My research interests focus on the long term effects of chronic lung disease on respiratory structure and resultant lung function. Lab research involves measuring structural function with serial CT imaging at similar lung volumes and expiratory CT scans to optimize evaluation of regional small airway disease. The advantage of understanding the molecular and physiologic events of lung disease provides the opportunity for preemptive medical intervention before symptoms appear.
Emeritus Faculty - University Medical Line, Pediatrics - Pulmonary Medicine
Packard Children's Hospital Resident Education Committee, LPCH (2001 - 2002)
Medical Specialties Peer Review Committee, LPCH (2005 - 2007)
Honors & Awards
Honorary Invited Speaker Annual Scientific Meeting, Sydney, Australia, Auckland, New Zealand,, The Thoracic Society of Australia & New Zealand and ANZSRS (March 2007)
Honorary Invited Participant, Leuven, Belgium, European Respiratory Society (February 2007)
Provider of the Year, Cystic Fibrosis Foundation, Northern California Chapter (October 2006)
Michael D. Black, Purna Prasad, Terry E. Robinson. "United States Patent 6,869,397 Non-tethered macro to micro endoscope", The Board of Trustees of the Leland Stanford Junior University, Mar 22, 2005
Terry Robinson, Wallace White, Nicholas Kalayjian. "United States Patent 6,631,716 Dynamic Respiratory Control", The Board of Trustees of the Leland Stanford Junior University, Oct 14, 2003
Current Research and Scholarly Interests
My research interests focus on detection of early and progressive Cystic fibrosis (CF) structural lung disease by utilizing chest CT imaging and CT post-processing methodology. Current research efforts involve utilization of low dose infant & children CT imaging protocols and quantitative airway and air trapping algorithms to evaluate early and progressive CF disease. Additional areas of research in our laboratory include defining more direct pulmonary outcome measures to evaluate treatment effects in chronic diseases such as cystic fibrosis and pulmonary alveolar proteinosis.
Infant Study of Inhaled Saline in Cystic Fibrosis
The purpose of this study is to assess whether 7% hypertonic saline (HS) is an effective and safe therapy in infants and young children with CF.
Rare Genetic Disorders of the Breathing Airways
Mucociliary clearance, in which mucus secretions are cleared from the breathing airways, is the primary defense mechanism for the lungs. Inhaled particles, including microbes that can cause infections, are normally entrapped in mucus on the airway surfaces and then cleared out by the coordinated action of tiny hair-like structures called cilia. Individuals with primary ciliary dyskinesia, variant cystic fibrosis, and pseudohypoaldosteronism have defective mucociliary clearance. The purpose of this study is to collect clinical and genetic information about these three airway diseases to improve current diagnostic procedures.
Controlled Ventilation CT in CF Infants
The objective of the study is to implement a new method of performing chest CT imaging in young children with cystic fibrosis at Packard Children's Hospital. This technique will be used to evaluate early lung disease comparing quantitative chest CT air trapping and airway measurements with lung function measurements in infants, toddlers, and young children with chronic lung disease.
Stanford is currently not accepting patients for this trial. For more information, please contact Colleen Dunn, 650-736-0388.
Outcome Measures in Infant/Early Childhood Lung Disease w/ Chest CT Scanning & Lung Function Testing
To implement a new method of performing chest CT imaging in young children at Packard Children's Hospital entitled controlled ventilation infant/young child chest CT scanning. This technique will be used to evaluate early lung disease comparing quantitative chest CT air trapping and airway measurements with lung function measurements in infants, toddlers, and young children with chronic lung disease.
Stanford is currently not accepting patients for this trial. For more information, please contact Yan Ki Angela Leung, 650-723-5193.
Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects
This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV), administered for 8 or 12 weeks of treatment in participants with chronic genotype 1 hepatitis C virus (HCV) infection who are treatment-naive, and for 12 weeks in participants who had previously received a regimen containing a protease inhibitor for the treatment of HCV.
Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H Nguyen, 650-498-7878.
The EPIC Observational Study
The purpose of this study is to better define risk factors preceding first isolation of Pseudomonas aeruginosa (Pa) from respiratory cultures in cystic fibrosis (CF) lung disease and to better define clinical outcomes associated with acquisition of Pa. This study will also collect and bank DNA samples for current and future studies designed to enhance the understanding of the pathogenesis of CF.
Stanford is currently not accepting patients for this trial. For more information, please contact Colleen Dunn, (650) 736 - 0388.
