Toshiro Kitagawa

Prospective versus Retrospective ECG-gated 64-Detector Coronary CT Angiography: Assessment of Image Quality, Stenosis, and Radiation Dose

PURPOSE To show that prospective electrocardiographically (ECG)-triggered coronary computed tomographic (CT) angiography (hereafter, prospective CT angiography) is at least as effective as retrospective ECG-gated coronary CT angiography (hereafter, retrospective CT angiography). MATERIALS AND METHODS Institutional review committee approval and informed consent were obtained. Sixty patients with heart rates of less than 75 beats per minute who were referred for coronary CT angiography were enrolled. Both prospective and retrospective CT angiography were performed with a 64-detector scanner. Data acquisition times were recorded. Two independent cardiac radiologists evaluated subjective image quality (1, excellent; 4, poor) and severity of stenosis (0% occlusion, 1%-49% occlusion, 50%-75% occlusion, and >75% occlusion) with the 17-segment American Heart Association classification model. Discrepancies were settled by consensus. Effective radiation doses of prospective and retrospective CT angiography were calculated with volume CT dose index. Data regarding acquisition time and radiation exposure for prospective and retrospective CT angiography were compared. The Student t test was performed, and kappa statistics were calculated. RESULTS Mean data acquisition time of prospective CT angiography was shorter than that of retrospective CT angiography (5.6 seconds +/- 1.1 [standard deviation] vs 6.7 seconds +/- 1.1, respectively; P < .01). Consensus-determined image quality in coronary artery branches was similar between prospective CT angiography and retrospective CT angiography (1.15 vs 1.13, respectively; P = .992). Excellent agreement between prospective CT angiography and retrospective CT angiography was observed in the detection of significant (>or=50% occlusion) coronary artery stenoses per segment (kappa = 0.882) and in the grading of stenoses per patient (kappa = 0.829). Calculated effective dose with prospective CT angiography was 79% lower than that with retrospective CT angiography (4.1 mSv +/- 1.8 vs 20.0 mSv +/- 3.5, respectively; P < .001). CONCLUSION Prospective CT angiography can reduce radiation dose below that of retrospective CT angiography with dose modulation, while maintaining image quality and the ability to assess luminal obstructions in patients with heart rates of less than 75 beats per minute.

Characterization of Noncalcified Coronary Plaques and Identification of Culprit Lesions in Patients With Acute Coronary Syndrome by 64-Slice Computed Tomography

OBJECTIVES We sought to characterize noncalcified coronary atherosclerotic plaques in culprit and remote coronary atherosclerotic lesions in patients with acute coronary syndrome (ACS) with 64-slice computed tomography (CT). BACKGROUND Lower CT density, positive remodeling, and adjacent spotty coronary calcium are characteristic vessel changes in unstable coronary plaques. METHODS Of 147 consecutive patients who underwent contrast-enhanced 64-slice CT examination for coronary artery visualization, 101 (ACS; n = 21, non-ACS; n = 80) having 228 noncalcified coronary atherosclerotic plaques (NCPs) were studied. Each NCP detected within the vessel wall was evaluated by determining minimum CT density, vascular remodeling index (RI), and morphology of adjacent calcium deposits. RESULTS The CT visualized more NCPs in ACS patients (65 lesions, 3.1 +/- 1.2/patient) than in non-ACS patients (163 lesions, 2.0 +/- 1.1/patient). Minimum CT density (24 +/- 22 vs. 42 +/- 29 Hounsfield units [HU], p < 0.01), RI (1.14 +/- 0.18 vs. 1.08 +/- 0.19, p = 0.02), and frequency of adjacent spotty calcium of NCPs (60% vs. 38%, p < 0.01) were significantly different between ACS and non-ACS patients. Frequency of NCPs with minimum CT density <40 HU, RI >1.05, and adjacent spotty calcium was approximately 2-fold higher in the ACS group than in the non-ACS group (43% vs. 22%, p < 0.01). In the ACS group, only RI was significantly different between 21 culprit and 44 nonculprit lesions (1.26 +/- 0.16 vs. 1.09 +/- 0.17, p < 0.01), and a larger RI (> or = 1.23) was independently related to the culprit lesions (odds ratio: 12.3; 95% confidential interval: 2.9 to 68.7, p < 0.01), but there was a substantial overlap of the distribution of RI values in these 2 groups of lesions. CONCLUSIONS Sixty-four-slice CT angiography demonstrates a higher prevalence of NCPs with vulnerable characteristics in patients with ACS as compared with stable clinical presentation.

