David Lewis Levin

All Publications

• Quantitative Analysis of Lung Shape in Idiopathic Pulmonary Fibrosis: Insights Into Disease- and Age-Associated Patterns. Academic radiology John, J., Clark, A. R., Kumar, H., Burrowes, K. S., Vandal, A. C., Wilsher, M. L., Milne, D. G., Bartholmai, B. J., Levin, D. L., Tawhai, M. H. 2024

  Abstract

  Fibrotic scarring in idiopathic pulmonary fibrosis (IPF) typically develops first in the posterior-basal lung tissue before advancing to involve more of the lung. The complexity of lung shape in the costo-diaphragmatic region has been proposed as a potential factor in this regional development. Intrinsic and disease-related shape could therefore be important for understanding IPF risk and its staging. We hypothesized that lung and lobe shape in IPF would have important differences from controls.A principal component (PC) analysis was used to derive a statistical shape model (SSM) of the lung for a control cohort aged > 50 years (N = 39), using segmented lung and fissure surface data from CT imaging. Individual patient shape models derived for baseline (N = 18) and follow-up (N = 16) CT scans in patients with IPF were projected to the SSM to describe shape as the sum of the SSM average and weighted PC modes. Associations between the first four PC shape modes, lung function, percentage of fibrosis (fibrosis%) and pulmonary vessel-related structures (PVRS%), and other tissue metrics were assessed and compared between the two cohorts.Shape was different between IPF and controls (P < 0.05 for all shape modes), with IPF shape forming a distinct shape cluster. Shape had a negative relationship with age in controls (P = 0.013), but a positive relationship with age in IPF (P = 0.026). Some features of shape changed on follow-up. Shape in IPF was associated with fibrosis% (P < 0.05) and PVRS% (P < 0.05).Quantitative comparison of lung and lobe shape in IPF with controls of a similar age reveals shape differences that are strongly associated with age and percent fibrosis. The clustering of IPF cohort shape suggests that it could be an important feature to describe disease.

  View details for DOI 10.1016/j.acra.2024.04.026

  View details for PubMedID 38679527

• Evaluating Tissue Heterogeneity in the Radiologically Normal-Appearing Tissue in IPF Compared to Healthy Controls. Academic radiology John, J., Clark, A. R., Kumar, H., Burrowes, K. S., Vandal, A. C., Wilsher, M. L., Milne, D. G., Bartholmai, B. J., Levin, D. L., Karwoski, R., Tawhai, M. H. 2024; 31 (4): 1676-1685

  Abstract

  Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease characterised by heterogeneously distributed fibrotic lesions. The inter- and intra-patient heterogeneity of the disease has meant that useful biomarkers of severity and progression have been elusive. Previous quantitative computed tomography (CT) based studies have focussed on characterising the pathological tissue. However, we hypothesised that the remaining lung tissue, which appears radiologically normal, may show important differences from controls in tissue characteristics.Quantitative metrics were derived from CT scans in IPF patients (N = 20) and healthy controls with a similar age (N = 59). An automated quantitative software (CALIPER, Computer-Aided Lung Informatics for Pathology Evaluation and Rating) was used to classify tissue as normal-appearing, fibrosis, or low attenuation area. Densitometry metrics were calculated for all lung tissue and for only the normal-appearing tissue. Heterogeneity of lung tissue density was quantified as coefficient of variation and by quadtree. Associations between measured lung function and quantitative metrics were assessed and compared between the two cohorts.All metrics were significantly different between controls and IPF (p < 0.05), including when only the normal tissue was evaluated (p < 0.04). Density in the normal tissue was 14% higher in the IPF participants than controls (p < 0.001). The normal-appearing tissue in IPF had heterogeneity metrics that exhibited significant positive relationships with the percent predicted diffusion capacity for carbon monoxide.We provide quantitative assessment of IPF lung tissue characteristics compared to a healthy control group of similar age. Tissue that appears visually normal in IPF exhibits subtle but quantifiable differences that are associated with lung function and gas exchange.

  View details for DOI 10.1016/j.acra.2023.08.046

  View details for PubMedID 37758587

• Accuracy of Nodule Volume and Airway Wall Thickness Measurement Using Low-Dose Chest CT on a Photon-Counting Detector CT Scanner. Investigative radiology Dunning, C. A., Marsh, J. F., Winfree, T., Rajendran, K., Leng, S., Levin, D. L., Johnson, T. F., Fletcher, J. G., McCollough, C. H., Yu, L. 2023; 58 (4): 283-292

  Abstract

  A comparison of high-resolution photon-counting detector computed tomography (PCD-CT) versus energy-integrating detector (EID) CT via a phantom study using low-dose chest CT to evaluate nodule volume and airway wall thickness quantification.Twelve solid and ground-glass lung nodule phantoms with 3 diameters (5 mm, 8 mm, and 10 mm) and 2 shapes (spherical and star-shaped) and 12 airway tube phantoms (wall thicknesses, 0.27-1.54 mm) were placed in an anthropomorphic chest phantom. The phantom was scanned with EID-CT and PCD-CT at 5 dose levels (CTDI vol = 0.1-0.8 mGy at Sn-100 kV, 7.35 mGy at 120 kV). All images were iteratively reconstructed using matched kernels for EID-CT and medium-sharp kernel (MK) PCD-CT and an ultra-sharp kernel (USK) PCD-CT kernel, and image noise at each dose level was quantified. Nodule volumes were measured using semiautomated segmentation software, and the accuracy was expressed as the percentage error between segmented and reference volumes. Airway wall thicknesses were measured, and the root-mean-square error across all tubes was evaluated.MK PCD-CT images had the lowest noise. At 0.1 mGy, the mean volume accuracy for the solid and ground-glass nodules was improved in USK PCD-CT (3.1% and 3.3% error) compared with MK PCD-CT (9.9% and 10.2% error) and EID-CT images (11.4% and 9.2% error), respectively. At 0.2 mGy and 0.8 mGy, the wall thickness root-mean-square error values were 0.42 mm and 0.41 mm for EID-CT, 0.54 mm and 0.49 mm for MK PCD-CT, and 0.23 mm and 0.16 mm for USK PCD-CT.USK PCD-CT provided more accurate lung nodule volume and airway wall thickness quantification at lower radiation dose compared with MK PCD-CT and EID-CT.

  View details for DOI 10.1097/RLI.0000000000000933

  View details for PubMedID 36525385

  View details for PubMedCentralID PMC10023282

• Pulmonary vessel volume in idiopathic pulmonary fibrosis compared with healthy controls aged > 50 years. Scientific reports John, J., Clark, A. R., Kumar, H., Vandal, A. C., Burrowes, K. S., Wilsher, M. L., Milne, D. G., Bartholmai, B., Levin, D. L., Karwoski, R., Tawhai, M. H. 2023; 13 (1): 4422

  Abstract

  Idiopathic pulmonary fibrosis (IPF) is characterised by progressive fibrosing interstitial pneumonia with an associated irreversible decline in lung function and quality of life. IPF prevalence increases with age, appearing most frequently in patients aged > 50 years. Pulmonary vessel-like volume (PVV) has been found to be an independent predictor of mortality in IPF and other interstitial lung diseases, however its estimation can be impacted by artefacts associated with image segmentation methods and can be confounded by adjacent fibrosis. This study compares PVV in IPF patients (N = 21) with PVV from a healthy cohort aged > 50 years (N = 59). The analysis includes a connected graph-based approach that aims to minimise artefacts contributing to calculation of PVV. We show that despite a relatively low extent of fibrosis in the IPF cohort (20% of the lung volume), PVV is 2-3 times higher than in controls. This suggests that a standardised method to calculate PVV that accounts for tree connectivity could provide a promising tool to provide early diagnostic or prognostic information in IPF patients and other interstitial lung disease.

  View details for DOI 10.1038/s41598-023-31470-6

  View details for PubMedID 36932117

  View details for PubMedCentralID PMC10023743

• Quantitative Imaging Metrics for the Assessment of Pulmonary Pathophysiology: An Official American Thoracic Society and Fleischner Society Joint Workshop Report. Annals of the American Thoracic Society Hsia, C. C., Bates, J. H., Driehuys, B., Fain, S. B., Goldin, J. G., Hoffman, E. A., Hogg, J. C., Levin, D. L., Lynch, D. A., Ochs, M., Parraga, G., Prisk, G. K., Smith, B. M., Tawhai, M., Vidal Melo, M. F., Woods, J. C., Hopkins, S. R. 2023; 20 (2): 161-195

  Abstract

  Multiple thoracic imaging modalities have been developed to link structure to function in the diagnosis and monitoring of lung disease. Volumetric computed tomography (CT) renders three-dimensional maps of lung structures and may be combined with positron emission tomography (PET) to obtain dynamic physiological data. Magnetic resonance imaging (MRI) using ultrashort-echo time (UTE) sequences has improved signal detection from lung parenchyma; contrast agents are used to deduce airway function, ventilation-perfusion-diffusion, and mechanics. Proton MRI can measure regional ventilation-perfusion ratio. Quantitative imaging (QI)-derived endpoints have been developed to identify structure-function phenotypes, including air-blood-tissue volume partition, bronchovascular remodeling, emphysema, fibrosis, and textural patterns indicating architectural alteration. Coregistered landmarks on paired images obtained at different lung volumes are used to infer airway caliber, air trapping, gas and blood transport, compliance, and deformation. This document summarizes fundamental "good practice" stereological principles in QI study design and analysis; evaluates technical capabilities and limitations of common imaging modalities; and assesses major QI endpoints regarding underlying assumptions and limitations, ability to detect and stratify heterogeneous, overlapping pathophysiology, and monitor disease progression and therapeutic response, correlated with and complementary to, functional indices. The goal is to promote unbiased quantification and interpretation of in vivo imaging data, compare metrics obtained using different QI modalities to ensure accurate and reproducible metric derivation, and avoid misrepresentation of inferred physiological processes. The role of imaging-based computational modeling in advancing these goals is emphasized. Fundamental principles outlined herein are critical for all forms of QI irrespective of acquisition modality or disease entity.

  View details for DOI 10.1513/AnnalsATS.202211-915ST

  View details for PubMedID 36723475

  View details for PubMedCentralID PMC9989862

• Lung Cancer Screening Using Clinical Photon-Counting Detector Computed Tomography and Energy-Integrating-Detector Computed Tomography: A Prospective Patient Study. Journal of computer assisted tomography Inoue, A., Johnson, T. F., Walkoff, L. A., Levin, D. L., Hartman, T. E., Burke, K. A., Rajendran, K., Yu, L., McCollough, C. H., Fletcher, J. G. 2022; 47 (2): 229-235

  Abstract

  To evaluate the diagnostic quality of photon-counting detector (PCD) computed tomography (CT) in patients undergoing lung cancer screening compared with conventional energy-integrating detector (EID) CT in a prospective multireader study.Patients undergoing lung cancer screening with conventional EID-CT were prospectively enrolled and scanned on a PCD-CT system using similar automatic exposure control settings and reconstruction kernels. Three thoracic radiologists blinded to CT system compared PCD-CT and EID-CT images and scored examinations using a 5-point Likert comparison score (-2 [left image is worse] to +2 [left image is better]) for artifacts, sharpness, image noise, diagnostic image quality, emphysema visualization, and lung nodule evaluation focusing on the border. Post hoc correction of Likert scores was performed such that they reflected PCD-CT performance in comparison to EID-CT. A nonreader radiologist measured objective image noise.Thirty-three patients (mean, 66.9 ± 5.6 years; 11 female; body mass index; 30.1 ± 5.1 kg/m 2 ) were enrolled. Mean volume CT dose index for PCD-CT was lower (0.61 ± 0.21 vs 0.73 ± 0.22; P < 0.001). Pooled reader results showed significant differences between imaging modalities for all comparative rankings ( P < 0.001), with PCD-CT favored for sharpness, image noise, image quality, and emphysema visualization and lung nodule border, but not artifacts. Photon-counting detector CT had significantly lower image noise (74.4 ± 10.5 HU vs 80.1 ± 8.6 HU; P = 0.048).Photon-counting detector CT with similar acquisition and reconstruction settings demonstrated improved image quality and less noise despite lower radiation dose, with improved ability to depict pulmonary emphysema and lung nodule borders compared with EID-CT at low-dose lung cancer CT screening.

  View details for DOI 10.1097/RCT.0000000000001419

  View details for PubMedID 36573321

• Emphysematous Lung Lesions Caused by Perivascular and Alveolar-Septal Deposition of Amyloid Light-Chain Amyloidosis. Chest Martin, M. J., Pennington, K. M., Skalski, J. H., Yi, E. S., Levin, D. L., Durani, U., Ryu, J. H. 2021; 160 (2): e169-e171

  Abstract

  Pulmonary amyloidosis, whether isolated or seen as part of systemic amyloidosis, has a variety of radiographic manifestations. Known parenchymal lung findings include reticulonodular opacities, diffuse interstitial infiltrates, or cystic lesions. Here, we present a case of systemic amyloid light-chain (AL) amyloidosis presenting with severe exertional dyspnea and emphysematous lung lesions on chest CT, a finding described only once before. Although factors that influence the pattern of pulmonary amyloid deposition remain unclear, CT image findings typically reflect the histopathologic patterns of deposition. In this case, we hypothesize that the emphysematous changes in the lower lung zones are likely a manifestation of severe alveolar-septal involvement. This case suggests that radiographic findings of pulmonary amyloidosis are not limited to the more common findings of reticular opacities or interstitial infiltrates. Emphysematous changes are possible, and clinicians should maintain a broad differential when seen in the setting of dyspnea.