- Independent Studies (5)
Graduate and Fellowship Programs
Pediatric Pulmonology (Fellowship Program)
Pediatric Radiology (Fellowship Program)
Influence of radiation dose and reconstruction algorithm in MDCT assessment of airway wall thickness: A phantom study
2015; 42 (10): 5919-5927
Wall thickness (WT) is an airway feature of great interest for the assessment of morphological changes in the lung parenchyma. Multidetector computed tomography (MDCT) has recently been used to evaluate airway WT, but the potential risk of radiation-induced carcinogenesis-particularly in younger patients-might limit a wider use of this imaging method in clinical practice. The recent commercial implementation of the statistical model-based iterative reconstruction (MBIR) algorithm, instead of the conventional filtered back projection (FBP) algorithm, has enabled considerable radiation dose reduction in many other clinical applications of MDCT. The purpose of this work was to study the impact of radiation dose and MBIR in the MDCT assessment of airway WT.An airway phantom was scanned using a clinical MDCT system (Discovery CT750 HD, GE Healthcare) at 4 kV levels and 5 mAs levels. Both FBP and a commercial implementation of MBIR (Veo(TM), GE Healthcare) were used to reconstruct CT images of the airways. For each kV-mAs combination and each reconstruction algorithm, the contrast-to-noise ratio (CNR) of the airways was measured, and the WT of each airway was measured and compared with the nominal value; the relative bias and the angular standard deviation in the measured WT were calculated. For each airway and reconstruction algorithm, the overall performance of WT quantification across all of the 20 kV-mAs combinations was quantified by the sum of squares (SSQs) of the difference between the measured and nominal WT values. Finally, the particular kV-mAs combination and reconstruction algorithm that minimized radiation dose while still achieving a reference WT quantification accuracy level was chosen as the optimal acquisition and reconstruction settings.The wall thicknesses of seven airways of different sizes were analyzed in the study. Compared with FBP, MBIR improved the CNR of the airways, particularly at low radiation dose levels. For FBP, the relative bias and the angular standard deviation of the measured WT increased steeply with decreasing radiation dose. Except for the smallest airway, MBIR enabled significant reduction in both the relative bias and angular standard deviation of the WT, particularly at low radiation dose levels; the SSQ was reduced by 50%-96% by using MBIR. The optimal reconstruction algorithm was found to be MBIR for the seven airways being assessed, and the combined use of MBIR and optimal kV-mAs selection resulted in a radiation dose reduction of 37%-83% compared with a reference scan protocol with a dose level of 1 mGy.The quantification accuracy of airway WT is strongly influenced by radiation dose and reconstruction algorithm. The MBIR algorithm potentially allows the desired WT quantification accuracy to be achieved with reduced radiation dose, which may enable a wider clinical use of MDCT for the assessment of airway WT, particularly for younger patients who may be more sensitive to exposures with ionizing radiation.
View details for DOI 10.1118/1.4930797
View details for Web of Science ID 000362570100035
View details for PubMedID 26429266
View details for PubMedCentralID PMC4575323
- Chest CT in Children: Anesthesia and Atelectasis Pediatric Radiology 2014; 44 (2): 164-72
Improved air trapping evaluation in chest computed tomography in children with CF using real-time spirometric monitoring and biofeedback
Journal of Cystic Fibrosis
2013; 12 (6): 559-66
View details for DOI 10.1016/j.jcf.2013.05.012
Comparison of Different Methods of Calculating CT Radiation Effective Dose in Children
Annual Meeting of the Society-for-Pediatric-Radiology
AMER ROENTGEN RAY SOC. 2012: W232–W239
CT radiation dose is a subject of intense interest and concern, especially in children. Effective dose, a summation of whole-body exposure weighted by specific organ sensitivities, is most often used to compute and compare radiation dose; however, there is little standardization, and there are numerous different methods of calculating effective dose. This study compares five such methods in a group of children undergoing routine chest CT and explores their advantages and pitfalls.Patient data from 120 pediatric chest CT examinations were retrospectively used to calculate effective dose: two scanner dose-length product (DLP) methods using published sets of conversion factors by Shrimpton and Deak, the imaging performance and assessment of CT (ImPact) calculator method, the Alessio online calculator, and the Huda method.The Huda method mean effective dose (4.4 ± 2.2 mSv) and Alessio online calculator (5.2 ± 2.8 mSv) yielded higher mean numbers for effective dose than both DLP calculations (Shrimpton, 3.65 ± 1.8 mSv, and Deak, 3.2 ± 1.5 mSv) as well as the ImPact calculator effective dose (3.4 ± 1.7 mSv). Mean differences ranged from 10.2% ± 10.1% lower to 28% ± 37.3% higher than the Shrimpton method (used as the standard for comparison). Differences were more marked at 120 kVp than at 80 or 100 kVp and varied at different ages. Concordance coefficients relative to the Shrimpton DLP method were Deak DLP, 0.907; Alessio online calculator, 0.735; ImPact calculator, 0.926; and Huda, 0.777.Different methods of computing effective dose for pediatric CT produce varying results. The method used must be clearly described to allay confusion about documenting and communicating dose for archiving as well as comparative research purposes.
