Prospective machine learning CT quantitative evaluation of idiopathic pulmonary fibrosis in patients undergoing anti-fibrotic treatment using low- and ultra-low-dose CT.

AIM: To compare the machine learning computed tomography (CT) quantification tool, Computer-Aided Lung Informatics for Pathology Evaluation and Ratings (CALIPER) to pulmonary function testing (PFT) in assessing idiopathic pulmonary fibrosis (IPF) for patients undergoing treatment and determine the effects of limited (LD) and ultra-low dose (ULD) CT on CALIPER performance. MATERIALS AND METHODS: Thirty-eight IPF patients underwent PFT and standard, LD, and ULD CT. CALIPER classified each CT voxel into either vessel-related structures (VRS), normal, reticular (R), honeycomb (HC) or ground-glass (GG) features. CALIPER-derived interstitial lung disease (ILD) extent represented the sum of GG, R and HC values. Repeated-measures correlation coefficient (ρrm) and 95% confidence interval (CI) evaluated CALIPER features correlation with PFT. Lin's concordance correlation coefficient (CCC) assessed concordance of CALIPER parameters across different CT dosages. RESULTS: Twenty patients completed 12 months of follow-up. CALIPER ILD correlated significantly with percent predicted (%) forced vital capacity (FVC) and forced expiratory volume in 1 second (%FEV1; p=0.004, ρrm -0.343, 95% CI [-0.547, -0.108] and 0.008, -0.321, [-0.518, -0.07], respectively). VRS significantly correlated with %FVC and %FEV1 (p=0.000, ρrm -0.491, 95% CI [-0.685, -0.251] and -0.478, 0.000, [-0.653, -0.231], respectively). There was near perfect LD and moderate ULD concordance with standard dose CT for both ILD (CCC 0.995, 95% CI 0.988-0.999 and 0.9, 0.795-0.983, respectively) and VRS (CCC 0.989, 95% CI 0.963-0.997 and 0.915, 0.806-0.956, respectively). CONCLUSIONS: CALIPER parameters correlate well with PFTs for evaluation of IPF in patients undergoing anti-fibrotic treatment without being influenced by dose variation. CALIPER may serve as a robust, objective adjunct to PFTs in assessing anti-fibrotic treatment related changes.

Immune signatures underlying post-acute COVID-19 lung sequelae.

Severe coronavirus disease 2019 (COVID-19) pneumonia survivors often exhibit long-term pulmonary sequelae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. We found that chronic lung impairment was accompanied by persistent respiratory immune alterations. We showed that functional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)­specific memory T and B cells were enriched at the site of infection compared with those of blood. Detailed evaluation of the lung immune compartment revealed that dysregulated respiratory CD8+ T cell responses were associated with the impaired lung function after acute COVID-19. Single-cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8+ T cells contributing to persistent tissue conditions after COVID-19. Our results have revealed pathophysiological and immune traits that may support the development of lung sequelae after SARS-CoV-2 pneumonia in older individuals, with implications for the treatment of chronic COVID-19 symptoms.

Automated computer-based CT stratification as a predictor of outcome in hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) has a variable clinical course. Modelling of quantitative CALIPER-derived CT data can identify distinct disease phenotypes. Mortality prediction using CALIPER analysis was compared to the interstitial lung disease gender, age, physiology (ILD-GAP) outcome model. METHODS: CALIPER CT analysis of parenchymal patterns in 98 consecutive HP patients was compared to visual CT scoring by two radiologists. Functional indices including forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco) in univariate and multivariate Cox mortality models. Automated stratification of CALIPER scores was evaluated against outcome models. RESULTS: Univariate predictors of mortality included visual and CALIPER CT fibrotic patterns, and all functional indices. Multivariate analyses identified only two independent predictors of mortality: CALIPER reticular pattern (p = 0.001) and DLco (p < 0.0001). Automated stratification distinguished three distinct HP groups (log-rank test p < 0.0001). Substitution of automated stratified groups for FVC and DLco in the ILD-GAP model demonstrated no loss of model strength (C-Index = 0.73 for both models). Model strength improved when automated stratified groups were combined with the ILD-GAP model (C-Index = 0.77). CONCLUSIONS: CALIPER-derived variables are the strongest CT predictors of mortality in HP. Automated CT stratification is equivalent to functional indices in the ILD-GAP model for predicting outcome in HP. KEY POINTS: • Computer CT analysis better predicts mortality than visual CT analysis in HP. • Quantitative CT analysis is equivalent to functional indices for prognostication in HP. • Prognostication using the ILD-GAP model improves when combined with quantitative CT analysis.

Asymptomatic and unrecognized cement pulmonary embolism commonly occurs with vertebroplasty.

BACKGROUND AND PURPOSE: Cement PE represents a potentially serious complication following vertebroplasty. To determine the frequency and extent of cement PE during percutaneous vertebroplasty, we performed a retrospective review of chest CT scans obtained in patients who had previously undergone ≥1 vertebroplasty procedure. MATERIALS AND METHODS: After approval by our local institutional review board, we retrospectively evaluated 244 patients who had undergone vertebroplasty at 465 levels and subsequently underwent chest CT. A thoracic radiologist evaluated the presence, number, size, and location of discrete cement PEs. We catalogued the following data: age, sex, number of treated vertebrae, cement volume per vertebra, operator, presence of cement leakage noted by the operator during the procedure, and clinical presentation at postvertebroplasty CT. RESULTS: At least 1 cement PE was detected in 23 (9.4%; 95% CI, 6%-13%) of 244 patients; 1 patient was symptomatic from a cement PE. The mean number of discrete cement PEs was 3.2 ± 3.4 (median, 2; range, 1-12). There was no correlation among the total number of treatment sessions, number of levels treated per session, cement volume per level, operator, or time between vertebroplasty and chest CT in the detection of cement PE. Those with PE were significantly younger (P=.0229) and had significantly more total levels treated (P=.0260). Cement PE was recognized by the operator during the vertebroplasty in 2 (8.7%) of 23 patients found to have it on CT. CONCLUSIONS: Small asymptomatic cement PEs are common during vertebroplasty and usually are not recognized by the operator during the procedure.