  View details for DOI 10.1016/j.chest.2021.03.038

  View details for PubMedID 34366038

• Observer Performance for Detection of Pulmonary Nodules at Chest CT over a Large Range of Radiation Dose Levels. Radiology Fletcher, J. G., Levin, D. L., Sykes, A. G., Lindell, R. M., White, D. B., Kuzo, R. S., Suresh, V., Yu, L., Leng, S., Holmes, D. R., Inoue, A., Johnson, M. P., Carter, R. E., McCollough, C. H. 2020; 297 (3): 699-707

  Abstract

  Background There is a wide variation in radiation dose levels that can be used with chest CT in order to detect indeterminate pulmonary nodules. Purpose To compare the performance of lower-radiation-dose chest CT with that of routine dose in the detection of indeterminate pulmonary nodules 5 mm or greater. Materials and Methods In this retrospective study, CT projection data from 83 routine-dose chest CT examinations performed in 83 patients (120 kV, 70 quality reference mAs [QRM]) were collected between November 2013 and April 2014. Reference indeterminate pulmonary nodules were identified by two nonreader thoracic radiologists. By using validated noise insertion, five lower-dose data sets were reconstructed with filtered back projection (FBP) or iterative reconstruction (IR; 30 QRM with FBP, 10 QRM with IR, 5 QRM with FBP, 5 QRM with IR, and 2.5 QRM with IR). Three thoracic radiologists circled pulmonary nodules, rating confidence that the nodule was a 5-mm-or-greater indeterminate pulmonary nodule, and graded image quality. Analysis was performed on a per-nodule basis by using jackknife alternative free-response receiver operating characteristic figure of merit (FOM) and noninferiority limit of -0.10. Results There were 66 indeterminate pulmonary nodules (mean size, 8.6 mm ± 3.4 [standard deviation]; 21 part-solid nodules) in 42 patients (mean age, 51 years ± 17; 21 men and 21 women). Compared with the FOM for routine-dose CT (size-specific dose estimate, 6.5 mGy ± 1.8; FOM, 0.86 [95% confidence interval: 0.80, 0.91]), FOM was noninferior for all lower-dose configurations except for 2.5 QRM with IR. The sensitivity for subsolid nodules at 70 QRM was 60% (range, 48%-72%) and was significantly worse at a dose of 5 QRM and lower, whether or not IR was used (P < .05). Diagnostic image quality decreased with decreasing dose (P < .001) and was better with IR at 5 QRM (P < .05). Conclusion CT images reconstructed at dose levels down to 10 quality reference mAs (size-specific dose estimate, 0.9 mGy) had noninferior performance compared with routine dose in depicting pulmonary nodules. Iterative reconstruction improved subjective image quality but not performance at low dose levels. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by White and Kazerooni in this issue.

  View details for DOI 10.1148/radiol.2020200969

  View details for PubMedID 32990514

  View details for PubMedCentralID PMC7706885

• Deep-learning-based model observer for a lung nodule detection task in computed tomography. Journal of medical imaging (Bellingham, Wash.) Gong, H., Hu, Q., Walther, A., Koo, C. W., Takahashi, E. A., Levin, D. L., Johnson, T. F., Hora, M. J., Leng, S., Fletcher, J. G., McCollough, C. H., Yu, L. 2020; 7 (4): 042807

  Abstract

  Purpose: Task-based image quality assessment using model observers (MOs) is an effective approach to radiation dose and scanning protocol optimization in computed tomography (CT) imaging, once the correlation between MOs and radiologists can be established in well-defined clinically relevant tasks. Conventional MO studies were typically simplified to detection, classification, or localization tasks using tissue-mimicking phantoms, as traditional MOs cannot be readily used in complex anatomical background. However, anatomical variability can affect human diagnostic performance. Approach: To address this challenge, we developed a deep-learning-based MO (DL-MO) for localization tasks and validated in a lung nodule detection task, using previously validated projection-based lesion-/noise-insertion techniques. The DL-MO performance was compared with 4 radiologist readers over 12 experimental conditions, involving varying radiation dose levels, nodule sizes, nodule types, and reconstruction types. Each condition consisted of 100 trials (i.e., 30 images per trial) generated from a patient cohort of 50 cases. DL-MO was trained using small image volume-of-interests extracted across the entire volume of training cases. For each testing trial, the nodule searching of DL-MO was confined to a 3-mm thick volume to improve computational efficiency, and radiologist readers were tasked to review the entire volume. Results: A strong correlation between DL-MO and human readers was observed (Pearson's correlation coefficient: 0.980 with a 95% confidence interval of [0.924, 0.994]). The averaged performance bias between DL-MO and human readers was 0.57%. Conclusion: The experimental results indicated the potential of using the proposed DL-MO for diagnostic image quality assessment in realistic chest CT tasks.

  View details for DOI 10.1117/1.JMI.7.4.042807

  View details for PubMedID 32647740

  View details for PubMedCentralID PMC7324744

• EXPRESS: Statement on imaging and pulmonary hypertension from the Pulmonary Vascular Research Institute (PVRI). Pulmonary circulation Kiely, D. G., Levin, D., Hassoun, P., Ivy, D. D., Jone, P. N., Bwika, J., Kawut, S. M., Lordan, J., Lungu, A., Mazurek, J., Moledina, S., Olschewski, H., Peacock, A., Puri, G. D., Rahaghi, F., Schafer, M., Schiebler, M., Screaton, N., Tawhai, M., Van Beek, E. J., Vonk-Noordegraaf, A., Vanderpool, R. R., Wort, J., Zhao, L., Wild, J., Vogel-Claussen, J., Swift, A. J. 2019; 9 (3): 2045894019841990

  Abstract

  Pulmonary hypertension (PH) is highly heterogeneous and despite treatment advances it remains a life-shortening condition. There have been significant advances in imaging technologies, but despite evidence of their potential clinical utility, practice remains variable, dependent in part on imaging availability and expertise. This statement summarizes current and emerging imaging modalities and their potential role in the diagnosis and assessment of suspected PH. It also includes a review of commonly encountered clinical and radiological scenarios, and imaging and modeling-based biomarkers. An expert panel was formed including clinicians, radiologists, imaging scientists, and computational modelers. Section editors generated a series of summary statements based on a review of the literature and professional experience and, following consensus review, a diagnostic algorithm and 55 statements were agreed. The diagnostic algorithm and summary statements emphasize the key role and added value of imaging in the diagnosis and assessment of PH and highlight areas requiring further research.

  View details for DOI 10.1177/2045894019841990

  View details for PubMedID 30880632

  View details for PubMedCentralID PMC6732869

• Noncontrast Chest Computed Tomographic Imaging of Obesity and the Metabolic Syndrome: Part I Cardiovascular Findings. Journal of thoracic imaging Schlett, C. L., Nattenmüller, J., Tsuchiya, N., Vogel-Claussen, J., Kauczor, H. U., Levin, D., Hatabu, H., Estépar, J. R., Wu, M. T., van Beek, E. J., Schiebler, M. L. 2019; 34 (2): 116-125

  Abstract

  There are physiological consequences of overeating that can lead to increased morbidity and mortality. The purpose of this review article is to acquaint the reader with the current state of the art in the non-cardiac-gated, noncontrast chest computed tomographic (NCCT) imaging biomarkers of the metabolic syndrome and their prognostic significance found in the lower neck and chest. NCCT imaging biomarkers associated with metabolic syndrome in the chest include premature coronary artery calcification, acceleration of large vessel arterial and valvular calcifications associated with atherosclerosis, and pulmonary arterial enlargement from pulmonary hypertension associated with sleep apnea. These easily identified imaging biomarkers have prognostic implications for major adverse cardiac events (MACE). These NCCT chest-imaging biomarkers are likely targets for artificial intelligence algorithms to harvest for longitudinal assessment of their individual and multifactorial contributions to chronic disease, MACE, and mortality. Early recognition and treatment of these common disorders may help improve patient outcomes and quality of life while decreasing medical costs.

  View details for DOI 10.1097/RTI.0000000000000391

  View details for PubMedID 30802234

• Combined pulmonary fibrosis and emphysema as a clinicoradiologic entity: Characterization of presenting lung fibrosis and implications for survival. Respiratory medicine Alsumrain, M., De Giacomi, F., Nasim, F., Koo, C. W., Bartholmai, B. J., Levin, D. L., Moua, T. 2019; 146: 106-112

  Abstract

  The prevalence of classifiable and unclassifiable causes of lung fibrosis and its implications for survival are mostly unknown in combined pulmonary fibrosis and emphysema (CPFE).Patients with >10% involvement of both emphysema and lung fibrosis seen over 11 years at our institution were reviewed independently by expert radiologists for fibrotic and emphysematous findings and overall fibrotic CT pattern. Underlying interstitial lung disease (ILD) diagnoses and baseline demographic and clinical characteristics were collated and assessed for predictors of comparative survival.In this retrospective cohort, 179 CPFE patients were identified and categorized as 58 usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) (32%), 42 secondary ILD (23%), and 79 unclassifiable ILD (44%). The most prevalent (47%) radiologic pattern was 'unclassifiable', followed by 'consistent' and 'possible' UIP pattern in 38%. Adjusted predictors of mortality for the cohort as a whole included age (HR 1.03[1.01-1.06], P = 0.002), percent predicted diffusing capacity for carbon monoxide (unit HR 0.97 [0.96-0.99], P = 0.001), honeycombing (HR 1.58 [1.02-2.43], P = 0.04), and right ventricular dysfunction (HR 2.28 [1.39-3.97], P = 0.002). Survival was similar between CPFE with secondary ILD and CPFE with UIP/IPF, while CPFE with unclassifiable ILD had better comparative survival (Log rank = 0.026).Our findings suggest only about a third of CPFE patients represent suspected UIP/IPF; the majority were clinically and radiologically unclassifiable ILD whose survival was comparatively better. Identifiable or secondary causes of lung fibrosis in CPFE occurred in about a fifth of presenting patients.

  View details for DOI 10.1016/j.rmed.2018.12.003

  View details for PubMedID 30665507

• Deep learning and the evaluation of pulmonary fibrosis. The Lancet. Respiratory medicine Levin, D. L. 2018; 6 (11): 803-805

  View details for DOI 10.1016/S2213-2600(18)30371-0

  View details for PubMedID 30232047

  View details for PubMedCentralID PMC6293056

• Prospective Pilot Evaluation of Radiologists and Computer-aided Pulmonary Nodule Detection on Ultra-low-Dose CT With Tin Filtration. Journal of thoracic imaging Takahashi, E. A., Koo, C. W., White, D. B., Lindell, R. M., Sykes, A. G., Levin, D. L., Kuzo, R. S., Wolf, M., Bogoni, L., Carter, R. E., McCollough, C. H., Fletcher, J. G. 2018; 33 (6): 396-401

  Abstract

  The aim of this study was to evaluate the ability of computer-aided detection (CAD) and human readers to detect pulmonary nodules ≥5 mm using 100 kV ultra-low-dose computed tomography (ULDCT) utilizing a tin filter.After informed consent, 55 patients prospectively underwent standard-dose chest CT (SDCT) using 120 kV followed by ULDCT using 100 kV/tin. Reference nodules ≥5 mm were identified by a thoracic radiologist using SDCT. Four thoracic radiologists marked detected nodules on SDCT and ULDCT examinations using a dedicated computer workstation. After a 6-month memory extinction, readers were shown the same ULDCT cases with all CAD markings as well as their original detections, and characterized CAD detections as true positive or false positive.Volume CT Dose index (CTDIvol) for SDCT and ULDCT were 5.3±2 and 0.4±0.2 mGy (P<0.0001), respectively. Forty-five reference nodules were detected in 30 patients. Reader sensitivity varied widely but similarly for SDCT (ranging from 45% to 87%) and ULDCT (45% to 83%). CAD sensitivity was 76% (34/45) for SDCT and 71% (32/45) for ULDCT. After CAD, reader sensitivity substantially improved by 19% and 18% for 2 readers, and remained nearly unchanged for the other 2 readers (0% and 2%), despite reader perception that many more nodules were identified with CAD. There was a mean of 2 false-positive CAD detections/case.ULDCT with 100 kV/tin reduced patient dose by over 90% without compromising pulmonary nodule detection sensitivity. CAD can substantially improve nodule detection sensitivity at ULDCT for some readers, maintaining interobserver performance.

  View details for DOI 10.1097/RTI.0000000000000348

  View details for PubMedID 30048344

• The breadth of the diaphragm: updates in embryogenesis and role of imaging. The British journal of radiology Koo, C. W., Johnson, T. F., Gierada, D. S., White, D. B., Blackmon, S., Matsumoto, J. M., Choe, J., Allen, M. S., Levin, D. L., Kuzo, R. S. 2018; 91 (1088): 20170600

  Abstract

  The diaphragm is an unique skeletal muscle separating the thoracic and abdominal cavities with a primary function of enabling respiration. When abnormal, whether by congenital or acquired means, the consequences for patients can be severe. Abnormalities that affect the diaphragm are often first detected on chest radiographs as an alteration in position or shape. Cross-sectional imaging studies, primarily CT and occasionally MRI, can depict structural defects, intrinsic and adjacent pathology in greater detail. Fluoroscopy is the primary radiologic means of evaluating diaphragmatic motion, though MRI and ultrasound also are capable of this function. This review provides an update on diaphragm embryogenesis and discusses current imaging of various abnormalities, including the emerging role of three-dimensional printing in planning surgical repair of diaphragmatic derangements.

