Quantification of preexisting lung ground glass opacities on CT for predicting checkpoint inhibitor pneumonitis in advanced non-small cell lung cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can lead to life-threatening pneumonitis, and pre-existing interstitial lung abnormalities (ILAs) are a risk factor for checkpoint inhibitor pneumonitis (CIP). However, the subjective assessment of ILA and the lack of standardized methods restrict its clinical utility as a predictive factor. This study aims to identify non-small cell lung cancer (NSCLC) patients at high risk of CIP using quantitative imaging. METHODS: This cohort study involved 206 cases in the training set and 111 cases in the validation set. It included locally advanced or metastatic NSCLC patients who underwent ICI therapy. A deep learning algorithm labeled the interstitial lesions and computed their volume. Two predictive models were developed to predict the probability of grade ≥ 2 CIP or severe CIP (grade ≥ 3). Cox proportional hazard models were employed to analyze predictors of progression-free survival (PFS). RESULTS: In a training cohort of 206 patients, 21.4% experienced CIP. Two models were developed to predict the probability of CIP based on different predictors. Model 1 utilized age, histology, and preexisting ground glass opacity (GGO) percentage of the whole lung to predict grade ≥ 2 CIP, while Model 2 used histology and GGO percentage in the right lower lung to predict grade ≥ 3 CIP. These models were validated, and their accuracy was assessed. In another exploratory analysis, the presence of GGOs involving more than one lobe on pretreatment CT scans was identified as a risk factor for progression-free survival. CONCLUSIONS: The assessment of GGO volume and distribution on pre-treatment CT scans could assist in monitoring and manage the risk of CIP in NSCLC patients receiving ICI therapy. CLINICAL RELEVANCE STATEMENT: This study's quantitative imaging and computational analysis can help identify NSCLC patients at high risk of CIP, allowing for better risk management and potentially improved outcomes in those receivingICI treatment.

Covariation of preadult environmental exposures, adult brain imaging phenotypes, and adult personality traits.

Exposure to preadult environmental exposures may have long-lasting effects on mental health by affecting the maturation of the brain and personality, two traits that interact throughout the developmental process. However, environment-brain-personality covariation patterns and their mediation relationships remain unclear. In 4297 healthy participants (aged 18-30 years), we combined sparse multiple canonical correlation analysis with independent component analysis to identify the three-way covariation patterns of 59 preadult environmental exposures, 760 adult brain imaging phenotypes, and five personality traits, and found two robust environment-brain-personality covariation models with sex specificity. One model linked greater stress and less support to weaker functional connectivity and activity in the default mode network, stronger activity in subcortical nuclei, greater thickness and volume in the occipital, parietal and temporal cortices, and lower agreeableness, consciousness and extraversion as well as higher neuroticism. The other model linked higher urbanicity and better socioeconomic status to stronger functional connectivity and activity in the sensorimotor network, smaller volume and surface area and weaker functional connectivity and activity in the medial prefrontal cortex, lower white matter integrity, and higher openness to experience. We also conducted mediation analyses to explore the potential bidirectional mediation relationships between adult brain imaging phenotypes and personality traits with the influence of preadult environmental exposures and found both environment-brain-personality and environment-personality-brain pathways. We finally performed moderated mediation analyses to test the potential interactions between macro- and microenvironmental exposures and found that one category of exposure moderated the mediation pathways of another category of exposure. These results improve our understanding of the effects of preadult environmental exposures on the adult brain and personality traits and may facilitate the design of targeted interventions to improve mental health by reducing the impact of adverse environmental exposures.

Radiomics in cone-beam breast CT for the prediction of axillary lymph node metastasis in breast cancer: a multi-center multi-device study.

