Imaging of Pulmonary Fibrosis: An Update, From the AJR Special Series on Imaging of Fibrosis.

Pulmonary fibrosis is recognized as occurring in association with a wide and increasing array of conditions, and it presents with a spectrum of chest CT appearances. Idiopathic pulmonary fibrosis (IPF), which corresponds histologically with usual interstitial pneumonia and represents the most common idiopathic interstitial pneumonia, is a chronic progressive fibrotic interstitial lung disease (ILD) of unknown cause. Progressive pulmonary fibrosis (PPF) describes the radiologic development of pulmonary fibrosis in patients with ILD of a known or unknown cause other than IPF. The recognition of PPF impacts management of patients with ILD-for example, in guiding initiation of antifibrotic therapy. Interstitial lung abnormalities are an incidental CT finding in patients without suspected ILD and may represent an early intervenable form of pulmonary fibrosis. Traction bronchiectasis and/or bronchiolectasis, when detected in the setting of chronic fibrosis, is generally considered evidence of irreversible disease, and progression predicts worsening mortality risk. Awareness of the association between pulmonary fibrosis and connective tissue diseases, particularly rheumatoid arthritis, is increasing. This review provides an update on the imaging of pulmonary fibrosis, with attention given to recent advances in disease understanding with relevance to radiologic practice. The essential role of a multidisciplinary approach to clinical and radiologic data is highlighted.

Suspected Interstitial Lung Disease in COPDGene Study.

Rationale: Although interstitial lung abnormalities (ILA), specific patterns of incidentally-detected abnormal density on computed tomography, have been associated with abnormal lung function and increased mortality, it is unclear if a subset with incidental interstitial lung disease (ILD) accounts for these adverse consequences. Objectives: To define the prevalence and risk factors of suspected ILD and assess outcomes. Methods: Suspected ILD was evaluated in the COPDGene (Chronic Obstructive Pulmonary Disease Genetic Epidemiology) study, defined as ILA and at least one additional criterion: definite fibrosis on computed tomography, FVC less than 80% predicted, or DLCO less than 70% predicted. Multivariable linear, longitudinal, and Cox proportional hazards regression models were used to assess associations with St. George's Respiratory Questionnaire, 6-minute-walk test, supplemental oxygen use, respiratory exacerbations, and mortality. Measurements and Main Results: Of 4,361 participants with available data, 239 (5%) had evidence for suspected ILD, whereas 204 (5%) had ILA without suspected ILD. In multivariable analyses, suspected ILD was associated with increased St. George's Respiratory Questionnaire score (mean difference [MD], 3.9 points; 95% confidence interval [CI], 0.6-7.1; P = 0.02), reduced 6-minute-walk test (MD, -35 m; 95% CI, -56 m to -13 m; P = 0.002), greater supplemental oxygen use (odds ratio [OR], 2.3; 95% CI, 1.1-5.1; P = 0.03) and severe respiratory exacerbations (OR, 2.9; 95% CI, 1.1-7.5; P = 0.03), and higher mortality (hazard ratio, 2.4; 95% CI, 1.2-4.6; P = 0.01) compared with ILA without suspected ILD. Risk factors associated with suspected ILD included self-identified Black race (OR, 2.0; 95% CI, 1.1-3.3; P = 0.01) and pack-years smoking history (OR, 1.2; 95% CI, 1.1-1.3; P = 0.0005). Conclusions: Suspected ILD is present in half of those with ILA in COPDGene and is associated with exercise decrements and increased symptoms, supplemental oxygen use, severe respiratory exacerbations, and mortality.

Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers.

