Artificial Intelligence framework with traditional computer vision and deep learning approaches for optimal automatic segmentation of left ventricle with scar.

Automatic segmentation of the cardiac left ventricle with scars remains a challenging and clinically significant task, as it is essential for patient diagnosis and treatment pathways. This study aimed to develop a novel framework and cost function to achieve optimal automatic segmentation of the left ventricle with scars using LGE-MRI images. To ensure the generalization of the framework, an unbiased validation protocol was established using out-of-distribution (OOD) internal and external validation cohorts, and intra-observation and inter-observer variability ground truths. The framework employs a combination of traditional computer vision techniques and deep learning, to achieve optimal segmentation results. The traditional approach uses multi-atlas techniques, active contours, and k-means methods, while the deep learning approach utilizes various deep learning techniques and networks. The study found that the traditional computer vision technique delivered more accurate results than deep learning, except in cases where there was breath misalignment error. The optimal solution of the framework achieved robust and generalized results with Dice scores of 82.8 ± 6.4% and 72.1 ± 4.6% in the internal and external OOD cohorts, respectively. The developed framework offers a high-performance solution for automatic segmentation of the left ventricle with scars using LGE-MRI. Unlike existing state-of-the-art approaches, it achieves unbiased results across different hospitals and vendors without the need for training or tuning in hospital cohorts. This framework offers a valuable tool for experts to accomplish the task of fully automatic segmentation of the left ventricle with scars based on a single-modality cardiac scan.

Automatic development of 3D anatomical models of border zone and core scar regions in the left ventricle.

Patients with myocardial infarction are at elevated risk of sudden cardiac death, and scar tissue arising from infarction is known to play a role. The accurate identification of scars therefore is crucial for risk assessment, quantification and guiding interventions. Typically, core scars and grey peripheral zones are identified by radiologists and clinicians based on cardiac late gadolinium enhancement magnetic resonance images (LGE-MRI). Scar regions from LGE-MRI vary in size, shape, heterogeneity, artifacts, and image resolution. Thus, manual segmentation is time consuming, and influenced by the observer's experience (bias effect). We propose a fully automatic framework that develops 3D anatomical models of the left ventricle with border zone and core scar regions that are free from bias effect. Our myocardium (SOCRATIS), border scar and core scar (BZ-SOCRATIS) segmentation pipelines were evaluated using internal and external validation datasets. The automatic myocardium segmentation framework performed a Dice score of 81.9% and 70.0% in the internal and external validation dataset. The automatic scar segmentation pipeline achieved a Dice score of 60.9% for the core scar segmentation and 43.7% for the border zone scar segmentation in the internal dataset and in the external dataset a Dice score of 44.2% for the core scar segmentation and 54.8% for the border scar segmentation respectively. To the best of our knowledge, this is the first study outlining a fully automatic framework to develop 3D anatomical models of the left ventricle with border zone and core scar regions. Our method exhibits high performance without the need for training or tuning in an unseen cohort (unsupervised).

Prevalence of Cryptococcus gattii in Ugandan HIV-infected patients presenting with cryptococcal meningitis.

INTRODUCTION: Cryptococcal meningitis (CM) is a life threatening disease and leading cause of opportunistic fungal-related mortality in HIV/AIDS. Most CM infections are caused by C. neoformans species complexes but the prevalence of Cryptococcus gattii species complexes in Uganda is unknown however, it is known in a few other parts of Africa. We estimated the prevalence of C. gattii in patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda. METHODS: Cryptococcus isolates (n = 200) obtained from cerebrospinal fluid of patients with CM recruited at the Infectious Diseases Institute, Kampala, Uganda, were tested by phenotypic methods. The Cryptococcus isolates were sub-cultured on Sabouraud Dextrose Agar plates for 48 hours. The yeast colonies were examined by India ink stain, urea hydrolysis, and C. gattii was identified by blue pigmentation on CGB agar. The results were analyzed for frequency of C. gattii. Patient demographic characteristics were collected from the case record forms. RESULTS: From the 200 patients' case record forms, 87 (43.5%) were female and 113 (56.5%) were male. The median age was 35 (19-64) years. Most patients, 93% (187/200) were from Central Uganda in the districts of Kampala and Wakiso. 97.51% (157/161) of the patients had absolute CD4 lymphocyte counts of less than 200 cells per cubic millimeter; 1.86% (3/161) 200-350 cells per cubic millimeter and 0.62% (1/161) above 500 cells per cubic millimeter. 45.4% (74/163) were not yet on HAART and 54.6% (89/163) were on HAART. 66.7% (58/87) had poor adherence to HAART treatment and 33.3% (29/87) had reported good adherence to HAART treatment. A total of 200 clinical isolates of Cryptococcus isolates were tested. No (0% (0/200) C. gattii was identified among the Cryptococcus isolates. CONCLUSION: In this study among patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda, we found no C. gattii infections.

