Lemuel Puglisi

Lemuel Puglisi, Frederik Barkhof, Daniel C. Alexander et al.

Recent advances in MRI have led to the creation of large datasets. With the increase in data volume, it has become difficult to locate previous scans of the same patient within these datasets (a process known as re-identification). To address this issue, we propose an AI-powered medical imaging retrieval framework called DeepBrainPrint, which is designed to retrieve brain MRI scans of the same patient. Our framework is a semi-self-supervised contrastive deep learning approach with three main innovations. First, we use a combination of self-supervised and supervised paradigms to create an effective brain fingerprint from MRI scans that can be used for real-time image retrieval. Second, we use a special weighting function to guide the training and improve model convergence. Third, we introduce new imaging transformations to improve retrieval robustness in the presence of intensity variations (i.e. different scan contrasts), and to account for age and disease progression in patients. We tested DeepBrainPrint on a large dataset of T1-weighted brain MRIs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and on a synthetic dataset designed to evaluate retrieval performance with different image modalities. Our results show that DeepBrainPrint outperforms previous methods, including simple similarity metrics and more advanced contrastive deep learning frameworks.

Lemuel Puglisi, Daniel C. Alexander, Daniele Ravì

The growing availability of longitudinal Magnetic Resonance Imaging (MRI) datasets has facilitated Artificial Intelligence (AI)-driven modeling of disease progression, making it possible to predict future medical scans for individual patients. However, despite significant advancements in AI, current methods continue to face challenges including achieving patient-specific individualization, ensuring spatiotemporal consistency, efficiently utilizing longitudinal data, and managing the substantial memory demands of 3D scans. To address these challenges, we propose Brain Latent Progression (BrLP), a novel spatiotemporal model designed to predict individual-level disease progression in 3D brain MRIs. The key contributions in BrLP are fourfold: (i) it operates in a small latent space, mitigating the computational challenges posed by high-dimensional imaging data; (ii) it explicitly integrates subject metadata to enhance the individualization of predictions; (iii) it incorporates prior knowledge of disease dynamics through an auxiliary model, facilitating the integration of longitudinal data; and (iv) it introduces the Latent Average Stabilization (LAS) algorithm, which (a) enforces spatiotemporal consistency in the predicted progression at inference time and (b) allows us to derive a measure of the uncertainty for the prediction at the global and voxel level. We train and evaluate BrLP on 11,730 T1-weighted (T1w) brain MRIs from 2,805 subjects and validate its generalizability on an external test set comprising 2,257 MRIs from 962 subjects. Our experiments compare BrLP-generated MRI scans with real follow-up MRIs, demonstrating state-of-the-art accuracy compared to existing methods. The code is publicly available at: https://github.com/LemuelPuglisi/BrLP.

Alec Sargood, Lemuel Puglisi, James H. Cole et al.

Synthesizing amyloid PET scans from the more widely available and accessible structural MRI modality offers a promising, cost-effective approach for large-scale Alzheimer's Disease (AD) screening. This is motivated by evidence that, while MRI does not directly detect amyloid pathology, it may nonetheless encode information correlated with amyloid deposition that can be uncovered through advanced modeling. However, the high dimensionality and structural complexity of 3D neuroimaging data pose significant challenges for existing MRI-to-PET translation methods. Modeling the cross-modality relationship in a lower-dimensional latent space can simplify the learning task and enable more effective translation. As such, we present CoCoLIT (ControlNet-Conditioned Latent Image Translation), a diffusion-based latent generative framework that incorporates three main innovations: (1) a novel Weighted Image Space Loss (WISL) that improves latent representation learning and synthesis quality; (2) a theoretical and empirical analysis of Latent Average Stabilization (LAS), an existing technique used in similar generative models to enhance inference consistency; and (3) the introduction of ControlNet-based conditioning for MRI-to-PET translation. We evaluate CoCoLIT's performance on publicly available datasets and find that our model significantly outperforms state-of-the-art methods on both image-based and amyloid-related metrics. Notably, in amyloid-positivity classification, CoCoLIT outperforms the second-best method with improvements of +10.5% on the internal dataset and +23.7% on the external dataset. The code and models of our approach are available at https://github.com/brAIn-science/CoCoLIT.

Andrea Moschetto, Lemuel Puglisi, Alec Sargood et al.

Magnetic Resonance Imaging (MRI) enables the acquisition of multiple image contrasts, such as T1-weighted (T1w) and T2-weighted (T2w) scans, each offering distinct diagnostic insights. However, acquiring all desired modalities increases scan time and cost, motivating research into computational methods for cross-modal synthesis. To address this, recent approaches aim to synthesize missing MRI contrasts from those already acquired, reducing acquisition time while preserving diagnostic quality. Image-to-image (I2I) translation provides a promising framework for this task. In this paper, we present a comprehensive benchmark of generative models$\unicode{x2013}$specifically, Generative Adversarial Networks (GANs), diffusion models, and flow matching (FM) techniques$\unicode{x2013}$for T1w-to-T2w 2D MRI I2I translation. All frameworks are implemented with comparable settings and evaluated on three publicly available MRI datasets of healthy adults. Our quantitative and qualitative analyses show that the GAN-based Pix2Pix model outperforms diffusion and FM-based methods in terms of structural fidelity, image quality, and computational efficiency. Consistent with existing literature, these results suggest that flow-based models are prone to overfitting on small datasets and simpler tasks, and may require more data to match or surpass GAN performance. These findings offer practical guidance for deploying I2I translation techniques in real-world MRI workflows and highlight promising directions for future research in cross-modal medical image synthesis. Code and models are publicly available at https://github.com/AndreaMoschetto/medical-I2I-benchmark.