OBJECTIVE: To investigate the prevalence and mortality impact of interstitial lung abnormalities (ILAs) in RA and non-RA comparators. METHODS: We analysed associations between ILAs, RA, and mortality in COPDGene, a multicentre prospective cohort study of current and past smokers, excluding known interstitial lung disease (ILD) or bronchiectasis. All participants had research chest high-resolution CT (HRCT) reviewed by a sequential reading method to classify ILA as present, indeterminate or absent. RA cases were identified by self-report RA and DMARD use; non-RA comparators had neither an RA diagnosis nor used DMARDs. We examined the association and mortality risk of RA and ILA using multivariable logistic regression and Cox regression. RESULTS: We identified 83 RA cases and 8725 non-RA comparators with HRCT performed for research purposes. ILA prevalence was 16.9% in RA cases and 5.0% in non-RA comparators. After adjusting for potential confounders, including genetics, current/past smoking and other lifestyle factors, ILAs were more common among those with RA compared with non-RA [odds ratio 4.76 (95% CI 2.54, 8.92)]. RA with ILAs or indeterminate for ILAs was associated with higher all-cause mortality compared with non-RA without ILAs [hazard ratio (HR) 3.16 (95% CI 2.11, 4.74)] and RA cases without ILA [HR 3.02 (95% CI 1.36, 6.75)]. CONCLUSIONS: In this cohort of smokers, RA was associated with ILAs and this persisted after adjustment for current/past smoking and genetic/lifestyle risk factors. RA with ILAs in smokers had a 3-fold increased all-cause mortality, emphasizing the importance of further screening and treatment strategies for preclinical ILD in RA.

Bronchial epithelial gene expression and interstitial lung abnormalities.

INTRODUCTION: Interstitial lung abnormalities (ILA) often represent early fibrotic changes that can portend a progressive fibrotic phenotype. In particular, the fibrotic subtype of ILA is associated with increased mortality and rapid decline in lung function. Understanding the differential gene expression that occurs in the lungs of participants with fibrotic ILA may provide insight into development of a useful biomarker for early detection and therapeutic targets for progressive pulmonary fibrosis. METHODS: Measures of ILA and gene expression data were available in 213 participants in the Detection of Early Lung Cancer Among Military Personnel (DECAMP1 and DECAMP2) cohorts. ILA was defined using Fleischner Society guidelines and determined by sequential reading of computed tomography (CT) scans. Primary analysis focused on comparing gene expression in ILA with usual interstitial pneumonia (UIP) pattern with those with no ILA. RESULTS: ILA was present in 51 (24%) participants, of which 16 (7%) were subtyped as ILA with a UIP pattern. One gene, pro platelet basic protein (PPBP) and seventeen pathways (e.g. TNF-α signalling) were significantly differentially expressed between those with a probable or definite UIP pattern of ILA compared to those without ILA. 16 of these 17 pathways, but no individual gene, met significance when comparing those with ILA to those without ILA. CONCLUSION: Our study demonstrates that abnormal inflammatory processes are apparent in the bronchial airway gene expression profiles of smokers with and without lung cancer with ILA. Future studies with larger and more diverse populations will be needed to confirm these findings.

The Proteomic Profile of Interstitial Lung Abnormalities.