View details for DOI 10.2214/AJR.10.5895
View details for Web of Science ID 000306686200012
View details for PubMedID 22826426
Development and Validation of Automated 2D-3D Bronchial Airway Matching to Track Changes in Regional Bronchial Morphology Using Serial Low-Dose Chest CT Scans in Children with Chronic Lung Disease
JOURNAL OF DIGITAL IMAGING
2010; 23 (6): 744-754
To address potential concern for cumulative radiation exposure with serial spiral chest computed tomography (CT) scans in children with chronic lung disease, we developed an approach to match bronchial airways on low-dose spiral and low-dose high-resolution CT (HRCT) chest images to allow serial comparisons. An automated algorithm matches the position and orientation of bronchial airways obtained from HRCT slices with those in the spiral CT scan. To validate this algorithm, we compared manual matching vs automatic matching of bronchial airways in three pediatric patients. The mean absolute percentage difference between the manually matched spiral CT airway and the index HRCT airways were 9.4 ± 8.5% for the internal diameter measurements, 6.0 ± 4.1% for the outer diameter measurements, and 10.1 ± 9.3% for the wall thickness measurements. The mean absolute percentage difference between the automatically matched spiral CT airway measurements and index HRCT airway measurements were 9.2 ± 8.6% for the inner diameter, 5.8 ± 4.5% for the outer diameter, and 9.9 ± 9.5% for the wall thickness. The overall difference between manual and automated methods was 2.1 ± 1.2%, which was significantly less than the interuser variability of 5.1 ± 4.6% (p<0.05). Tests of equivalence had p<0.05, demonstrating no significant difference between the two methods. The time required for matching was significantly reduced in the automated method (p<0.01) and was as accurate as manual matching, allowing efficient comparison of airways obtained on low-dose spiral CT imaging with low-dose HRCT scans.
View details for DOI 10.1007/s10278-009-9199-3
View details for Web of Science ID 000284163300011
View details for PubMedID 19756866
View details for PubMedCentralID PMC3046688
Cystic Fibrosis HRCT Scores Correlate Strongly With Pseudomonas Infection
2009; 44 (11): 1107-1117
In order to establish a valid surrogate outcome measure, it must be shown that the outcome measure (chest HRCT scores in cystic fibrosis [CF] patients) demonstrates strong statistical association with established endpoints of disease, such as Pseudomonas aeruginosa (Pa) airway acquisition, acute exacerbations, or mortality.We estimated and tested the association between Pa infection status (Pa+ vs. Pa-) and baseline chest HRCT scores in 25 children with mild-to-moderate CF lung disease. For comparison, we estimated the association between Pa status and pulmonary function tests (PFTs), chest X-rays (CXR) scores, and BMI. Pa acquisition was determined from respiratory culture results and systematic review of clinic notes.All subjects had respiratory cultures performed prior to or at baseline with a median of 19 months of retrospective culture observation (SD = 15.7 months, range: 0-52.5 months). The difference between age-adjusted mean total HRCT score for Pa+ versus Pa- was highly significant (P < 0.00001) with a near-perfect separation between scores in Pa+ versus Pa- patients. Similar results were found for several HRCT sub-scores. Among PFTs, only residual volume-to-total lung capacity (RV/TLC) had a significant difference between group means (P = 0.03), but the overlap between groups in RV/TLC measurements was large.CF HRCT scores correlate highly with Pa acquisition, a clinically meaningful measure of progressing CF lung disease. HRCT scores are highly sensitive at predicting Pa acquisition status, while most PFT measures, chest radiograph (CXR) scores, and body mass index are not. These results provide further evidence that HRCT is appropriate for use in patient care and as an outcome measure in clinical trials.