Antonio Scardace, Lemuel Puglisi, Francesco Guarnera et al.

Deep generative models have emerged as a transformative tool in medical imaging, offering substantial potential for synthetic data generation. However, recent empirical studies highlight a critical vulnerability: these models can memorize sensitive training data, posing significant risks of unauthorized patient information disclosure. Detecting memorization in generative models remains particularly challenging, necessitating scalable methods capable of identifying training data leakage across large sets of generated samples. In this work, we propose DeepSSIM, a novel self-supervised metric for quantifying memorization in generative models. DeepSSIM is trained to: i) project images into a learned embedding space and ii) force the cosine similarity between embeddings to match the ground-truth SSIM (Structural Similarity Index) scores computed in the image space. To capture domain-specific anatomical features, training incorporates structure-preserving augmentations, allowing DeepSSIM to estimate similarity reliably without requiring precise spatial alignment. We evaluate DeepSSIM in a case study involving synthetic brain MRI data generated by a Latent Diffusion Model (LDM) trained under memorization-prone conditions, using 2,195 MRI scans from two publicly available datasets (IXI and CoRR). Compared to state-of-the-art memorization metrics, DeepSSIM achieves superior performance, improving F1 scores by an average of +52.03% over the best existing method. Code and data of our approach are publicly available at the following link: https://github.com/brAIn-science/DeepSSIM.

Lemuel Puglisi, Alessia Rondinella, Linda De Meo et al.

Brain age is a critical measure that reflects the biological ageing process of the brain. The gap between brain age and chronological age, referred to as brain PAD (Predicted Age Difference), has been utilized to investigate neurodegenerative conditions. Brain age can be predicted using MRIs and machine learning techniques. However, existing methods are often sensitive to acquisition-related variabilities, such as differences in acquisition protocols, scanners, MRI sequences, and resolutions, significantly limiting their application in highly heterogeneous clinical settings. In this study, we introduce Synthetic Brain Age (SynthBA), a robust deep-learning model designed for predicting brain age. SynthBA utilizes an advanced domain randomization technique, ensuring effective operation across a wide array of acquisition-related variabilities. To assess the effectiveness and robustness of SynthBA, we evaluate its predictive capabilities on internal and external datasets, encompassing various MRI sequences and resolutions, and compare it with state-of-the-art techniques. Additionally, we calculate the brain PAD in a large cohort of subjects with Alzheimer's Disease (AD), demonstrating a significant correlation with AD-related measures of cognitive dysfunction. SynthBA holds the potential to facilitate the broader adoption of brain age prediction in clinical settings, where re-training or fine-tuning is often unfeasible. The SynthBA source code and pre-trained models are publicly available at https://github.com/LemuelPuglisi/SynthBA.

Riccardo Raciti, Lemuel Puglisi, Francesco Guarnera et al.

Percentage Brain Volume Change (PBVC) derived from Magnetic Resonance Imaging (MRI) is a widely used biomarker of brain atrophy, with SIENA among the most established methods for its estimation. However, SIENA relies on classical image processing steps, particularly skull stripping and tissue segmentation, whose failures can propagate through the pipeline and bias atrophy estimates. In this work, we examine whether targeted deep learning substitutions can improve SIENA while preserving its established and interpretable framework. To this end, we integrate SynthStrip and SynthSeg into SIENA and evaluate three pipeline variants on the ADNI and PPMI longitudinal cohorts. Performance is assessed using three complementary criteria: correlation with longitudinal clinical and structural decline, scan-order consistency, and end-to-end runtime. Replacing the skull-stripping module yields the most consistent gains: in ADNI, it substantially strengthens associations between PBVC and multiple measures of disease progression relative to the standard SIENA pipeline, while across both datasets it markedly improves robustness under scan reversal. The fully integrated pipeline achieves the strongest scan-order consistency, reducing the error by up to 99.1%. In addition, GPU-enabled variants reduce execution time by up to 46% while maintaining CPU runtimes comparable to standard SIENA. Overall, these findings show that deep learning can meaningfully strengthen established longitudinal atrophy pipelines when used to reinforce their weakest image processing steps. More broadly, this study highlights the value of modularly modernizing clinically trusted neuroimaging tools without sacrificing their interpretability. Code is publicly available at https://github.com/Raciti/Enhanced-SIENA.git.

Alec Sargood, Lemuel Puglisi, Elinor Thompson et al.

Tractography is the process of inferring the trajectories of white-matter pathways in the brain from diffusion magnetic resonance imaging (dMRI). Local tractography methods, which construct streamlines by following local fiber orientation estimates stepwise through an image, are prone to error accumulation and high false positive rates, particularly on noisy or low-resolution data. In contrast, global methods, which attempt to optimize a collection of streamlines to maximize compatibility with underlying fiber orientation estimates, are computationally expensive. To address these challenges, we introduce GenTract, the first generative model for global tractography. We frame tractography as a generative task, learning a direct mapping from dMRI to complete, anatomically plausible streamlines. We compare both diffusion-based and flow matching paradigms and evaluate GenTract's performance against state-of-the-art baselines. Notably, GenTract achieves precision 2.1x higher than the next-best method, TractOracle. This advantage becomes even more pronounced in challenging low-resolution and noisy settings, where it outperforms the closest competitor by an order of magnitude. By producing tractograms with high precision on research-grade data while also maintaining reliability on imperfect, lower-resolution data, GenTract represents a promising solution for global tractography.