Clinical Trial Validation of Automated Segmentation and Scoring of Pulmonary Cysts in Thoracic CT Scans.

In cystic lung diseases such as lymphangioleiomyomatosis (LAM), a CT-based cyst score that measures the percentage of the lung volume occupied by cysts is a common index of the cyst burden in the lungs. Although the current semi-automatic measurement of the cyst score is well established, it is susceptible to human operator variabilities. We recently developed a fully automatic method incorporating adaptive features in place of manual adjustments. In this clinical study, the automatic method is validated against the standard method in several aspects. These include the agreement between the cyst scores of the two methods, the agreement of each method with independent tests of pulmonary function, and the temporal consistency of the measurements in the consecutive visits of the same patients. We found that the automatic method agreed with the standard method as well as the agreement between two trained operators running the same standard method; both methods obtained the same level of correlation with laboratory pulmonary function tests; the automated method had better temporal consistency than the standard method (p < 0.0001). The study indicates that the automatic method could replace the standard method and provide better consistency in assessing the extent of cystic changes in the lungs of patients.

Splenic Size and Volume Measurements in Patients with Chronic Lymphocytic Leukemia.

RATIONALE AND OBJECTIVES: To determine which methods of assessment of splenic size most accurately represent the actual spleen volume in patients with Chronic Lymphocytic Leukemia (CLL). MATERIALS AND METHODS: The Abdominal Computed Tomography images of 48 patients with CLL enrolled on a phase 2 clinical trial at two time-points before and after 2-months of continuous acalabrutinib treatment were analyzed. Linear one-dimensional measurements of the spleen were taken in different planes. Two-dimensional and three-dimensional measurements were calculated from the linear measurements using mathematical formulae. The spleen volume was determined by manual segmentation as the ground truth. Data derived were analyzed using Pearson correlation and statistical significance was set at p < 0.05. RESULTS: Among the single-dimensional measurements, the strongest correlation with the segmented splenic volume was the sagittal long axis diameter (LAD) (r = 0.89, p < 0.05), followed closely by Coronal LAD (r = 0.87, p < 0.05) and cephalocaudal length (iwCLL) (r = 0.84, p < 0.05). For the two-dimensional indices, the sum of LAD and short axis diameter (SAD) of the spleen in axial plane showed good correlation with the splenic volume (r = 0.77, p < 0.05). Among the three-dimensional indices, the splenic index (0.523 x axial LAD x axial SAD x coronal height) and a formula for volume (30 + 0.58 x axial LAD x axial SAD x coronal height) had the strongest correlation (both r = 0.92, p < 0.05) with the spleen volume. CONCLUSION: The three-dimensional formulae showed the strongest correlation with volumetric reference spleen measurement. Among unidimensional measurements, the sagittal LAD had the best correlation with the actual splenic volume. The two-dimensional calculation methods were less reliable.

Cardiovascular magnetic resonance predictors of heart failure in hypertrophic cardiomyopathy: the role of myocardial replacement fibrosis and the microcirculation.