  View details for DOI 10.1259/bjr.20170600

  View details for PubMedID 29485899

  View details for PubMedCentralID PMC6209484

• Quantitative assessment of lung stiffness in patients with interstitial lung disease using MR elastography. Journal of magnetic resonance imaging : JMRI Marinelli, J. P., Levin, D. L., Vassallo, R., Carter, R. E., Hubmayr, R. D., Ehman, R. L., McGee, K. P. 2017; 46 (2): 365-374

  Abstract

  To investigate the use of magnetic resonance elastography (MRE) in the quantitative assessment of pulmonary fibrosis by comparing quantitative shear stiffness measurements of lung parenchyma in patients diagnosed with fibrotic interstitial lung disease (ILD) and healthy controls.A 1.5T spin-echo, echo planar imaging MRE (SE-EPI MRE) pulse sequence was utilized to assess absolute lung shear stiffness in 15 patients with diagnosed ILD and in 11 healthy controls. Data were collected at residual volume (RV) and total lung capacity (TLC). Spirometry data were obtained immediately prior to scanning. To test for statistical significance between RV and TLC shear stiffness estimates a two-sample t-test was performed. To assess variability within individual subject shear stiffness estimates, the intraclass correlation coefficient (ICC) and Krippendorff's alpha were calculated.Patients with ILD exhibited an average (±1 standard deviation) shear stiffness of 2.74 (±0.896) kPa at TLC and 1.32 (±0.300) kPa at RV. The corresponding values for healthy individuals were 1.33 (±0.195) kPa and 0.849 (±0.250) kPa, respectively. The difference in shear stiffness between RV and TLC was statistically significant (P < 0.001). At TLC, the ICC and alpha values were 0.909 and 0.887, respectively. At RV, the ICC and alpha values were 0.852 and 0.862, respectively.In subjects with known fibrotic interstitial lung disease, parenchymal shear stiffness is increased when compared to normal controls at both RV and TLC, with TLC demonstrating the most significant difference. MRE-derived parenchymal shear stiffness is a promising new noninvasive imaging-based biomarker of interstitial lung disease.1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:365-374.

  View details for DOI 10.1002/jmri.25579

  View details for PubMedID 28117930

• Air embolism: diagnosis and management. Future cardiology Malik, N., Claus, P. L., Illman, J. E., Kligerman, S. J., Moynagh, M. R., Levin, D. L., Woodrum, D. A., Arani, A., Arunachalam, S. P., Araoz, P. A. 2017; 13 (4): 365-378

  Abstract

  Air embolism is an uncommon, but potentially life-threatening event for which prompt diagnosis and management can result in significantly improved patient outcomes. Most air emboli are iatrogenic. Arterial air emboli may occur as a complication from lung biopsy, arterial catheterization or cardiopulmonary bypass. Immediate management includes placing the patient on high-flow oxygen and in the right lateral decubitus position. Venous air emboli may occur during pressurized venous infusions, or catheter manipulation. Immediate management includes placement of the patient on high-flow oxygen and in the left lateral decubitus and/or Trendelenburg position. Hyperbaric oxygen therapy is the definitive treatment which may decrease the size of air emboli by facilitating gas reabsorption, while also improving tissue oxygenation and reducing ischemic reperfusion injury.

  View details for DOI 10.2217/fca-2017-0015

  View details for PubMedID 28644058

• Estimation of Observer Performance for Reduced Radiation Dose Levels in CT: Eliminating Reduced Dose Levels That Are Too Low Is the First Step. Academic radiology Fletcher, J. G., Yu, L., Fidler, J. L., Levin, D. L., DeLone, D. R., Hough, D. M., Takahashi, N., Venkatesh, S. K., Sykes, A. G., White, D., Lindell, R. M., Kotsenas, A. L., Campeau, N. G., Lehman, V. T., Bartley, A. C., Leng, S., Holmes, D. R., Toledano, A. Y., Carter, R. E., McCollough, C. H. 2017; 24 (7): 876-890

  Abstract

  This study aims to estimate observer performance for a range of dose levels for common computed tomography (CT) examinations (detection of liver metastases or pulmonary nodules, and cause of neurologic deficit) to prioritize noninferior dose levels for further analysis.Using CT data from 131 examinations (abdominal CT, 44; chest CT, 44; head CT, 43), CT images corresponding to 4%-100% of the routine clinical dose were reconstructed with filtered back projection or iterative reconstruction. Radiologists evaluated CT images, marking specified targets, providing confidence scores, and grading image quality. Noninferiority was assessed using reference standards, reader agreement rules, and jackknife alternative free-response receiver operating characteristic figures of merit. Reader agreement required that a majority of readers at lower dose identify target lesions seen by the majority of readers at routine dose.Reader agreement identified dose levels lower than 50% and 4% to have inadequate performance for detection of hepatic metastases and pulmonary nodules, respectively, but could not exclude any low dose levels for head CT. Estimated differences in jackknife alternative free-response receiver operating characteristic figures of merit between routine and lower dose configurations found that only the lowest dose configurations tested (ie, 30%, 4%, and 10% of routine dose levels for abdominal, chest, and head CT examinations, respectively) did not meet criteria for noninferiority. At lower doses, subjective image quality declined before observer performance. Iterative reconstruction was only beneficial when filtered back projection did not result in noninferior performance.Opportunity exists for substantial radiation dose reduction using existing CT technology for common diagnostic tasks.

  View details for DOI 10.1016/j.acra.2016.12.017

  View details for PubMedID 28262519

  View details for PubMedCentralID PMC6481673

• A virtual clinical trial using projection-based nodule insertion to determine radiologist reader performance in lung cancer screening CT. Proceedings of SPIE--the International Society for Optical Engineering Yu, L., Hu, Q., Koo, C. W., Takahashi, E. A., Levin, D. L., Johnson, T. F., Hora, M. J., Dirks, S., Chen, B., McMillan, K., Leng, S., Fletcher, J. G., McCollough, C. H. 2017; 10132

  Abstract

  Task-based image quality assessment using model observers is promising to provide an efficient, quantitative, and objective approach to CT dose optimization. Before this approach can be reliably used in practice, its correlation with radiologist performance for the same clinical task needs to be established. Determining human observer performance for a well-defined clinical task, however, has always been a challenge due to the tremendous amount of efforts needed to collect a large number of positive cases. To overcome this challenge, we developed an accurate projection-based insertion technique. In this study, we present a virtual clinical trial using this tool and a low-dose simulation tool to determine radiologist performance on lung-nodule detection as a function of radiation dose, nodule type, nodule size, and reconstruction methods. The lesion insertion and low-dose simulation tools together were demonstrated to provide flexibility to generate realistically-appearing clinical cases under well-defined conditions. The reader performance data obtained in this virtual clinical trial can be used as the basis to develop model observers for lung nodule detection, as well as for dose and protocol optimization in lung cancer screening CT.

  View details for DOI 10.1117/12.2255593

  View details for PubMedID 28392614

  View details for PubMedCentralID PMC5384330

• Evaluation of a projection-domain lung nodule insertion technique in thoracic computed tomography. Journal of medical imaging (Bellingham, Wash.) Ma, C., Yu, L., Chen, B., Koo, C. W., Takahashi, E. A., Fletcher, J. G., Levin, D. L., Kuzo, R. S., Viers, L. D., Vincent-Sheldon, S. A., Leng, S., McCollough, C. H. 2017; 4 (1): 013510

  Abstract

  Task-based assessment of computed tomography (CT) image quality requires a large number of cases with ground truth. Prospective case acquisition can be time-consuming. Inserting lesions into existing cases to simulate positive cases is a promising alternative. The aim was to evaluate a recently developed projection-based lesion insertion technique in thoracic CT. In total, 32 lung nodules of various attenuations were segmented from 21 patient cases, forward projected, inserted into projections, and reconstructed. Two experienced radiologists and two residents independently evaluated these nodules in two substudies. First, the 32 inserted and the 32 original nodules were presented in a randomized order and each received a score from 1 to 10 (1 = absolutely artificial to 10 = absolutely realistic). Second, the inserted and the corresponding original lesions were presented side-by-side to each reader. For the randomized evaluation, discrimination of real versus inserted nodules was poor with areas under the receiver operative characteristic curves being 0.57 [95% confidence interval (CI): 0.46 to 0.68], 0.69 (95% CI: 0.58 to 0.78), and 0.62 (95% CI: 0.54 to 0.69) for the two residents, two radiologists, and all four readers, respectively. Our projection-based lung nodule insertion technique provides a robust method to artificially generate positive cases that prove to be difficult to differentiate from real cases.

  View details for DOI 10.1117/1.JMI.4.1.013510

  View details for PubMedID 28401176

  View details for PubMedCentralID PMC5374359

• Physiology for the pulmonary functional imager. European journal of radiology Levin, D. L., Schiebler, M. L., Hopkins, S. R. 2017; 86: 308-312

  Abstract

  As pulmonary functional imaging moves beyond the realm of the radiologist and physicist, it is important that imagers have a common language and understanding of the relevant physiology of the lung. This review will focus on key physiological concepts and pitfalls relevant to functional lung imaging.

  View details for DOI 10.1016/j.ejrad.2016.09.027

  View details for PubMedID 27707586

  View details for PubMedCentralID PMC6375311

• The role of dual-energy computed tomography in the assessment of pulmonary function. European journal of radiology Hwang, H. J., Hoffman, E. A., Lee, C. H., Goo, J. M., Levin, D. L., Kauczor, H. U., Seo, J. B. 2017; 86: 320-334

  Abstract

  The assessment of pulmonary function, including ventilation and perfusion status, is important in addition to the evaluation of structural changes of the lung parenchyma in various pulmonary diseases. The dual-energy computed tomography (DECT) technique can provide the pulmonary functional information and high resolution anatomic information simultaneously. The application of DECT for the evaluation of pulmonary function has been investigated in various pulmonary diseases, such as pulmonary embolism, asthma and chronic obstructive lung disease and so on. In this review article, we will present principles and technical aspects of DECT, along with clinical applications for the assessment pulmonary function in various lung diseases.

  View details for DOI 10.1016/j.ejrad.2016.11.010

  View details for PubMedID 27865580

• Dose-efficient ultrahigh-resolution scan mode using a photon counting detector computed tomography system. Journal of medical imaging (Bellingham, Wash.) Leng, S., Yu, Z., Halaweish, A., Kappler, S., Hahn, K., Henning, A., Li, Z., Lane, J., Levin, D. L., Jorgensen, S., Ritman, E., McCollough, C. 2016; 3 (4): 043504

  Abstract

  An ultrahigh-resolution (UHR) data collection mode was enabled on a whole-body, research photon counting detector (PCD) computed tomography system. In this mode, 64 rows of [Formula: see text] detector pixels were used, which corresponded to a pixel size of [Formula: see text] at the isocenter. Spatial resolution and image noise were quantitatively assessed for the UHR PCD scan mode, as well as for a commercially available UHR scan mode that uses an energy-integrating detector (EID) and a set of comb filters to decrease the effective detector size. Images of an anthropomorphic lung phantom, cadaveric swine lung, swine heart specimen, and cadaveric human temporal bone were qualitatively assessed. Nearly equivalent spatial resolution was demonstrated by the modulation transfer function measurements: 15.3 and [Formula: see text] spatial frequencies were achieved at 10% and 2% modulation, respectively, for the PCD system and 14.2 and [Formula: see text] for the EID system. Noise was 29% lower in the PCD UHR images compared to the EID UHR images, representing a potential dose savings of 50% for equivalent image noise. PCD UHR images from the anthropomorphic phantom and cadaveric specimens showed clear delineation of small structures.

  View details for DOI 10.1117/1.JMI.3.4.043504

  View details for PubMedID 28042589

  View details for PubMedCentralID PMC5177779

• Evaluation of a projection-domain lung nodule insertion technique in thoracic CT. Proceedings of SPIE--the International Society for Optical Engineering Ma, C., Chen, B., Koo, C. W., Takahashi, E. A., Fletcher, J. G., McCollough, C. H., Levin, D. L., Kuzo, R. S., Viers, L. D., Sheldon, S. A., Leng, S., Yu, L. 2016; 9783

  Abstract

  Task-based assessment of computed tomography (CT) image quality requires a large number of cases with ground truth. Inserting lesions into existing cases to simulate positive cases is a promising alternative approach. The aim of this study was to evaluate a recently-developed raw-data based lesion insertion technique in thoracic CT. Lung lesions were segmented from patient CT images, forward projected, and reinserted into the same patient CT projection data. In total, 32 nodules of various attenuations were segmented from 21 CT cases. Two experienced radiologists and 2 residents blinded to the process independently evaluated these inserted nodules in two sub-studies. First, the 32 inserted and the 32 original nodules were presented in a randomized order and each received a rating score from 1 to 10 (1=absolutely artificial to 10=absolutely realistic). Second, the inserted and the corresponding original lesions were presented side-by-side to each reader, who identified the inserted lesion and provided a confidence score (1=no confidence to 5=completely certain). For the randomized evaluation, discrimination of real versus artificial nodules was poor with areas under the receiver operative characteristic curves being 0.69 (95% CI: 0.58-0.78), 0.57 (95% CI: 0.46-0.68), and 0.62 (95% CI: 0.54-0.69) for the 2 radiologists, 2 residents, and all 4 readers, respectively. For the side-by-side evaluation, although all 4 readers correctly identified inserted lesions in 103/128 pairs, the confidence score was moderate (2.6). Our projection-domain based lung nodule insertion technique provides a robust method to artificially generate clinical cases that prove to be difficult to differentiate from real cases.

