Hemodynamic impact of coronary stenosis using computed tomography: comparison between noninvasive fractional flow reserve and 3D fusion of coronary angiography with stress myocardial perfusion.

Vasodilator-stress CT perfusion imaging in addition to CT coronary angiography (CTCA) may provide a single-test alternative to nuclear stress testing, commonly used to assess hemodynamic significance of stenosis. Another alternative is fractional flow reserve (FFR) calculated from cardiac CT images. We studied the concordance between these two approaches and their relationship to outcomes. We prospectively studied 150 patients with chest pain, who underwent CTCA and regadenoson CT. CTCA images were interpreted for presence and severity of stenosis. Fused 3D displays of subendocardial X-ray attenuation with coronary arteries were created to detect stress perfusion defects (SPD) in each coronary territory. In patients with stenosis > 25%, CT-FFR was quantified. Significant stenosis was determined by: (1) combination of stenosis > 50% with an SPD, (2) CT-FFR ≤ 0.80. Patients were followed-up for 36 ± 25 months for death, myocardial infarction or revascularization. After excluding patients with normal arteries and technical/quality issues, in final analysis of 76 patients, CTCA depicted stenosis > 70% in 13/224 arteries, 50-70% in 24, and < 50% in 187. CT-FFR ≤ 0.80 was found in 41/224 arteries, and combination of SPD with > 50% stenosis in 31/224 arteries. Inter-technique agreement was 89%. Despite high incidence of abnormal CT-FFR (30/76 patients), only 7 patients experienced adverse outcomes; 6/7 also had SPDs. Only 1/9 patients with CT-FFR ≤ 0.80 but normal perfusion had an event. Fusion of CTCA and stress perfusion can help determine the hemodynamic impact of stenosis in one test, in good agreement with CT-FFR. Adding stress CT perfusion analysis may help risk-stratify patients with abnormal CT-FFR.

Myocardial perfusion reserve and global longitudinal strain as potential markers of coronary allograft vasculopathy in late-stage orthotopic heart transplantation.

Coronary allograft vasculopathy (CAV) is a major cause of mortality in late-stage orthotopic heart transplantation (OHT) patients. Recent evidence has shown that myocardial perfusion reserve (MPR) derived from vasodilator cardiovascular magnetic resonance imaging (vCMR) and global longitudinal strain (GLS) from transthoracic echocardiography (TTE) are useful to detect CAV. However, previous studies have not comprehensively addressed whether these parameters are confounded by allograft rejection, myocardial scar/fibrosis, or allograft dysfunction. Our aim was to determine whether changes in late post-OHT MPR and GLS are due to CAV or other confounding factors. Twenty OHT patients (time from transplant to vCMR was 8.1 ± 4.1 years) and 30 controls (10 healthy volunteers and 20 with prior myocardial infarction to provide perspective with regards to the severity of any abnormalities seen in post-OHT patients) underwent vasodilator vCMR from which MPR index (MPRi), left ventricular ejection fraction (LVEF), and burden of late gadolinium enhancement (LGE) were quantified. TTE was used to measure GLS. The presence of CAV was determined from invasive coronary angiograms using thrombolysis in myocardial infarction (TIMI) frame counts and grading severity per guidelines. Previous endomyocardial biopsies were reviewed to assess association with episodes of rejection. We examined the correlations between MPRi and GLS with markers of CAV, allograft function, scar/fibrosis, and rejection. MPRi was abnormal in post-OHT patients compared to both healthy volunteers and MI controls. While there was no relationship between MPRi or GLS and LVEF, episodes of rejection, or LGE burden, both MPRi and GLS were associated with TIMI frame counts and presence and severity of CAV. Additionally, MPRi correlated with GLS (R = 0.68, P = 0.0002). In conclusion, MPRi and GLS are abnormal in late-stage OHT and associated with CAV, but not related to allograft rejection, myocardial scar/fibrosis, or allograft dysfunction. Non-invasive monitoring of MPRi and GLS may be a useful strategy to detect CAV.

Fusion of Three-Dimensional Echocardiographic Regional Myocardial Strain with Cardiac Computed Tomography for Noninvasive Evaluation of the Hemodynamic Impact of Coronary Stenosis in Patients with Chest Pain.