MA-SOCRATIS: An automatic pipeline for robust segmentation of the left ventricle and scar.

Multi-atlas segmentation of cardiac regions and total infarct scar (MA-SOCRATIS) is an unsupervised automatic pipeline to segment left ventricular myocardium and scar from late gadolinium enhanced MR images (LGE-MRI) of the heart. We implement two different pipelines for myocardial and scar segmentation from short axis LGE-MRI. Myocardial segmentation has two steps; initial segmentation and re-estimation. The initial segmentation step makes a first estimate of myocardium boundaries by using multi-atlas segmentation techniques. The re-estimation step refines the myocardial segmentation by a combination of k-means clustering and a geometric median shape variation technique. An active contour technique determines the unhealthy and healthy myocardial wall. The scar segmentation pipeline is a combination of a Rician-Gaussian mixture model and full width at half maximum (FWHM) thresholding, to determine the intensity pixels in scar regions. Following this step a watershed method with an automatic seed-points framework segments the final scar region. MA-SOCRATIS was evaluated using two different datasets. In both datasets ground truths were based on manual segmentation of short axis images from LGE-MRI scans. The first dataset included 40 patients from the MS-CMRSeg 2019 challenge dataset (STACOM at MICCAI 2019). The second is a collection of 20 patients with scar regions that are challenging to segment. MA-SOCRATIS achieved robust and accurate performance in automatic segmentation of myocardium and scar regions without the need of training or tuning in both cohorts, compared with state-of-the-art techniques (intra-observer and inter observer myocardium segmentation: 81.9% and 70% average Dice value, and scar (intra-observer and inter observer segmentation: 70.5% and 70.5% average Dice value).

The Role of Cardiac MRI in the Management of Ventricular Arrhythmias in Ischaemic and Non-ischaemic Dilated Cardiomyopathy.

Ventricular tachycardia (VT) and VF account for the majority of sudden cardiac deaths worldwide. Treatments for VT/VF include anti-arrhythmic drugs, ICDs and catheter ablation, but these treatments vary in effectiveness and carry substantial risks and/or expense. Current methods of selecting patients for ICD implantation are imprecise and fail to identify some at-risk patients, while leading to others being overtreated. In this article, the authors discuss the current role and future direction of cardiac MRI (CMRI) in refining diagnosis and personalising ventricular arrhythmia management. The capability of CMRI with gadolinium contrast delayed-enhancement patterns and, more recently, T1 mapping to determine the aetiology of patients presenting with heart failure is well established. Although CMRI imaging in patients with ICDs can be challenging, recent technical developments have started to overcome this. CMRI can contribute to risk stratification, with precise and reproducible assessment of ejection fraction, quantification of scar and 'border zone' volumes, and other indices. Detailed tissue characterisation has begun to enable creation of personalised computer models to predict an individual patient's arrhythmia risk. When patients require VT ablation, a substrate-based approach is frequently employed as haemodynamic instability may limit electrophysiological activation mapping. Beyond accurate localisation of substrate, CMRI could be used to predict the location of re-entrant circuits within the scar to guide ablation.

A multi-landing pad DNA integration platform for mammalian cell engineering.

Engineering mammalian cell lines that stably express many transgenes requires the precise insertion of large amounts of heterologous DNA into well-characterized genomic loci, but current methods are limited. To facilitate reliable large-scale engineering of CHO cells, we identified 21 novel genomic sites that supported stable long-term expression of transgenes, and then constructed cell lines containing one, two or three 'landing pad' recombination sites at selected loci. By using a highly efficient BxB1 recombinase along with different selection markers at each site, we directed recombinase-mediated insertion of heterologous DNA to selected sites, including targeting all three with a single transfection. We used this method to controllably integrate up to nine copies of a monoclonal antibody, representing about 100 kb of heterologous DNA in 21 transcriptional units. Because the integration was targeted to pre-validated loci, recombinant protein expression remained stable for weeks and additional copies of the antibody cassette in the integrated payload resulted in a linear increase in antibody expression. Overall, this multi-copy site-specific integration platform allows for controllable and reproducible insertion of large amounts of DNA into stable genomic sites, which has broad applications for mammalian synthetic biology, recombinant protein production and biomanufacturing.

