Quantitative Imaging Metrics for the Assessment of Pulmonary Pathophysiology: An Official American Thoracic Society and Fleischner Society Joint Workshop Report.

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.

Computer-aided quantitative bone scan assessment of prostate cancer treatment response.

OBJECTIVE: The development and evaluation of a computer-aided bone scan analysis technique to quantify changes in tumor burden and assess treatment effects in prostate cancer clinical trials. METHODS: We have developed and report on a commercial fully automated computer-aided detection (CAD) system. Using this system, scan images were intensity normalized, and then lesions were identified and segmented by anatomic region-specific intensity thresholding. Detected lesions were compared against expert markings to assess the accuracy of the CAD system. The metrics Bone Scan Lesion Area, Bone Scan Lesion Intensity, and Bone Scan Lesion Count were calculated from identified lesions, and their utility in assessing treatment effects was evaluated by analyzing before and after scans from metastatic castration-resistant prostate cancer patients: 10 treated and 10 untreated. In this study, patients were treated with cabozantinib, a MET/vascular endothelial growth factor inhibitor resulting in high rates of resolution of bone scan abnormalities. RESULTS: Our automated CAD system identified bone lesion pixels with 94% sensitivity, 89% specificity, and 89% accuracy. Significant differences in changes from baseline were found between treated and untreated groups in all assessed measurements derived by our system. The most significant measure, Bone Scan Lesion Area, showed a median (interquartile range) change from baseline at week 6 of 7.13% (27.61) in the untreated group compared with -73.76% (45.38) in the cabozantinib-treated group (P=0.0003). CONCLUSION: Our system accurately and objectively identified and quantified metastases in bone scans, allowing for interpatient and intrapatient comparison. It demonstrates potential as an objective measurement of treatment effects, laying the foundation for validation against other clinically relevant outcome measures.

Quantitative texture-based assessment of one-year changes in fibrotic reticular patterns on HRCT in scleroderma lung disease treated with oral cyclophosphamide.

OBJECTIVES: The Scleroderma Lung Study showed the efficacy of cyclophosphamide in modestly improving the forced vital capacity (FVC) compared with placebo over 1 year. Using changes in texture-based scores that quantify lung fibrosis as the percentage involvement of reticulation patterns, the effectiveness of cyclophosphamide was re-assessed by examining its impact on quantitative lung fibrosis (QLF). METHODS: Axial HRCT images were acquired (1-mm slice thickness, 10-mm increments) in the prone position at inspiration. A validated model for quantifying interstitial disease patterns was applied to images from 83 subjects at baseline and 12 months. Scores were calculated for six zones (upper, mid, lower of the right/left lung) and the whole lung. Average changes were compared. Correlations were performed between QLF and physiological and clinical scores. RESULTS: From the most severe zones identified at baseline, QLF scores decreased by 2.6% in the cyclophosphamide group, whereas they increased by 9.1% in the placebo group, leading to ~12% difference (p = 0.0027). Between-treatment difference in whole lung QLF was ~5% (p = 0.0190). Significant associations were observed between changes in QLF and FVC (r = -0.33), dyspnea score (r = -0.29), and consensus visual score (p = 0.0001). CONCLUSIONS: QLF scores provide an objective quantitative tool for assessing treatment efficacy in scleroderma-related interstitial lung disease.

Impact and costs of targeted recruitment of minorities to the National Lung Screening Trial.

BACKGROUND: To promote results in the National Lung Screening Trial (NLST) that are generalizable across the entire US population, a subset of NLST sites developed dedicated strategies for minority recruitment. PURPOSE: To report the effects of targeted strategies on the accrual of underrepresented groups, to describe participant characteristics, and to estimate the costs of targeted enrollment. METHODS: The 2002-2004 Tobacco Use Supplement was used to estimate eligible proportions of racial and ethnic categories. Strategic planning included meetings/conferences with key stakeholders and minority organizations. Potential institutions were selected based upon regional racial/ethnic diversity and proven success in recruitment of underrepresented groups. Seven institutions submitted targeted recruitment strategies with budgets. Accrual by racial/ethnic category was tracked for each institution. Cost estimates were based on itemized receipts for minority strategies relative to minority accrual. RESULTS: Of 18,842 participants enrolled, 1576 (8.4%) were minority participants. The seven institutions with targeted recruitment strategies accounted for 1223 (77.6%) of all minority participants enrolled. While there was a significant increase in the rate of minority accrual pre-implementation to post-implementation for the institutions with targeted recruitment (9.3% vs. 15.2%, p < 0.0001), there was no significant difference for the institutions without (3.5% vs. 3.8%, p = 0.46). Minority enrollees at the seven institutions tended to have less than a high school education, be economically disadvantaged, and were more often uninsured. These socio-demographic differences persisted at the seven institutions even after adjusting for race and ethnicity. The success of different strategies varied by institution, and no one strategy was successful across all institutions. Costs for implementation were also highly variable, ranging from $146 to $749 per minority enrollee. LIMITATIONS: Data on minority recruitment processes were not consistently kept at the individual institutions. In addition, participant responses via newspaper advertisements and the efforts of minority staff hired by the institutions could not be coded on Case Report Forms. CONCLUSIONS: Strategic efforts were associated with significant increases in minority enrollment. The greatest successes require that a priori goals be established based on eligible racial/ethnic proportions; the historical performance of sites in minority accrual should factor into the selection of sites; recruitment planning must begin well in advance of trial launch; and there must be endorsement by prominent representatives of the racial groups of interest.

