A 3D Sequential Thinning Scheme Based on Critical Kernels

International audienceWe propose a new generic sequential thinning scheme based on the critical kernels framework. From this scheme, we derive sequential algorithms for obtaining ultimate skeletons and curve skeletons. We prove some properties of these algorithms, and we provide the results of a quantitative evaluation that compares our algorithm for curve skeletons with both sequential and parallel ones

Cellular Skeletons: A New Approach to Topological Skeletons with Geometric Features

This paper introduces a new kind of skeleton for binary volumes called the cellular skeleton. This skeleton is not a subset of voxels of a volume nor a subcomplex of a cubical complex: it is a chain complex together with a reduction from the original complex. Starting from the binary volume we build a cubical complex which represents it regarding 6 or 26-connectivity. Then the complex is thinned using the proposed method based on elementary collapses, which preserves significant geometric features. The final step reduces the number of cells using Discrete Morse Theory. The resulting skeleton is a reduction which preserves the homology of the original complex and the geometrical information of the output of the previous step. The result of this method, besides its skeletonization content, can be used for computing the homology of the original complex, which usually provides well shaped homology generators

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

Analysis of lateralization of brain dopamine function in psychosis: [18F] FDOPA PET imaging study

Abnormal dopamine brain function is a hallmark of psychotic disorders like schizophrenia, and the main pharmacological target for psychotic treatment. However, the functional organization and regulation of the dopamine system are not completely known, due to its complex topology and interplay with other neuroreceptor systems. The primary objective of this research is to comprehend the normal state of dopamine lateralization in the human brain and identify whether dopamine lateralization is altered in schizophrenia. This study considered a dataset of 136 patients with psychosis matched to 143 healthy controls acquired with the [18F] FDOPA PET imaging, a biomarker for measuring dopamine synthesis capacity in vivo in humans. For each subject, neuroimaging metrics from 41 regions of interest (ROIs) were derived using the Desikan-Killiany atlas for each brain hemisphere. For each ROI and each subject, a lateralization index (lx) was computed to compare the dopamine function between the left and right hemispheres. The same metrics were fed into the Random Forest, XGBoost, SVM, KNN, Naïve Bayes, and Logistic Regression classifier models to distinguish patients and controls by exploiting the difference with the best-performing model in brain dopamine lateralization. In normal individuals, brain dopamine is mainly lateralized in the Inferior Parietal (p=0.039) and Transverse Temporal (p=0.004) with a significant effect of age and gender. Moreover, when comparing lateralization between controls and patients, left-biased lateralization in Putamen decreases by 50%, right-biased lateralization in Accumbens decreases by 60%, and right-biased lateralization in Pallidum changes direction and shows a significant increase around 300% in Ki levels. In terms of patient classification, the best performing model was XGBoost with the metrics of 79% accuracy, 79% precision, 79% recall, and 78% f1-score on the test set. Finally, the post hoc model agnostic explainability method SHAP reported the Accumbens, Fusiform, Posterior Cingulate, Thalamus, and Pallidum as the top 5 most salient features which have a significant effect on the decision. In conclusion, healthy controls present a clear lateralization of dopamine function that can change its direction and magnitude in the case of schizophrenia. Further studies should focus to investigate the biological rationale behind these differences and their implication for the stratification of patients with psychosis.Abnormal dopamine brain function is a hallmark of psychotic disorders like schizophrenia, and the main pharmacological target for psychotic treatment. However, the functional organization and regulation of the dopamine system are not completely known, due to its complex topology and interplay with other neuroreceptor systems. The primary objective of this research is to comprehend the normal state of dopamine lateralization in the human brain and identify whether dopamine lateralization is altered in schizophrenia. This study considered a dataset of 136 patients with psychosis matched to 143 healthy controls acquired with the [18F] FDOPA PET imaging, a biomarker for measuring dopamine synthesis capacity in vivo in humans. For each subject, neuroimaging metrics from 41 regions of interest (ROIs) were derived using the Desikan-Killiany atlas for each brain hemisphere. For each ROI and each subject, a lateralization index (lx) was computed to compare the dopamine function between the left and right hemispheres. The same metrics were fed into the Random Forest, XGBoost, SVM, KNN, Naïve Bayes, and Logistic Regression classifier models to distinguish patients and controls by exploiting the difference with the best-performing model in brain dopamine lateralization. In normal individuals, brain dopamine is mainly lateralized in the Inferior Parietal (p=0.039) and Transverse Temporal (p=0.004) with a significant effect of age and gender. Moreover, when comparing lateralization between controls and patients, left-biased lateralization in Putamen decreases by 50%, right-biased lateralization in Accumbens decreases by 60%, and right-biased lateralization in Pallidum changes direction and shows a significant increase around 300% in Ki levels. In terms of patient classification, the best performing model was XGBoost with the metrics of 79% accuracy, 79% precision, 79% recall, and 78% f1-score on the test set. Finally, the post hoc model agnostic explainability method SHAP reported the Accumbens, Fusiform, Posterior Cingulate, Thalamus, and Pallidum as the top 5 most salient features which have a significant effect on the decision. In conclusion, healthy controls present a clear lateralization of dopamine function that can change its direction and magnitude in the case of schizophrenia. Further studies should focus to investigate the biological rationale behind these differences and their implication for the stratification of patients with psychosis

Exploring Mechanical Niches Identified by Hair Follicle Compression and How These Transduce Proliferation and Differentiation Cues in Epidermally Derived cells.