OBJECTIVES: To develop a radiomics model in contrast-enhanced cone-beam breast CT (CE-CBBCT) for preoperative prediction of axillary lymph node (ALN) status and metastatic burden of breast cancer. METHODS: Two hundred and seventy-four patients who underwent CE-CBBCT examination with two scanners between 2012 and 2021 from two institutions were enrolled. The primary tumor was annotated in each patient image, from which 1781 radiomics features were extracted with PyRadiomics. After feature selection, support vector machine models were developed to predict ALN status and metastatic burden. To avoid overfitting on a specific patient subset, 100 randomly stratified splits were made to assign the patients to either training/fine-tuning or test set. Area under the receiver operating characteristic curve (AUC) of these radiomics models was compared to those obtained when training the models only with clinical features and combined clinical-radiomics descriptors. Ground truth was established by histopathology. RESULTS: One hundred and eighteen patients had ALN metastasis (N + (≥ 1)). Of these, 74 had low burden (N + (1~2)) and 44 high burden (N + (≥ 3)). The remaining 156 patients had none (N0). AUC values across the 100 test repeats in predicting ALN status (N0/N + (≥ 1)) were 0.75 ± 0.05 (0.67~0.93, radiomics model), 0.68 ± 0.07 (0.53~0.85, clinical model), and 0.74 ± 0.05 (0.67~0.88, combined model). For metastatic burden prediction (N + (1~2)/N + (≥ 3)), AUC values were 0.65 ± 0.10 (0.50~0.88, radiomics model), 0.55 ± 0.10 (0.40~0.80, clinical model), and 0.64 ± 0.09 (0.50~0.90, combined model), with all the ranges spanning 0.5. In both cases, the radiomics model was significantly better than the clinical model (both p < 0.01) and comparable with the combined model (p = 0.56 and 0.64). CONCLUSIONS: Radiomics features of primary tumors could have potential in predicting ALN metastasis in CE-CBBCT imaging. CLINICAL RELEVANCE STATEMENT: The findings support potential clinical use of radiomics for predicting axillary lymph node metastasis in breast cancer patients and addressing the limited axilla coverage of cone-beam breast CT. KEY POINTS: • Contrast-enhanced cone-beam breast CT-based radiomics could have potential to predict N0 vs. N + (≥ 1) and, to a limited extent, N + (1~2) vs. N + (≥ 3) from primary tumor, and this could help address the limited axilla coverage, pending future verifications on larger cohorts. • The average AUC of radiomics and combined models was significantly higher than that of clinical models but showed no significant difference between themselves. • Radiomics features descriptive of tumor texture were found informative on axillary lymph node status, highlighting a higher heterogeneity for tumor with positive axillary lymph node.

Structural covariances of prefrontal subregions selectively associate with dopamine-related gene coexpression and schizophrenia.

Evidence highlights that dopamine (DA) system dysregulation and prefrontal cortex (PFC) dysfunction may underlie the pathophysiology of schizophrenia. However, the associations among DA genes, PFC morphometry, and schizophrenia have not yet been fully clarified. Based on the brain gene expression dataset from Allen Human Brain Atlas and structural magnetic resonance imaging data (NDIS = 1727, NREP = 408), we first identified 10 out of 22 PFC subregions whose gray matter volume (GMV) covariance profiles were reliably associated with their DA genes coexpression profiles, then four out of the identified 10 PFC subregions demonstrated abnormally increased GMV covariance with the hippocampus, insula, and medial frontal areas in schizophrenia patients (NCASE = 100; NCONTROL = 102). Moreover, based on a schizophrenia postmortem expression dataset, we found that the DA genes coexpression of schizophrenia was significantly reduced between the middle frontal gyrus and hippocampus, in which 21 DA genes showed significantly unsynchronized expression changes, and the 21 genes' brain expression were enriched in brain activity invoked by working memory, reward, speech production, and episodic memory. Our findings indicate the DA genes selectively regulate the structural covariance of PFC subregions by their coexpression profiles, which may underlie the disrupted GMV covariance and impaired cognitive functions in schizophrenia.

Assessing the effect of scanning parameter on the size and density of pulmonary nodules: a phantom study.

BACKGROUND: Lung cancer remains a leading cause of death among cancer patients. Computed tomography (CT) plays a key role in lung cancer screening. Previous studies have not adequately quantified the effect of scanning protocols on the detected tumor size. The aim of this study was to assess the effect of various CT scanning parameters on tumor size and densitometry based on a phantom study and to investigate the optimal energy and mA image quality for screening assessment. METHODS: We proposed a new model using the LUNGMAN N1 phantom multipurpose anthropomorphic chest phantom (diameters: 8, 10, and 12 mm; CT values: - 100, - 630, and - 800 HU) to evaluate the influence of changes in tube voltage and tube current on the size and density of pulmonary nodules. In the LUNGMAN N1 model, three types of simulated lung nodules representing solid tumors of different sizes were used. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were used to evaluate the image quality of each scanning combination. The consistency between the calculated results based on segmentation from two physicists was evaluated using the interclass correlation coefficient (ICC). RESULTS: In terms of nodule size, the longest diameters of ground-glass nodules (GGNs) were closest to the ground truth on the images measured at 100 kVp tube voltage, and the longest diameters of solid nodules were closest to the ground truth on the images measured at 80 kVp tube voltage. In respect to density, the CT values of GGNs and solid nodules were closest to the ground truth when measured at 80 kVp and 100 kVp tube voltage, respectively. The overall agreement demonstrates that the measurements were consistent between the two physicists. CONCLUSIONS: Our proposed model demonstrated that a combination of 80 kVp and 140 mA scans was preferred for measuring the size of the solid nodules, and a combination of 100 kVp and 100 mA scans was preferred for measuring the size of the GGNs when performing lung cancer screening. The CT values at 80 kVp and 100 kVp were preferred for the measurement of GGNs and solid nodules, respectively, which were closest to the true CT values of the nodules. Therefore, the combination of scanning parameters should be selected for different types of nodules to obtain more accurate nodal data.

