Associations between longitudinal fluoride intakes from birth to age 23 and multi-row detector computed tomography bone densitometry outcomes at age 23.

OBJECTIVES: To assess the relationships between longitudinal fluoride intakes and bone densitometry outcomes in young adults. METHODS: Data were analyzed from the Iowa Fluoride Study and Iowa Bone Development Study, which followed 1,882 infants from birth in 1992. Daily fluoride intakes were assessed using detailed questionnaires sent every 1.5-6 months, and multi-row detector computed tomography (MDCT) scans of distal tibia were obtained from 330 participants aged 23 years. Sex-specific bivariate and multivariable associations with MDCT outcomes were examined using linear regression. Because of the multiple statistical analyses being conducted, p-values < 0.01 were considered statistically significant. RESULTS: In fully adjusted analyses, no statistically significant (p < 0.01) or suggestive (0.01 < p < 0.05) associations were found between period-specific or cumulative fluoride intake and bone measures for either sex, although there were suggestive positive relationships in unadjusted analyses. CONCLUSIONS: Longitudinal fluoride intakes had little association with bone measures at age 23. As there were no adverse effects from fluoride intake on bone health in young adults, results support the continued use of fluorides, particularly community water fluoridation is the most cost-effective method of dental caries prevention.

Ultra-low dose hip CT-based automated measurement of volumetric bone mineral density at proximal femoral subregions.

BACKGROUND: Forty to fifty percent of women and 13%-22% of men experience an osteoporosis-related fragility fracture in their lifetimes. After the age of 50 years, the risk of hip fracture doubles in every 10 years. x-Ray based DXA is currently clinically used to diagnose osteoporosis and predict fracture risk. However, it provides only 2-D representation of bone and is associated with other technical limitations. Thus, alternative methods are needed. PURPOSE: To develop and evaluate an ultra-low dose (ULD) hip CT-based automated method for assessment of volumetric bone mineral density (vBMD) at proximal femoral subregions. METHODS: An automated method was developed to segment the proximal femur in ULD hip CT images and delineate femoral subregions. The computational pipeline consists of deep learning (DL)-based computation of femur likelihood map followed by shape model-based femur segmentation and finite element analysis-based warping of a reference subregion labeling onto individual femur shapes. Finally, vBMD is computed over each subregion in the target image using a calibration phantom scan. A total of 100 participants (50 females) were recruited from the Genetic Epidemiology of COPD (COPDGene) study, and ULD hip CT imaging, equivalent to 18 days of background radiation received by U.S. residents, was performed on each participant. Additional hip CT imaging using a clinical protocol was performed on 12 participants and repeat ULD hip CT was acquired on another five participants. ULD CT images from 80 participants were used to train the DL network; ULD CT images of the remaining 20 participants as well as clinical and repeat ULD CT images were used to evaluate the accuracy, generalizability, and reproducibility of segmentation of femoral subregions. Finally, clinical CT and repeat ULD CT images were used to evaluate accuracy and reproducibility of ULD CT-based automated measurements of femoral vBMD. RESULTS: Dice scores of accuracy (n = 20), reproducibility (n = 5), and generalizability (n = 12) of ULD CT-based automated subregion segmentation were 0.990, 0.982, and 0.977, respectively, for the femoral head and 0.941, 0.970, and 0.960, respectively, for the femoral neck. ULD CT-based regional vBMD showed Pearson and concordance correlation coefficients of 0.994 and 0.977, respectively, and a root-mean-square coefficient of variation (RMSCV) (%) of 1.39% with the clinical CT-derived reference measure. After 3-digit approximation, each of Pearson and concordance correlation coefficients as well as intraclass correlation coefficient (ICC) between baseline and repeat scans were 0.996 with RMSCV of 0.72%. Results of ULD CT-based bone analysis on 100 participants (age (mean ± SD) 73.6 ± 6.6 years) show that males have significantly greater (p < 0.01) vBMD at the femoral head and trochanteric regions than females, while females have moderately greater vBMD (p = 0.05) at the medial half of the femoral neck than males. CONCLUSION: Deep learning, combined with shape model and finite element analysis, offers an accurate, reproducible, and generalizable algorithm for automated segmentation of the proximal femur and anatomic femoral subregions using ULD hip CT images. ULD CT-based regional measures of femoral vBMD are accurate and reproducible and demonstrate regional differences between males and females.

MSO-GP: 3-D segmentation of large and complex conjoined tree structures.

Robust segmentation of large and complex conjoined tree structures in 3-D is a major challenge in computer vision. This is particularly true in computational biology, where we often encounter large data structures in size, but few in number, which poses a hard problem for learning algorithms. We show that merging multiscale opening with geodesic path propagation, can shed new light on this classic machine vision challenge, while circumventing the learning issue by developing an unsupervised visual geometry approach (digital topology/morphometry). The novelty of the proposed MSO-GP method comes from the geodesic path propagation being guided by a skeletonization of the conjoined structure that helps to achieve robust segmentation results in a particularly challenging task in this area, that of artery-vein separation from non-contrast pulmonary computed tomography angiograms. This is an important first step in measuring vascular geometry to then diagnose pulmonary diseases and to develop image-based phenotypes. We first present proof-of-concept results on synthetic data, and then verify the performance on pig lung and human lung data with less segmentation time and user intervention needs than those of the competing methods.

