Combined model-based and deep learning-based automated 3D zonal segmentation of the prostate on T2-weighted MR images: clinical evaluation.

OBJECTIVE: To train and to test for prostate zonal segmentation an existing algorithm already trained for whole-gland segmentation. METHODS: The algorithm, combining model-based and deep learning-based approaches, was trained for zonal segmentation using the NCI-ISBI-2013 dataset and 70 T2-weighted datasets acquired at an academic centre. Test datasets were randomly selected among examinations performed at this centre on one of two scanners (General Electric, 1.5 T; Philips, 3 T) not used for training. Automated segmentations were corrected by two independent radiologists. When segmentation was initiated outside the prostate, images were cropped and segmentation repeated. Factors influencing the algorithm's mean Dice similarity coefficient (DSC) and its precision were assessed using beta regression. RESULTS: Eighty-two test datasets were selected; one was excluded. In 13/81 datasets, segmentation started outside the prostate, but zonal segmentation was possible after image cropping. Depending on the radiologist chosen as reference, algorithm's median DSCs were 96.4/97.4%, 91.8/93.0% and 79.9/89.6% for whole-gland, central gland and anterior fibromuscular stroma (AFMS) segmentations, respectively. DSCs comparing radiologists' delineations were 95.8%, 93.6% and 81.7%, respectively. For all segmentation tasks, the scanner used for imaging significantly influenced the mean DSC and its precision, and the mean DSC was significantly lower in cases with initial segmentation outside the prostate. For central gland segmentation, the mean DSC was also significantly lower in larger prostates. The radiologist chosen as reference had no significant impact, except for AFMS segmentation. CONCLUSIONS: The algorithm performance fell within the range of inter-reader variability but remained significantly impacted by the scanner used for imaging. KEY POINTS: • Median Dice similarity coefficients obtained by the algorithm fell within human inter-reader variability for the three segmentation tasks (whole gland, central gland, anterior fibromuscular stroma). • The scanner used for imaging significantly impacted the performance of the automated segmentation for the three segmentation tasks. • The performance of the automated segmentation of the anterior fibromuscular stroma was highly variable across patients and showed also high variability across the two radiologists.

Inflammatory cytokines in pulmonary hypertension.

Pulmonary hypertension is an "umbrella term" used for a spectrum of entities resulting in an elevation of the pulmonary arterial pressure. Clinical symptoms include dyspnea and fatigue which in the absence of adequate therapeutic intervention may lead to progressive right heart failure and death. The pathogenesis of pulmonary hypertension is characterized by three major processes including vasoconstriction, vascular remodeling and microthrombotic events. In addition accumulating evidence point to a cytokine driven inflammatory process as a major contributor to the development of pulmonary hypertension.This review summarizes the latest clinical and experimental developments in inflammation associated with pulmonary hypertension with special focus on Interleukin-6, and its role in vascular remodeling in pulmonary hypertension.

Comprehensive validation of computational fluid dynamics simulations of in-vivo blood flow in patient-specific cerebral aneurysms.

PURPOSE: Recently, image-based computational fluid dynamic (CFD) simulations have been proposed to investigate the local hemodynamics inside human cerebral aneurysms. It was suggested that the knowledge of the computed three-dimensional flow fields can be used to assist clinical risk assessment and treatment decision making. Therefore, it was desired to know the reliability of CFD for cerebral blood flow simulation, and be able to provide clinical feedback. However, the validations were not yet comprehensive as they lack either patient-specific boundary conditions (BCs) required for CFD simulations or quantitative comparison methods. METHODS: In this study, based on a recently proposed in-vitro quantitative CFD evaluation approach via virtual angiography, the CFD evaluation was extended from phantom to patient studies. In contrast to previous work, patient-specific blood flow rates obtained by transcranial color coded Doppler ultrasound measurements were used to impose CFD BCs. Virtual angiograms (VAs) were constructed which resemble clinically acquired angiograms (AAs). Quantitative measures were defined to thoroughly evaluate the correspondence of the detailed flow features between the AAs and the VAs, and thus, the reliability of CFD simulations. RESULTS: The proposed simulation pipeline provided a comprehensive validation method of CFD simulation for reproducing cerebral blood flow, with a focus on the aneurysm region. Six patient cases were tested and close similarities were found in terms of spatial and temporal variations of contrast agent (CA) distribution between AAs and VAs. For patient #1 to #5, discrepancies of less than 11% were found for the relative root mean square errors in time intensity curve comparisons from characteristic vasculature positions. For patient #6, where the CA concentration curve at vessel inlet cannot be directly extracted from the AAs and given as a BC, deviations about 20% were found. CONCLUSIONS: As a conclusion, the reliability of the CFD simulations was well confirmed. Besides, it was shown that the accuracy of CFD simulations was closely related to the input BCs.

Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy Adults.

BACKGROUND: We evaluated the efficacy of acetazolamide in preventing adverse altitude effects in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and in healthy lowlanders 40 years of age or older. METHODS: Trial 1 was a randomized, double-blind, parallel-design trial in which 176 patients with COPD were treated with acetazolamide capsules (375 mg/day) or placebo, starting 24 hours before staying for 2 days at 3100 m. The mean (±SD) age of participants was 57±9 years, and 34% were women. At 760 m, COPD patients had oxygen saturation measured by pulse oximetry of 92% or greater, arterial partial pressure of carbon dioxide less than 45 mm Hg, and mean forced expiratory volume in 1 second of 63±11% of predicted. The primary outcome in trial 1 was the incidence of the composite end point of altitude-related adverse health effects (ARAHE) at 3100 m. Criteria for ARAHE included acute mountain sickness (AMS) and symptoms or findings relevant to well-being and safety, such as severe hypoxemia, requiring intervention. Trial 2 comprised 345 healthy lowlanders. Their mean age was 53±7 years, and 69% were women. The participants in trial 2 underwent the same protocol as did the patients with COPD in trial 1. The primary outcome in trial 2 was the incidence of AMS assessed at 3100 m by the Lake Louise questionnaire score (the scale of self-assessed symptoms ranges from 0 to 15 points, indicating absent to severe, with 3 or more points including headache, indicating AMS). RESULTS: In trial 1 of patients with COPD, 68 of 90 (76%) receiving placebo and 42 of 86 (49%) receiving acetazolamide experienced ARAHE (hazard ratio, 0.54; 95% confidence interval [CI], 0.37 to 0.79; P<0.001). The number needed to treat (NNT) to prevent one case of ARAHE was 4 (95% CI, 3 to 8). In trial 2 of healthy individuals, 54 of 170 (32%) receiving placebo and 38 of 175 (22%) receiving acetazolamide experienced AMS (hazard ratio, 0.48; 95% CI, 0.29 to 0.80; chi-square statistic P=0.035). The NNT to prevent one case of AMS was 10 (95% CI, 5 to 141). No serious adverse events occurred in these trials. CONCLUSIONS: Preventive treatment with acetazolamide reduced the incidence of adverse altitude effects requiring an intervention in patients with COPD and the incidence of AMS in healthy lowlanders 40 years of age or older during a high-altitude sojourn. (Funded by the Swiss National Science Foundation [Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung], Lunge Zürich, and the Swiss Lung Foundation; ClinicalTrials.gov numbers, NCT03156231 and NCT03561675.)

Favorable Pregnancy Outcomes in Women With Well-Controlled Pulmonary Arterial Hypertension.

