Krishna S. Iyer

Baseline articular contact stress levels predict incident symptomatic knee osteoarthritis development in the MOST cohort.

We studied whether contact stress estimates from knee magnetic resonance images (MRI) predict the development of incident symptomatic tibiofemoral osteoarthritis (OA) 15 months later in an at‐risk cohort. This nested case‐control study was conducted within a cohort of 3,026 adults, age 50 to79 years. Thirty cases with incident symptomatic tibiofemoral OA by their 15 month follow‐up visit were randomly selected and matched with 30 control subjects. Symptomatic tibiofemoral OA was defined as daily knee pain/stiffness and Kellgren‐Lawrence Grade ≥2 on weight bearing, fixed‐flexion radiographs. Tibiofemoral geometry was segmented on baseline knee MRI, and contact stresses were estimated using discrete element analysis. Linear mixed models for repeated measures were used to examine the association between articular contact stress and case/control status. No significant intergroup differences were found for age, sex, BMI, weight, height, or limb alignment. However, the maximum articular contact stress was 0.54 ± 0.77 MPa (mean ± SD) higher in incident OA cases compared to that in control knees (p = 0.0007). The interaction between case‐control status and contact stress was significant above 3.20 MPa (p < 0.0001). The presence of differences in estimated contact stress 15 months prior to incidence suggests a biomechanical mechanism for symptomatic tibiofemoral OA and supports the ability to identify risk by subject‐specific biomechanical modeling.

Quantitative Dual-Energy Computed Tomography Supports a Vascular Etiology of Smoking-induced Inflammatory Lung Disease

RATIONALE Endothelial dysfunction is of interest in relation to smoking-associated emphysema, a component of chronic obstructive pulmonary disease (COPD). We previously demonstrated that computed tomography (CT)-derived pulmonary blood flow (PBF) heterogeneity is greater in smokers with normal pulmonary function tests (PFTs) but who have visual evidence of centriacinar emphysema (CAE) on CT. OBJECTIVES We introduced dual-energy CT (DECT) perfused blood volume (PBV) as a PBF surrogate to evaluate whether the CAE-associated increased PBF heterogeneity is reversible with sildenafil. METHODS Seventeen PFT-normal current smokers were divided into CAE-susceptible (SS; n = 10) and nonsusceptible (NS; n = 7) smokers, based on the presence or absence of CT-detected CAE. DECT-PBV images were acquired before and 1 hour after administration of 20 mg oral sildenafil. Regional PBV and PBV coefficients of variation (CV), a measure of spatial blood flow heterogeneity, were determined, followed by quantitative assessment of the central arterial tree. MEASUREMENTS AND MAIN RESULTS After sildenafil administration, regional PBV-CV decreased in SS subjects but did not decrease in NS subjects (P < 0.05), after adjusting for age and pack-years. Quantitative evaluation of the central pulmonary arteries revealed higher arterial volume and greater cross-sectional area (CSA) in the lower lobes of SS smokers, which suggested arterial enlargement in response to increased peripheral resistance. After sildenafil, arterial CSA decreased in SS smokers but did not decrease in NS smokers (P < 0.01). CONCLUSIONS These results demonstrate that sildenafil restores peripheral perfusion and reduces central arterial enlargement in normal SS subjects with little effect in NS subjects, highlighting DECT-PBV as a biomarker of reversible endothelial dysfunction in smokers with CAE.

Assessment of regional ventilation and deformation using 4D-CT imaging for healthy human lungs during tidal breathing

This study aims to assess regional ventilation, nonlinearity, and hysteresis of human lungs during dynamic breathing via image registration of four-dimensional computed tomography (4D-CT) scans. Six healthy adult humans were studied by spiral multidetector-row CT during controlled tidal breathing as well as during total lung capacity and functional residual capacity breath holds. Static images were utilized to contrast static vs. dynamic (deep vs. tidal) breathing. A rolling-seal piston system was employed to maintain consistent tidal breathing during 4D-CT spiral image acquisition, providing required between-breath consistency for physiologically meaningful reconstructed respiratory motion. Registration-derived variables including local air volume and anisotropic deformation index (ADI, an indicator of preferential deformation in response to local force) were employed to assess regional ventilation and lung deformation. Lobar distributions of air volume change during tidal breathing were correlated with those of deep breathing (R(2) ≈ 0.84). Small discrepancies between tidal and deep breathing were shown to be likely due to different distributions of air volume change in the left and the right lungs. We also demonstrated an asymmetric characteristic of flow rate between inhalation and exhalation. With ADI, we were able to quantify nonlinearity and hysteresis of lung deformation that can only be captured in dynamic images. Nonlinearity quantified by ADI is greater during inhalation, and it is stronger in the lower lobes (P < 0.05). Lung hysteresis estimated by the difference of ADI between inhalation and exhalation is more significant in the right lungs than that in the left lungs.