Rationale: Knowledge on biomarkers of interstitial lung disease is incomplete. Interstitial lung abnormalities (ILAs) are radiologic changes that may present in its early stages. Objectives: To uncover blood proteins associated with ILAs using large-scale proteomics methods. Methods: Data from two prospective cohort studies, the AGES-Reykjavik (Age, Gene/Environment Susceptibility-Reykjavik) study (N = 5,259) for biomarker discovery and the COPDGene (Genetic Epidemiology of COPD) study (N = 4,899) for replication, were used. Blood proteins were measured using DNA aptamers, targeting more than 4,700 protein analytes. The association of proteins with ILAs and ILA progression was assessed with regression modeling, as were associations with genetic risk factors. Adaptive Least Absolute Shrinkage and Selection Operator models were applied to bootstrap data samples to discover sets of proteins predictive of ILAs and their progression. Measurements and Main Results: Of 287 associations, SFTPB (surfactant protein B) (odds ratio [OR], 3.71 [95% confidence interval (CI), 3.20-4.30]; P = 4.28 × 10-67), SCGB3A1 (Secretoglobin family 3A member 1) (OR, 2.43 [95% CI, 2.13-2.77]; P = 8.01 × 10-40), and WFDC2 (WAP four-disulfide core domain protein 2) (OR, 2.42 [95% CI, 2.11-2.78]; P = 4.01 × 10-36) were most significantly associated with ILA in AGES-Reykjavik and were replicated in COPDGene. In AGES-Reykjavik, concentrations of SFTPB were associated with the rs35705950 MUC5B (mucin 5B) promoter polymorphism, and SFTPB and WFDC2 had the strongest associations with ILA progression. Multivariate models of ILAs in AGES-Reykjavik, ILAs in COPDGene, and ILA progression in AGES-Reykjavik had validated areas under the receiver operating characteristic curve of 0.880, 0.826, and 0.824, respectively. Conclusions: Novel, replicated associations of ILA, its progression, and genetic risk factors with numerous blood proteins are demonstrated as well as machine-learning-based models with favorable predictive potential. Several proteins are revealed as potential markers of early fibrotic lung disease.

Traction Bronchiectasis/Bronchiolectasis on CT Scans in Relationship to Clinical Outcomes and Mortality: The COPDGene Study.

Background The clinical impact of interstitial lung abnormalities (ILAs) on poor prognosis has been reported in many studies, but risk stratification in ILA will contribute to clinical practice. Purpose To investigate the association of traction bronchiectasis/bronchiolectasis index (TBI) with mortality and clinical outcomes in individuals with ILA by using the COPDGene cohort. Materials and Methods This study was a secondary analysis of prospectively collected data. Chest CT scans of participants with ILA for traction bronchiectasis/bronchiolectasis were evaluated and outcomes were compared with participants without ILA from the COPDGene study (January 2008 to June 2011). TBI was classified as follows: TBI-0, ILA without traction bronchiectasis/bronchiolectasis; TBI-1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; TBI-2, ILA with mild to moderate traction bronchiectasis; and TBI-3, ILA with severe traction bronchiectasis and/or honeycombing. Clinical outcomes and overall survival were compared among the TBI groups and the non-ILA group by using multivariable linear regression model and Cox proportional hazards model, respectively. Results Overall, 5295 participants (median age, 59 years; IQR, 52-66 years; 2779 men) were included, and 582 participants with ILA and 4713 participants without ILA were identified. TBI groups were associated with poorer clinical outcomes such as quality of life scores in the multivariable linear regression model (TBI-0: coefficient, 3.2 [95% CI: 0.6, 5.7; P = .01]; TBI-1: coefficient, 3.3 [95% CI: 1.1, 5.6; P = .003]; TBI-2: coefficient, 7.6 [95% CI: 4.0, 11; P < .001]; TBI-3: coefficient, 32 [95% CI: 17, 48; P < .001]). The multivariable Cox model demonstrated that ILA without traction bronchiectasis (TBI-0-1) and with traction bronchiectasis (TBI-2-3) were associated with shorter overall survival (TBI-0-1: hazard ratio [HR], 1.4 [95% CI: 1.0, 1.9; P = .049]; TBI-2-3: HR, 3.8 [95% CI: 2.6, 5.6; P < .001]). Conclusion Traction bronchiectasis/bronchiolectasis was associated with poorer clinical outcomes compared with the group without interstitial lung abnormalities; TBI-2 and 3 were associated with shorter survival. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee and Im in this issue.

Blood gene expression risk profiles and interstitial lung abnormalities: COPDGene and ECLIPSE cohort studies.