View details for DOI 10.1002/ppul.21107
View details for Web of Science ID 000271602200009
View details for PubMedID 19824046
An Airway Phantom to Standardize CT Acquisition in Multicenter Clinical Trials
2009; 16 (9): 1134-1141
The purpose of this study was to demonstrate the use of a phantom to standardize low-dose chest computed tomographic (CT) protocols in children with cystic fibrosis.Spiral chest CT scans of a Plexiglas phantom simulating airway sizes (internal diameter, 1.1-16.4 mm; wall thickness, 0.4-4.6 mm) in children with cystic fibrosis were obtained using two multidetector CT (MDCT) scanners (GE VCT and Siemens Sensation 64). Quantitative airway measurements from both scanners were compared with micro-CT airway measurements over a range of doses (0.2-1.8 mSv) to evaluate bias and variance of measurements. The effective doses for CT protocols were estimated using the ImPACT CT Patient Dosimetry Calculator.Both MDCT scanners were able to accurately measure airway sizes down to 3 mm internal diameter and 1.3 mm airway wall thickness, with errors of <3.5%. ImPACT estimates of effective dose were different for the MDCT scanners for a given peak tube voltage and product of tube current and exposure time. Accuracy and precision were not found to be associated with dose parameters for either machine. Bias in all measurements was strongly associated with airway diameter (P values < .00001), but the magnitude of bias was small (mean, 0.07 mm; maximum, 0.21 mm). Differences between machines in error components were on the order of a few micrometers.The use of a standard airway phantom confirms that different MDCT scanners have similar results within dose ranges planned for potential future clinical trials. Standardized protocols can be developed that adjust for differences in radiation exposure for different MDCT scanners.
View details for DOI 10.1016/j.acra.2009.02.018
View details for Web of Science ID 000269067000011
View details for PubMedID 19467609
Sampling density for the quantitative evaluation of air trapping
2009; 39 (3): 221-225
Concerns have been expressed recently about the radiation burden on patient populations, especially children, undergoing serial radiological testing. To reduce the dose one can change the CT acquisition settings or decrease the sampling density.In this study we determined the minimum desirable sampling density to ascertain the degree of air trapping in children with cystic fibrosis.Ten children with cystic fibrosis in stable condition underwent a volumetric spiral CT scan. The degree of air trapping was determined by an automated algorithm for all slices in the volume, and then for 1/2, 1/4, to 1/128 of all slices, or a sampling density ranging from 100% to 1% of the total volume. The variation around the true value derived from 100% sampling was determined for all other sampling densities.The precision of the measurement remained stable down to a 10% sampling density, but decreased markedly below 3.4%.For a disease marker with the regional variability of air trapping in cystic fibrosis, regardless of observer variability, a sampling density below 10% and even more so, below 3.4%, apparently decreases the precision of the evaluation.
View details for DOI 10.1007/s00247-008-1076-6
View details for Web of Science ID 000263097600005
View details for PubMedID 19096836
Quantitative Analysis of Longitudinal Response to Aerosolized Granulocyte-Macrophage Colony-Stimulating Factor in Two Adolescents With Autoimmune Pulmonary Alveolar Proteinosis
2009; 135 (3): 842-848
Autoimmune pulmonary alveolar proteinosis (APAP) is characterized by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in blood and tissues, resulting in alveolar surfactant protein accumulation. Patients with APAP present with ground-glass opacities (GGOs) and interlobular septal thickening on thin-slice chest CT scans. Aerosolized GM-CSF therapy (aeroGM-SCF) has qualitatively improved the clinical condition of patients with APAP. This report details quantitative chest CT responses to aeroGM-CSF.Two adolescent patients (aged 16 and 19 years) with APAP were treated with aeroGM-CSF. Clinical parameters, including pulmonary function tests and chest CT scans, were obtained before and after aeroGM-CSF therapy. To evaluate the effect of the therapy, serial chest CT scans were analyzed using a novel approach permitting quantitative assessment of improvement in GGOs, lung weight, and gas volume.In association with GM-CSF treatment, nutritional status and pulmonary function improved. Quantitative analysis of the CT scans demonstrated reduction in GGOs and lung weight, concomitant with an increase in airspace volume and lung inflation. The findings were consistent with a qualitative reduction in GGOs on chest CT imaging.Quantitative analysis of CT holds promise as a sensitive diagnostic tool permitting longitudinal and objective analysis of the therapeutic response to aeroGM-CSF in patients with APAP.
View details for DOI 10.1378/chest.08-1317
View details for Web of Science ID 000264310500034
View details for PubMedID 19265094
Successful pregnancy and cesarean delivery via noninvasive ventilation in mitochondrial myopathy
JOURNAL OF PERINATOLOGY
2009; 29 (2): 166-167
We report a case study of a 22-year-old woman with mitochondrial thymidine kinase 2 deficiency and chronic respiratory failure due to severe neuromuscular weakness requiring noninvasive positive pressure ventilation (NIPPV) since 12 years of age. During pregnancy and cesarean delivery, she was successfully supported with NIPPV. A multidisciplinary team approach should be used in pregnant patients with these disorders with specific attention to management of pulmonary complications, selection of route of delivery, anesthesia, and analgesia.
View details for DOI 10.1038/jp.2008.178
View details for Web of Science ID 000263492700016
View details for PubMedID 19177045
A critical discussion of computer analysis in medical imaging.
