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Background: Pulmonary microvasculature alterations are implicated in emphysema pathogenesis, but the association between pulmonary microvascular blood volume (PMBV) and emphysema has not been directly assessed at scale, and prior studies have used non-specific measures of emphysema., Methods: The Multi-Ethnic Study of Atherosclerosis Lung Study invited participants recruited from the community without renal impairment to undergo contrast-enhanced dual-energy CT. Pulmonary blood volume was calculated by material decomposition; PMBV was defined as blood volume in the peripheral 2 cm of the lung. Non-contrast CT was acquired to assess per cent emphysema and novel CT emphysema subtypes, which include the diffuse emphysema subtype and small-airways-related combined bronchitic-apical emphysema subtype. Generalised linear regression models included age, sex, race/ethnicity, body size, smoking, total lung volume and small airway count., Results: Among 495 participants, 53% were never-smokers and the race/ethnic distribution was 35% white, 31% black, 15% Hispanic and 18% Asian. Mean PMBV was 352±120 mL; mean per cent emphysema was 4.95±4.75%. Lower PMBV was associated with greater per cent emphysema (-0.90% per 100 mL PMBV, 95% CI: -1.29 to -0.51). The association was of larger magnitude in participants with 10 or more pack-years smoking and airflow obstruction, but present among participants with no smoking history or airflow limitation, and was specific to the diffuse CT emphysema subtype (-1.48% per 100 mL PMBV, 95% CI: -2.31 to -0.55)., Conclusion: In this community-based study, lower PMBV was associated with greater per cent emphysema, including in participants without a smoking history or airflow limitation, and was specific to the diffuse CT emphysema subtype., Competing Interests: Competing interests: EAHo is a founder and shareholder of VIDA Diagnostics, which makes the software used for secondary per cent emphysema measures in this article. YS and NA report receiving grants from the NIH. JG is a shareholder of VIDA Diagnostics and reports receiving grants from the NIH. DWK acknowledges grant support from the US Department of Defense and ZOLL Medical Corporation for work unrelated to this study, is a co-founder and shareholder of OscillaVent, and is listed as a co-inventor on US and European patents related to multi-frequency oscillatory ventilation. Unrelated to this work, EDM reports consulting fees paid by Amgen, AstraZeneca, Boehringer Ingelheim, Edwards Lifescience, Esperion, Medtronic, Merck, Novo Nordisk, Novartis, New Amsterdam and Pfizer. Unrelated to this work, PN reports receiving grant funding from GE Healthcare, consulting fees from Cannon, honoraria from the Society of Cardiovascular CT and American Society of Nuclear Cardiology, as well as owning stock in Moderna. BS reports receiving grants from the NIH, Canadian Institutes of Health Research, Fonds de la recherche en santé du Québec and the Research Institute of the McGill University Health Centre. RGB reports receiving grants from the COPD Foundation, the US Environmental Protection Agency, the American Lung Association and the NIH., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

High-resolution full lung CT scans now enable the detailed segmentation of airway trees up to the 6th branching generation. The airway binary masks display very complex tree structures that may encode biological information relevant to disease risk and yet remain challenging to exploit via traditional methods such as meshing or skeletonization. Recent clinical studies suggest that some variations in shape patterns and caliber of the human airway tree are highly associated with adverse health outcomes, including all-cause mortality and incident COPD. However, quantitative characterization of variations observed on CT segmented airway tree remain incomplete, as does our understanding of the clinical and developmental implications of such. In this work, we present an unsupervised deep-learning pipeline for feature extraction and clustering of human airway trees, learned directly from projections of 3D airway segmentations. We identify four reproducible and clinically distinct airway sub-types in the MESA Lung CT cohort.

Robust quantification of pulmonary emphysema on computed tomography (CT) remains challenging for large-scale research studies that involve scans from different scanner types and for translation to clinical scans. Although the domain shifts in different CT scanners are subtle compared to shifts existing in other modalities (e.g., MRI) or cross-modality, emphysema is highly sensitive to it. Such subtle difference limits the application of general domain adaptation methods, such as image translation-based methods, as the contrast difference is too subtle to be distinguished. Existing studies have explored several directions to tackle this challenge, including density correction, noise filtering, regression, hidden Markov measure field (HMMF) model-based segmentation, and volume-adjusted lung density. Despite some promising results, previous studies either required a tedious workflow or eliminated opportunities for downstream emphysema subtyping, limiting efficient adaptation on a large-scale study. To alleviate this dilemma, we developed an end-to-end deep learning framework based on an existing HMMF segmentation framework. We first demonstrate that a regular UNet cannot replicate the existing HMMF results because of the lack of scanner priors. We then design a novel domain attention block, a simple yet efficient cross-modal block to fuse image visual features with quantitative scanner priors (a sequence), which significantly improves the results.

Background: Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations., Methods: New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined., Results: The algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91-1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near DRD1 , which is implicated in mucin hypersecretion (p=1.1 ×10 -8 ). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome., Conclusion: Large-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD., Competing Interests: Competing interests: EDA, PPB, AM, YS, WS, JHMA, MHC, DC, EH, DRJ, SK, JDK, TL, JL, ECO, WP, MRP, SSR, EKS, KEW and AFL reports receiving grants from the National Institutes of Health (NIH). JY performed the work at Columbia University but is now an employee of Google. EAH reports receiving grants from the NIH; being a founder and shareholder of VIDA Diagnostics; and holding patents for an apparatus for analysing CT images to determine the presence of pulmonary tissue pathology, an apparatus for image display and analysis, and a method for multiscale meshing of branching biological structures. EBA reports receiving grants from the American Heart Association and the NIH. CBC reports receiving personal fees from GlaxoSmithKline. MTD reports receiving a grant from the NHLBI and personal fees from AstraZeneca, GlaxoSmithKline, Pulmonx, PneumRx/BTG and Quark. MKH reports consulting for GlaxoSmithKline, AstraZeneca and Boehringer Ingelheim receiving research support from Novartis and Sunovion. NNH reports receiving grants from the NIH, Boehringer Ingelheim, and the COPD Foundation. JDK reports receiving grants from US Environmental Protection Agency and the NIH. FJM reports serving on COPD advisory boards for AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Sunovion and Teva; serving as a consultant for ProterixBio and Verona; serving on the steering committees of studies sponsored by the NHLBI, AstraZeneca, and GlaxoSmithKline; having served on data safety and monitoring boards of COPD studies supported by Genentech and GlaxoSmithKline. BMS reports receiving grants from the NIH, Canadian Institutes of Health Research (CIHR), Fonds de la recherche en santé du Québec (FRQS), the Research Institute of the McGill University Health Centre, the Quebec Lung Association and AstraZeneca. PGW reports receiving personal fees for consultancy from Theravance, AstraZeneca, Regeneron, Sanofi, Genentech, Roche and Janssen. RGB reports receiving grants from the COPD Foundation, the US Environmental Protection Agency (EPA), the American Lung Association and the NIH., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Non-alcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease, affecting approximately 30% of people worldwide. Histopathology reading of fibrosis patterns is crucial to diagnosing NAFLD. In particular, separating mild from severe stages corresponds to a critical transition as it correlates with clinical outcomes. Deep Learning for digitized histopathology whole-slide images (WSIs) can reduce high inter- and intra-rater variability. We demonstrate a novel solution to score fibrosis severity on a retrospective cohort of 152 Sirius-Red WSIs, with fibrosis stage annotated at slide level by an expert pathologist. We exploit multiple instance learning and multiple-inferences to address the sparsity of pathological signs. We achieved an accuracy of , an F1 score of and an AUC of . These results set new state-of-the-art benchmarks for this application., Competing Interests: The authors declare no competing interests exist., (© The Author(s) 2023.)

