image: Low-resolution images (LR) are input, and feature maps are obtained through 3×3 convolution. After passing through a residual in residual (RIR) module, followed by upsampling and a 3×3 convolution layer, high-resolution images (HR) are obtained. RCAB, residual channel attention network; RG, residual group.
Credit: Hailong Liu, Tao Wan
Blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) is a cornerstone of non-invasive brain function investigation, yet its utility is constrained by inherent limitations in spatial and temporal resolution. This narrative review synthesizes recent advances in deep learning (DL) techniques aimed at overcoming these constraints through super-resolution reconstruction, automated segmentation, and robust image registration. By evaluating studies published between 2000 and 2023, we highlight how convolutional neural networks (CNNs), generative adversarial networks (GANs), and Transformer-based architectures are reshaping high-resolution BOLD-fMRI analysis and expanding its clinical applicability.
Current Landscape and Challenges in Deep Learning for BOLD-fMRI
Status of Research on Image Segmentation
DL has dramatically advanced medical image segmentation, with architectures such as U-Net and V-Net enabling precise 2D and 3D delineation of brain structures. Attention mechanisms, as seen in Attention U-Net, improve focus on relevant regions, while models like DeepLabv3+ capture multi-scale context through dilated convolutions. The self-configuring nnU-Net framework has demonstrated remarkable adaptability across diverse segmentation tasks. Transformer-based models, including Swin-Unet and TransUNet, further enhance performance by capturing long-range spatial dependencies, making them particularly effective for complex neuroanatomical segmentation.
Status of Super-Resolution Research
Super-resolution (SR) techniques reconstruct high-resolution (HR) images from low-resolution (LR) inputs, addressing a fundamental challenge in fMRI. Early CNN-based methods like SRCNN and very-deep super-resolution (VDSR) networks improved reconstruction quality by increasing network depth, though they often introduced artifacts or blurring. The integration of residual learning (e.g., in SRResNet) and channel attention mechanisms (e.g., RCAN) helped preserve structural details. GAN-based approaches, such as ESRGAN, further enhanced perceptual quality by leveraging adversarial training, though they sometimes introduced unnatural textures. Recent methods incorporating gradient guidance and structural priors have improved edge clarity and reduced distortion, making SR outputs more suitable for clinical use.
Status of Image Registration Algorithm Research
Image registration aligns fMRI data across time, subjects, or modalities. Traditional feature-based methods (e.g., SIFT, SURF) rely on manually designed descriptors and are computationally intensive. DL has revolutionized this domain: early approaches used autoencoders to extract features or learn similarity metrics, while newer methods employ CNNs to directly estimate deformation parameters. Unsupervised models like VoxelMorph and DIRNet use spatial transformer networks to achieve end-to-end, label-free registration, outperforming conventional algorithms in speed and accuracy. However, challenges remain in handling large deformations and ensuring consistency across multi-modal data.
Application Prospects
DL-based enhancement of BOLD-fMRI holds significant promise:
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Improved Spatial Resolution: DL models infer high-frequency details from LR data, enabling finer localization of neural activity.
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Enhanced Quantitative Analysis: HR images support more precise brain activity quantification and functional mapping.
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Brain Network Connectivity: Reliable SR and registration improve the accuracy of network-based analyses.
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Clinical Diagnostics: High-resolution fMRI can aid in pre-surgical planning, disease monitoring, and functional assessment.
Limitations and Challenges
Despite promising results, several barriers impede clinical translation:
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Computational Costs: GPU/TPU dependencies and long training times limit accessibility.
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Data Heterogeneity: Variability across scanners, protocols, and populations reduces model generalizability.
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Interpretability: The "black-box" nature of DL models undermines clinical trust.
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Validation Gaps: Most studies are retrospective; multi-center prospective trials are scarce.
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Integration Challenges: Mismatches with existing clinical workflows and regulatory hurdles slow adoption.
Conclusions
Deep learning has profoundly enhanced the reconstruction and analysis of high-resolution BOLD-fMRI through innovations in super-resolution, segmentation, and registration. CNNs, GANs, and Transformers have each contributed to improvements in image quality, anatomical accuracy, and functional insight. Nevertheless, widespread clinical implementation requires addressing issues of scalability, generalizability, and interpretability. Future efforts should prioritize standardized benchmarking, multi-institutional validation, and the development of efficient, transparent models to fully realize the potential of DL in functional neuroimaging.
Full text:
https://www.xiahepublishing.com/3067-6150/NSSS-2025-00004
The study was recently published in the Neurosurgical Subspecialties.
Neurosurgical Subspecialties (NSSS) is the official scientific journal of the Department of Neurosurgery at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. NSSS aims to provide a forum for clinicians and scientists in the field, dedicated to publishing high-quality and peer-reviewed original research, reviews, opinions, commentaries, case reports, and letters across all neurosurgical subspecialties. These include but are not limited to traumatic brain injury, spinal and spinal cord neurosurgery, cerebrovascular disease, stereotactic radiosurgery, neuro-oncology, neurocritical care, neurosurgical nursing, neuroendoscopy, pediatric neurosurgery, peripheral neuropathy, and functional neurosurgery.
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Journal
Neurosurgical Subspecialties
Article Title
Deep Learning for Enhancing High-resolution BOLD-fMRI: A Narrative Review of Super-resolution, Segmentation, and Registration Methods
Article Publication Date
17-Jun-2025