ISG15 targets glycosylated PD-L1 and promotes its degradation to enhance antitumor immune effects in lung adenocarcinoma.

BACKGROUND: Immunocheckpoint inhibitors (ICIs) have been widely used in the clinical treatment of lung cancer. Although clinical studies and trials have shown that patients can benefit significantly after PD-1/PD-L1 blocking therapy, less than 20% of patients can benefit from ICIs therapy due to tumor heterogeneity and the complexity of immune microenvironment. Several recent studies have explored the immunosuppression of PD-L1 expression and activity by post-translational regulation. Our published articles demonstrate that ISG15 inhibits lung adenocarcinoma progression. Whether ISG15 can enhance the efficacy of ICIs by modulating PD-L1 remains unknown. METHODS: The relationship between ISG15 and lymphocyte infiltration was identified by IHC. The effects of ISG15 on tumor cells and T lymphocytes were assessed using RT-qPCR and Western Blot and in vivo experiments. The underlying mechanism of PD-L1 post-translational modification by ISG15 was revealed by Western blot, RT-qPCR, flow cytometry, and Co-IP. Finally, we performed validation in C57 mice as well as in lung adenocarcinoma tissues. RESULTS: ISG15 promotes the infiltration of CD4+ T lymphocytes. In vivo and in vitro experiments demonstrated that ISG15 induces CD4+ T cell proliferation and invalidity and immune responses against tumors. Mechanistically, we demonstrated that the ubiquitination-like modifying effect of ISG15 on PD-L1 increased the modification of K48-linked ubiquitin chains thus increasing the degradation rate of glycosylated PD-L1 targeting proteasomal pathway. The expression of ISG15 and PD-L1 was negatively correlated in NSCLC tissues. In addition, reduced accumulation of PD-L1 by ISG15 in mice also increased splenic lymphocyte infiltration as well as promoted cytotoxic T cell infiltration in the tumor microenvironment, thereby enhancing anti-tumor immunity. CONCLUSIONS: The ubiquitination modification of PD-L1 by ISG15 increases K48-linked ubiquitin chain modification, thereby increasing the degradation rate of glycosylated PD-L1-targeted proteasome pathway. More importantly, ISG15 enhanced the sensitivity to immunosuppressive therapy. Our study shows that ISG15, as a post-translational modifier of PD-L1, reduces the stability of PD-L1 and may be a potential therapeutic target for cancer immunotherapy.

Interaction between childhood trauma experience and TPH2 rs7305115 gene polymorphism in brain gray matter volume.

BACKGROUND: Childhood trauma is one of the most extensively studied and well-supported environmental risk factors for the development of mental health problems. The human tryptophan hydroxylase 2 (TPH2) gene is one of the most promising candidate genes in numerous psychiatric disorders. However, it is now widely acknowledged that neither genetic variation nor environmental exposure alone can fully explain all the phenotypic variance observed in psychiatric disorders. Therefore, it is necessary to consider the interaction between the two factors in psychiatric research. METHODS: We enrolled a sizable nonclinical cohort of 786 young, healthy adults who underwent structural MRI scans and completed genotyping, the Childhood Trauma Questionnaire (CTQ) and behavioural scores. We identified the interaction between childhood trauma and the TPH2 rs7305115 gene polymorphism in the gray matter volume (GMV) of specific brain subregions and the behaviour in our sample using a multiple linear regression framework. We utilized mediation effect analysis to identify environment /gene-brain-behaviour relationships. RESULTS: We found that childhood trauma and TPH2 rs7305115 interacted in both behaviour and the GMV of brain subregions. Our findings indicated that the GMV of the right posterior parietal thalamus served as a significant mediator supporting relationship between childhood trauma (measured by CTQ score) and anxiety scores in our study population, and the process was partly modulated by the TPH2 rs7305115 gene polymorphism. Moreover, we found only a main effect of childhood trauma in the GMV of the right parahippocampal gyrus area, supporting the relationship between childhood trauma and anxiety scores as a significant mediator. CONCLUSIONS: Our findings suggest that early-life trauma may have a specific and long-term structural effect on brain GMV, potentially leading to altered cognitive and emotional processes involving the parahippocampal gyrus and thalamus that may also be modulated by the TPH2 gene polymorphism. This finding highlights the importance of considering genetic factors when examining the impact of early-life experiences on brain structure and function. Gene‒environment studies can be regarded as a powerful objective supplement for targeted therapy, early diagnosis and treatment evaluation in the future.

