Publications by Year: 2009

2009
Washko GR, Dransfield MT, San José Estépar R, Diaz A, Matsuoka S, Yamashiro T, Hatabu H, Silverman EK, Bailey WC, Reilly JJ. Airway wall attenuation: a biomarker of airway disease in subjects with COPD. J Appl Physiol (1985) 2009;107(1):185-91.Abstract
The computed tomographic (CT) densities of imaged structures are a function of the CT scanning protocol, the structure size, and the structure density. For objects that are of a dimension similar to the scanner point spread function, CT will underestimate true structure density. Prior investigation suggests that this process, termed contrast reduction, could be used to estimate the strength of thin structures, such as cortical bone. In this investigation, we endeavored to exploit this process to provide a CT-based measure of airway disease that can assess changes in airway wall thickening and density that may be associated with the mural remodeling process in subjects with chronic obstructive pulmonary disease (COPD). An initial computer-based study using a range of simulated airway wall sizes and densities suggested that CT measures of airway wall attenuation could detect changes in both wall thickness and structure density. A second phantom-based study was performed using a series of polycarbonate tubes of known density. The results of this again demonstrated the process of contrast reduction and further validated the computer-based simulation. Finally, measures of airway wall attenuation, wall thickness, and wall area (WA) divided by total cross-sectional area, WA percent (WA%), were performed in a cohort of 224 subjects with COPD and correlated with spirometric measures of lung function. The results of this analysis demonstrated that wall attenuation is comparable to WA% in predicting lung function on univariate correlation and remain as a statistically significant correlate to the percent forced expiratory volume in 1 s predicted when adjusted for measures of both emphysema and WA%. These latter findings suggest that the quantitative assessment of airway wall attenuation may offer complementary information to WA% in characterizing airway disease in subjects with COPD.
Kim WJ, Silverman EK, Hoffman E, Criner GJ, Mosenifar Z, Sciurba FC, Make BJ, Carey V, San José Estépar R, Diaz A, Reilly JJ, Martinez FJ, Washko GR. CT metrics of airway disease and emphysema in severe COPD. Chest 2009;136(2):396-404.Abstract
BACKGROUND: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. METHODS: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of -950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV(1) and percent predicted value of FEV(1) with CT scan measures of emphysema and airway disease. RESULTS: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = -0.28, p = 0.0001) and SRWA (r = -0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV(1)% predicted (R = -0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (beta = -5.2, p = 0.009; beta = -2.6, p = 0.008, respectively) and %LAA-950 (beta = -10.6, p = 0.03) with the postbronchodilator FEV(1)% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). CONCLUSIONS: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.
Ross JC, San José Estépar R, Díaz A, Westin C-F, Kikinis R, Silverman EK, Washko GR. Lung extraction, lobe segmentation and hierarchical region assessment for quantitative analysis on high resolution computed tomography images. Med Image Comput Comput Assist Interv 2009;12(Pt 2):690-8.Abstract
Regional assessment of lung disease (such as chronic obstructive pulmonary disease) is a critical component to accurate patient diagnosis. Software tools than enable such analysis are also important for clinical research studies. In this work, we present an image segmentation and data representation framework that enables quantitative analysis specific to different lung regions on high resolution computed tomography (HRCT) datasets. We present an offline, fully automatic image processing chain that generates airway, vessel, and lung mask segmentations in which the left and right lung are delineated. We describe a novel lung lobe segmentation tool that produces reproducible results with minimal user interaction. A usability study performed across twenty datasets (inspiratory and expiratory exams including a range of disease states) demonstrates the tool's ability to generate results within five to seven minutes on average. We also describe a data representation scheme that involves compact encoding of label maps such that both "regions" (such as lung lobes) and "types" (such as emphysematous parenchyma) can be simultaneously represented at a given location in the HRCT.
Yamashiro T, Matsuoka S, San José Estépar R, Diaz A, Newell JD, Sandhaus RA, Mergo PJ, Brantly ML, Murayama S, Reilly JJ, Hatabu H, Silverman EK, Washko GR. Quantitative airway assessment on computed tomography in patients with alpha1-antitrypsin deficiency. COPD 2009;6(6):468-77.Abstract
The relationship between quantitative airway measurements on computed tomography (CT) and airflow limitation in individuals with severe alpha (1)-antitrypsin deficiency (AATD) is undefined. Thus, we planned to clarify the relationship between CT-based airway indices and airflow limitation in AATD. 52 patients with AATD underwent chest CT and pre-bronchodilator spirometry at three institutions. In the right upper (RUL) and lower (RLL) lobes, wall area percent (WA%) and luminal area (Ai) were measured in the third, fourth, and fifth generations of the bronchi. The severity of emphysema was also calculated in each lobe and expressed as low attenuation area percent (LAA%). Correlations between obtained measurements and FEV(1)% predicted (FEV(1)%P) were evaluated by the Spearman rank correlation test. In RUL, WA% of all generations was significantly correlated with FEV(1)%P (3rd, R = -0.33, p = 0.02; 4th, R = -0.39, p = 0.004; 5th, R = -0.57, p < 0.001; respectively). Ai also showed significant correlations (3rd, R = 0.32, p = 0.02; 4th, R = 0.34, p = 0.01; 5th, R = 0.56, p < 0.001; respectively). Measured correlation coefficients improved when the airway progressed distally from the third to fifth generations. LAA% also correlated with FEV(1)%P (R = -0.51, p < 0.001). In RLL, WA% showed weak correlations with FEV(1)%P in all generations (3rd, R = -0.34, p = 0.01; 4th, R = -0.30, p = 0.03; 5th, R = -0.31, p = 0.03; respectively). Only Ai from the fifth generation significantly correlated with FEV(1)%P in this lobe (R = 0.34, p = 0.01). LAA% strongly correlated with FEV(1)%P (R = -0.71, p < 0.001). We conclude therefore that quantitative airway measurements are significantly correlated with airflow limitation in AATD, particularly in the distal airways of RUL. Emphysema of the lower lung is the predominant component; however, airway disease also has a significant impact on airflow limitation in AATD.
