Synthetic data generation for a longitudinal cohort study - evaluation, method extension and reproduction of published data analysis results.

Access to individual-level health data is essential for gaining new insights and advancing science. In particular, modern methods based on artificial intelligence rely on the availability of and access to large datasets. In the health sector, access to individual-level data is often challenging due to privacy concerns. A promising alternative is the generation of fully synthetic data, i.e., data generated through a randomised process that have similar statistical properties as the original data, but do not have a one-to-one correspondence with the original individual-level records. In this study, we use a state-of-the-art synthetic data generation method and perform in-depth quality analyses of the generated data for a specific use case in the field of nutrition. We demonstrate the need for careful analyses of synthetic data that go beyond descriptive statistics and provide valuable insights into how to realise the full potential of synthetic datasets. By extending the methods, but also by thoroughly analysing the effects of sampling from a trained model, we are able to largely reproduce significant real-world analysis results in the chosen use case.

Artificial intelligence for clinical decision support for monitoring patients in cardiovascular ICUs: A systematic review.

Background: Artificial intelligence (AI) and machine learning (ML) models continue to evolve the clinical decision support systems (CDSS). However, challenges arise when it comes to the integration of AI/ML into clinical scenarios. In this systematic review, we followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), the population, intervention, comparator, outcome, and study design (PICOS), and the medical AI life cycle guidelines to investigate studies and tools which address AI/ML-based approaches towards clinical decision support (CDS) for monitoring cardiovascular patients in intensive care units (ICUs). We further discuss recent advances, pitfalls, and future perspectives towards effective integration of AI into routine practices as were identified and elaborated over an extensive selection process for state-of-the-art manuscripts. Methods: Studies with available English full text from PubMed and Google Scholar in the period from January 2018 to August 2022 were considered. The manuscripts were fetched through a combination of the search keywords including AI, ML, reinforcement learning (RL), deep learning, clinical decision support, and cardiovascular critical care and patients monitoring. The manuscripts were analyzed and filtered based on qualitative and quantitative criteria such as target population, proper study design, cross-validation, and risk of bias. Results: More than 100 queries over two medical search engines and subjective literature research were developed which identified 89 studies. After extensive assessments of the studies both technically and medically, 21 studies were selected for the final qualitative assessment. Discussion: Clinical time series and electronic health records (EHR) data were the most common input modalities, while methods such as gradient boosting, recurrent neural networks (RNNs) and RL were mostly used for the analysis. Seventy-five percent of the selected papers lacked validation against external datasets highlighting the generalizability issue. Also, interpretability of the AI decisions was identified as a central issue towards effective integration of AI in healthcare.

Predicting readmission to the cardiovascular intensive care unit using recurrent neural networks.

If a patient can be discharged from an intensive care unit (ICU) is usually decided by the treating physicians based on their clinical experience. However, nowadays limited capacities and growing socioeconomic burden of our health systems increase the pressure to discharge patients as early as possible, which may lead to higher readmission rates and potentially fatal consequences for the patients. Therefore, here we present a long short-term memory-based deep learning model (LSTM) trained on time series data from Medical Information Mart for Intensive Care (MIMIC-III) dataset to assist physicians in making decisions if patients can be safely discharged from cardiovascular ICUs. To underline the strengths of our LSTM we compare its performance with a logistic regression model, a random forest, extra trees, a feedforward neural network and with an already known, more complex LSTM as well as an LSTM combined with a convolutional neural network. The results of our evaluation show that our LSTM outperforms most of the above models in terms of area under receiver operating characteristic curve. Moreover, our LSTM shows the best performance with respect to the area under precision-recall curve. The deep learning solution presented in this article can help physicians decide on patient discharge from the ICU. This may not only help to increase the quality of patient care, but may also help to reduce costs and to optimize ICU resources. Further, the presented LSTM-based approach may help to improve existing and develop new medical machine learning prediction models.

Evaluating a Machine Learning Tool for the Classification of Pathological Uptake in Whole-Body PSMA-PET-CT Scans.

The importance of machine learning (ML) in the clinical environment increases constantly. Differentiation of pathological from physiological tracer-uptake in positron emission tomography/computed tomography (PET/CT) images is considered time-consuming and attention intensive, hence crucial for diagnosis and treatment planning. This study aimed at comparing and validating supervised ML algorithms to classify pathological uptake in prostate cancer (PC) patients based on prostate-specific membrane antigen (PSMA)-PET/CT. Retrospective analysis of 68Ga-PSMA-PET/CTs of 72 PC patients resulted in a total of 77 radiomics features from 2452 manually delineated hotspots for training and labeled pathological (1629) or physiological (823) as ground truth (GT). As the held-out test dataset, 331 hotspots (path.:128, phys.: 203) were delineated in 15 other patients. Three ML classifiers were trained and ranked to assess classification performance. As a result, a high overall average performance (area under the curve (AUC) of 0.98) was achieved, especially to detect pathological uptake (0.97 mean sensitivity). However, there is still room for improvement to detect physiological uptake (0.82 mean specificity), especially for glands. The ML algorithm applied to manually delineated lesions predicts hotspot labels with high accuracy on unseen data and may be an important tool to assist in clinical diagnosis.

