Radiomic profiles improve prognostication and reveal targets for therapy in cervical cancer.

Cervical cancer (CC) is a major global health problem with 570,000 new cases and 266,000 deaths annually. Prognosis is poor for advanced stage disease, and few effective treatments exist. Preoperative diagnostic imaging is common in high-income countries and MRI measured tumor size routinely guides treatment allocation of cervical cancer patients. Recently, the role of MRI radiomics has been recognized. However, its potential to independently predict survival and treatment response requires further clarification. This retrospective cohort study demonstrates how non-invasive, preoperative, MRI radiomic profiling may improve prognostication and tailoring of treatments and follow-ups for cervical cancer patients. By unsupervised clustering based on 293 radiomic features from 132 patients, we identify three distinct clusters comprising patients with significantly different risk profiles, also when adjusting for FIGO stage and age. By linking their radiomic profiles to genomic alterations, we identify putative treatment targets for the different patient clusters (e.g., immunotherapy, CDK4/6 and YAP-TEAD inhibitors and p53 pathway targeting treatments).

Unveiling Promising Neuroimaging Biomarkers for Schizophrenia Through Clinical and Genetic Perspectives.

Schizophrenia is a complex and serious brain disorder. Neuroscientists have become increasingly interested in using magnetic resonance-based brain imaging-derived phenotypes (IDPs) to investigate the etiology of psychiatric disorders. IDPs capture valuable clinical advantages and hold biological significance in identifying brain abnormalities. In this review, we aim to discuss current and prospective approaches to identify potential biomarkers for schizophrenia using clinical multimodal neuroimaging and imaging genetics. We first described IDPs through their phenotypic classification and neuroimaging genomics. Secondly, we discussed the applications of multimodal neuroimaging by clinical evidence in observational studies and randomized controlled trials. Thirdly, considering the genetic evidence of IDPs, we discussed how can utilize neuroimaging data as an intermediate phenotype to make association inferences by polygenic risk scores and Mendelian randomization. Finally, we discussed machine learning as an optimum approach for validating biomarkers. Together, future research efforts focused on neuroimaging biomarkers aim to enhance our understanding of schizophrenia.

Statistical and Machine Learning Analysis in Brain-Imaging Genetics: A Review of Methods.

Brain-imaging-genetic analysis is an emerging field of research that aims at aggregating data from neuroimaging modalities, which characterize brain structure or function, and genetic data, which capture the structure and function of the genome, to explain or predict normal (or abnormal) brain performance. Brain-imaging-genetic studies offer great potential for understanding complex brain-related diseases/disorders of genetic etiology. Still, a combined brain-wide genome-wide analysis is difficult to perform as typical datasets fuse multiple modalities, each with high dimensionality, unique correlational landscapes, and often low statistical signal-to-noise ratios. In this review, we outline the progress in brain-imaging-genetic methodologies starting from early massive univariate to current deep learning approaches, highlighting each approach's strengths and weaknesses and elongating it with the field's development. We conclude by discussing selected remaining challenges and prospects for the field.

Radiogenomics of adult intracranial gliomas after the 2021 World Health Organisation classification: a review of changes, challenges and opportunities.

The classification of diffuse gliomas has undergone substantial changes over the last decade, starting with the 2016 World Health Organisation (WHO) classification, which introduced the importance of molecular markers for glioma diagnosis, in particular, isocitrate dehydrogenase (IDH) status and 1p/19-codeletion. This has spurred research into the correlation of imaging features with the key molecular markers, known as "radiogenomics" or "imaging genomics". Radiogenomics has a variety of possible benefits, including supplementing immunohistochemistry to refine the histological diagnosis and overcoming some of the limitations of the histological assessment. The recent 2021 WHO classification has introduced a variety of changes and continues the trend of increasing the importance of molecular markers in the diagnosis. Key changes include a formal distinction between adult- and paediatric-type diffuse gliomas, the addition of new diagnostic entities, refinements to the nomenclature for IDH-mutant (IDHmut) and IDH-wildtype (IDHwt) gliomas, a shift to grading within tumour types, and the addition of molecular markers as a determinant of tumour grade in addition to phenotype. These changes provide both challenges and opportunities for the field of radiogenomics, which are discussed in this review. This includes implications for the interpretation of research performed prior to the 2021 classification, based on the shift to first classifying gliomas based on genotype ahead of grade, as well as opportunities for future research and priorities for clinical integration.