Kindlmann GL, San José Estépar R, Smith SM, Westin C-F. Sampling and visualizing creases with scale-space particles. IEEE Trans Vis Comput Graph 2009;15(6):1415-24.Abstract
Particle systems have gained importance as a methodology for sampling implicit surfaces and segmented objects to improve mesh generation and shape analysis. We propose that particle systems have a significantly more general role in sampling structure from unsegmented data. We describe a particle system that computes samplings of crease features (i.e. ridges and valleys, as lines or surfaces) that effectively represent many anatomical structures in scanned medical data. Because structure naturally exists at a range of sizes relative to the image resolution, computer vision has developed the theory of scale-space, which considers an n-D image as an (n+1)-D stack of images at different blurring levels. Our scale-space particles move through continuous four-dimensional scale-space according to spatial constraints imposed by the crease features, a particle-image energy that draws particles towards scales of maximal feature strength, and an inter-particle energy that controls sampling density in space and scale. To make scale-space practical for large three-dimensional data, we present a spline-based interpolation across scale from a small number of pre-computed blurrings at optimally selected scales. The configuration of the particle system is visualized with tensor glyphs that display information about the local Hessian of the image, and the scale of the particle. We use scale-space particles to sample the complex three-dimensional branching structure of airways in lung CT, and the major white matter structures in brain DTI.
Dransfield MT, Nahm MH, Han MLK, Harnden S, Criner GJ, Martinez FJ, Scanlon PD, Woodruff PG, Washko GR, Connett JE, Anthonisen NR, Bailey WC. Superior immune response to protein-conjugate versus free pneumococcal polysaccharide vaccine in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009;180(6):499-505.Abstract
RATIONALE: Debate exists about the immunogenicity and protective efficacy of antibodies produced by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in chronic obstructive pulmonary disease (COPD). The 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) induces a more robust immune response than PPSV23 in healthy elderly adults. OBJECTIVES: We hypothesized that serotype-specific IgG antibody concentration and functional antibody activity would be superior after PCV7 vaccination compared with PPSV23 in moderate to severe COPD. We also posited that older age and prior PPSV23 vaccination would be associated with reduced vaccine responsiveness. METHODS: One hundred twenty patients with COPD were randomized to PPSV23 (63 subjects) or PCV7 (57 subjects). IgG concentrations were determined by ELISA; functional antibody activity was assayed with a standardized opsonophagocytosis assay and reported as an opsonization killing index (OPK). Increases in serotype-specific IgG and OPK at 1 month post vaccination were compared within and between vaccine groups. MEASUREMENTS AND MAIN RESULTS: Both vaccines were well tolerated. Within each study group, postvaccination IgG and OPK were higher than baseline (P < 0.01) for all serotypes. Adjusted for baseline levels, postvaccination IgG was higher in the PCV7 group than the PPSV23 group for all seven serotypes, reaching statistical significance for five (P < 0.05). PCV7 resulted in a higher OPK for six of seven serotypes (statistically greater for four) compared with PPSV23. In multivariate analyses, younger age, vaccine naivety, and receipt of PCV7 were associated with increased OPK responses. CONCLUSIONS: PCV7 induces a superior immune response at 1 month post vaccination compared with PPSV23 in COPD. Older age and prior PPSV23 reduce vaccine responsiveness. Clinical trial registered with www.clinicaltrials.gov (NCT00457977).
San José Estépar R, Westin C-F, Vosburgh KG. Towards real time 2D to 3D registration for ultrasound-guided endoscopic and laparoscopic procedures. Int J Comput Assist Radiol Surg 2009;4(6):549-60.Abstract
PURPOSE: A method to register endoscopic and laparoscopic ultrasound (US) images in real time with pre-operative computed tomography (CT) data sets has been developed with the goal of improving diagnosis, biopsy guidance, and surgical interventions in the abdomen. METHODS: The technique, which has the potential to operate in real time, is based on a new phase correlation technique: LEPART, which specifies the location of a plane in the CT data which best corresponds to the US image. Validation of the method was carried out using an US phantom with cyst regions and with retrospective analysis of data sets from animal model experiments. RESULTS: The phantom validation study shows that local translation displacements can be recovered for each US frame with a root mean squared error of 1.56 +/- 0.78 mm in less than 5 sec, using non-optimized algorithm implementations. CONCLUSION: A new method for multimodality (preoperative CT and intraoperative US endoscopic images) registration to guide endoscopic interventions was developed and found to be efficient using clinically realistic datasets. The algorithm is inherently capable of being implemented in a parallel computing system so that full real time operation appears likely.
Shams R, San Jose Estépar R, Patil V, Vosburgh KG. Intraoperative Ultrasound Probe Calibration in a Sterile Environment. In: Medical Image Computing and Computer-Assisted Intervention (MICCAI) 5th workshop on Augmented Environments for Medical Imaging and Computer-aided Surgery (AMI-ARCS)Medical Image Computing and Computer-Assisted Intervention (MICCAI) 5th workshop on Augment. London, UK: 2009 p. 53-60.
Washko GR, Dransfield MT, San Jose Estépar R, Diaz A, Matsuoka S, Yamashiro T, Hatabu H, Silverman EK, Bailey WC, Reilly JJ. Airway wall attenuation: a biomarker of airway disease in subjects with COPD. Journal of applied physiology (Bethesda, Md. : 1985)Journal of applied physiology (Bethesda, Md. : 1985) 2009;107:185-191.Abstract

