Razvan Marinescu

Jueqi Wang, Jacob Levman, Walter Hugo Lopez Pinaya et al.

High-resolution (HR) MRI scans obtained from research-grade medical centers provide precise information about imaged tissues. However, routine clinical MRI scans are typically in low-resolution (LR) and vary greatly in contrast and spatial resolution due to the adjustments of the scanning parameters to the local needs of the medical center. End-to-end deep learning methods for MRI super-resolution (SR) have been proposed, but they require re-training each time there is a shift in the input distribution. To address this issue, we propose a novel approach that leverages a state-of-the-art 3D brain generative model, the latent diffusion model (LDM) trained on UK BioBank, to increase the resolution of clinical MRI scans. The LDM acts as a generative prior, which has the ability to capture the prior distribution of 3D T1-weighted brain MRI. Based on the architecture of the brain LDM, we find that different methods are suitable for different settings of MRI SR, and thus propose two novel strategies: 1) for SR with more sparsity, we invert through both the decoder of the LDM and also through a deterministic Denoising Diffusion Implicit Models (DDIM), an approach we will call InverseSR(LDM); 2) for SR with less sparsity, we invert only through the LDM decoder, an approach we will call InverseSR(Decoder). These two approaches search different latent spaces in the LDM model to find the optimal latent code to map the given LR MRI into HR. The training process of the generative model is independent of the MRI under-sampling process, ensuring the generalization of our method to many MRI SR problems with different input measurements. We validate our method on over 100 brain T1w MRIs from the IXI dataset. Our method can demonstrate that powerful priors given by LDM can be used for MRI reconstruction.

Sreyes Venkatesh, Razvan Marinescu, Jason K. Eshraghian

Weight quantization is used to deploy high-performance deep learning models on resource-limited hardware, enabling the use of low-precision integers for storage and computation. Spiking neural networks (SNNs) share the goal of enhancing efficiency, but adopt an 'event-driven' approach to reduce the power consumption of neural network inference. While extensive research has focused on weight quantization, quantization-aware training (QAT), and their application to SNNs, the precision reduction of state variables during training has been largely overlooked, potentially diminishing inference performance. This paper introduces two QAT schemes for stateful neurons: (i) a uniform quantization strategy, an established method for weight quantization, and (ii) threshold-centered quantization, which allocates exponentially more quantization levels near the firing threshold. Our results show that increasing the density of quantization levels around the firing threshold improves accuracy across several benchmark datasets. We provide an ablation analysis of the effects of weight and state quantization, both individually and combined, and how they impact models. Our comprehensive empirical evaluation includes full precision, 8-bit, 4-bit, and 2-bit quantized SNNs, using QAT, stateful QAT (SQUAT), and post-training quantization methods. The findings indicate that the combination of QAT and SQUAT enhance performance the most, but given the choice of one or the other, QAT improves performance by the larger degree. These trends are consistent all datasets. Our methods have been made available in our Python library snnTorch: https://github.com/jeshraghian/snntorch.

Alexander Aghili, Andy Bruce, Daniel Sabo et al.

The rapid evolution of molecular dynamics (MD) methods, including machine-learned dynamics, has outpaced the development of standardized tools for method validation. Objective comparison between simulation approaches is often hindered by inconsistent evaluation metrics, insufficient sampling of rare conformational states, and the absence of reproducible benchmarks. To address these challenges, we introduce a modular benchmarking framework that systematically evaluates protein MD methods using enhanced sampling analysis. Our approach uses weighted ensemble (WE) sampling via The Weighted Ensemble Simulation Toolkit with Parallelization and Analysis (WESTPA), based on progress coordinates derived from Time-lagged Independent Component Analysis (TICA), enabling fast and efficient exploration of protein conformational space. The framework includes a flexible, lightweight propagator interface that supports arbitrary simulation engines, allowing both classical force fields and machine learning-based models. Additionally, the framework offers a comprehensive evaluation suite capable of computing more than 19 different metrics and visualizations across a variety of domains. We further contribute a dataset of nine diverse proteins, ranging from 10 to 224 residues, that span a variety of folding complexities and topologies. Each protein has been extensively simulated at 300K for one million MD steps per starting point (4 ns). To demonstrate the utility of our framework, we perform validation tests using classic MD simulations with implicit solvent and compare protein conformational sampling using a fully trained versus under-trained CGSchNet model. By standardizing evaluation protocols and enabling direct, reproducible comparisons across MD approaches, our open-source platform lays the groundwork for consistent, rigorous benchmarking across the molecular simulation community.

