Bridging MRI and PET physiology: Untangling complementarity through orthogonal representations

Multimodal imaging analysis often relies on joint latent representations, yet these approaches rarely define what information is shared versus modality-specific. Clarifying this distinction is clinically relevant, as it delineates the irreducible contribution of each modality and informs rational acquisition strategies. We propose a subspace decomposition framework that reframes multimodal fusion as a problem of orthogonal subspace separation rather than translation. We decompose Prostate-Specific Membrane Antigen (PSMA) PET uptake into an MRI-explainable physiological envelope and an orthogonal residual reflecting signal components not expressible within the MRI feature manifold. Using multiparametric MRI, we train an intensity-based, non-spatial implicit neural representation (INR) to map MRI feature vectors to PET uptake. We introduce a projection-based regularization using singular value decomposition to penalize residual components lying within the span of the MRI feature manifold. This enforces mathematical orthogonality between tissue-level physiological properties (structure, diffusion, perfusion) and intracellular PSMA expression. Tested on 13 prostate cancer patients, the model demonstrates that residual components spanned by MRI features are absorbed into the learned envelope, while the orthogonal residual is largest in tumour regions. This indicates that PSMA PET contains signal components not recoverable from MRI-derived physiological descriptors. The resulting decomposition provides a structured characterization of modality complementarity grounded in representation geometry rather than image translation.

Energy-based Tissue Manifolds for Longitudinal Multiparametric MRI Analysis

We propose a geometric framework for longitudinal multi-parametric MRI analysis based on patient-specific energy modelling in sequence space. Rather than operating on images with spatial networks, each voxel is represented by its multi-sequence intensity vector ($T1$, $T1c$, $T2$, FLAIR, ADC), and a compact implicit neural representation is trained via denoising score matching to learn an energy function $E_θ(\mathbf{u})$ over $\mathbb{R}^d$ from a single baseline scan. The learned energy landscape provides a differential-geometric description of tissue regimes without segmentation labels. Local minima define tissue basins, gradient magnitude reflects proximity to regime boundaries, and Laplacian curvature characterises local constraint structure. Importantly, this baseline energy manifold is treated as a fixed geometric reference: it encodes the set of contrast combinations observed at diagnosis and is not retrained at follow-up. Longitudinal assessment is therefore formulated as evaluation of subsequent scans relative to this baseline geometry. Rather than comparing anatomical segmentations, we analyse how the distribution of MRI sequence vectors evolves under the baseline energy function. In a paediatric case with later recurrence, follow-up scans show progressive deviation in energy and directional displacement in sequence space toward the baseline tumour-associated regime before clear radiological reappearance. In a case with stable disease, voxel distributions remain confined to established low-energy basins without systematic drift. The presented cases serve as proof-of-concept that patient-specific energy manifolds can function as geometric reference systems for longitudinal mpMRI analysis without explicit segmentation or supervised classification, providing a foundation for further investigation of manifold-based tissue-at-risk tracking in neuro-oncology.

Physiological neural representation for personalised tracer kinetic parameter estimation from dynamic PET

Dynamic positron emission tomography (PET) with [$^{18}$F]FDG enables non-invasive quantification of glucose metabolism through kinetic analysis, often modelled by the two-tissue compartment model (TCKM). However, voxel-wise kinetic parameter estimation using conventional methods is computationally intensive and limited by spatial resolution. Deep neural networks (DNNs) offer an alternative but require large training datasets and significant computational resources. To address these limitations, we propose a physiological neural representation based on implicit neural representations (INRs) for personalized kinetic parameter estimation. INRs, which learn continuous functions, allow for efficient, high-resolution parametric imaging with reduced data requirements. Our method also integrates anatomical priors from a 3D CT foundation model to enhance robustness and precision in kinetic modelling. We evaluate our approach on an [$^{18}$F]FDG dynamic PET/CT dataset and compare it to state-of-the-art DNNs. Results demonstrate superior spatial resolution, lower mean-squared error, and improved anatomical consistency, particularly in tumour and highly vascularized regions. Our findings highlight the potential of INRs for personalized, data-efficient tracer kinetic modelling, enabling applications in tumour characterization, segmentation, and prognostic assessment.

Anatomy-constrained modelling of image-derived input functions in dynamic PET using multi-organ segmentation

Accurate kinetic analysis of [$^{18}$F]FDG distribution in dynamic positron emission tomography (PET) requires anatomically constrained modelling of image-derived input functions (IDIFs). Traditionally, IDIFs are obtained from the aorta, neglecting anatomical variations and complex vascular contributions. This study proposes a multi-organ segmentation-based approach that integrates IDIFs from the aorta, portal vein, pulmonary artery, and ureters. Using high-resolution CT segmentations of the liver, lungs, kidneys, and bladder, we incorporate organ-specific blood supply sources to improve kinetic modelling. Our method was evaluated on dynamic [$^{18}$F]FDG PET data from nine patients, resulting in a mean squared error (MSE) reduction of $13.39\%$ for the liver and $10.42\%$ for the lungs. These initial results highlight the potential of multiple IDIFs in improving anatomical modelling and fully leveraging dynamic PET imaging. This approach could facilitate the integration of tracer kinetic modelling into clinical routine.

Fine-Tuning TransMorph with Gradient Correlation for Anatomical Alignment

Unsupervised deep learning is a promising method in brain MRI registration to reduce the reliance on anatomical labels, while still achieving anatomically accurate transformations. For the Learn2Reg2024 LUMIR challenge, we propose fine-tuning of the pre-trained TransMorph model to improve the convergence stability as well as the deformation smoothness. The former is achieved through the FAdam optimizer, and consistency in structural changes is incorporated through the addition of gradient correlation in the similarity measure, improving anatomical alignment. The results show slight improvements in the Dice and HdDist95 scores, and a notable reduction in the NDV compared to the baseline TransMorph model. These are also confirmed by inspecting the boundaries of the tissue. Our proposed method highlights the effectiveness of including Gradient Correlation to achieve smoother and structurally consistent deformations for interpatient brain MRI registration.