Total lung volume (TLV) at full inspiration is a parameter of significant interest in pulmonary physiology but requires computed tomography (CT) scanning of the full axial extent of the lung. There is a growing interest to infer TLV from cardiac CT scans, which are much more widely available in epidemiologic studies. In this study, we present an original approach to train a multi-view convolutional neural network (CNN) model to infer TLV from cardiac CT scans, which visualize about 2/3rd of the lung volume. Supervised learning is used, exploiting paired full-lung and cardiac CT scans in the Multi-Ethnic Study of Atherosclerosis (MESA). Our results show that our network outperforms existing regression models for TLV estimation, and achieves accuracy and reproducibility comparable to the scan-rescan reproducibility of TLV on full-lung CT.

Purpose: To develop an end-to-end deep learning (DL) framework to segment ventilation defects on pulmonary hyperpolarized MRI., Materials and Methods: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease (COPD) study is a nested longitudinal case-control study in older smokers. Between February 2016 and July 2017, 56 participants (age, mean ± SD, 74 ± 8 years; 34 men) underwent same breath-hold proton ( 1 H) and helium ( 3 He) MRI, which were annotated for non-ventilated, hypo-ventilated, and normal-ventilated lungs. In this retrospective DL study, 820 1 H and 3 He slices from 42/56 (75%) participants were randomly selected for training, with the remaining 14/56 (25%) for test. Full lung masks were segmented using a traditional U-Net on 1 H MRI and were imported into a cascaded U-Net, which were used to segment ventilation defects on 3 He MRI. Models were trained with conventional data augmentation (DA) and generative adversarial networks (GAN)-DA., Results: Conventional-DA improved 1 H and 3 He MRI segmentation over the non-DA model (P = 0.007 to 0.03) but GAN-DA did not yield further improvement. The cascaded U-Net improved non-ventilated lung segmentation (P < 0.005). Dice similarity coefficients (DSC) between manually and DL-segmented full lung, non-ventilated, hypo-ventilated, and normal-ventilated regions were 0.965 ± 0.010, 0.840 ± 0.057, 0.715 ± 0.175, and 0.883 ± 0.060, respectively. We observed no statistically significant difference in DCSs between participants with and without COPD (P = 0.41, 0.06, and 0.18 for non-ventilated, hypo-ventilated, and normal-ventilated regions, respectively)., Conclusion: The proposed cascaded U-Net framework generated fully-automated segmentation of ventilation defects on 3 He MRI among older smokers with and without COPD that is consistent with our reference method., (Copyright © 2022. Published by Elsevier Inc.)

Pulmonary emphysema overlaps considerably with chronic obstructive pulmonary disease (COPD), and is traditionally subcategorized into three subtypes previously identified on autopsy. Unsupervised learning of emphysema subtypes on computed tomography (CT) opens the way to new definitions of emphysema subtypes and eliminates the need of thorough manual labeling. However, CT-based emphysema subtypes have been limited to texture-based patterns without considering spatial location. In this work, we introduce a standardized spatial mapping of the lung for quantitative study of lung texture location and propose a novel framework for combining spatial and texture information to discover spatially-informed lung texture patterns (sLTPs) that represent novel emphysema subtype candidates. Exploiting two cohorts of full-lung CT scans from the MESA COPD (n = 317) and EMCAP (n = 22) studies, we first show that our spatial mapping enables population-wide study of emphysema spatial location. We then evaluate the characteristics of the sLTPs discovered on MESA COPD, and show that they are reproducible, able to encode standard emphysema subtypes, and associated with physiological symptoms.

