Age (years) | 67.5 ± 7.9 |
Hypertension | 13 (43.3%) |
Hyperlipidemia | 14 (46.7%) |
Diabetes mellitus | 8 (26.7%) |
Smoking | 12 (40.0%) |
Family history of CAD | 8 (26.7%) |
Time between coronary CTA and MR-MPI (days) | 29 (11.5 - 49) |
Calcium score (Agatston score) | 405.4 (95.4 - 1031.8) |
*Number of diseased vessels confirmed with ICA | 46/90 |
*Single-vessel disease | 16 |
*Double-vessel disease | 12 |
*Triple-vessel disease | 2 |
CAD = coronary artery disease; CTA = computed tomography angiography; MR-MPI = magnetic resonance myocardial perfusion imaging; ICA = invasive coronary angiography; presented as N (%), mean ± SD or median (interquartile range), unless otherwise stated. *Invasive coronary angiography stenosis of ≥50% are significant stenosis.
inter-observer agreements of the significant CTA-related myocardial territories were 0.99 and 0.99, respectively. The mean differences for intra- and inter-ob- server measurements of CT-based MAAR were 0.004% (95% confidence interval [CI], −0.053% to 0.045%) and −0.003 (95% CI, −0.030% to 0.024%), respectively.
Using the standard of ≥50% CTA stenosis, the median value of significant CTA-based MAAR was 48.2% (range: 31.6% - 64.3%). Marked CTA stenosis- based CT-MAAR correlated with MR-based ischemic burden statistically significantly (r = 0.73; p < 0.001) (
burden as assessed with MR to within ±6.3% in 40% (12/30) of patients, but overestimated the area at risk by 6.3% in 60% (18/30) patients.
Using the standard of ≥70% CTA stenosis, the median value of obstructive CTA stenosis-based CT-MAAR was 32.5% (range: 23.7% - 51.9%). The correlation between obstructive CTA stenosis-based CT-MAAR and MR-based ische- mic burden was statistically significant (r = 0.97, p < 0.001) (
In this study, we showed that: 1) the reproducibility of the procedural steps for assessment of the CTA-based MAAR was good, and that 2) severe coronary CTA stenosis-based MAAR more accurately estimated the MR-based myocardial ischemic burden than did moderate stenosis.
Stress MR-MPI has been established as a useful diagnostic tool for detecting obstructive CAD [
By using a Voronoi diagram, CTA-based myocardial segmentation can indicate the theoretical maximum potential myocardial territory to a seeded point on the coronary CT angiogram. A recent study has demonstrated the high reproducibility of CTA-based LV myocardial territory and the good correlation of CT- based MAAR with SPECT-based MAAR [
Some researchers have reported clinical application of Voronoi diagrams in cardiovascular imaging [
We considered that the CTA stenosis-based CT MAAR might contain some artificial post-processing. The study evaluated the intra- and inter-observer agreements of the CTA stenosis semi-quantification and (0.71 and 0.67, respectively) and those of the stenosis-related myocardial segmentation (0.99 and 0.99, respectively). These may indicate that the former ispotentially variable, while the stenosis-based myocardial segmentation on CT scans is highly reproducible, although the region of interest for coronary CTA stenosis was manually placed. A previous study reported the relationship between the extent of the severity of coronary artery stenosis on CT to myocardial ischemia as assessed with stress SPECT-MPI [
The present study has several limitations. First, the study population was relatively small. Second, stress MR-MPI as a reference was obtained with three cardiac short axial images, assessed using a conventional 16-segment model (excluding the apex), with a step-formed ordinal scale per 6.3%, independent from the morphological volume-based or the transmural extent-based evaluation. It is to be noted that these differences between CT-MAAR and stress MR-MPI might potential place a limitation on the evaluation of CT-MAAR in the study. Third, this study excluded patients with myocardial infarction because a myocardial scar may influence the quantification of CT-MAAR, by affecting the volumetric estimation of CT-MAAR, and the true extent of myocardial ischemia. Fourth, the CT-MAAR was estimated based on the anatomical location of coronary stenosis, independent of whether the lesion was diagnosed as hemodynamically significant. Fifth, the precision of the ischemic burden in stress MR-MPI was not objectively validated on anatomical territory that corresponded to coronary artery stenosis. Further studies with a large number of patients will be required to clarify the significance of these findings in clinical practice.
Voronoi diagram-based myocardial segmentation has the potential for predicting the MAAR in patients with obstructive coronary stenosis on CTA. The estimation of MAAR using resting coronary CTA may provide useful information in clinical decision-making.
Fukuyama, N., Kido, T., Kurata, A., Tanabe, Y., Kido, T., Yokoi, T., Ogawa, R., Nishiyama, H., Uetani, T. and Mochizuki, T. (2017) Myocardial Segmentation of Area at Risk Based on Coronary Computed Tomography Angiography and Voronoi Diagram in Comparison with Magnetic Resonance Perfusion Imaging. Open Journal of Radiology, 7, 9- 22. https://doi.org/10.4236/ojrad.2017.71002