Differential privacy preserved federated transfer learning for multi-institutional 68Ga-PET image artefact detection and disentanglement.

PURPOSE: Image artefacts continue to pose challenges in clinical molecular imaging, resulting in misdiagnoses, additional radiation doses to patients and financial costs. Mismatch and halo artefacts occur frequently in gallium-68 (68Ga)-labelled compounds whole-body PET/CT imaging. Correcting for these artefacts is not straightforward and requires algorithmic developments, given that conventional techniques have failed to address them adequately. In the current study, we employed differential privacy-preserving federated transfer learning (FTL) to manage clinical data sharing and tackle privacy issues for building centre-specific models that detect and correct artefacts present in PET images. METHODS: Altogether, 1413 patients with 68Ga prostate-specific membrane antigen (PSMA)/DOTA-TATE (TOC) PET/CT scans from 3 countries, including 8 different centres, were enrolled in this study. CT-based attenuation and scatter correction (CT-ASC) was used in all centres for quantitative PET reconstruction. Prior to model training, an experienced nuclear medicine physician reviewed all images to ensure the use of high-quality, artefact-free PET images (421 patients' images). A deep neural network (modified U2Net) was trained on 80% of the artefact-free PET images to utilize centre-based (CeBa), centralized (CeZe) and the proposed differential privacy FTL frameworks. Quantitative analysis was performed in 20% of the clean data (with no artefacts) in each centre. A panel of two nuclear medicine physicians conducted qualitative assessment of image quality, diagnostic confidence and image artefacts in 128 patients with artefacts (256 images for CT-ASC and FTL-ASC). RESULTS: The three approaches investigated in this study for 68Ga-PET imaging (CeBa, CeZe and FTL) resulted in a mean absolute error (MAE) of 0.42 ± 0.21 (CI 95%: 0.38 to 0.47), 0.32 ± 0.23 (CI 95%: 0.27 to 0.37) and 0.28 ± 0.15 (CI 95%: 0.25 to 0.31), respectively. Statistical analysis using the Wilcoxon test revealed significant differences between the three approaches, with FTL outperforming CeBa and CeZe (p-value < 0.05) in the clean test set. The qualitative assessment demonstrated that FTL-ASC significantly improved image quality and diagnostic confidence and decreased image artefacts, compared to CT-ASC in 68Ga-PET imaging. In addition, mismatch and halo artefacts were successfully detected and disentangled in the chest, abdomen and pelvic regions in 68Ga-PET imaging. CONCLUSION: The proposed approach benefits from using large datasets from multiple centres while preserving patient privacy. Qualitative assessment by nuclear medicine physicians showed that the proposed model correctly addressed two main challenging artefacts in 68Ga-PET imaging. This technique could be integrated in the clinic for 68Ga-PET imaging artefact detection and disentanglement using multicentric heterogeneous datasets.

Machine learning-based analysis of 68Ga-PSMA-11 PET/CT images for estimation of prostate tumor grade.

Early diagnosis of prostate cancer, the most common malignancy in men, can improve patient outcomes. Since the tissue sampling procedures are invasive and sometimes inconclusive, an alternative image-based method can prevent possible complications and facilitate treatment management. We aim to propose a machine-learning model for tumor grade estimation based on 68 Ga-PSMA-11 PET/CT images in prostate cancer patients. This study included 90 eligible participants out of 244 biopsy-proven prostate cancer patients who underwent staging 68Ga-PSMA-11 PET/CT imaging. The patients were divided into high and low-intermediate groups based on their Gleason scores. The PET-only images were manually segmented, both lesion-based and whole prostate, by two experienced nuclear medicine physicians. Four feature selection algorithms and five classifiers were applied to Combat-harmonized and non-harmonized datasets. To evaluate the model's generalizability across different institutions, we performed leave-one-center-out cross-validation (LOOCV). The metrics derived from the receiver operating characteristic curve were used to assess model performance. In the whole prostate segmentation, combining the ANOVA algorithm as the feature selector with Random Forest (RF) and Extra Trees (ET) classifiers resulted in the highest performance among the models, with an AUC of 0.78 and 083, respectively. In the lesion-based segmentation, the highest AUC was achieved by MRMR feature selector + Linear Discriminant Analysis (LDA) and Logistic Regression (LR) classifiers (0.76 and 0.79, respectively). The LOOCV results revealed that both the RF_ANOVA and ET_ANOVA models showed high levels of accuracy and generalizability across different centers, with an average AUC value of 0.87 for the ET_ANOVA combination. Machine learning-based analysis of radiomics features extracted from 68Ga-PSMA-11 PET/CT scans can accurately classify prostate tumors into low-risk and intermediate- to high-risk groups.

