Risk stratification using coronary artery calcium scoring based on low tube voltage computed tomography

To determine if coronary artery calcium (CAC) scoring using computed tomography at 80 kilovolt-peak (kVp) and 70-kVp and tube voltage-adapted scoring-thresholds allow for accurate risk stratification as compared to the standard 120-kVp protocol. We prospectively included 170 patients who underwent standard CAC scanning at 120-kVp and 200 milliamperes and additional scans with 80-kVp and 70-kVp tube voltage with adapted tube current to normalize image noise across scans. Novel kVp-adapted thresholds were applied to calculate CAC scores from the low-kVp scans and were compared to those from standard 120-kVp scans by assessing risk reclassification rates and agreement using Kendall’s rank correlation coefficients (Τb) for risk categories bounded by 0, 1, 100, and 400. Interreader reclassification rates for the 120-kVp scans were assessed. Agreement for risk classification obtained from 80-kVp and 70-kVp scans as compared to 120-kVp was good (Τb = 0.967 and 0.915, respectively; both p < 0.001) with reclassification rates of 7.1% and 17.2%, respectively, mostly towards a lower risk category. By comparison, the interreader reclassification rate was 4.1% (Τb = 0.980, p < 0.001). Reclassification rates were dependent on body mass index (BMI) with 7.1% and 13.6% reclassifications for the 80-kVp and 70-kVp scans, respectively, in patients with a BMI < 30 kg/m2 (n = 140), and 2.9% and 7.4%, respectively, in patients with a BMI < 25 kg/m2 (n = 68). Mean effective radiation dose from the 120-kVp, the 80-kVp, and 70-kVp scans was 0.54 ± 0.03, 0.42 ± 0.02, and 0.26 ± 0.02 millisieverts. CAC scoring with reduced tube voltage allows for accurate risk stratification if kVp-adapted thresholds for calculation of CAC scores are applied

Non-Invasive Assessment of Endothelial Shear Stress in Myocardial Bridges Using Coronary Computed Tomography Angiography

Myocardial bridging (MB) is a segment of coronary arteries with an intramural course, typically spared from atherosclerosis, while the adjacent proximal segment is reported to be atherosclerosis-prone, a phenomenon contributed to local endothelial shear stress (ESS). We aimed to describe the ESS milieu in coronaries with MBs combining coronary computed tomography angiography with computational fluid dynamics and to investigate the association of atherosclerosis presence proximal to MBs with hemorheological characteristics. Patients (n = 36) were identified and 36 arteries with MBs (11 deep and 25 superficial) were analyzed. ESS did not fluctuate 5 mm proximally to MBs vs 5 mm within MBs (0.94 vs 1.06 Pa, p = .56). There was no difference when comparing ESS in the proximal versus mid versus distal MB segments (1.48 vs 1.37 vs 1.9 Pa, p = ns). In arteries with plaques (n = 12), no significant ESS variances were observed around the MB entrance, when analyzing all arteries (p = .81) and irrespective of morphological features of the bridged segment (deep MBs; p = .65, superficial MBs; p = .84). MBs are characterized by homogeneous, atheroprotective ESS, possibly explaining the absence of atherosclerosis within bridged segments. The interplay between ESS and atherosclerosis is potentially not different in arteries with MB compared with arteries without bridges

Long-term impact of myocardial inflammation on quantitative myocardial perfusion-a descriptive PET/MR myocarditis study.

PURPOSE Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. METHODS Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18). RESULTS Compared to remote segments, healed segments showed higher stress MBF (2.71 mL*min-1*g-1 [IQR 2.18-3.08] vs. 2.20 mL*min-1*g-1 [1.75-2.68], p < 0.0001), MFR (3.78 [2.83-4.79] vs. 3.36 [2.60-4.03], p < 0.0001), and washout (rest 0.24/min [0.18-0.31] and stress 0.53/min [0.40-0.67] vs. 0.22/min [0.16-0.27] and 0.46/min [0.32-0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE. CONCLUSION In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation. CMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement

Long-term impact of myocardial inflammation on quantitative myocardial perfusion-a descriptive PET/MR myocarditis study

