Brain-wide correspondence of neuronal epigenomics and distant projections.

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.

Epigenomic diversity of cortical projection neurons in the mouse brain.

Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain1, neuronal cell types are often studied out of the context of their anatomical properties. To improve our understanding of the relationship between molecular and anatomical features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing to link neural epigenomic properties to projections. We examined 11,827 single neocortical neurons from 63 cortico-cortical and cortico-subcortical long-distance projections. Our results showed unique epigenetic signatures of projection neurons that correspond to their laminar and regional location and projection patterns. On the basis of their epigenomes, intra-telencephalic cells that project to different cortical targets could be further distinguished, and some layer 5 neurons that project to extra-telencephalic targets (L5 ET) formed separate clusters that aligned with their axonal projections. Such separation varied between cortical areas, which suggests that there are area-specific differences in L5 ET subtypes, which were further validated by anatomical studies. Notably, a population of cortico-cortical projection neurons clustered with L5 ET rather than intra-telencephalic neurons, which suggests that a population of L5 ET cortical neurons projects to both targets. We verified the existence of these neurons by dual retrograde labelling and anterograde tracing of cortico-cortical projection neurons, which revealed axon terminals in extra-telencephalic targets including the thalamus, superior colliculus and pons. These findings highlight the power of single-cell epigenomic approaches to connect the molecular properties of neurons with their anatomical and projection properties.

High-resolution, wavefront-sensing, full-field polarimetry of arbitrary beams using phase retrieval.

Recent advances in structured illumination are enabling a wide range of applications from imaging to metrology, which can benefit from advanced beam characterization techniques. Solving uniquely for the spatial distribution of polarization in a beam typically involves the use of two or more polarization optics, such as a polarizer and a waveplate, which is prohibitive for some wavelengths outside of the visible spectrum. We demonstrate a technique that circumvents the use of a waveplate by exploiting extended Gerchberg-Saxton phase retrieval to extract the phase. The technique enables high-resolution, wavefront-sensing, full-field polarimetry capable of solving for both simple and exotic polarization states, and moreover, is extensible to shorter wavelength light.

Subjective control of polystable illusory apparent motion: Is control possible when the stimulus affords countless motion possibilities?

We investigate whether a new polystable illusion, illusory apparent motion (IAM), is susceptible to subjective perceptual control as has been shown in other polystable stimuli (e.g., the Necker cube, apparent motion quartets). Previous research has demonstrated that, although IAM shares some properties in common with other polystable stimuli, it also has some unique ones that make it unclear whether it should have similar susceptibility to subjective control. For example, IAM can be perceived in a countless number of directions and motion patterns (e.g., up-down, left-left, contracting-expanding, shear, diagonal). To explore perceptual control of IAM, in experiment 1 (n = 99) we used a motion persistence paradigm where participants are primed with different motion patterns and are instructed to control (change or hold) the initial motion pattern and indicate when the motion pattern changes. Building on experiment 1, experiment 2 (n = 76) brings the method more in line with previous subjective control research, testing whether participants can control their perception of IAM in a context without priming and while dynamically reporting their percepts throughout the trial. Findings from the two experiments demonstrate that participants were able to control their perception of IAM across paradigms. We explore the implications of these findings, strategies reported, and open questions for future research.

Reliable segmentation of 2D cardiac magnetic resonance perfusion image sequences using time as the 3rd dimension.

OBJECTIVES: Cardiac magnetic resonance (CMR) first-pass perfusion is an established noninvasive diagnostic imaging modality for detecting myocardial ischemia. A CMR perfusion sequence provides a time series of 2D images for dynamic contrast enhancement of the heart. Accurate myocardial segmentation of the perfusion images is essential for quantitative analysis and it can facilitate automated pixel-wise myocardial perfusion quantification. METHODS: In this study, we compared different deep learning methodologies for CMR perfusion image segmentation. We evaluated the performance of several image segmentation methods using convolutional neural networks, such as the U-Net in 2D and 3D (2D plus time) implementations, with and without additional motion correction image processing step. We also present a modified U-Net architecture with a novel type of temporal pooling layer which results in improved performance. RESULTS: The best DICE scores were 0.86 and 0.90 for LV myocardium and LV cavity, while the best Hausdorff distances were 2.3 and 2.1 pixels for LV myocardium and LV cavity using 5-fold cross-validation. The methods were corroborated in a second independent test set of 20 patients with similar performance (best DICE scores 0.84 for LV myocardium). CONCLUSIONS: Our results showed that the LV myocardial segmentation of CMR perfusion images is best performed using a combination of motion correction and 3D convolutional networks which significantly outperformed all tested 2D approaches. Reliable frame-by-frame segmentation will facilitate new and improved quantification methods for CMR perfusion imaging. KEY POINTS: • Reliable segmentation of the myocardium offers the potential to perform pixel level perfusion assessment. • A deep learning approach in combination with motion correction, 3D (2D + time) methods, and a deep temporal connection module produced reliable segmentation results.