BACKGROUND: Combined evaluation of coronary stenosis and the extent of ischemia is essential in patients with chest pain. Intermediate-grade stenosis on computed tomographic coronary angiography (CTCA) frequently triggers downstream nuclear stress testing. Alternative approaches without stress and/or radiation may have important implications. Myocardial strain measured from echocardiographic images can be used to detect subclinical dysfunction. The authors recently tested the feasibility of fusion of three-dimensional (3D) echocardiography-derived regional resting longitudinal strain with coronary arteries from CTCA to determine the hemodynamic significance of stenosis. The aim of the present study was to validate this approach against accepted reference techniques. METHODS: Seventy-eight patients with chest pain referred for CTCA who also underwent 3D echocardiography and regadenoson stress computed tomography were prospectively studied. Left ventricular longitudinal strain data (TomTec) were used to generate fused 3D displays and detect resting strain abnormalities (RSAs) in each coronary territory. Computed tomographic coronary angiographic images were interpreted for the presence and severity of stenosis. Fused 3D displays of subendocardial x-ray attenuation were created to detect stress perfusion defects (SPDs). In patients with stenosis >25% in at least one artery, fractional flow reserve was quantified (HeartFlow). RSA as a marker of significant stenosis was validated against two different combined references: stenosis >50% on CTCA and SPDs seen in the same territory (reference standard A) and fractional flow reserve < 0.80 and SPDs in the same territory (reference standard B). RESULTS: Of the 99 arteries with no stenosis >50% and no SPDs, considered as normal, 19 (19%) had RSAs. Conversely, with stenosis >50% and SPDs, RSAs were considerably more frequent (17 of 24 [71%]). The sensitivity, specificity, and accuracy of RSA were 0.71, 0.81, and 0.79, respectively, against reference standard A and 0.83, 0.81, and 0.82 against reference standard B. CONCLUSIONS: Fusion of CTCA and 3D echocardiography-derived resting myocardial strain provides combined displays, which may be useful in determination of the hemodynamic or functional impact of coronary abnormalities, without additional ionizing radiation or stress testing.

A fast, noniterative approach for accelerated high-temporal resolution cine-CMR using dynamically interleaved streak removal in the power-spectral encoded domain with low-pass filtering (DISPEL) and modulo-prime spokes (MoPS).

PURPOSE: To introduce a pair of accelerated non-Cartesian acquisition principles that when combined, exploit the periodicity of k-space acquisition, and thereby enable acquisition of high-temporal cine Cardiac Magnetic Resonance (CMR). METHODS: The mathematical formulation of a noniterative, undersampled non-Cartesian cine acquisition and reconstruction is presented. First, a low-pass filtering step that exploits streaking artifact redundancy is provided (i.e., Dynamically Interleaved Streak removal in the Power-spectrum Encoded domain with Low-pass filtering [DISPEL]). Next, an effective radial acquisition for the DISPEL approach that exploits the property of prime numbers is described (i.e., Modulo-Prime Spoke [MoPS]). Both DISPEL and MoPS are examined using numerical simulation of a digital heart phantom to show that high-temporal cine-CMR is feasible without removing physiologic motion vs aperiodic interleaving using Golden Angles. The combined high-temporal cine approach is next examined in 11 healthy subjects for a time-volume curve assessment of left ventricular systolic and diastolic performance vs conventional Cartesian cine-CMR reference. RESULTS: The DISPEL method was first shown using simulation under different streak cycles to allow separation of undersampled radial streaking artifacts from physiologic motion with a sufficiently frequent streak-cycle interval. Radial interleaving with MoPS is next shown to allow interleaves with pseudo-Golden-Angle variants, and be more compatible with DISPEL against irrational and nonperiodic rotation angles, including the Golden-Angle-derived rotations. In the in vivo data, the proposed method showed no statistical difference in the systolic performance, while diastolic parameters sensitive to the cine's temporal resolution were statistically significant (P < 0.05 vs Cartesian cine). CONCLUSIONS: We demonstrate a high-temporal resolution cine-CMR using DISPEL and MoPS, whose streaking artifact was separated from physiologic motion.

3D late gadolinium enhanced cardiovascular MR with CENTRA-PLUS profile/view ordering: Feasibility of right ventricular myocardial damage assessment using a swine animal model.

AIMS: To develop a high-resolution, 3D late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (MRI) technique for improved assessment of myocardial scars, and evaluate its performance against 2D breath-held (BH) LGE MRI using a surgically implanted animal scar model in the right ventricle (RV). METHODS AND RESULTS: A k-space segmented 3D LGE acquisition using CENTRA-PLUS (Contrast ENhanced Timing Robust Acquisition with Preparation of LongitUdinal Signal; or CP) ordering is proposed. 8 pigs were surgically prepared with cardiac patch implantation in the RV, followed in 60days by 1.5T MRI. LGE with Phase-Sensitive Inversion Recovery (PSIR) were performed as follows: 1) 2DBH using pneumatic control, and 2) navigator-gated, 3D free-breathing (3DFB)-CP-LGE with slice-tracking. The animal heart was excised immediately after cardiac MR for scar volume quantification. RV scar volumes were also delineated from the 2DBH and 3DFB-CP-LGE images for comparison against the surgical standard. Apparent scar/normal tissue signal-to-noise ratio (aSNR) and contrast-to-noise ratio (aCNR) were also calculated. 3DFB-CP-LGE technique was successfully performed in all animals. No difference in aCNR was noted, but aSNR was significantly higher using the 3D technique (p<0.05). Against the surgical reference volume, the 3DFB-CP-LGE-derived delineation yielded significantly less volume quantification error compared to 2DBH-derived volumes (15±10% vs 55±33%; p<0.05). CONCLUSION: Compared to conventional 2DBH-LGE, 3DFB-LGE acquisition using CENTRA-PLUS provided superior scar volume quantification and improved aSNR.