Proceedings of the American Thoracic Society
2007; 4 (4): 347-349
Medical imaging has increasingly provided surrogate endpoints in therapeutic trials. This use assumes that the interpretation of the images can be unbiased and reproducible and that the image attributes included in the interpretation are relevant to the mechanism of the trial. The principal motivation for computer analysis is to evaluate an attribute of the image as a metric in an algorithmic manner, independent of observer bias or variability. The metric is expected to reflect change in rough proportion with at least one aspect of the degree of disease or the effectiveness of the therapeutic intervention. If either condition is satisfied, the measure is quantitative. Visual interpretation explicitly or implicitly tends to be based on multiple image attributes. Explicit combination of multiple attributes yields composite scores. To evaluate the risk or probability of disease, they are useful. But the components of the scores can be combined only if they are mathematically isomorphic. For the evaluation of interventions, they are less useful because the effect on one component may be obscured by the lack of effect on other components. This article reviews quantification of air trapping in cystic fibrosis and quantification in general. Validation of any computer analysis can rely on agreement with visual interpreters (on average), they can be derived from first principles, or by agreement with an alternative method that measures the pathophysiological mechanism directly (xenon washout for air trapping). However, in the context of trials, the validation may come from a superior ability to detect objective change and to discriminate between affected and unaffected individuals.
View details for PubMedID 17652499
Computed tomography scanning techniques for the evaluation of cystic fibrosis lung disease.
Proceedings of the American Thoracic Society
2007; 4 (4): 310-315
Multidetector computed tomography (MDCT) scanners allow diagnosis and monitoring of cystic fibrosis (CF) lung disease at substantially lower radiation doses than with prior scanners. Complete spiral chest CT scans are accomplished in less than 10 seconds and scanner advances now allow the acquisition of comprehensive volumetric datasets for three-dimensional reconstruction of the lungs and airways. There are two types of CT scanning protocols currently used to assess CF lung disease: (1) high-resolution CT (HRCT) imaging, in which thin 0.5-1.5-mm slices are obtained every 0.5, 1, or 2 cm from apex to base for inspiratory scans, and limited, spaced HRCT slices obtained for expiratory scans; and (2) complete spiral CT imaging covering the entire lung for inspiratory and expiratory scanning. These scanning protocols allow scoring of CF lung disease and provide CT datasets to quantify airway and air-trapping measurements. CF CT scoring systems typically assess bronchiectasis, bronchial wall thickening, mucus plugging, and atelectasis/consolidation from inspiratory scans, whereas air trapping is scored from expiratory imaging. Recently, CT algorithms have been developed for both HRCT and complete spiral CT imaging to quantify several airway indices, to determine the volume and density of the lung, and to assess regional and global air trapping. CT scans are currently acquired by either controlled-volume scanning techniques (controlled-ventilation infant CT scanning or spirometer-controlled CT scanning in children and adults) or by voluntary breath holds at full inflation and deflation.
View details for PubMedID 17652492
Imaging of the chest in cystic fibrosis
CLINICS IN CHEST MEDICINE
2007; 28 (2): 405-?
In the last 2 decades significant strides have been made in the application of chest imaging modalities to assess cystic fibrosis (CF) lung disease. This article covers current chest imaging modalities. It discusses CT, the research modality most commonly used to assess lung disease in CF, new insights regarding CF lung disease, and future directions in research and clinical care.
View details for DOI 10.1016/j.ccm.2007.02.012
View details for Web of Science ID 000246780300012
View details for PubMedID 17467556
Fully automated system for three-dimensional bronchial morphology analysis using volumetric multidetector computed tomography of the chest
JOURNAL OF DIGITAL IMAGING
2006; 19 (2): 132-139
Recent advancements in computed tomography (CT) have enabled quantitative assessment of severity and progression of large airway damage in chronic pulmonary disease. The advent of fast multidetector computed tomography scanning has allowed the acquisition of rapid, low-dose 3D volumetric pulmonary scans that depict the bronchial tree in great detail. Volumetric CT allows quantitative indices of bronchial airway morphology to be calculated, including airway diameters, wall thicknesses, wall area, airway segment lengths, airway taper indices, and airway branching patterns. However, the complexity and size of the bronchial tree render manual measurement methods impractical and inaccurate. We have developed an integrated software package utilizing a new measurement algorithm termed mirror-image Gaussian fit that enables the user to perform automated bronchial segmentation, measurement, and database archiving of the bronchial morphology in high resolution and volumetric CT scans and also allows 3D localization, visualization, and registration.
