Imaging of Pulmonary Embolism and t-PA Therapy Effects Using MDCT and Liposomal Iohexol Blood Pool Agent

HYPOTHESIS AND OBJECTIVES: PEGylated liposomal blood pool contrast agents maintain contrast enhancement over several hours. This study aimed to evaluate (long-term) imaging of pulmonary arteries, comparing conventional iodinated contrast with a liposomal blood pool contrast agent. Secondly, visualization of the (real-time) therapeutic effects of tissue-Plasminogen Activator (t-PA) on pulmonary embolism (PE) was attempted. MATERIALS AND METHODS: Six rabbits (approximate 4 kg weight) had autologous blood clots injected through the superior vena cava. Imaging was performed using conventional contrast (iohexol, 350 mg I/ml, GE HealthCare, Princeton, NJ) at a dose of 1400 mgI per animal and after wash-out, animals were imaged using an iodinated liposomal blood pool agent (88 mg I/mL, dose 900 mgI/animal). Subsequently, five animals were injected with 2mg t-PA and imaging continued for up to 4 ½ hours. RESULTS: Both contrast agents identified PE in the pulmonary trunk and main pulmonary arteries in all rabbits. Liposomal blood pool agent yielded uniform enhancement, which remained relatively constant throughout the experiments. Conventional agents exhibited non uniform opacification and rapid clearance post injection. Three out of six rabbits had mistimed bolus injections, requiring repeat injections. Following t-PA, Pulmonary embolus volume (central to segmental) decreased in four of five treated rabbits (range 10–57%, mean 42%). One animal showed no response to t-PA. CONCLUSIONS: Liposomal blood pool agents effectively identified acute PE without need for re-injection. PE resolution following t-PA was quantifiable over several hours. Blood pool agents offer the potential for repeated imaging procedures without need for repeated (nephrotoxic) contrast injections

“Pharmacokinetic modelling for the simultaneous assessment of perfusion and ¹⁸F-flutemetamol uptake in cerebral amyloid angiopathy using a reduced PET-MR acquisition time: proof of concept.

Purpose Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease associated with perivascular β-amyloid deposition. CAA is also associated with strokes due to lobar intracerebral haemorrhage (ICH). 18F-flutemetamol amyloid ligand PET may improve the early detection of CAA. We performed pharmacokinetic modelling using both full (0–30, 90–120 min) and reduced (30 min) 18F-flutemetamol PET-MR acquisitions, to investigate regional cerebral perfusion and amyloid deposition in ICH patients. Methods Dynamic 18F-flutemetamol PET-MR was performed in a pilot cohort of sixteen ICH participants; eight lobar ICH cases with probable CAA and eight deep ICH patients. A model-based input function (mIF) method was developed for compartmental modelling. mIF 1-tissue (1-TC) and 2-tissue (2-TC) compartmental modelling, reference tissue models and standardized uptake value ratios were assessed in the setting of probable CAA detection. Results The mIF 1-TC model detected perfusion deficits and 18F-flutemetamol uptake in cases with probable CAA versus deep ICH patients, in both full and reduced PET acquisition time (all P < 0.05). In the reduced PET acquisition, mIF 1-TC modelling reached the highest sensitivity and specificity in detecting perfusion deficits (0.87, 0.77) and 18F-flutemetamol uptake (0.83, 0.71) in cases with probable CAA. Overall, 52 and 48 out of the 64 brain areas with 18F-flutemetamol-determined amyloid deposition showed reduced perfusion for 1-TC and 2-TC models, respectively. Conclusion Pharmacokinetic (1-TC) modelling using a 30 min PET-MR time frame detected impaired haemodynamics and increased amyloid load in probable CAA. Perfusion deficits and amyloid burden co-existed within cases with CAA, demonstrating a distinct imaging pattern which may have merit in elucidating the pathophysiological process of CAA

Use of Coronary Computed Tomographic Angiography to guide management of patients with coronary disease

Background In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA). Objectives The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes. Methods In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records. Results Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95$303 to $621). Conclusions In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590

Effect of Segmental Bronchoalveolar Lavage on Quantitative Computed Tomography of the Lung

