Biomedical subjects
Publications and source records attributed to Jonathan G Goldin.
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BACKGROUND: It is currently unclear whether the small airways (diameter <2 microm) contribute significantly to late asthmatic reactions to inhaled allergen. OBJECTIVES: We sought to determine whether naturalistic exposure to cat allergen induced late responses in the small airways as measured by pulmonary function testing and high-resolution computed tomography (HRCT) of the chest performed at end-expiration. METHODS: In a group of 10 subjects with cat-induced asthma, physiologic studies (spirometry and lung volumes, including closing volume) and HRCT were performed before and 6 and 23 hours after a cat room challenge that caused a 20% or greater acute fall in FEV(1). RESULTS: There was no significant decline in FEV(1) at 6 or 23 hours after cat exposure. Forced expiratory flow at 25% to 75% of forced vital capacity was significantly decreased at 6 hours after the challenge and returned to normal by 23 hours. HRCT image analysis as well as closing volume demonstrated increased air trapping from baseline at both 6 and 23 hours after the challenge. In addition, image analysis demonstrated a significant increase in small airways hyperresponsiveness to methacholine at 23 hours after the challenge. No significant mean changes were noted in lung volumes at either 6 or 23 hours or in PC(20) FEV(1) at 23 hours postchallenge. CONCLUSION: These findings demonstrate that naturalistic exposure to cat allergen results in significant small airways obstruction and hyperresponsiveness persisting for at least 23 hours, at which time these changes cannot be detected by conventional physiologic measures. CLINICAL IMPLICATIONS: Physiologically silent distal lung inflammation persists after an antigenic challenge.
PURPOSE: To determine whether conventional nodule densitometry or analysis based on contrast enhancement maps of indeterminate lung nodules imaged with contrast-enhanced CT can distinguish benign from malignant lung nodules. MATERIALS AND METHOD: Thin section, contrast-enhanced CT (baseline, and post-contrast series acquired at 45, 90,180, and 360 s) was performed on 29 patients with indeterminate lung nodules (14 benign, 15 malignant). A thoracic radiologist identified the boundary of each nodule using semi-automated contouring to form a 3D region-of-interest (ROI) on each image series. The post-contrast series having the maximum mean enhancement was then volumetrically registered to the baseline series. The two series were subtracted volumetrically and the subtracted voxels were quantized into seven color-coded bins, forming a contrast enhancement map (CEM). Conventional nodule densitometry was performed to obtain the maximum difference in mean enhancement values for each nodule from a circular ROI. Three thoracic radiologists performed visual semi-quantitative analysis of each nodule, scoring each map for: (a) magnitude and (b) heterogeneity of enhancement throughout the entire volume of the nodule on a five-point scale. Receiver operator characteristic (ROC) analysis was conducted on these features to evaluate their diagnostic efficacy. Finally, 14 quantitative texture features were calculated for each map. A statistical analysis was performed to combine the 14 texture features to a single factor. ROC analysis of the derived aggregate factor was done as an indicator of malignancy. All features were analyzed for differences between benign and malignant nodules. RESULTS: Using 15 HU as a threshold, 93% (14/15) of malignant and 79% (11/14) of benign nodules demonstrated enhancement. The ROC curve when higher values of enhancement indicate malignancy was generated and area under the curve (AUC) was 0.76. The visually scored magnitude of enhancement was found to be less effective in distinguishing malignant from benign lesions, with an average AUC of 0.62. The visually scored pattern of enhancement was found to be more effective with an average AUC of 0.79. From the statistical analysis performed to combine the texture features to a single factor, the area under the ROC curve was 0.84. CONCLUSION: The present study suggests that visual semi-quantitative and quantitative characterization of contrast enhancement patterns may potentially enhance the discrimination between benign and malignant nodules. Further studies and correlation with pathologic material will be important to better understand the potential interplay between CT enhancement features, host stromal elements, and neovascularity that may contribute to these patterns.