Emmanouil Nikolakakis, Amine Ouasfi, Julie Digne et al.

We present RibPull, a methodology that utilizes implicit occupancy fields to bridge computational geometry and medical imaging. Implicit 3D representations use continuous functions that handle sparse and noisy data more effectively than discrete methods. While voxel grids are standard for medical imaging, they suffer from resolution limitations, topological information loss, and inefficient handling of sparsity. Coordinate functions preserve complex geometrical information and represent a better solution for sparse data representation, while allowing for further morphological operations. Implicit scene representations enable neural networks to encode entire 3D scenes within their weights. The result is a continuous function that can implicitly compesate for sparse signals and infer further information about the 3D scene by passing any combination of 3D coordinates as input to the model. In this work, we use neural occupancy fields that predict whether a 3D point lies inside or outside an object to represent CT-scanned ribcages. We also apply a Laplacian-based contraction to extract the medial axis of the ribcage, thus demonstrating a geometrical operation that benefits greatly from continuous coordinate-based 3D scene representations versus voxel-based representations. We evaluate our methodology on 20 medical scans from the RibSeg dataset, which is itself an extension of the RibFrac dataset. We will release our code upon publication.

Prathamesh Pradeep Khole, Zahra Kais Petiwala, Shri Prathaa Magesh et al.

We propose ReMiDi, a novel method for inferring neuronal microstructure as arbitrary 3D meshes using a differentiable diffusion Magnetic Resonance Imaging (dMRI) simulator. We first implemented in PyTorch a differentiable dMRI simulator that simulates the forward diffusion process using a finite-element method on an input 3D microstructure mesh. To achieve significantly faster simulations, we solve the differential equation semi-analytically using a matrix formalism approach. Given a reference dMRI signal $S_{ref}$, we use the differentiable simulator to iteratively update the input mesh such that it matches $S_{ref}$ using gradient-based learning. Since directly optimizing the 3D coordinates of the vertices is challenging, particularly due to ill-posedness of the inverse problem, we instead optimize a lower-dimensional latent space representation of the mesh. The mesh is first encoded into spectral coefficients, which are further encoded into a latent $\textbf{z}$ using an auto-encoder, and are then decoded back into the true mesh. We present an end-to-end differentiable pipeline that simulates signals that can be tuned to match a reference signal by iteratively updating the latent representation $\textbf{z}$. We demonstrate the ability to reconstruct microstructures of arbitrary shapes represented by finite-element meshes, with a focus on axonal geometries found in the brain white matter, including bending, fanning and beading fibers. Our source code is available online.

Utkarsh Gupta, Emmanouil Nikolakakis, Moritz Zaiss et al.

Reconstructing digital brain phantoms in the form of voxel-based, multi-channeled tissue probability maps for individual subjects is essential for capturing brain anatomical variability, understanding neurological diseases, as well as for testing image processing methods. We demonstrate the first framework that estimates brain tissue probability maps (Grey Matter - GM, White Matter - WM, and Cerebrospinal fluid - CSF) with the help of a Physics-based differentiable MRI simulator that models the magnetization signal at each voxel in the volume. Given an observed $T_1$/$T_2$-weighted MRI scan, the corresponding clinical MRI sequence, and the MRI differentiable simulator, we estimate the simulator's input probability maps by back-propagating the L2 loss between the simulator's output and the $T_1$/$T_2$-weighted scan. This approach has the significant advantage of not relying on any training data and instead uses the strong inductive bias of the MRI simulator. We tested the model on 20 scans from the BrainWeb database and demonstrated a highly accurate reconstruction of GM, WM, and CSF. Our source code is available online: https://github.com/BioMedAI-UCSC/BMapEst.