Decision-support for treatment with 177Lu-PSMA: machine learning predicts response with high accuracy based on PSMA-PET/CT and clinical parameters.

BACKGROUND: Treatment with radiolabeled ligands to prostate-specific membrane antigen (PSMA) is gaining importance in the treatment of patients with advanced prostate carcinoma. Previous imaging with positron emission tomography/computed tomography (PET/CT) is mandatory. The aim of this study was to investigate the role of radiomics features in PSMA-PET/CT scans and clinical parameters to predict response to 177Lu-PSMA treatment given just baseline PSMA scans using state-of-the-art machine learning (ML) methods. METHODS: A total of 2,070 pathological hotspots annotated in 83 prostate cancer patients undergoing PSMA therapy were analyzed. Two main tasks are performed: (I) analyzing correlation of averaged (per patient) values of radiomics features of individual hotspots and clinical parameters with difference in prostate specific antigen levels (ΔPSA) in pre- and post-therapy as a therapy response indicator. (II) ML-based classification of patients into responders and non-responders based on averaged features values and clinical parameters. To achieve this, machine learning (ML) algorithms and linear regression tests are applied. Grid search, cross validation (CV) and permutation test were performed to assure that the results were significant. RESULTS: Radiomics features (PET_Min, PET_Correlation, CT_Min, CT_Busyness and CT_Coarseness) and clinical parameters such as Alp1 and Gleason score showed best correlations with ΔPSA. For the treatment response prediction task, 80% area under the curve (AUC), 75% sensitivity (SE), and 75% specificity (SP) were obtained, applying ML support vector machine (SVM) classifier with radial basis function (RBF) kernel on a selection of radiomics features and clinical parameters with strong correlations with ΔPSA. CONCLUSIONS: Machine learning based on 68Ga-PSMA PET/CT radiomics features holds promise for the prediction of response to 177Lu-PSMA treatment, given only base-line 68Ga-PSMA scan. In addition, it was shown that, the best correlating set of radiomics features with ΔPSA are superior to clinical parameters for this therapy response prediction task using ML classifiers.

Estimating the Potential of Radiomics Features and Radiomics Signature from Pretherapeutic PSMA-PET-CT Scans and Clinical Data for Prediction of Overall Survival When Treated with 177Lu-PSMA.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PSMA-PET/CT) scans can facilitate diagnosis and treatment of prostate disease. Radiomics signature (RS) is widely used for the analysis of overall survival (OS) in cancer diseases. This study aims at investigating the role of radiomics features (RFs) and RS from pretherapeutic gallium-68 (68Ga)-PSMA-PET/CT findings and patient-specific clinical parameters to analyze overall survival of prostate cancer (PC) patients when treated with lutethium-177 (177Lu)-PSMA. A cohort of 83 patients with advanced PC was retrospectively analyzed. Average values of 73 RFs of 2070 malignant hotspots as well as 22 clinical parameters were analyzed for each patient. From the Cox proportional hazard model, the least absolute shrinkage and selection operator (LASSO) regularization method is used to select most relevant features (standardized uptake value (SUV)Min and kurtosis with the coefficients of 0.984 and -0.118, respectively) and to calculate the RS from the RFs. Kaplan-Meier (KM) estimator was used to analyze the potential of RFs and conventional clinical parameters, such as metabolic tumor volume (MTV) and standardized uptake value (SUV) for the prediction of survival. As a result, SUVMin, kurtosis, the calculated RS, SUVMean, as well as Hemoglobin (Hb)1, C-reactive protein (CRP)1, and ECOG1 (clinical parameters) achieved p-values less than 0.05, which suggest the potential of findings from 68Ga-PSMA-PET/CT scans as well as patient-specific clinical parameters for the prediction of OS for patients with advanced PC treated with 177Lu-PSMA therapy.

Machine Learning Facilitates Hotspot Classification in PSMA-PET/CT with Nuclear Medicine Specialist Accuracy.

Gallium-68 prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET) is a highly sensitive method to detect prostate cancer (PC) metastases. Visual discrimination between malignant and physiologic/unspecific tracer accumulation by a nuclear medicine (NM) specialist is essential for image interpretation. In the future, automated machine learning (ML)-based tools will assist physicians in image analysis. The aim of this work was to develop a tool for analysis of 68Ga-PSMA-PET images and to compare its efficacy to that of human readers. Five different ML methods were compared and tested on multiple positron emission tomography/computed tomography (PET/CT) data-sets. Forty textural features extracted from both PET- and low-dose CT data were analyzed. In total, 2419 hotspots from 72 patients were included. Comparing results from human readers to those of ML-based analyses, up to 98% area under the curve (AUC), 94% sensitivity (SE), and 89% specificity (SP) were achieved. Interestingly, textural features assessed in native low-dose CT increased the accuracy significantly. Thus, ML based on 68Ga-PSMA-PET/CT radiomics features can classify hotspots with high precision, comparable to that of experienced NM physicians. Additionally, the superiority of multimodal ML-based analysis considering all PET and low-dose CT features was shown. Morphological features seemed to be of special additional importance even though they were extracted from native low-dose CTs.