Risk of Ventricular Arrhythmias and Association with Ondansetron.

OBJECTIVES: To evaluate the use of ondansetron in a tertiary care pediatric health system, assess the incidence of ventricular tachyarrhythmia within 24 hours of ondansetron, and identify the characteristics of children experiencing a ventricular tachyarrhythmia after ondansetron, to identify potential risk factors. STUDY DESIGN: This retrospective chart review identified children ≤18 years of age who received ondansetron within 24 hours prior to a ventricular tachyarrhythmia. Those identified were evaluated for other diagnoses, concomitant medication use, electrolyte abnormalities, or underlying conduction abnormalities that may have contributed to the arrhythmia. RESULTS: A total of 199 773 doses of ondansetron were administered to 37 794 patients over 58 009 visits. Average dose was 0.13 mg/kg/dose (range 0.005-0.86 mg/kg/dose). Seven patients received ondansetron within 24 hours prior to a ventricular arrhythmia. All 7 patients had underlying congenital cardiac conduction abnormalities (n = 3) or other major cardiac diagnoses (n = 4). In clinical review, torsades de pointes was found in only 1 of the 7 patients. CONCLUSIONS: This retrospective study found the risk of ventricular arrhythmia within 24 hours after ondansetron administration was 3 in 100 000 patients treated annually (0.003%). Children with major cardiac conditions could be considered for electrocardiogram screening and continuous cardiac monitoring while receiving ondansetron. Our findings do not support recommendations for electrocardiogram screening or continuous monitoring of other pediatric populations receiving ondansetron.

Gabapentin use in pediatric spinal fusion patients: a randomized, double-blind, controlled trial.

BACKGROUND: Gabapentin has opioid-sparing effects in adult surgical patients, but no reported studies have involved children and adolescents. In a double-blind, randomized, controlled trial, we examined whether gabapentin decreases postoperative opioid consumption for pediatric spinal fusion patients with idiopathic scoliosis. METHODS: Patients, aged 9 to 18 years, received preoperative gabapentin (15 mg/kg, treatment) or placebo. Anesthesia was standardized. After surgery, all patients received standardized patient-controlled analgesia opioid and continued on either gabapentin (5 mg/kg) or placebo 3 times per day for 5 days. Opioid use was calculated in mg/kg/time intervals. Pain scores and opioid side effects were recorded. RESULTS: Data from 59 patients (30 placebo and 29 gabapentin) did not differ in demographics. Total morphine consumption (mg/kg/h +/- SD) was significantly lower in the gabapentin group in the recovery room (0.044 +/- 0.017 vs 0.064 +/- 0.031, P = 0.003), postoperative day 1 (0.046 +/- 0.016 vs 0.055 +/- 0.017, P = 0.051), and postoperative day 2 (0.036 +/- 0.016 vs 0.047 +/- 0.019, P = 0.018). In addition, gabapentin significantly reduced first pain scores in the recovery room (2.5 +/- 2.8 vs 6.0 +/- 2.4, P < 0.001) and the morning after surgery (3.2 +/- 2.6 vs 5.0 +/- 2.2, P < 0.05), but otherwise pain scores were not significantly different. There were no differences in opioid-related side effects over the course of the study. CONCLUSION: Perioperative oral gabapentin reduced the amount of morphine used for postoperative pain after spinal fusion surgery, but not overall opioid-related side effects. Initial pain scores were lower in the treatment group. Perioperative use of gabapentin seems to be an effective adjunct to improve pain control in the early stages of recovery in children and adolescents undergoing spinal fusion.

Vomiting of liquid corticosteroids in children with asthma.

