Cemile AVCI AKAN
Journal of Experimental and Clinical Medicine - 2026;43(2):220-229
The hippocampus is a brain structure located in the medial temporal lobe that plays a key role in fundamental cognitive processes such as memory, learning, and spatial orientation, exhibiting significant structural and functional heterogeneity at the subregional level. Conventional magnetic resonance imaging relies primarily on volumetric measurements to assess the shape, structure, and macroscopic integrity of the hippocampus; however, these measurements are limited in evaluating microstructural changes in neuronal and dendritic organization. Detecting microstructural alterations in hippocampal subregions that appear volumetrically preserved necessitates more advanced imaging approaches. Diffusion magnetic resonance imaging (dMRI) is an important neuroimaging technique that enables in vivo assessment of tissue microstructure. The commonly preferred diffusion tensor imaging (DTI) method has various limitations in structures such as the hippocampus, which are gray matter-dominant and exhibit significant intravoxel heterogeneity. New approaches have gone beyond the tensor model to integrate biophysical models that enable the determination of more advanced and specific features of tissue microstructure. Within this methodological framework, advanced diffusion techniques particularly High Angular Resolution Diffusion Imaging (HARDI) combined with multi-compartment modeling have improved our ability to investigate the structural organization of the hippocampus in greater detail. In particular, Neurite Orientation Dispersion and Density Imaging (NODDI) provides quantitative measures such as neurite density and orientation dispersion, facilitating a more nuanced interpretation of gray matter microstructure at the subregional level. This review summarizes current methodological and clinical developments regarding the use of HARDI and NODDI for the in vivo assessment of hippocampal microstructure. The present review examines the integration of hippocampal subregion segmentation with advanced diffusion MRI techniques and considers how this framework advances understanding beyond volumetric assessment. Methodological constraints and emerging research directions are also addressed.