The computed tomographic (CT) densities of imaged structures are a function of the CT scanning protocol, the structure size, and the structure density. For objects that are of a dimension similar to the scanner point spread function, CT will underestimate true structure density. Prior investigation suggests that this process, termed contrast reduction, could be used to estimate the strength of thin structures, such as cortical bone. In this investigation, we endeavored to exploit this process to provide a CT-based measure of airway disease that can assess changes in airway wall thickening and density that may be associated with the mural remodeling process in subjects with chronic obstructive pulmonary disease (COPD). An initial computer-based study using a range of simulated airway wall sizes and densities suggested that CT measures of airway wall attenuation could detect changes in both wall thickness and structure density. A second phantom-based study was performed using a series of polycarbonate tubes of known density. The results of this again demonstrated the process of contrast reduction and further validated the computer-based simulation. Finally, measures of airway wall attenuation, wall thickness, and wall area (WA) divided by total cross-sectional area, WA percent (WA%), were performed in a cohort of 224 subjects with COPD and correlated with spirometric measures of lung function. The results of this analysis demonstrated that wall attenuation is comparable to WA% in predicting lung function on univariate correlation and remain as a statistically significant correlate to the percent forced expiratory volume in 1 s predicted when adjusted for measures of both emphysema and WA%. These latter findings suggest that the quantitative assessment of airway wall attenuation may offer complementary information to WA% in characterizing airway disease in subjects with COPD.