Association between epicardial adipose tissue volume and characteristics of non-calcified plaques assessed by coronary computed tomographic angiography

BACKGROUND The aim of this study was to investigate whether high epicardial adipose tissue (EAT) volume is related to the presence of vulnerable coronary plaque components as assessed by computed tomography (CT). METHODS We evaluated 357 patients referred for 64-slice CT, and assessed coronary plaque components and EAT volume. Vulnerable coronary plaque components were defined as the presence of non-calcified plaque (NCP), including low-density plaque (LDP: <39 HU) and positive remodeling (PR: remodeling index>1.05). In accordance with a previous report, patients were assigned to two groups: low (<100 ml) or high (≥100 ml) EAT volume. RESULTS Compared to the low EAT volume group, the high EAT volume group had a higher prevalence of NCP (74% vs. 59%, p=0.003). Additionally, the high EAT volume group had a higher prevalence of LDP with PR than the low EAT volume group (46% vs. 25%, p<0.001). Interestingly, a high EAT volume was an independent predictor of LDP with PR (odds ratio 2.56, 95% confidence interval 1.38-4.85, p=0.003) after adjusting for age, gender, traditional cardiovascular risk factors, body mass index (BMI), abdominal visceral adipose tissue (VAT), and coronary artery calcium (CAC) scores. CONCLUSIONS A high EAT volume was associated with the presence of vulnerable plaque components, independent of obesity measurements (BMI and VAT) and CAC scores.

Association between visceral adipose tissue area and coronary plaque morphology assessed by CT angiography.

OBJECTIVES We sought to investigate the association between visceral adipose tissue (VAT) with the presence, extent, and characteristics of noncalcified coronary plaques (NCPs) using 64-slice computed tomography angiography (CTA). BACKGROUND Although visceral adiposity is associated with cardiovascular events, its association with NCP burden and vulnerability is not well known. METHODS The study population consisted of 427 patients (age 67 ± 11 years; 63% men) with proven or suspected coronary artery disease who underwent 64-slice CTA. We assessed the presence and number of NCPs for each patient. The extent of NCP was tested for the difference between high (≥ 2) and low (≤ 1) counts. We further evaluated the vulnerable characteristics of NCPs with positive remodeling (remodeling index >1.05), low CT density (≤ 38 HU), and the presence of adjacent spotty calcium. Plain abdominal scans were also performed to measure the VAT and subcutaneous adipose tissue area. RESULTS A total of 260 (61%) patients had identifiable NCPs. Multivariate analyses revealed that increased VAT area (per 1 standard deviation, 58 cm(2)) was significantly associated with both the presence (odds ratio [OR]: 1.68; 95% confidence interval [CI]: 1.28 to 2.22) and extent (OR: 1.31; 95% CI: 1.03 to 1.68) of NCP. Other body composition measures, including subcutaneous adipose tissue area, body mass index, and waist circumference were not significantly associated with either presence or extent of NCP. Increased VAT area was also independently associated with the presence of NCP with positive remodeling (OR: 1.71; 95% CI: 1.18 to 2.53), low CT density (OR: 1.69; 95% CI: 1.17 to 2.47), and adjacent spotty calcium (OR: 1.52; 95% CI: 1.03 to 2.27). CONCLUSIONS Increased VAT area was significantly associated with NCP burden and vulnerable characteristics identified by CTA. Our findings may explain the excessive cardiovascular risk in patients with visceral adiposity, and support the potential role of CTA to improve risk stratification in such patients.

Visceral fat accumulation as a predictor of coronary artery calcium as assessed by multislice computed tomography in Japanese patients

The impact of visceral adiposity on subclinical coronary atherosclerosis is unclear in Japanese patients. We investigated the sex-specific relationship between the amount of visceral fat and coronary artery calcium (CAC) using multislice computed tomography (MSCT). This is a cross-sectional study of 321 consecutive Japanese patients (213 men and 108 women) who underwent MSCT scanning for the examination of coronary heart disease. CAC score, visceral fat area (VFA), subcutaneous fat area (SFA), and waist circumference (WC) were determined by MSCT for all patients. The prevalence of detectable CAC was 73% and 57% in men and women, respectively. Using a multivariable logistic and ordinal regression analyses adjusting for traditional cardiovascular risk factors and adiposity measurements, VFA represented an independent predictor of the presence and extent of CAC (odds ratio (95% confidence interval) per one-unit-standard deviation increase in VFA: 2.48 (1.23-6.05) in logistic regression analysis; 2.05 (1.18-3.98) in ordinal regression analysis). Similar relationships were observed across the gender. We further assessed the sex-specific cut-off levels of VFA and WC to predict the presence of CAC. The results of receiver operator characteristic analysis indicated that the VFA cut-off level in men was 116cm(2); and in women, it was 82cm(2), corresponding to WC values of 87.7cm in men and 82.6cm in women. In conclusion, we found that visceral adiposity measured by MSCT is significantly associated with the presence and extent of CAC as a marker of subclinical atherosclerosis in Japanese patients.