PURPOSE Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. METHODS Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18). RESULTS Compared to remote segments, healed segments showed higher stress MBF (2.71 mL*min$^{-1}$*g$^{-1}$ [IQR 2.18-3.08] vs. 2.20 mL*min$^{-1}$*g$^{-1}$ [1.75-2.68], p < 0.0001), MFR (3.78 [2.83-4.79] vs. 3.36 [2.60-4.03], p < 0.0001), and washout (rest 0.24/min [0.18-0.31] and stress 0.53/min [0.40-0.67] vs. 0.22/min [0.16-0.27] and 0.46/min [0.32-0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE. CONCLUSION In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation. CMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement

Splenic switch-off as a predictor for coronary adenosine response: validation against 13N-ammonia during co-injection myocardial perfusion imaging on a hybrid PET/CMR scanner

BACKGROUND Inadequate coronary adenosine response is a potential cause for false negative ischemia testing. Recently, the splenic switch-off (SSO) sign has been identified as a promising tool to ascertain the efficacy of adenosine during vasodilator stress cardiovascular magnetic resonance imaging (CMR). We assessed the value of SSO to predict adenosine response, defined as an increase in myocardial blood flow (MBF) during quantitative stress myocardial perfusion 13 N-ammonia positron emission tomography (PET). METHODS We prospectively enrolled 64 patients who underwent simultaneous CMR and PET myocardial perfusion imaging on a hybrid PET/CMR scanner with co-injection of gadolinium based contrast agent (GBCA) and 13N-ammonia during rest and adenosine-induced stress. A myocardial flow reserve (MFR) of  > 1.5 or ischemia as assessed by PET were defined as markers for adequate coronary adenosine response. The presence or absence of SSO was visually assessed. The stress-to-rest intensity ratio (SIR) was calculated as the ratio of stress over rest peak signal intensity for splenic tissue. Additionally, the spleen-to-myocardium ratio, defined as the relative change of spleen to myocardial signal, was calculated for stress (SMR$_{stress}$) and rest. RESULTS Sixty-one (95%) patients were coronary adenosine responders, but SSO was absent in 18 (28%) patients. SIR and SMR$_{stress}$ were significantly lower in patients with SSO (SIR: 0.56 ± 0.13 vs. 0.93 ± 0.23; p < 0.001 and SMR$_{stress}$: 1.09 ± 0.47 vs. 1.68 ± 0.62; p < 0.001). Mean hyperemic and rest MBF were 2.12 ± 0.68 ml/min/g and 0.78 ± 0.26 ml/min/g, respectively. MFR was significantly higher in patients with vs. patients without presence of SSO (3.07 ± 1.03 vs. 2.48 ± 0.96; p = 0.038), but there was only a weak inverse correlation between SMR$_{stress}$ and MFR (R = -0.378; p = 0.02) as well as between SIR and MFR (R = -0.356; p = 0.004). CONCLUSIONS The presence of SSO implies adequate coronary adenosine-induced MBF response. Its absence, however, is not a reliable indicator for failed adenosine-induced coronary vasodilatation

Non-Invasive Assessment of Endothelial Shear Stress in Myocardial Bridges Using Coronary Computed Tomography Angiography.

Myocardial bridging (MB) is a segment of coronary arteries with an intramural course, typically spared from atherosclerosis, while the adjacent proximal segment is reported to be atherosclerosis-prone, a phenomenon contributed to local endothelial shear stress (ESS). We aimed to describe the ESS milieu in coronaries with MBs combining coronary computed tomography angiography with computational fluid dynamics and to investigate the association of atherosclerosis presence proximal to MBs with hemorheological characteristics. Patients (n = 36) were identified and 36 arteries with MBs (11 deep and 25 superficial) were analyzed. ESS did not fluctuate 5 mm proximally to MBs vs 5 mm within MBs (0.94 vs 1.06 Pa, p = .56). There was no difference when comparing ESS in the proximal versus mid versus distal MB segments (1.48 vs 1.37 vs 1.9 Pa, p = ns). In arteries with plaques (n = 12), no significant ESS variances were observed around the MB entrance, when analyzing all arteries (p = .81) and irrespective of morphological features of the bridged segment (deep MBs; p = .65, superficial MBs; p = .84). MBs are characterized by homogeneous, atheroprotective ESS, possibly explaining the absence of atherosclerosis within bridged segments. The interplay between ESS and atherosclerosis is potentially not different in arteries with MB compared with arteries without bridges