Personalized radiomics signature to screen for KIT-11 mutation genotypes among patients with gastrointestinal stromal tumors: a retrospective multicenter study.

OBJECTIVES: Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring. METHODS: Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability. RESULTS: The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812-0.884), 0.759 (95% CI 0.722-0.797), 0.956 (95% CI 0.938-0.974), and 0.876 (95% CI 0.844-0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660-0.786), 0.688 (95% CI 0.643-0.732), 0.870 (95% CI 0.824-0.918), and 0.830 (95% CI 0.780-0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820-0.855) in the TC to 0.758 (95% CI 0.758-0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660-0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595-0.679). CONCLUSIONS: CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

Multiparametric magnetic resonance imaging discerns glioblastoma immune microenvironmental heterogeneity.

RATIONALE AND OBJECTIVE: Poor clinical outcomes for patients with glioblastoma are in part due to dysfunction of the tumor-immune microenvironment. An imaging approach able to characterize immune microenvironmental signatures could provide a framework for biologically based patient stratification and response assessment. We hypothesized spatially distinct gene expression networks can be distinguished by multiparametric Magnetic Resonance Imaging (MRI) phenotypes. MATERIALS AND METHODS: Patients with newly diagnosed glioblastoma underwent image-guided tissue sampling allowing for co-registration of MRI metrics with gene expression profiles. MRI phenotypes based on gadolinium contrast enhancing lesion (CEL) and non-enhancing lesion (NCEL) regions were subdivided based on imaging parameters (relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC)). Gene set enrichment analysis and immune cell type abundance was estimated using CIBERSORT methodology. Significance thresholds were set at a p-value cutoff 0.005 and an FDR q-value cutoff of 0.1. RESULTS: Thirteen patients (eight men, five women, mean age 58 ± 11 years) provided 30 tissue samples (16 CEL and 14 NCEL). Six non-neoplastic gliosis samples differentiated astrocyte repair from tumor associated gene expression. MRI phenotypes displayed extensive transcriptional variance reflecting biological networks, including multiple immune pathways. CEL regions demonstrated higher immunologic signature expression than NCEL, while NCEL regions demonstrated stronger immune signature expression levels than gliotic non-tumor brain. Incorporation of rCBV and ADC metrics identified sample clusters with differing immune microenvironmental signatures. CONCLUSION: Taken together, our study demonstrates that MRI phenotypes provide an approach for non-invasively characterizing tumoral and immune microenvironmental glioblastoma gene expression networks.

Correlating MRI features with additional genetic markers and patient survival in histological grade 2-3 IDH-mutant astrocytomas.

PURPOSE: The increasing importance of molecular markers for classification and prognostication of diffuse gliomas has prompted the use of imaging features to predict genotype ("radiogenomics"). CDKN2A/B homozygous deletion has only recently been added to the diagnostic paradigm for IDH[isocitrate dehydrogenase]-mutant astrocytomas; thus, associated radiogenomic literature is sparse. There is also little data on whether different IDH mutations are associated with different imaging appearances. Furthermore, given that molecular status is now generally obtained routinely, the additional prognostic value of radiogenomic features is less clear. This study correlated MRI features with CDKN2A/B status, IDH mutation type and survival in histological grade 2-3 IDH-mutant brain astrocytomas. METHODS: Fifty-eight grade 2-3 IDH-mutant astrocytomas were identified, 50 with CDKN2A/B results. IDH mutations were stratified into IDH1-R132H and non-canonical mutations. Background and survival data were obtained. Two neuroradiologists independently assessed the following MRI features: T2-FLAIR mismatch (<25%, 25-50%, >50%), well-defined tumour margins, contrast-enhancement (absent, wispy, solid) and central necrosis. RESULTS: 8/50 tumours with CDKN2A/B results demonstrated homozygous deletion; slightly shorter survival was not significant (p=0.571). IDH1-R132H mutations were present in 50/58 (86%). No MRI features correlated with CDKN2A/B status or IDH mutation type. T2-FLAIR mismatch did not predict survival (p=0.977), but well-defined margins predicted longer survival (HR 0.36, p=0.008), while solid enhancement predicted shorter survival (HR 3.86, p=0.004). Both correlations remained significant on multivariate analysis. CONCLUSION: MRI features did not predict CDKN2A/B homozygous deletion, but provided additional positive and negative prognostic information which correlated more strongly with prognosis than CDKN2A/B status in our cohort.