  View details for DOI 10.1117/12.2217009

  View details for PubMedID 27695156

  View details for PubMedCentralID PMC5045053

• A High-Resolution Imaging Technique using a Whole-body, Research Photon Counting Detector CT System. Proceedings of SPIE--the International Society for Optical Engineering Leng, S., Yu, Z., Halaweish, A., Kappler, S., Hahn, K., Henning, A., Li, Z., Lane, J., Levin, D. L., Jorgensen, S., Ritman, E., McCollough, C. 2016; 9783

  Abstract

  A high-resolution (HR) data collection mode has been introduced to the whole-body, research photon-counting-detector CT system installed in our laboratory. In this mode, 64 rows of 0.45 mm × 0.45 mm detectors pixels were used, which corresponded to a pixel size of 0.225 mm × 0.225 mm at the iso-center. Spatial resolution of this HR mode was quantified by measuring the MTF from a scan of a 50 micron wire phantom. An anthropomorphic lung phantom, cadaveric swine lung, temporal bone and heart specimens were scanned using the HR mode, and image quality was subjectively assessed by two experienced radiologists. Comparison of the HR mode images against their energy integrating system (EID) equivalents using comb filters was also performed. High spatial resolution of the HR mode was evidenced by the MTF measurement, with 15 lp/cm and 20 lp/cm at 10% and 2% MTF. Images from anthropomorphic phantom and cadaveric specimens showed clear delineation of small structures, such as lung vessels, lung nodules, temporal bone structures, and coronary arteries. Temporal bone images showed critical anatomy (i.e. stapes superstructure) that was clearly visible in the PCD system but hardly visible with the EID system. These results demonstrated the potential application of this imaging mode in lung, temporal bone, and vascular imaging. Other clinical applications that require high spatial resolution, such as musculoskeletal imaging, may also benefit from this high resolution mode.

  View details for DOI 10.1117/12.2217180

  View details for PubMedID 27330238

  View details for PubMedCentralID PMC4912329

• Triage for suspected acute Pulmonary Embolism: Think before opening Pandora's Box. European journal of radiology Levin, D., Seo, J. B., Kiely, D. G., Hatabu, H., Gefter, W., van Beek, E. J., Schiebler, M. L. 2015; 84 (6): 1202-11

  Abstract

  This is a review of the current strengths and weaknesses of the various imaging modalities available for the diagnosis of suspected non-massive Pulmonary Embolism (PE). Without careful consideration for the clinical presentation, and the timely application of clinical decision support (CDS) methodology, the current overutilization of imaging resources for this disease will continue. For a patient with a low clinical risk profile and a negative D-dimer there is no reason to consider further workup with imaging; as the negative predictive value in this scenario is the same as imaging. While the current efficacy and effectiveness data support the continued use of Computed Tomographic angiography (CTA) as the imaging golden standard for the diagnosis of PE; this test does have the unintended consequences of radiation exposure, possible overdiagnosis and overuse. There is a persistent lack of appreciation on the part of ordering physicians for the effectiveness of the alternatives to CTA (ventilation-perfusion imaging and contrast enhanced magnetic resonance angiography) in these patients. Careful use of standardized protocols for patient triage and the application of CDS will allow for a better use of imaging resources.

  View details for DOI 10.1016/j.ejrad.2015.03.023

  View details for PubMedID 25864020

• Estimation of the absolute shear stiffness of human lung parenchyma using (1) H spin echo, echo planar MR elastography. Journal of magnetic resonance imaging : JMRI Mariappan, Y. K., Glaser, K. J., Levin, D. L., Vassallo, R., Hubmayr, R. D., Mottram, C., Ehman, R. L., McGee, K. P. 2014; 40 (5): 1230-7

  Abstract

  To develop a rapid proton MR elastography (MRE) technique that can quantify the absolute shear stiffness of lung parenchyma, to investigate the ability to differentiate respiration-dependent stiffness variations of the lung, and to demonstrate clinical feasibility.A spin-echo echo planar imaging MRE sequence (SE-EPI MRE) with a very short echo time was developed and tested in a series of five healthy volunteers at three different lung volumes: (i) residual volume (RV), (ii) total lung capacity (TLC), (iii) and midway between RV and TLC (MID). At each volume, lung density was quantified using a MR-based density mapping sequence. For reference, data were acquired using the previously described spin-echo lung MRE sequence (SE-MRE). MRE data were also acquired in a patient with proven Idiopathic Pulmonary Fibrosis (IPF) to test clinical feasibility.The SE-EPIMRE sequence reduced total acquisition time by a factor of 2 compared with the SE-MRE sequence. Lung parenchyma median shear stiffness for the 5 volunteers quantified with the SE-EPI MRE sequence was 0.9 kPa, 1.1 kPa, and 1.6 kPa at RV, MID, and TLC, respectively. The corresponding values obtained with the SE-MRE sequence were 0.9 kPa, 1.1 kPa, and 1.5 kPa. Absolute shear stiffness was also successfully measured in the IPF patient.The results indicate that stiffness variations due to respiration could be measured with the SE-EPIMRE technique and were equivalent to values generated by the previously described SE-MRE approach. Preliminary data obtained from the patient demonstrate clinical feasibility.

  View details for DOI 10.1002/jmri.24479

  View details for PubMedID 24390975

  View details for PubMedCentralID PMC4019718

• Supine to upright lung mechanics: do changes in lung shape influence lung tissue deformation? Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Chan, H. F., Tawhai, M. H., Levin, D. L., Bartholmai, B. B., Clark, A. R. 2014; 2014: 832-5

  Abstract

  In this study we analyze lung shape change between the upright and supine postures and the effect of this shape change on the deformation of lung tissue under gravity. We use supine computed tomography images along with upright tomosynthesis images obtained on the same day to show that there is significant diaphragmatic movement between postures. Using a continuum model of lung tissue deformation under gravity we show that the shape changes due to this diaphragmatic movement could result in different lung tissue expansion patterns between supine and upright lungs. This is an essential consideration when interpreting imaging data acquired in different postures or translating data acquired in supine imaging to upright function.

  View details for DOI 10.1109/EMBC.2014.6943720

  View details for PubMedID 25570088

• Influence of interstitial lung disease on outcome in systemic sclerosis: a population-based historical cohort study. Chest Bauer, P. R., Schiavo, D. N., Osborn, T. G., Levin, D. L., St Sauver, J., Hanson, A. C., Schroeder, D. R., Ryu, J. H. 2013; 144 (2): 571-577

  Abstract

  Interstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc) and a major cause of SSc-related deaths. This study aimed to determine the influence of ILD on SSc in a population-based historical cohort study. The hypothesis was that patients with SSc who develop ILD have increased morbidity and mortality when compared with patients with SSc without ILD.Using the record linkage system of the Rochester Epidemiology Project in Olmsted County, Minnesota, this study identified the incidence of SSc between 1980 and 2010 and point prevalence on December 31, 2010 and determined the progression of organ involvement and its influence on outcome.During the 30-year interval, we identified 64 incident cases of SSc: 57 women and seven men, median age 49.1 years (interquartile range [IQR], 39.8-67.6 years). There were 43 prevalent cases. ILD occurred in 19 cases, usually after the diagnosis of SSc (median, 2 years; IQR, 0-10 years), with only three cases occurring 6 to 24 months beforehand. Pulmonary arterial hypertension (PAH) was diagnosed in 14 cases, heart failure in 27 cases, and chronic kidney disease (CKD) in 21 cases. Seventeen patients died during the study period, with a median survival time after diagnosis of 22.9 years. ILD, PAH, and CKD were associated with an increased risk of death.The incidence of ILD associated with SSc was relatively low in this population-based cohort. ILD appeared to be a contributing factor to mortality. Other factors, including age, PAH, and CKD, were also associated with poor outcome.

  View details for DOI 10.1378/chest.12-2768

  View details for PubMedID 23450327

  View details for PubMedCentralID PMC3734889

• Response. Chest Moua, T., Levin, D. L., Ryu, J. H. 2013; 144 (1): 362

  View details for DOI 10.1378/chest.13-0942

  View details for PubMedID 23880695

• Frequency of mediastinal lymphadenopathy in patients with idiopathic pulmonary arterial hypertension. Chest Moua, T., Levin, D. L., Carmona, E. M., Ryu, J. H. 2013; 143 (2): 344-348

  Abstract

  The objective of this study was to assess the frequency of mediastinal lymphadenopathy in patients with idiopathic pulmonary arterial hypertension (IPAH) and describe the correlative clinical features.We conducted a retrospective review of patients with IPAH who underwent right-sided heart catheterization (RHC) and chest CT scan within 3 months of each other. Patients were from a single tertiary institution. CT scans were reviewed for the presence of mediastinal lymphadenopathy (MLAD) with correlating demographic and clinical data, including lymph node size and location, right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), and the presence of pleural and pericardial effusion.The study population included 85 patients with a mean age of 48 17.3 years; 70 (82%) were women. Fifteen patients (18%) had MLAD on chest CT scan. The mean short-axis diameter of the largest lymph node in these patients was 13.6 mm (range, 11-20 mm). The enlarged lymph nodes were located predominantly in the lower paratracheal and subcarinal stations. There was no association of MLAD with age, sex, RAP, or mPAP. MLAD was associated with presence of pleural effusion ( P , .02) but not pericardial effusion. Mean left ventricular ejection fraction for those with lymphadenopathy was 63% (range, 45%-76%).MLAD without other identifiable causes is seen in approximately one in fi ve patients with IPAH and is associated with pleural effusion but not mPAP, RAP, or left ventricular function.

  View details for DOI 10.1378/chest.12-0663

  View details for PubMedID 22922444

• Magnetic resonance assessment of parenchymal elasticity in normal and edematous, ventilator-injured lung. Journal of applied physiology (Bethesda, Md. : 1985) McGee, K. P., Mariappan, Y. K., Hubmayr, R. D., Carter, R. E., Bao, Z., Levin, D. L., Manduca, A., Ehman, R. L. 2012; 113 (4): 666-76

  Abstract

  Magnetic resonance elastography (MRE) is a MR imaging method capable of spatially resolving the intrinsic mechanical properties of normal lung parenchyma. We tested the hypothesis that the mechanical properties of edematous lung exhibit local properties similar to those of a fluid-filled lung at transpulmonary pressures (P(tp)) up to 25 cm H(2)O. Pulmonary edema was induced in anesthetized female adult Sprague-Dawley rats by mechanical ventilation to a pressure of 40 cm H(2)O for ≈ 30 min. Prior to imaging the wet weight of each ex vivo lung set was measured. MRE, high-resolution T(1)-weighted spin echo and T(2)* gradient echo data were acquired at each P(tp) for both normal and injured ex vivo lungs. At P(tp)s of 6 cm H(2)O and greater, the shear stiffness of normal lungs was greater than injured lungs (P ≤ 0.0003). For P(tp)s up to 12 cm H(2)O, shear stiffness was equal to 1.00, 1.07, 1.16, and 1.26 kPa for the injured and 1.31, 1.89, 2.41, and 2.93 kPa for normal lungs at 3, 6, 9, and 12 cm H(2)O, respectively. For injured lungs MRE magnitude signal and shear stiffness within regions of differing degrees of alveolar flooding were calculated as a function of P(tp). Differences in shear stiffness were statistically significant between groups (P < 0.001) with regions of lower magnitude signal being stiffer than those of higher signal. These data demonstrate that when the alveolar space filling material is fluid, MRE-derived parenchymal shear stiffness of the lung decreases, and the lung becomes inherently softer compared with normal lung.

  View details for DOI 10.1152/japplphysiol.01628.2011

  View details for PubMedID 22678969

  View details for PubMedCentralID PMC3424061

• Lung volume does not alter the distribution of pulmonary perfusion in dependent lung in supine humans. The Journal of physiology Hopkins, S. R., Arai, T. J., Henderson, A. C., Levin, D. L., Buxton, R. B., Kim Prisk, G. 2010; 588 (Pt 23): 4759-68

  Abstract

  There is a gravitational influence on pulmonary perfusion, including in the most dependent lung, where perfusion is reduced, termed Zone 4. Studies using xenon-133 show Zone 4 behaviour, present in the dependent 4 cm at total lung capacity (TLC), affects the dependent 11 cm at functional residual capacity (FRC) and almost all the lung at residual volume (RV). These differences were ascribed to increased resistance in extra-alveolar vessels at low lung volumes although other mechanisms have been proposed. To further evaluate the behaviour of perfusion in dependent lung using a technique that directly measures pulmonary perfusion and corrects for tissue distribution by measuring regional proton density, seven healthy subjects (age = 38 ± 6 years, FEV₁ = 104 ± 7% predicted) underwent magnetic resonance imaging in supine posture. Data were acquired in the right lung during breath-holds at RV, FRC and TLC. Arterial spin labelling quantified regional pulmonary perfusion, which was normalized for regional proton density measured using a fast low-angle shot technique. The height of the onset of Zone 4 behaviour was not different between lung volumes (P = 0.23). There were no significant differences in perfusion (expressed as ml min⁻¹ g⁻¹) between lung volumes in the gravitationally intermediate (RV = 8.9 ± 3.1, FRC = 8.1 ± 2.9, TLC = 7.4 ± 3.6; P = 0.26) and dependent lung (RV = 6.6 ± 2.4, FRC = 6.1 ± 2.1, TLC = 6.4 ± 2.6; P = 0.51). However, at TLC perfusion was significantly lower in non-dependent lung than at FRC or RV (3.6 ± 3.3, 7.7 ± 1.5, 7.9 ± 2.0, respectively; P < 0.001). These data suggest that the mechanism of the reduction in perfusion in dependent lung is unlikely to be a result of lung volume related increases in resistance in extra-alveolar vessels. In supine posture, the gravitational influence on perfusion is remarkably similar over most of the lung, irrespective of lung volume.