INTRODUCTION: Heart failure (HF) in hypertrophic cardiomyopathy (HCM) is associated with high morbidity and mortality. Predictors of HF, in particular the role of myocardial fibrosis and microvascular ischemia remain unclear. We assessed the predictive value of cardiovascular magnetic resonance (CMR) for development of HF in HCM in an observational cohort study. METHODS: Serial patients with HCM underwent CMR, including adenosine first-pass perfusion, left atrial (LA) and left ventricular (LV) volumes indexed to body surface area (i) and late gadolinium enhancement (%LGE- as a % of total myocardial mass). We used a composite endpoint of HF death, cardiac transplantation, and progression to NYHA class III/IV. RESULTS: A total of 543 patients with HCM underwent CMR, of whom 94 met the composite endpoint at baseline. The remaining 449 patients were followed for a median of 5.6 years. Thirty nine patients (8.7%) reached the composite endpoint of HF death (n = 7), cardiac transplantation (n = 2) and progression to NYHA class III/IV (n = 20). The annual incidence of HF was 2.0 per 100 person-years, 95% CI (1.6-2.6). Age, previous non-sustained ventricular tachycardia, LV end-systolic volume indexed to body surface area (LVESVI), LA volume index ; LV ejection fraction, %LGE and presence of mitral regurgitation were significant univariable predictors of HF, with LVESVI (Hazard ratio (HR) 1.44, 95% confidence interval (95% CI) 1.16-1.78, p = 0.001), %LGE per 10% (HR 1.44, 95%CI 1.14-1.82, p = 0.002) age (HR 1.37, 95% CI 1.06-1.77, p = 0.02) and mitral regurgitation (HR 2.6, p = 0.02) remaining independently predictive on multivariable analysis. The presence or extent of inducible perfusion defect assessed using a visual score did not predict outcome (p = 0.16, p = 0.27 respectively). DISCUSSION: The annual incidence of HF in a contemporary ambulatory HCM population undergoing CMR is low. Myocardial fibrosis and LVESVI are strongly predictive of future HF, however CMR visual assessment of myocardial perfusion was not.

Microvascular Dysfunction in Dilated Cardiomyopathy: A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study.

OBJECTIVES: This study sought to quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) in dilated cardiomyopathy (DCM) and examine the relationship between myocardial perfusion and adverse left ventricular (LV) remodeling. BACKGROUND: Although regarded as a nonischemic condition, DCM has been associated with microvascular dysfunction, which is postulated to play a role in its pathogenesis. However, the relationship of the resulting perfusion abnormalities to myocardial fibrosis and the degree of LV remodeling is unclear. METHODS: A total of 65 patients and 35 healthy control subjects underwent adenosine (140 µg/kg/min) stress perfusion cardiovascular magnetic resonance with late gadolinium enhancement imaging. Stress and rest MBF and MPR were derived using a modified Fermi-constrained deconvolution algorithm. RESULTS: Patients had significantly higher global rest MBF compared with control subjects (1.73 ± 0.42 ml/g/min vs. 1.14 ± 0.42 ml/g/min; p < 0.001). In contrast, global stress MBF was significantly lower versus control subjects (3.07 ± 1.02 ml/g/min vs. 3.53 ± 0.79 ml/g/min; p = 0.02), resulting in impaired MPR in the DCM group (1.83 ± 0.58 vs. 3.50 ± 1.45; p < 0.001). Global stress MBF (2.70 ± 0.89 ml/g/min vs. 3.44 ± 1.03 ml/g/min; p = 0.017) and global MPR (1.67 ± 0.61 vs. 1.99 ± 0.50; p = 0.047) were significantly reduced in patients with DCM with LV ejection fraction ≤35% compared with those with LV ejection fraction >35%. Segments with fibrosis had lower rest MBF (mean difference: -0.12 ml/g/min; 95% confidence interval: -0.23 to -0.01 ml/g/min; p = 0.035) and lower stress MBF (mean difference: -0.15 ml/g/min; 95% confidence interval: -0.28 to -0.03 ml/g/min; p = 0.013). CONCLUSIONS: Patients with DCM exhibit microvascular dysfunction, the severity of which is associated with the degree of LV impairment. However, rest MBF is elevated rather than reduced in DCM. If microvascular dysfunction contributes to the pathogenesis of DCM, then the underlying mechanism is more likely to involve stress-induced repetitive stunning rather than chronic myocardial hypoperfusion.

Fully quantitative pixel-wise analysis of cardiovascular magnetic resonance perfusion improves discrimination of dark rim artifact from perfusion defects associated with epicardial coronary stenosis.