DADFN: dynamic adaptive deep fusion network based on imaging genomics for prediction recurrence of lung cancer.

Objective. Recently, imaging genomics has increasingly shown great potential for predicting postoperative recurrence of lung cancer patients. However, prediction methods based on imaging genomics have some disadvantages such as small sample size, high-dimensional information redundancy and poor multimodal fusion efficiency. This study aim to develop a new fusion model to overcome these challenges.Approach. In this study, a dynamic adaptive deep fusion network (DADFN) model based on imaging genomics is proposed for predicting recurrence of lung cancer. In this model, the 3D spiral transformation is used to augment the dataset, which better retains the 3D spatial information of the tumor for deep feature extraction. The intersection of genes screened by LASSO, F-test and CHI-2 selection methods is used to eliminate redundant data and retain the most relevant gene features for the gene feature extraction. A dynamic adaptive fusion mechanism based on the cascade idea is proposed, and multiple different types of base classifiers are integrated in each layer, which can fully utilize the correlation and diversity between multimodal information to better fuse deep features, handcrafted features and gene features.Main results. The experimental results show that the DADFN model achieves good performance, and its accuracy and AUC are 0.884 and 0.863, respectively. This indicates that the model is effective in predicting lung cancer recurrence.Significance. The proposed model has the potential to help physicians to stratify the risk of lung cancer patients and can be used to identify patients who may benefit from a personalized treatment option.

Data-Driven Radiogenomic Approach for Deciphering Molecular Mechanisms Underlying Imaging Phenotypes in Lung Adenocarcinoma: A Pilot Study.

The heterogeneity of lung tumor nodules is reflected in their phenotypic characteristics in radiological images. The radiogenomics field employs quantitative image features combined with transcriptome expression levels to understand tumor heterogeneity molecularly. Due to the different data acquisition techniques for imaging traits and genomic data, establishing meaningful connections poses a challenge. We analyzed 86 image features describing tumor characteristics (such as shape and texture) with the underlying transcriptome and post-transcriptome profiles of 22 lung cancer patients (median age 67.5 years, from 42 to 80 years) to unravel the molecular mechanisms behind tumor phenotypes. As a result, we were able to construct a radiogenomic association map (RAM) linking tumor morphology, shape, texture, and size with gene and miRNA signatures, as well as biological correlates of GO terms and pathways. These indicated possible dependencies between gene and miRNA expression and the evaluated image phenotypes. In particular, the gene ontology processes "regulation of signaling" and "cellular response to organic substance" were shown to be reflected in CT image phenotypes, exhibiting a distinct radiomic signature. Moreover, the gene regulatory networks involving the TFs TAL1, EZH2, and TGFBR2 could reflect how the texture of lung tumors is potentially formed. The combined visualization of transcriptomic and image features suggests that radiogenomic approaches could identify potential image biomarkers for underlying genetic variation, allowing a broader view of the heterogeneity of the tumors. Finally, the proposed methodology could also be adapted to other cancer types to expand our knowledge of the mechanistic interpretability of tumor phenotypes.

A Comprehensive Landscape of Imaging Feature-Associated RNA Expression Profiles in Human Breast Tissue.

The expression abundance of transcripts in nondiseased breast tissue varies among individuals. The association study of genotypes and imaging phenotypes may help us to understand this individual variation. Since existing reports mainly focus on tumors or lesion areas, the heterogeneity of pathological image features and their correlations with RNA expression profiles for nondiseased tissue are not clear. The aim of this study is to discover the association between the nucleus features and the transcriptome-wide RNAs. We analyzed both microscopic histology images and RNA-sequencing data of 456 breast tissues from the Genotype-Tissue Expression (GTEx) project and constructed an automatic computational framework. We classified all samples into four clusters based on their nucleus morphological features and discovered feature-specific gene sets. The biological pathway analysis was performed on each gene set. The proposed framework evaluates the morphological characteristics of the cell nucleus quantitatively and identifies the associated genes. We found image features that capture population variation in breast tissue associated with RNA expressions, suggesting that the variation in expression pattern affects population variation in the morphological traits of breast tissue. This study provides a comprehensive transcriptome-wide view of imaging-feature-specific RNA expression for healthy breast tissue. Such a framework could also be used for understanding the connection between RNA expression and morphology in other tissues and organs. Pathway analysis indicated that the gene sets we identified were involved in specific biological processes, such as immune processes.