Computed tomography-based radiomics machine learning classifiers to differentiate type I and type II epithelial ovarian cancers.

OBJECTIVES: To compare computed tomography (CT)-based radiomics for preoperatively differentiating type I and II epithelial ovarian cancers (EOCs) using different machine learning classifiers and to construct and validate the best diagnostic model. METHODS: A total of 470 patients with EOCs were included retrospectively. Patients were divided into a training dataset (N = 329) and a test dataset (N = 141). A total of 1316 radiomics features were extracted from the portal venous phase of contrast-enhanced CT images for each patient, followed by dimension reduction of the features. The support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), naïve Bayes (NB), logistic regression (LR), and eXtreme Gradient Boosting (XGBoost) classifiers were trained to obtain the radiomics signatures. The performance of each radiomics signature was evaluated and compared by the area under the receiver operating characteristic curve (AUC) and relative standard deviation (RSD). The best radiomics signature was selected and combined with clinical and radiological features to establish a combined model. The diagnostic value of the combined model was assessed. RESULTS: The LR-based radiomics signature performed well in the test dataset, with an AUC of 0.879 and an accuracy of 0.773. The combined model performed best in both the training and test datasets, with AUCs of 0.900 and 0.934 and accuracies of 0.848 and 0.823, respectively. CONCLUSION: The combined model showed the best diagnostic performance for distinguishing between type I and II EOCs preoperatively. Therefore, it can be a useful tool for clinical individualized EOC classification. KEY POINTS: • Radiomics features extracted from computed tomography (CT) could be used to differentiate type I and II epithelial ovarian cancers (EOCs). • Machine learning can improve the performance of differentiating type I and II EOCs. • The combined model exhibited the best diagnostic capability over the other models in both the training and test datasets.

Prediction of histologic types in solid lung lesions using preoperative contrast-enhanced CT.

OBJECTIVES: This study aimed to develop and validate a predicting model for the histologic classification of solid lung lesions based on preoperative contrast-enhanced CT. METHODS: A primary dataset of 1012 patients from Tianjin Medical University Cancer Institute and Hospital (TMUCIH) was randomly divided into a development cohort (708) and an internal validation cohort (304). Patients from the Second Hospital of Shanxi Medical University (SHSMU) were set as an external validation cohort (212). Two clinical factors (age, gender) and twenty-one characteristics on contrast-enhanced CT were used to construct a multinomial multivariable logistic regression model for the classification of seven common histologic types of solid lung lesions. The area under the receiver operating characteristic curve was used to assess the diagnostic performance of the model in the development and validation cohorts, separately. RESULTS: Multivariable analysis showed that two clinical factors and twenty-one characteristics on contrast-enhanced CT were predictive in lung lesion histologic classification. The mean AUC of the proposed model for histologic classification was 0.95, 0.94, and 0.92 in the development, internal validation, and external validation cohort, respectively. When determining the malignancy of lung lesions based on histologic types, the mean AUC of the model was 0.88, 0.86, and 0.90 in three cohorts. CONCLUSIONS: We demonstrated that by utilizing both clinical and CT characteristics on contrast-enhanced CT images, the proposed model could not only effectively stratify histologic types of solid lung lesions, but also enabled accurate assessment of lung lesion malignancy. Such a model has the potential to avoid unnecessary surgery for patients and to guide clinical decision-making for preoperative treatment. KEY POINTS: • Clinical and CT characteristics on contrast-enhanced CT could be used to differentiate histologic types of solid lung lesions. • Predicting models using preoperative contrast-enhanced CT could accurately assessment of tumor malignancy based on predicted histologic types.