Idiopathic pulmonary fibrosis (IPF), also referred to as cryptogenic fibrosing alveolitis (CFA), is the clinical-radiological-pathological syndrome associated with the most common form of fibrosing interstitial pneumonia, usual interstitial pneumonia (UIP). Unfortunately, the diagnosis of IPF carries with it a relatively poor prognosis. The characteristic features on high-resolution computed tomography (HRCT), consisting of reticular abnormality and honeycombing with basal and peripheral predominance, are virtually diagnostic within the correct clinical context. The extent of fibrosis on HRCT is an important prognostic indicator. When ground-glass attenuation is seen in patients with IPF, it commonly progresses to fibrosis and honeycombing. Complications of IPF include accelerated progression and deterioration, lung cancer, spontaneous air leak, and secondary infection. This article discusses the key imaging features as correlated with histopathology, differential diagnosis, complications, and follow-up evaluation of idiopathic pulmonary fibrosis.
OBJECTIVES: We examined the relationship between computed tomography (CT)-quantified calcium and histopathologic atherosclerotic plaque morphology and rupture. MATERIALS AND METHODS: Seven aortae were harvested from autopsy cases. All were scanned, ex vivo, on a 16-slice CT scanner and CT calcium scores (CTCS) were calculated using a Siemens Calcium Scoring package. The aorta segments were physically cross sectioned at 3-mm intervals corresponding to CT reconstructions. Two pathologists evaluated the cross sections for histology calcium score (HCS), plaque fibrous cap disruption, overlying thrombus, internal hemorrhage, size, lipid content, and inflammation. CT and histology data were subsequently paired using predetermined quadrant and slice conventions. RESULTS: Three hundred forty-nine aorta cross sections yielded 41 atherosclerotic plaques. Eleven plaques demonstrated plaque disruption and thrombosis and all contained calcium. CTCS was not significantly different between atherosclerotic plaques with and without evidence of disruption/thrombosis (F[1,30] = 1.525, P = 0.227). CT was 100% sensitive for nodular calcification, but only 56% (5 of 9 plaques) sensitive for non-nodular calcification. There was no significant relationship between CTCS and intraplaque hemorrhage, lipid content, inflammation, and plaque size (P = 0.179, P = 0.230, P = 0.314, and P = 0.054). There was significant correlation between CTCS and HCS (Pearson coefficient = 0.535; P < 0.01). CONCLUSIONS: Calcium quantity does not appear to predict plaque morphology or likelihood of rupture. CT has lower sensitivity for non-nodular compared with nodular calcification.
BACKGROUND: Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema. METHODS: One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 +/- 12.0% of predicted] and CT density mask (38.5 +/- 12.8% of voxels <- 910 Hounsfield units) [mean +/- SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period. RESULTS: No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild. CONCLUSIONS: No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time- and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation.
RATIONALE AND OBJECTIVES: To investigate the performance of observers with different levels of experience in distinguishing between benign and malignant solitary pulmonary nodules (SPN) on CT, and to determine the effects on interpretation of three different conditions: image data alone, the addition of clinical data, and the addition of output from a computer-aided diagnosis (CAD) system. MATERIALS AND METHODS: 28 thin-section CT datasets of SPNs with proven diagnoses (15 malignant and 13 benign) were used to measure observer performance. Readers were categorized according to their experience and read the cases in random order. For each case readers were asked to assign a level of confidence on a scale from 0.0-1.0 (0.0 benign, 1.0 malignant) for the diagnosis of the nodule. Each reader scored the cases based on review of image data alone (phase 1), then with limited clinical data (phase 2), and finally with CAD output (phase 3). To assess performance, multiple reader multiple case (MRMC) receiver operating characteristic (ROC) analysis was used. RESULTS: 2 thoracic radiologists, 1 thoracic radiology fellow, 2 nonthoracic radiologists, and 3 radiology residents read the cases. The average area under the ROC curve for all readers (A(z)) at each stage was 0.68, 0.75, and 0.81, for image data alone, with clinical data, and with CAD output respectively. The difference in performance between phases (2 and 3) and (1 and 3) was significantly different (P = 0.018 and P = 0.020). However, the difference between phases (1 and 2) was not significantly different (P = 0.155). CONCLUSION: Diagnostic performance increased significantly with the addition of CAD output. With further validation CAD output may play a significant role in SPN management.