Chest CT-based automated vertebral fracture assessment using artificial intelligence and morphologic features.

BACKGROUND: Spinal degeneration and vertebral compression fractures are common among the elderly that adversely affect their mobility, quality of life, lung function, and mortality. Assessment of vertebral fractures in chronic obstructive pulmonary disease (COPD) is important due to the high prevalence of osteoporosis and associated vertebral fractures in COPD. PURPOSE: We present new automated methods for (1) segmentation and labelling of individual vertebrae in chest computed tomography (CT) images using deep learning (DL), multi-parametric freeze-and-grow (FG) algorithm, and separation of apparently fused vertebrae using intensity autocorrelation and (2) vertebral deformity fracture detection using computed vertebral height features and parametric computational modelling of an established protocol outlined for trained human experts. METHODS: A chest CT-based automated method was developed for quantitative deformity fracture assessment following the protocol by Genant et al. The computational method was accomplished in the following steps: (1) computation of a voxel-level vertebral body likelihood map from chest CT using a trained DL network; (2) delineation and labelling of individual vertebrae on the likelihood map using an iterative multi-parametric FG algorithm; (3) separation of apparently fused vertebrae in CT using intensity autocorrelation; (4) computation of vertebral heights using contour analysis on the central anterior-posterior (AP) plane of a vertebral body; (5) assessment of vertebral fracture status using ratio functions of vertebral heights and optimized thresholds. The method was applied to inspiratory or total lung capacity (TLC) chest scans from the multi-site Genetic Epidemiology of COPD (COPDGene) (ClinicalTrials.gov: NCT00608764) study, and the performance was examined (n = 3231). One hundred and twenty scans randomly selected from this dataset were partitioned into training (n = 80) and validation (n = 40) datasets for the DL-based vertebral body classifier. Also, generalizability of the method to low dose CT imaging (n = 236) was evaluated. RESULTS: The vertebral segmentation module achieved a Dice score of .984 as compared to manual outlining results as reference (n = 100); the segmentation performance was consistent across images with the minimum and maximum of Dice scores among images being .980 and .989, respectively. The vertebral labelling module achieved 100% accuracy (n = 100). For low dose CT, the segmentation module produced image-level minimum and maximum Dice scores of .995 and .999, respectively, as compared to standard dose CT as the reference; vertebral labelling at low dose CT was fully consistent with standard dose CT (n = 236). The fracture assessment method achieved overall accuracy, sensitivity, and specificity of 98.3%, 94.8%, and 98.5%, respectively, for 40,050 vertebrae from 3231 COPDGene participants. For generalizability experiments, fracture assessment from low dose CT was consistent with the reference standard dose CT results across all participants. CONCLUSIONS: Our CT-based automated method for vertebral fracture assessment is accurate, and it offers a feasible alternative to manual expert reading, especially for large population-based studies, where automation is important for high efficiency. Generalizability of the method to low dose CT imaging further extends the scope of application of the method, particularly since the usage of low dose CT imaging in large population-based studies has increased to reduce cumulative radiation exposure.

Vessel and Airway Characteristics in One-Year Computed Tomography-defined Rapid Emphysema Progression: SPIROMICS.

Rationale: Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationships with vascular and airway pathophysiology remain unclear. Objectives: We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial dilation measured on computed tomography (CT) are associated with a 1-year index of emphysema (EI; percentage of voxels <-950 Hounsfield units) progression. Methods: Five hundred ninety-nine former and never-smokers (Global Initiative for Chronic Obstructive Lung Disease stages 0-3) were evaluated from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort: rapid emphysema progressors (RPs; n = 188, 1-year ΔEI > 1%), nonprogressors (n = 301, 1-year ΔEI ± 0.5%), and never-smokers (n = 110). Segmental pulmonary arterial cross-sectional areas were standardized to associated airway luminal areas (segmental pulmonary artery-to-airway ratio [PAARseg]). Full-inspiratory CT scan-derived total (arteries and veins) pulmonary vascular volume (TPVV) was compared with small vessel volume (radius smaller than 0.75 mm). Ratios of airway to lung volume (an index of dysanapsis and COPD risk) were compared with ratios of TPVV to lung volume. Results: Compared with nonprogressors, RPs exhibited significantly larger PAARseg (0.73 ± 0.29 vs. 0.67 ± 0.23; P = 0.001), lower ratios of TPVV to lung volume (3.21 ± 0.42% vs. 3.48 ± 0.38%; P = 5.0 × 10-12), lower ratios of airway to lung volume (0.031 ± 0.003 vs. 0.034 ± 0.004; P = 6.1 × 10-13), and larger ratios of small vessel volume to TPVV (37.91 ± 4.26% vs. 35.53 ± 4.89%; P = 1.9 × 10-7). In adjusted analyses, an increment of 1 standard deviation in PAARseg was associated with a 98.4% higher rate of severe exacerbations (95% confidence interval, 29-206%; P = 0.002) and 79.3% higher odds of being in the RP group (95% confidence interval, 24-157%; P = 0.001). At 2-year follow-up, the CT-defined RP group demonstrated a significant decline in postbronchodilator percentage predicted forced expiratory volume in 1 second. Conclusions: Rapid one-year progression of emphysema was associated with indices indicative of higher peripheral pulmonary vascular resistance and a possible role played by pulmonary vascular-airway dysanapsis.