BACKGROUND: Interstitial lung abnormalities (ILA) are radiologic findings that may progress to idiopathic pulmonary fibrosis (IPF). Blood gene expression profiles can predict IPF mortality, but whether these same genes associate with ILA and ILA outcomes is unknown. This study evaluated if a previously described blood gene expression profile associated with IPF mortality is associated with ILA and all-cause mortality. METHODS: In COPDGene and ECLIPSE study participants with visual scoring of ILA and gene expression data, we evaluated the association of a previously described IPF mortality score with ILA and mortality. We also trained a new ILA score, derived using genes from the IPF score, in a subset of COPDGene. We tested the association with ILA and mortality on the remainder of COPDGene and ECLIPSE. RESULTS: In 1469 COPDGene (training n = 734; testing n = 735) and 571 ECLIPSE participants, the IPF score was not associated with ILA or mortality. However, an ILA score derived from IPF score genes was associated with ILA (meta-analysis of test datasets OR 1.4 [95% CI: 1.2-1.6]) and mortality (HR 1.25 [95% CI: 1.12-1.41]). Six of the 11 genes in the ILA score had discordant directions of effects compared to the IPF score. The ILA score partially mediated the effects of age on mortality (11.8% proportion mediated). CONCLUSIONS: An ILA gene expression score, derived from IPF mortality-associated genes, identified genes with concordant and discordant effects on IPF mortality and ILA. These results suggest shared, and unique biologic processes, amongst those with ILA, IPF, aging, and death.

Interstitial Lung Abnormalities at CT: Subtypes, Clinical Significance, and Associations with Lung Cancer.

Interstitial lung abnormality (ILA) is defined as an interstitial change detected incidentally on CT images. It is seen in 4%-9% of smokers and 2%-7% of nonsmokers. ILA has a tendency to progress with time and is associated with respiratory symptoms, decreased exercise capability, reduced pulmonary function, and increased mortality. ILAs can be classified into three subcategories: nonsubpleural, subpleural nonfibrotic, and subpleural fibrotic. In cases of ILA, clinically significant interstitial lung disease should be identified and requires clinically driven management by a pulmonologist. Risk factors for the progression of ILA include clinical elements (ie, inhalation exposures, medication use, radiation therapy, thoracic surgery, physiologic findings, and gas exchange findings) and radiologic elements (ie, basal and peripheral predominance and fibrotic findings). It is recommended that individuals with one or more clinical or radiologic risk factors for progression of ILA be actively monitored with pulmonary function testing and CT. To avoid overcalling ILA at CT, radiologists must recognize the imaging pitfalls, including centrilobular nodularity, dependent abnormality, suboptimal inspiration, osteophyte-related lesions, apical cap and pleuroparenchymal fibroelastosis-like lesions, aspiration, and infection. There is a close association between ILA and lung cancer, and many studies have reported an increased incidence of lung cancer, worse prognoses, and/or increased pulmonary complications in relation to cancer treatment in patients with ILA. ILA is considered to be an important comorbidity in patients with lung cancer. Accordingly, all radiologists involved with body CT must have sound knowledge of ILAs owing to the high prevalence and potential clinical significance of these anomalies. An overview of ILAs, including a literature review of the associations between ILAs and lung cancer, is presented. ©RSNA, 2022.

Interstitial Lung Abnormalities in Patients With Locally Advanced Esophageal Cancer: Prevalence, Risk Factors, and Clinical Implications.

PURPOSE: Interstitial lung abnormalities (ILAs) represent nondependent abnormalities on chest computed tomography (CT) indicating lung parenchymal damages due to inflammation and fibrosis. Interstitial lung abnormalities have been studied as a predictor of clinical outcome in lung cancer, but not in other thoracic malignancies. The present study investigated the prevalence of ILA in patients with esophageal cancer and identified risk factors and clinical implications of ILA in these patients. METHODS: The study included 208 patients with locally advanced esophageal cancer (median age, 65.6 years; 166 males, 42 females). Interstitial lung abnormality was scored on baseline CT scans before treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA). Clinical characteristics and overall survival were compared in patients with ILA (score 2) and others. RESULTS: An ILA was present in 14 of 208 patients (7%) with esophageal cancer on pretreatment chest CT. Patients with ILA were significantly older (median age, 69 vs 65, respectively; P = 0.011), had a higher number of pack-years of smoking ( P = 0.02), and more commonly had T4 stage disease ( P = 0.026) than patients with ILA score of 1 or 0. Interstitial lung abnormality on baseline scan was associated with a lack of surgical resection after chemoradiotherapy (7/14, 50% vs 39/194, 20% respectively; P = 0.016). Interstitial lung abnormality was not associated with overall survival (log-rank P = 0.75, Cox P = 0.613). CONCLUSIONS: An ILA was present in 7% of esophageal cancer patients, which is similar to the prevalence in general population and in smokers. Interstitial lung abnormality was strongly associated with a lack of surgical resection after chemoradiotherapy, indicating an implication of ILA in treatment selection in these patients, which can be further studied in larger cohorts.