View details for DOI 10.1007/s10278-005-9240-0
View details for Web of Science ID 000238317500007
View details for PubMedID 16341571
View details for PubMedCentralID PMC3045191
Computed tomography in the evaluation of cystic fibrosis lung disease
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
2005; 172 (10): 1246-1252
The first report of computed tomography (CT) scanning to monitor cystic fibrosis (CF)-related lung disease was published in 1986. Further publications followed, but in general there was little interest in this technique until recently. Two factors in particular have led to this increased interest. First is an increasing realization that pulmonary function tests, long the mainstay of CF evaluation, often underestimate the presence and severity of mild and moderate lung disease. Second is the need for more sensitive outcome measures to assess new therapies. This had led to new interest and a series of important publications. The goal of this article is to present the current status of CT scanning in CF.
View details for DOI 10.1164/rccm.200503-401PP
View details for Web of Science ID 000233182200004
View details for PubMedID 16100011
Dornase alfa reduces air trapping in children with mild cystic fibrosis lung disease - A quantitative analysis
2005; 128 (4): 2327-2335
To evaluate quantitative air trapping measurements in children with mild cystic fibrosis (CF) lung disease during a 1-year, double-blind, placebo-controlled, recombinant human deoxyribonuclease (rhDNase) [dornase alfa] intervention trial and compare results from quantitative air trapping with those from spirometry or visually scored high-resolution CT (HRCT) scans of the chest.Twenty-five children with CF randomized to either daily rhDNase or placebo aerosol were evaluated at baseline, and at 3 months and 12 months by spirometer-triggered HRCT and spirometry. Outcome variables were percentage of predicted FVC, FEV1, and forced expiratory flow, midexpiratory phase (FEF(25-75%)); total and subcomponent visual HRCT scores; and quantitative air trapping measurements derived from chest HRCT images.At baseline, there were no statistical differences between groups in any of the variables used as an outcome. After 3 months of treatment, both groups had improvements in percentage of predicted FEV1 and FEF(25-75%), and total HRCT visual scores. In contrast, the rhDNase group had a 13% decrease in quantitative air trapping from baseline (severe air trapping [A3]), compared to an increase of 48% in the placebo group (p = 0.023). After 12 months, both groups had declines in percentage of predicted FVC and FEV1, but the rhDNase group retained improvements in percentage of predicted FEF(25-75%) and quantitative air trapping. The mucus plugging and total HRCT visual scores were also improved in the rhDNase group after 12 months of treatment, with and without significant differences between groups (p = 0.026 and p = 0.676). Quantitative air trapping (A3) remained improved in the rhDNase group (- 15.4%) and worsened in the placebo group (+61.3%) with nearly significant differences noted between groups (p = 0.053) after 12 months of treatment.Quantitative air trapping is a more consistent sensitive outcome measure than either spirometry or total HRCT scores, and can discriminate differences in treatment effects in children with minimal CF lung disease.
View details for Web of Science ID 000232679400063
View details for PubMedID 16236891
Quantitative air-trapping analysis in children with mild cystic fibrosis lung disease
2004; 38 (5): 396-405
The purpose of this study was to compare quantitative computed tomography air trapping (AT) and pulmonary function measurements between subjects with mild cystic fibrosis lung disease (MCF; forced expiratory volume in 1 sec (FEV1) > 70% predicted) and normal age-matched controls. Quantitative AT measurements at different levels of expiration were evaluated. Ten subjects from the MCF group and 10 normal subjects underwent inspiratory and expiratory spirometer-triggered chest high-resolution computed tomography (HRCT) and pulmonary function tests. Six matched CT images were obtained at full inflation and at a lung volume near residual volume (nRV). Quantitative measurements of AT were determined by evaluating expiratory CT lung density and by the percent of segmented lung which demonstrated AT on expiratory scans. Percent AT was evaluated for all lung slices combined (global AT), and also by regional assessment. Additional comparisons of lung density and percent air trapping were made in 10 CF subjects with three matched axial HRCT images at lung volumes corresponding to full inflation, near functional residual capacity (nFRC), and nRV. All measurements of expiratory lung density in CF subjects were significantly lower and % AT significantly higher than normal controls. Significant correlations for all subjects were observed between % global AT and RV/TLC as well as forced expiratory flow between 25-75% of forced vital capacity (FEF(25-75)) % predicted. Pulmonary density measurements and % AT better discriminated differences between groups than PFTs. Measurements made on expiratory scans near FRC showed significantly higher values for AT than those made near RV.