RATIONALE AND OBJECTIVES: We sought to investigate the utility of a computer-aided diagnosis in the task of differentiating malignant nodules from benign nodules based on single thin-section computed tomography image data. MATERIALS AND METHODS: Eighty-one thin-section computed tomography data sets of solitary pulmonary nodules with proven diagnoses (48 malignant and 33 benign) were contoured manually on a single representative slice by a thoracic radiologist (>10 years of experience). Two separate contours were created for each nodule, one including only the solid portion of the nodule and one including any ground-glass components. For each contour 75 features were calculated that measured the attenuation, shape, and texture of the nodule. These features were than input into a feature selection step and four different classifiers to determine if the diagnosis could be predicted from the feature vector. Training and testing was conducted in a resubstitution and leave-one-out fashion and performance was evaluated using ROC techniques. RESULTS: In a leave-one-out testing methodology the classifiers resulted with areas under the ROC curve (A(Z)) that ranged from 0.68 to 0.92. When evaluating with resubstitution the A(Z) ranged from 0.93 to 1.00. CONCLUSION: Computer-aided diagnosis has the potential to assist radiologists in the task of differentiating solitary pulmonary nodules and in the management of these patients.
RATIONALE AND OBJECTIVES: The objective is to study the incremental effects of using a computer-aided lung nodule detection (CAD) system on the performance of a large pool of observers. MATERIALS AND METHODS: A set of eight thin-section computed tomographic data sets with limited longitudinal coverage, containing a total of 22 lung nodules, was analyzed by using the automated nodule detection system. When applied to all eight cases, the CAD system alone achieved a detection rate of 86.4%, with 2.64 false-positive results per case. This study included 202 observers at a national radiology meeting: 39 thoracic radiologists, 95 non-thoracic radiologists, and 68 non-radiologists. Each participant read from one to eight cases in random order, first without and then with CAD system output available. Observer performance in nodule detection was measured before and after CAD was made available. Differences in performance of groups of observers before and after CAD were tabulated by mean, median, and SD in detection rate and number of false-positive results and tested by using nonparametric methods. RESULTS: In an analysis involving only the first randomly selected case read by all 202 participants, there were statistically significant increases in nodule detection rates and numbers of false-positive results for all types of observers. There was a significant difference in detection rates between radiologists and non-radiologists before CAD, but after CAD, there was no significant difference in detection rates between these observer types. In a second analysis involving 13 participants who read all eight cases, mean detection rates were 64.0% before CAD and 81.9% after CAD. Mean numbers of false-positive results were 0.144 per case before CAD and 0.173 after CAD. CONCLUSION: In a large observer study, use of a CAD system for nodule detection resulted in an incremental increase in detection rate, but also led to an increase in number of false-positive results. Also, CAD appears to be an equalizer of detection rates between observers of different levels of experience.
RATIONALE AND OBJECTIVES: To investigate the utility of a computer-aided diagnosis (CAD) in the task of differentiating malignant nodules from benign nodules based on quantitative features extracted from volumetric thin section CT image data acquired before and after the injection of contrast media. MATERIALS AND METHODS: 35 volumetric CT datasets of solitary pulmonary nodules (SPN) with proven diagnoses (19 malignant/16 benign) were contoured by a thoracic radiologist. All studies had at least a baseline series obtained without contrast media and at least one series following an intravenous contrast injection at 45, 90, 180, and 360 seconds. Two separate contours were created for each nodule: one including only the solid portion and another including the ground-glass component, if any, of the nodule. For each contour 31 features were calculated that measured the attenuation, shape, and enhancement of the nodule due to the injection of contrast. These features were input into a feature selection step and three different classifiers to determine if the diagnosis could be predicted from the resulting feature vector. In addition, observer input was introduced to two of the classifiers as an a priori probability of malignancy and the resulting performance was compared. Training and testing was conducted in a resubstitution and leave-one-out fashion and performance was evaluated using ROC analysis. RESULTS: In a leave-one-out testing methodology, the classifiers achieved areas under the ROC curves AZ that ranged from 0.69 to 0.92. A classifier based on logistic regression performed the best with an AZ of 0.92 while a classifier based on quadratic discriminant analysis performed the poorest (AZ, 0.69). The AZ increased when using a priori observer input in most cases reaching a maximum of 0.95. CONCLUSION: Based on this initial work with a limited number of nodules in our dataset, it appears that CAD using volumetric and contrast-enhanced data has the potential to assist radiologists in the task of differentiating solitary pulmonary nodules and in the management of these patients. Further studies with an increased number of patients are required to validate these results.