Introduction: Since pregnancy in women with pulmonary arterial hypertension (PAH) is associated with a high risk of morbidity and mortality, it is recommended that pregnancy should be avoided in PAH. However, some women with mild PAH may consider this recommendation as unsuitable. Unfortunately knowledge on pregnancy outcomes and best management of PAH during pregnancy is limited. Methods: Data from all women with PAH who were followed during pregnancy by a multidisciplinary team at a tertiary referral center for PAH and who delivered between 2004 and 2020 were retrospectively analyzed in a case series. PAH risk factor profiles including WHO functional class (WHO-FC), NT-pro-BNP, echocardiographic pulmonary arterial pressure (PAP) and right heart function were analyzed prior to, during and following pregnancy. Results: In seven pregnancies of five women with PAH (median age 29 (27; 31) years), there were no abortions or terminations. Five pregnancies were planned (all in WHO-FC I-II), two incidental (WHO-FC II, III). During pregnancy none of the women had complications or clinical worsening of PAH. After a median pregnancy duration of 37 1/7 weeks all gave birth to healthy babies by cesarean section in spinal anesthesia. During pregnancy, PAP tended to increase, whilst the course of WHO-FC and NT-pro-BNP were variable and no trend could be detected. Conclusion: Women with PAH with a low risk profile closely followed by a multidisciplinary team had a favorable course during and after pregnancy, resulting in successful deliveries of healthy newborns.

Acute Hemodynamic Effect of Acetazolamide in Patients With Pulmonary Hypertension Whilst Breathing Normoxic and Hypoxic Gas: A Randomized Cross-Over Trial.

Aims: To test the acute hemodynamic effect of acetazolamide in patients with pulmonary hypertension (PH) under ambient air and hypoxia. Methods: Patients with pulmonary arterial or chronic thromboembolic PH (PAH/CTEPH) undergoing right heart catheterization were included in this randomized, placebo-controlled, double-blinded, crossover trial. The main outcome, pulmonary vascular resistance (PVR), further hemodynamics, blood- and cerebral oxygenation were measured 1 h after intravenous administration of 500 mg acetazolamide or placebo-saline on ambient air (normoxia) and at the end of breathing hypoxic gas (FIO2 0.15, hypoxia) for 15 min. Results: 24 PH-patients, 71% men, mean ± SD age 59 ± 14 years, BMI 28 ± 5 kg/m2, PVR 4.7 ± 2.1 WU participated. Mean PVR after acetazolamide vs. placebo was 5.5 ± 3.0 vs. 5.3 ± 3.0 WU; mean difference (95% CI) 0.2 (-0.2-0.6, p = 0.341). Heart rate was higher after acetazolamide (79 ± 12 vs. 77 ± 11 bpm, p = 0.026), pH was lower (7.40 ± 0.02 vs. 7.42 ± 0.03, p = 0.002) but PaCO2 and PaO2 remained unchanged while cerebral tissue oxygenation increased (71 ± 6 vs. 69 ± 6%, p = 0.017). In acute hypoxia, acetazolamide decreased PVR by 0.4 WU (0.0-0.9, p = 0.046) while PaO2 and PaCO2 were not changed. No adverse effects occurred. Conclusions: In patients with PAH/CTEPH, i.v. acetazolamide did not change pulmonary hemodynamics compared to placebo after 1 hour in normoxia but it reduced PVR after subsequent acute exposure to hypoxia. Our findings in normoxia do not suggest a direct acute pulmonary vasodilator effect of acetazolamide. The reduction of PVR during hypoxia requires further corroboration. Whether acetazolamide improves PH when given over a prolonged period by stimulating ventilation, increasing oxygenation, and/or altering vascular inflammation and remodeling remains to be investigated.

Phantom-based experimental validation of computational fluid dynamics simulations on cerebral aneurysms.

PURPOSE: Recently, image-based computational fluid dynamics (CFD) simulation has been applied to investigate the hemodynamics inside human cerebral aneurysms. The knowledge of the computed three-dimensional flow fields is used for clinical risk assessment and treatment decision making. However, the reliability of the application specific CFD results has not been thoroughly validated yet. METHODS: In this work, by exploiting a phantom aneurysm model, the authors therefore aim to prove the reliability of the CFD results obtained from simulations with sufficiently accurate input boundary conditions. To confirm the correlation between the CFD results and the reality, virtual angiograms are generated by the simulation pipeline and are quantitatively compared to the experimentally acquired angiograms. In addition, a parametric study has been carried out to systematically investigate the influence of the input parameters associated with the current measuring techniques on the flow patterns. RESULTS: Qualitative and quantitative evaluations demonstrate good agreement between the simulated and the real flow dynamics. Discrepancies of less than 15% are found for the relative root mean square errors of time intensity curve comparisons from each selected characteristic position. The investigated input parameters show different influences on the simulation results, indicating the desired accuracy in the measurements. CONCLUSIONS: This study provides a comprehensive validation method of CFD simulation for reproducing the real flow field in the cerebral aneurysm phantom under well controlled conditions. The reliability of the CFD is well confirmed. Through the parametric study, it is possible to assess the degree of validity of the associated CFD model based on the parameter values and their estimated accuracy range.