Manuka Honey: Feasibility and Safety in Postoperative Neurosurgical Wound Care.

OBJECTIVE: To date, no reports have been published on active Leptospermum manuka honey (ALH) feasibility as a postoperative topical wound supplement in neurosurgical patients. The objective of the study is to present the authors' initial experience with using ALH in postoperative neurosurgical patients. METHODS: A single-surgeon retrospective case series review of cranial and spinal operations between 2018 and 2020 was performed in patients with nonhealing wounds or wounds deemed "at risk" as defined by grade 1 Sandy surgical wound dehiscence grading classification. An ALH gel or ointment was applied to these incisions once a day for 2 to 4 weeks. Patients were followed up in the clinic every 2 weeks until incisions had healed. RESULTS: Twenty-five postoperative patients (12 cranial, 13 spinal) were identified to be at high risk of operative debridement. All 25 patients were prescribed a topical application of ALH, which was easily adopted without patient-related adverse events. Seven (four cranial, three spinal) patients required operative debridement and treatment with long-term antibiotic therapy. CONCLUSIONS: In this small case series of neurosurgical patients who were at risk of poor wound healing, the application of medical-grade ALH was well tolerated without patient-reported adverse events. The ALH may have prevented the need for operative debridement in the majority of patients. Further prospective studies are necessary to establish its efficacy in wound healing in the neurosurgical population.

Frequency of goose and duck down causation of hypersensitivity pneumonitis within an 80-patient cohort.

BACKGROUND: A variety of antigens have been identified as causative of hypersensitivity pneumonitis (HP), which is characterized by inflammation to the lung parenchyma that is induced by exposure. Goose and duck down (GDD) bedding is often overlooked by physicians as a potential cause, yet the use of GDD has markedly increased in recent years, paralleling an increased frequency of reports of GDD-induced HP. OBJECTIVE: To determine the frequency of GDD as the causative antigen in patients with HP who use bedding that contains GDD. METHODS: Patients referred with a working diagnosis of HP underwent a detailed environmental history. Those who were using GDD were asked to remove it as an avoidance procedure. Signs, symptoms, spirometry, and inflammatory markers were followed up at weekly intervals for up to 1 month to determine the effect of remediation. RESULTS: Eighty patients with HP were seen during an 8-year period. Thirty-two patients (40%) were using GDD bedding. Of these 32 patients, 12 (37.5% of those exposed and 15% of the total HP population experienced remission (or nonprogression) of disease by simply avoiding GDD bedding. Eleven (92%) of these 12 patients were female. In patients with GDD-induced HP, lung biopsy patterns were varied. CONCLUSION: Approximately one-third of patients with HP, who slept with GDD, had persistent improvement or remission with simple avoidance. The higher incidence of GDD-induced HP in females may be hormonal and/or sociocultural related. Lung biopsy findings were across the spectrum of histopathologic patterns. Avoidance-challenge techniques were effective in confirming diagnoses and causation and mitigating the need for additional remediation.

Assessment of Antifouling Potential of Novel Transparent Sol Gel Coatings for Application in the Marine Environment.

In recent years, there has become a growing need for the development of antifouling technology for application in the marine environment. The accumulation of large quantities of biomass on these surfaces cause substantial economic burdens within the marine industry, or adversely impact the performance of sensor technologies. Here, we present a study of transparent coatings with potential for applications on sensors or devices with optical windows. The focus of the study is on the abundance and diversity of biofouling organisms that accumulate on glass panels coated with novel transparent or opaque organically modified silicate (ORMOSIL) coatings. The diatom assessment was used to determine the effectiveness of the coatings against biofouling. Test panels were deployed in a marine environment in Galway Bay for durations of nine and thirteen months to examine differences in biofilm formation in both microfouling and macrofouling conditions. The most effective coating is one which consists of precursor, tetraethyl orthosilicate (HC006) that has a water contact angle > 100, without significant roughness (43.52 nm). However, improved roughness and wettability of a second coating, diethoxydimethylsilane (DMDEOS), showed real promise in relation to macrofouling reduction.