BACKGROUND: Oral corticosteroids are an essential part of the management of children with acute asthma exacerbations. Vomiting is a frequently cited problem attributed to oral corticosteroids. A new formulation of prednisolone, Orapred, claims to have improved palatability that may decrease the incidence of vomiting. OBJECTIVE: To compare the incidence of vomiting and taste between patients who are given the generic preparation of prednisolone with those given Orapred. DESIGN/METHODS: A randomized, double blind clinical trial was conducted at a tertiary care children s hospital emergency department. Children age 2 to 10 years presenting with acute asthma exacerbation were eligible. Patients with allergy to prednisolone, corticosteroid use within 2 weeks, history of vomiting in the last 24 hours, requirement for vascular access, and preference for other forms of corticosteroid were excluded. Enrolled patients were randomized and given either generic prednisolone (15 mg/5 ml) or Orapred (15 mg/5 ml). In children 6 years or older, a taste score was obtained using a 5 point hedonic face scale (1 = bad to 5 = great). After the administration, patients were observed for 30 minutes for vomiting. The Mann-Whitney U test was used to compare the median taste score between the two study groups. Relative risk (RR) of vomiting was calculated. Other confidence intervals were calculated when appropriate. RESULTS: During the study period, 211 eligible children were enrolled, of whom 23 were excluded. Of the remaining 188 subjects, 96 received generic prednisolone and 92 received Orapred. All baseline characteristics were similar in both groups. In the generic prednisolone group, 17 (17.7%) children vomited compared with 5 (5.4%) in the Orapred group (RR = 3.26, 95% CI, 1.25, 8.47). Taste scores were obtained from 18 children in the generic prednisolone group and from 19 children in the Orapred group. The median taste score was 2 for the generic prednisolone group and 4 for the Orapred group (Delta = -2.0, 95% CI, -3.0, -1.0) (P = 0.0001). CONCLUSIONS: In our study population, Orapred was associated with a significant less incidence of vomiting and better taste score compared to the generic prednisolone.

Screening of the entire ryanodine receptor type 1 coding region for sequence variants associated with malignant hyperthermia susceptibility in the north american population.

BACKGROUND: Malignant hyperthermia (MH) is a life-threatening and frequently fatal disorder triggered by commonly used anesthetics. MH susceptibility is a genetically determined predisposition to the development of MH. Mutations in the ryanodine receptor type 1 (RYR1) gene are the major cause of MH susceptibility. The authors sought to develop a reliable genetic screening strategy based on efficient and relatively inexpensive mutation-detection procedures. METHODS: A cohort (n = 30) of North American MH patients and MH-susceptible individuals was studied. RNA and DNA extracted from muscle tissue or blood lymphocytes were used for analysis. The entire RYR1 coding region was amplified in 57 overlapping fragments and subjected to denaturing high-performance liquid chromatography analysis followed by direct nucleotide sequencing to characterize RYR1 alterations. RESULTS: Nine previously reported and nine unknown RYR1 mutations were identified in 21 of 30 studied patients (70%). Some of the new mutations were located outside of known mutational "hot spots," suggesting that RYR1 contains previously unknown mutation-prone areas requiring analysis. The North American MH/MH-susceptible population is characterized by a high RYR1 allelic heterogeneity. CONCLUSIONS: Denaturing high-performance liquid chromatography analysis of RNA samples extracted from the biopsied skeletal muscle followed by DNA sequencing is a highly efficient methodology for RYR1 mutation detection. This approach allows increasing the rate of mutation detection to 70% and identifying mutations in the entire RYR1 coding region.

Prenatal evaluation of facial clefts with two-dimensional and adjunctive three-dimensional ultrasonography: a prospective trial.

OBJECTIVE: The purpose of this study was to compare the prenatal diagnostic capabilities of two-dimensional ultrasonography versus adjunctive three-dimensional ultrasonography for fetal cleft lip and palate. STUDY DESIGN: Fetuses that were suspected of a facial cleft were then examined sequentially with two-dimensional ultrasonography then with a targeted scan of the fetal face with three-dimensional ultrasonography. The images were coded as cleft, no cleft, or equivocal for lip and palate. Postnatal outcome follow-up was obtained. RESULTS: Fifty-three of 57 fetuses had outcome results available. The diagnostic accuracy (true positive + true negative) of adjunct three-dimensional ultrasonography versus two-dimensional ultrasonography alone were improved for cleft lip (100% [53/53 fetuses] vs 91% [48/53 fetuses], P <.05) and cleft palate (89% [47/53 fetuses] vs 57% [30/53 fetuses], P <.05) CONCLUSION: There is significant improvement in diagnostic accuracy with two-dimensional ultrasonography with adjunctive three-dimensional ultrasonography compared with two-dimensional ultrasonography alone for the prenatal evaluation of facial clefts.