Characterization of parotid gland tumors: added value of permeability MR imaging to DWI and DCE-MRI.

OBJECTIVES: To determine added value of permeability MRI in parotid tumor characterization to T2-weighted imaging (T2WI), semi-quantitative analysis of time-intensity curve (TIC), and intra-voxel incoherent motion diffusion-weighted imaging (IVIM-DWI). METHODS: This retrospective study was approved by the institutional review board, and the informed consent was waived. Sixty-one parotid tumors in 61 patients were examined using T2WI, IVIM-DWI, and permeability MRI. TIC patterns were categorized as persistent, washout, or plateau. Signal intensity ratio of lesion-to-muscle on T2WI, apparent diffusion coefficients (ADCs), D and f values from IVIM-DWI, and Ktrans, kep, Ve, and Vp values from permeability MRI were measured. Multiple comparisons were applied to determine whether any differences among 4 histopathologic types (pleomorphic adenomas, Warthin's tumors, other benign tumors, and malignant tumors) existed. Diagnostic accuracy was compared before and after modification diagnosis referring to permeability MRI. In a validation study, 60 parotid tumors in 60 patients were examined. RESULTS: ADC and D values of malignant tumors were significantly lower than those of benign tumors other than Warthin's tumors, but higher than those of Warthin's tumors. kep and Vp values of Warthin's tumors were significantly higher than those of malignant tumors. Multivariate analyses showed that TIC pattern, D, and kep values were suitable parameters. McNemar's test showed a significant increase of sensitivity (11/12, 92%) and specificity (46/49, 94%) with adding kep. The validation study yielded high sensitivity (14/16, 88%) and specificity (41/44, 93%). CONCLUSION: Permeability MRI offers added value to IVIM-MRI and semi-quantitative TIC analysis of DCE-MRI in characterization of parotid tumors KEY POINTS: • Permeability MR imaging offers added value in the characterization of parotid gland tumors in combination with semi-quantitative TIC analysis and IVIM analyses with D parameter. • The combination of TIC pattern, D, and kep might facilitate accurate characterization of parotid gland tumor, thereby avoiding unnecessary surgery for benign tumors or delayed treatment for malignant tumors. • A combination of permeability and diffusion MR imaging can be used to guide the selection of an appropriate biopsy site.

Clinical usefulness of right ventricular 3D area strain in the assessment of treatment effects of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: comparison with 2D feature-tracking MRI.

