J Clin Neurol.  2018 Apr;14(2):158-164. 10.3988/jcn.2018.14.2.158.

Glucose Hypometabolism in Hippocampal Subdivisions in Alzheimer's Disease: A Pilot Study Using High-Resolution ¹⁸F-FDG PET and 7.0-T MRI

Affiliations
  • 1Neuroscience Research Institute, Gachon University, Incheon, Korea.
  • 2Department of Biomedical Engineering, College of Health Science, Gachon University, Incheon, Korea.
  • 3Department of Neurology, Gachon University Gil Medical Center, Incheon, Korea. khpark@gachon.ac.kr
  • 4Department of Neurosurgery, Gachon University Gil Medical Center, Incheon, Korea. neurokim@gachon.ac.kr

Abstract

BACKGROUND AND PURPOSE
Atrophy of the hippocampus is an important clinical diagnostic marker of Alzheimer's disease (AD), and so assessments of hippocampal activity and its subdivisions might provide invaluable information. This study compared the glucose metabolism of hippocampal subdivisions in mild-AD patients and healthy controls.
METHODS
High-resolution T2*-weighted gradient-echo magnetic resonance imaging (MRI) images and ¹â¸F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) images were acquired using 7.0-T MRI and high-resolution research tomograph FDG-PET, respectively, in 9 early-stage AD patients and 10 healthy subjects. The hippocampal body was divided into three equal parts (anterior, middle, and posterior), and in each part a region of interest (ROI) was drawn over the cornus ammonis (CA)1, CA2/3, CA4/dentate gyrus (DG), and subiculum. The standardized uptake values of the hippocampal subdivisions were calculated for each ROI as ratios relative to the pons standardized uptake value. Statistical analysis was conducted using the Mann-Whitney U test.
RESULTS
Patients with early-stage AD patients showed significantly less metabolic activity than healthy controls focally in the middle (p=0.050) and posterior (p=0.034) CA2/3 regions of the right hippocampus, and significantly less activity throughout the left hippocampal body in the anterior CA2/3 (p=0.027) and CA4/DG (p=0.027) regions, the middle CA1 region (p=0.011), and the posterior CA1 (p=0.034), CA2/3 (p=0.007), and CA4/DG (p=0.014) regions.
CONCLUSIONS
It was possible to use high-resolution PET-MRI fusion images to identify hippocampus subdivisions and assess glucose metabolism in the subfields. Reductions in metabolic activity were found to vary along the hippocampal axis in early-stage AD patients.

Keyword

Alzheimer's disease; hippocampus; hypometabolism; fluorodeoxyglucose

MeSH Terms

Alzheimer Disease*
Atrophy
Cornus
Glucose*
Healthy Volunteers
Hippocampus
Humans
Magnetic Resonance Imaging*
Metabolism
Pilot Projects*
Pons
Positron-Emission Tomography
Glucose

Figure

  • Fig. 1 ROIs in the hippocampal subfields and three divisions of the hippocampal body along the hippocampus. (A) Slice positions in the sagittal reference images. Each of the five slices from the hippocampal head to tail were divided into the anterior (Ant, yellow), middle (Mid, red), and posterior (Post, blue) parts. The separating slices (white dotted lines) were not included in the data analysis. (B) Hippocampal ROIs drawn in the coronal planes. A line crossing the CA4/DG region from the hippocampal sulcus to the outer edge of the temporal horn was drawn as the reference line. A perpendicular line dividing the reference line in half defined the boundary between CA2/3 and CA1. The boundary between CA1 and the subiculum (Sub) was placed at the hippocampal sulcus. CA: cornus ammonis, DG: dentate gyrus, ROI: region of interest.

  • Fig. 2 Superimposed 7.0-T MRI images and HRRT-PET images of bilateral hippocampi in a healthy subject (A) and an early-stage AD patient (B). HRRT-PET images were produced using the same thresholds in healthy controls and AD patients. The white and black arrows indicate the location of the hippocampus. (C) Glucose metabolism quantified in the entire hippocampi. The asterisks indicate significant differences at p<0.05. Data are mean and SD values. AD: Alzheimer's disease, CA: cornus ammonis, DG: dentate gyrus, HRRT: high-resolution research tomograph, MRI: magnetic resonance imaging, PET: positron-emission tomography.

  • Fig. 3 Distribution of glucose metabolism within subfields along longitudinal axis of hippocampus. (A) Representative manually drawn ROIs on 7.0-T MRI images. ROIs were drawn on each slice along the longitudinal axis of the hippocampus bilaterally, and the hippocampus was divided into anterior, middle, and posterior parts. (B) Glucose metabolism in the right hippocampus. (C) Glucose metabolism in the left hippocampus. The asterisks indicate significant differences at p<0.05. Data are mean and SD values. AD: Alzheimer's disease, CA: cornus ammonis, DG: dentate gyrus, MRI: magnetic resonance imaging, ROI: region of interest.


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