Toward Clinical Translation of Deep Learning-Based Intracranial Super-Resolution 4D Flow MRI Using Multi-Cohort Transfer Learning

Super-resolution is widely used in medical imaging to enhance low-quality data, reducing scan time and improving abnormality detection. Conventional super-resolution approaches typically rely on paired datasets of downsampled and original high resolution images, training models to reconstruct high resolution images from their artificially degraded counterparts. However, in real-world clinical settings, low resolution data often arise from acquisition mechanisms that differ significantly from simple downsampling. As a result, these inputs may lie outside the domain of the training data, leading to poor model generalization due to domain shift. To address this limitation, we propose a distributional deep learning framework that improves model robustness and domain generalization. We develop this approch for enhancing the resolution of 4D Flow MRI (4DF). This is a novel imaging modality that captures hemodynamic flow velocity and clinically relevant metrics such as vessel wall stress. These metrics are critical for assessing aneurysm rupture risk. Our model is initially trained on high resolution computational fluid dynamics (CFD) simulations and their downsampled counterparts. It is then fine-tuned on a small, harmonized dataset of paired 4D Flow MRI and CFD samples. We derive the theoretical properties of our distributional estimators and demonstrate that our framework significantly outperforms traditional deep learning approaches through real data applications. This highlights the effectiveness of distributional learning in addressing domain shift and improving super-resolution performance in clinically realistic scenarios.

Four-dimensional (4D) flow magnetic resonance imaging (MRI) is a powerful non-invasive technique for visualizing and quantifying complex blood flow patterns in vivo. Despite its clinical promise, broader adoption is limited by low spatial resolution and sensitivity to noise, which restrict accurate assessment of critical hemodynamic biomarkers such as wall shear stress, pressure gradients, and turbulent kinetic energy. To overcome these challenges, we propose a deep learning-based super-resolution framework that integrates multi-scale feature extraction and attention mechanisms to enhance the quality of 4D flow MRI data. The model was trained on a dataset of 120 patients with 240 stenosed carotid arteries. High-resolution ground truth data were generated using patient-specific computational fluid dynamics (CFD) simulations based on segmented vascular geometries and physiologically realistic boundary conditions, and the resulting velocity fields served as targets for supervised learning. The proposed architecture uses convolutional block attention modules (CBAM) to guide the network toward clinically relevant spatial features and to suppress noise in low-resolution inputs. Quantitative results show that the attention-guided model substantially reduces the root mean square error (RMSE) compared with a baseline model without attention, and qualitative velocity contour analysis confirms improved reconstruction of intricate flow patterns. These findings highlight the capacity of the model to restore high-fidelity flow fields under noisy conditions and support the use of deep learning to extend the clinical utility of 4D flow MRI for non-invasive hemodynamic assessment.

4D Flow MRI promises opportunities for non-invasive mapping of neurovascular hemodynamics, but its clinical utility faces trade-offs between resolution, acquisition time, and noise. Deep learning-based super-resolution offers a post-scan solution, but supervised approaches require paired or domain-specific data, while patient-specific physics-informed models can be computationally demanding. This creates a need for unsupervised reconstruction models that can adapt to individual acquisitions without paired high-resolution training data, while remaining robust across anatomy, disease severity, and acquisition quality. To address this, we introduce a spectrally tuned implicit neural representation (INR) framework for intracranial 4D Flow MRI, representing the velocity field as a continuous coordinate-based neural field using WIRE activation functions with tunable spectral bias. Data-driven and physics-informed variants were evaluated in nine cerebrovascular cases spanning healthy controls and moderate-to-severe intracranial atherosclerotic disease, using CFD-derived high-resolution reference fields, MR-realistic synthetic low-resolution inputs, and direct fitting to acquired in-vivo data. Cohort-optimal spectral-bias settings generalized across subjects with only small increases in relative error compared with subject-specific optima, reducing the need for case-specific hyperparameter tuning. Physics-informed regularization provided modest additional accuracy but required substantially longer optimization, whereas the data-driven INR achieved near-comparable reconstruction performance within minutes. The framework also remained robust to acquisition-realistic noise and moderate VENC-dependent aliasing. These findings establish spectrally optimized INRs as a flexible unsupervised approach for mitigating acquisition-related trade-offs in intracranial 4D Flow MRI.