A machine learning-based sonomics for prediction of thyroid nodule malignancies.

OBJECTIVES: This study aims to use ultrasound derived features as biomarkers to assess the malignancy of thyroid nodules in patients who were candidates for FNA according to the ACR TI-RADS guidelines. METHODS: Two hundred and ten patients who met the selection criteria were enrolled in the study and subjected to ultrasound-guided FNA of thyroid nodules. Different radiomics features were extracted from sonographic images, including intensity, shape, and texture feature sets. Least Absolute Shrinkage and Selection Operator (LASSO), Minimum Redundancy Maximum Relevance (MRMR), and Random Forests/Extreme Gradient Boosting Machine (XGBoost) algorithms were used for feature selection and classification of the univariate and multivariate modeling, respectively. Evaluation of models performed using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: In the univariate analysis, Gray Level Run Length Matrix - Run-Length Non-Uniformity (GLRLM-RLNU) and gray-level zone length matrix - Run-Length Non-Uniformity (GLZLM-GLNU) (both with an AUC of 0.67) were top-performing for predicting nodules malignancy. In the multivariate analysis of the training dataset, the AUC of all combinations of feature selection algorithms and classifiers was 0.99, and the highest sensitivity was for XGBoost classifier and MRMR feature selection algorithms (0.99). Finally, the test dataset was used to evaluate our model in which XGBoost classifier with MRMR and LASSO feature selection algorithms had the highest performance (AUC = 0.95). CONCLUSIONS: Ultrasound-extracted features can be used as non-invasive biomarkers for thyroid nodules' malignancy prediction.

Artificial intelligence-based analysis of whole-body bone scintigraphy: The quest for the optimal deep learning algorithm and comparison with human observer performance.

PURPOSE: Whole-body bone scintigraphy (WBS) is one of the most widely used modalities in diagnosing malignant bone diseases during the early stages. However, the procedure is time-consuming and requires vigour and experience. Moreover, interpretation of WBS scans in the early stages of the disorders might be challenging because the patterns often reflect normal appearance that is prone to subjective interpretation. To simplify the gruelling, subjective, and prone-to-error task of interpreting WBS scans, we developed deep learning (DL) models to automate two major analyses, namely (i) classification of scans into normal and abnormal and (ii) discrimination between malignant and non-neoplastic bone diseases, and compared their performance with human observers. MATERIALS AND METHODS: After applying our exclusion criteria on 7188 patients from three different centers, 3772 and 2248 patients were enrolled for the first and second analyses, respectively. Data were split into two parts, including training and testing, while a fraction of training data were considered for validation. Ten different CNN models were applied to single- and dual-view input (posterior and anterior views) modes to find the optimal model for each analysis. In addition, three different methods, including squeeze-and-excitation (SE), spatial pyramid pooling (SPP), and attention-augmented (AA), were used to aggregate the features for dual-view input models. Model performance was reported through area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, and specificity and was compared with the DeLong test applied to ROC curves. The test dataset was evaluated by three nuclear medicine physicians (NMPs) with different levels of experience to compare the performance of AI and human observers. RESULTS: DenseNet121_AA (DensNet121, with dual-view input aggregated by AA) and InceptionResNetV2_SPP achieved the highest performance (AUC = 0.72) for the first and second analyses, respectively. Moreover, on average, in the first analysis, Inception V3 and InceptionResNetV2 CNN models and dual-view input with AA aggregating method had superior performance. In addition, in the second analysis, DenseNet121 and InceptionResNetV2 as CNN methods and dual-view input with AA aggregating method achieved the best results. Conversely, the performance of AI models was significantly higher than human observers for the first analysis, whereas their performance was comparable in the second analysis, although the AI model assessed the scans in a drastically lower time. CONCLUSION: Using the models designed in this study, a positive step can be taken toward improving and optimizing WBS interpretation. By training DL models with larger and more diverse cohorts, AI could potentially be used to assist physicians in the assessment of WBS images.