  View details for DOI 10.1113/jphysiol.2010.196063

  View details for PubMedID 20921195

  View details for PubMedCentralID PMC3010144

• Nodular senile pulmonary amyloidosis: a unique case confirmed by immunohistochemistry, mass spectrometry, and genetic study. Human pathology Roden, A. C., Aubry, M. C., Zhang, K., Brady, J. O., Levin, D., Dogan, A., Yi, E. S. 2010; 41 (7): 1040-5

  Abstract

  Nodular pulmonary amyloidosis, characterized by solitary or multiple parenchymal nodules, is primarily composed of amyloid immunoglobulin light chain protein. Pulmonary involvement by senile amyloidosis has been reported as an incidental finding with scattered or diffuse interstitial deposition of amyloid protein transthyretin mostly in patients with cardiac senile amyloidosis in a small number of autopsy cases. We report a unique case of pulmonary senile amyloidosis presenting with conglomerated nodular deposition of amyloid protein transthyretin as the main clinical manifestation. The patient was an 82-year-old man who presented with recurrent pleural effusions and nodular replacement of pulmonary parenchyma on a chest computed tomographic scan. He underwent a wedge resection of the lesion. Histologic examination revealed a massive deposition of Congo red-positive amyloid identified as amyloid protein transthyretin by both immunohistochemistry and mass spectrometry using formalin-fixed, paraffin-embedded tissues. Molecular testing did not show any mutation associated with familial amyloidosis in the TTR gene, further supporting the diagnosis of senile amyloidosis. To our knowledge, this is the first documented case of nodular senile amyloidosis of the lung that was confirmed with the current state-of-the-art methods.

  View details for DOI 10.1016/j.humpath.2009.11.019

  View details for PubMedID 20381118

• Characterizing pulmonary blood flow distribution measured using arterial spin labeling. NMR in biomedicine Henderson, A. C., Prisk, G. K., Levin, D. L., Hopkins, S. R., Buxton, R. B. 2009; 22 (10): 1025-35

  Abstract

  The arterial spin labeling (ASL) method provides images in which, ideally, the signal intensity of each image voxel is proportional to the local perfusion. For studies of pulmonary perfusion, the relative dispersion (RD, standard deviation/mean) of the ASL signal across a lung section is used as a reliable measure of flow heterogeneity. However, the RD of the ASL signals within the lung may systematically differ from the true RD of perfusion because the ASL image also includes signals from larger vessels, which can reflect the blood volume rather than blood flow if the vessels are filled with tagged blood during the imaging time. Theoretical studies suggest that the pulmonary vasculature exhibits a lognormal distribution for blood flow and thus an appropriate measure of heterogeneity is the geometric standard deviation (GSD). To test whether the ASL signal exhibits a lognormal distribution for pulmonary blood flow, determine whether larger vessels play an important role in the distribution, and extract physiologically relevant measures of heterogeneity from the ASL signal, we quantified the ASL signal before and after an intervention (head-down tilt) in six subjects. The distribution of ASL signal was better characterized by a lognormal distribution than a normal distribution, reducing the mean squared error by 72% (p < 0.005). Head-down tilt significantly reduced the lognormal scale parameter (p = 0.01) but not the shape parameter or GSD. The RD increased post-tilt and remained significantly elevated (by 17%, p < 0.05). Test case results and mathematical simulations suggest that RD is more sensitive than the GSD to ASL signal from tagged blood in larger vessels, a probable explanation of the change in RD without a statistically significant change in GSD. This suggests that the GSD is a useful measure of pulmonary blood flow heterogeneity with the advantage of being less affected by the ASL signal from tagged blood in larger vessels.

  View details for DOI 10.1002/nbm.1407

  View details for PubMedID 19492332

  View details for PubMedCentralID PMC2836845

• Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans. Journal of applied physiology (Bethesda, Md. : 1985) Arai, T. J., Henderson, A. C., Dubowitz, D. J., Levin, D. L., Friedman, P. J., Buxton, R. B., Prisk, G. K., Hopkins, S. R. 2009; 106 (4): 1057-64

  Abstract

  We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.

  View details for DOI 10.1152/japplphysiol.90759.2008

  View details for PubMedID 19057006

  View details for PubMedCentralID PMC2698636

• Feasibility of quantifying the mechanical properties of lung parenchyma in a small-animal model using (1)H magnetic resonance elastography (MRE). Journal of magnetic resonance imaging : JMRI McGee, K. P., Hubmayr, R. D., Levin, D., Ehman, R. L. 2009; 29 (4): 838-45

  Abstract

  To evaluate the feasibility of spatially resolving the shear modulus of lung parenchyma using conventional (1)H magnetic resonance elastography (MRE) imaging techniques in a small animal model.A 10-cm diameter transmit-receive radiofrequency coil was modified to include a specimen stage, an MRE pneumatic drum driver, and needle system. MRE was performed on 10 female Sprague-Dawley rats using a (1)H spin-echo based MRE imaging sequence with a field of view of 7 cm and slice thickness of 5 mm. Air-filled lungs were imaged at transpulmonary inflation pressures of 5, 10, and 15 cm H(2)O while fluid-filled lungs were imaged after infusion of 4 mL of normal saline.The average shear modulus of air-filled lungs was 0.840 +/- 0.0524 kPa, 1.07 +/- 0.114 kPa and 1.30 +/- 0.118 kPa at 5, 10, and 15 cm H(2)O, respectively. Analysis of variance indicated that these population means were statistically significantly different from one another (F-value = 26.279, P = 0.00004). The shear modulus of the fluid-filled lungs was 1.65 +/- 0.360 kPa.It is feasible to perform lung MRE in small animals using conventional MR imaging technologies.

  View details for DOI 10.1002/jmri.21720

  View details for PubMedID 19306407

  View details for PubMedCentralID PMC2931322

• Echocardiographic assessment of the accuracy of computed tomography in the diagnosis of hemodynamically significant pericardial effusions. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Kolski, B. C., Kakimoto, W., Levin, D. L., Blanchard, D. G. 2008; 21 (4): 377-9

  Abstract

  Although Doppler echocardiography is the noninvasive test of choice for the diagnosis of hemodynamically significant pericardial effusion (HSPE), pericardial effusion is often first detected by computed tomography (CT). Few data are available, however, regarding the accuracy of CT in the diagnosis of cardiac tamponade.We retrospectively identified 28 consecutive hospitalized patients with pericardial effusion who underwent both chest CT and echocardiography within 48 hours between 2001 and 2005. CT images were analyzed by experienced radiologists without knowledge of the echo results. Radiologic findings were evaluated with Doppler echocardiography.Of the 28 patients, 15 had HSPE by echo criteria. Right ventricular wall flattening and pericardial thickening on CT correlated with HSPE with a positive predictive value of 79% and 67%, respectively. Inferior vena cava diameter by CT was not a useful predictor of HSPE. CT was most accurate in diagnosing HSPE when the effusions were large (n = 6) and was 100% sensitive and specific in this group. Of the small- to moderate-sized effusions (n = 22), the sensitivity and specificity were 80% and 75%, respectively.CT findings of right ventricular wall flattening, pericardial thickening, and a large pericardial effusion significantly increase the likelihood of tamponade. In this study, the majority of patients diagnosed with HSPE by CT did indeed have tamponade by standard echo criteria. Although not a useful screening tool in the diagnosis of HSPE, CT is of some help, and abnormal results warrant more urgent clinical evaluation.

  View details for DOI 10.1016/j.echo.2007.08.017

  View details for PubMedID 17928200

• Pulmonary perfusion in the prone and supine postures in the normal human lung. Journal of applied physiology (Bethesda, Md. : 1985) Prisk, G. K., Yamada, K., Henderson, A. C., Arai, T. J., Levin, D. L., Buxton, R. B., Hopkins, S. R. 2007; 103 (3): 883-94

  Abstract

  Prone posture increases cardiac output and improves pulmonary gas exchange. We hypothesized that, in the supine posture, greater compression of dependent lung limits regional blood flow. To test this, MRI-based measures of regional lung density, MRI arterial spin labeling quantification of pulmonary perfusion, and density-normalized perfusion were made in six healthy subjects. Measurements were made in both the prone and supine posture at functional residual capacity. Data were acquired in three nonoverlapping 15-mm sagittal slices covering most of the right lung: central, middle, and lateral, which were further divided into vertical zones: anterior, intermediate, and posterior. The density of the entire lung was not different between prone and supine, but the increase in lung density in the anterior lung with prone posture was less than the decrease in the posterior lung (change: +0.07 g/cm(3) anterior, -0.11 posterior; P < 0.0001), indicating greater compression of dependent lung in supine posture, principally in the central lung slice (P < 0.0001). Overall, density-normalized perfusion was significantly greater in prone posture (7.9 +/- 3.6 ml.min(-1).g(-1) prone, 5.1 +/- 1.8 supine, a 55% increase; P < 0.05) and showed the largest increase in the posterior lung as it became nondependent (change: +71% posterior, +58% intermediate, +31% anterior; P = 0.08), most marked in the central lung slice (P < 0.05). These data indicate that central posterior portions of the lung are more compressed in the supine posture, likely by the heart and adjacent structures, than are central anterior portions in the prone and that this limits regional perfusion in the supine posture.

  View details for DOI 10.1152/japplphysiol.00292.2007

  View details for PubMedID 17569767

  View details for PubMedCentralID PMC2399900

• Vertical gradients in regional lung density and perfusion in the supine human lung: the Slinky effect. Journal of applied physiology (Bethesda, Md. : 1985) Hopkins, S. R., Henderson, A. C., Levin, D. L., Yamada, K., Arai, T., Buxton, R. B., Prisk, G. K. 2007; 103 (1): 240-8

  Abstract

  In vivo radioactive tracer and microsphere studies have differing conclusions as to the magnitude of the gravitational effect on the distribution of pulmonary blood flow. We hypothesized that some of the apparent vertical perfusion gradient in vivo is due to compression of dependent lung increasing local lung density and therefore perfusion/volume. To test this, six normal subjects underwent functional magnetic resonance imaging with arterial spin labeling during breath holding at functional residual capacity, and perfusion quantified in nonoverlapping 15 mm sagittal slices covering most of the right lung. Lung proton density was measured in the same slices using a short echo 2D-Fast Low-Angle SHot (FLASH) sequence. Mean perfusion was 1.7 +/- 0.6 ml x min(-1) x cm(-3) and was related to vertical height above the dependent lung (slope = -3%/cm, P < 0.0001). Lung density averaged 0.34 +/- 0.08 g/cm3 and was also related to vertical height (slope = -4.9%/cm, P < 0.0001). By contrast, when perfusion was normalized for regional lung density, the slope of the height-perfusion relationship was not significantly different from zero (P = 0.2). This suggests that in vivo variations in regional lung density affect the interpretation of vertical gradients in pulmonary blood flow and is consistent with a simple conceptual model: the lung behaves like a Slinky (Slinky is a registered trademark of Poof-Slinky Incorporated), a deformable spring distorting under its own weight. The greater density of lung tissue in the dependent regions of the lung is analogous to a greater number of coils in the dependent portion of the vertically oriented spring. This implies that measurements of perfusion in vivo will be influenced by density distributions and will differ from excised lungs where density gradients are reduced by processing.

  View details for DOI 10.1152/japplphysiol.01289.2006

  View details for PubMedID 17395757

  View details for PubMedCentralID PMC2399899

• Advances in magnetic resonance imaging of lung physiology. Journal of applied physiology (Bethesda, Md. : 1985) Hopkins, S. R., Levin, D. L., Emami, K., Kadlecek, S., Yu, J., Ishii, M., Rizi, R. R. 2007; 102 (3): 1244-54

  Abstract

  This review presents an overview of some recent magnetic resonance imaging (MRI) techniques for measuring aspects of local physiology in the lung. MRI is noninvasive, relatively high resolution, and does not expose subjects to ionizing radiation. Conventional MRI of the lung suffers from low signal intensity caused by the low proton density and the large degree of microscopic field inhomogeneity that degrades the magnetic resonance signal and interferes with image acquisition. However, in recent years, there have been rapid advances in both hardware and software design, allowing these difficulties to be minimized. This review focuses on some newer techniques that measure regional perfusion, ventilation, gas diffusion, ventilation-to-perfusion ratio, partial pressure of oxygen, and lung water. These techniques include contrast-enhanced and arterial spin-labeling techniques for measuring perfusion, hyperpolarized gas techniques for measuring regional ventilation, and apparent diffusion coefficient and multiecho and gradient echo techniques for measuring proton density and lung water. Some of the major advantages and disadvantages of each technique are discussed. In addition, some of the physiological issues associated with making measurements are discussed, along with strategies for understanding large and complex data sets.