Non-invasive assessment of the haemodynamic significance of coronary stenosis using fusion of cardiac computed tomography and 3D echocardiography.

AIMS: Abnormal computed tomography coronary angiography (CTCA) often leads to stress testing to determine haemodynamic significance of stenosis. We hypothesized that instead, this could be achieved by fusion imaging of the coronary anatomy with 3D echocardiography (3DE)-derived resting myocardial deformation. METHODS AND RESULTS: We developed fusion software that creates combined 3D displays of the coronary arteries with colour maps of longitudinal strain and tested it in 28 patients with chest pain, referred for CTCA (256 Philips scanner) who underwent 3DE (Philips iE33) and regadenoson stress CT. To obtain a reference for stenosis significance, coronaries were also fused with colour maps of stress myocardial perfusion. 3D displays were used to detect stress perfusion defect (SPD) and/or resting strain abnormality (RSA) in each territory. CTCA showed 56 normal arteries, stenosis <50% in 17, and >50% in 8 arteries. Of the 81 coronary territories, SPDs were noted in 20 and RSAs in 29. Of the 59 arteries with no stenosis >50% and no SPDs, considered as normal, 12 (20%) had RSAs. Conversely, with stenosis >50% and SPDs (haemodynamically significant), RSAs were considerably more frequent (5/6 = 83%). Overall, resting strain and stress perfusion findings were concordant in 64/81 arteries (79% agreement). CONCLUSIONS: Fusion of CTCA and 3DE-derived data allows direct visualization of each coronary artery and strain in its territory. In this feasibility study, resting strain showed good agreement with stress perfusion, indicating that it may be potentially used to assess haemodynamic impact of coronary stenosis, as an alternative to stress testing that entails additional radiation exposure.

Role of Perfusion at Rest in the Diagnosis of Myocardial Infarction Using Vasodilator Stress Cardiovascular Magnetic Resonance.

In clinical practice, perfusion at rest in vasodilator stress single-photon emission computed tomography is commonly used to confirm myocardial infarction (MI) and ischemia and to rule out artifacts. It is unclear whether perfusion at rest carries similar information in cardiovascular magnetic resonance (CMR). We sought to determine whether chronic MI is associated with abnormal perfusion at rest on CMR. We compared areas of infarct and remote myocardium in 31 patients who underwent vasodilator stress CMR (1.5 T), had MI confirmed by late gadolinium enhancement (LGE scar), and coronary angiography within 6 months. Stress perfusion imaging during gadolinium first pass was followed by reversal with aminophylline (75 to 125 mg), rest perfusion, and LGE imaging. Resting and peak-stress time-intensity curves were used to obtain maximal upslopes (normalized by blood pool upslopes), which were compared between infarcted and remote myocardial regions of interest. At rest, there was no significant difference between the slopes in the regions of interest supplied by arteries with and without stenosis >70% (0.31 ± 0.16 vs 0.26 ± 0.15 1/s), irrespective of LGE scar. However, at peak stress, we found significant differences (0.20 ± 0.11 vs 0.30 ± 0.22 1/s; p <0.05), reflecting the expected stress-induced ischemia. Similarly, at rest, there was no difference between infarcted and remote myocardium (0.27 ± 0.14 vs 0.30 ± 0.17 1/s), irrespective of stenosis, but significant differences were seen during stress (0.21 ± 0.16 vs 0.28 ± 0.18 1/s; p <0.001), reflecting inducible ischemia. In conclusion, abnormalities in myocardial perfusion at rest associated with chronic MI are not reliably detectable on CMR images. Accordingly, unlike single-photon emission computed tomography, normal CMR perfusion at rest should not be used to rule out chronic MI.

Right Heart Involvement in Patients with Sarcoidosis.

