Non-coplanar CBCT image reconstruction using a generative adversarial network for non-coplanar radiotherapy.

PURPOSE: To develop a non-coplanar cone-beam computed tomography (CBCT) image reconstruction method using projections within a limited angle range for non-coplanar radiotherapy. METHODS: A generative adversarial network (GAN) was utilized to reconstruct non-coplanar CBCT images. Data from 40 patients with brain tumors and two head phantoms were used in this study. In the training stage, the generator of the GAN used coplanar CBCT and non-coplanar projections as the input, and an encoder with a dual-branch structure was utilized to extract features from the coplanar CBCT and non-coplanar projections separately. Non-coplanar CBCT images were then reconstructed using a decoder by combining the extracted features. To improve the reconstruction accuracy of the image details, the generator was adversarially trained using a patch-based convolutional neural network as the discriminator. A newly designed joint loss was used to improve the global structure consistency rather than the conventional GAN loss. The proposed model was evaluated using data from eight patients and two phantoms at four couch angles (±45°, ±90°) that are most commonly used for brain non-coplanar radiotherapy in our department. The reconstructed accuracy was evaluated by calculating the root mean square error (RMSE) and an overall registration error ε, computed by integrating the rigid transformation parameters. RESULTS: In both patient data and phantom data studies, the qualitative and quantitative metrics results indicated that ± 45° couch angle models performed better than ±90° couch angle models and had statistical differences. In the patient data study, the mean RMSE and ε values of couch angle at 45°, -45°, 90°, and -90° were 58.5 HU and 0.42 mm, 56.8 HU and 0.41 mm, 73.6 HU and 0.48 mm, and 65.3 HU and 0.46 mm, respectively. In the phantom data study, the mean RMSE and ε values of couch angle at 45°, -45°, 90°, and -90° were 91.2 HU and 0.46 mm, 95.0 HU and 0.45 mm, 114.6 HU and 0.58 mm, and 102.9 HU and 0.52 mm, respectively. CONCLUSIONS: The results show that the reconstructed non-coplanar CBCT images can potentially enable intra-treatment three-dimensional position verification for non-coplanar radiotherapy.

Strategy for Identifying a Robust Metabolomic Signature Reveals the Altered Lipid Metabolism in Pituitary Adenoma.

Despite the well-established connection between systematic metabolic abnormalities and the pathophysiology of pituitary adenoma (PA), current metabolomic studies have reported an extremely limited number of metabolites associated with PA. Moreover, there was very little consistency in the identified metabolite signatures, resulting in a lack of robust metabolic biomarkers for the diagnosis and treatment of PA. Herein, we performed a global untargeted plasma metabolomic profiling on PA and identified a highly robust metabolomic signature based on a strategy. Specifically, this strategy is unique in (1) integrating repeated random sampling and a consensus evaluation-based feature selection algorithm and (2) evaluating the consistency of metabolomic signatures among different sample groups. This strategy demonstrated superior robustness and stronger discriminative ability compared with that of other feature selection methods including Student's t-test, partial least-squares-discriminant analysis, support vector machine recursive feature elimination, and random forest recursive feature elimination. More importantly, a highly robust metabolomic signature comprising 45 PA-specific differential metabolites was identified. Moreover, metabolite set enrichment analysis of these potential metabolic biomarkers revealed altered lipid metabolism in PA. In conclusion, our findings contribute to a better understanding of the metabolic changes in PA and may have implications for the development of diagnostic and therapeutic approaches targeting lipid metabolism in PA. We believe that the proposed strategy serves as a valuable tool for screening robust, discriminating metabolic features in the field of metabolomics.

Decoding Drug Response with Structurized Gridding Map-based Cell Representation.