Sungmin Hong, Razvan Marinescu, Adrian V. Dalca et al.

Image synthesis via Generative Adversarial Networks (GANs) of three-dimensional (3D) medical images has great potential that can be extended to many medical applications, such as, image enhancement and disease progression modeling. However, current GAN technologies for 3D medical image synthesis need to be significantly improved to be readily adapted to real-world medical problems. In this paper, we extend the state-of-the-art StyleGAN2 model, which natively works with two-dimensional images, to enable 3D image synthesis. In addition to the image synthesis, we investigate the controllability and interpretability of the 3D-StyleGAN via style vectors inherited form the original StyleGAN2 that are highly suitable for medical applications: (i) the latent space projection and reconstruction of unseen real images, and (ii) style mixing. We demonstrate the 3D-StyleGAN's performance and feasibility with ~12,000 three-dimensional full brain MR T1 images, although it can be applied to any 3D volumetric images. Furthermore, we explore different configurations of hyperparameters to investigate potential improvement of the image synthesis with larger networks. The codes and pre-trained networks are available online: https://github.com/sh4174/3DStyleGAN.

Razvan V. Marinescu, Arman Eshaghi, Marco Lorenzi et al.

Here we present DIVE: Data-driven Inference of Vertexwise Evolution. DIVE is an image-based disease progression model with single-vertex resolution, designed to reconstruct long-term patterns of brain pathology from short-term longitudinal data sets. DIVE clusters vertex-wise biomarker measurements on the cortical surface that have similar temporal dynamics across a patient population, and concurrently estimates an average trajectory of vertex measurements in each cluster. DIVE uniquely outputs a parcellation of the cortex into areas with common progression patterns, leading to a new signature for individual diseases. DIVE further estimates the disease stage and progression speed for every visit of every subject, potentially enhancing stratification for clinical trials or management. On simulated data, DIVE can recover ground truth clusters and their underlying trajectory, provided the average trajectories are sufficiently different between clusters. We demonstrate DIVE on data from two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Dementia Research Centre (DRC), UK, containing patients with Posterior Cortical Atrophy (PCA) as well as typical Alzheimer's disease (tAD). DIVE finds similar spatial patterns of atrophy for tAD subjects in the two independent datasets (ADNI and DRC), and further reveals distinct patterns of pathology in different diseases (tAD vs PCA) and for distinct types of biomarker data: cortical thickness from Magnetic Resonance Imaging (MRI) vs amyloid load from Positron Emission Tomography (PET). Finally, DIVE can be used to estimate a fine-grained spatial distribution of pathology in the brain using any kind of voxelwise or vertexwise measures including Jacobian compression maps, fractional anisotropy (FA) maps from diffusion imaging or other PET measures. DIVE source code is available online: https://github.com/mrazvan22/dive

Razvan V. Marinescu, Marco Lorenzi, Stefano B. Blumberg et al.

We introduce Disease Knowledge Transfer (DKT), a novel technique for transferring biomarker information between related neurodegenerative diseases. DKT infers robust multimodal biomarker trajectories in rare neurodegenerative diseases even when only limited, unimodal data is available, by transferring information from larger multimodal datasets from common neurodegenerative diseases. DKT is a joint-disease generative model of biomarker progressions, which exploits biomarker relationships that are shared across diseases. Our proposed method allows, for the first time, the estimation of plausible, multimodal biomarker trajectories in Posterior Cortical Atrophy (PCA), a rare neurodegenerative disease where only unimodal MRI data is available. For this we train DKT on a combined dataset containing subjects with two distinct diseases and sizes of data available: 1) a larger, multimodal typical AD (tAD) dataset from the TADPOLE Challenge, and 2) a smaller unimodal Posterior Cortical Atrophy (PCA) dataset from the Dementia Research Centre (DRC), for which only a limited number of Magnetic Resonance Imaging (MRI) scans are available. Although validation is challenging due to lack of data in PCA, we validate DKT on synthetic data and two patient datasets (TADPOLE and PCA cohorts), showing it can estimate the ground truth parameters in the simulation and predict unseen biomarkers on the two patient datasets. While we demonstrated DKT on Alzheimer's variants, we note DKT is generalisable to other forms of related neurodegenerative diseases. Source code for DKT is available online: https://github.com/mrazvan22/dkt.