Deep learning-based harmonization of trabecular bone microstructures between high- and low-resolution CT imaging.

BACKGROUND: Osteoporosis is a bone disease related to increased bone loss and fracture-risk. The variability in bone strength is partially explained by bone mineral density (BMD), and the remainder is contributed by bone microstructure. Recently, clinical CT has emerged as a viable option for in vivo bone microstructural imaging. Wide variations in spatial-resolution and other imaging features among different CT scanners add inconsistency to derived bone microstructural metrics, urging the need for harmonization of image data from different scanners. PURPOSE: This paper presents a new deep learning (DL) method for the harmonization of bone microstructural images derived from low- and high-resolution CT scanners and evaluates the method's performance at the levels of image data as well as derived microstructural metrics. METHODS: We generalized a three-dimensional (3D) version of GAN-CIRCLE that applies two generative adversarial networks (GANs) constrained by the identical, residual, and cycle learning ensemble (CIRCLE). Two GAN modules simultaneously learn to map low-resolution CT (LRCT) to high-resolution CT (HRCT) and vice versa. Twenty volunteers were recruited. LRCT and HRCT scans of the distal tibia of their left legs were acquired. Five-hundred pairs of LRCT and HRCT image blocks of 64 × 64 × 64 $64 \times 64 \times 64 $ voxels were sampled for each of the twelve volunteers and used for training in supervised as well as unsupervised setups. LRCT and HRCT images of the remaining eight volunteers were used for evaluation. LRCT blocks were sampled at 32 voxel intervals in each coordinate direction and predicted HRCT blocks were stitched to generate a predicted HRCT image. RESULTS: Mean ± standard deviation of structural similarity (SSIM) values between predicted and true HRCT using both 3DGAN-CIRCLE-based supervised (0.84 ± 0.03) and unsupervised (0.83 ± 0.04) methods were significantly (p < 0.001) higher than the mean SSIM value between LRCT and true HRCT (0.75 ± 0.03). All Tb measures derived from predicted HRCT by the supervised 3DGAN-CIRCLE showed higher agreement (CCC  ∈ $ \in $ [0.956 0.991]) with the reference values from true HRCT as compared to LRCT-derived values (CCC  ∈ $ \in $ [0.732 0.989]). For all Tb measures, except Tb plate-width (CCC = 0.866), the unsupervised 3DGAN-CIRCLE showed high agreement (CCC  ∈ $ \in $ [0.920 0.964]) with the true HRCT-derived reference measures. Moreover, Bland-Altman plots showed that supervised 3DGAN-CIRCLE predicted HRCT reduces bias and variability in residual values of different Tb measures as compared to LRCT and unsupervised 3DGAN-CIRCLE predicted HRCT. The supervised 3DGAN-CIRCLE method produced significantly improved performance (p < 0.001) for all Tb measures as compared to the two DL-based supervised methods available in the literature. CONCLUSIONS: 3DGAN-CIRCLE, trained in either unsupervised or supervised fashion, generates HRCT images with high structural similarity to the reference true HRCT images. The supervised 3DGAN-CIRCLE improves agreements of computed Tb microstructural measures with their reference values and outperforms the unsupervised 3DGAN-CIRCLE. 3DGAN-CIRCLE offers a viable DL solution to retrospectively improve image resolution, which may aid in data harmonization in multi-site longitudinal studies where scanner mismatch is unavoidable.

Continuum finite element analysis generalizesin vivotrabecular bone microstructural strength measures between two CT scanners with different image resolution.

Fragility of trabecular bone (Tb) microstructure is increased in osteoporosis, which is associated with rapid bone loss and enhanced fracture-risk. Accurate assessment of Tb strength usingin vivoimaging available in clinical settings will be significant for management of osteoporosis and understanding its pathogenesis. Emerging CT technology, featured with high image resolution, fast scan-speed, and wide clinical access, is a promising alternative forin vivoTb imaging. However, variation in image resolution among different CT scanners pose a major hurdle in CT-based bone studies. This paper presents nonlinear continuum finite element (FE) methods for computation of Tb strength fromin vivoCT imaging and evaluates their generalizability between two scanners with different image resolution. Continuum FE-based measures of Tb strength under different loading conditions were found to be highly reproducible (ICC ≥ 0.93) using ankle images of twenty healthy volunteers acquired on low- and high-resolution CT scanners 44.6 ± 2.7 days apart. FE stress propagation was mostly confined to Tb micro-network (2.3 ± 1.7 MPa) with nominal leakages over the marrow space (0.4 ± 0.5 MPa) complying with the fundamental principle of mechanics atin vivoimaging. In summary, nonlinear continuum FE-based Tb strength measures are reproducible among different CT scanners and suitable for multi-site longitudinal human studies.