  View details for DOI 10.1152/japplphysiol.00738.2006

  View details for PubMedID 17158249

• Steep head-down tilt has persisting effects on the distribution of pulmonary blood flow. Journal of applied physiology (Bethesda, Md. : 1985) Henderson, A. C., Levin, D. L., Hopkins, S. R., Olfert, I. M., Buxton, R. B., Prisk, G. K. 2006; 101 (2): 583-9

  Abstract

  Head-down tilt has been shown to increase lung water content in animals and alter the distribution of ventilation in humans; however, its effects on the distribution of pulmonary blood flow in humans are unknown. We hypothesized that head-down tilt would increase the heterogeneity of pulmonary blood flow in humans, an effect analogous to the changes seen in the distribution of ventilation, by increasing capillary hydrostatic pressure and fluid efflux in the lung. To test this, we evaluated changes in the distribution of pulmonary blood flow in seven normal subjects before and after 1 h of 30 degrees head-down tilt using the magnetic resonance imaging technique of arterial spin labeling. Data were acquired in triplicate before tilt and at 10-min intervals for 1 h after tilt. Pulmonary blood flow heterogeneity was quantified by the relative dispersion (standard deviation/mean) of signal intensity for all voxels within the right lung. Relative dispersion was significantly increased by 29% after tilt and remained elevated during the 1 h of measurements after tilt (0.84 +/- 0.06 pretilt, 1.09 +/- 0.09 calculated for all time points posttilt, P < 0.05). We speculate that the mechanism most likely responsible for our findings is that increased pulmonary capillary pressures and fluid efflux in the lung resulting from head-down tilt alters regional blood flow distribution.

  View details for DOI 10.1152/japplphysiol.00087.2006

  View details for PubMedID 16601308

  View details for PubMedCentralID PMC3373314

• Quantification of regional pulmonary blood flow using ASL-FAIRER. Magnetic resonance in medicine Bolar, D. S., Levin, D. L., Hopkins, S. R., Frank, L. F., Liu, T. T., Wong, E. C., Buxton, R. B. 2006; 55 (6): 1308-17

  Abstract

  Pulsed arterial spin labeling (ASL) techniques have been theoretically and experimentally validated for cerebral blood flow (CBF) quantification. In this study ASL-FAIRER was used to measure regional pulmonary blood flow (rPBF) in seven healthy subjects. Two general ASL strategies were investigated: 1) a single-subtraction approach using one tag-control pair acquisition at an inversion time (TI) matched to the RR-interval, and 2) a multiple-subtraction approach using tag-control pairs acquired at various TIs. The mean rPBF averaged 1.70 +/- 0.38 ml/min/ml when measured with the multiple-subtraction approach, and was approximately 2% less when measured with the single-subtraction method (1.66 +/- 0.24 ml/min/ml). Assuming an average lung density of 0.33 g/ml, this translates into a regional perfusion of approximately 5.5 ml/g/min, which is comparable to other measures of pulmonary perfusion. As with other ASL applications, a key problem with quantitative interpretation of the results is the physical gap between the tagging region and imaged slice. Because of the high pulsatility of PBF, ASL acquisition and data analysis differ significantly between the lung and the brain. The advantages and drawbacks of the single- vs. multiple-subtraction approaches are considered within a theoretical framework tailored to PBF.

  View details for DOI 10.1002/mrm.20891

  View details for PubMedID 16680681

• Acute schistosomiasis in nonimmune travelers: chest CT findings in 10 patients. AJR. American journal of roentgenology Nguyen, L. Q., Estrella, J., Jett, E. A., Grunvald, E. L., Nicholson, L., Levin, D. L. 2006; 186 (5): 1300-3

  Abstract

  We describe the findings of unenhanced chest CT in 10 patients with acute schistosomiasis.Despite the absence of pulmonary symptoms in four individuals, all patients had parenchymal abnormalities. Small pulmonary nodules were the most common finding, identified in nine patients. These nodules ranged in size from 2 to 5 mm in five patients, with larger nodules ranging up to 15 mm seen in four patients. In one patient, the only parenchymal abnormality was a single 5-mm focus of ground-glass attenuation. No relationship was seen between either the presence of pulmonary symptoms or the presence of peripheral eosinophilia and the severity of parenchymal disease. No additional significant findings were identified.

  View details for DOI 10.2214/AJR.05.0213

  View details for PubMedID 16632722

• Heterogeneous pulmonary blood flow in response to hypoxia: a risk factor for high altitude pulmonary edema? Respiratory physiology & neurobiology Hopkins, S. R., Levin, D. L. 2006; 151 (2-3): 217-28

  Abstract

  High altitude pulmonary edema (HAPE) is a rapidly reversible hydrostatic edema that occurs in individuals who travel to high altitude. The difficulties associated with making physiologic measurements in humans who are ill or at high altitude, along with the idiosyncratic nature of the disease and lack of appropriate animal models, has meant that our understanding of the mechanism of HAPE is incomplete, despite considerable effort. Bronchoalveolar lavage studies at altitude in HAPE-susceptible subjects have shown that mechanical stress-related damage to the pulmonary blood gas barrier likely precedes the development of edema. Although HAPE-susceptible individuals have increased pulmonary arterial pressure in hypoxia, how this high pressure is transmitted to the capillaries has been uncertain. Using functional magnetic resonance imaging of pulmonary blood flow, we have been able to show that regional pulmonary blood flow in HAPE-susceptible subjects becomes more heterogeneous when they are exposed to normobaric hypoxia. This is not observed in individuals who have not had HAPE, providing novel data supporting earlier suggestions by Hultgren that uneven hypoxic pulmonary vasoconstriction is an important feature of those who develop HAPE. This brief review discusses how uneven hypoxic pulmonary vasoconstriction increases regional pulmonary capillary pressure leading to stress failure of pulmonary capillaries and HAPE. We hypothesize that, in addition to the well-documented increase in pulmonary vascular pressure in HAPE-susceptible individuals, increased perfusion heterogeneity in hypoxia results in lung regions that are vulnerable to increased mechanical stress.

  View details for DOI 10.1016/j.resp.2005.10.007

  View details for PubMedID 16377263

• Whole-body CT screening: spectrum of findings and recommendations in 1192 patients. Radiology Furtado, C. D., Aguirre, D. A., Sirlin, C. B., Dang, D., Stamato, S. K., Lee, P., Sani, F., Brown, M. A., Levin, D. L., Casola, G. 2005; 237 (2): 385-94

  Abstract

  To retrospectively determine the frequency and spectrum of findings and recommendations reported with whole-body computed tomographic (CT) screening at a community screening center.This HIPAA-compliant study received institutional review board approval, with waiver of informed consent. The radiologic reports of 1192 consecutive patients who underwent whole-body CT screening of the chest, abdomen, and pelvis at an outpatient imaging center from January to June 2000 were reviewed. Scans were obtained with electron-beam CT without oral or intravenous contrast material. Reported imaging findings and recommendations were retrospectively tabulated and assigned scores. Descriptive statistics were used (means, standard deviations, and percentages); comparisons between subgroups were performed with univariate analysis of variance and chi(2) or Fisher exact tests.Screening was performed in 1192 patients (mean age, 54 years). Sixty-five percent (774 of 1192) were men and 35% (418 of 1192) were women. Nine hundred three (76%) of 1192 patients were self referred, and 1030 (86%) of 1192 subjects had at least one abnormal finding described in the whole-body CT screening report. There were a total of 3361 findings, with a mean of 2.8 per patient. Findings were described most frequently in the spine (1065 [32%] of 3361), abdominal blood vessels (561 [17%] of 3361), lungs (461 [14%] of 3361), kidneys (353 [11%] of 3361), and liver (183 [5%] of 3361). Four hundred forty-five (37%) patients received at least one recommendation for further evaluation. The most common recommendations were for additional imaging of the lungs or the kidneys.With whole-body CT screening, findings were detected in a large number of subjects, and most findings were benign by description and required no further evaluation. Thirty-seven percent of patients had findings that elicited recommendations for additional evaluation, but further research is required to determine the clinical importance of these findings and the effect on patient care.

  View details for DOI 10.1148/radiol.2372041741

  View details for PubMedID 16170016

• Lymphangioleiomyomatosis: clinical, pathologic, and radiologic manifestations. Journal of thoracic imaging Niku, S., Stark, P., Levin, D. L., Friedman, P. J. 2005; 20 (2): 98-102

  View details for DOI 10.1097/01.rti.0000154071.31873.e2

  View details for PubMedID 15818208

• Pulmonary blood flow heterogeneity during hypoxia and high-altitude pulmonary edema. American journal of respiratory and critical care medicine Hopkins, S. R., Garg, J., Bolar, D. S., Balouch, J., Levin, D. L. 2005; 171 (1): 83-7

  Abstract

  Uneven hypoxic pulmonary vasoconstriction has been proposed to expose parts of the pulmonary capillary bed to high pressure and vascular injury in high-altitude pulmonary edema (HAPE). We hypothesized that subjects with a history of HAPE would demonstrate increased heterogeneity of pulmonary blood flow during hypoxia. A functional magnetic resonance imaging technique (arterial spin labeling) was used to quantify spatial pulmonary blood flow heterogeneity in three subject groups: (1) HAPE-susceptible (n = 5), individuals with a history of physician-documented HAPE; (2) HAPE-resistant (n = 6), individuals with repeated high-altitude exposure without illness; and (3) unselected (n = 6), individuals with a minimal history of altitude exposure. Data were collected in normoxia and after 5, 10, 20, and 30 minutes of normobaric hypoxia FI(O(2)) = 0.125. Relative dispersion (SD/mean) of the signal intensity was used as an index of perfusion heterogeneity. Oxygen saturation was not different between groups during hypoxia. Relative dispersion was not different between groups (HAPE-susceptible 0.94 +/- 0.05, HAPE-resistant 0.94 +/- 0.05, unselected 0.87 +/- 0.06; means +/- SEM) during normoxia, but it was increased by hypoxia in HAPE-susceptible (to 1.10 +/- 0.05 after 30 minutes, p < 0.0001) but not in HAPE-resistant (0.91 +/- 0.05) or unselected subjects (0.87 +/- 0.05). HAPE-susceptible individuals have increased pulmonary blood flow heterogeneity in acute hypoxia, consistent with uneven hypoxic pulmonary vasoconstriction.

  View details for DOI 10.1164/rccm.200406-707OC

  View details for PubMedID 15486339

• MR evaluation of pulmonary blood flow. Journal of thoracic imaging Levin, D. L., Hatabu, H. 2004; 19 (4): 241-9

  Abstract

  Pulmonary blood flow is one of the primary determinants of gas exchange. While a number of methods can be used to evaluation pulmonary perfusion, these have substantial limitations. In this paper, we discuss the use of magnetic resonance imaging techniques for the evaluation of pulmonary blood flow. While these methods are not commonly used at present, they have the potential to contribute greatly to the evaluation of suspected pulmonary vascular disease.

  View details for DOI 10.1097/01.rti.0000142836.14611.f2

  View details for PubMedID 15502611

• Radiology of pulmonary vascular disease. Cardiology clinics Levin, D. L., Goodman, E. T. 2004; 22 (3): 375-82, vi

  Abstract

  Diagnostic radiology plays an important role in the evaluation of suspected pulmonary vascular disease. This article discusses the use of various radiographic modalities and the radiographic features of several pulmonary vascular diseases.

  View details for DOI 10.1016/j.ccl.2004.04.008

  View details for PubMedID 15302358

• Characterization of small nodules by automatic segmentation of X-ray computed tomography images. Journal of computer assisted tomography Tao, P., Griess, F., Lvov, Y., Mineyev, M., Zhao, B., Levin, D., Kaufman, L. 2004; 28 (3): 372-7

  Abstract

  To characterize the ability of an automatic lung nodule segmentation algorithm to measure small nodule dimensions and growth rates.A phantom of 20 sets of 6 balls each (11 different nylon balls and 9 acrylic balls) of 1 to 9.5 mm in diameter, in foam, was imaged using x-ray computed tomography with slice thicknesses of 5, 2.5, and 1.25 mm, pitches of 3 and 6, and standard and lung resolution. Measurements consisted of volume and maximum in-plane cross-sectional areas and their derived maximum and effective diameters. Growth rates were simulated using pairs of groups of balls.Volume measurements overestimate volume, more so for thicker slices. For the largest balls, the error is 60% for 5-mm slices and 20% for 1.25-mm slices. Effective diameter calculated from volume better approximates actual diameter. For area measurements, errors are 0% to 5% for the largest balls, and the effective and actual diameters are closely matched.Below 5 mm in diameter, changes in volume should reach 100% for reliable indication of growth. Above 6 mm, the threshold for detecting change is on the order of 25% growth. Even under ideal conditions, results indicate the need for caution when making a diagnosis of malignancy on the basis of volume change.