Emmanouil Nikolakakis, Utkarsh Gupta, Jonathan Vengosh et al.

We present GaSpCT, a novel view synthesis and 3D scene representation method used to generate novel projection views for Computer Tomography (CT) scans. We adapt the Gaussian Splatting framework to enable novel view synthesis in CT based on limited sets of 2D image projections and without the need for Structure from Motion (SfM) methodologies. Therefore, we reduce the total scanning duration and the amount of radiation dose the patient receives during the scan. We adapted the loss function to our use-case by encouraging a stronger background and foreground distinction using two sparsity promoting regularizers: a beta loss and a total variation (TV) loss. Finally, we initialize the Gaussian locations across the 3D space using a uniform prior distribution of where the brain's positioning would be expected to be within the field of view. We evaluate the performance of our model using brain CT scans from the Parkinson's Progression Markers Initiative (PPMI) dataset and demonstrate that the rendered novel views closely match the original projection views of the simulated scan, and have better performance than other implicit 3D scene representations methodologies. Furthermore, we empirically observe reduced training time compared to neural network based image synthesis for sparse-view CT image reconstruction. Finally, the memory requirements of the Gaussian Splatting representations are reduced by 17% compared to the equivalent voxel grid image representations.

Ehsan Mirafzali, Utkarsh Gupta, Patrick Wyrod et al.

We introduce a new framework based on Malliavin calculus to derive exact analytical expressions for the score function $\nabla \log p_t(x)$, i.e., the gradient of the log-density associated with the solution to stochastic differential equations (SDEs). Our approach combines classical integration-by-parts techniques with modern stochastic analysis tools, such as Bismut's formula and Malliavin calculus, and it works for both linear and nonlinear SDEs. In doing so, we establish a rigorous connection between the Malliavin derivative, its adjoint, the Malliavin divergence (Skorokhod integral), and diffusion generative models, thereby providing a systematic method for computing $\nabla \log p_t(x)$. In the linear case, we present a detailed analysis showing that our formula coincides with the analytical score function derived from the solution of the Fokker--Planck equation. For nonlinear SDEs with state-independent diffusion coefficients, we derive a closed-form expression for $\nabla \log p_t(x)$. We evaluate the proposed framework across multiple generative tasks and find that its performance is comparable to state-of-the-art methods. These results can be generalised to broader classes of SDEs, paving the way for new score-based diffusion generative models.

Alexander Aghili, Andy Bruce, Daniel Sabo et al.

Molecular dynamics (MD) simulations provide atomistic insight into biomolecular systems but are often limited by high computational costs required to access long timescales. Coarse-grained machine learning models offer a promising avenue for accelerating sampling, yet conventional force matching approaches often fail to capture the full thermodynamic landscape as fitting a model on the gradient may not fit the absolute differences between low-energy conformational states. In this work, we incorporate a complementary energy matching term into the loss function. We evaluate our framework on the Chignolin protein using the CGSchNet model, systematically varying the weight of the energy loss term. While energy matching did not yield statistically significant improvements in accuracy, it revealed distinct tendencies in how models generalize the free energy surface. Our results suggest future opportunities to enhance coarse-grained modeling through improved energy estimation techniques and multi-modal loss formulations.

Rahul Nadkarni, Emmanouil Nikolakakis, Razvan Marinescu

We present AFEN (Audio Feature Ensemble Learning), a model that leverages Convolutional Neural Networks (CNN) and XGBoost in an ensemble learning fashion to perform state-of-the-art audio classification for a range of respiratory diseases. We use a meticulously selected mix of audio features which provide the salient attributes of the data and allow for accurate classification. The extracted features are then used as an input to two separate model classifiers 1) a multi-feature CNN classifier and 2) an XGBoost Classifier. The outputs of the two models are then fused with the use of soft voting. Thus, by exploiting ensemble learning, we achieve increased robustness and accuracy. We evaluate the performance of the model on a database of 920 respiratory sounds, which undergoes data augmentation techniques to increase the diversity of the data and generalizability of the model. We empirically verify that AFEN sets a new state-of-the-art using Precision and Recall as metrics, while decreasing training time by 60%.