Imaging genomics: data fusion in uncovering disease heritability.

Sequencing of the human genome in the early 2000s enabled probing of the genetic basis of disease on a scale previously unimaginable. Now, two decades later, after interrogating millions of markers in thousands of individuals, a significant portion of disease heritability still remains hidden. Recent efforts to unravel this 'missing heritability' have focused on garnering new insight from merging different data types, including medical imaging. Imaging offers promising intermediate phenotypes to bridge the gap between genetic variation and disease pathology. In this review we outline this fusion and provide examples of imaging genomics in a range of diseases, from oncology to cardiovascular and neurodegenerative disease. Finally, we discuss how ongoing revolutions in data science and sharing are primed to advance the field.

Construction of a classification model for image subtypes based on the radiomics features of patients with dermatomyositis/polymyositis-related interstitial lung disease for machine learning / 中华风湿病学杂志

Objective:To investigate the feasibility of classifying imaging patterns of dermatomyositis/polymyositis-related interstitial lung disease (DM/PM-ILD) into subtypes based on chest CT radiomics features and a model was constructed by machine learning algorithms.Methods:From November 2011 to November 2020, 107 patients diagnosed with PM/DM-ILD at the First Affiliated Hospital of Xi′an Jiaotong University were retrospectively analyzed. A total of 315 cases with chest CT were collected. Doctors pre-classified image patterns, including 105 cases with non-specific interstitial pneumonia (NSIP), 90 cases with organizing pneumonia (OP), and 66 cases with non-specific interstitial pneumonia combined with organizing pneumonia (NSIP+OP), 35 cases with common interstitial pneumonia (UIP), and 19 cases with diffuse alveolar damage (DAD), ANOVA was used to test the difference of baseline clinical information among the imaging classification groups. All images were divided into the training set and the est set by stratified random sampling at a ratio of 4∶1. In each CT scan, 3D slicer was used to segment each lung lobe, and then reconstructed into 3 mm 3 of voxels, and Pyradiomics library was used to extract the radiomic features of the whole lung and each lobe. The multi-classification goal was achieved by constructing random forest base classifiers for each of the five groups and then voting as the final model. In the process of constructing the base classifier, firstly, the balance between sample groups was achieved by SMOTETomek comprehensive sampling, and the optimal feature set was selected by independent sample t test and L1 regularized least absolute shrinkage and selection operator (LASSO) regression. In this study, the Radiomics model was constructed based on chest CT radiomics features, and the Radiomics + model was constructed by introducing gender and age information. The base classifier and the integration model use the mean accuracy and the area under the receiver operator characteristics analysis curve (AUC) to evaluate the performance, respectively. Results:There was a statistically significant difference ( P<0.05) between the ages of the NSIP, OP, NSIP+OP, UIP, and DAD groups [(57±13),(53±8),(54±10),(44±11), and (46±8)years old, respectively], F=11.82, P<0.001. In the Radiomics model, for each group of NSIP, OP, NSIP+OP, UIP, and DAD, the AUCs of the training set were 0.87, 0.91, 0.91, 0.96, and 0.99, respectively, and the AUC of the test set were 0.81, 0.82, 0.79, 0.93, 0.89. In the final Radiomics + model, for each group of NSIP, OP, NSIP+OP, UIP, and DAD, the AUCs of the training set were 0.89, 0.91, 0.92, 0.97, and 0.99, respectively, and the AUCs of the test set were 0.84, 0.82, 0.78, 0.94, 0.90. Conclusion:Based on chest CT radiomics features and key clinical features (sex, age), the Radiomics + model constructed by machine learning has good classification performance for the imaging patterns of PM/DM-LD.