j._appl._physiol._2009_washko.pdf
Kim WJ, Silverman EK, Hoffman E, Criner GJ, Mosenifar Z, Sciurba FC, Make BJ, Carey V, San Jose Estépar R, Diaz A, Reilly JJ, Martinez FJ, Washko GR, Washko GR. CT metrics of airway disease and emphysema in severe COPD. ChestChest 2009;136:396-404.Abstract

BACKGROUND: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. METHODS: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of -950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV(1) and percent predicted value of FEV(1) with CT scan measures of emphysema and airway disease. RESULTS: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = -0.28, p = 0.0001) and SRWA (r = -0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV(1)% predicted (R = -0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (beta = -5.2, p = 0.009; beta = -2.6, p = 0.008, respectively) and %LAA-950 (beta = -10.6, p = 0.03) with the postbronchodilator FEV(1)% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). CONCLUSIONS: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

chest_2009_kim.pdf
Fitzsimmons J, Kubicki M, Smith K, Bushell G, San Jose Estépar R, Westin CF, Nestor PG, Niznikiewicz MA, Kikinis R, McCarley RW, Shenton ME. Diffusion tractography of the fornix in schizophrenia. Schizophrenia researchSchizophrenia research 2009;107:39-46.Abstract

BACKGROUND: White matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in pathophysiology of schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from the hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provides a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix diffusion anisotropy in schizophrenia. METHODS: DTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age, parental socioeconomic status, and handedness. Regions of interest were drawn manually, blind to group membership, to guide tractography, and fractional anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. The Doors and People test (DPT) was used to evaluate visual and verbal memory, combined recall and combined recognition. RESULTS: Analysis of variance was performed and findings demonstrated a difference between patients with schizophrenia and controls for fornix FA (p=0.006). Protected post-hoc independent sample t-tests demonstrated a bilateral FA decrease in schizophrenia, compared with control subjects (left side: p=0.048; right side p=0.006). Higher fornix FA was statistically significantly correlated with DPT and measures of combined visual memory (r=0.554, p=0.026), combined verbal memory (r=0.647, p=0.007), combined recall (r=0.516, p=0.041), and combined recognition (r=0.710, p=0.002) for the control group. No such statistically significant correlations were found in the patient group. CONCLUSIONS: Our findings show the utility of applying DTI and tractography to study white matter fiber tracts in vivo in schizophrenia. Specifically, we observed a bilateral disruption in fornix integrity in schizophrenia, thus broadening our understanding of the pathophysiology of this disease.

schizophr._res._2009_fitzsimmons.pdf
Ross JC, San Jose Estépar R, Diaz A, Westin C-F, Kikinis R, Silverman EK, Washko GR. Lung extraction, lobe segmentation and hierarchical region assessment for quantitative analysis on high resolution computed tomography images. Medical image computing and computer-assisted intervention : MICCAI .. International Conference on Medical Image Computing and Computer-Assisted InterventionMedical image computing and computer-assisted intervention : MICCAI .. International Conference 2009;12:690-698.Abstract

