Hippocampal Imaging Techniques in Epilepsy and Alzheimer's Disease

The hippocampus lies at the heart of memory and is uniquely prone to pathological change in both temporal lobe epilepsy and Alzheimer’s disease. Advances in magnetic resonance imaging (MRI) have enabled ever finer interrogation of hippocampal structure and function, from macroscopic volume measurements to submillimetre resolution of internal subfields and microstructural connectivity. In epilepsy, the principal aim is to identify hippocampal sclerosis accurately and non-invasively, guiding surgical planning and predicting postoperative seizure freedom. Structural sequences (T1- and T2-weighted) yield volumetric and signal-relaxation metrics, while automated algorithms for subfield segmentation and asymmetry analysis enhance sensitivity to subtle atrophy. In Alzheimer’s disease, imaging focuses on early detection of neurodegenerative markers such as tau neurofibrillary tangles and amyloid deposition within specific subregions, alongside measures of diffuse atrophy. Ex vivo MRI combined with histological atlases refines the spatial mapping of pathology, informing in vivo protocols. Diffusion-weighted techniques extend this by delineating hippocampal white-matter tracts and their alterations in ageing and disease. Machine-learning approaches integrate these quantitative features to distinguish preclinical stages, track progression and assess reserve capacities. Collectively, these imaging modalities provide a multi-scale view of hippocampal integrity, informing diagnosis, prognosis and the development of targeted therapies in two of the most prevalent neurological disorders worldwide.

Research from Nature Portfolio

Recent studies have employed high-resolution ex vivo MRI coupled with three-dimensional histological reconstruction to chart the distribution of tau neurofibrillary tangles across hippocampal subfields. This work reveals an anterior–posterior gradient of tau burden, with peak accumulation in CA1 and the transentorhinal region, and identifies focal zones of early neurodegeneration that may serve as sensitive biomarkers in vivo. Another line of investigation has applied ultra-high angular resolution diffusion MRI to map the hippocampal connectome in individual subjects. Six dominant white-matter pathways were characterised, including a prominent spinal–limbic projection and strong thalamic connections. Age-related variations in connectivity to occipital regions were documented, demonstrating that super-resolution diffusion protocols can provide reliable, individual-level insights into hippocampal network integrity.

Hippocampal Imaging Techniques in Epilepsy and Alzheimer's Disease publication trend

The graph below shows the total number of articles in hippocampal imaging techniques in epilepsy and alzheimer's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Ex vivo MRI: High-resolution magnetic resonance imaging performed on tissue samples outside the living organism to attain microscopic detail.

Tau neurofibrillary tangles: Aggregates of hyperphosphorylated tau protein within neurons, characteristic of Alzheimer’s pathology.

Hippocampal sclerosis: Neuronal cell loss and gliosis in hippocampal subfields, most commonly associated with temporal lobe epilepsy.

Diffusion MRI: An imaging modality sensitive to the movement of water molecules, used to infer white-matter tract architecture.

Hippocampal subfield segmentation: The process of delineating and measuring discrete subdivisions of the hippocampus (e.g., CA1, dentate gyrus) on MRI scans.

References

1. Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer’s disease. Nature Communications (2024).
2. Brain reserve contributes to distinguishing preclinical Alzheimer’s stages 1 and 2. Alzheimer's Research & Therapy (2023).
3. Automated and Interpretable Detection of Hippocampal Sclerosis in Temporal Lobe Epilepsy: AID‐HS. Annals of Neurology (2024).
4. Revealing the Hippocampal Connectome through Super-Resolution 1150-Direction Diffusion MRI. Scientific Reports (2019).