Associations Between Muscle Weakness and Clinical Outcomes in Current and Former Smokers.

Introduction: Smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of muscle weakness. There are limited data describing weakness in smokers with normal spirometry and preserved ratio-impaired spirometry (PRISm), 2 subgroups at risk of respiratory symptom burden and activity limitations. In this study, we evaluated the associations of 2 weakness measures, sit-to-stand (STS) and handgrip strength (HGS), with clinical outcomes in smokers with COPD, normal spirometry, and PRISm. Methods: We evaluated 1972 current and former smokers from the COPD Genetic Epidemiology (COPDGene®) cohort with STS and HGS measurements at their 10-year study visit. Multivariable regression modeling was used to assess associations between weakness measures and the 6-minute walk distance (6MWD) test, the St George's Respiratory Questionnaire (SGRQ), the Short-Form-36 (SF-36), severe exacerbations, and prospective mortality, reported as standardized coefficients (ß), odds ratios (ORs), or hazard ratios (HRs). Results: Compared with HGS, STS was more strongly associated with the 6MWD (ß=0.45, p<0.001 versus. ß=0.25, p<0.001), SGRQ (ß=-0.24, p<0.001 versus ß=-0.18, p<0.001), SF-36 Physical Functioning (ß=0.36, p<0.001 versus ß=0.25, p<0.001), severe exacerbations (OR 0.95, p=0.04 versus OR 0.97, p=0.01), and prospective mortality (HR 0.83, p=0.001 versus HR 0.94, p=0.03). Correlations remained after stratification by spirometric subgroups. Compared with males, females had larger magnitude effect sizes between STS and clinical outcomes. Conclusions: STS and HGS are easy to perform weakness measures that provide important information about functional performance, health-related quality of life, severe exacerbations, and survival in smokers, regardless of spirometric subgroup. This iterates the importance of screening current and former smokers for weakness in the outpatient setting.

A Survey on Artificial Intelligence in Pulmonary Imaging.

Over the last decade, deep learning (DL) has contributed a paradigm shift in computer vision and image recognition creating widespread opportunities of using artificial intelligence in research as well as industrial applications. DL has been extensively studied in medical imaging applications, including those related to pulmonary diseases. Chronic obstructive pulmonary disease, asthma, lung cancer, pneumonia, and, more recently, COVID-19 are common lung diseases affecting nearly 7.4% of world population. Pulmonary imaging has been widely investigated toward improving our understanding of disease etiologies and early diagnosis and assessment of disease progression and clinical outcomes. DL has been broadly applied to solve various pulmonary image processing challenges including classification, recognition, registration, and segmentation. This paper presents a survey of pulmonary diseases, roles of imaging in translational and clinical pulmonary research, and applications of different DL architectures and methods in pulmonary imaging with emphasis on DL-based segmentation of major pulmonary anatomies such as lung volumes, lung lobes, pulmonary vessels, and airways as well as thoracic musculoskeletal anatomies related to pulmonary diseases.

Computed Tomography-Based Stiffness Measures of Trabecular Bone Microstructure: Cadaveric Validation and In Vivo Application.

Osteoporosis causes bone fragility and elevates fracture risk. Applications of finite element (FE) analysis (FEA) for assessment of trabecular bone (Tb) microstructural strength at whole-body computed tomography (CT) imaging are limited due to challenges with Tb microstructural segmentation. We present a nonlinear FEA method for distal tibia CT scans evading binary segmentation of Tb microstructure, while accounting for bone microstructural distribution. First, the tibial axis in a CT scan was aligned with the FE loading axis. FE cubic mesh elements were modeled using image voxels, and CT intensity values were calibrated to ash density defining mechanical properties at individual elements. For FEA of an upright volume of interest (VOI), the bottom surface was fixed, and a constant displacement was applied at each vertex on the top surface simulating different loading conditions. The method was implemented and optimized using the ANSYS software. CT-derived computational modulus values were repeat scan reproducible (intraclass correlation coefficient [ICC] ≥ 0.97) and highly correlated (r ≥ 0.86) with the micro-CT (µCT)-derived values. FEA-derived von Mises stresses over the segmented Tb microregion were significantly higher (p < 1 × 10-11) than that over the marrow space. In vivo results showed that both shear and compressive modulus for males were higher (p < 0.01) than for females. Effect sizes for different modulus measures between males and females were moderate-to-high (≥0.55) and reduced to small-to-negligible (<0.40) when adjusted for pure lean mass. Among body size and composition attributes, pure lean mass and height showed highest (r ∈ [0.45 0.56]) and lowest (r ∈ [0.25 0.39]) linear correlation, respectively, with FE-derived modulus measures. In summary, CT-based nonlinear FEA provides an effective surrogate measure of Tb microstructural stiffness, and the relaxation of binary segmentation will extend the scope for FEA in human studies using in vivo imaging at relatively low-resolution. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Finite element analysis of trabecular bone microstructure using CT imaging and continuum mechanical modeling.