Diffuse glioma, not otherwise specified: imaging-based risk stratification achieves histomolecular-level prognostication.

OBJECTIVES: To determine whether imaging-based risk stratification enables prognostication in diffuse glioma, NOS (not otherwise specified). METHODS: Data from 220 patients classified as diffuse glioma, NOS, between January 2011 and December 2020 were retrospectively included. Two neuroradiologists analyzed pre-surgical CT and MRI to assign gliomas to the three imaging-based risk types considering well-known imaging phenotypes (e.g., T2/FLAIR mismatch). According to the 2021 World Health Organization classification, the three risk types included (1) low-risk, expecting oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant, and 1p/19q-codeleted; (2) intermediate-risk, expecting astrocytoma, IDH-mutant; and (3) high-risk, expecting glioblastoma, IDH-wildtype. Progression-free survival (PFS) and overall survival (OS) were estimated for each risk type. Time-dependent receiver operating characteristic analysis using 10-fold cross-validation with 100-fold bootstrapping was used to compare the performance of an imaging-based survival model with that of a historical molecular-based survival model published in 2015, created using The Cancer Genome Archive data. RESULTS: Prognostication according to the three imaging-based risk types was achieved for both PFS and OS (log-rank test, p < 0.001). The imaging-based survival model showed high prognostic value, with areas under the curves (AUCs) of 0.772 and 0.650 for 1-year PFS and OS, respectively, similar to the historical molecular-based survival model (AUC = 0.74 for PFS and 0.87 for OS). The imaging-based survival model achieved high long-term performance in both 3-year PFS (AUC = 0.806) and 5-year OS (AUC = 0.812). CONCLUSION: Imaging-based risk stratification achieved histomolecular-level prognostication in diffuse glioma, NOS, and could aid in guiding patient referral for insufficient or unsuccessful molecular diagnosis. KEY POINTS: • Three imaging-based risk types enable distinct prognostication in diffuse glioma, NOS (not otherwise specified). • The imaging-based survival model achieved similar prognostic performance as a historical molecular-based survival model. • For long-term prognostication of 3 and 5 years, the imaging-based survival model showed high performance.

Artificial Intelligence in Neuro-Oncologic Imaging: A Brief Review for Clinical Use Cases and Future Perspectives.

The artificial intelligence (AI) techniques, both deep learning end-to-end approaches and radiomics with machine learning, have been developed for various imaging-based tasks in neuro-oncology. In this brief review, use cases of AI in neuro-oncologic imaging are summarized: image quality improvement, metastasis detection, radiogenomics, and treatment response monitoring. We then give a brief overview of generative adversarial network and potential utility of synthetic images for various deep learning algorithms of imaging-based tasks and image translation tasks as becoming new data input. Lastly, we highlight the importance of cohorts and clinical trial as a true validation for clinical utility of AI in neuro-oncologic imaging.

A review ofimaging genetics in Alzheimer's disease.

Determining the association between genetic variation and phenotype is a key step to study the mechanism of Alzheimer's disease (AD), laying the foundation for studying drug therapies and biomarkers. AD is the most common type of dementia in the aged population. At present, three early-onset AD genes (APP, PSEN1, PSEN2) and one late-onset AD susceptibility gene apolipoprotein E (APOE) have been determined. However, the pathogenesis of AD remains unknown. Imaging genetics, an emerging interdisciplinary field, is able to reveal the complex mechanisms from the genetic level to human cognition and mental disorders via macroscopic intermediates. This paper reviews methods of establishing genotype-phenotype to explore correlations, including sparse canonical correlation analysis, sparse reduced rank regression, sparse partial least squares and so on. We found that most research work did poorly in supervised learning and exploring the nonlinear relationship between SNP-QT.

Radiogenomic Predictors of Recurrence in Glioblastoma-A Systematic Review.