Probing skin physiology through the volatile footprint: Discriminating volatile emissions before and after acute barrier disruption.

Volatile organic compounds emitted by human skin were sampled before and after acute barrier disruption of the volar forearm to investigate the significance of this approach to skin physiology research. A small wearable housing integrating a solid-phase micro-extraction fibre permitting rapid enclosed headspace sampling of human skin volatiles is presented, enabling non-invasive sample collection in 15 minutes, in a comfortable wearable format. Gas chromatography-mass spectrometry was utilised to separate and identify the volatile metabolites. A total of 37 compounds were identified, with aldehydes (hexanal, nonanal, decanal), acids (nonanoic, decanoic, dodecanoic, tetradecanoic and pentadecanoic acids) and hydrocarbons (squalane, squalene) predominant within the chemical profile. Acute barrier disruption was achieved through tape stripping (TS) of the stratum corneum to determine the impact on the volatile signature. Principle component analysis demonstrated there to be a discriminating volatile signature before and after TS. The dysregulation of significant features was examined. Several compounds derived from sebaceous components and their oxidation products were altered following barrier disruption, including squalane, squalene, octanal and nonanal. The upregulation of glycine was also observed, which may indicate a perturbation to the skin's natural moisturising factor production. TS impacted the hydro-lipid film that functions within the skin barrier, resulting in a differing volatile signature from affected skin. This provides a valuable non-invasive approach for scientific and clinical studies in dermatology, particularly around dermatological disorders associated with compromised barrier function.

Robust universal nonrigid motion correction framework for first-pass cardiac MR perfusion imaging.

PURPOSE: To present and assess an automatic nonrigid image registration framework that compensates motion in cardiac magnetic resonance imaging (MRI) perfusion series and auxiliary images acquired under a wide range of conditions to facilitate myocardial perfusion quantification. MATERIALS AND METHODS: Our framework combines discrete feature matching for large displacement estimation with a dense variational optical flow formulation in a multithreaded architecture. This framework was evaluated on 291 clinical subjects to register 1.5T and 3.0T steady-state free-precession (FISP) and fast low-angle shot (FLASH) dynamic contrast myocardial perfusion images, arterial input function (AIF) images, and proton density (PD)-weighted images acquired under breath-hold (BH) and free-breath (FB) settings. RESULTS: Our method significantly improved frame-to-frame appearance consistency compared to raw series, expressed in correlation coefficient (R2 = 0.996 ± 3.735E-3 vs. 0.978 ± 2.024E-2, P < 0.0001) and mutual information (3.823 ± 4.098E-1 vs. 2.967 ± 4.697E-1, P < 0.0001). It is applicable to both BH (R2 = 0.998 ± 3.217E-3 vs. 0.990 ± 7.527E-3) and FB (R2 = 0.995 ± 3.410E-3 vs. 0.968 ± 2.257E-3) paradigms as well as FISP and FLASH sequences. The method registers PD images to perfusion T1 series (9.70% max increase in R2 vs. no registration, P < 0.001) and also corrects motion in low-resolution AIF series (R2 = 0.987 ± 1.180E-2 vs. 0.964 ± 3.860E-2, P < 0.001). Finally, we showed the myocardial perfusion contrast dynamic was preserved in the motion-corrected images compared to the raw series (R2 = 0.995 ± 6.420E-3). CONCLUSION: The critical step of motion correction prior to pixel-wise cardiac MR perfusion quantification can be performed with the proposed universal system. It is applicable to a wide range of perfusion series and auxiliary images with different acquisition settings. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1060-1072.

Evaluation of an automated method for arterial input function detection for first-pass myocardial perfusion cardiovascular magnetic resonance.