OBJECTIVES: To evaluate the usefulness of right ventricular (RV) area strain analysis via cardiac MRI (CMRI) as a tool for assessing the treatment effects of balloon pulmonary angioplasty (BPA) in inoperable chronic thromboembolic pulmonary hypertension (CTEPH), RV area strain was compared to two-dimensional (2D) strain with feature-tracking MRI (FTMRI) before and after BPA. METHODS: We retrospectively analyzed 21 CTEPH patients who underwent BPA. End-systolic global area strain (GAS), longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) were measured before and after BPA. Changes in GAS and RV ejection fraction (RVEF) values after BPA were defined as ΔGAS and ΔRVEF. Receiver operating characteristic (ROC) analyses were performed to determine the optimal cutoff of the strain at after BPA for detection of improved patients with decreased mean pulmonary artery pressure (mPAP) less than 30 mmHg and increased RVEF more than 50%. RESULTS: ROC analysis revealed the optimal cutoffs of strains (GAS, LS, CS, and RS) for identifying improved patients with mPAP < 30 mmHg (cutoff (%) = - 41.2, - 13.8, - 16.7, and 14.4: area under the curve, 0.75, 0.56, 0.65, and 0.75) and patients with RVEF > 50% (cutoff (%) = - 37.2, - 29.5, - 2.9, and 14.4: area under the curve, 0.81, 0.60, 0.56, and 0.56). CONCLUSIONS: Area strain analysis via CMRI may be a more useful tool for assessing the treatment effects of BPA in patients with CTEPH than 2D strains with FTMRI. KEY POINTS: • Area strain values can detect improvement of right ventricular (RV) pressure and function after balloon pulmonary angioplasty (BPA) equally or more accurately than two-dimensional strains. • Area strain analysis is a useful analytical method that reflects improvements in complex RV myocardial deformation by BPA. • Area strain analysis is a robust method with reproducibility equivalent to that of 2D strain analysis.

Assessment of pulmonary function in COPD patients using dynamic digital radiography: A novel approach utilizing lung signal intensity changes during forced breathing.

Objectives: To investigate the association of lung signal intensity changes during forced breathing using dynamic digital radiography (DDR) with pulmonary function and disease severity in patients with chronic obstructive pulmonary disease (COPD). Methods: This retrospective study included 46 healthy subjects and 33 COPD patients who underwent posteroanterior chest DDR examination. We collected raw signal intensity and gray-scale image data. The lung contour was extracted on the gray-scale images using our previously developed automated lung field tracking system and calculated the average of signal intensity values within the extracted lung contour on gray-scale images. Lung signal intensity changes were quantified as SImax/SImin, representing the maximum ratio of the average signal intensity in the inspiratory phase to that in the expiratory phase. We investigated the correlation between SImax/SImin and pulmonary function parameters, and differences in SImax/SImin by disease severity. Results: SImax/SImin showed the highest correlation with VC (rs = 0.54, P < 0.0001), followed by FEV1 (rs = 0.44, P < 0.0001), both of which are key indicators of COPD pathophysiology. In a multivariate linear regression analysis adjusted for confounding factors, SImax/SImin was significantly lower in the severe COPD group compared to the normal group (P = 0.0004) and mild COPD group (P=0.0022), suggesting its potential usefulness in assessing COPD severity. Conclusion: This study suggests that the signal intensity changes of lung fields during forced breathing using DDR reflect the pathophysiology of COPD and can be a useful index in assessing pulmonary function in COPD patients, potentially improving COPD diagnosis and management.

Dynamic chest radiography for pulmonary vascular diseases: clinical applications and correlation with other imaging modalities.

Dynamic chest radiography (DCR) is a novel functional radiographic imaging technique that can be used to visualize pulmonary perfusion without using contrast media. Although it has many advantages and clinical utility, most radiologists are unfamiliar with this technique because of its novelty. This review aims to (1) explain the basic principles of lung perfusion assessment using DCR, (2) discuss the advantages of DCR over other imaging modalities, and (3) review multiple specific clinical applications of DCR for pulmonary vascular diseases and compare them with other imaging modalities.

Prediction Model for Tumor Volume Nadir in EGFR -mutant NSCLC Patients Treated With EGFR Tyrosine Kinase Inhibitors.