A thorough understanding of cell-line drug response mechanisms is crucial for drug development, repurposing, and resistance reversal. While targeted anticancer therapies have shown promise, not all cancers have well-established biomarkers to stratify drug response. Single-gene associations only explain a small fraction of the observed drug sensitivity, so a more comprehensive method is needed. However, while deep learning models have shown promise in predicting drug response in cell lines, they still face significant challenges when it comes to their application in clinical applications. Therefore, this study proposed a new strategy called DD-Response for cell-line drug response prediction. First, a limitation of narrow modeling horizons was overcome to expand the model training domain by integrating multiple datasets through source-specific label binarization. Second, a modified representation based on a two-dimensional structurized gridding map (SGM) was developed for cell lines & drugs, avoiding feature correlation neglect and potential information loss. Third, a dual-branch, multi-channel convolutional neural network-based model for pairwise response prediction was constructed, enabling accurate outcomes and improved exploration of underlying mechanisms. As a result, the DD-Response demonstrated superior performance, captured cell-line characteristic variations, and provided insights into key factors impacting cell-line drug response. In addition, DD-Response exhibited scalability in predicting clinical patient responses to drug therapy. Overall, because of DD-response's excellent ability to predict drug response and capture key molecules behind them, DD-response is expected to greatly facilitate drug discovery, repurposing, resistance reversal, and therapeutic optimization.

A subregion-based prediction model for local-regional recurrence risk in head and neck squamous cell carcinoma.

BACKGROUND AND PURPOSE: Given that the intratumoral heterogeneity of head and neck squamous cell carcinoma may be related to the local control rate of radiotherapy, the aim of this study was to construct a subregion-based model that can predict the risk of local-regional recurrence, and to quantitatively assess the relative contribution of subregions. MATERIALS AND METHODS: The CT images, PET images, dose images and GTVs of 228 patients with head and neck squamous cell carcinoma from four different institutions of the The Cancer Imaging Archive(TCIA) were included in the study. Using a supervoxel segmentation algorithm called maskSLIC to generate individual-level subregions. After extracting 1781 radiomics and 1767 dosiomics features from subregions, an attention-based multiple instance risk prediction model (MIR) was established. The GTV model was developed based on the whole tumour area and was used to compare the prediction performance with the MIR model. Furthermore, the MIR-Clinical model was constructed by integrating the MIR model with clinical factors. Subregional analysis was carried out through the Wilcoxon test to find the differential radiomic features between the highest and lowest weighted subregions. RESULTS: Compared with the GTV model, the C-index of MIR model was significantly increased from 0.624 to 0.721(Wilcoxon test, p value < 0.0001). When MIR model was combined with clinical factors, the C-index was further increased to 0.766. Subregional analysis showed that for LR patients, the top three differential radiomic features between the highest and lowest weighted subregions were GLRLM_ShortRunHighGrayLevelEmphasis, GRLM_HghGrayLevelRunEmphasis and GLRLM_LongRunHighGrayLevelEmphasis. CONCLUSION: This study developed a subregion-based model that can predict the risk of local-regional recurrence and quantitatively assess relevant subregions, which may provide technical support for the precision radiotherapy in head and neck squamous cell carcinoma.

Machine Learning Based on a Multiparametric and Multiregional Radiomics Signature Predicts Radiotherapeutic Response in Patients with Glioblastoma.

METHODS: The MRI images, genetic data, and clinical data of 152 patients with GBM were analyzed. 122 patients from the TCIA dataset (training set: n = 82; validation set: n = 40) and 30 patients from local hospitals were used as an independent test dataset. Radiomics features were extracted from multiple regions of multiparameter MRI. Kaplan-Meier survival analysis was used to verify the ability of the imaging signature to predict the response of GBM patients to radiotherapy before an operation. Multivariate Cox regression including radiomics signature and preoperative clinical risk factors was used to further improve the ability to predict the overall survival (OS) of individual GBM patients, which was presented in the form of a nomogram. RESULTS: The radiomics signature was built by eight selected features. The C-index of the radiomics signature in the TCIA and independent test cohorts was 0.703 (P < 0.001) and 0.757 (P = 0.001), respectively. Multivariate Cox regression analysis confirmed that the radiomics signature (HR: 0.290, P < 0.001), age (HR: 1.023, P = 0.01), and KPS (HR: 0.968, P < 0.001) were independent risk factors for OS in GBM patients before surgery. When the radiomics signature and preoperative clinical risk factors were combined, the radiomics nomogram further improved the performance of OS prediction in individual patients (C-index = 0.764 and 0.758 in the TCIA and test cohorts, respectively). CONCLUSION: This study developed a radiomics signature that can predict the response of individual GBM patients to radiotherapy and may be a new supplement for precise GBM radiotherapy.