Background: Intrauterine and postnatal weight are widely regarded as biomarkers of fetal and neonatal wellbeing, but optimal weight gain following preterm birth is unknown. We aimed to describe changes over time in birthweight and postnatal weight gain in very and extremely preterm babies, in relation to major morbidity and healthy survival., Methods: In this cohort study, we used whole-population data from the UK National Neonatal Research Database for infants below 32 weeks gestation admitted to neonatal units in England and Wales between Jan 1, 2008, and Dec 31, 2019. We used non-linear Gaussian process to estimate monthly trends, and Bayesian multilevel regression to estimate unadjusted and adjusted coefficients. We evaluated birthweight; weight change from birth to 14 days; weight at 36 weeks postmenstrual age; associated Z scores; and longitudinal weights for babies surviving to 36 weeks postmenstrual age with and without major morbidities. We adjusted birthweight for antenatal, perinatal, and demographic variables. We additionally adjusted change in weight at 14 days and weight at 36 weeks postmenstrual age, and their Z scores, for postnatal variables., Findings: The cohort comprised 90 817 infants. Over the 12-year period, mean differences adjusted for antenatal, perinatal, demographic, and postnatal variables were 0 g (95% compatibility interval -7 to 7) for birthweight (-0·01 [-0·05 to 0·03] for change in associated Z score); 39 g (26 to 51) for change in weight from birth to 14 days (0·14 [0·08 to 0·19] for change in associated Z score); and 105 g (81 to 128) for weight at 36 weeks postmenstrual age (0·27 [0·21 to 0·33] for change in associated Z score). Greater weight at 36 weeks postmenstrual age was robust to additional adjustment for enteral nutritional intake. In babies surviving without major morbidity, weight velocity in all gestational age groups stabilised at around 34 weeks postmenstrual age at 16-25 g per day along parallel percentile lines., Interpretation: The birthweight of very and extremely preterm babies has remained stable over 12 years. Early postnatal weight loss has decreased, and subsequent weight gain has increased, but weight at 36 weeks postmenstrual age is consistently below birth percentile. In babies without major morbidity, weight velocity follows a consistent trajectory, offering opportunity to construct novel preterm growth curves despite lack of knowledge of optimal postnatal weight gain., Funding: UK Medical Research Council., Competing Interests: Declaration of interests NM reports grants outside the submitted work from the UK Medical Research Council, UK National Institute of Health Research, March of Dimes, British Heart Foundation, HCA international, Health Data Research UK, Shire Pharmaceuticals, Chiesi Pharmaceuticals, Prolacta Life Sciences, and Westminster Children's Research Fund; is a member of the Nestle Scientific Advisory Board and accepts no personal remuneration for this role; and reports travel and accommodation reimbursements from Chiesi, Nestle, and Shire. CG reports grants from the UK National Institute for Health Research and Canadian Institute for Health Research in support of randomised controlled trials of nutritional interventions in preterm neonates. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: The COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes and outcomes., Design: Observational cohort study using the UK National Neonatal Research Database., Setting: England and Wales., Participants: Admissions to National Health Service neonatal units from 2012 to 2020., Main Outcome Measures: Admissions by gestational age, ethnicity and Index of Multiple Deprivation, and key care processes and outcomes., Methods: We calculated differences in numbers and rates between April and June 2020 (spring), the first 3 months of national lockdown (COVID-19 period), and December 2019-February 2020 (winter), prior to introduction of mitigation measures, and compared them with the corresponding differences in the previous 7 years. We considered the COVID-19 period highly unusual if the spring-winter difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion., Results: Marked fluctuations occurred in all measures over the 8 years with several highly unusual changes during the COVID-19 period. Total admissions fell, having risen over all previous years (COVID-19 difference: -1492; previous 7-year difference range: +100, +1617; p<0.001); full-term black admissions rose (+66; -64, +35; p<0.001) whereas Asian (-137; -14, +101; p<0.001) and white (-319; -235, +643: p<0.001) admissions fell. Transfers to higher and lower designation neonatal units increased (+129; -4, +88; p<0.001) and decreased (-47; -25, +12; p<0.001), respectively. Total preterm admissions decreased (-350; -26, +479; p<0.001). The fall in extremely preterm admissions was most marked in the two lowest socioeconomic quintiles., Conclusions: Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

The morphology of the proximal human airway tree is highly variable in the general population, and known variants in airway branching patterns are associated with increased risk of COPD and with polymorphisms in growth factors involved in pulmonary development. Variation in the geometry and topology of the airway tree remains incompletely characterized, and their clinical implications are not yet understood. In this work, we present an approach to unsupervised clustering of airway tree structures in Billera-Holmes-Vogtmann tree-space. We validate our pipeline on synthetic airway tree data, and apply our algorithm to identify reproducible and morphologically distinct airway tree subtypes in the MESA Lung CT cohort.

We used agnostic, unsupervised machine learning to cluster a large clinical database of information on infants admitted to neonatal units in England. Our aim was to obtain insights into nutritional practice, an area of central importance in newborn care, utilising the UK National Neonatal Research Database (NNRD). We performed clustering on time-series data of daily nutritional intakes for very preterm infants born at a gestational age less than 32 weeks (n = 45,679) over a six-year period. This revealed 46 nutritional clusters heterogeneous in size, showing common interpretable clinical practices alongside rarer approaches. Nutritional clusters with similar admission profiles revealed associations between nutritional practice, geographical location and outcomes. We show how nutritional subgroups may be regarded as distinct interventions and tested for associations with measurable outcomes. We illustrate the potential for identifying relationships between nutritional practice and outcomes with two examples, discharge weight and bronchopulmonary dysplasia (BPD). We identify the well-known effect of formula milk on greater discharge weight as well as support for the plausible, but insufficiently evidenced view that human milk is protective against BPD. Our framework highlights the potential of agnostic machine learning approaches to deliver clinical practice insights and generate hypotheses using routine data.

Identifying arrhythmia substrates and quantifying their heterogeneity has great potential to provide critical guidance for radio frequency ablation. However, quantitative analysis of heterogeneity on cardiac optical coherence tomography (OCT) images is lacking. In this paper, we conduct the first study on quantifying cardiac tissue heterogeneity from human OCT images. Our proposed method applies a dropout-based Monte Carlo sampling technique to measure the model uncertainty. The heterogeneity information is extracted by decoupling the intra/inter-tissue heterogeneity and tissue boundary uncertainty from the uncertainty measurement. We empirically demonstrate that our model can highlight the subtle features from OCT images, and the heterogeneity information extracted is positively correlated with the tissue heterogeneity information from corresponding histology images.

Neuroimaging and genetic biomarkers have been widely studied from discriminative perspectives towards Alzheimer's disease (AD) classification, since neuroanatomical patterns and genetic variants are jointly critical indicators for AD diagnosis. Generative methods, designed to model common occurring patterns, could potentially advance the understanding of this disease, but have not been fully explored for AD characterization. Moreover, the introduction of a supervised component into the generative process can constrain the model for more discriminative characterization. In this study, we propose an original method based on supervised topic modeling to characterize AD from a generative perspective, yet maintaining discriminative power at differentiating disease populations. Our topic modeling jointly exploits discretized image features and categorical genetic features. Diagnostic information - cognitively normal (CN), mild cognitive impairment (MCI) and AD - is introduced as a supervision variable. Experimental results on the ADNI cohort demonstrate that our model, while achieving competitive discriminative performance, can discover topics revealing both well-known and novel neuroanatomical patterns including temporal, parietal and frontal regions; as well as associations between genetic factors and neuroanatomical patterns.