PURPOSE: In patients with advanced non-small cell lung cancer (NSCLC) and oncogenic driver mutations treated with effective targeted therapy, a characteristic pattern of tumor volume dynamics with an initial regression, nadir, and subsequent regrowth is observed on serial computed tomography (CT) scans. We developed and validated a linear model to predict the tumor volume nadir in EGFR -mutant advanced NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKI). MATERIALS AND METHODS: Patients with EGFR -mutant advanced NSCLC treated with EGFR-TKI as their first EGFR-directed therapy were studied for CT tumor volume kinetics during therapy, using a previously validated CT tumor measurement technique. A linear regression model was built to predict tumor volume nadir in a training cohort of 34 patients, and then was validated in an independent cohort of 84 patients. RESULTS: The linear model for tumor nadir prediction was obtained in the training cohort of 34 patients, which utilizes the baseline tumor volume before initiating therapy (V 0 ) to predict the volume decrease (mm 3 ) when the nadir volume (V p ) was reached: V 0 -V p =0.717×V 0 -1347 ( P =2×10 -16 ; R2 =0.916). The model was tested in the validation cohort, resulting in the R2 value of 0.953, indicating that the prediction model generalizes well to another cohort of EGFR -mutant patients treated with EGFR-TKI. Clinical variables were not significant predictors of tumor volume nadir. CONCLUSION: The linear model was built to predict the tumor volume nadir in EGFR -mutant advanced NSCLC patients treated with EGFR-TKIs, which provide an important metrics in treatment monitoring and therapeutic decisions at nadir such as additional local abrasive therapy.

Amide proton transfer (APT) imaging of breast cancers and its correlation with biological status.

PURPOSE: To assess the usefulness of amide proton transfer (APT) imaging to predict the biological status of breast cancers. METHOD: Sixty-six patients (age range 31-85 years, mean 58.9 years) with histopathologically proven invasive ductal carcinomas of 2 cm or larger in diameter were included in this study. 3D APT weighted imaging was conducted on a 3 T scanner. Mean APT signal intensity (SI) was analyzed in relation to biological subtypes, Ki-67 labeling index, and nuclear grades (NGs). RESULTS: The triple-negative (TN) cancers (n = 10; 2.75 ± 0.42%) showed significantly higher APT SI than the luminal type cancers (n = 48; 1.74 ± 0.83) and HER2 cancers (n = 8; 1.83 ± 0.21) (P = 0.0007, 0.03). APT SI had weakly positive correlation with the Ki-67 labeling index (r = 0.38, P = 0.002). The mean APT SIs were significantly higher for high-Ki-67 (>30%) (n = 31; 2.25 ± 0.70) than low-Ki-67 (≤30%) cancers (n = 35; 1.60 ± 0.79) (P = 0.0007). There was no significant difference in the APT SIs between NG 1-2 (n = 31; 1.71 ± 0.84) and NG 3 (n = 35; 2.08 ± 0.76%) cancers (P = 0.06). CONCLUSIONS: TN and high-Ki-67 breast cancers showed high APT SIs. APT imaging can help to predict the biological status of breast cancers.

Virtual monochromatic spectral CT imaging in preoperative evaluations for intraductal spread of breast cancer: comparison with conventional CT and MRI.

PURPOSE: To investigate the efficacy of virtual monochromatic spectral computed tomography imaging (VMI) in the preoperative evaluation for intraductal spread of breast cancer. MATERIALS AND METHODS: Twenty-four women who underwent spectral CT and were pathologically diagnosed with ductal carcinoma with a ≥ 2-cm noninvasive component were retrospectively enrolled in Group 1. Twenty-two women with 22 lesions pathologically diagnosed with ductal carcinoma in situ or microinvasive carcinoma were enrolled in Group 2. We compared the contrast-to-noise ratios (CNRs) of the lesions on conventional 120-kVp CT images and 40-keV VMIs in Group 1. Two board-certified radiologists measured the maximum diameters of enhancing areas on 120-kVp CT, 40-keV VMI, and MRI in Group 2 and compared with histopathological sizes. RESULTS: The quantitative assessment of Group 1 revealed that the mean ± SD of the CNRs in the 40-keV images were significantly greater than those in the 120-kVp images (5.5 ± 1.9 vs. 3.6 ± 1.5, p < 0.0001). The quantitative assessment of Group 2 demonstrated that the lesion size observed in the conventional 120-kVp CT images by both readers was significantly underestimated as compared to the histopathological size (p = 0.017, 0.048), whereas both readers identified no significant differences between the lesion size measured on 40-keV VMI and the histopathological data. In a comparison with MRI, 40-keV VMI provided measurement within a 10-mm error range in more lesions as compared to the conventional 120-kVp CT. CONCLUSION: VMI improves the evaluation of intraductal spread and is useful for the preoperative evaluations of breast cancer.