Radiomics nomogram for the prediction of microvascular invasion of HCC and patients' benefit from postoperative adjuvant TACE: a multi-center study.

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.

Added value of CE-CT radiomics to predict high Ki-67 expression in hepatocellular carcinoma.

BACKGROUND: This study aimed to develop a computed tomography (CT) model to predict Ki-67 expression in hepatocellular carcinoma (HCC) and to examine the added value of radiomics to clinico-radiological features. METHODS: A total of 208 patients (training set, n = 120; internal test set, n = 51; external validation set, n = 37) with pathologically confirmed HCC who underwent contrast-enhanced CT (CE-CT) within 1 month before surgery were retrospectively included from January 2014 to September 2021. Radiomics features were extracted and selected from three phases of CE-CT images, least absolute shrinkage and selection operator regression (LASSO) was used to select features, and the rad-score was calculated. CE-CT imaging and clinical features were selected using univariate and multivariate analyses, respectively. Three prediction models, including clinic-radiologic (CR) model, rad-score (R) model, and clinic-radiologic-radiomic (CRR) model, were developed and validated using logistic regression analysis. The performance of different models for predicting Ki-67 expression was evaluated using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis (DCA). RESULTS: HCCs with high Ki-67 expression were more likely to have high serum α-fetoprotein levels (P = 0.041, odds ratio [OR] 2.54, 95% confidence interval [CI]: 1.04-6.21), non-rim arterial phase hyperenhancement (P = 0.001, OR 15.13, 95% CI 2.87-79.76), portal vein tumor thrombus (P = 0.035, OR 3.19, 95% CI: 1.08-9.37), and two-trait predictor of venous invasion (P = 0.026, OR 14.04, 95% CI: 1.39-144.32). The CR model achieved relatively good and stable performance compared with the R model (AUC, 0.805 [95% CI: 0.683-0.926] vs. 0.678 [95% CI: 0.536-0.839], P = 0.211; and 0.805 [95% CI: 0.657-0.953] vs. 0.667 [95% CI: 0.495-0.839], P = 0.135) in the internal and external validation sets. After combining the CR model with the R model, the AUC of the CRR model increased to 0.903 (95% CI: 0.849-0.956) in the training set, which was significantly higher than that of the CR model (P = 0.0148). However, no significant differences were found between the CRR and CR models in the internal and external validation sets (P = 0.264 and P = 0.084, respectively). CONCLUSIONS: Preoperative models based on clinical and CE-CT imaging features can be used to predict HCC with high Ki-67 expression accurately. However, radiomics cannot provide added value.

Comparison of malignant calcification identification between breast cone-beam computed tomography and digital mammography.

BACKGROUND: Calcifications are important abnormal findings in breast imaging and help in the diagnosis of breast cancer. PURPOSE: To compare breast cone-beam computed tomography (CBCT) with digital mammography (DM) in terms of the ability to identify malignant calcifications. MATERIAL AND METHODS: In total, 115 paired examinations were performed utilizing breast CBCT and DM; 86 pathology-proven malignant lesions with calcifications detected on DM and 29 randomly selected breasts without calcifications were reviewed by three radiologists. The ability to detect calcifications was assessed on CBCT images. The characterization agreement of two imaging modalities was evaluated by the kappa coefficient. For breast CBCT images, the parameters for the display of calcifications were recorded. The Kruskal-Wallis test was used to compare the preferred slice thickness chosen by each of the three radiologists. The degree of calcification clarity was compared between two modalities using the Mann-Whitney U-test. RESULTS: The combined sensitivity and specificity of three radiologists in 85 DM-detected calcifications detection on breast CBCT images were 98.43% (251/255) and 98.85% (86/87), respectively. CBCT images showed substantial agreement with mammograms in terms of the characterization of calcifications morphology (k = 0.703; P < 0.05) and distribution (k = 0.629; P < 0.05). CBCT images with a slice thickness of 0.273 mm and three-dimensional maximum-intensity projection (3D-MIP) were more beneficial for calcifications identification. No statistically significant difference was found between standard DM views and CBCT images for three radiologists on calcification display clarity. CONCLUSION: CBCT images were comparable to mammograms in calcification identification and may be sufficient for malignant calcifications detection and characterization.

Radiomics nomogram for predicting axillary lymph node metastasis-a potential method to address the limitation of axilla coverage in cone-beam breast CT: a bi-center retrospective study.