Quantitative image analysis (QIA) goes beyond subjective visual assessment to provide computer measurements of the image content, typically following image segmentation to identify anatomical regions of interest (ROIs). Commercially available picture archiving and communication systems focus on storage of image data. They are not well suited to efficient storage and mining of new types of quantitative data. In this paper, we present a system that integrates image segmentation, quantitation, and characterization with database and data mining facilities. The paper includes generic process and data models for QIA in medicine and describes their practical use. The data model is based upon the Digital Imaging and Communications in Medicine (DICOM) data hierarchy, which is augmented with tables to store segmentation results (ROIs) and quantitative data from multiple experiments. Data mining for statistical analysis of the quantitative data is described along with example queries. The database is implemented in PostgreSQL on a UNIX server. Database requirements and capabilities are illustrated through two quantitative imaging experiments related to lung cancer screening and assessment of emphysema lung disease. The system can manage the large amounts of quantitative data necessary for research, development, and deployment of computer-aided diagnosis tools.
PURPOSE: To quantify scanner and participant variability in attenuation values for computed tomographic (CT) images assessed for coronary calcium and define a method for standardizing attenuation values and calibrating calcium measurements. MATERIALS AND METHODS: Institutional review board approval and participant informed consent were obtained at all study sites. An image attenuation adjustment method involving the use of available calibration phantom data to define standard attenuation values was developed. The method was applied to images from two population-based multicenter studies: the Coronary Artery Risk Development in Young Adults study (3041 participants) and the Multi-Ethnic Study of Atherosclerosis (6814 participants). To quantify the variability in attenuation, analysis of variance techniques were used to compare the CT numbers of standardized torso phantom regions across study sites, and multivariate linear regression models of participant-specific calibration phantom attenuation values that included participant age, race, sex, body mass index (BMI), smoking status, and site as covariates were developed. To assess the effect of the calibration method on calcium measurements, Pearson correlation coefficients between unadjusted and attenuation-adjusted calcium measurements were computed. Multivariate models were used to examine the effect of sex, race, BMI, smoking status, unadjusted score, and site on Agatston score adjustments. RESULTS: Mean attenuation values (CT numbers) of a standard calibration phantom scanned beneath participants varied significantly according to scanner and participant BMI (P < .001 for both). Values were lowest for Siemens multi-detector row CT scanners (110.0 HU), followed by GE-Imatron electron-beam (116.0 HU) and GE LightSpeed multi-detector row scanners (121.5 HU). Values were also lower for morbidly obese (BMI, > or =40.0 kg/m(2)) participants (108.9 HU), followed by obese (BMI, 30.0-39.9 kg/m(2)) (114.8 HU), overweight (BMI, 25.0-29.9 kg/m(2)) (118.5 HU), and normal-weight or underweight (BMI, <25.0 kg/m(2)) (120.1 HU) participants. Agatston score calibration adjustments ranged from -650 to 1071 (mean, -8 +/- 50 [standard deviation]) and increased with Agatston score (P < .001). The direction and magnitude of adjustment varied significantly according to scanner and BMI (P < .001 for both) and were consistent with phantom attenuation results in that calibration resulted in score decreases for images with higher phantom attenuation values. CONCLUSION: Image attenuation values vary by scanner and participant body size, producing calcium score differences that are not due to true calcium burden disparities. Use of calibration phantoms to adjust attenuation values and calibrate calcium measurements in research studies and clinical practice may improve the comparability of such measurements between persons scanned with different scanners and within persons over time.