Regional assessment of lung disease (such as chronic obstructive pulmonary disease) is a critical component to accurate patient diagnosis. Software tools than enable such analysis are also important for clinical research studies. In this work, we present an image segmentation and data representation framework that enables quantitative analysis specific to different lung regions on high resolution computed tomography (HRCT) datasets. We present an offline, fully automatic image processing chain that generates airway, vessel, and lung mask segmentations in which the left and right lung are delineated. We describe a novel lung lobe segmentation tool that produces reproducible results with minimal user interaction. A usability study performed across twenty datasets (inspiratory and expiratory exams including a range of disease states) demonstrates the tool's ability to generate results within five to seven minutes on average. We also describe a data representation scheme that involves compact encoding of label maps such that both "regions" (such as lung lobes) and "types" (such as emphysematous parenchyma) can be simultaneously represented at a given location in the HRCT.

med_image_comput_comput_assist_interv_2009_ross.pdf
Kindlmann GL, San Jose Estépar R, Smith SM, Westin CF. Sampling and Visualizing Creases with Scale-Space Particles. IEEE Transactions on Visualization and Computer GraphicsIEEE Transactions on Visualization and Computer Graphics 2009;15:1415-1424.Abstract
  1. Abstract—Particle systems have gained importance as a methodology for sampling implicit surfaces and segmented objects to improve mesh generation and shape analysis. We propose that particle systems have a significantly more general role in sampling structure from unsegmented data. We describe a particle system that computes samplings of crease features (i.e. ridges and valleys, as lines or surfaces) that effectively represent many anatomical structures in scanned medical data. Because structure naturally exists at a range of sizes relative to the image resolution, computer vision has developed the theory of scale-space, which considers an n-D image as an (n+1)-D stack of images at different blurring levels. Our scale-space particles move through continuous four- dimensional scale-space according to spatial constraints imposed by the crease features, a particle-image energy that draws particles towards scales of maximal feature strength, and an inter-particle energy that controls sampling density in space and scale. To make scale-space practical for large three-dimensional data, we present a spline-based interpolation across scale from a small number of pre-computed blurrings at optimally selected scales. The configuration of the particle system is visualized with tensor glyphs that display information about the local Hessian of the image, and the scale of the particle. We use scale-space particles to sample the complex three-dimensional branching structure of airways in lung CT, and the major white matter structures in brain DTI. 

ieee_trans._visual._comput._graphics_2009_kindlmann.pdf
San Jose Estépar R, Westin C-F, Vosburgh KG. Towards real time 2D to 3D registration for ultrasound-guided endoscopic and laparoscopic procedures. International journal of computer assisted radiology and surgeryInternational journal of computer assisted radiology and surgery 2009;4:549-560.Abstract

PURPOSE:A method to register endoscopic and laparoscopic ultrasound (US) images in real time with pre-operative computed tomography (CT) data sets has been developed with the goal of improving diagnosis, biopsy guidance, and surgical interventions in the abdomen.METHODS:The technique, which has the potential to operate in real time, is based on a new phase correlation technique: LEPART, which specifies the location of a plane in the CT data which best corresponds to the US image. Validation of the method was carried out using an US phantom with cyst regions and with retrospective analysis of data sets from animal model experiments.RESULTS:The phantom validation study shows that local translation displacements can be recovered for each US frame with a root mean squared error of 1.56 +/- 0.78 mm in less than 5 sec, using non-optimized algorithm implementations.CONCLUSION:A new method for multimodality (preoperative CT and intraoperative US endoscopic images) registration to guide endoscopic interventions was developed and found to be efficient using clinically realistic datasets. The algorithm is inherently capable of being implemented in a parallel computing system so that full real time operation appears likely.

int_j_comput_assist_radiol_surg_2009_san_jose_estepar.pdf