Related Experiment Video
Updated: Jun 25, 2025
Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
PET/MRI multimodality imaging to evaluate changes in glymphatic system function and biomarkers of Alzheimer's disease
Hidehiko Okazawa1, Munenobu Nogami2,3, Shota Ishida4
1Biomedical Imaging Research Center, University of Fukui, 23-3, Matsuoka-Shimaizuki, Eiheiji-cho, Fukui, 910-1193, Japan. okazawa@u-fukui.ac.jp.
Abstract:
The glymphatic system is considered to play a pivotal role in the clearance of disease-causing proteins in neurodegenerative diseases. This study employed MR diffusion tensor imaging (DTI) to evaluate glymphatic system function and its correlation with brain amyloid accumulation levels measured using [11C]Pittsburgh compound-B (PiB) PET/MRI. Fifty-six patients with mild cognitive impairment and early Alzheimer's disease (AD: 70 ± 11 y) underwent [11C]PiB PET/MRI to assess amyloid deposition and were compared with 27 age-matched cognitively normal volunteers (CN: 69 ± 10y). All participants were evaluated for cognitive function using the Mini Mental State Examination (MMSE) before [11C]PiB PET/MRI. DTI images were acquired during the PET/MRI scan with several other MR sequences. The DTI analysis along the perivascular space index (DTI-ALPS index) was calculated to estimate the functional activity of the glymphatic system. Centiloid scale was applied to quantify amyloid deposition levels from [11C]PiB PET images. All patients in the AD group showed positive [11C]PiB accumulation, whereas all CN participants were negative. ALPS-index for all subjects linearly correlated with PiB centiloid, MMSE scores, and hippocampal volume. The correlation between the ALPS-index and PiB accumulation was more pronounced than with any other biomarkers. These findings suggest that glymphatic system dysfunction is a significant factor in the early stages of Alzheimer's disease.
Insights
Glymphatic system dysfunction, measured by DTI-ALPS index, is strongly linked to amyloid buildup in early Alzheimer's disease (AD). This highlights the glymphatic system's role in AD pathogenesis and potential as a biomarker.
Area of Science:
- Neuroscience
- Radiology
- Biomedical Engineering
Background:
- The glymphatic system facilitates waste clearance in the brain, crucial for preventing neurodegenerative diseases.
- Impaired glymphatic function is implicated in the accumulation of toxic proteins, such as amyloid-beta, in Alzheimer's disease (AD).
- Early detection of glymphatic dysfunction is vital for understanding AD progression.
Purpose of the Study:
- To investigate the relationship between glymphatic system function and amyloid-beta deposition in patients with mild cognitive impairment and early AD.
- To evaluate the utility of Diffusion Tensor Imaging Analysis along the Perivascular Space (DTI-ALPS) as a measure of glymphatic function.
- To correlate glymphatic function with cognitive status and brain structure in AD.
Main Methods:
- Fifty-six patients with mild cognitive impairment/early AD and 27 cognitively normal (CN) controls underwent [11C]Pittsburgh compound-B (PiB) PET/MRI and Diffusion Tensor Imaging (DTI).
- Amyloid deposition was quantified using the Centiloid scale from [11C]PiB PET/MRI.
- Glymphatic system function was assessed using the DTI-ALPS index derived from DTI scans.
Main Results:
- All AD patients exhibited positive [11C]PiB accumulation, while all CN participants were negative.
- The DTI-ALPS index showed a significant linear correlation with PiB centiloid values, indicating reduced glymphatic function with increased amyloid burden.
- ALPS-index also correlated with Mini Mental State Examination (MMSE) scores and hippocampal volume, with the strongest correlation observed between ALPS-index and PiB accumulation.
Conclusions:
- Glymphatic system dysfunction is a significant factor in the early stages of Alzheimer's disease.
- DTI-ALPS index serves as a sensitive biomarker for assessing glymphatic function and its association with amyloid pathology.
- These findings underscore the potential of targeting the glymphatic system for AD diagnosis and treatment.