Dose to radiosensitive organs during routine chest CT: effects of tube current modulation.

OBJECTIVE: The aims of this study were to estimate the dose to radiosensitive organs (glandular breast and lung) in patients of various sizes undergoing routine chest CT examinations with and without tube current modulation; to quantify the effect of tube current modulation on organ dose; and to investigate the relation between patient size and organ dose to breast and lung resulting from chest CT examinations. MATERIALS AND METHODS: Thirty voxelized models generated from images of patients were extended to include lung contours and were used to represent a cohort of women of various sizes. Monte Carlo simulation-based virtual MDCT scanners had been used in a previous study to estimate breast dose from simulations of a fixed-tube-current and a tube current-modulated chest CT examinations of each patient model. In this study, lung doses were estimated for each simulated examination, and the percentage organ dose reduction attributed to tube current modulation was correlated with patient size for both glandular breast and lung tissues. RESULTS: The average radiation dose to lung tissue from a chest CT scan obtained with fixed tube current was 23 mGy. The use of tube current modulation reduced the lung dose an average of 16%. Reductions in organ dose (up to 56% for lung) due to tube current modulation were more substantial among smaller patients than larger. For some larger patients, use of tube current modulation for chest CT resulted in an increase in organ dose to the lung as high as 33%. For chest CT, lung dose and breast dose estimates had similar correlations with patient size. On average the two organs receive approximately the same dose effects from tube current modulation. CONCLUSION: The dose to radiosensitive organs during fixed-tube-current and tube current-modulated chest CT can be estimated on the basis of patient size. Organ dose generally decreases with the use of tube current-modulated acquisition, but patient size can directly affect the dose reduction achieved.

Monte Carlo simulations to assess the effects of tube current modulation on breast dose for multidetector CT.

Tube current modulation was designed to reduce radiation dose in CT imaging while maintaining overall image quality. This study aims to develop a method for evaluating the effects of tube current modulation (TCM) on organ dose in CT exams of actual patient anatomy. This method was validated by simulating a TCM and a fixed tube current chest CT exam on 30 voxelized patient models and estimating the radiation dose to each patient's glandular breast tissue. This new method for estimating organ dose was compared with other conventional estimates of dose reduction. Thirty detailed voxelized models of patient anatomy were created based on image data from female patients who had previously undergone clinically indicated CT scans including the chest area. As an indicator of patient size, the perimeter of the patient was measured on the image containing at least one nipple using a semi-automated technique. The breasts were contoured on each image set by a radiologist and glandular tissue was semi-automatically segmented from this region. Previously validated Monte Carlo models of two multidetector CT scanners were used, taking into account details about the source spectra, filtration, collimation and geometry of the scanner. TCM data were obtained from each patient's clinical scan and factored into the model to simulate the effects of TCM. For each patient model, two exams were simulated: a fixed tube current chest CT and a tube current modulated chest CT. X-ray photons were transported through the anatomy of the voxelized patient models, and radiation dose was tallied in the glandular breast tissue. The resulting doses from the tube current modulated simulations were compared to the results obtained from simulations performed using a fixed mA value. The average radiation dose to the glandular breast tissue from a fixed tube current scan across all patient models was 19 mGy. The average reduction in breast dose using the tube current modulated scan was 17%. Results were size dependent with smaller patients getting better dose reduction (up to 64% reduction) and larger patients getting a smaller reduction, and in some cases the dose actually increased when using tube current modulation (up to 41% increase). The results indicate that radiation dose to glandular breast tissue generally decreases with the use of tube current modulated CT acquisition, but that patient size (and in some cases patient positioning) may affect dose reduction.

Computer-aided diagnosis in lung nodule assessment.

Computed tomography (CT) imaging is playing an increasingly important role in cancer detection, diagnosis, and lesion characterization, and it is the most sensitive test for lung nodule detection. Interpretation of lung nodules involves characterization and integration of clinical and other imaging information. Advances in lung nodule management using CT require optimization of CT data acquisition, postprocessing tools, and computer-aided diagnosis (CAD). The goal of CAD systems being developed is to both assist radiologists in the more sensitive detection of nodules and noninvasively differentiate benign from malignant lesions; the latter is important given that malignant lesions account for between 1% and 11% of pulmonary nodules. The aim of this review is to summarize the current state of the art regarding CAD techniques for the detection and characterization of solitary pulmonary nodules and their potential applications in the clinical workup of these lesions.