Glioblastoma, as the most aggressive brain tumor, is associated with a poor prognosis and outcome. To optimize prognosis and clinical therapy decisions, there is an urgent need to stratify patients with increased risk for recurrent tumors and low therapeutic success to optimize individual treatment. Radiogenomics establishes a link between radiological and pathological information. This review provides a state-of-the-art picture illustrating the latest developments in the use of radiogenomic markers regarding prognosis and their potential for monitoring recurrence. Databases PubMed, Google Scholar, and Cochrane Library were searched. Inclusion criteria were defined as diagnosis of glioblastoma with histopathological and radiological follow-up. Out of 321 reviewed articles, 43 articles met these inclusion criteria. Included studies were analyzed for the frequency of radiological and molecular tumor markers whereby radiogenomic associations were analyzed. Six main associations were described: radiogenomic prognosis, MGMT status, IDH, EGFR status, molecular subgroups, and tumor location. Prospective studies analyzing prognostic features of glioblastoma together with radiological features are lacking. By reviewing the progress in the development of radiogenomic markers, we provide insights into the potential efficacy of such an approach for clinical routine use eventually enabling early identification of glioblastoma recurrence and therefore supporting a further personalized monitoring and treatment strategy.

Impact of feature harmonization on radiogenomics analysis: Prediction of EGFR and KRAS mutations from non-small cell lung cancer PET/CT images.

OBJECTIVE: To investigate the impact of harmonization on the performance of CT, PET, and fused PET/CT radiomic features toward the prediction of mutations status, for epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) genes in non-small cell lung cancer (NSCLC) patients. METHODS: Radiomic features were extracted from tumors delineated on CT, PET, and wavelet fused PET/CT images obtained from 136 histologically proven NSCLC patients. Univariate and multivariate predictive models were developed using radiomic features before and after ComBat harmonization to predict EGFR and KRAS mutation statuses. Multivariate models were built using minimum redundancy maximum relevance feature selection and random forest classifier. We utilized 70/30% splitting patient datasets for training/testing, respectively, and repeated the procedure 10 times. The area under the receiver operator characteristic curve (AUC), accuracy, sensitivity, and specificity were used to assess model performance. The performance of the models (univariate and multivariate), before and after ComBat harmonization was compared using statistical analyses. RESULTS: While the performance of most features in univariate modeling was significantly improved for EGFR prediction, most features did not show any significant difference in performance after harmonization in KRAS prediction. Average AUCs of all multivariate predictive models for both EGFR and KRAS were significantly improved (q-value < 0.05) following ComBat harmonization. The mean ranges of AUCs increased following harmonization from 0.87-0.90 to 0.92-0.94 for EGFR, and from 0.85-0.90 to 0.91-0.94 for KRAS. The highest performance was achieved by harmonized F_R0.66_W0.75 model with AUC of 0.94, and 0.93 for EGFR and KRAS, respectively. CONCLUSION: Our results demonstrated that regarding univariate modelling, while ComBat harmonization had generally a better impact on features for EGFR compared to KRAS status prediction, its effect is feature-dependent. Hence, no systematic effect was observed. Regarding the multivariate models, ComBat harmonization significantly improved the performance of all radiomics models toward more successful prediction of EGFR and KRAS mutation statuses in lung cancer patients. Thus, by eliminating the batch effect in multi-centric radiomic feature sets, harmonization is a promising tool for developing robust and reproducible radiomics using vast and variant datasets.

A comprehensive texture feature analysis framework of renal cell carcinoma: pathological, prognostic, and genomic evaluation based on CT images.