  View details for DOI 10.1097/00004728-200405000-00012

  View details for PubMedID 15100543

• A pig model of high altitude pulmonary edema. High altitude medicine & biology Kleinsasser, A., Levin, D. L., Loeckinger, A., Hopkins, S. R. 2003; 4 (4): 465-74

  Abstract

  High altitude pulmonary edema (HAPE) affects unacclimatized individuals ascending rapidly to high altitude. The pathogenesis of HAPE is not fully elucidated, and many investigative techniques that could provide valuable information are not suitable for use in humans; thus, an animal model is desirable. Rabbits, sheep, dogs, and ferrets have been shown not to consistently develop HAPE, and studies in rats are limited by the animal's small size and inconsistent response. Pigs develop a marked pulmonary vasoconstrictive response to hypoxia, and preliminary studies of HAPE in pigs have been promising. To determine the suitability of pigs as an animal model of HAPE, we exposed six subadult (20 to 25 kg) pigs to normobaric hypoxia (10% oxygen) for 48 hr. One week before, and immediately after exposure to hypoxia, under anesthesia, arterial blood gases were obtained and bronchoalveolar lavage (BAL) and chest x-ray were performed. Hypoxia increased alveolar-arterial pressure difference for oxygen from 22 +/- 9 to 38 +/- 5 torr, p < 0.01) and red cell (from 12.3 +/- 5.9 to 27.4 +/- 5.3 cells x 10(5)/mL(-1), p < 0.001) and white cell (from 1.59 +/- 0.90 to 7.88 +/- 3.36 cells x 10(5)/mL(-1), p < 0.05) concentrations in BAL in all animals. Total BAL protein concentration increased by 64% and fractional albumin by 38% (both p < 0.05) posthypoxia. One animal had evidence of pulmonary edema on X ray. Some pigs develop findings consistent with early HAPE when exposed to normobaric hypoxia. Increasing the duration of hypoxic exposure or exercising the animals in hypoxia may better model the disease process observed in humans with clinically significant HAPE.

  View details for DOI 10.1089/152702903322616218

  View details for PubMedID 14672549

• Nonneoplastic lesions of the tracheobronchial wall: radiologic findings with bronchoscopic correlation. Radiographics : a review publication of the Radiological Society of North America, Inc Prince, J. S., Duhamel, D. R., Levin, D. L., Harrell, J. H., Friedman, P. J. 2002; 22 Spec No: S215-30

  Abstract

  Nonneoplastic diseases of the central airways are uncommon but can be categorized as either focal or diffuse, although there is some overlap. Focal diseases include postintubation stenosis, postinfectious stenosis, posttransplantation stenosis, and various systemic diseases that may involve the airways and lead to focal stenosis (eg, Crohn disease, sarcoidosis, Behçet syndrome). Diffuse diseases of the central airways include Wegener granulomatosis, relapsing polychondritis, tracheobronchopathia osteochondroplastica, amyloidosis, papillomatosis, and rhinoscleroma. Conventional radiography is often the first step in the evaluation of suspected central airway disease and may be adequate in itself to identify the abnormality. However, computed tomography (CT) improves both the detection and characterization of central airway disease. Bronchoscopy remains the primary procedure for the diagnostic work-up of these disease entities. Nevertheless, a thorough radiologic evaluation with radiography and CT may demonstrate specific imaging findings (eg, calcification) that can help narrow the differential diagnosis and aid in the planning of bronchoscopy or therapeutic intervention.

  View details for DOI 10.1148/radiographics.22.suppl_1.g02oc02s215

  View details for PubMedID 12376612

• Radiology of pulmonary Mycobacterium avium-intracellulare complex. Clinics in chest medicine Levin, D. L. 2002; 23 (3): 603-12

  Abstract

  Although the radiographic appearance of pulmonary MAC infection in the immunocompetent host can be varied, there are several generalizations that can be made. The classic radiographic appearance is indistinguishable from that of pulmonary tuberculosis. The classic form is seen most commonly in males and is typically associated with other predisposing diseases, especially chronic obstructive pulmonary disease. Most patients have upper lobe disease with associated pleural thickening. Widespread disease is common, as is cavitation. Pleural effusions and adenopathy are uncommon. The Lady Windermere syndrome is a special form of pulmonary MAC seen primarily in middle-aged and elderly women. The radiographic findings are bronchiectasis and small nodules, predominately located within the middle lobe and lingula. The combination of bronchiectasis involving exclusively, or primarily, the right middle lobe and lingula is highly suggestive of pulmonary MAC, even in the face of negative sputum cultures. Pulmonary infection with MAC in the immunocompromised patient generally reflects a widespread systemic disease. As such, the radiographic appearance is highly variable. Diffuse pulmonary opacities and adenopathy are common features. Plain radiographs are frequently normal despite active pulmonary infection. Regardless of the clinical situation, pulmonary MAC infection is often omitted from the radiographic differential even when the appearance is characteristic. In general, when pulmonary abnormalities are identified that are consistent with a granulomatous infection, pulmonary MAC needs to be considered along with tuberculosis and fungal infection. Especially with pulmonary MAC, radiographic stability over several years does not exclude active disease. The radiographic appearance may be suggestive of the diagnosis of pulmonary MAC, but correlation with the clinical and microbiological data is necessary to confirm the diagnosis.

  View details for DOI 10.1016/s0272-5231(02)00009-6

  View details for PubMedID 12370996

• Evaluation of regional pulmonary perfusion using ultrafast magnetic resonance imaging. Magnetic resonance in medicine Levin, D. L., Chen, Q., Zhang, M., Edelman, R. R., Hatabu, H. 2001; 46 (1): 166-71

  Abstract

  An ultrafast MR sequence was used to measure changes in signal intensity during the first pass of intravascular contrast through the pulmonary circulation. From this, mean transit time, relative blood volume, and relative blood flow were calculated. Data were collected in an isogravitational plane in six healthy subjects. A slight but significant gradient in transit time was present, with faster times at the lung apex. A significant decrease in blood volume, compared with the lung base, was also seen in the apex. Significant decreases in blood volume and blood flow, compared with central portions of the lung, were seen in the lung periphery. Six additional subjects were imaged along a gravitational plane. A significant gradient in transit time was seen, with faster transit in dependent regions of the lung. MRI is able to evaluate regional differences in pulmonary perfusion with high spatial and temporal resolution. Magn Reson Med 46:166-171, 2001.

  View details for DOI 10.1002/mrm.1172

  View details for PubMedID 11443723

• Quantification of pulmonary perfusion with MR imaging: recent advances. European journal of radiology Uematsu, H., Levin, D. L., Hatabu, H. 2001; 37 (3): 155-63

  Abstract

  Recent advances in magnetic resonance pulmonary perfusion imaging are reviewed, focusing on magnetic resonance perfusion imaging using gadolinium contrasts agents or spin labeling of blood using naturally flowing spins as the source of intravascular signal. These recent developments in magnetic resonance imaging have made it possible to analyze data quantitatively which holds significant potential for clinical imaging of lung perfusion and opens windows to functional MR imaging of the lung. We believe that fast magnetic resonance functional imaging will play an important role in the assessment of pulmonary function and the pulmonary disease process.

  View details for DOI 10.1016/s0720-048x(00)00300-4

  View details for PubMedID 11274843

• Magnetic resonance imaging of the thorax. Past, present, and future. Radiologic clinics of North America Hatabu, H., Stock, K. W., Sher, S., Edinburgh, K. J., Levin, D. L., Garpestad, E., Albert, M. S., Mai, V. M., Chen, Q., Edelman, R. R. 2000; 38 (3): 593-620, x

  Abstract

  Magnetic resonance imaging is a valuable modality of extreme flexibility for specific problem-solving capability in the thorax. This article reviews MR applications in the imaging of great vessels, which are currently the most important applications in the thorax; other established applications in the thorax; and pulmonary functional MR imaging.

  View details for DOI 10.1016/s0033-8389(05)70187-1

  View details for PubMedID 10855264

• Magnetic resonance imaging of the thorax. Past, present, and future. Clinics in chest medicine Hatabu, H., Stock, K. W., Sher, S., Edinburgh, K. J., Levin, D. L., Garpestad, E., Albert, M. S., Mai, V. M., Chen, Q., Edelman, R. R. 1999; 20 (4): 775-803, viii-ix

  Abstract

  Magnetic resonance is a valuable modality of extreme flexibility for specific problem-solving capability in the thorax. This article reviews MR applications in the imaging of great vessels, which are currently the most important applications in the thorax; other established applications in the thorax; and pulmonary functional MR imaging.

  View details for DOI 10.1016/s0272-5231(05)70255-0

  View details for PubMedID 10587798

• Quantitative assessment of pulmonary perfusion with dynamic contrast-enhanced MRI. Magnetic resonance in medicine Hatabu, H., Tadamura, E., Levin, D. L., Chen, Q., Li, W., Kim, D., Prasad, P. V., Edelman, R. R. 1999; 42 (6): 1033-8

  Abstract

  The feasibility of qualitative assessment of pulmonary perfusion using dynamic contrast enhanced MRI with ultra-short TE has recently been demonstrated. In the current study, quantitative analysis was attempted based on the indicator dilution principle using a pig model of pulmonary embolism. The results were compared with the absolute pulmonary perfusion obtained with colored microspheres. The inverse of apparent mean transit time (1/tau(app)), distribution volume (V), and V/tau(app) were correlated well with the absolute lung perfusion. This study demonstrates that MR has the potential to evaluate pulmonary perfusion quantitatively. Magn Reson Med 42:1033-1038, 1999.

  View details for DOI 10.1002/(sici)1522-2594(199912)42:6<1033::aid-mrm7>3.0.co;2-7

  View details for PubMedID 10571924

• Pulmonary disorders: ventilation-perfusion MR imaging with animal models. Radiology Chen, Q., Levin, D. L., Kim, D., David, V., McNicholas, M., Chen, V., Jakob, P. M., Griswold, M. A., Goldfarb, J. W., Hatabu, H., Edelman, R. R. 1999; 213 (3): 871-9

  Abstract

  To demonstrate the capability of magnetic resonance (MR) imaging to assess alteration in regional pulmonary ventilation and perfusion with animal models of airway obstruction and pulmonary embolism.Airway obstruction was created by inflating a 5-F balloon catheter into a secondary bronchus. Pulmonary emboli were created by injecting thrombi into the inferior vena cava. Regional pulmonary ventilation was assessed with 100% oxygen as a T1 contrast agent. Regional pulmonary perfusion was assessed with a two-dimensional fast low-angle shot, or FLASH, sequence with short repetition and echo times after intravenous administration of gadopentetate dimeglumine.Matched ventilation and perfusion abnormalities were identified in all animals with airway obstruction. MR perfusion defects without ventilation abnormalities were seen in all animals with pulmonary emboli.Ventilation and perfusion MR imaging are able to provide regional pulmonary functional information with high spatial and temporal resolution. The ability of MR imaging to assess both the magnitude and regional distribution of pulmonary functional impairment could have an important effect on the evaluation of lung disease.

  View details for DOI 10.1148/radiology.213.3.r99dc31871

  View details for PubMedID 10580969

• Ventilation-perfusion MR imaging of the lung. Magnetic resonance imaging clinics of North America Hatabu, H., Chen, Q., Levin, D. L., Tadamura, E., Edelman, R. R. 1999; 7 (2): 379-92, x

  Abstract

  The assessment of regional ventilation in human lungs is important for the diagnosis and evaluation of a variety of pulmonary disorders, including pulmonary emphysema, diffuse lung disease (e.g., sarcoidosis, and pulmonary fibrosis), lung cancer, and pulmonary embolism. This article introduces new MR imaging techniques of pulmonary ventilation and perfusion that will provide a framework for assessing regional pulmonary functions of the lung.

  View details for PubMedID 10382168

• Quiz case 6. Bronchiolitis obliterans organizing pneumonia (BOOP). European journal of radiology Edinburgh, K. J., Levin, D. L., Hatabu, H. 1999; 30 (1): 39-41

  View details for DOI 10.1016/s0720-048x(99)00024-8

  View details for PubMedID 10389011

• Demonstration of gravity-dependent lung perfusion with contrast-enhanced magnetic resonance imaging. Journal of magnetic resonance imaging : JMRI Stock, K. W., Chen, Q., Levin, D., Hatabu, H., Edelman, R. R. 1999; 9 (4): 557-61

  Abstract

  Imaging of lung perfusion using contrast-enhanced dynamic magnetic resonance (MR) was performed in both the supine and prone positions in six volunteers. Regions of interest (ROIs) were chosen in the dependent and non-dependent portions of the right lung. The percentage increase in signal intensity (SI) and the mean slope were calculated. In the supine position, the dorsal ROI had a greater increase in SI (236.0% vs. 156.9%, P < 0.05) and a faster rise in the slope of enhancement (55.1%/sec vs. 30.1%/sec, P < 0.05) than the ventral ROI. After changing to the prone position, higher peak enhancement (234.3% vs. 177.4%, P < 0.05) and faster slopes (59.6%/sec vs. 35.3%/sec, P < 0.05) shifted to the anterior ROI. We conclude that dynamic contrast-enhanced MR imaging is sensitive to demonstrate gravitationally dependent differences in lung perfusion.

  View details for DOI 10.1002/(sici)1522-2586(199904)9:4<557::aid-jmri8>3.0.co;2-y

  View details for PubMedID 10232514

• Imaging techniques for pleural space infections. Seminars in respiratory infections Levin, D. L., Klein, J. S. 1999; 14 (1): 31-8

  Abstract

  Radiology plays a central role in the evaluation and management of pleural space infections. Conventional radiographs, including decubitus films, remain the primary radiological study in the detection of parapneumonic pleural effusions. Loculated collections develop as a result of visceral-to-parietal pleural adhesions and appear radiographically as longitudinally oriented, lenticular-shaped opacities. Contrast-enhanced computed tomography scans accurately distinguish lung abscess from loculated empyema and provide a global view of the extent and complexity of the pleural collection. Sonography allows portable bedside examination of critically ill patients and is useful in the detection and sampling of small effusions. Real-time ultrasound evaluation of pleural collections accurately determines the size and nature of the effusion and may be useful in predicting the success of thoracentesis. As cross-sectional studies are obtained in the majority of patients with complex pleural space infection and provide valuable information, the precise clinical utility of computed tomography scans and ultrasound in these patients remains undetermined.

