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.
Authors
- Maricel Agop (ORCID: https://orcid.org/0000-0003-2293-5803)
- Lăcrămioara Ochiuz (ORCID: https://orcid.org/0000-0001-6447-0958)
- Diana Carmen Mirila
- Monica Molcăluţ
- Florin Nedeff
- Dragoș Teodor Iancu
- Valentin Nedeff
- Călin Gheorghe Buzea
Institutions
- 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)
Publication Details
- Journal
- Fractal and Fractional
- Published
- 2025-12-23
- DOI
- https://doi.org/10.3390/fractalfract10010008
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00