BACKGROUND: Quantitative assessment of myocardial blood flow (MBF) with first-pass perfusion cardiovascular magnetic resonance (CMR) requires a measurement of the arterial input function (AIF). This study presents an automated method to improve the objectivity and reduce processing time for measuring the AIF from first-pass perfusion CMR images. This automated method is used to compare the impact of different AIF measurements on MBF quantification. METHODS: Gadolinium-enhanced perfusion CMR was performed on a 1.5 T scanner using a saturation recovery dual-sequence technique. Rest and stress perfusion series from 270 clinical studies were analyzed. Automated image processing steps included motion correction, intensity correction, detection of the left ventricle (LV), independent component analysis, and LV pixel thresholding to calculate the AIF signal. The results were compared with manual reference measurements using several quality metrics based on the contrast enhancement and timing characteristics of the AIF. The median and 95% confidence interval (CI) of the median were reported. Finally, MBF was calculated and compared in a subset of 21 clinical studies using the automated and manual AIF measurements. RESULTS: Two clinical studies were excluded from the comparison due to a congenital heart defect present in one and a contrast administration issue in the other. The proposed method successfully processed 99.63% of the remaining image series. Manual and automatic AIF time-signal intensity curves were strongly correlated with median correlation coefficient of 0.999 (95% CI [0.999, 0.999]). The automated method effectively selected bright LV pixels, excluded papillary muscles, and required less processing time than the manual approach. There was no significant difference in MBF estimates between manually and automatically measured AIFs (p = NS). However, different sizes of regions of interest selection in the LV cavity could change the AIF measurement and affect MBF calculation (p = NS to p = 0.03). CONCLUSION: The proposed automatic method produced AIFs similar to the reference manual method but required less processing time and was more objective. The automated algorithm may improve AIF measurement from the first-pass perfusion CMR images and make quantitative myocardial perfusion analysis more robust and readily available.

The spectrum of disease in chronic traumatic encephalopathy.

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer's disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.

CMR provides comparable measurements of diastolic function as echocardiography.

Clinical application of cardiac magnetic resonance (CMR) is expanding but CMR assessment of LV diastolic function is still being validated. The purpose of this study was to validate assessments of left ventricular (LV) diastolic dysfunction (DD) using CMR by comparing with transthoracic echocardiography (TTE) performed on the same day. Patients with suspected or diagnosed cardiomyopathy (n = 63) and healthy volunteers (n = 24) were prospectively recruited and included in the study. CMR diastolic parameters were measured on cine images and velocity-encoded phase contrast cine images and compared with corresponding parameters measured on TTE. A contextual correlation feature tracking method was developed to calculate the mitral annular velocity curve. LV DD was classified by CMR and TTE following 2016 guidelines. Overall DD classification was 78.1% concordant between CMR and TTE (p < 0.0001). The trans-mitral inflow parameters correlated well between the two modalities (E, r = 0.78; A, r = 0.90; E/A, r = 0.82; all p < 0.0001) while the remaining diastolic parameters showed moderate correlation (e', r = 0.64; E/e', r = 0.54; left atrial volume index (LAVi), r = 0.61; all p < 0.0001). Classification of LV diastolic function by CMR showed good concordance with standardized grades established for TTE. CMR-based LV diastolic function may be integrated in routine clinical practice.Name of the registry: Technical Development of Cardiovascular Magnetic Resonance Imaging. Trial registration number: NCT00027170. Date of registration: November 26, 2001. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT00027170.

Hydralazine-Associated Vasculitis and Pulmonary Hemorrhage.

Hydralazine is a potent vasodilating medication used as adjunctive therapy for the treatment of hypertension. Rarely, hydralazine may cause the development of antineutrophil cytoplasmic antibody vasculitis with the pulmonary-renal syndrome. We are presenting a case of hydralazine-associated vasculitis and pulmonary hemorrhage.

Fatherhood is life changing: Uncovering structural and functional changes in the dad brain.

What are the cellular-level structural and functional changes underlying newly adaptive behaviors in the mammalian brain? In this issue of Neuron, Inada et al. (2022) identify the brain-wide connectivity and synaptic plasticity changes of hypothalamic oxytocin+ neurons in male mice contributing to their parental behaviors.

Assessment of anthropogenic pollution by monitoring occurrence and distribution of chemicals in the river Liffey in Dublin.

This paper evaluates for the first time the spatial distribution of a wide group of organic (phthalates, nitro, aliphatic, halogen, aromatic, phenol and amino compounds) and inorganic pollutants along the Liffey river in Dublin city. The work takes into account the effect of short-term weather conditions on the occurrence of these contaminants. The results showed that rainfall conditions affect the levels of pollutants along the river in the days following a rainfall event. In addition, the tributaries entering the river Liffey were not found to impact its water quality. In relation to organic pollutants, 2,4,6-trichlorophenol, 2-nitrophenol and phthalate compounds were found in many water samples between concentrations of 0.21 and 2.17 µg L-1. On the other hand, dimethyl phthalate was present in certain samples at levels around 100 µg L-1. The levels of these contaminants in the river were lower than the toxicity values reported in the literature. Regarding inorganic pollutants, nitrates were detected from 0.59 to 6.81 mg L-1 increasing from upstream to downstream. Based on the chemical nature and applications of detected pollutants, the river contamination can be mainly related to agricultural, industrial activities as well as diffuse urban contributions. These vary with location within a short distance and have the potential to impact aquatic biodiversity as the chemical composition changes with rainfall events.