PURPOSE: Osteoporosis is a bone disease associated with enhanced bone loss, microstructural degeneration, and fracture-risk. Finite element (FE) modeling is used to estimate trabecular bone (Tb) modulus from high-resolution three-dimensional (3-D) imaging modalities including micro-computed tomography (CT), magnetic resonance imaging (MRI), and high-resolution peripheral quantitative CT (HR-pQCT). This paper validates an application of voxel-based continuum finite element analysis (FEA) to predict Tb modulus from clinical CT imaging under a condition similar to in vivo imaging by comparing with measures derived by micro-CT and experimental approaches. METHOD: Voxel-based continuum FEA methods for CT imaging were implemented using linear and nonlinear models and applied on distal tibial scans under a condition similar to in vivo imaging. First, tibial axis in a CT scan was aligned with the coordinate z-axis at 150 µm isotropic voxels. FEA was applied on an upright cylindrical volume of interests (VOI) with its axis coinciding with the tibial bone axis. Voxel volume, edge, and vertex elements and their connectivity were defined as per the isotropic image grid. A calibration phantom was used to calibrate CT numbers in Hounsfield unit to bone mineral density (BMD) values, which was then converted into calcium hydroxyapatite (CHA) density. Mechanical properties at each voxel volume element was defined using its ash-density defined on CT-derived CHA density. For FEA, the bottom surface of the cylindrical VOI was fixed and a constant displacement was applied along the z-direction at each vertex element on the top surface to simulate a physical axial compressive loading condition. Finally, a Poisson's ratio of 0.3 was applied, and Tb modulus (MPa) was computed as the ratio of average von Mises stress (MPa) of volume elements on the top surface and the applied displacement. FEA parameters including mesh element size, substep number, and different tolerance values were optimized. RESULTS: CT-derived Tb modulus values using continuum FEA showed high linear correlation with the micro-CT-derived reference values (r ∈ [0.87 0.90]) as well as experimentally measured values (r ∈ [0.80 0.87]). Linear correlation of computed modulus with their reference values using continuum FEA with linear modeling was comparable with that obtained by nonlinear modeling. Nonlinear continuum FEA-based modulus values (mean of 1087.2 MPa) showed greater difference from their reference values (mean of 1498.9 MPa using micro-CT-based FEA) as compared with linear continuum methods. High repeat CT scan reproducibility (intra-class correlation [ICC] = 0.98) was observed for computed modulus values using both linear and nonlinear continuum FEA. It was observed that high stress regions coincide with Tb microstructure as fuzzily characterized by BMD values. Distributions of von Mises stress over Tb microstructure and marrow regions were significantly different (p < 10-8 ). CONCLUSION: Voxel-based continuum FEA offers surrogate measures of Tb modulus from CT imaging under a condition similar to in vivo imaging that alleviates the need for segmentation of Tb and marrow regions, while accounting for bone distribution at the microstructural level. This relaxation of binary segmentation will extend the scope of FEA application to assess mechanical properties of bone microstructure at relatively low-resolution imaging.

Airway Detection in COPD at Low-Dose CT Using Deep Learning and Multiparametric Freeze and Grow.

Purpose: To present and validate a fully automated airway detection method at low-dose CT in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods: In this retrospective study, deep learning (DL) and freeze-and-grow (FG) methods were optimized and applied to automatically detect airways at low-dose CT. Four data sets were used: two data sets consisting of matching standard- and low-dose CT scans from the Genetic Epidemiology of COPD (COPDGene) phase II (2014-2017) cohort (n = 2 × 236; mean age ± SD, 70 years ± 9; 123 women); one data set consisting of low-dose CT scans from the COPDGene phase III (2018-2020) cohort (n = 335; mean age ± SD, 73 years ± 8; 173 women); and one data set consisting of low-dose, anonymized CT scans from the 2003 Dutch-Belgian Randomized Lung Cancer Screening trial (n = 55) acquired by using different CT scanners. Performance measures for different methods were computed and compared by using the Wilcoxon signed rank test. Results: At low-dose CT, 56 294 of 62 480 (90.1%) airways of the reference total airway count (TAC) and 32 109 of 37 864 (84.8%) airways of the peripheral TAC (TACp), detected at standard-dose CT, were detected. Significant losses (P < .001) of 14 526 of 76 453 (19.0%) airways and 884 of 6908 (12.8%) airways in the TAC and 12 256 of 43 462 (28.2%) airways and 699 of 3882 (18.0%) airways in the TACp were observed, respectively, for the multiprotocol and multiscanner data without retraining. When using the automated low-dose CT method, TAC values of 347, 342, 323, and 266 and TACp values of 205, 202, 289, and 141 were observed for those who have never smoked and participants at Global Initiative for Chronic Obstructive Lung Disease stages 0, 1, and 2, respectively, which were superior to the respective values previously reported for matching groups when using a semiautomated method at standard-dose CT. Conclusion: A low-cost, automated CT-based airway detection method was suitable for investigation of airway phenotypes at low-dose CT.Keywords: Airway, Airway Count, Airway Detection, Chronic Obstructive Pulmonary Disease, CT, Deep Learning, Generalizability, Low-Dose CT, Segmentation, Thorax, LungClinical trial registration no. NCT00608764 Supplemental material is available for this article. © RSNA, 2022.

