1. Brain Structure Alterations Revealed Using MRI in an Ethanol Mouse Model

2. Why a mouse model? Ethically acceptable Ethically acceptable Abundant with relatively low costs Abundant with relatively low costs Approximately 99% of mice Approximately 99% of mice have genes that have a homologue have genes that have a homologue in the human genome in the human genome

3. Magnetic Resonance Imaging (MRI) 9.4T Magnet used 9.4T Magnet used Based on the detection of oscillating magnetic field produced by a set of hydrogen nuclei Based on the detection of oscillating magnetic field produced by a set of hydrogen nuclei Tool for non-invasive detection of abnormal morphological patterns Tool for non-invasive detection of abnormal morphological patterns 20 Mice were scanned for approximately an hour each 20 Mice were scanned for approximately an hour each MICe Software used to manipulate MR images MICe Software used to manipulate MR images

4. Image Registration Process of determining the optimal spatial transformation that best aligns a given source image to a given target image Objective is to achieve the maximum similarity between all of the MR images, in order to construct an unbiased average image Feature-based and intensity-based approaches Registration is very complex, it uses an algorithm that considers a transformation model, a similarity measure and optimization

5. Group-wise Registration Each individual image is associated with a deformation field that aligns it with the consensus average

6. Importance of Averaging

7. Average Image Top view Side view Front view 124 Slices 84 Slices 55 Slices

8. Brain Atlas

9. Hippocampus Ventricles

12. HippocampusVentricles Student t-test for alcohol versus control, equal variances not assumed Sample size (Both the same) 3 Significance Value 0.05 Significance (1-tailed) 0.2480  Student t-test for alcohol versus control, equal variances not assumed Sample size (Both the same) 3 Significance Value 0.05 Significance (1-tailed) 0.0076 

13. Why does alcohol affect the ventricles more than the hippocampus? Alcohol known to kill brain cells and decrease brain volume Alcohol known to kill brain cells and decrease brain volume Ventricles are fluid-filled sacs and therefore much more susceptible to change in volume compared to the more rigid hippocampus region Ventricles are fluid-filled sacs and therefore much more susceptible to change in volume compared to the more rigid hippocampus region Function of hippocampus lies in long-term memory, which is not usually associated with the effects of alcohol Function of hippocampus lies in long-term memory, which is not usually associated with the effects of alcohol

14. However, While it has been agreed that alcohol decreases brain volume in general, it has been shown to increase ventricular volume in humans While it has been agreed that alcohol decreases brain volume in general, it has been shown to increase ventricular volume in humans Perhaps long term alcoholism has dramatic effects on the ventricles Perhaps long term alcoholism has dramatic effects on the ventricles Mouse brain model is not always reliable for predicting similar physiological effects in humans! Mouse brain model is not always reliable for predicting similar physiological effects in humans!

15. Brain atlases are exceptionally useful in determining abnormal morphological patterns Brain ventricles in mice significantly decreased in size when introduced to alcohol, while the hippocampus did not

16. Many Thanks to: Supervisor: Dr. Ravi Menon Technical Support and Guidance: Dr. Alex Li Site: Robarts Research Institute

17. Thank you for listening, any questions?