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Tammie L. S. Benzinger

Publications and source records attributed to Tammie L. S. Benzinger.

3 recordsLinked to original sources

Development and in silico imaging trial evaluation of a deep-learning-based transmission-less attenuation compensation method for DaT SPECT

Quantitative measures of dopamine transporter (DaT) uptake in caudate, putamen, and globus pallidus derived from DaT-single-photon emission computed tomography (SPECT) images are being investigated as biomarkers to diagnose, assess disease status, and track the progression of Parkinsonism. Reliable quantification from DaT-SPECT images requires performing attenuation compensation (AC), typically with a separate X-ray CT scan. Such CT-based AC (CTAC) has multiple challenges, a key one being the non-availability of X-ray CT component on many clinical SPECT systems. Even when a CT is available, the additional CT scan leads to increased radiation dose, costs, and complexity, potential quantification errors due to SPECT-CT misalignment, and higher training and regulatory requirements. To overcome the challenges with the requirement of a CT scan for AC in DaT SPECT, we propose a deep learning (DL)-based transmission-less AC method for DaT-SPECT (DaT-CTLESS). An in silico imaging trial, titled ISIT-DaT, was designed to evaluate the performance of DaT-CTLESS on the regional uptake quantification task. We observed that DaT-CTLESS yielded a significantly higher correlation with CTAC than that between UAC and CTAC on the regional DaT uptake quantification task. Further, DaT-CLTESS had an excellent agreement with CTAC on this task, significantly outperformed UAC in distinguishing patients with normal versus reduced putamen SBR, yielded good generalizability across two scanners, was generally insensitive to intra-regional uptake heterogeneity, demonstrated good repeatability, exhibited robust performance even as the size of the training data was reduced, and generally outperformed the other considered DL methods on the task of quantifying regional uptake across different training dataset sizes. These results provide a strong motivation for further clinical evaluation of DaT-CTLESS.

physics.med-ph↗

Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers

INTRODUCTION: Previous studies have applied normative modeling on a single neuroimaging modality to investigate Alzheimer Disease (AD) heterogeneity. We employed a deep learning-based multimodal normative framework to analyze individual-level variation across ATN (amyloid-tau-neurodegeneration) imaging biomarkers. METHODS: We selected cross-sectional discovery (n = 665) and replication cohorts (n = 430) with available T1-weighted MRI, amyloid and tau PET. Normative modeling estimated individual-level abnormal deviations in amyloid-positive individuals compared to amyloid-negative controls. Regional abnormality patterns were mapped at different clinical group levels to assess intra-group heterogeneity. An individual-level disease severity index (DSI) was calculated using both the spatial extent and magnitude of abnormal deviations across ATN. RESULTS: Greater intra-group heterogeneity in ATN abnormality patterns was observed in more severe clinical stages of AD. Higher DSI was associated with worse cognitive function and increased risk of disease progression. DISCUSSION: Subject-specific abnormality maps across ATN reveal the heterogeneous impact of AD on the brain.

q-bio.NC↗

Gene-SGAN: a method for discovering disease subtypes with imaging and genetic signatures via multi-view weakly-supervised deep clustering

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and SNP data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-driven neuroimaging phenotypes.

q-bio.QM↗