Tumor Volume Nadir in Patients With ALK-Rearranged Non-Small-Cell Lung Cancer Treated With Alectinib.

PURPOSE: Patients with oncogene-driven advanced non-small-cell lung cancer (NSCLC) treated with effective targeted therapy demonstrate characteristic tumor volume dynamics with initial response, nadir, and subsequent regrowth. This study investigated tumor volume nadir and time to nadir in patients with ALK-rearranged advanced NSCLC treated with alectinib. MATERIALS AND METHODS: In patients with advanced ALK-rearranged NSCLC treated with alectinib monotherapy, tumor volume dynamics were evaluated on serial computed tomography (CT) scans using a previously validated CT tumor measurement technique. A linear regression model was built to predict tumor volume nadir. Time-to-event analyses were performed to evaluate time to nadir. RESULTS: Among 45 patients who experienced initial volume decrease, 37 patients (25 with tumor regrowth and 12 without regrowth but >6 months follow-up) were studied for nadir volume (Vp). The linear model to predict tumor volume nadir was built using the baseline tumor volume (V0): V0-Vp = .696 × V0 + 5,326 (P < 2 × 10-16; adjusted R2 = 0.86). The percent volume changes at nadir (median, -90.9%, mean, -85.3%) showed larger decrease in patients who were treated with alectinib as first-line therapy than in the ≥2nd-line group and were independent of V0 and clinical variables. Time to nadir had a median of 11.5 months and was longer in the first-line group (P = .04). CONCLUSION: The tumor nadir volume in patients with ALK-rearranged advanced NSCLC treated with alectinib can be predicted by the liner regression model and consists of approximately 30% of the baseline volume minus 5 cm3, providing additional insights into precision therapy monitoring and potential guides for local ablative therapy to prolong disease control.

Incidence and severity of pulmonary embolism in COVID-19 infection: Ancestral, Alpha, Delta, and Omicron variants.

Little information is available regarding incidence and severity of pulmonary embolism (PE) across the periods of ancestral strain, Alpha, Delta, and Omicron variants. The aim of this study is to investigate the incidence and severity of PE over the dominant periods of ancestral strain and Alpha, Delta, and Omicron variants. We hypothesized that the incidence and the severity by proximity of PE in patients with the newer variants and vaccination would be decreased compared with those in ancestral and earlier variants. Patients with COVID-19 diagnosis between March 2020 and February 2022 and computed tomography pulmonary angiogram performed within a 6-week window around the diagnosis (-2 to +4 weeks) were studied retrospectively. The primary endpoints were the associations of the incidence and location of PE with the ancestral strain and each variant. Of the 720 coronavirus disease 2019 patients with computed tomography pulmonary angiogram (58.6 ± 17.2 years; 374 females), PE was diagnosed among 42/358 (12%) during the ancestral strain period, 5/60 (8%) during the Alpha variant period, 16/152 (11%) during the Delta variant period, and 13/150 (9%) during the Omicron variant period. The most proximal PE (ancestral strain vs variants) was located in the main/lobar arteries (31% vs 6%-40%), in the segmental arteries (52% vs 60%-75%), and in the subsegmental arteries (17% vs 0%-19%). There was no significant difference in both the incidence and location of PE across the periods, confirmed by multivariable logistic regression models. In summary, the incidence and severity of PE did not significantly differ across the periods of ancestral strain and Alpha, Delta, and Omicron variants.