Purpose: Measurement of vertebral axial rotation (VAR) is relevant for the assessment of scoliosis. Stokes method allows estimating VAR in frontal X-rays from the relative position of the pedicles and the vertebral body. This method requires identifying these landmarks for each vertebral level, which is time-consuming. In this work, a quasi-automated method for pedicle detection and VAR estimation was proposed., Method: A total of 149 healthy and adolescent idiopathic scoliotic (AIS) subjects were included in this retrospective study. Their frontal X-rays were collected from multiple sites and manually annotated to identify the spinal midline and pedicle positions. Then, an automated pedicle detector was developed based on image analysis, machine learning and fast manual identification of a few landmarks. VARs were calculated using the Stokes method in a validation dataset of 11 healthy (age 6-33 years) and 46 AIS subjects (age 6-16 years, Cobb 10°-46°), both from detected pedicles and those manually annotated to compare them. Sensitivity of pedicle location to the manual inputs was quantified on 20 scoliotic subjects, using 10 perturbed versions of the manual inputs., Results: Pedicles centers were localized with a precision of 84% and mean difference of 1.2 ± 1.2 mm, when comparing with manual identification. Comparison of VAR values between automated and manual pedicle localization yielded a signed difference of - 0.2 ± 3.4°. The uncertainty on pedicle location was smaller than 2 mm along each image axis., Conclusion: The proposed method allowed calculating VAR values in frontal radiographs with minimal user intervention and robust quasi-automated pedicle localization. These slides can be retrieved under Electronic Supplementary Material.

Full quantification of regional cerebral metabolic rate of glucose (rCMRglu) with [ 18 F]fluorodeoxy-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging requires measurement of an arterial input function (AIF) curve, which is obtained with an invasive arterial blood sampling procedure during the scan. We previously proposed a non-invasive simultaneous estimation (nSIME) method that quantifies binding of a PET radioligand by combining individual electronic health records information and a pharmacokinetic AIF (PK-AIF) model. Initially applied only to [ 11 C]DASB data, in this study we validate nSIME for a different radioligand, [ 18 F]FDG, adapting the algorithm to the specific distribution and metabolism of this radioligand. We evaluate the impact of the PK-AIF model, the number of [ 18 F]FDG-specific soft constraints, and the type of predictive strategy. The accuracy of nSIME is then compared to a population-based approach. All analyses are conducted on 67 [ 18 F]FDG PET scans with arterial blood data available for comparison. nSIME performance is optimal for [ 18 F]FDG when using the PK-AIF model, two soft constraints, and an aggregate model to predict the soft constraint values. Higher correlation and lower Bland-Altman spread against gold standard rCMRglu values based on arterial blood measurements are observed for nSIME (r = 0.83, spread = 1.55) compared to the population-based approach (r = 0.77, spread = 2.12). nSIME provides a data-driven estimation of both amplitude and shape of the AIF curve at the individual level and potentially enables non-invasive quantification of PET data across radioligands, avoiding the need for arterial blood sampling.

Emphysema quantification and sub-typing is actively studied on cohorts of full-lung high-resolution CT (HRCT) scans, with promising results. Transfer of quantification and classification tools to cardiac CT scans, which involve 70% of the lungs, is challenging due to lower image resolution and degradation of textural patterns. In this study, we propose an original deep-learning domain-adaptation framework to use a pre-existing dictionary of lung texture patterns (LTP), learned on gold-standard full-lung HRCT scans, to label emphysema regions on cardiac CT scans. The method exploits convolutional neural networks (CNNs) trained for: 1) supervised lung texture classification on synthetic cardiac images, and 2) adversarial learning to discriminate between real and synthetic cardiac images. Combination of the classification and adversarial tasks enables to label real cardiac CT scans, and is evaluated on the MESA cohort (N = 15,357 scans). Our results show that image features derived from the adversarial training preserve the labeling accuracy on synthetic scans. LTP histogram signatures generated on 4,315 longitudinal pairs of cardiac CT scans, show high level of consistency over time and scanner generations. The ability to robustly label emphysema texture patterns on cardiac CT scans will enable large-scale longitudinal studies over 10 years of follow-up, for better understanding of the disease progression.

This paper reviews the state-of-the-art in denoising methods for biological microscopy images and introduces a new and original sparsity-based algorithm. The proposed method combines total variation (TV) spatial regularization, enhancement of low-frequency information, and aggregation of sparse estimators and is able to handle simple and complex types of noise (Gaussian, Poisson, and mixed), without any a priori model and with a single set of parameter values. An extended comparison is also presented, that evaluates the denoising performance of the thirteen (including ours) state-of-the-art denoising methods specifically designed to handle the different types of noises found in bioimaging. Quantitative and qualitative results on synthetic and real images show that the proposed method outperforms the other ones on the majority of the tested scenarios.

Automated detection and segmentation of pulmonary nodules on lung computed tomography (CT) scans can facilitate early lung cancer diagnosis. Existing supervised approaches for automated nodule segmentation on CT scans require voxel-based annotations for training, which are labor- and time-consuming to obtain. In this work, we propose a weakly-supervised method that generates accurate voxel-level nodule segmentation trained with image-level labels only. By adapting a convolutional neural network (CNN) trained for image classification, our proposed method learns discriminative regions from the activation maps of convolution units at different scales, and identifies the true nodule location with a novel candidate-screening framework. Experimental results on the public LIDC-IDRI dataset demonstrate that, our weakly-supervised nodule segmentation framework achieves competitive performance compared to a fully-supervised CNN-based segmentation method.

Unsupervised discovery of pulmonary emphysema subtypes offers the potential for new definitions of emphysema on lung computed tomography (CT) that go beyond the standard subtypes identified on autopsy. Emphysema subtypes can be defined on CT as a variety of textures with certain spatial prevalence. However, most existing approaches for learning emphysema subtypes on CT are limited to texture features, which are sub-optimal due to the lack of spatial information. In this work, we exploit a standardized spatial mapping of the lung and propose a novel framework for combining spatial and texture information to discover spatially-informed lung texture patterns (sLTPs). Our spatial mapping is demonstrated to be a powerful tool to study emphysema spatial locations over different populations. The discovered sLTPs are shown to have high reproducibility, ability to encode standard emphysema subtypes, and significant associations with clinical characteristics.

Pulmonary emphysema overlaps considerably with chronic obstructive pulmonary disease (COPD), and is traditionally subcategorized into three subtypes: centrilobular emphysema (CLE), panlobular emphysema (PLE) and paraseptal emphysema (PSE). Automated classification methods based on supervised learning are generally based upon the current definition of emphysema subtypes, while unsupervised learning of texture patterns enables the objective discovery of possible new radiological emphysema subtypes. In this work, we use a variant of the Latent Dirichlet Allocation (LDA) model to discover lung macroscopic patterns (LMPs) in an unsupervised way from lung regions that encode emphysematous areas. We evaluate the possible utility of the LMPs as potential novel emphysema subtypes via measuring their level of reproducibility when varying the learning set and by their ability to predict traditional radiological emphysema subtypes. Experimental results show that our algorithm can discover highly reproducible LMPs, that predict traditional emphysema subtypes.