The left ventricle (LV) is affected in 20-25% of patients with sarcoidosis and its involvement is associated with morbidity and mortality. However, effects of sarcoidosis on the right ventricle (RV) are not well documented. Our aims were to investigate the prevalence of RV dysfunction in patients with sarcoidosis and determine whether it is predominantly associated with direct cardiac involvement, severity of lung disease, or pulmonary hypertension (PH). We identified 50 patients with biopsy-proven extra-cardiac sarcoidosis and preserved LV function, who underwent echocardiography, pulmonary function (PF) testing, and cardiovascular magnetic resonance. RV function was quantified by free wall longitudinal strain. Tricuspid valve Doppler and estimated right atrial pressure were used to estimate systolic pulmonary artery pressure. Myocardial late gadolinium enhancement was considered diagnostic for cardiac sarcoidosis and assumed to involve both ventricles. Of the 50 patients, 28 (56%) had RV dysfunction, 4 with poorly defined PF status. Of the remaining 24 patients, 16 (67%) had lung disease, 8 (33%) had PH, and 10 (42%) had LV involvement. Ten patients had greater than one of these findings, and 4 had all 3. In contrast, in 4/24 patients (17%), RV dysfunction could not be explained by these mechanisms, despite severely reduced RV strain. In conclusion, RV dysfunction is common in patients with sarcoidosis and is usually associated with either direct LV involvement, lung disease, or PH, but may occur in the absence of these mechanisms, suggesting the possibility of isolated RV involvement and underscoring the need for imaging protocols that would include RV strain analysis.

Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events.

BACKGROUND AND PURPOSE: Histological data associate proliferation of adventitial vasa vasorum and intraplaque neovascularization with vulnerable plaques represented by symptomatic vascular disease. In this observational study, the presence of carotid intraplaque neovascularization and adventitial vasa vasorum were correlated with the presence and occurrence of cardiovascular disease (CVD) and events (CVE). METHODS: The contrast-enhanced carotid ultrasound examinations of 147 subjects (mean age 64+/-11 years, 61% male) were analyzed for the presence of intraluminal plaque, plaque neovascularization (Grade 1=absent; Grade 2=present), and degree of adventitial vasa vasorum (Grade 1=absent, Grade 2=present). These observations were correlated with preexisting cardiovascular risk factors, presence of CVD, and history of CVE (myocardial infarction and transient ischemic attack/stroke). RESULTS: The presence of intraluminal carotid plaque was directly correlated to cardiovascular risk factors, CVD, and CVE (P<0.05). Adventitial vasa vasorum Grade 2 was associated with significant more subjects with CVD than vasa vasorum Grade 1 (73 versus 54%, P=0.029). Subjects with intraplaque neovascularization Grade 2 had significantly more often a history of CVE than subjects with intraplaque neovascularization Grade 1 (38 versus 20%, P=0.031). Multivariate logistic regression analysis revealed that presence of plaque was significantly associated with CVD (odds ratio 4.7, 95% CI 1.6 to 13.8) and intraplaque neovascularization grade 2 with CVE (odds ratio 4.0, 95% CI 1.3 to 12.6). CONCLUSIONS: The presence and degree of adventitial vasa vasorum and plaque neovascularization were directly associated with CVD and CVE in a retrospective study of 147 patients undergoing contrast-enhanced carotid ultrasound.

A dosimetric comparison of MammoSite and ClearPath high-dose-rate breast brachytherapy devices.

PURPOSE: A new form of partial breast irradiation (PBI), ClearPath (CP) breast brachytherapy, has been introduced. We present our results of a dosimetric comparison of MammoSite (MS) and CP PBI. METHODS AND MATERIALS: The dimensions of the CP device were reconstructed onto the MS planning CT scans for 15 previously treated patients. The mean %V(100), %V(150), %V(200) (percent of the PTV that received 100%, 150%, and 200% of the prescription dose, respectively), ipsilateral breast %V(50) (percent of the ipsilateral normal breast that received 50% of the prescription dose), ipsilateral lung %V(30) (percent of the ipsilateral lung that received 30% of the prescription dose), the heart %V(5) (percent of the heart that received 5% of the prescription dose), and the maximum skin point dose per fraction were then determined for each patient using the two methods of balloon-based PBI. RESULTS: The mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 42.1% vs. 42.9% (p=ns), and the mean V(200) was 11.4% vs. 15.2% (p<.05) for the MS and CP methods, respectively. The mean ipsilateral breast %V(50) was 19.8% vs.18.0% (p<.05), the mean ipsilateral lung %V(30) was 3.7% vs. 2.8% (p<.05), the mean heart %V(5) was 57.0% vs. 54.3% (p<.05), and the maximum skin point dose per fraction was 312.2 and 273.6cGy (p<.05) for the MS and CP methods, respectively. CONCLUSIONS: The MS and CP methods of PBI offer comparable target volume coverage; however, the CP device achieves increased normal tissue sparing.