OBJECTIVE: Interstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc). Although early identification and treatment of alveolitis may prevent deterioration of lung function, the best approach for diagnosing active alveolitis remains controversial. This study was undertaken to investigate the utility of high-resolution computed tomography (HRCT) of the chest, in comparison with bronchoalveolar lavage (BAL), in the diagnosis of alveolitis in these patients. METHODS: Eighteen patients with SSc and dyspnea were evaluated for ILD by pulmonary function testing and bronchoalveolar lavage (BAL), and 15 of these patients underwent chest HRCT. BAL was performed in either the middle lobe or the lingula, and also in a lower lung segment. Differential cell counts were determined by clinical cytopathology, with retrospective recounting in a blinded manner by a single technician. Active alveolitis was defined as the presence of > or =3.0% polymorphonuclear cells and/or > or =2% eosinophils in BAL fluid. BAL fluids were cultured for bacteria, mycobacteria, and fungi. HRCT scans were evaluated in a blinded manner for ground-glass opacification and fibrosis in the lavaged lobes. RESULTS: Nine of the 18 patients had active alveolitis recorded in both lavaged segments, while in 4 patients it was recorded in only 1 segment (lower lobe in 3). Following repeat differential cell counting, 3 patients were reclassified as having active alveolitis and 1 as having no alveolitis. Culture of BAL fluid identified clinically unsuspected infection in 3 patients. For the right middle lung lobe or lingula there was excellent agreement between ground-glass opacification and the finding of alveolitis on BAL from segments in the same lung regions, but this was not observed for the lower lobes. The correlation between fibrosis on HRCT and the presence of alveolitis on BAL was significant for the lower lobes but not the middle lung fields. CONCLUSION: BAL of the middle lobe or lingula may underestimate the presence of active alveolitis. Similarly, while ground-glass opacification on HRCT accurately predicted alveolitis in the middle lung fields, HRCT did not detect all sites of inflammation and did not identify infectious etiologies. These data suggest that, in addition to HRCT, BAL with lavage, differential cell counting, and culture from at least 2 segments of lung be performed for diagnosing SSc alveolitis.
RATIONALE AND OBJECTIVES: To study the agreement in treatment response classifications between unidimensional (1D), bidimensional (2D), and volumetric (3D) methods of measuring metastatic lung nodules on chest computed tomography (CT). MATERIALS AND METHODS: Chest CT scans of 15 patients undergoing treatment for metastatic colorectal, renal cell, or breast carcinoma to the lungs were analyzed. CT images were acquired with 3 mm collimation and contiguous reconstruction. Two or three lung lesions were selected for each patient. Lesions were analyzed at baseline and two follow-up intervals of 1-4 months. 1D and 2D measurements were made with electronic calipers, while nodule volume was measured using a semiautomated segmentation system. Following the World Health Organization and RECIST (Response Evaluation Criteria in Solid Tumors) criteria, patients were categorized into four treatment response classifications. Volumetric criteria were used to classify response based on 3D measurements. RESULTS: Thirty-two lesions from 15 patients were analyzed. Because each patient had a baseline and two follow-up scans, this yielded 30 response classifications for each measurement technique. The 1D, 2D, and 3D measurements were concordant in 21 of 30 classifications. The 1D and 3D measurements were concordant in 29 of 30 classifications, while the 2D and 3D measurements were concordant in 23 of 30 classifications. Level of agreement among the three methods was measured using a kappa statistic (K). For 1D compared with 3D, K = 0.739 +/- 0.345 (visits 1, 2) and 0.273 +/- 0.323 (visits 2, 3). For 2D compared with 3D, K = 0.655 +/- 0.325 (visits 1, 2) and 0.200 +/- 0.208 (visits 2, 3). Agreement among the methods for round and ovoid nodules was also fair to poor. CONCLUSION: The three methods of tumor measurement show fair to poor agreement in treatment response classification. These findings have negative implications for the accuracy in which patients are classified under the World Health Organization or RECIST criteria and managed under cancer treatment protocols.