Acute hemodynamic changes by breathing hypoxic and hyperoxic gas mixtures in pulmonary arterial and chronic thromboembolic pulmonary hypertension.

BACKGROUND: There is insufficient evidence to counsel patients with pulmonary hypertension undergoing altitude or air travel. We thus aimed to study hemodynamic response of patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH) during changes in inspiratory oxygen partial pressure. METHODS AND RESULTS: Consecutive patients undergoing right heart catheterization had hemodynamic assessments whilst breathing ambient air (normoxia, FiO2 0.21, at altitude 490 m), nitrogen-enriched air (hypoxia, FiO2 0.16, simulated altitude 2600 m) and oxygen (hyperoxia, FiO2 1.0), each for 10 min. Data from patients with PAH/CTEPH with mean pulmonary artery pressure (mPAP) ≥25 mmHg, pulmonary artery wedge pressure ≤15 mmHg, were compared to data from controls, mPAP <20 mmHg. 28 PAH/CTEPH-patients, 15 women, median age (quartiles) 62y (49;73), mPAP 35 mmHg (31;44), PaO2 7.1 kPa (6.8;9.3) and 16 controls, 12 women, 60y (52;69), mPAP 18 mmHg (16;18), PaO2 9.5 kPa (8.5;10.6) were included. Hypoxia reduced the PaO2 in PAH/CTEPH-patients by median of 2.3 kPa, in controls by 3.3 kPa, difference (95%CI) in change 1.0 (0.02 to 1.9), p < 0.05. Corresponding changes in pulmonary vascular resistance, mPAP and cardiac output were nonsignificant in both groups. Hyperoxia decreased mPAP in PAH/CTEPH-patients by 4 mmHg (2 to 6), in controls by 2 mmHg (0 to 3), difference in change 3 mmHg (0 to 5), p < 0.05. CONCLUSIONS: In patients with PAH/CTEPH, very short-term exposure to moderate hypoxia similar to 2600 m altitude or during commercial air travel did not deteriorate hemodynamics. These results encourage studying the response of PAH/CTEPH during daytrips to the mountain or air travel.

Automatic multi-model-based segmentation of the left atrium in cardiac MRI scans.

Model-based segmentation approaches have been proven to produce very accurate segmentation results while simultaneously providing an anatomic labeling for the segmented structures. However, variations of the anatomy, as they are often encountered e.g. on the drainage pattern of the pulmonary veins to the left atrium, cannot be represented by a single model. Automatic model selection extends the model-based segmentation approach to handling significant variational anatomies without user interaction. Using models for the three most common anatomical variations of the left atrium, we propose a method that uses an estimation of the local fit of different models to select the best fitting model automatically. Our approach employs the support vector machine for the automatic model selection. The method was evaluated on 42 very accurate segmentations of MRI scans using three different models. The correct model was chosen in 88.1% of the cases. In a second experiment, reflecting average segmentation results, the model corresponding to the clinical classification was automatically found in 78.0% of the cases.

Automatic whole heart segmentation in static magnetic resonance image volumes.

We present a fully automatic segmentation algorithm for the whole heart (four chambers, left ventricular myocardium and trunks of the aorta, the pulmonary artery and the pulmonary veins) in cardiac MR image volumes with nearly isotropic voxel resolution, based on shape-constrained deformable models. After automatic model initialization and reorientation to the cardiac axes, we apply a multi-stage adaptation scheme with progressively increasing degrees of freedom. Particular attention is paid to the calibration of the MR image intensities. Detailed evaluation results for the various anatomical heart regions are presented on a database of 42 patients. On calibrated images, we obtain an average segmentation error of 0.76mm.