Pulmonary emphysema is traditionally subcategorized into three subtypes, which have distinct radiological appearances on computed tomography (CT) and can help with the diagnosis of chronic obstructive pulmonary disease (COPD). Automated texture-based quantification of emphysema subtypes has been successfully implemented via supervised learning of these three emphysema subtypes. In this work, we demonstrate that unsupervised learning on a large heterogeneous database of CT scans can generate texture prototypes that are visually homogeneous and distinct, reproducible across subjects, and capable of predicting accurately the three standard radiological subtypes. These texture prototypes enable automated labeling of lung volumes, and open the way to new interpretations of lung CT scans with finer subtyping of emphysema.

Cardiac computed tomography (CT) scans include approximately 2/3 of the lung and can be obtained with low radiation exposure. Large cohorts of population-based research studies reported high correlations of emphysema quantification between full-lung (FL) and cardiac CT scans, using thresholding-based measurements. This work extends a hidden Markov measure field (HMMF) model-based segmentation method for automated emphysema quantification on cardiac CT scans. We show that the HMMF-based method, when compared with several types of thresholding, provides more reproducible emphysema segmentation on repeated cardiac scans, and more consistent measurements between longitudinal cardiac and FL scans from a diverse pool of scanner types and thousands of subjects with ten thousands of scans.

Automated texture analysis of lung computed tomography (CT) images is a critical tool in subtyping pulmonary emphysema and diagnosing chronic obstructive pulmonary disease (COPD). Texton-based methods encode lung textures with nearest-texton frequency histograms, and have achieved high performance for supervised classification of emphysema subtypes from annotated lung CT images. In this work, we first explore characterizing lung textures with sparse decomposition from texton dictionaries, using different regularization strategies, and then extend the sparsity-inducing constraint to the construction of the dictionaries. The methods were evaluated on a publicly available lung CT database of annotated emphysema subtypes. We show that enforcing sparse decompositions from texton dictionaries and unsupervised dictionary learning can achieve high classification accuracy (>90%). The flexibility of sparse-inducing models embedded either in the representation stage or dictionary learning stage has potential in providing consistency in classification performance on heterogeneous lung CT datasets with further parameter tuning.

This paper presents a novel variational segmentation framework combining shape priors and parametric intensity distribution modeling for extracting the fetal envelope on 3D obstetric ultrasound images. To overcome issues related to poor image quality and missing boundaries, we inject three types of information in the segmentation process: tissue-specific parametric modeling of pixel intensities, a shape prior for the fetal envelope and a shape model of the fetus' back. The shape prior is encoded with Legendre moments and used to constraint the evolution of a level-set function. The back model is used to post-process the segmented fetal envelope. Results are presented on 3D ultrasound data and compared to a set of manual segmentations. The robustness of the algorithm is studied, and both visual and quantitative comparisons show satisfactory results obtained by the proposed method on the tested dataset., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Quantitative analysis of positron emission tomography (PET) brain imaging data requires a metabolite-corrected arterial input function (AIF) for estimation of distribution volume and related outcome measures. Collecting arterial blood samples adds risk, cost, measurement error, and patient discomfort to PET studies. Minimally invasive AIF estimation is possible with simultaneous estimation (SIME), but at least one arterial blood sample is necessary. In this study, we describe a noninvasive SIME (nSIME) approach that utilizes a pharmacokinetic input function model and constraints derived from machine learning applied to an electronic health record database consisting of "long tail" data (digital records, paper charts, and handwritten notes) that were collected ancillary to the PET studies. We evaluated the performance of nSIME on 95 [(11)C]DASB PET scans that had measured AIFs. The results indicate that nSIME is a promising alternative to invasive AIF measurement. The general framework presented here may be expanded to other metabolized radioligands, potentially enabling quantitative analysis of PET studies without blood sampling. A glossary of technical abbreviations is provided at the end of this paper.

Quantification of regional cerebral metabolic rate of glucose (rCMRglu) via positron emission tomography (PET) imaging requires measuring the arterial input function (AIF) via invasive arterial blood sampling. In this study we describe a non-invasive approach, the non-invasive simultaneous estimation (nSIME), for the estimation of rCMRglu that considers a pharmacokinetic input function model and constraints derived from machine learning applied to a fusion of individual medical health records and dynamic [(18)F]-FDG-PET brain images data. The results obtained with our data indicate potential for future clinical application of nSIME, with correlation measures of 0.87 for rCMRglu compared to quantification with full arterial blood sampling.

The extent of pulmonary emphysema is commonly estimated from CT scans by computing the proportional area of voxels below a predefined attenuation threshold. However, the reliability of this approach is limited by several factors that affect the CT intensity distributions in the lung. This work presents a novel method for emphysema quantification, based on parametric modeling of intensity distributions and a hidden Markov measure field model to segment emphysematous regions. The framework adapts to the characteristics of an image to ensure a robust quantification of emphysema under varying CT imaging protocols, and differences in parenchymal intensity distributions due to factors such as inspiration level. Compared to standard approaches, the presented model involves a larger number of parameters, most of which can be estimated from data, to handle the variability encountered in lung CT scans. The method was applied on a longitudinal data set with 87 subjects and a total of 365 scans acquired with varying imaging protocols. The resulting emphysema estimates had very high intra-subject correlation values. By reducing sensitivity to changes in imaging protocol, the method provides a more robust estimate than standard approaches. The generated emphysema delineations promise advantages for regional analysis of emphysema extent and progression.

Ultrasonic transient elastography (TE), enables to assess, under active mechanical constraints, the elasticity of the liver, which correlates with hepatic fibrosis stages. This technique is routinely used in clinical practice to assess noninvasively liver stiffness. The Fibroscan system used in this work generates a shear wave via an impulse stress applied on the surface of the skin and records a temporal series of radio-frequency (RF) lines using a single-element ultrasound probe. A shear wave propagation map (SWPM) is generated as a 2-D map of the displacements along depth and time, derived from the correlations of the sequential 1-D RF lines, assuming that the direction of propagation (DOP) of the shear wave coincides with the ultrasound beam axis (UBA). Under the assumption of pure elastic tissue, elasticity is proportional to the shear wave speed. This paper introduces a novel approach to the processing of the SWPM, deriving the maximum likelihood estimate of the shear wave speed when comparing the observed displacements and the estimates provided by the Green's functions. A simple parametric model is used to interface Green's theoretical values of noisy measures provided by the SWPM, taking into account depth-varying attenuation and time-delay. The proposed method was evaluated on numerical simulations using a finite element method simulator and on physical phantoms. Evaluation on this test database reported very high agreements of shear wave speed measures when DOP and UBA coincide.