A robust and efficient curve skeletonization algorithm for tree-like objects using minimum cost paths

Conventional curve skeletonization algorithms using the principle of Blums transform, often, produce unwanted spurious branches due to boundary irregularities, digital effects, and other artifacts. This paper presents a new robust and efficient curve skeletonization algorithm for three-dimensional (3-D) elongated fuzzy objects using a minimum cost path approach, which avoids spurious branches without requiring post-pruning. Starting from a root voxel, the method iteratively expands the skeleton by adding new branches in each iteration that connects the farthest quench voxel to the current skeleton using a minimum cost path. The path-cost function is formulated using a novel measure of local significance factor defined by the fuzzy distance transform field, which forces the path to stick to the centerline of an object. The algorithm terminates when dilated skeletal branches fill the entire object volume or the current farthest quench voxel fails to generate a meaningful skeletal branch. Accuracy of the algorithm has been evaluated using computer-generated phantoms with known skeletons. Performance of the method in terms of false and missing skeletal branches, as defined by human experts, has been examined using in vivo CT imaging of human intrathoracic airways. Results from both experiments have established the superiority of the new method as compared to the existing methods in terms of accuracy as well as robustness in detecting true and false skeletal branches. The new algorithm makes a significant reduction in computation complexity by enabling detection of multiple new skeletal branches in one iteration. Specifically, this algorithm reduces the number of iterations from the number of terminal tree branches to the worst case performance of tree depth. In fact, experimental results suggest that, on an average, the order of computation complexity is reduced to the logarithm of the number of terminal branches of a tree-like object.

Automated Assessment of Pulmonary Arterial Morphology in Multi-row Detector CT Imaging Using Correspondence with Anatomic Airway Branches

Multi-row detector CT (MDCT) provides high resolution structural and functional imaging that has been helpful in studying altered physiology, making early diagnosis, and evaluating treatments in pulmonary research. There is growing evidence suggesting that pulmonary vascular dysfunction plays a major role in progression of centrilobular emphysema, a component of chronic obstructive disease (COPD). Few studies have attempted to quantify central pulmonary vessel morphology and to compare these measurements across COPD groups. However, the scope of vascular structures examined in such studies has been limited, primarily, due to lack of an automated and standardized method of comparing matching vessel branches. In this paper, we present a fully automated method, using a novel arc skeletonization and a local correspondence analysis, to identify matching pulmonary arteries by linking those with anatomically defined specific airway branches. This method provides a standardized way of establishing correspondence between matched pulmonary arteries for intra- and inter-subject scans. The accuracy and repeatability of the method was examined on non-contrast MDCT scans of 10 normal subjects. It was observed that 83% of the arteries classified by our automated method agree with “true” arteries as labelled by an interactive manual artery-vein separation tool. Repeat scan intra-class correlation of arterial morphological measures over six anatomic airway branches was observed as 91%.

A semi-automatic framework of measuring pulmonary arterial metrics at anatomic airway locations using CT imaging

Pulmonary vascular dysfunction has been implicated in smoking-related susceptibility to emphysema. With the growing interest in characterizing arterial morphology for early evaluation of the vascular role in pulmonary diseases, there is an increasing need for the standardization of a framework for arterial morphological assessment at airway segmental levels. In this paper, we present an effective and robust semi-automatic framework to segment pulmonary arteries at different anatomic airway branches and measure their cross-sectional area (CSA). The method starts with user-specified endpoints of a target arterial segment through a custom-built graphical user interface. It then automatically detect the centerline joining the endpoints, determines the local structure orientation and computes the CSA along the centerline after filtering out the adjacent pulmonary structures, such as veins or airway walls. Several new techniques are presented, including collision-impact based cost function for centerline detection, radial sample-line based CSA computation, and outlier analysis of radial distance to subtract adjacent neighboring structures in the CSA measurement. The method was applied to repeat-scan pulmonary multirow detector CT (MDCT) images from ten healthy subjects (age: 21-48 Yrs, mean: 28.5 Yrs; 7 female) at functional residual capacity (FRC). The reproducibility of computed arterial CSA from four airway segmental regions in middle and lower lobes was analyzed. The overall repeat-scan intra-class correlation (ICC) of the computed CSA from all four airway regions in ten subjects was 96% with maximum ICC found at LB10 and RB4 regions.

A New Approach of Arc Skeletonization for Tree-like Objects Using Minimum Cost Path

Traditional arc skeletonization algorithms using the principle of Blums transform, often, produce unwanted spurious branches due to boundary irregularities and digital effects on objects and other artifacts. This paper presents a new robust approach of extracting arc skeletons for three-dimensional (3-D) elongated fuzzy objects, which avoids spurious branches without requiring post-pruning. Starting from a root voxel, the method iteratively expands the skeleton by adding a new branch in each iteration that connects the farthest voxel to the current skeleton using a minimum-cost geodesic path. The path-cost function is formulated using a novel measure of local significance factor defined by fuzzy distance transform field, which forces the path to stick to the centerline of the object. The algorithm terminates when dilated skeletal branches fill the entire object volume or the current farthest voxel fails to generate a meaningful branch. Accuracy of the algorithm has been evaluated using computer-generated blurred and noisy phantoms with known skeletons. Performance of the method in terms of false and missing skeletal branches, as defined by human expert, has been examined using in vivo CT imaging of human intrathoracic airways. Experimental results from both experiments have established the superiority of the new method as compared to a widely used conventional method in terms of accuracy of medialness as well as robustness of true and false skeletal branches.