View details for DOI 10.1002/ppul.20091
View details for Web of Science ID 000224625500004
View details for PubMedID 15390349
High-resolution CT scanning: potential outcome measure
CURRENT OPINION IN PULMONARY MEDICINE
2004; 10 (6): 537-541
High-resolution CT (HRCT) imaging of the chest can provide both structural and functional lung analysis useful to evaluate initial and progressive cystic fibrosis (CF) lung disease. Chest HRCT scoring systems have been used to evaluate the extent and severity of CF specific airway and lung parenchymal disease. The purpose of this review is to summarize recent developments in HRCT and volumetric chest CT imaging, CF chest CT scoring systems, and review how HRCT/volumetric CT can provide useful outcome measures for future CF clinical research.Early manifestation of CF lung disease determined by chest CT/HRCT imaging in CF infants and children with mild disease include regional air trapping and bronchial wall thickness. The distribution of findings in more progressed CF lung disease are heterogeneous, and there appears to be a large amount of nonhomogeneity of progressive lung pathology. Recent CF studies have used new clinical CT parameters such as quantitative air trapping, quantitative airway measurements, and a composite CT/pulmonary function test (PFT) score, which appear to be promising new outcome measures that are more sensitive than global pulmonary function measurements or total chest CT scores in discriminating early or mild CF lung disease and treatment effects during clinical interventions.Chest HRCT and volumetric CT imaging can detect regional CF lung changes before changes in global pulmonary function measurements. Chest HRCT scoring has been used in descriptive studies defining CF lung disease severity, in longitudinal studies to define progression of disease, and in clinical intervention studies to evaluate treatment effects. In the last 2 years, CF CT research has evolved from solely using chest HRCT scoring systems to utilization of composite CT/PFT scores, quantitative airway and air trapping measurements, and the utilization of volumetric CT imaging to evaluate three-dimensional data sets in patients with CF lung disease.
View details for Web of Science ID 000224924300014
View details for PubMedID 15510063
Composite spirometric-computed tomography outcome measure in early cystic fibrosis lung disease
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
2003; 168 (5): 588-593
With the advent of therapies aimed at young patients with cystic fibrosis, who have mildly reduced pulmonary function, the need for improved outcome measures that discriminate treatment effects has become important. Pulmonary function measurements or chest high-resolution computed tomography (HRCT) scores have been separately used to assess interventions. We evaluated these modalities separately and together during a treatment study to develop a more sensitive outcome measure. In a 1-year trial, 25 children randomized either to daily Pulmozyme or to normal saline aerosol were evaluated at randomization and at 3 and 12 months. Outcome variables were pulmonary function test (PFT) results, a global HRCT score, and a composite score incorporating PFTs and HRCT scoring. Regression analyses with generalized estimating equations permitted estimation of the difference in treatment effect between groups over time for each outcome. The largest difference in treatment effects observed at 12 months, measured by the percentage change from baseline, were with the composite total and maximal CT/PFT scores (35.4 and 30.4%), compared with mean forced expiratory flow during the middle half of the FVC (FEF25-75%) (13.0%) and total and maximal global HRCT scores (6.2%, 7.2%). The composite total and maximal CT/PFT scores were the most sensitive outcome measures for discriminating a treatment effect in children with cystic fibrosis with normal or mildly reduced pulmonary function during a 1-year trial of Pulmozyme.
View details for DOI 10.1164/rccm.200209-1093OC
View details for PubMedID 12746252
Pulmonary glial heterotopia in a monoamniotic twin
2003; 36 (2): 162-166
Brain heterotopia in the lungs is rare, but when it occurs in an otherwise healthy newborn, it presents a difficult diagnostic problem and uncertain pathophysiology. We report on a 2-week-old premature infant who presented with respiratory distress and widespread cystic lung changes identified by chest imaging studies. Autopsy demonstrated that the cyst walls were composed of well-differentiated neuroglial tissue, which was confirmed by immunohistochemistry. The cysts were partially lined by bronchial epithelium and contained keratinous debris. For the first time, we demonstrate that the debris stain for human chorionic gonadotropin, compatible with aspirated amnion. There were no other congenital abnormalities. Her monoamniotic twin was anencephalic and died at birth. Although the etiology of glial heterotopia in the lungs is unknown, the majority of cases are associated with anencephalic newborns. Some authors postulated that this heterotopia may therefore be a consequence of fetal aspiration of brain tissue. Other possibilities include glial predominant teratomas, hamartomatous malformations, and abnormal neural crest migration. Our review of the 21 cases reported over the past century suggests that in utero aspiration of glial cells, or abnormal neural crest migration, are the most likely explanations for this rare and fatal disease.