The behavior and performance of denoising algorithms are governed by one or several parameters, whose optimal settings depend on the content of the processed image and the characteristics of the noise, and are generally designed to minimize the mean squared error (MSE) between the denoised image returned by the algorithm and a virtual ground truth. In this paper, we introduce a new Poisson-Gaussian unbiased risk estimator (PG-URE) of the MSE applicable to a mixed Poisson-Gaussian noise model that unifies the widely used Gaussian and Poisson noise models in fluorescence bioimaging applications. We propose a stochastic methodology to evaluate this estimator in the case when little is known about the internal machinery of the considered denoising algorithm, and we analyze both theoretically and empirically the characteristics of the PG-URE estimator. Finally, we evaluate the PG-URE-driven parametrization for three standard denoising algorithms, with and without variance stabilizing transforms, and different characteristics of the Poisson-Gaussian noise mixture.

Iterative reconstruction with point spread function (PSF) modeling improves contrast recovery in positron emission tomography (PET) images, but also introduces ringing artifacts and over enhancement that is contrast and object size dependent. Mitigation of these artifacts is crucial for clinical and research purposes. In this work we introduce a new iterative regularized reconstruction method that incorporates locally-weighted total variation denoising designed to suppress artifacts induced by PSF modeling. The reconstruction method is evaluated on a simulated cylindrical phantom and preliminary results show that ringing artifacts are suppressed while contrast recovery is maintained.

The development of 3-D ultrasonic probes and 3-D ultrasound (3DUS) imaging offers new functionalities that call for specific image processing developments. In this paper, we propose an original method for the segmentation of the utero-fetal unit (UFU) from 3DUS volumes, acquired during the first trimester of gestation. UFU segmentation is required for a number of tasks, such as precise organ delineation, 3-D modeling, quantitative measurements, and evaluation of the clinical impact of 3-D imaging. The segmentation problem is formulated as the optimization of a partition of the image into two classes of tissues: the amniotic fluid and the fetal tissues. A Bayesian formulation of the partition problem integrates statistical models of the intensity distributions in each tissue class and regularity constraints on the contours. An energy functional is minimized using a level set implementation of a deformable model to identify the optimal partition. We propose to combine Rayleigh, Normal, Exponential, and Gamma distribution models to compute the region homogeneity constraints. We tested the segmentation method on a database of 19 antenatal 3DUS images. Promising results were obtained, showing the flexibility of the level set formulation and the interest of learning the most appropriate statistical models according to the idiosyncrasies of the data and the tissues. The segmentation method was shown to be robust to different types of initialization and to provide accurate results, with an average overlap measure of 0.89 when comparing with manual segmentations.

This paper presents a study of the effects of scanning parameters variability when assessing glioma sizes on MRI. A database of lesions of various shapes and sizes, segmented on 3D-SPGR MRI images, was acquired on 65 patients with low-grade glioma. Simulations of large slice thickness and patient's head rotation were performed, allowing us to study their influence on two size indices: the bi-dimensional diameter product index (computed with the two largest diameters method) and the equivalent diameter index (computed with the volume segmentation method). Results show that thick slices and axial plane rotation can induce average (maximal) uncertainties on the bi-dimensional diameter product index between 32 and 6 % (150 %) for small and large tumors (size range 0.5-286 ml). The uncertainty on the equivalent diameter index, for the same categories of tumors, drops below 8 and 0.1 % (23 %). This study shows that the volume segmentation method is subject to less variability inherent to scanning conditions compared to the two largest diameters method. It also emphasizes the need for strict clinical guidelines on the replication of scanning conditions when performing MRI follow-ups on patients harboring small tumors. These implications await confirmation on a series of real patients being re-scanned with FLAIR MRI.

Over the past two decades, intravascular ultrasound (IVUS) image segmentation has remained a challenge for researchers while the use of this imaging modality is rapidly growing in catheterization procedures and in research studies. IVUS provides cross-sectional grayscale images of the arterial wall and the extent of atherosclerotic plaques with high spatial resolution in real time. In this paper, we review recently developed image processing methods for the detection of media-adventitia and luminal borders in IVUS images acquired with different transducers operating at frequencies ranging from 20 to 45 MHz. We discuss methodological challenges, lack of diversity in reported datasets, and weaknesses of quantification metrics that make IVUS segmentation still an open problem despite all efforts. In conclusion, we call for a common reference database, validation metrics, and ground-truth definition with which new and existing algorithms could be benchmarked.

A differential analysis framework of longitudinal FLAIR MRI volumes is proposed, based on non-linear gray value mapping, to quantify low-grade glioma growth. First, MRI volumes were mapped to a common range of gray levels via a midway-based histogram mapping. This mapping enabled direct comparison of MRI data and computation of difference maps. A statistical analysis framework of intensity distributions in midway-mapped MRI volumes as well as in their difference maps was designed to identify significant difference values, enabling quantification of low-grade glioma growth, around the borders of an initial segmentation. Two sets of parameters, corresponding to optimistic and pessimistic growth estimations, were proposed. The influence and modeling of MRI inhomogeneity field on a novel midway-mapping framework using image models with multiplicative contrast changes was studied. Clinical evaluation was performed on 32 longitudinal clinical cases from 13 patients. Several growth indices were measured and evaluated in terms of accuracy, compared to manual tracing. Results from the clinical evaluation showed that millimetric precision on a specific volumetric radius growth index measurement can be obtained automatically with the proposed differential analysis. The automated optimistic and pessimistic growth estimates behaved as expected, providing upper and lower bounds around the manual growth estimations., (Copyright © 2011. Published by Elsevier B.V.)

Ultrasonic elastography, via vibration-controlled transient elastography (VCTE), enables to assess, under active mechanical constraints, the elasticity of the liver, correlating with fibrosis stages. On the other hand, the same VCTE probe can also be used in passive mode, acquiring RF lines at different locations in the liver. This paper presents a thorough evaluation of passive-mode RF spectral parameters (integrated backscatter coefficient, power spectral index, effective scattering size and spectral variance), for tissue characterization on a large cohort of volunteers with various ranges of elasticity measures. Results showed that capabilities to discriminate between liver and subcutaneous fat tissues were highly variable among spectral parameters. Furthermore, it appears that no in vivo discrimination of liver elasticity/fibrosis stage can be performed with passive RF spectral analysis, at 3.5MHz.