Myocardial creep-induced misalignment artifacts in PET/MR myocardial perfusion imaging

PURPOSE Misalignment between positron emission tomography (PET) datasets and attenuation correction (AC) maps is a potential source of artifacts in myocardial perfusion imaging (MPI). We assessed the impact of adenosine on the alignment of AC maps derived from magnetic resonance (MR) and PET datasets during MPI on a hybrid PET/MR scanner. METHODS Twenty-eight volunteers underwent adenosine stress and rest 13N-ammonia MPI on a PET/MR. We acquired Dixon sequences for the creation of MRAC maps. After reconstruction of the original non-shifted PET images, we examined MRAC and PET datasets for cardiac spatial misalignment and, if necessary, reconstructed a second set of shifted PET images after manually adjusting co-registration. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were compared between shifted and non-shifted PET images. Additionally, we measured the amount of cranial movement of the heart (i.e., myocardial creep) after termination of adenosine infusion. RESULTS Realignment was necessary for 25 (89.3%) stress and 12 (42.9%) rest PET datasets. Median SRS, SSS, and SDS of the non-shifted images were 6 (IQR = 4-7), 12 (IQR = 7-18), and 8 (IQR = 2-11), respectively, and of the shifted images 2 (IQR = 1-6), 4 (IQR = 7-18), and 1 (IQR = 0-2), respectively. All three scores were significantly higher in non-shifted versus shifted images (all p < 0.05). The difference in SDS correlated moderately but significantly with the amount of myocardial creep (r = 0.541, p = 0.005). CONCLUSION Misalignment of MRAC and PET datasets commonly occurs during adenosine stress MPI on a hybrid PET/MR device, potentially leading to an increase in false-positive findings. Our results suggest that myocardial creep may substantially account for this and prompt for a careful review and correction of PET/MRAC data

Coronary artery lumen volume index as a marker of flow-limiting atherosclerosis-validation against 13 N-ammonia positron emission tomography

Objectives: Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), has been proposed as an indicator of diffuse atherosclerosis. We investigated the association of CAVi with quantitative flow parameters and its ability to predict ischemia as derived from 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI). Methods: Sixty patients who underwent hybrid CCTA/PET-MPI due to suspected CAD were retrospectively included. CAVi was defined as total coronary artery lumen volume over myocardial mass, both derived from CCTA. From PET-MPI, quantitative stress and rest myocardial blood flow (MBF) and myocardial flow reserve (MFR) were obtained and correlated with CAVi, and semi-quantitative perfusion images were analyzed for the presence of ischemia. Harrell's c-statistic and net reclassification improvement (NRI) analysis were performed to evaluate the incremental value of CAVi over the CCTA model (i.e., stenosis > 50% and > 70%). Results: CAVi correlated moderately with stress MBF and MFR (R = 0.50, p 20.2 mm3/g, n = 36) CAVi (p < 0.001 for both comparisons). CAVi was independently associated with abnormal stress MBF (OR 0.90, 95% CI 0.82-0.998, p = 0.045). CAVi increased the predictive ability of the CCTA model for abnormal stress MBF and ischemia (c-statistic 0.763 versus 0.596, pdiff < 0.05 and 0.770 versus 0.645, pdiff < 0.05, NRI 0.84, p = 0.001 and 0.96, p < 0.001, respectively). Conclusions: CAVi exhibits incremental value to predict both abnormal stress MBF and ischemia over CCTA alone. Key points: • Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), is correlated with myocardial blood flow indices derived from 13N-ammonia positron emission tomography myocardial perfusion imaging. • CAVi is independently associated with abnormal stress myocardial blood flow. • CAVi provides incremental diagnostic value over CCTA for both abnormal stress MBF and ischemia. Keywords: Computed tomography angiography; Myocardial ischemia; Positron emission tomograph