arXiv subjects

David L. Thomas

Publications and source records attributed to David L. Thomas.

4 recordsLinked to original sources

arXiv2025

Real-time, inline quantitative MRI enabled by scanner-integrated machine learning: a proof of principle with NODDI

Purpose: The clinical feasibility and translation of many advanced quantitative MRI (qMRI) techniques are inhibited by their restriction to 'research mode', due to resource-intensive, offline parameter estimation. This work aimed to achieve 'clinical mode' qMRI, by real-time, inline parameter estimation with a trained neural network (NN) fully integrated into a vendor's image reconstruction environment, therefore facilitating and encouraging clinical adoption of advanced qMRI techniques. Methods: The Siemens Image Calculation Environment (ICE) pipeline was customised to deploy trained NNs for advanced diffusion MRI parameter estimation with Open Neural Network Exchange (ONNX) Runtime. Two fully-connected NNs were trained offline with data synthesised with the neurite orientation dispersion and density imaging (NODDI) model, using either conventionally estimated (NNMLE) or ground truth (NNGT) parameters as training labels. The strategy was demonstrated online in two healthy volunteers (one rescanned) and evaluated offline with synthetic data, testing two diffusion protocols. Results: NNs were successfully integrated and deployed natively in ICE, performing inline, whole-brain, in vivo NODDI parameter estimation in <10 seconds. The proposed workflow was reproducible across protocols, volunteers and rescans. DICOM parametric maps were exported from the scanner for further analyses. Comparisons between NNMLE and NNGT suggested NNMLE parameter estimates to be more consistent with conventional fitting, a finding supported by offline evaluations. Conclusion: Real-time, inline parameter estimation with the proposed generalisable framework resolves a key practical barrier to the potential clinical uptake of advanced qMRI methods, enabling their efficient integration into clinical workflows. Next steps include incorporation of pre-processing methods and evaluation in pathology.

physics.med-ph↗

arXiv2022

Modeling in higher dimensions to improve diagnostic testing accuracy: theory and examples for multiplex saliva-based SARS-CoV-2 antibody assays

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has emphasized the importance and challenges of correctly interpreting antibody test results. Identification of positive and negative samples requires a classification strategy with low error rates, which is hard to achieve when the corresponding measurement values overlap. Additional uncertainty arises when classification schemes fail to account for complicated structure in data. We address these problems through a mathematical framework that combines high dimensional data modeling and optimal decision theory. Specifically, we show that appropriately increasing the dimension of data better separates positive and negative populations and reveals nuanced structure that can be described in terms of mathematical models. We combine these models with optimal decision theory to yield a classification scheme that better separates positive and negative samples relative to traditional methods such as confidence intervals (CIs) and receiver operating characteristics. We validate the usefulness of this approach in the context of a multiplex salivary SARS-CoV-2 immunoglobulin G assay dataset. This example illustrates how our analysis: (i) improves the assay accuracy (e.g. lowers classification errors by up to 42 % compared to CI methods); (ii) reduces the number of indeterminate samples when an inconclusive class is permissible (e.g. by 40 % compared to the original analysis of the example multiplex dataset); and (iii) decreases the number of antigens needed to classify samples. Our work showcases the power of mathematical modeling in diagnostic classification and highlights a method that can be adopted broadly in public health and clinical settings.

q-bio.QM↗

arXiv2022

Optimal Decision Theory for Diagnostic Testing: Minimizing Indeterminate Classes with Applications to Saliva-Based SARS-CoV-2 Antibody Assays

In diagnostic testing, establishing an indeterminate class is an effective way to identify samples that cannot be accurately classified. However, such approaches also make testing less efficient and must be balanced against overall assay performance. We address this problem by reformulating data classification in terms of a constrained optimization problem that (i) minimizes the probability of labeling samples as indeterminate while (ii) ensuring that the remaining ones are classified with an average target accuracy X. We show that the solution to this problem is expressed in terms of a bathtub principle that holds out those samples with the lowest local accuracy up to an X-dependent threshold. To illustrate the usefulness of this analysis, we apply it to a multiplex, saliva-based SARS-CoV-2 antibody assay and demonstrate up to a 30 % reduction in the number of indeterminate samples relative to more traditional approaches.

stat.ME↗

arXiv2021

Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($α_1$-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n=18,547) and three cohorts with pneumonia (n=400,907). Federated across two ARD cohorts, we find that patients exposed to $α_1$-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR=0.70, p=0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of $α_1$-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.

q-bio.TO↗