PURPOSE: Cone-beam breast CT (CBBCT) has an inherent limitation that the axilla cannot be imaged in its entirety. We aimed to develop and validate a nomogram based on clinical factors and contrast-enhanced (CE) CBBCT radiomics features to predict axillary lymph node (ALN) metastasis and complement limited axilla coverage. MATERIAL AND METHODS: This retrospective study included 312 patients with breast cancer from two hospitals who underwent CE-CBBCT examination in a clinical trial (NCT01792999) during 2012-2020. Patients from TCIH comprised training set (n = 176) and validation set (n = 43), and patients from SYSUCC comprised external test set (n = 93). 3D ROIs were delineated manually and radiomics features were extracted by 3D Slicer software. RadScore was calculated and radiomics model was constructed after feature selection. Clinical model was built on independent predictors. Nomogram was developed with independent clinical predictors and RadScore. Diagnostic performance was compared among three models by ROC curve, and decision curve analysis (DCA) was used to evaluate the clinical utility of nomogram. RESULTS: A total of 139 patients were ALN positive and 173 patients were negative. Twelve radiomics features remained after feature selection. Location and focality were selected as independent predictors for ALN status. The AUC of nomogram in external test set was higher than that of clinical model (0.80 vs. 0.66, p = 0.012). DCA demonstrated that the nomogram had higher overall net benefit than that of clinical model. CONCLUSION: The nomogram combined CE-CBBCT-based radiomics features and clinical factors could have potential in distinguishing ALN positive from negative and addressing the limitation of axilla coverage in CBBCT.

Methodological quality of machine learning-based quantitative imaging analysis studies in esophageal cancer: a systematic review of clinical outcome prediction after concurrent chemoradiotherapy.

PURPOSE: Studies based on machine learning-based quantitative imaging techniques have gained much interest in cancer research. The aim of this review is to critically appraise the existing machine learning-based quantitative imaging analysis studies predicting outcomes of esophageal cancer after concurrent chemoradiotherapy in accordance with PRISMA guidelines. METHODS: A systematic review was conducted in accordance with PRISMA guidelines. The citation search was performed via PubMed and Embase Ovid databases for literature published before April 2021. From each full-text article, study characteristics and model information were summarized. We proposed an appraisal matrix with 13 items to assess the methodological quality of each study based on recommended best-practices pertaining to quality. RESULTS: Out of 244 identified records, 37 studies met the inclusion criteria. Study endpoints included prognosis, treatment response, and toxicity after concurrent chemoradiotherapy with reported discrimination metrics in validation datasets between 0.6 and 0.9, with wide variation in quality. A total of 30 studies published within the last 5 years were evaluated for methodological quality and we found 11 studies with at least 6 "good" item ratings. CONCLUSION: A substantial number of studies lacked prospective registration, external validation, model calibration, and support for use in clinic. To further improve the predictive power of machine learning-based models and translate into real clinical applications in cancer research, appropriate methodologies, prospective registration, and multi-institution validation are recommended.

Prediction of microvascular invasion in HCC by a scoring model combining Gd-EOB-DTPA MRI and biochemical indicators.

OBJECTIVES: This study aimed to establish a reliable diagnostic scoring model for the preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biochemical indicators. METHODS: This retrospective study included 129 patients with HCC at our hospital from 2014 to 2020. Based on the intratumoral and peritumoral features on Gd-EOB-DTPA MRI and biochemical indicators, a scoring model was developed for preoperative prediction of MVI, and examined for diagnostic efficacy according to postoperative pathological results. The scoring model was further externally validated in an independent cohort of 63 HCC patients. RESULTS: Logistic regression analysis was performed to identify five parameters related to MVI, including maximum tumor diameter, peritumoral low intensity in the hepatobiliary phase, incomplete capsule, apparent diffusion coefficient (ADC), and [alkaline phosphatase (ALP) (U/L) + gamma-glutamyl transpeptidase (GGT) (U/L)] / lymphocyte count (× 109/L) ratio (AGLR). Based on these five parameters, a scoring model was developed, and the accuracy, sensitivity, specificity, PPV, and NPV in predicting MVI were 93.6%, 94.7%, 93.2%, 85.7%, and 97.6%, respectively, with a score > 8 set as the threshold. CONCLUSION: The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators provides a reliable tool for preoperative prediction of MVI in HCC patients. KEY POINTS: • The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators is practical for preoperative prediction of MVI in HCC patients. • AGLR is an independent risk factor for MVI. • The scoring model could help implement more appropriate interventions, potentially leading to precise and individualized treatments based on the biological characteristics of the tumor.