BACKGROUND: Dark rim artifacts in first-pass cardiovascular magnetic resonance (CMR) perfusion images can mimic perfusion defects and affect diagnostic accuracy for coronary artery disease (CAD). We evaluated whether quantitative myocardial blood flow (MBF) can differentiate dark rim artifacts from true perfusion defects in CMR perfusion. METHODS: Regadenoson perfusion CMR was performed at 1.5 T in 76 patients. Significant CAD was defined by quantitative invasive coronary angiography (QCA) ≥ 50% diameter stenosis. Non-significant CAD (NonCAD) was defined as stenosis by QCA < 50% diameter stenosis or computed tomographic coronary angiography (CTA) < 30% in all major epicardial arteries. Dark rim artifacts had study specific and guideline-based definitions for comparison purposes. MBF was quantified at the pixel-level and sector-level. RESULTS: In a NonCAD subgroup with dark rim artifacts, stress MBF was lower in the subendocardial than midmyocardial and epicardial layers (2.17 ± 0.61 vs. 3.06 ± 0.75 vs. 3.24 ± 0.80 mL/min/g, both p < 0.001) and was also 30% lower than in remote regions (2.17 ± 0.61 vs. 2.83 ± 0.67 mL/min/g, p < 0.001). However, subendocardial stress MBF in dark rim artifacts was 37-56% higher than in true perfusion defects (2.17 ± 0.61 vs. 0.95 ± 0.43 mL/min/g, p < 0.001). Absolute stress MBF differentiated CAD from NonCAD with an accuracy ranging from 86 to 89% (all p < 0.001) using pixel-level analyses. Similar results were seen at a sector level. CONCLUSION: Quantitative stress MBF is lower in dark rim artifacts than remote myocardium but significantly higher than in true perfusion defects. If confirmed in larger series, this approach may aid the interpretation of clinical stress perfusion exams. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00027170 ; first posted 11/28/2001; updated 11/27/2017.

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

BACKGROUND: Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. METHODS: CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. RESULTS: Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P<0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P<0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P=0.021). There was a significant negative association between hyperemic MBF and wall thickness (ß=-0.047 ml/g/min per mm, 95% CI: -0.057 to -0.038, P<0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P=0.003). CONCLUSIONS: Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia.

Regadenoson and adenosine are equivalent vasodilators and are superior than dipyridamole- a study of first pass quantitative perfusion cardiovascular magnetic resonance.

BACKGROUND: Regadenoson, dipyridamole and adenosine are commonly used vasodilators in myocardial perfusion imaging for the detection of obstructive coronary artery disease. There are few comparative studies of the vasodilator properties of regadenoson, adenosine and dipyridamole in humans. The specific aim of this study was to determine the relative potency of these three vasodilators by quantifying stress and rest myocardial perfusion in humans using cardiovascular magnetic resonance (CMR). METHODS: Fifteen healthy normal volunteers, with Framingham score less than 1% underwent vasodilator stress testing with regadenoson (400 µg bolus), dipyridamole (0.56 mg/kg) and adenosine (140 µg /kg/min) on separate days. Rest perfusion imaging was performed initially. Twenty minutes later, stress imaging was performed at peak vasodilation, i.e. 70 seconds after regadenoson, 4 minutes after dipyridamole infusion and between 3-4 minutes of the adenosine infusion. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using a fully quantitative model constrained deconvolution. RESULTS: Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 µl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 µl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted for heart rate (2.04 ± 0.34 vs. 2.12 ± 0.27, p = NS), but persisted between regadenoson and dipyridamole (2.04 ± 0.34 vs. 1.77 ± 0.33, p = 0.07) and between adenosine and dipyridamole (2.12 ± 0.27 vs. 1.77 ± 0.33, p = 0.01). CONCLUSIONS: Based on fully quantitative perfusion using CMR, regadenoson and adenosine have similar vasodilator efficacy and are superior to dipyridamole.

A quantitative pixel-wise measurement of myocardial blood flow by contrast-enhanced first-pass CMR perfusion imaging: microsphere validation in dogs and feasibility study in humans.