Anatomical models of pregnant women are used in several applications, such as numerical dosimetry, to assess the potential effects of electromagnetic fields on biological tissues, or medical simulation. Recent advances in medical imaging have enabled the generation of realistic and detailed models of human beings. The construction of pregnant woman models remains a complex task, since it is not possible to acquire whole-body images. Only few models have been developed up to now, and they all present some limitations regarding the representation of anatomical variability of the fetus shape and position over the entire gestation. This paper describes a complete methodology that intends to automate each step of the construction of pregnant women models. The proposed approach relies on the segmentation of 3-D ultrasonic and 3-D magnetic resonance imaging (MRI) data, and on dedicated computer graphics tools. The lack of complete anatomical information for the mother in image data is compensated, in an original way, by merging the available information with a synthetic woman model, deformed to match the image-based information. A set of models anatomically validated by clinical experts is presented. They include detailed information on uterofetal units and cover different gestational stages with various fetal positions.

Recent advances in 4D imaging and real-time imaging provide image data with clinically important cardiac dynamic information at high spatial or temporal resolution. However, the enormous amount of information contained in these data has also raised a challenge for traditional image analysis algorithms in terms of efficiency. In this paper, a novel deformable model framework, Active Geometric Functions (AGF), is introduced to tackle the real-time segmentation problem. As an implicit framework paralleling to level-set, AGF has mathematical advantages in efficiency and computational complexity as well as several flexible feature similar to level-set framework. AGF is demonstrated in two cardiac applications: endocardial segmentation in 4D ultrasound and myocardial segmentation in MRI with super high temporal resolution. In both applications, AGF can perform real-time segmentation in several milliseconds per frame, which was less than the acquisition time per frame. Segmentation results are compared to manual tracing with comparable performance with inter-observer variability. The ability of such real-time segmentation will not only facilitate the diagnoses and workflow, but also enables novel applications such as interventional guidance and interactive image acquisition with online segmentation., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

We present a new technique to delineate lumen borders in intravascular ultrasound (IVUS) volumes of images acquired with a high-frequency Volcano (Rancho Cordova, CA) 45MHz transducer. Our technique relies on projection of IVUS sub-volumes onto orthogonal directional brushlet functions. Through selective projection of IVUS sub-volumes images and their Fourier transforms, tissue-specific backscattered magnitudes and phases identified within brushlet coefficients. We take advantage of such characteristics and construct 2.5-dimensional (2.5-D) magnitudes-phase histograms of coefficients in the transformed complex brushlet domain that contain distinct peaks corresponding to blood and non-blood regions. We exploit these peaks to mask out coefficients that represent blood regions and ultimately detect the luminal border after spatial regularization employing a parametric deformable model. We quantify our results by comparing them to manually traced borders by an expert on 2 datasets, containing 108 frames. We show that our approach is well suited for isolating coherent (i.e. plaque) structures from incoherent (i.e. blood) ones in IVUS pullbacks and detecting the lumen border, a challenging problem particularly in images acquired with high frequency transducers.

Vibration-controlled transient elastography (VCTETM) technique is routinely used in clinical practice to assess non-invasively the liver stiffness which is correlated to hepatic fibrosis. Adequate use of the VCTETM probe requires the knowledge of the distance between the skin and the liver parenchyma. This paper compares two methods to estimate this distance using spatial variations of the spectral content of ultrasound radiofrequency (RF) lines, obtained from a probe consisting of a single element ultrasound transducer placed in front of the liver right lobe. Results on a database of 188 patients, including normal-weight and obese persons, show that the spectral variance can accurately discriminate the subcutaneous fat from the liver tissue. The proposed algorithm works in real-time and is suitable for VCTETM scanning protocol setup.

Vascular diseases are among the most important public health problems in developed countries. Given the size and complexity of modern angiographic acquisitions, segmentation is a key step toward the accurate visualization, diagnosis and quantification of vascular pathologies. Despite the tremendous amount of past and on-going dedicated research, vascular segmentation remains a challenging task. In this paper, we review state-of-the-art literature on vascular segmentation, with a particular focus on 3D contrast-enhanced imaging modalities (MRA and CTA). We structure our analysis along three axes: models, features and extraction schemes. We first detail model-based assumptions on the vessel appearance and geometry which can embedded in a segmentation approach. We then review the image features that can be extracted to evaluate these models. Finally, we discuss how existing extraction schemes combine model and feature information to perform the segmentation task. Each component (model, feature and extraction scheme) plays a crucial role toward the efficient, robust and accurate segmentation of vessels of interest. Along each axis of study, we discuss the theoretical and practical properties of recent approaches and highlight the most advanced and promising ones.

Dynamic cardiac metrics, including myocardial strains and displacements, provide a quantitative approach to evaluate cardiac function. However, in current clinical diagnosis, largely 2D strain measures are used despite the fact that cardiac motions are complex 3D volumes over time. Recent advances in 4D ultrasound enable the capability to capture such complex motion in a single image data set. In our previous work, a 4D optical flow based motion tracking algorithm was developed to extract fully 4D dynamic cardiac metrics from such 4D ultrasound data. In order to quantitatively evaluate our tracking method, in-vivo coronary artery occlusion experiments at various locations were performed on three canine hearts. Each dog was screened with 4D ultrasound and sonomicrometry data was acquired during each occlusion study. The 4D ultrasound data from these experiments was then analyzed with our tracking method and estimated principal strain measures were directly compared to those recorded by sonomicrometry, and showed strong agreement. This is the first validation study of optical flow based strain estimation for 4D ultrasound with direct comparison with sonomicrometry using in-vivo data.

Matrix-phased array transducers for real-time 3-D ultrasound enable fast, noninvasive visualization of cardiac ventricles. Typically, 3-D ultrasound images are semiautomatically segmented to extract the left ventricular endocardial surface at end-diastole and end-systole. Automatic segmentation and propagation of this surface throughout the entire cardiac cycle is a challenging and cumbersome task. If the position of the endocardial surface is provided at one or two time frames during the cardiac cycle, automated tracking of the surface over the remaining time frames could reduce the workload of cardiologists and optimize analysis of 3-D ultrasound data. In this paper, we applied a region-based tracking algorithm to track the endocardial surface between two reference frames that were manually segmented. To evaluate the tracking of the endocardium, the method was applied to 40 open-chest dog datasets with 484 frames in total. Ventricular geometry and volumes derived from region-based endocardial surfaces and manual tracing were quantitatively compared, showing strong correlation between the two approaches. Statistical analysis showed that the errors from tracking were within the range of interobserver variability of manual tracing. Moreover, our algorithm performed well on ischemia datasets, suggesting that the method is robust-to-abnormal wall motion. In conclusion, the proposed optical flow-based surface tracking method is very efficient and accurate, providing dynamic "interpolation" of segmented endocardial surfaces.

