Detection of volume loss in hippocampal layers in Alzheimer's disease using 7 T MRI: a feasibility study

Abstract

In Alzheimer's disease (AD), the hippocampus is an early site of tau pathology and neurodegeneration. Histological studies have shown that lesions are not uniformly distributed within the hippocampus. Moreover, alterations of different hippocampal layers may reflect distinct pathological processes. 7 T MRI dramatically improves the visualization of hippocampal subregions and layers. In this study, we aimed to assess whether 7 T MRI can detect volumetric changes in hippocampal layers in vivo in patients with AD. We studied four AD patients and seven control subjects. MR images were acquired using a whole-body 7 T scanner with an eight channel transmit-receive coil. Hippocampal subregions were manually segmented from coronal T2*-weighted gradient echo images with 0.3 × 0.3 × 1.2 mm3 resolution using a protocol that distinguishes between layers richer or poorer in neuronal bodies. Five subregions were segmented in the region of the hippocampal body: alveus, strata radiatum, lacunosum and moleculare (SRLM) of the cornu Ammonis (CA), hilum, stratum pyramidale of CA and stratum pyramidale of the subiculum. We found strong bilateral reductions in the SRLM of the cornu Ammonis and in the stratum pyramidale of the subiculum (p < 0.05), with average cross-sectional area reductions ranging from -29% to -49%. These results show that it is possible to detect volume loss in distinct hippocampal layers using segmentation of 7 T MRI. 7 T MRI-based segmentation is a promising tool for AD research.

Keywords: 7 T, 7 Tesla; AD, Alzheimer's disease; Alzheimer's disease; CA, cornu Ammonis; CN, cognitively normal; DG, dentate gyrus; Hippocampal layers; Hippocampus; Human 7 T MRI; MRI, magnetic resonance imaging; SP, stratum pyramidale; SRLM, strata radiatum, lacunosum and moleculare; Segmentation; Volumetry.

Graphical abstract

Fig. 1

Illustration of the positioning of the three acquisition slabs of the T2*-weighted GRE sequence, based on a T1-weighted parasagittal view. The last posterior slice of the first acquisition slab was positioned on the last slice of the head of the hippocampus. The first acquisition slab is represented in orange, the second in green and the third in blue.

Fig. 2

Coronal slices of a TE2 T2*-weighted acquisition in a single AD patient: complete set of slices of the second slab used to define hippocampal layers, in an anterior-to-posterior direction from a to i.

Fig. 3

Coronal slices of a T2×−weighted acquisition (first echo TE1 and second echo TE2) in a CN subject and an AD patient at the level of the hippocampal body and corresponding segmentations. Segmentations were performed on the second echo image. Purple, alveus; dark blue, CA_SP; yellow, SRLM; cyan, hilum and green, subiculum_SP. Abbreviations: CA_SP = stratum pyramidale of CA1–3; SRLM = strata radiatum, lacunosum and moleculare of CA1–3, strata lacunosum and moleculare of the subiculum and stratum moleculare of gyrus dentatus; hilum = stratum pyramidale of CA4 and stratum granulosum and polymorphic layer of gyrus dentatus; subiculum_SP = stratum pyramidale of the subiculum. CN = cognitively normal, AD = Alzheimer's disease.

Fig. 4

Three-dimensional renderings of the segmentations. Purple, alveus; dark blue, CA_SP; yellow, SRLM; cyan, hilum and green, subiculum_SP. Abbreviations: CA_SP = stratum pyramidale of CA1–3; SRLM = strata radiatum, lacunosum and moleculare of CA1–3, strata lacunosum and moleculare of the subiculum and stratum moleculare of gyrus dentatus; hilum = stratum pyramidale of CA4 and stratum granulosum and polymorphic layer of gyrus dentatus; subiculum_SP = stratum pyramidale of the subiculum. CN = cognitively normal, AD = Alzheimer's disease.

Fig. 5

Right and left hippocampal subregional average cross-sectional area in CN and AD subjects (in mm²). Abbreviations: CA_SP = stratum pyramidale of CA1–3; SRLM = strata radiatum, lacunosum and moleculare of CA1–3, strata lacunosum and moleculare of the subiculum and stratum moleculare of gyrus dentatus; hilum = stratum pyramidale of CA4 and stratum granulosum and polymorphic layer of gyrus dentatus; subiculum_SP = stratum pyramidale of the subiculum. CN = cognitively Normal subjects, AD = Alzheimer's disease patients. *Indicates a significant difference between AD and CN (Mann–Whitney U test, p < 0.05). ^#Indicates a trend which did not reach the significance threshold (Mann–Whitney U test, p = 0.058).