  View details for PubMedID 10197395

• Quiz case 4. Churg-Strauss syndrome. European journal of radiology Levin, D. L., Edinburgh, K. J., Hatabu, H. 1999; 29 (2): 149-51

  View details for DOI 10.1016/s0720-048x(98)00166-1

  View details for PubMedID 10374662

• Oxygen enhanced MR ventilation imaging of the lung. Magma (New York, N.Y.) Chen, Q., Jakob, P. M., Griswold, M. A., Levin, D. L., Hatabu, H., Edelman, R. R. 1998; 7 (3): 153-61

  Abstract

  The current work is a continuation of a new MRI technique that was proposed for the non-invasive assessment of regional lung ventilation using inhaled molecular oxygen as a T1 contrast agent. Several improvements of this technique are described in this work. The signal-to-noise ratio in the ventilation-scan images was optimized using a centrically reordered single-shot RARE sequence with a short effective echo time and short inter-echo spacing. The contrast-to-noise ratio was improved using an optimized inversion delay time. The optimized MR-ventilation-scan was successfully performed in healthy volunteers and in an animal model with airway obstruction. The experimental results demonstrate the feasibility and clinical potential of the MR ventilation imaging technique for assessment of regional pulmonary function.

  View details for DOI 10.1007/BF02591332

  View details for PubMedID 10050941

• Distinguishing hantavirus pulmonary syndrome from acute respiratory distress syndrome by chest radiography: are there different radiographic manifestations of increased alveolar permeability? Journal of thoracic imaging Ketai, L. H., Kelsey, C. A., Jordan, K., Levin, D. L., Sullivan, L. M., Williamson, M. R., Wiest, P. W., Sell, J. J. 1998; 13 (3): 172-7

  Abstract

  Hantavirus infection may cause diffuse air space disease, termed hantavirus pulmonary syndrome (HPS). The authors sought to determine if chest radiographs could differentiate HPS from typical acute respiratory distress syndrome (ARDS). The authors identified patients with either HPS (n = 11) or acute ARDS (n = 32) and selected the earliest chest radiograph showing diffuse airspace disease, and a chest radiograph taken 24 to 48 hours previously. Thoracic and general radiologists first viewed the chest radiograph showing diffuse air space disease, and ranked the likelihood that each case represented HPS versus ARDS. Afterward, readers viewed earlier chest radiographs and rescored each case. Receiver operating characteristic (ROC) curves from both scoring sessions were generated. The mean areas under the ROC curves for the entire group was 0.83 +/- 0.12 initially, and improved to 0.87 +/- 0.09 (p < 0.05) after viewing prior chest radiographs. Receiver operating characteristic curves of thoracic radiologists described greater areas than those of general radiologists both before and after viewing prior chest radiographs; 0.95 +/- 0.01 versus 0.78 +/- 0.08 (p < 0.05) and 96 +/- 0.02 versus 0.80 +/- 0.05 (p < 0.05). The mean sensitivity and specificity of chest radiograph interpretation for HPS was 86 +/- 13% and 74 +/- 11%, respectively. Chest radiographs can differentiate HPS from ARDS. Accuracy is improved by the use of serial radiographs and more highly trained readers. The chest radiograph findings may represent differences in the extent of alveolar epithelial damage seen in HPS and ARDS.

  View details for DOI 10.1097/00005382-199807000-00002

  View details for PubMedID 9671418

• Emphysema and chronic obstructive pulmonary disease. AJR. American journal of roentgenology Hall, F. M., Levin, D. L. 1997; 169 (5): 1460-1

  View details for DOI 10.2214/ajr.169.5.9353482

  View details for PubMedID 9353482

• Pulmonary alveolar proteinosis: high-resolution CT, chest radiographic, and functional correlations. Chest Lee, K. N., Levin, D. L., Webb, W. R., Chen, D., Storto, M. L., Golden, J. A. 1997; 111 (4): 989-95

  Abstract

  To determine whether a correlation exists between pulmonary function and both frontal chest radiographs and high-resolution chest CT findings in patients with pulmonary alveolar proteinosis (PAP).Retrospective review of radiographic and clinical data.Tertiary referral hospital.Seven patients with PAP were studied on 25 occasions using high-resolution chest CT (n=21), frontal chest radiographs (n=19), and pulmonary function tests (PFTs) (n=25).Visual estimates of the extent, degree, and overall severity of parenchymal abnormalities were determined for plain radiographs and high-resolution chest CT, and were correlated with PFTs. With high-resolution CT, the extent and severity of ground-glass opacity correlated significantly with the presence of a restrictive ventilatory defect, reduced diffusing capacity, and hypoxemia. Chest radiographic findings also correlated significantly with restrictive ventilatory defect, diffusing capacity, and hypoxemia.In patients with PAP, although high-resolution CT correlates more closely with pulmonary function, plain radiographs should be sufficient for follow-up.

  View details for DOI 10.1378/chest.111.4.989

  View details for PubMedID 9106579

• Temporal image database design for outcome analysis of lung nodule. Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society Zhu, X., Lee, K. N., Levin, D. L., Wong, S. T., Huang, H. K., Soo Hoo, K., Gamsu, G., Webb, W. R. 1996; 20 (4): 347-56

  Abstract

  This paper presents the design of a temporal image database system and its application in thoracic imaging. The design of this information system is based on the client/server architecture. The system consists of a chest imaging database server, a library of image processing modules, a link to the picture archiving and communication system (PACS) archive, and a low end client workstation with motif-based graphic user interface (GUI). The database system can be used to aid the radiologists in quantitating solitary or multiple long nodules and in assessing effectiveness of therapeutic procedures for these lung cancers. The GUI allows a user to retrieve any patient study from PACS. After a nodule is visually identified, it will be segmented automatically to obtain relevant features, such as the center of mass, volume, and surface area. Such 3D nodule information, together with the patient textual information, is subsequently organized in the chest imaging database to facilitate outcome analysis.

  View details for DOI 10.1016/s0895-6111(96)00024-9

  View details for PubMedID 8954239

• Carcinoma of the prostate gland: MR imaging with pelvic phased-array coils versus integrated endorectal--pelvic phased-array coils. Radiology Hricak, H., White, S., Vigneron, D., Kurhanewicz, J., Kosco, A., Levin, D., Weiss, J., Narayan, P., Carroll, P. R. 1994; 193 (3): 703-9

  Abstract

  To compare the performance of pelvic phased-array (PPA) coils and integrated endorectal PPA coils in evaluation of local extent of prostate cancer.Seventy-one men underwent magnetic resonance (MR) imaging within 3 weeks of radical prostatectomy. MR findings of tumor, extracapsular extension, seminal vesicle invasion, nodal involvement, and stage were compared with step-sectioned (3-4-mm intervals) whole-mounted pathologic specimens. Prospective consensus versus single-reader interpretation (kappa statistics) and PPA versus integrated endorectal PPA coils (McNemar test) were compared, and a rating scale of 1-6 was developed for analysis of receiver operating characteristics. Statistical significance was calculated at delta = .05.Comparison between consensus and single-reader image interpretation showed positive but poor agreement (kappa = .38) and no statistical significance. Staging accuracy was better (difference approached significance) for integrated endorectal PPA coils (77%) than for PPA coils (68%).The integrated endorectal PPA coil is better for evaluation of local prostatic cancer than is the PPA coil.

  View details for DOI 10.1148/radiology.193.3.7972810

  View details for PubMedID 7972810

• Measurement of internal carotid artery stenosis from source MR angiograms. Radiology Anderson, C. M., Lee, R. E., Levin, D. L., de la Torre Alonso, S., Saloner, D. 1994; 193 (1): 219-26

  Abstract

  To determine whether interpretation of internal carotid artery (ICA) stenosis from source partitions is more accurate than interpretation from maximum-intensity projections (MIPs) from three-dimensional (3D) time-of-flight (TOF) magnetic resonance (MR) angiography.The percentage of diameter ICA stenosis was measured on source images and MIPs from sagittal (n = 150) and transverse (n = 140) 3D TOF MR angiography. Measurements were compared with those from conventional angiography.Sensitivity and specificity for distinguishing 70%-99% stenosis were 96% and 78%, respectively, for sagittal MIPs, 88% and 90% for sagittal source images, 92% and 86% for transverse MIPs, and 92% and 95% for transverse source images. Areas under the receiver operating characteristic curves statistically significantly increased (P < .05) with interpretation from source images. Complete loss of intravascular signal was not encountered on source partitions except within a greater than 85% stenosis.Interpretation of source partitions rather than MIPs reduces the tendency for overestimation of stenosis with MR angiography and improves the specificity for discriminating 70%-99% stenosis.

  View details for DOI 10.1148/radiology.193.1.8090894

  View details for PubMedID 8090894

• MR gradient echo imaging of intravascular blood oxygenation: T2* determination in the presence of flow. Magnetic resonance in medicine Chien, D., Levin, D. L., Anderson, C. M. 1994; 32 (4): 540-5

  Abstract

  The T2* relaxation time of blood varies with its oxygen saturation. To evaluate the feasibility of imaging intravascular blood oxygenation in humans using a conventional 1.5T MR system, we have implemented a method to measure T2* of blood despite the presence of pulsatile flow. The method was tested in a) stationary and flow phantoms, b) blood samples at different levels of oxygen saturation, and c) a human hypoxia model. Our results demonstrate the ability of cardiac-triggered, flow compensated gradient echo imaging to obtain reproducible T2* measurements of flowing blood in vivo.

  View details for DOI 10.1002/mrm.1910320419

  View details for PubMedID 7997123

• Reflex effect of skeletal muscle mechanoreceptor stimulation on the cardiovascular system. Journal of applied physiology (Bethesda, Md. : 1985) Stebbins, C. L., Brown, B., Levin, D., Longhurst, J. C. 1988; 65 (4): 1539-47

  Abstract

  To determine the potential for mechanical stimulation of skeletal muscle to contribute to the reflex cardiovascular response to static contraction (exercise reflex), we examined the cardiovascular effects caused by either passive stretch or external pressure applied to the triceps surae muscles. First, the triceps surae were stretched to an average developed tension of 4.8 +/- 0.3 kg. This resulted in increases in mean arterial pressure (MAP) of 28 +/- 7 mmHg, dP/dt of 1,060 +/- 676 mmHg/s, and heart rate (HR) of 6 +/- 2 beats/min (P less than 0.05). Additionally, increments of 0.3, 0.5, 1.0, 2.0, 4.0, and 8.0 kg of tension produced by passive stretch elicited pressor responses of -6 +/- 1, 7 +/- 1, 16 +/- 3, 21 +/- 8, 28 +/- 6, and 54 +/- 9 mmHg, respectively. External pressure, applied with a cuff to the triceps surae to produce intramuscular pressures (125-300 mmHg) that were similar to those seen during static contraction, also elicited small increases in MAP (4 +/- 1 to 10 +/- 1 mmHg) but did not alter HR. Transection of dorsal roots L5-L7 and S1 abolished the responses to passive stretch and external pressure. Moreover, when the triceps surae were stretched passively to produce a pattern and amount of tension similar to that seen during static hindlimb contraction, a significant reflex cardiovascular response occurred. During this maneuver, the pressor response averaged 51% of that seen during contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for DOI 10.1152/jappl.1988.65.4.1539

  View details for PubMedID 3182517

• Dissociation of the stellate morphology from intracellular cyclic AMP levels in cultured rat brain astroglial cells: effects of ganglioside GM1 and lysophosphatidylserine. Journal of neurochemistry Facci, L., Skaper, S. D., Levin, D. L., Varon, S. 1987; 48 (2): 566-73

  Abstract

  Secondary microcultures of newborn rat cerebrum astroglial (AG) cells, maintained in a serum-free, chemically defined medium, were treated with various agents known to elevate intracellular cyclic AMP (cAMP) levels. Earlier studies had shown these drugs to induce a process-bearing (stellate) morphology in the AG cells, a response that was antagonized by the presence of gangliosides. One millimolar dibutyryl cyclic AMP (dBcAMP), 10 microM forskolin, 12 nM cholera toxin, and 30 microM isoproterenol all raised intracellular cAMP levels, from basal values of 3 pmol/10(6) cells to 30-30,000 pmol/10(6) cells, depending on the agent tested. dBcAMP caused the greatest elevation, and forskolin the least. The timing and/or the level of the AMP response did not precisely correlate with those of the stellation response. Values of ED50 with the four agents, as determined for the cAMP response, were always higher than stellation ED50 values in all treatments, and ED50 did not correlate with the maximal levels of cyclic AMP induced by the four agents. The capacity of ganglioside GM1 to block the stellation response to the four agents was not accompanied by a similar capacity to block the cAMP responses. Lysophosphatidylserine (lysoPS) had the capacity to induce AG cell stellation as well, without altering the basal level of cAMP. Both lysoPS and gangliosides, therefore, may act directly on the cellular machinery underlying the stellation response without involving changes in intracellular AMP.

  View details for DOI 10.1111/j.1471-4159.1987.tb04130.x

  View details for PubMedID 3025372