OBJECTIVES: We tried to realize accurate pathological classification, assessment of prognosis, and genomic molecular typing of renal cell carcinoma by CT texture feature analysis. To determine whether CT texture features can perform accurate pathological classification and evaluation of prognosis and genomic characteristics in renal cell carcinoma. METHODS: Patients with renal cell carcinoma from five open-source cohorts were analyzed retrospectively in this study. These data were randomly split to train and test machine learning algorithms to segment the lesion, predict the histological subtype, tumor stage, and pathological grade. Dice coefficient and performance metrics such as accuracy and AUC were calculated to evaluate the segmentation and classification model. Quantitative decomposition of the predictive model was conducted to explore the contribution of each feature. Besides, survival analysis and the statistical correlation between CT texture features, pathological, and genomic signatures were investigated. RESULTS: A total of 569 enhanced CT images of 443 patients (mean age 59.4, 278 males) were included in the analysis. In the segmentation task, the mean dice coefficient was 0.96 for the kidney and 0.88 for the cancer region. For classification of histologic subtype, tumor stage, and pathological grade, the model was on a par with radiologists and the AUC was 0.83 [Formula: see text] 0.1, 0.80 [Formula: see text] 0.1, and 0.77 [Formula: see text] 0.1 at 95% confidence intervals, respectively. Moreover, specific quantitative CT features related to clinical prognosis were identified. A strong statistical correlation (R2 = 0.83) between the feature crosses and genomic characteristics was shown. The structural equation modeling confirmed significant associations between CT features, pathological (ß = - 0.75), and molecular subtype (ß = - 0.30). CONCLUSIONS: The framework illustrates high performance in the pathological classification of renal cell carcinoma. Prognosis and genomic characteristics can be inferred by quantitative image analysis. KEY POINTS: • The analytical framework exhibits high-performance pathological classification of renal cell carcinoma and is on a par with human radiologists. • Quantitative decomposition of the predictive model shows that specific texture features contribute to histologic subtype and tumor stage classification. • Structural equation modeling shows the associations of genomic characteristics to CT texture features. Overall survival and molecular characteristics can be inferred by quantitative CT texture analysis in renal cell carcinoma.

Gastrointestinal stromal tumors: associations between contrast-enhanced CT images and KIT exon 11 gene mutation.

BACKGROUND: Mutation screening for gastrointestinal stromal tumor (GIST) is crucial and the c kit gene (KIT) exon 11 mutation is the most common type. This study aimed to explore the associations between GIST with KIT exon 11 mutation and contrast-enhanced computed tomography (CT) images. METHODS: Pathologically proven GISTs with definitive genotype testing results in our hospital were retrospectively included. Abdominal contrast-enhanced CT images were analyzed. Conventional CT image features and radiomic features were recorded and extracted to build the following models: model [CT], model [radiomic + clinic] and model [CT + radiomic + clinic]. The diagnostic performances of GISTs with KIT exon 11 mutation and KIT exon 11 deletion involving codons 557-558 were evaluated. RESULTS: In total, 327 GISTs (255 with KIT exon 11 mutation, and 73 with KIT exon 11 mutation deletion involving codons 557-558) were included. Significant CT features were found for GISTs with KIT exon 11 mutation. The area under curves (AUCs) of the models for KIT exon 11 mutation were 0.7158, 0.7530, and 0.8375 in the training cohort, and 0.6777, 0.7349, and 0.8105 in validation cohort, respectively. The AUCs of the models for KIT exon 11 mutation deletion involving codons 557-558 were 0.7155, 8621, and 0.8691 in the training cohort, and 0.7099, 0.8355, and 0.8488 in the validation cohort, respectively. The model [CT + radiomic + clinic] demonstrated the highest AUCs for prediction of KIT exon 11 mutation and those with deletion involving codons 557-558 (P<0.05), respectively. The model [radiomic + clinic] showed higher diagnostic performance than model [CT] significantly. CONCLUSIONS: Our results demonstrated the associations between GIST with KIT exon 11 mutation and contrast-enhanced CT images. We found combing conventional image analysis and texture analysis is a useful tool to distinguish GIST with KIT exon 11 mutation. CT radiogenomics exhibited good application potential in predict the KIT exon 11 mutation of GIST.

Signaling Pathways and Sex Differential Processes in Autism Spectrum Disorder.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders associated with deficits in social communication and restrictive, repetitive patterns of behavior, that affect up to 1 in 54 children. ASDs clearly demonstrate a male bias, occurring ~4 times more frequently in males than females, though the basis for this male predominance is not well-understood. In recent years, ASD risk gene discovery has accelerated, with many whole-exome sequencing studies identifying genes that converge on common pathways, such as neuronal communication and regulation of gene expression. ASD genetics studies have suggested that there may be a "female protective effect," such that females may have a higher threshold for ASD risk, yet its etiology is not well-understood. Here, we review common biological pathways implicated by ASD genetics studies as well as recent analyses of sex differential processes in ASD using imaging genomics, transcriptomics, and animal models. Additionally, we discuss recent investigations of ASD risk genes that have suggested a potential role for estrogens as modulators of biological pathways in ASD, and highlight relevant molecular and cellular pathways downstream of estrogen signaling as potential avenues for further investigation.