Glucose: a tracer to assess the brain's drainage system function
The team carried out the experiments using a 3T MRI animal scanner at CityU, the only of its kind in Hong Kong. They injected glucose into genetically modified mice with Alzheimer's disease and healthy mice aged 6 months and 16 months. The dynamic response of glucose both in the cerebrospinal fluid and brain parenchyma were then measured simultaneously using the CEST MRI.
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According to the MRI results, the team observed that the Alzheimer's disease mice have shown significantly slower cerebrospinal fluid clearance rates than the age-matched healthy mice, which is consistent with previous neuropathological findings. "Clearance rates are reduced because of abnormalities in the brain's drainage system," explained Dr Chan.
Moreover, significantly higher glucose uptake was detected in brain parenchyma of the 6 months old mice with Alzheimer's disease compared to the healthy mice of the same age. For the 16 months old mice with Alzheimer's disease, significantly lower glucose uptake was found in both brain parenchyma and cerebrospinal fluid compared to the age-matched healthy mice. These results echo with the previous research findings using other methodologies. These also serve as hallmarks to identify Alzheimer's disease from normal ageing.
The imaging of glucose uptake and clearance in the cerebrospinal fluid and brain parenchyma enables the assessment of the brain glymphatic system. Importantly, abnormalities are detected at the early stage of Alzheimer's disease when little neuropathology develops in the brain. The team believes this non-invasive assessment of the glymphatic system can serve as an imaging biomarker to reveal the early pathology in Alzheimer's disease.
"By using glucose as a 'tracer', our imaging method can sensitively detect the distinctive changes of glymphatic system function at the molecular level at an early stage of the disease, helping us to differentiate it from normal ageing," said Dr Chan. "Besides, glucose is natural, biodegradable, and commonly used in hospitals, such as the glucose tolerance test. Using it as a contrast agent for MRI is non-invasive and safe."
Low set-up cost and high translatability
She pointed out that the new imaging method is compatible with the MRI machines commonly-used in clinics or hospitals, which means low set-up cost and technically easy to transfer into clinical application. "We have already obtained positive results on identifying changes in the tiny brains of mice at 3T (low magnetic field) scanner. We expect changes in human brains are more detectable at 3T clinical scanner since human brains are much larger," added Dr Chan.