OBJECTIVES: The aim of this study was to evaluate fully quantitative myocardial blood flow (MBF) at a pixel level based on contrast-enhanced first-pass cardiac magnetic resonance (CMR) imaging in dogs and in patients. BACKGROUND: Microspheres can quantify MBF in subgram regions of interest, but CMR perfusion imaging may be able to quantify MBF and differentiate blood flow at a much higher resolution. METHODS: First-pass CMR perfusion imaging was performed in a dog model with local hyperemia induced by intracoronary adenosine. Fluorescent microspheres were the reference standard for MBF validation. CMR perfusion imaging was also performed on patients with significant coronary artery disease (CAD) by invasive coronary angiography. Myocardial time-signal intensity curves of the images were quantified on a pixel-by-pixel basis using a model-constrained deconvolution analysis. RESULTS: Qualitatively, color CMR perfusion pixel maps were comparable to microsphere MBF bull's-eye plots in all animals. Pixel-wise CMR MBF estimates correlated well against subgram (0.49 ± 0.14 g) microsphere measurements (r = 0.87 to 0.90) but showed minor underestimation of MBF. To reduce bias due to misregistration and minimize issues related to repeated measures, 1 hyperemic and 1 remote sector per animal were compared with the microsphere MBF, which improved the correlation (r = 0.97 to 0.98), and the bias was close to zero. Sector-wise and pixel-wise CMR MBF estimates also correlated well (r = 0.97). In patients, color CMR stress perfusion pixel maps showed regional blood flow decreases and transmural perfusion gradients in territories served by stenotic coronary arteries. MBF estimates in endocardial versus epicardial subsectors, and ischemic versus remote sectors, were all significantly different (p < 0.001 and p < 0.01, respectively). CONCLUSIONS: Myocardial blood flow can be quantified at the pixel level (∼32 µl of myocardium) on CMR perfusion images, and results compared well with microsphere measurements. High-resolution pixel-wise CMR perfusion maps can quantify transmural perfusion gradients in patients with CAD.

Bright-blood T(2)-weighted MRI has high diagnostic accuracy for myocardial hemorrhage in myocardial infarction: a preclinical validation study in swine.

BACKGROUND: Myocardial hemorrhage after myocardial infarction (MI) usually goes undetected. We investigated the diagnostic accuracy of bright-blood T(2)-weighted cardiac MRI for myocardial hemorrhage in experimental MI. METHODS AND RESULTS: MI was created in swine by occluding the left anterior descending (n=10) or circumflex (n=5) coronary arteries for 90 minutes followed by reperfusion for ≤3 days (n=2), 10 days (n=7), or 60 days (n=6). MRI was performed at 1.5 T, using bright-blood T(2)-prepared steady-state free-precession, T(2)* and early (1 minute) and late (10-15 minutes) gadolinium enhancement (EGE, LGE, respectively) MRI. Left ventricular sections and histology were assessed for hemorrhage by an experienced cardiac pathologist blinded to the MRI data. Hypointense regions on T(2)-weighted and contrast-enhanced MRI were independently determined by 3 cardiologists experienced in MRI who were also blinded to the pathology results. Eighty ventricular pathological sections were matched with MRI (n=68 for EGE MRI). All sections with evidence of MI (n=63, 79%) also exhibited hyperintense zones consistent with edema on T(2)-weighted MRI and infarct on LGE MRI. Myocardial hemorrhage occurred in 49 left ventricular sections (61%) and corresponded with signal voids on 48 T(2)-weighted (98%) and 26 LGE-MRI (53%). Alternatively, signal voids occurred in the absence of hemorrhage in 3 T(2)-weighted (90% specificity) and 5 LGE MRI (84% specificity). On EGE MRI, 27 of 43 cases of early microvascular obstruction corresponded with hemorrhage (63% sensitivity), whereas 5 of 25 defects occurred in the absence of hemorrhage (80% specificity). The positive and negative predictive values for pathological evidence of hemorrhage were 94% and 96% for T(2)-weighted, 84% and 55% for LGE MRI, and 85% and 56% for EGE MRI. CONCLUSIONS: Bright-blood T(2)-weighted MRI has high diagnostic accuracy for myocardial hemorrhage.