[18F]FDG-PET/CT Radiomics and Artificial Intelligence in Lung Cancer: Technical Aspects and Potential Clinical Applications.

Lung cancer is the second most common cancer and the leading cause of cancer-related death worldwide. Molecular imaging using [18F]fluorodeoxyglucose Positron Emission Tomography and/or Computed Tomography ([18F]FDG-PET/CT) plays an essential role in the diagnosis, evaluation of response to treatment, and prediction of outcomes. The images are evaluated using qualitative and conventional quantitative indices. However, there is far more information embedded in the images, which can be extracted by sophisticated algorithms. Recently, the concept of uncovering and analyzing the invisible data extracted from medical images, called radiomics, is gaining more attention. Currently, [18F]FDG-PET/CT radiomics is growingly evaluated in lung cancer to discover if it enhances the diagnostic performance or implication of [18F]FDG-PET/CT in the management of lung cancer. In this review, we provide a short overview of the technical aspects, as they are discussed in different articles of this special issue. We mainly focus on the diagnostic performance of the [18F]FDG-PET/CT-based radiomics and the role of artificial intelligence in non-small cell lung cancer, impacting the early detection, staging, prediction of tumor subtypes, biomarkers, and patient's outcomes.

COVID-19 prognostic modeling using CT radiomic features and machine learning algorithms: Analysis of a multi-institutional dataset of 14,339 patients.

BACKGROUND: We aimed to analyze the prognostic power of CT-based radiomics models using data of 14,339 COVID-19 patients. METHODS: Whole lung segmentations were performed automatically using a deep learning-based model to extract 107 intensity and texture radiomics features. We used four feature selection algorithms and seven classifiers. We evaluated the models using ten different splitting and cross-validation strategies, including non-harmonized and ComBat-harmonized datasets. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were reported. RESULTS: In the test dataset (4,301) consisting of CT and/or RT-PCR positive cases, AUC, sensitivity, and specificity of 0.83 ± 0.01 (CI95%: 0.81-0.85), 0.81, and 0.72, respectively, were obtained by ANOVA feature selector + Random Forest (RF) classifier. Similar results were achieved in RT-PCR-only positive test sets (3,644). In ComBat harmonized dataset, Relief feature selector + RF classifier resulted in the highest performance of AUC, reaching 0.83 ± 0.01 (CI95%: 0.81-0.85), with a sensitivity and specificity of 0.77 and 0.74, respectively. ComBat harmonization did not depict statistically significant improvement compared to a non-harmonized dataset. In leave-one-center-out, the combination of ANOVA feature selector and RF classifier resulted in the highest performance. CONCLUSION: Lung CT radiomics features can be used for robust prognostic modeling of COVID-19. The predictive power of the proposed CT radiomics model is more reliable when using a large multicentric heterogeneous dataset, and may be used prospectively in clinical setting to manage COVID-19 patients.

Treatment response prediction using MRI-based pre-, post-, and delta-radiomic features and machine learning algorithms in colorectal cancer.