RATIONALE AND OBJECTIVES: With employment of both multi-detector computed tomography (MDCT) and endobronchial procedures in multi-center studies, effects of timing of endobronchial procedures on quantitative imaging (Q-MDCT) metrics is a question of increasing importance. MATERIALS AND METHODS: Six subjects were studied via MDCT at baseline, immediately following and at 4hrs and 24hrs post-BAL (right middle lobe (RML) and lingula). Through quantitative image analysis, non-air, or ‘tissue’ volume (TV) in each lung and lobe was recorded. Change in TV from baseline was used to infer retention and re-distribution of lavage fluid. RESULTS: Bronchoscopist reported unrecovered BAL volume correlated well with Q-MDCT for whole lung measures, but less well with individual lobes indicating redistribution. TV in all lobes except the RLL differed significantly (p<.05) from baseline immediately post lavage. At 24hrs, all lobes except the LLL (small 1% mean difference at 24hrs.) returned to baseline. CONCLUSIONS: These findings suggest fluid movement, effecting Q-MDCT metrics, between lobes and between lungs before eventual resolution, and preclude protocols involving the lavage of one lung and imaging of the other to avoid interactions. We demonstrate that Q-MDCT is sensitive to lavage fluid retention and re-distribution, and endobronchial procedures should not precede Q-MDCT imaging by less than 24hrs

Machine-learning with 18F-sodium fluoride PET and quantitative plaque analysis on CT angiography for the future risk of myocardial infarction

Coronary (18)F-sodium fluoride ((18)F-NaF) PET and CT angiography–based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both of these novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. Methods: Patients with known coronary artery disease underwent coronary (18)F-NaF PET and CT angiography on a hybrid PET/CT scanner. Machine-learning by extreme gradient boosting was trained using clinical data, CT quantitative plaque analysis, measures and (18)F-NaF PET, and it was tested using repeated 10-fold hold-out testing. Results: Among 293 study participants (65 ± 9 y; 84% male), 22 subjects experienced a myocardial infarction over the 53 (40–59) months of follow-up. On univariable receiver-operator-curve analysis, only (18)F-NaF coronary uptake emerged as a predictor of myocardial infarction (c-statistic 0.76, 95% CI 0.68–0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53–0.76) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60–0.84). After inclusion of all available data (clinical, quantitative plaque and (18)F-NaF PET), we achieved a substantial improvement (P = 0.008 versus (18)F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79–0.91). Conclusion: Both (18)F-NaF uptake and quantitative plaque analysis measures are additive and strong predictors of outcome in patients with established coronary artery disease. Optimal risk stratification can be achieved by combining clinical data with these approaches in a machine-learning model

Coronary CT Angiography and 5-Year Risk of Myocardial Infarction.

BACKGROUND: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown. METHODS: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. RESULTS: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause. CONCLUSIONS: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590 .)

Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD

Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality. pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic–femoral pulse wave velocity. pDES was elevated in patients with cardiovascular disease (p&lt;0.005) and correlated with age (rho=0.39, p&lt;0.0005), CACS (rho=0.19, p&lt;0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p&lt;0.0005), 6-min walking distance (rho=−0.17, p&lt;0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p&lt;0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p&lt;0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p&lt;0.05). In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.Elastin degradation is a hallmark of emphysema and may have a role in the pathogenesis of atherosclerosis with COPD http://ow.ly/Y9Gs

The Lung Image Database Consortium (LIDC):ensuring the integrity of expert-defined "truth"

RATIONALE AND OBJECTIVES: Computer-aided diagnostic (CAD) systems fundamentally require the opinions of expert human observers to establish “truth” for algorithm development, training, and testing. The integrity of this “truth,” however, must be established before investigators commit to this “gold standard” as the basis for their research. The purpose of this study was to develop a quality assurance (QA) model as an integral component of the “truth” collection process concerning the location and spatial extent of lung nodules observed on computed tomography (CT) scans to be included in the Lung Image Database Consortium (LIDC) public database. MATERIALS AND METHODS: One hundred CT scans were interpreted by four radiologists through a two-phase process. For the first of these reads (the “blinded read phase”), radiologists independently identified and annotated lesions, assigning each to one of three categories: “nodule ≥ 3mm,” “nodule < 3mm,” or “non-nodule ≥ 3mm.” For the second read (the “unblinded read phase”), the same radiologists independently evaluated the same CT scans but with all of the annotations from the previously performed blinded reads presented; each radiologist could add marks, edit or delete their own marks, change the lesion category of their own marks, or leave their marks unchanged. The post-unblinded-read set of marks was grouped into discrete nodules and subjected to the QA process, which consisted of (1) identification of potential errors introduced during the complete image annotation process (such as two marks on what appears to be a single lesion or an incomplete nodule contour) and (2) correction of those errors. Seven categories of potential error were defined; any nodule with a mark that satisfied the criterion for one of these categories was referred to the radiologist who assigned that mark for either correction or confirmation that the mark was intentional. RESULTS: A total of 105 QA issues were identified across 45 (45.0%) of the 100 CT scans. Radiologist review resulted in modifications to 101 (96.2%) of these potential errors. Twenty-one lesions erroneously marked as lung nodules after the unblinded reads had this designation removed through the QA process. CONCLUSION: The establishment of “truth” must incorporate a QA process to guarantee the integrity of the datasets that will provide the basis for the development, training, and testing of CAD systems