In this study the hair follicle structure and surrounding tissue was investigated before, during and after the shaving process in order to better characterise the hair follicle hysteresis (lag in response) observed during the shaving process. Individual hair shafts were loaded with weights designed to mimic the forces generated during the shaving process and deformations in nuclear morphology were used as an indicator of force transduction. Upon identifying distinct mechanical compartments corresponding to regions consistent with the infundibulum, isthmus and suprabulbar regions the study then focussed on elucidating how dermal collagen may facilitate this. Multiphoton microscopy was utilised to interrogate the extrafollicular collagen and the subsequent images were analysed to reveal distinct differences in collagen bundling at the infundibulum, isthmus and suprabulbar regions. To model how heterogeneities in collagen bundling could impact upon epidermal and follicle homeostasis collagen hydrogels were constructed and characterised. Assessment of involucrin and Ki67 levels in HaCaT cells by confocal microscopy revealed elevated proliferation rates in cells on high density (HD) matrices compared with those on low density (LD) matrices which also correlated with increased nuclear volume. HD matrices have smaller collagen bundles and therefor represent a less stiff matrix compared with the low density LD matrices. ERK1/2, JNK and p38 MAPKs have been well reported as effectors on keratinocyte proliferation and differentiation rates in response to mechanical cues and so inhibitors of each were used to identify if these MAPKs were also important in transducing matrix density/stiffness cues that impact upon proliferation and differentiation rates. P38, ERK1/2 and JNK were all found to be important in mediating the proliferation advantage derived from the HD matrices, with JNK being a potential candidate in linking nuclear dynamics with collagen density-mediated proliferation and differentiation rates. JNK was further demonstrated as being the dominant player in transducing the proliferation advantage conferred by the HD matrix

Methods for Arrhythmogenic Substrate Identification and Procedural Improvements for Ventricular Arrhythmias.

Ventricular arrhythmias (VA) are a frequent precursor to sudden cardiac death (SCD) in patients with structural heart disease (SHD). Patients with SHD are at risk of recurrent ventricular tachycardia (VT), which generally occurs due to re-entry within and around the presence of an arrhythmogenic scar. Therefore, scarred myocardium forms the necessary substrate for arrhythmogenesis to occur. A scar may occur due to obstructive coronary artery disease, causing ischaemic cardiomyopathy (ICM), or from cardiac injury due to several other causes, including inflammatory, infiltrative, toxin-mediated, or genetic heart disease, termed non-ischaemic cardiomyopathy (NICM). An implantable cardioverting defibrillator (ICD) can abort SCD from recurrent VAs. However, they do not stop VAs from occurring in the first place. Anti-arrhythmic drugs (AADs) may reduce the frequency and burden of VAs but have limited efficacy. Some have a narrow therapeutic window or the potential for multiorgan toxicity and can be poorly tolerated. Catheter ablation (CA) is a class I indication for treating sustained monomorphic VT refractory to AADs. CA reduces VT burden, the number of defibrillator therapies, greater freedom from recurrent ventricular arrhythmia, and improves quality of life. However, recurrences can be experienced in up to 50% of patients with SHD-related VT. Some reasons for the failure of CA include reliable identification of critical components of substrate that can harbour VAs both in sinus rhythm and during ongoing VT using electroanatomic mapping (EAM) and imaging techniques, as well as limitations in assessing intraprocedural endpoints. Further refinement of electroanatomic mapping techniques is required to improve the efficacy of CA. This thesis aims to expand on current techniques for substrate identification and methods to improve the efficacy of VA ablation procedures

The aorta in transposition of the great arteries

The thesis summarizes the results on the prevalence and evolution of neo-aortic root pathology and surgical cardiovascular outcomes in patients after arterial switch operation (ASO) for transposition of the great arteries. Furthermore, thoracic aortic blood flow hemodynamics were investigated in relation to post-ASO geometry and root pathology with advanced non-invasive four-dimensional flow cardiovascular magnetic resonance imaging techniques. Dutch Heart Foundation (DHF grant number 2014T087); Willem Alexander Children's Hospital; Pie Medical Imaging B.V.LUMC / Geneeskund

Cortical thickness estimation of the proximal femur from multi-view dual-energy X-ray absorptiometry

Hip fracture is the leading cause of acute orthopaedic hospital admission amongst the elderly, with around a third of patients not surviving one-year post-fracture. Current risk assessment tools ignore cortical bone thinning, a focal structural defect characterizing hip fragility. Cortical thickness can be measured using computed tomography, but this is expensive and involves a significant radiation dose. Dual-energy X-ray absorptiometry (DXA) is the preferred imaging modality for assessing fracture risk, and is used routinely in clinical practice. This thesis proposes two novel methods which measure the cortical thickness of the proximal femur from multi-view DXA scans. First, a data-driven algorithm is designed, implemented and evaluated. It relies on a femoral B-spline template which can be deformed to fit an individual’s scans. In a series of experiments on the trochanteric regions of 120 proximal femurs, the algorithm’s performance limits were established using twenty views in the range 0° – 171°: estimation errors were 0.00 ± 0.50 mm. In a clinically viable protocol using four views in the range −20° to 40°, measurement errors were −0.05 ± 0.54 mm. The second algorithm accomplishes the same task by deforming statistical shape and thickness models, both trained using Principal Component Analysis (PCA). Three training cohorts are used to investigate (a) the estimation efficacy as a function of the diversity in the training set and (b) the possibility of improving performance by building tailored models for different populations. In a series of cross-validation experiments involving 120 femurs, minimum estimation errors were 0.00 ± 0.59 mm and −0.01 ± 0.61 mm for the twenty- and four-view experiments respectively, when fitting the tailored models. Statistical significance tests reveal that the template algorithm is more precise than the statistical, and that both are superior to a blind estimator which naively assumes the population mean, but only in regions of thicker cortex. It is concluded that cortical thickness measured from DXA is unlikely to assist fracture prediction in the femoral neck and trochanters, but might have applicability in the sub-trochanteric region.This work was funded by the W. D. Armstrong Trust Fun