Morphodynamic Modeling of Glioblastoma Using 3D Autoencoders and Neural Ordinary Differential Equations: Identification of Morphological Attractors and Dynamic Phase Maps

Background: Glioblastoma (GBM) is among the most aggressive and morphologically heterogeneous brain tumors. Beyond static imaging biomarkers, its structural organization can be viewed as a nonlinear dynamical system. Characterizing morphodynamic attractors within such a system may reveal latent stability patterns of morphological change and potential indicators of morphodynamic organization. Methods: We analyzed 494 subjects from the multi-institutional BraTS 2020 dataset using a fully automated computational pipeline. Each multimodal MRI volume was encoded into a 16-dimensional latent space using a 3D convolutional autoencoder. Synthetic morphological trajectories, generated through bidirectional growth–shrinkage transformations of tumor masks, enabled training of a contraction-regularized Neural Ordinary Differential Equation (Neural ODE) to model continuous-time latent morphodynamics. Morphological complexity was quantified using fractal dimension (DF), and local dynamical stability was measured via a Lyapunov-like exponent (λ). Robustness analyses assessed the stability of DF–λ regimes under multi-scale perturbations, synthetic-order reversal (directionality; sign-aware comparison) and stochastic noise, including cross-generator generalization against a time-shuffled negative control. Results: The DF–λ morphodynamic phase map revealed three characteristic regimes: (1) stable morphodynamics (λ < 0), associated with compact, smoother boundaries; (2) metastable dynamics (λ ≈ 0), reflecting weakly stable or transitional behavior; and (3) unstable or chaotic dynamics (λ > 0), associated with divergent latent trajectories. Latent-space flow fields exhibited contraction-induced attractor-like basins and smoothly diverging directions. Kernel-density estimation of DF–λ distributions revealed a prominent population cluster within the metastable regime, characterized by moderate-to-high geometric irregularity (DF ≈ 1.85–2.00) and near-neutral dynamical stability (λ ≈ −0.02 to +0.01). Exploratory clinical overlays showed that fractal dimension exhibited a modest negative association with survival, whereas λ did not correlate with clinical outcome, suggesting that the two descriptors capture complementary and clinically distinct aspects of tumor morphology. Conclusions: Glioblastoma morphology can be represented as a continuous dynamical process within a learned latent manifold. Combining Neural ODE–based dynamics, fractal morphometry, and Lyapunov stability provides a principled framework for dynamic radiomics, offering interpretable morphodynamic descriptors that bridge fractal geometry, nonlinear dynamics, and deep learning. Because BraTS is cross-sectional and the synthetic step index does not represent biological time, any clinical interpretation is hypothesis-generating; validation in longitudinal and covariate-rich cohorts is required before prognostic or treatment-monitoring use. The resulting DF–λ morphodynamic map provides a hypothesis-generating morphodynamic representation that should be evaluated in covariate-rich and longitudinal cohorts before any prognostic or treatment-monitoring use.

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Journal
Fractal and Fractional
Published
2025-12-23
DOI
https://doi.org/10.3390/fractalfract10010008
Primary Topic
Glioma Diagnosis and Treatment
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article
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article

Morphodynamic Modeling of Glioblastoma Using 3D Autoencoders and Neural Ordinary Differential Equations: Identification of Morphological Attractors and Dynamic Phase Maps

Maricel Agop, Lăcrămioara Ochiuz, Diana Carmen Mirila, Monica Molcăluţ et al.
Fractal and Fractional
Glioma Diagnosis and Treatment
article

Morphodynamic Modeling of Glioblastoma Using 3D Autoencoders and Neural Ordinary Differential Equations: Identification of Morphological Attractors and Dynamic Phase Maps

Maricel Agop, Lăcrămioara Ochiuz, Diana Carmen Mirila, Monica Molcăluţ, Florin Nedeff, Dragoș Teodor Iancu, Valentin Nedeff, Călin Gheorghe Buzea
article en

Abstract

Background: Glioblastoma (GBM) is among the most aggressive and morphologically heterogeneous brain tumors. Beyond static imaging biomarkers, its structural organization can be viewed as a nonlinear dynamical system. Characterizing morphodynamic attractors within such a system may reveal latent stability patterns of morphological change and potential indicators of morphodynamic organization. Methods: We analyzed 494 subjects from the multi-institutional BraTS 2020 dataset using a fully automated computational pipeline. Each multimodal MRI volume was encoded into a 16-dimensional latent space using a 3D convolutional autoencoder. Synthetic morphological trajectories, generated through bidirectional growth–shrinkage transformations of tumor masks, enabled training of a contraction-regularized Neural Ordinary Differential Equation (Neural ODE) to model continuous-time latent morphodynamics. Morphological complexity was quantified using fractal dimension (DF), and local dynamical stability was measured via a Lyapunov-like exponent (λ). Robustness analyses assessed the stability of DF–λ regimes under multi-scale perturbations, synthetic-order reversal (directionality; sign-aware comparison) and stochastic noise, including cross-generator generalization against a time-shuffled negative control. Results: The DF–λ morphodynamic phase map revealed three characteristic regimes: (1) stable morphodynamics (λ < 0), associated with compact, smoother boundaries; (2) metastable dynamics (λ ≈ 0), reflecting weakly stable or transitional behavior; and (3) unstable or chaotic dynamics (λ > 0), associated with divergent latent trajectories. Latent-space flow fields exhibited contraction-induced attractor-like basins and smoothly diverging directions. Kernel-density estimation of DF–λ distributions revealed a prominent population cluster within the metastable regime, characterized by moderate-to-high geometric irregularity (DF ≈ 1.85–2.00) and near-neutral dynamical stability (λ ≈ −0.02 to +0.01). Exploratory clinical overlays showed that fractal dimension exhibited a modest negative association with survival, whereas λ did not correlate with clinical outcome, suggesting that the two descriptors capture complementary and clinically distinct aspects of tumor morphology. Conclusions: Glioblastoma morphology can be represented as a continuous dynamical process within a learned latent manifold. Combining Neural ODE–based dynamics, fractal morphometry, and Lyapunov stability provides a principled framework for dynamic radiomics, offering interpretable morphodynamic descriptors that bridge fractal geometry, nonlinear dynamics, and deep learning. Because BraTS is cross-sectional and the synthetic step index does not represent biological time, any clinical interpretation is hypothesis-generating; validation in longitudinal and covariate-rich cohorts is required before prognostic or treatment-monitoring use. The resulting DF–λ morphodynamic map provides a hypothesis-generating morphodynamic representation that should be evaluated in covariate-rich and longitudinal cohorts before any prognostic or treatment-monitoring use.

Fractal and FractionalVol. 10(1)
Alexandru Ioan Cuza University (RO), Grigore T. Popa University of Medicine and Pharmacy (RO), Institutul Regional de Oncologie (RO), University of Bacău (RO), National Institute of Research and Development for Technical Physics (RO)
Openalex Percentile: Top 26%
Glioma Diagnosis and Treatment
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