Noncalcified atherosclerotic lesions with vulnerable characteristics detected by coronary CT angiography and future coronary events

BACKGROUND The ability of coronary CT angiography (CTA) findings such as plaque characteristics to predict future coronary events remains controversial. OBJECTIVE We investigated whether noncalcified atherosclerotic lesions (NCALs) detected by coronary CTA were predictive of future coronary events. METHODS A total of 511 patients who underwent coronary CTA were followed for cardiovascular events over a period of 3.3 ± 1.2 years. The primary end point was defined as hard events, including cardiac death, nonfatal myocardial infarction, or unstable angina that required urgent hospitalization. Early elective coronary revascularizations (n = 58) were excluded. The relationship between features of NCALs and outcomes is described. RESULTS A total of 15 hard events (2 cardiac deaths, 7 myocardial infarctions, 6 cases of unstable angina that required urgent hospitalization) were documented in the remaining 453 patients with modest risks during a follow-up period of 3.3 ± 1.2 years. For these hard events, a univariate Cox proportional hazard model showed that the hazard ratio for the presence of >50% stenosis was 7.27 (95% CI, 2.62-21.7; P = .0002). Although the presence of NCAL by itself was not statistically significant, NCALs with low attenuation and positive remodeling (low-attenuation plaque [LAP] and positive remodeling [PR]; plaque CT number ≤ 34 HU and remodeling index ≥ 1.20) showed an adjusted hazard ratio of 11.2 (95% CI, 3.71-36.7; P < .0001). With C-statistics analysis, when both LAP and PR and >50% stenosis were added, the C-statistic was significantly improved compared with the basal model adjusted for age, sex, and log2 (Agatston score +1) (0.900 vs 0.704; P = .0018). CONCLUSIONS Identification of NCALs with LAP and PR characteristics by coronary CTA provides additional prognostic information to coronary stenosis for the prediction of future coronary events.

Near Infrared Imaging and Photothermal Ablation of Vascular Inflammation Using Single-Walled Carbon Nanotubes

Background Macrophages are critical contributors to atherosclerosis. Single-walled carbon nanotubes (SWNTs) show promising properties for cellular imaging and thermal therapy, which may have application to vascular macrophages. Methods and Results In vitro uptake and photothermal destruction of mouse macrophage cells (RAW264.7) were performed with SWNTs (14.7 nmol/L) exposed to an 808-nm light source. SWNTs were taken up by 94±6% of macrophages, and light exposure induced 93±3% cell death. In vivo vascular macrophage uptake and ablation were then investigated in carotid-ligated FVB mice (n=33) after induction of hyperlipidemia and diabetes. Two weeks postligation, near-infrared fluorescence (NIRF) carotid imaging (n=12) was performed with SWNT-Cy5.5 (8 nmol of Cy5.5) given via the tail vein. Photothermal heating and macrophage apoptosis were evaluated on freshly excised carotid arteries (n=21). NIRF of SWNTs showed higher signal intensity in ligated carotids compared with sham, confirmed by both in situ and ex vivo NIRF imaging (P<0.05, ligation versus sham). Immunofluorescence staining showed colocalization of SWNT-Cy5.5 and macrophages in atherosclerotic lesions. Light (808 nm) exposure of freshly excised carotids showed heating and induction of macrophage apoptosis in ligated left carotid arteries with SWNTs, but not in control groups without SWNTs or without light exposure. Conclusions Carbon nanotubes accumulate in atherosclerotic macrophages in vivo and provide a multifunctional platform for imaging and photothermal therapy of vascular inflammation.

RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease

PurposeInflammation and angiogenesis are important contributors to vascular disease. We evaluated imaging both of these biological processes, using Arg–Gly–Asp (RGD)-conjugated human ferritin nanoparticles (HFn), in experimental carotid and abdominal aortic aneurysm (AAA) disease.ProceduresMacrophage-rich carotid lesions were induced by ligation in hyperlipidemic and diabetic FVB mice (n = 16). AAAs were induced by angiotensin II infusion in apoE−/− mice (n=10). HFn, with or without RGD peptide, was labeled with Cy5.5 and injected intravenously for near-infrared fluorescence imaging.ResultsRGD-HFn showed significantly higher signal than HFn in diseased carotids and AAAs relative to non-diseased regions, both in situ (carotid: 1.88 ± 0.30 vs. 1.17 ± 0.10, p = 0.04; AAA: 2.59 ± 0.24 vs. 1.82 ± 0.16, p = 0.03) and ex vivo. Histology showed RGD-HFn colocalized with macrophages in carotids and both macrophages and neoangiogenesis in AAA lesions.ConclusionsRGD-HFn enhances vascular molecular imaging by targeting both vascular inflammation and angiogenesis, and allows more comprehensive detection of high-risk atherosclerotic and aneurysmal vascular diseases.

Combined presence of aortic valve calcification and mitral annular calcification as a marker of the extent and vulnerable characteristics of coronary artery plaque assessed by 64-multidetector computed tomography

OBJECTIVE We examined the association of aortic valve calcification (AVC) and mitral annular calcification (MAC) to coronary atherosclerosis using 64-multidetector computed tomography (MDCT). BACKGROUND Valvular calcification is considered a manifestation of atherosclerosis. The impact of multiple heart valve calcium deposits on the distribution and characteristics of coronary plaque is unknown. METHODS We evaluated 322 patients referred for 64-MDCT, and assessed valvular calcification and the extent of calcified (CAP), mixed (MCAP), and noncalcified coronary atherosclerotic plaque (NCAP) in accordance with the 17-coronary segments model. We assessed the vulnerable characteristics of coronary plaque with positive remodeling, low-density plaque (CT density ≤38 Hounsfield units), and the presence of adjacent spotty calcification. RESULTS In 49 patients with both AVC and MAC, the segment numbers of CAP and MCAP were larger than in those with a lack of valvular calcification and an isolated AVC (p<0.001 for both). Multivariate analyses revealed that a combined presence of AVC and MAC was independently associated with the presence (odds ratio [OR] 9.36, 95% confidence interval [95%CI] 1.55-56.53, p=0.015) and extent (β-estimate 1.86, p<0.001) of overall coronary plaque. When stratified by plaque composition, it was associated with the extent of CAP (β-estimate 1.77, p<0.001) and MCAP (β-estimate 1.04, p<0.001), but not with NCAP. Moreover, it was also related to the presence of coronary plaque with all three vulnerable characteristics (OR 4.87, 95%CI 1.85-12.83, p=0.001). CONCLUSION The combined presence of AVC and MAC is highly associated with the presence, extent, and vulnerable characteristics of coronary plaque identified by 64-MDCT.

Variability of repeated coronary artery calcium measurements by 1.25-mm- and 2.5-mm-thickness images on prospective electrocardiograph-triggered 64-slice CT

High reproducibility on coronary artery calcium scoring is a key requirement in monitoring the progression of coronary atherosclerosis. The purpose of this prospective study is to assess the reproducibility of 1.25-mm- and 2.5-mm-thickness images on prospective electrocardiograph-triggered 64-slice CT with respect to 2.5-mm-thickness images on spiral overlapping reconstruction. One hundred patients suspected of coronary artery disease were scanned twice repeatedly, both on prospective electrocardiograph-triggered step-and-shoot and retrospective electrocardiograph-gated spiral scans. Using 1.25-mm-thickness collimation, 1.25-mm- and 2.5-mm-thickness image sets on prospective scans and 2.5-mm-thickness image sets with 1.25-mm increment (overlapping) on retrospective scans were obtained. Coronary artery calcium scores, interscan variability and interobserver variability were evaluated. The mean interscan variability in coronary artery calcium measurement on 1.25-mm prospective/2.5-mm prospective/2.5-mm overlapping retrospective scans were Agatston: 10%/18%/12%, volume: 10%/12%/10% and mass: 8%/13%/11% for observer 1 and Agatston: 8%/14%/10%, volume: 7%/9%/10% and mass: 7%/10%/9% for observer 2, respectively. The mean interobserver variability was 5% to 14%. In conclusion, prospective electrocardiograph-triggered 64-slice CT using the 1.25-mm prospective scan shows the lowest variability. The 2.5-mm prospective scan on volume or mass scoring shows variability of around 10%, comparable to 2.5-mm-thickness spiral overlapping reconstruction images.