Probabilistic nested model selection in pharmacokinetic analysis of DCE-MRI data in animal model of cerebral tumor

Document Type

Article

Publication Date

1-13-2025

Publication Title

Sci Rep

Keywords

Animals, Magnetic Resonance Imaging, Rats, Brain Neoplasms, Contrast Media, Disease Models, Animal, Humans, Models, Statistical, Cell Line, Tumor

Abstract

Best current practice in the analysis of dynamic contrast enhanced (DCE)-MRI is to employ a voxel-by-voxel model selection from a hierarchy of nested models. This nested model selection (NMS) assumes that the observed time-trace of contrast-agent (CA) concentration within a voxel, corresponds to a singular physiologically nested model. However, admixtures of different models may exist within a voxel's CA time-trace. This study introduces an unsupervised feature engineering technique (Kohonen-Self-Organizing-Map (K-SOM)) to estimate the voxel-wise probability of each nested model. Sixty-six immune-compromised-RNU rats were implanted with human U-251 N cancer cells, and DCE-MRI data were acquired from all the rat brains. The time-trace of change in the longitudinal-relaxivity (ΔR(1)) for all animals' brain voxels was calculated. DCE-MRI pharmacokinetic (PK) analysis was performed using NMS to estimate three model regions: Model-1: normal vasculature without leakage, Model-2: tumor tissues with leakage without back-flux to the vasculature, Model-3: tumor vessels with leakage and back-flux. Approximately two hundred thirty thousand (229,314) normalized ΔR(1) profiles of animals' brain voxels along with their NMS results were used to build a K-SOM (topology-size: 8 × 8, with competitive-learning algorithm) and probability map of each model. K-fold nested-cross-validation (NCV, k  =  10) was used to evaluate the performance of the K-SOM probabilistic-NMS (PNMS) technique against the NMS technique. The K-SOM PNMS's estimation for the leaky tumor regions were strongly similar (Dice-Similarity-Coefficient, DSC  =  0.774 [CI: 0.731-0.823], and 0.866 [CI: 0.828-0.912] for Models 2 and 3, respectively) to their respective NMS regions. The mean-percent-differences (MPDs, NCV, k  =  10) for the estimated permeability parameters by the two techniques were: -28%, + 18%, and + 24%, for v(p), K(trans), and v(e), respectively. The KSOM-PNMS technique produced microvasculature parameters and NMS regions less impacted by the arterial-input-function dispersion effect. This study introduces an unsupervised model-averaging technique (K-SOM) to estimate the contribution of different nested-models in PK analysis and provides a faster estimate of permeability parameters.

Medical Subject Headings

Animals; Magnetic Resonance Imaging; Rats; Brain Neoplasms; Contrast Media; Disease Models; Animal; Humans; Models; Statistical; Cell Line; Tumor

PubMed ID

39805838

Volume

15

Issue

1

First Page

1786

Last Page

1786

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