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Early changes in the apparent diffusion coefficient (ADC) in a mouse model of Sandhoff's disease occur prior to
Lingyun Hu1, Yingying Sun, Laura E Villasana
1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Abstract:
Sandhoff's disease is a lysosomal storage disease in which the ganglioside GM2 accumulates in lysosomes. It has been reported that MRI cannot detect abnormalities in spin echo images in clinically presymptomatic Sandhoff's disease patients. Because one of the results of GM2 accumulation is cell swelling and lysosomal distension, our goal was to determine if changes in the diffusion of water is perturbed. We utilized the MRI imaging modality diffusion-weighted imaging to measure the apparent diffusion coefficient in a mouse models of Sandhoff's disease, the hexb-/- mouse, and determined if diffusion-weighted imaging could be utilized to detect early changes prior to behavioral or overt disease symptom onset. Here we report for the first time a comprehensive behavioral characterization of the hexb-/- mouse in conjunction with the apparent diffusion coefficient measurement. Our data indicate that the apparent diffusion coefficient decreases in the hexb-/- mouse in many but not all brain regions prior to disease symptoms (<3.5 to 4 months of age) and behavioral deficits (3 months of age). The magnitude of the decrease ranged from 4-18%.
Insights
Sandhoff
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Sandhoff's disease is a lysosomal storage disorder characterized by GM2 ganglioside accumulation.
- Conventional MRI techniques often fail to detect abnormalities in presymptomatic Sandhoff's disease.
- GM2 accumulation leads to cellular swelling and lysosomal distension, suggesting potential alterations in water diffusion.
Purpose of the Study:
- To investigate if diffusion-weighted imaging (DWI) can detect early pathological changes in Sandhoff's disease.
- To measure the apparent diffusion coefficient (ADC) in a mouse model of Sandhoff's disease.
- To correlate ADC changes with disease onset and behavioral deficits.
Main Methods:
- Utilized diffusion-weighted imaging (DWI) on hexb-/- mice, a model for Sandhoff's disease.
- Measured the apparent diffusion coefficient (ADC) across various brain regions.
- Conducted comprehensive behavioral characterization of the hexb-/- mice.
Main Results:
- A significant decrease in ADC was observed in multiple brain regions of hexb-/- mice before symptom onset.
- ADC reductions ranged from 4-18%.
- Behavioral deficits were noted around 3 months of age, with pathological changes detectable earlier via ADC.
Conclusions:
- Diffusion-weighted imaging can detect early, sub-symptomatic brain changes in Sandhoff's disease.
- ADC measurements show promise as a sensitive biomarker for early diagnosis and monitoring of Sandhoff's disease progression.
- This study highlights the utility of DWI in understanding the pathophysiology of lysosomal storage diseases.