The presence of non-coherent blood speckle patterns makes the assessment of lumen size in intravascular ultrasound (IVUS) images a challenging problem, especially for images acquired with recent high frequency transducers. In this paper, we present a robust three-dimensional (3D) feature extraction algorithm based on the expansion of IVUS cross-sectional images and pullback directions onto an orthonormal complex brushlet basis. Several features are selected from the projections of low-frequency 3D brushlet coefficients. These representations are used as inputs to a neural network that is trained to classify blood maps on IVUS images. We evaluated the algorithm performance using repeated randomized experiments on sub-samples to validate the quantification of the blood maps when compared to expert manual tracings of 258 frames collected from three patients. Our results demonstrate that the proposed features extracted in the brushlet domain capture well the non-coherent structures of blood speckle, enabling identification of blood pools and enhancement of the lumen area.

We propose a recursive Bayesian model for the delineation of coronary arteries from 3D CT angiograms (cardiac CTA) and discuss the use of discrete minimal path techniques as an efficient optimization scheme for the propagation of model realizations on a discrete graph. Design issues such as the definition of a suitable accumulative metric are analyzed in the context of our probabilistic formulation. Our approach jointly optimizes the vascular centerline and associated radius on a 4D space+scale graph. It employs a simple heuristic scheme to dynamically limit scale-space exploration for increased computational performance. It incorporates prior knowledge on radius variations and derives the local data likelihood from a multiscale, oriented gradient flux-based feature. From minimal cost path techniques, it inherits practical properties such as computational efficiency and workflow versatility. We quantitatively evaluated a two-point interactive implementation on a large and varied cardiac CTA database. Additionally, results from the Rotterdam Coronary Artery Algorithm Evaluation Framework are provided for comparison with existing techniques. The scores obtained are excellent (97.5% average overlap with ground truth delineated by experts) and demonstrate the high potential of the method in terms of robustness to anomalies and poor image quality.

This paper presents the implementation and quantitative evaluation of a multiphase three-dimensional deformable model in a level set framework for automated segmentation of brain MRIs. The segmentation algorithm performs an optimal partitioning of three-dimensional data based on homogeneity measures that naturally evolves to the extraction of different tissue types in the brain. Random seed initialization was used to minimize the sensitivity of the method to initial conditions while avoiding the need for a priori information. This random initialization ensures robustness of the method with respect to the initialization and the minimization set up. Postprocessing corrections with morphological operators were applied to refine the details of the global segmentation method. A clinical study was performed on a database of 10 adult brain MRI volumes to compare the level set segmentation to three other methods: "idealized" intensity thresholding, fuzzy connectedness, and an expectation maximization classification using hidden Markov random fields. Quantitative evaluation of segmentation accuracy was performed with comparison to manual segmentation computing true positive and false positive volume fractions. A statistical comparison of the segmentation methods was performed through a Wilcoxon analysis of these error rates and results showed very high quality and stability of the multiphase three-dimensional level set method.

Protein production has experienced great advances in recent years. In particular, high throughput protein production, coupled with the use of robotics, outputs thousands of mixtures in micro-array wells. To detect the presence of protein crystal formation, images of these wells are acquired regularly using robotic cameras. Traditionally, a crystallographer would manually process each image--identifying the wells that resulted in protein crystal formation. This manual inspection process is slow and given the high rate of mixture output, it has become near impossible for crystallographers keep up. Our aim is to create an automated method of detecting which wells have crystals and which ones do not. We make use of a neural network that is trained based on manually classified ground truth data. After it is trained, the automatic classifier would give a binary output --a value of one for the detection of crystals and precipitates in images and a value of zero otherwise. In our previous papers, the core methods of using multi-scale Laplacian image representation to extract image features and the implementation of the neural network classifier were discussed. Here we present a new, optimized approach to training the neural network and results from a large-scale test. We claim that the neural network can be better trained if the training image dataset is optimized in the sense that ambiguous images are removed during the initial training processes. Incremental training is implemented so that the network can be improved as more data becomes available. From initial results with training based on a 6,000 optimized image dataset, the accuracy of the improved classifier approaches 95% in identifying a wide array of images.

Quantitative analysis of cardiac motion is of great clinical interest in assessment of ventricular function. Ultrasound imaging, especially matrix transducers acquiring real-time three dimensional data, provide valuable information, from which quantitative measures of cardiac function can be extracted via optical flow computation. Such analysis requires tracking of the image brightness patterns with underlying assumptions of visual persistency. We present a review of myocardial motion analysis on cardiac ultrasound, based on optical-flow computation, with phantom and clinical evaluations for segmental wall assessment and motion features quantification.

Among screening modalities, echocardiography is the fastest, least expensive and least invasive method for imaging the heart. A new generation of three-dimensional (3-D) ultrasound (US) technology has been developed with real-time 3-D (RT3-D) matrix phased-array transducers. These transducers allow interactive 3-D visualization of cardiac anatomy and fast ventricular volume estimation without tomographic interpolation as required with earlier 3-D US acquisition systems. However, real-time acquisition speed is performed at the cost of decreasing spatial resolution, leading to echocardiographic data with poor definition of anatomical structures and high levels of speckle noise. The poor quality of the US signal has limited the acceptance of RT3-D US technology in clinical practice, despite the wealth of information acquired by this system, far greater than with any other existing echocardiography screening modality. We present, in this work, a clinical study for segmentation of right and left ventricular volumes using RT3-D US. A preprocessing of the volumetric data sets was performed using spatiotemporal brushlet denoising, as presented in previous articles Two deformable-model segmentation methods were implemented in 2-D using a parametric formulation and in 3-D using an implicit formulation with a level set implementation for extraction of endocardial surfaces on denoised RT3-D US data. A complete and rigorous validation of the segmentation methods was carried out for quantification of left and right ventricular volumes and ejection fraction, including comparison of measurements with cardiac magnetic resonance imaging as the reference. Results for volume and ejection fraction measurements report good performance of quantification of cardiac function on RT3-D data compared with magnetic resonance imaging with better performance of semiautomatic segmentation methods than with manual tracing on the US data.