Quantitative CT-Based Methods for Bone Microstructural Measures and Their Relationships With Vertebral Fractures in a Pilot Study on Smokers.

Osteoporosis causes fragile bone, and bone microstructural quality is a critical determinant of bone strength and fracture risk. This study pursues technical validation of novel CT-based methods for assessment of peripheral bone microstructure together with a human pilot study examining relationships between bone microstructure and vertebral fractures in smokers. To examine the accuracy and reproducibility of the methods, repeat ultra-high-resolution (UHR) CT and micro-CT scans of cadaveric ankle specimens were acquired. Thirty smokers from the University of Iowa COPDGene cohort were recruited at their 5-year follow-up visits. Chest CT scans, collected under the parent study, were used to assess vertebral fractures. UHR CT scans of distal tibia were acquired for this pilot study to obtain peripheral cortical and trabecular bone (Cb and Tb) measures. UHR CT-derived Tb measures, including volumetric bone mineral density (BMD), network area, transverse trabecular density, and mean plate width, showed high correlation (r > 0.901) with their micro-CT-derived values over small regions of interest (ROIs). Both Cb and Tb measures showed high reproducibility-intra-class correlation (ICC) was greater than 0.99 for all Tb measures except erosion index and greater than 0.97 for all Cb measures. Female sex was associated with lower transverse Tb density (p < 0.1), higher Tb spacing (p < 0.05), and lower cortical thickness (p < 0.001). Participants with vertebral fractures had significantly degenerated values (p < 0.05) for all Tb measures except thickness. There were no statistically significant differences for Cb measures between non-fracture and fracture groups. Vertebral fracture-group differences of Tb measures remained significant after adjustment with chronic obstructive pulmonary disease (COPD) status. Although current smokers at baseline had more fractures-81.8% versus 63.2% for former smokers-the difference was not statistically significant. This pilot cross-sectional human study demonstrates CT-based peripheral bone microstructural differences among smokers with and without vertebral fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Effects of fluoride intake on cortical and trabecular bone microstructure at early adulthood using multi-row detector computed tomography (MDCT).

PURPOSE: The aim of this study was to examine the effects of period-specific and cumulative fluoride (F) intake on bone at the levels of cortical and trabecular bone microstructural outcomes at early adulthood using emerging multi-row detector computed tomography (MDCT)-based novel techniques. METHODS: Ultra-high resolution MDCT distal tibia scans were collected at age 19 visits under the Iowa Bone Development Study (IBDS), and cortical and trabecular bone microstructural outcomes were computed at the distal tibia using previously validated methods. CT scans of a tissue characterization phantom were used to calibrate CT numbers (Hounsfield units) into bone mineral density (mg/cc). Period-specific and cumulative F intakes from birth up to the age of 19 years were assessed for IBDS participants through questionnaire, and their relationships with MDCT-derived bone microstructural outcomes were examined using bivariable and multivariable analyses, adjusting for height, weight, maturity offset (years since age of peak height velocity (PHV)), physical activity (questionnaire for adolescents (PAQ-A)), healthy eating index version 2010 (HEI-2010) scores, and calcium and protein intakes. RESULTS: MDCT distal tibia scans were acquired for 324 participants from among the total of 329 participants at age 19 visits. No motion artifacts were observed in any MDCT scans, and all images were successfully processed to measure cortical and trabecular bone microstructural outcomes. At early adulthood, males were observed to have stronger trabecular bone microstructural features, as well as thicker cortical bone (p < 0.01), as compared to age-similar females; however, females were found to have less cortical bone porosity as compared to males. Among participants with available F intake estimates (75 to 91% of the 324 with MDCT scans, depending on the period-specific F intake measure), no statistically significant associations were detected between any period-specific or cumulative F intake and bone microstructural outcomes of the tibia at the p < 0.01 level. Only for females, statistically suggestive associations (p < 0.05) were found between recent F intake (from 14 to 19 years) and trabecular mean plate width and trabecular thickness at the tibia. Those associations became somewhat weaker, but still statistically suggestive, for trabecular thickness in fully adjusted analysis with height, weight, PHV, calcium and protein intake, and HEI-2010 and PAQ-A scores as covariates. CONCLUSION: The findings show that the effects of lifelong or period-specific F intake from combined sources for adolescents typical to the United States Midwest region are not strongly associated with bone microstructural outcomes at age 19 years. These findings are generally consistent with previously reported results of IBDS analyses, which further confirms that effects of lifelong or period-specific F intake on skeletons in early adulthood are absent or weak, even at the levels of cortical and trabecular bone microstructural details.

A CT-Based Automated Algorithm for Airway Segmentation Using Freeze-and-Grow Propagation and Deep Learning.