View details for DOI 10.1002/ppul.10292
View details for Web of Science ID 000184621100011
View details for PubMedID 12833496
An automated approach to quantitative air trapping measurements in mild cystic fibrosis
2003; 123 (5): 1655-1663
To automatically derive the degree of air trapping in mild cystic fibrosis (CF) disease from high-resolution CT (HRCT) data, and to evaluate the discriminating power of the measurement.The data consist of six pairs of anatomically matched tomographic slices, obtained during breath-holding in triggered HRCT acquisitions. The pairs consist of an inspiratory slice, at > or = 95% of slow vital capacity, and an expiratory slice at near residual volume (nRV). The subjects are 25 patients with mild CF and 10 age-matched, normal control subjects.Lung segmentation is automatic. The limits defining air trapping in the expiratory slices are determined by the distribution of densities in the expanded lung. They are modulated by density changes between expiration and inspiration. Air trapping defects consist of contiguous low-density voxels. The difference between patients and control subjects was evaluated in comparison to pulmonary function test (PFT) results and lung density distribution descriptors (global density descriptors).In mild CF, air trapping does not correlate with global PFT results, except for the ratio of residual volume (RV) to total lung capacity (TLC); however, the size of air trapping defects was the best discriminator between patients and control subjects (p < 0.005). Of PFT results, only RV/TLC reached significance at p < 0.05. The global density descriptors reached near significance in the nRV images only.Air trapping defined as defect size and measured in an objective automated manner is a powerful discriminator for mild CF.
View details for PubMedID 12740287
- Acute stress disorder following ventilation PSYCHOSOMATICS 2002; 43 (1): 74-76
Spirometer-triggered high-resolution computed tomography and pulmonary function measurements during an acute exacerbation in patients with cystic fibrosis
JOURNAL OF PEDIATRICS
2001; 138 (4): 553-559
To evaluate a high-resolution computed tomography (HRCT) scoring system, clinical parameters, and pulmonary function measurements in patients with cystic fibrosis (CF) before and after therapy for a pulmonary exacerbation.Patients (n = 17) were evaluated by spirometer-triggered HRCT imaging, clinical parameters, and pulmonary function tests (PFTs) before and after treatment. HRCT scans were reviewed by 3 radiologists using a modified Bhalla scoring system.Bronchiectasis, bronchial wall thickening, and air trapping were identified in all subjects on initial evaluation. The initial total HRCT score correlated significantly with the Brasfield score (r = -.91, P <.001) and several PFT measures. After treatment, there were improvements in the acute change clinical score (ACCS) (P <.001), most pulmonary function measurements, and total HRCT score (P <.05). Bronchiectasis, bronchial wall thickening, and air trapping did not significantly change. Mucus plugging subcomponent HRCT score, slow vital capacity (SVC), forced expiratory volume in 1 second (FEV(1)), and forced vital capacity (FVC) (percent predicted) and reversible and total HRCT scores were most sensitive to change by effect size analysis.Improvements occurred with treatment in total and reversible HRCT scores, PFTs, and ACCS. Total and reversible HRCT scores and percent predicted SVC, FEV1, and FVC were the most sensitive to change. The greatest change was seen in the mucus plugging subcomponent HRCT score.
View details for PubMedID 11295720
- Standardized high-resolution CT of the lung using a spirometer-triggered electron beam CT scanner AMERICAN JOURNAL OF ROENTGENOLOGY 1999; 172 (6): 1636-1638
Inspiratory flow rate and dynamic lung function in cystic fibrosis and chronic obstructive lung diseases
1998; 114 (4): 988-992
The peak inspiratory flow rates (PIFRs) generated by cystic fibrosis (CF) and COPD patients through a range of clinically relevant resistances have not yet been reported (to our knowledge). The objectives of this study were to (1) explore a relevant range of resistive loads and address whether patients with stable CF and COPD can generate the PIFR sufficient to disperse dry-powder inhalants (DPI) and (2) determine whether the optimal inspiratory flow rate effective for delivery of aerosolized pharmacologic therapeutic agents can be attained with a comfort rating acceptable to subjects.Prospective, controlled, subject-blinded study.Pulmonary function laboratory at the VA Palo Alto Health Care System.Thirty-six subjects, including 12 healthy volunteers, 12 subjects with CF, and 12 subjects with COPD were studied.Studies of dynamic lung function and PIFR without and with varying resistances were obtained at a single laboratory visit.Dynamic lung function and PIFR varied inversely with the resistive load for all patient groups and did not correlate with the disease severity, as indicated by FEV1 of percent predicted. The average subjective comfort rating for any given resistive load was similar for subjects with CF and COPD.These results support the conclusion that subjects with stable CF and COPD of varying severity can comfortably generate the necessary flow rates to operate new and currently available DPIs over a wide range of inspiratory resistances.
View details for Web of Science ID 000076498000011
View details for PubMedID 9792566