OBJECTIVES: We evaluate the feasibility of treatment response prediction using MRI-based pre-, post-, and delta-radiomic features for locally advanced rectal cancer (LARC) patients treated by neoadjuvant chemoradiation therapy (nCRT). MATERIALS AND METHODS: This retrospective study included 53 LARC patients divided into a training set (Center#1, n = 36) and external validation set (Center#2, n = 17). T2-weighted (T2W) MRI was acquired for all patients, 2 weeks before and 4 weeks after nCRT. Ninety-six radiomic features, including intensity, morphological and second- and high-order texture features were extracted from segmented 3D volumes from T2W MRI. All features were harmonized using ComBat algorithm. Max-Relevance-Min-Redundancy (MRMR) algorithm was used as feature selector and k-nearest neighbors (KNN), Naïve Bayes (NB), Random forests (RF), and eXtreme Gradient Boosting (XGB) algorithms were used as classifiers. The evaluation was performed using the area under the receiver operator characteristic (ROC) curve (AUC), sensitivity, specificity and accuracy. RESULTS: In univariate analysis, the highest AUC in pre-, post-, and delta-radiomic features were 0.78, 0.70, and 0.71, for GLCM_IMC1, shape (surface area and volume) and GLSZM_GLNU features, respectively. In multivariate analysis, RF and KNN achieved the highest AUC (0.85 ± 0.04 and 0.81 ± 0.14, respectively) among pre- and post-treatment features. The highest AUC was achieved for the delta-radiomic-based RF model (0.96 ± 0.01) followed by NB (0.96 ± 0.04). Overall. Delta-radiomics model, outperformed both pre- and post-treatment features (P-value <0.05). CONCLUSION: Multivariate analysis of delta-radiomic T2W MRI features using machine learning algorithms could potentially be used for response prediction in LARC patients undergoing nCRT. We also observed that multivariate analysis of delta-radiomic features using RF classifiers can be used as powerful biomarkers for response prediction in LARC.

Enhancement of chemoradiation by co-incorporation of gold nanoparticles and cisplatin into alginate hydrogel.

Nonspecificity and high toxicity limit the treatment efficacy and safety of chemoradiation therapy. Effective tumor targeting of anticancer drugs and radiosensitizing agents is highly desirable to amplify the efficacy of this standard cancer therapy approach. To achieve this goal, we exploited the synergy of cisplatin and gold nanoparticles (AuNPs) co-loaded into alginate hydrogel network, forming so-called ACA nanocomplex, and X-ray radiation. Cisplatin is a commonly used anticancer agent, and at the same time, along with AuNPs could function as radiosensitizers to enhance the radiation-induced damages through various pathways. The ACA nanocomplex improved the therapeutic efficiency of standard chemotherapy and yielded 79% growth inhibition in CT26 colon adenocarcinoma tumor after 28 days, which was significantly higher than that of 9% for free cisplatin administration. Moreover, the combination of ACA nanocomplex with 6 MV X-ray dramatically suppressed tumor growth up to 95%, showing 51% enhancement in antitumor activity compared to standard chemoradiation. The nanocomplex developed herein holds the promise to promote the efficiency of standard chemoradiation while maintaining the patient's safety through reducing the clinically administered doses of anticancer drug and X-ray. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2658-2663, 2019.

Investigating the Therapeutic Effects of Alginate Nanogel Co-loaded with Gold Nanoparticles and Cisplatin on U87-MG Human Glioblastoma Cells.

BACKGROUND AND PURPOSE: It has been well-known both gold nanoparticles (AuNPs) and cisplatin are potential radiosensitizers for radiotherapy of cancer. In this in vitro study, we investigated the chemoradiotherapeutic effects of alginate nanogel co-loaded with AuNPs and cisplatin (ACA) on U87-MG human glioblastoma cells. METHODS: Based on the accomplished pilot studies, U87-MG cells were incubated with ACA and cisplatin at 10% inhibitory concentration (IC10) for 4h. Then, the cells were irradiated to different doses of 6MV X-rays (2 and 10 Gy). MTT assay was performed to evaluate the cell survival rate. Apoptosis was determined by flow cytometry using an annexinV-fluorescein isothiocyanate/propidium iodide apoptosis detection kit. RESULTS: The results showed that ACA at the concentration of 4 µg/ml (per cisplatin) and free cisplatin at concentration of 15 µg/ml have the same effects on U87-MG cells (survival rate: 90%). The combination of ACA with radiation resulted in a significant decrease in cell viability (survival rate: 30%). The flow cytometry assay also showed that such a combination therapy induces more apoptosis than necrosis. CONCLUSION: It may be concluded that co-delivery of AuNPs and cisplatin with a single nanoplatform like ACA nanocomplex enhances the therapeutic ratio of human glioblastoma radiation therapy.