Automated Segmental Analysis of Fully Quantitative Myocardial Blood Flow Maps by First-Pass Perfusion Cardiovascular Magnetic Resonance.

First pass gadolinium-enhanced cardiovascular magnetic resonance (CMR) perfusion imaging allows fully quantitative pixel-wise myocardial blood flow (MBF) assessment, with proven diagnostic value for coronary artery disease. Segmental analysis requires manual segmentation of the myocardium. This work presents a fully automatic method of segmenting the left ventricular myocardium from MBF pixel maps, validated on a retrospective dataset of 247 clinical CMR perfusion studies, each including rest and stress images of three slice locations, performed on a 1.5T scanner. Pixel-wise MBF maps were segmented using an automated pipeline including region growing, edge detection, principal component analysis, and active contours to segment the myocardium, detect key landmarks, and divide the myocardium into sectors appropriate for analysis. Automated segmentation results were compared against a manually defined reference standard using three quantitative metrics: Dice coefficient, Cohen Kappa and myocardial border distance. Sector-wise average MBF and myocardial perfusion reserve (MPR) were compared using Pearson's correlation coefficient and Bland-Altman Plots. The proposed method segmented stress and rest MBF maps of 243 studies automatically. Automated and manual myocardial segmentation had an average (± standard deviation) Dice coefficient of 0.86 ± 0.06, Cohen Kappa of 0.86 ± 0.06, and Euclidian distances of 1.47 ± 0.73 mm and 1.02 ± 0.51 mm for the epicardial and endocardial border, respectively. Automated and manual sector-wise MBF and MPR values correlated with Pearson's coefficient of 0.97 and 0.92, respectively, while Bland-Altman analysis showed bias of 0.01 and 0.07 ml/g/min. The validated method has been integrated with our fully automated MBF pixel mapping pipeline to aid quantitative assessment of myocardial perfusion CMR.

Nondestructive, high-resolution, chemically specific 3D nanostructure characterization using phase-sensitive EUV imaging reflectometry.

Next-generation nano- and quantum devices have increasingly complex 3D structure. As the dimensions of these devices shrink to the nanoscale, their performance is often governed by interface quality or precise chemical or dopant composition. Here, we present the first phase-sensitive extreme ultraviolet imaging reflectometer. It combines the excellent phase stability of coherent high-harmonic sources, the unique chemical sensitivity of extreme ultraviolet reflectometry, and state-of-the-art ptychography imaging algorithms. This tabletop microscope can nondestructively probe surface topography, layer thicknesses, and interface quality, as well as dopant concentrations and profiles. High-fidelity imaging was achieved by implementing variable-angle ptychographic imaging, by using total variation regularization to mitigate noise and artifacts in the reconstructed image, and by using a high-brightness, high-harmonic source with excellent intensity and wavefront stability. We validate our measurements through multiscale, multimodal imaging to show that this technique has unique advantages compared with other techniques based on electron and scanning probe microscopies.

Simultaneous Multi-Structure Segmentation of the Heart and Peripheral Tissues in Contrast Enhanced Cardiac Computed Tomography Angiography.

Contrast enhanced cardiac computed tomography angiography (CTA) is a prominent imaging modality for diagnosing cardiovascular diseases non-invasively. It assists the evaluation of the coronary artery patency and provides a comprehensive assessment of structural features of the heart and great vessels. However, physicians are often required to evaluate different cardiac structures and measure their size manually. Such task is very time-consuming and tedious due to the large number of image slices in 3D data. We present a fully automatic method based on a combined multi-atlas and corrective segmentation approach to label the heart and its associated cardiovascular structures. This method also automatically separates other surrounding intrathoracic structures from CTA images. Quantitative assessment of the proposed method is performed on 36 studies with a reference standard obtained from expert manual segmentation of various cardiac structures. Qualitative evaluation is also performed by expert readers to score 120 studies of the automatic segmentation. The quantitative results showed an overall Dice of 0.93, Hausdorff distance of 7.94 mm, and mean surface distance of 1.03 mm between automatically and manually segmented cardiac structures. The visual assessment also attained an excellent score for the automatic segmentation. The average processing time was 2.79 minutes. Our results indicate the proposed automatic framework significantly improves accuracy and computational speed in conventional multi-atlas based approach, and it provides comprehensive and reliable multi-structural segmentation of CTA images that is valuable for clinical application.