Prathamesh Pradeep Khole, Mario M. Brenes, Zahra Kais Petiwala et al.

Diffusion MRI (dMRI) is sensitive to microstructural barriers, yet most existing methods either assume impermeable boundaries or estimate voxel-level parameters without recovering explicit interfaces. We present Spinverse, a permeability-aware reconstruction method that inverts dMRI measurements through a fully differentiable Bloch-Torrey simulator. Spinverse represents tissue on a fixed tetrahedral grid and treats each interior face permeability as a learnable parameter; low-permeability faces act as diffusion barriers, so microstructural boundaries whose topology is not fixed a priori (up to the resolution of the ambient mesh) emerge without changing mesh connectivity or vertex positions. Given a target signal, we optimize face permeabilities by backpropagating a signal-matching loss through the PDE forward model, and recover an interface by thresholding the learned permeability field. To mitigate the ill-posedness of permeability inversion, we use mesh-based geometric priors; to avoid local minima, we use a staged multi-sequence optimization curriculum. Across a collection of synthetic voxel meshes, Spinverse reconstructs diverse geometries and demonstrates that sequence scheduling and regularization are critical to avoid outline-only solutions while improving both boundary accuracy and structural validity.

Kevin Bachelor, Sanya Murdeshwar, Daniel Sabo et al.

Machine-learned coarse-grained (CG) potentials are fast, but degrade over time when simulations reach under-sampled bio-molecular conformations, and generating widespread all-atom (AA) data to combat this is computationally infeasible. We propose a novel active learning (AL) framework for CG neural network potentials in molecular dynamics (MD). Building on the CGSchNet model, our method employs root mean squared deviation (RMSD)-based frame selection from MD simulations in order to generate data on-the-fly by querying an oracle during the training of a neural network potential. This framework preserves CG-level efficiency while correcting the model at precise, RMSD-identified coverage gaps. By training CGSchNet, a coarse-grained neural network potential, we empirically show that our framework explores previously unseen configurations and trains the model on unexplored regions of conformational space. Our active learning framework enables a CGSchNet model trained on the Chignolin protein to achieve a 33.05\% improvement in the Wasserstein-1 (W1) metric in Time-lagged Independent Component Analysis (TICA) space on an in-house benchmark suite.

Razvan V Marinescu, Daniel Moyer, Polina Golland

Machine learning models are commonly trained end-to-end and in a supervised setting, using paired (input, output) data. Examples include recent super-resolution methods that train on pairs of (low-resolution, high-resolution) images. However, these end-to-end approaches require re-training every time there is a distribution shift in the inputs (e.g., night images vs daylight) or relevant latent variables (e.g., camera blur or hand motion). In this work, we leverage state-of-the-art (SOTA) generative models (here StyleGAN2) for building powerful image priors, which enable application of Bayes' theorem for many downstream reconstruction tasks. Our method, Bayesian Reconstruction through Generative Models (BRGM), uses a single pre-trained generator model to solve different image restoration tasks, i.e., super-resolution and in-painting, by combining it with different forward corruption models. We keep the weights of the generator model fixed, and reconstruct the image by estimating the Bayesian maximum a-posteriori (MAP) estimate over the input latent vector that generated the reconstructed image. We further use variational inference to approximate the posterior distribution over the latent vectors, from which we sample multiple solutions. We demonstrate BRGM on three large and diverse datasets: (i) 60,000 images from the Flick Faces High Quality dataset (ii) 240,000 chest X-rays from MIMIC III and (iii) a combined collection of 5 brain MRI datasets with 7,329 scans. Across all three datasets and without any dataset-specific hyperparameter tuning, our simple approach yields performance competitive with current task-specific state-of-the-art methods on super-resolution and in-painting, while being more generalisable and without requiring any training. Our source code and pre-trained models are available online: https://razvanmarinescu.github.io/brgm/.