Iodixanol compared to iohexol for contrast procedures: a case-matched retrospective cohort study.

BACKGROUND: Previous studies that have attempted to evaluate the effectiveness of an iso-osmolar contrast medium (IOCM) iodixanol compared to a low-osmolar contrast medium (LOCM) for contrast procedures show variable results. PURPOSE: To evaluate the nephrotoxicity of the IOCM iodixanol compared to the LOCM iohexol. MATERIAL AND METHODS: We performed a retrospective cohort study from April 2004 to March 2006. All contrast procedures with a pre- and post-exposure creatinine value were evaluated for inclusion. Contrast nephropathy (CN) was defined as post-exposure creatinine elevation of > or = 25% or > 0.5 mg/dl within 7 days of contrast exposure. Cases of iodixanol exposure were matched to control cases of iohexol exposure (1:1) based on age, sex, presence of diabetes, pre-exposure creatinine value, and type of imaging study performed. We matched 397 cases of iodixanol (IOCM) exposure to 397 cases of iohexol (LOCM) exposure. Cases of iodixanol which could not be matched to controls were not included in the analysis. RESULTS: After adjustment for prior creatinine, medications, contrast iodine load, prior exposure to contrast material, heart failure, and hypertension, use of iodixanol did not significantly alter rates of CN compared to iohexol (OR 0.92, 95% CI 0.57-1.46; P = 0.71) or mortality (RR 0.79, 95% CI 0.59-1.06; P = 0.12). CONCLUSION: The use of the IOCM iodixanol was not associated with statistically significant protection against contrast nephropathy or all-cause mortality compared to a matched cohort of patients receiving the LOCM iohexol.

Quantitative characterization of lung disease.

The increase in prevalence, incidence and variety of pulmonary diseases has precipitated the need for more non-invasive quantitative assessment of structure/function relationships in the lung. This need requires concise description not only of lung anatomy but also of associated underlying mechanics of pulmonary function, as well as deviation from normal in specific diseases. This can be facilitated through the use of adaptive deformable surface models of the lung at end inspiratory and expiratory volumes. Lung surface deformation may be used to represent tissue excursion, which can characterize both global and regional lung mechanics. In this paper, we report a method for robust determination and visualization of pulmonary structure and function using clinical CT scans. The method provides both intuitive 3D parametric visualization and objective quantitative assessment of lung structure and associated function, in both normal and pathological cases.

Radiographic anatomy: multimedia interactive instructional software on CD-ROM.

OBJECTIVE: We wanted to create a filmless radiographic anatomy curriculum, a didactic software with a digital image database on CD-ROM for first-year medical students. CONCLUSION: We created a CD-ROM that includes an introduction, radiographic anatomy tutorial, and interactive questions. Additional features include Boolean text searching, links to related images, and Internet accessibility. The software can be updated.

Clinical correlations of immunophenotypic variations and the presence of trisomy 12 in B-cell chronic lymphocytic leukemia.

In a prospective study of 93 consecutive untreated patients with B-cell chronic lymphocytic leukemia, we examined the clinical relevance of surface immunoglobulin (sIg) heavy chain (HC) and light chain (LC) isotypes, CD11c or CD25 expression, and the presence of trisomy 12 by fluorescence in situ hybridization (FISH). Careful morphologic evaluation was performed to exclude patients with other forms of chronic lymphoid leukemias, including mantle cell lymphoma, prolymphocytic leukemia, and leukemia phase of lymphoma. In addition, clonally restricted sIg and CD5 surface determinant were expressed in all patients. Clinical presentation, including blood cell counts, clinical stage, and organomegaly, did not correlate with any of the measured variables. After a median follow-up period of 3 years, the particular HC or LC isotype or CD11c expression did not correlate with either disease progression or treatment-free survival. However, trisomy 12 and CD25 expressions were both associated with accelerated disease progression and a shorter treatment-free survival time. Our results confirm the adverse prognostic significance of trisomy 12 expression in chronic lymphocytic leukemia and suggest that CD25 expression may have an unfavorable clinical impact.

Heterogeneity and clinical relevance of the intensity of CD20 and immunoglobulin light-chain expression in B-cell chronic lymphocytic leukemia.

In a prospective study, peripheral lymphocytes of 93 previously untreated patients with B-cell chronic lymphocytic leukemia (B-CLL) were evaluated with flow cytometry for the intensity of CD20 and surface immunoglobulin (sIg) light-chain (LC) expression. Molecules of equivalent soluble fluorescence were used to classify intensity of surface antigen expression as "strong," "moderate," or "weak." Despite reproducible morphological consistency with B-CLL, variability in intensity of CD20 and sIg light chain expression was substantial. CD20 intensity was classified as weak in 62% of patients, moderate in 12%, and strong in 26%. Expression of sIg light chain was weak in 76% and strong in 24%. The patients were followed up for a median of 3.1 years. Intensity of expression of CD20 and sIg light chain was not correlated with any presenting feature at the time of phenotyping, including clinical stage and degree of lymphocytosis or organomegaly. Similarly, clinical course of the disease, time to progression, response to therapy, and overall and treatment-free survival were not predictable from the intensity of CD20 or sIg light chain expression. In conclusion, bright expression of CD20 or sIg light chain is not an unusual feature in B-CLL and may not influence clinical presentation or short-term prognosis.