Comparison of background parenchymal enhancement (BPE) on contrast-enhanced cone-beam breast CT (CE-CBBCT) and breast MRI.

OBJECTIVES: To compare the background parenchymal enhancement (BPE) levels on contrast-enhanced cone-beam breast CT (CE-CBBCT) and MRI, evaluate inter-reader reliability, and analyze the relationship between clinical factors and BPE level on CE-CBBCT. METHODS: In this retrospective study, patients who underwent both CE-CBBCT and MRI were analyzed. BPE levels on CE-CBBCT and MRI were assessed by five specialists independently in random fashion, with a wash-out period of 4 weeks. Weighted kappa was used to analyze the agreement between CE-CBBCT and MRI, and intraclass correlation coefficient (ICC) was used to evaluate the inter-reader reliability for each modality. The association between BPE level on CE-CBBCT and clinical factors was evaluated by univariate and multivariate logistic regression. RESULTS: A total of 221 patients from January 2017 to April 2021 were enrolled. CE-CBBCT showed substantial agreement (weighted kappa = 0.690) with MRI for BPE evaluation, with good degree of inter-reader reliability on both CE-CBBCT (ICC = 0.712) and MRI (ICC = 0.757). Based on majority reports, BPE levels on CE-CBBCT were lower than MRI (p < 0.001). BPE level on CE-CBBCT was significantly associated with menstrual status (odds ratio, OR = 0.125), breast density (OR = 2.308), and previously treated breast cancer (OR = 0.052) (all p < 0.05). BPE level for premenopausal patients was associated with menstrual cycle, with lower BPE level for the 2nd week of menstrual cycle (OR = 0.246). CONCLUSIONS: CE-CBBCT showed substantial agreement and comparable inter-reader reliability with MRI for BPE evaluation, indicating that the corresponding BI-RADS lexicons could be used to describe BPE level on CE-CBBCT. The 2nd week of menstrual cycle timing is suggested as the optimal examination period for CE-CBBCT. KEY POINTS: • CE-CBBCT showed substantial agreement and comparable inter-reader reliability with MRI for BPE evaluation. • Menstrual status, breast density, and previously treated breast cancer were associated with the BPE level on CE-CBBCT images. • The 2ndweek of the menstrual cycle is suggested as the optimal examination period for CE-CBBCT.

Dedicated breast CT: state of the art-Part I. Historical evolution and technical aspects.

Dedicated breast CT is an emerging 3D isotropic imaging technology for breast, which overcomes the limitations of 2D compression mammography and limited angle tomosynthesis while providing some of the advantages of magnetic resonance imaging. This first installment in a 2-part review describes the evolution of dedicated breast CT beginning with a historical perspective and progressing to the present day. Moreover, it provides an overview of state-of-the-art technology. Particular emphasis is placed on technical limitations in scan protocol, radiation dose, breast coverage, patient comfort, and image artifact. Proposed methods of how to address these technical challenges are also discussed. KEY POINTS: • Advantages of breast CT include no tissue overlap, improved patient comfort, rapid acquisition, and concurrent assessment of microcalcifications and contrast enhancement. • Current clinical and prototype dedicated breast CT systems differ in acquisition modes, imaging techniques, and detector types. • There are still details to be decided regarding breast CT techniques, such as scan protocol, radiation dose, breast coverage, patient comfort, and image artifact.

Dedicated breast CT: state of the art-Part II. Clinical application and future outlook.

Dedicated breast CT is being increasingly used for breast imaging. This technique provides images with no compression, removal of tissue overlap, rapid acquisition, and available simultaneous assessment of microcalcifications and contrast enhancement. In this second installment in a 2-part review, the current status of clinical applications and ongoing efforts to develop new imaging systems are discussed, with particular emphasis on how to achieve optimized practice including lesion detection and characterization, response to therapy monitoring, density assessment, intervention, and implant evaluation. The potential for future screening with breast CT is also addressed. KEY POINTS: • Dedicated breast CT is an emerging modality with enormous potential in the future of breast imaging by addressing numerous clinical needs from diagnosis to treatment. • Breast CT shows either noninferiority or superiority with mammography and numerical comparability to MRI after contrast administration in diagnostic statistics, demonstrates excellent performance in lesion characterization, density assessment, and intervention, and exhibits promise in implant evaluation, while potential application to breast cancer screening is still controversial. • New imaging modalities such as phase-contrast breast CT, spectral breast CT, and hybrid imaging are in the progress of R & D.

