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Iterative algorithms for the reconstruction of early states of prostate cancer growth (2409.12844v1)

Published 19 Sep 2024 in math.AP, cs.NA, math.NA, and q-bio.TO

Abstract: The development of mathematical models of cancer informed by time-resolved measurements has enabled personalised predictions of tumour growth and treatment response. However, frequent cancer monitoring is rare, and many tumours are treated soon after diagnosis with limited data. To improve the predictive capabilities of cancer models, we investigate the problem of recovering earlier tumour states from a single spatial measurement at a later time. Focusing on prostate cancer, we describe tumour dynamics using a phase-field model coupled with two reaction-diffusion equations for a nutrient and the local prostate-specific antigen. We generate synthetic data using a discretisation based on Isogeometric Analysis. Then, building on our previous analytical work (Beretta et al., SIAP (2024)), we propose an iterative reconstruction algorithm based on the Landweber scheme, showing local convergence with quantitative rates and exploring an adaptive step size that leads to faster reconstruction algorithms. Finally, we run simulations demonstrating high-quality reconstructions even with long time horizons and noisy data.

Summary

  • The paper presents iterative inverse algorithms that reconstruct initial prostate tumor conditions using a phase-field model with reaction-diffusion dynamics.
  • The study rigorously tests the Landweber iteration and adaptive gradient descent methods under both short and long time horizons using synthetic simulations.
  • Robust performance in noisy conditions highlights these algorithms' potential for early cancer detection and personalized treatment planning.

Iterative Algorithms for the Reconstruction of Early States of Prostate Cancer Growth

The paper presents a comprehensive investigation into the inverse problem of reconstructing the early states of prostate cancer using a model-based approach. This challenge is addressed by rigorously developing and analyzing iterative algorithms to infer tumor conditions at initial time points from a single subsequent spatial measurement, typically gathered through imaging techniques. Specifically, the authors focus on applications in prostate cancer and leverage a previously developed phase-field model.

Summary of the Methodology

The investigation primarily revolves around the feasibility and efficacy of the Landweber iteration scheme and an adaptive gradient descent (AGD) approach in reconstructing initial tumor conditions. The mathematical model describing prostate cancer dynamics integrates a phase-field method coupled with reaction-diffusion equations for a nutrient and prostate-specific antigen (PSA), which collectively embody the tumor progression.

Key Highlights:

  1. Phase-Field Model:
    • The model uses a continuous phase-field variable φ to delineate healthy and cancerous tissue regions.
    • Coupled reaction-diffusion equations describe the spatiotemporal behavior of a nutrient and local PSA dynamics, essential for tumor growth.
  2. Inverse Problem Formulation:
    • The inverse problem aims to reconstruct the initial spatial configuration of the tumor phase field (φ), nutrient concentration (σ), and PSA (p) based on observations at a later time (T).
    • This problem is inherently ill-posed, particularly for large T, necessitating robust regularization methods.
  3. Iterative Reconstruction Algorithms:
    • Landweber Iteration Scheme: The method iteratively adjusts initial conditions through gradient descent steps calibrated via an adaptive steepest descent step size. This involves solving the forward model, computing adjoint variables, and updating the initial tumor state accordingly.
    • Adaptive Gradient Descent (AGD): An alternative step size adaptation method aiming for greater efficiency in scenarios with longer time horizons. This method proved particularly effective for large T, albeit with considerations for computational expense and empirical adjustments to the initial guess and convergence criteria.

Numerical Experiments and Results

The performance of these reconstruction methods was subjected to rigorous testing through synthetic simulations:

  1. Simulation Setup:
    • The model parameters and initial conditions were selected to represent an aggressive prostate cancer scenario, characterized by significant geometric changes over time.
    • The tumor phase field was tracked in a 2D computational domain discretized using quadratic B-spline elements.
  2. Short Time Horizons (e.g., T=15 days):
    • The Landweber iteration scheme demonstrated accurate reconstructions of both initial and final tumor states.
    • Metric evaluations (e.g., tumor volume error, Dice similarity coefficient, L2L^2 error, and Concordance Correlation Coefficient) confirmed high-quality reconstructions with minimal error margins.
  3. Long Time Horizons (e.g., T=90, 365 days):
    • The AGD method efficiently facilitated reconstructions for longer time horizons.
    • Adjustments to initial guesses based on model dynamics and relaxed convergence tolerances were necessary to ensure convergence in the most challenging scenarios.
    • Robust convergence was observed, with the AGD method yielding satisfactory reconstructions despite inevitable algorithmic refinements.
  4. Noisy Measurements:
    • Robustness tests incorporating Gaussian noise in the measurements indicated that both reconstruction algorithms could effectively handle real-world uncertainties.
    • The AGD method maintained satisfactory reconstruction quality even under noisy conditions, demonstrating high practical applicability.

Implications and Future Directions

The presented methodologies exhibit potential for impactful applications in clinical oncology, particularly in scenarios where longitudinal data is sparse or unavailable. By efficiently reconstructing tumor initial conditions from a single spatial measurement, these algorithms provide a pivotal step towards personalized and predictive oncology.

Future research should expand on these methodologies by:

  • Incorporating diverse tumor growth models and clinical treatment effects.
  • Extending analyses to three-dimensional domains and patient-specific anatomies.
  • Integrating real-world clinical data to validate and refine these computational techniques further.
  • Exploring combined optimization strategies for simultaneous parameter estimation and initial condition reconstruction to enhance model personalization.

Overall, this paper's computational advances offer promising avenues for early detection and personalized treatment planning in oncological care, harnessing advanced mathematical models and efficient iterative algorithms.

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