Chronic lung disease is a leading cause of morbidity and mortality in the United States. Quantitative techniques for assessing emphysema and related airway disease have been slow to gain acceptance among radiologists, who have traditionally used description of structural changes to evaluate these diseases. This review provides an overview of these quantitative techniques.
PURPOSE: To assess the technical feasibility and safety of weekly outpatient percutaneous computed tomographic (CT)-guided intratumoral injections of interleukin-2 (IL-2) plasmid DNA in a wide variety of superficial and deep tumor sites. MATERIALS AND METHODS: Twenty-nine patients with metastatic renal cell carcinoma and a total of 30 lesions measuring 1.0 cm(2) or greater in accessible thoracic (n = 15) or abdominal (n = 15) locations underwent up to three cycles of six weekly intratumoral IL-2 plasmid DNA injections. CT was used to guide needle placement and injection. After injection cycle 1, patients whose tumors demonstrated stable (< or =25% increase and < or =50% decrease in product of lesion diameters) or decreased size (>50% decrease in product of lesion diameters) advanced to injection cycle 2. Patients whose lesions decreased in size by more than 50% over the course of injection cycle 2 were eligible to begin injection cycle 3. An acceptable safety and technical feasibility profile for this technique was deemed to be (a) a safety and feasibility profile similar to that of single-needle biopsy and (b) an absence of serious adverse events (as defined in Title 21 of the Code of Federal Regulations) and/or unacceptable toxicities (as graded according to the National Cancer Institute Common Toxicity Criteria). RESULTS: A total of 284 intratumoral injections were performed, with a mean of 9.8 injections (range, 6-18 injections) received by each patient. Technical success (needle placement and injection of gene therapy agent) was achieved in all cases. Complications were experienced after 42 (14.8%) of the 284 injections. The most common complication was pneumothorax (at 32 [28.6%] of 112 intrathoracic injections), for which only one patient required catheter drainage. Complications occurred randomly throughout injection cycles and did not appear to increase as patients received more injections (P =.532). No patient experienced serious adverse events or unacceptable toxicities. CONCLUSION: Percutaneous CT-guided intratumoral immunotherapy injections are technically feasible and can be safely performed.
In the current study, the effects of reconstruction algorithms on quantitative measures derived from computed tomographic (CT) lung images were assessed in patients with emphysema. CT image data sets were reconstructed with a standard algorithm and alternative algorithm(s) for 42 subjects. Algorithms were grouped as overenhancing, sharp, standard, or smooth. Density mask and volume measurements from the alternative algorithm data sets were compared with standard algorithm data sets. The overenhancing category yielded an average shift of 9.4% (ie, a shift in average score from 35.5% to 44.9%); the sharp category, a shift of 2.4%; and the smooth category, a shift of -1.0%. Differences in total lung volume measurements were less than 1%. In conclusion, the CT reconstruction algorithm may strongly affect density mask results, especially for certain reconstruction algorithms.
Our purpose was to determine if a home-based faculty radiologist equipped with a high-resolution workstation could add new information to residents' readings on overnight computed chest images that was equivalent to the new information generated by faculty reviewers inside the hospital. Teleconferencing software was installed on home workstations for online supervision of residents by faculty on chest images from a cardiothoracic intensive care unit. Critical observations that could affect patient care were recorded by first-year radiology residents before and after teleconferencing with the home-based radiologist. The amount of information added was compared with that which was added on the same 50 images through direct consultations with faculty inside the medical center. The amount of critical information that was added by teleconferencing with a chest radiologist at home was equivalent statistically to the information added through direct supervision of residents by faculty inside the hospital. Teleconferencing resulted in 149 changes in critical image findings as reported initially by the residents, out of 800 possible findings on 50 chest images, as opposed to 142 changes in residents' readings by faculty inside the medical center. Faculty subspecialists can supervise radiology residents effectively from their homes after hours, using high-resolution workstations and special teleconferencing software.