Association between visual emphysema and lung nodules on low-dose CT scan in a Chinese Lung Cancer Screening Program (Nelcin-B3).

OBJECTIVES: This study aimed to evaluate the association between visual emphysema and the presence of lung nodules, and Lung-RADS category with low-dose CT (LDCT). METHODS: Baseline LDCT scans of 1162 participants from a lung cancer screening study (Nelcin-B3) performed in a Chinese general population were included. The presence, subtypes, and severity of emphysema (at least trace) were visually assessed by one radiologist. The presence, size, and classification of non-calcified lung nodules (≥ 30 mm3) and Lung-RADS category were independently assessed by another two radiologists. Multivariable logistic regression and stratified analyses were performed to estimate the association between emphysema and lung nodules, Lung-RADS category, after adjusting for age, sex, BMI, smoking status, pack-years, and passive smoking. RESULTS: Emphysema and lung nodules were observed in 674 (58.0%) and 424 (36.5%) participants, respectively. Participants with emphysema had a 71% increased risk of having lung nodules (adjusted odds ratios, aOR: 1.71, 95% CI: 1.26-2.31) and 70% increased risk of positive Lung-RADS category (aOR: 1.70, 95% CI: 1.09-2.66) than those without emphysema. Participants with paraseptal emphysema (n = 47, 4.0%) were at a higher risk for lung nodules than those with centrilobular emphysema (CLE) (aOR: 2.43, 95% CI: 1.32-4.50 and aOR: 1.60, 95% CI: 1.23-2.09, respectively). Only CLE was associated with positive Lung-RADS category (p = 0.02). CLE severity was related to a higher risk of lung nodules (ranges aOR: 1.44-2.61, overall p < 0.01). CONCLUSION: In a Chinese general population, visual emphysema based on LDCT is independently related to the presence of lung nodules (≥ 30 mm3) and specifically CLE subtype is related to positive Lung-RADS category. The risk of lung nodules increases with CLE severity. KEY POINTS: • Participants with emphysema had an increased risk of having lung nodules, especially smokers. • Participants with PSE were at a higher risk for lung nodules than those with CLE, but nodules in participants with CLE had a higher risk of positive Lung-RADS category. • The risk of lung nodules increases with CLE severity.

Development and validation of a computed tomography-based immune ecosystem diversity index as an imaging biomarker in non-small cell lung cancer.

OBJECTIVES: To date, there are no data on the noninvasive surrogate of intratumoural immune status that could be prognostic of survival outcomes in non-small cell lung cancer (NSCLC). We aimed to develop and validate the immune ecosystem diversity index (iEDI), an imaging biomarker, to indicate the intratumoural immune status in NSCLC. We further investigated the clinical relevance of the biomarker for survival prediction. METHODS: In this retrospective study, two independent NSCLC cohorts (Resec1, n = 149; Resec2, n = 97) were included to develop and validate the iEDI to classify the intratumoural immune status. Paraffin-embedded resected specimens in Resec1 and Resec2 were stained by immunohistochemistry, and the density percentiles of CD3+, CD4+, and CD8+ T cells to all cells were quantified to estimate intratumoural immune status. Then, EDI features were extracted using preoperative computed tomography to develop an imaging biomarker, called iEDI, to determine the immune status. The prognostic value of iEDI was investigated on NSCLC patients receiving surgical resection (Resec1; Resec2; internal cohort Resec3, n = 419; external cohort Resec4, n = 96; and TCIA cohort Resec5, n = 55). RESULTS: iEDI successfully classified immune status in Resec1 (AUC 0.771, 95% confidence interval [CI] 0.759-0.783; and 0.770 through internal validation) and Resec2 (0.669, 0.647-0.691). Patients with higher iEDI-score had longer overall survival (OS) in Resec3 (unadjusted hazard ratio 0.335, 95%CI 0.206-0.546, p < 0.001), Resec4 (0.199, 0.040-1.000, p < 0.001), and TCIA (0.303, 0.098-0.944, p = 0.001). CONCLUSIONS: iEDI is a non-invasive surrogate of intratumoural immune status and prognostic of OS for NSCLC patients receiving surgical resection. KEY POINTS: • Decoding tumour immune microenvironment enables advanced biomarkers identification. • Immune ecosystem diversity index characterises intratumoural immune status noninvasively. • Immune ecosystem diversity index is prognostic for NSCLC patients.