Chronic obstructive pulmonary disease (COPD) is a common lung disease, and quantitative CT-based bronchial phenotypes are of increasing interest as a means of exploring COPD sub-phenotypes, establishing disease progression, and evaluating intervention outcomes. Reliable, fully automated, and accurate segmentation of pulmonary airway trees is critical to such exploration. We present a novel approach of multi-parametric freeze-and-grow (FG) propagation which starts with a conservative segmentation parameter and captures finer details through iterative parameter relaxation. First, a CT intensity-based FG algorithm is developed and applied for airway tree segmentation. A more efficient version is produced using deep learning methods generating airway lumen likelihood maps from CT images, which are input to the FG algorithm. Both CT intensity- and deep learning-based algorithms are fully automated, and their performance, in terms of repeat scan reproducibility, accuracy, and leakages, is evaluated and compared with results from several state-of-the-art methods including an industry-standard one, where segmentation results were manually reviewed and corrected. Both new algorithms show a reproducibility of 95% or higher for total lung capacity (TLC) repeat CT scans. Experiments on TLC CT scans from different imaging sites at standard and low radiation dosages show that both new algorithms outperform the other methods in terms of leakages and branch-level accuracy. Considering the performance and execution times, the deep learning-based FG algorithm is a fully automated option for large multi-site studies.

A comparative study of trabecular bone micro-structural measurements using different CT modalities.

Osteoporosis, characterized by reduced bone mineral density and micro-architectural degeneration, significantly enhances fracture-risk. There are several viable methods for trabecular bone micro-imaging, which widely vary in terms of technology, reconstruction principle, spatial resolution, and acquisition time. We have performed an excised cadaveric bone specimen study to evaluate different computed tomography (CT)-imaging modalities for trabecular bone micro-structural analysis. Excised cadaveric bone specimens from the distal radius were scanned using micro-CT and fourin vivoCT imaging modalities: high-resolution peripheral quantitative computed tomography (HR-pQCT), dental cone beam CT (CBCT), whole-body multi-row detector CT (MDCT), and extremity CBCT. A new algorithm was developed to optimize soft thresholding parameters for individualin vivoCT modalities for computing quantitative bone volume fraction maps. Finally, agreement of trabecular bone micro-structural measures, derived from differentin vivoCT imaging, with reference measures from micro-CT imaging was examined. Observed values of most trabecular measures, including trabecular bone volume, network area, transverse and plate-rod micro-structure, thickness, and spacing, forin vivoCT modalities were higher than their micro-CT-based reference values. In general, HR-pQCT-based trabecular bone measures were closer to their reference values as compared to otherin vivoCT modalities. Despite large differences in observed values of measures among modalities, high linear correlation (rε [0.94 0.99]) was found between micro-CT andin vivoCT-derived measures of trabecular bone volume, transverse and plate micro-structural volume, and network area. All HR-pQCT-derived trabecular measures, except the erosion index, showed high correlation (rε [0.91 0.99]). The plate-width measure showed a higher correlation (rε [0.72 0.91]) amongin vivoand micro-CT modalities than its counterpart binary plate-rod characterization-based measure erosion index (rε [0.65 0.81]). Although a strong correlation was observed between micro-structural measures fromin vivoand micro-CT imaging, large shifts in their values forin vivomodalities warrant proper scanner calibration prior to adopting in multi-site and longitudinal studies.

Lung-Specific Risk Factors Associated With Incident Hip Fracture in Current and Former Smokers.

Hip fractures are associated with significant morbidity and mortality in smokers with lung disease, but whether lung-specific factors are associated with fracture risk is unknown. Our goal was to determine whether lung-specific factors associate with incident hip fracture and improve risk discrimination of traditional fracture risk models in smokers. The analysis consisted of a convenience sample of 9187 current and former smokers (58,477 participant follow-up years) participating in the Genetic Epidemiology of chronic obstructive pulmonary disease (COPD) longitudinal observational cohort study. Participants were enrolled between 2008 and 2011 with follow-up data collection through July 2018. Traditional risk factors associated with incident hip fracture (n = 361) included age, female sex, osteoporosis, prevalent spine and hip fracture, rheumatoid arthritis, and diabetes. Lung-specific risk factors included post-bronchodilator percent forced expiratory volume in 1 s (FEV1 %) predicted (OR, 0.95; 95% CI, 0.92-0.99 for each 10% increase), Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification (OR, 1.09; 95% CI, 1.002-1.19 for each higher stage), presence of CT-determined emphysema (OR, 1.34; 95% CI, 1.06-1.69), symptom scores (OR, 1.10; 95% CI, 1.03-1.19 for each higher unit score), 6-min walk distance (OR, 0.92; 95% CI, 0.90-0.95 for each 30-m increase), body mass index, airflow obstruction, dyspnea, and exercise (BODE) index (OR, 1.07; 95% CI, 1.01-1.13 for each higher unit score), total exacerbations (OR, 1.13; 95% CI, 1.10-1.16 per exacerbation), and annual exacerbations (OR, 1.37; 95% CI, 1.21-1.55 per exacerbation). In multivariable modeling, age, black race, osteoporosis, prevalent hip and spine fracture, rheumatoid arthritis, and diabetes were associated with incident hip fracture. The presence of emphysema, 6-min walk distance, and total number of exacerbations added to traditional models improved risk discrimination (integrated discrimination improvement [IDI] values 0.001 [95% CI, 0.0003-0.002], 0.001 [95% CI, 0.0001-0.002], and 0.008 [95% CI, 0.003-0.013], corresponding to relative IDIs of 12.8%, 6.3%, and 34.6%, respectively). These findings suggest that the incorporation of lung-specific risk factors into fracture risk assessment tools may more accurately predict fracture risk in smokers. © 2020 American Society for Bone and Mineral Research.

Deep Learning Based High-Resolution Reconstruction of Trabecular Bone Microstructures from Low-Resolution CT Scans using GAN-CIRCLE.

Osteoporosis is a common age-related disease characterized by reduced bone density and increased fracture-risk. Microstructural quality of trabecular bone (Tb), commonly found at axial skeletal sites and at the end of long bones, is an important determinant of bone-strength and fracture-risk. High-resolution emerging CT scanners enable in vivo measurement of Tb microstructures at peripheral sites. However, resolution-dependence of microstructural measures and wide resolution-discrepancies among various CT scanners together with rapid upgrades in technology warrant data harmonization in CT-based cross-sectional and longitudinal bone studies. This paper presents a deep learning-based method for high-resolution reconstruction of Tb microstructures from low-resolution CT scans using GAN-CIRCLE. A network was developed and evaluated using post-registered ankle CT scans of nineteen volunteers on both low- and high-resolution CT scanners. 9,000 matching pairs of low- and high-resolution patches of size 64×64 were randomly harvested from ten volunteers for training and validation. Another 5,000 matching pairs of patches from nine other volunteers were used for evaluation. Quantitative comparison shows that predicted high-resolution scans have significantly improved structural similarity index (p < 0.01) with true high-resolution scans as compared to the same metric for low-resolution data. Different Tb microstructural measures such as thickness, spacing, and network area density are also computed from low- and predicted high-resolution images, and compared with the values derived from true high-resolution scans. Thickness and network area measures from predicted images showed higher agreement with true high-resolution CT (CCC = [0.95, 0.91]) derived values than the same measures from low-resolution images (CCC = [0.72, 0.88]).

CT-Based Characterization of Transverse and Longitudinal Trabeculae and Its Applications.

Osteoporosis is a common age-related disease characterized by reduced bone mineral density (BMD), micro-structural deterioration, and enhanced fracture-risk. Although, BMD is clinically used to define osteoporosis, there are compelling evidences that bone micro-structural properties are strong determinants of bone strength and fracture-risk. Reliable measures of effective trabecular bone (Tb) micro-structural features are of paramount clinical significance. Tb consists of transverse and longitudinal micro-structures, and there is a hypothesis that transverse trabeculae improve bone strength by arresting buckling of longitudinal trabeculae. In this paper, we present an emerging clinical CT-based new method for characterizing transverse and longitudinal trabeculae, validate the method, and examine its application in human studies. Specifically, we examine repeat CT scan reproducibility, and evaluate the relationships of these measures with gender and body size using human CT data from the Iowa Bone Development Study (IBDS) (n = 99; 49 female). Based on a cadaveric ankle study (n = 12), both transverse and longitudinal Tb measures are found reproducible (ICC > 0.94). It was observed in the IBDS human data that males have significantly higher trabecular bone measures than females for both inner (p < 0.05) and outer (p < 0.01) regions of interest (ROIs). For weight, Spearman correlations ranged 0.43-0.48 for inner ROI measures and 0.50-0.52 for outer ROI measures for females versus 0.30-0.34 and 0.23-0.25 for males. Correlation with height was lower (0.36-0.39), but still mostly significant for females. No association of trabecular measures with height was found for males.

CT Super-Resolution GAN Constrained by the Identical, Residual, and Cycle Learning Ensemble (GAN-CIRCLE).

In this paper, we present a semi-supervised deep learning approach to accurately recover high-resolution (HR) CT images from low-resolution (LR) counterparts. Specifically, with the generative adversarial network (GAN) as the building block, we enforce the cycle-consistency in terms of the Wasserstein distance to establish a nonlinear end-to-end mapping from noisy LR input images to denoised and deblurred HR outputs. We also include the joint constraints in the loss function to facilitate structural preservation. In this process, we incorporate deep convolutional neural network (CNN), residual learning, and network in network techniques for feature extraction and restoration. In contrast to the current trend of increasing network depth and complexity to boost the imaging performance, we apply a parallel 1×1 CNN to compress the output of the hidden layer and optimize the number of layers and the number of filters for each convolutional layer. The quantitative and qualitative evaluative results demonstrate that our proposed model is accurate, efficient and robust for super-resolution (SR) image restoration from noisy LR input images. In particular, we validate our composite SR networks on three large-scale CT datasets, and obtain promising results as compared to the other state-of-the-art methods.