Characterizing biophysical properties of the Central Nervous System tissue with quantitative Magnetic Resonance Imaging

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Magnetic Resonance Imaging (MRI) is one of the most versatile imaging techniques for studying fundamental properties of tissue. Since MRI signal is predominantly generated by protons in the water molecules, MRI can be used to study the water behaviour in different environments in different types of tissue, thus allowing characterization of biophysical properties of these tissues. Thanks to MRI's intrinsically non-invasive character, such studies can be carried out in living organisms, making MRI one of the most powerful techniques to non-invasively study basic biology and physiology. Quantitative T2 MRI has been successfully applied to characterize Central Nervous System (CNS) tissue in human brain. My laboratory has developed similar technology to study rodent spinal cord tissue. In the current application we propose to further develop and validate quantitative MRI techniques to characterize biophysical properties of the rodent CNS tissue.*Long term objective of the proposed research programme is the development, validation and application of quantitative MRI techniques to study biophysical properties of CNS tissue in animals. *Short term objectives of the proposed research are:*1. To develop 3D MWI of rat spinal cord in vivo.*We will extend our 2D Compressed Sensing Myelin Water Imaging (CS MWI) technique to three dimensions. The CS algorithm will take advantage of the data sparsity in the slice dimension, in addition to the two in-plane dimensions and the time dimension used in our 2D CS algorithm. *2. To study fundamental characteristics and limitations of MWI in rodent CNS tissue*We will study whether potential exchange of water molecules between the myelin compartment (i.e. the space in between the myelin bi-layers) and the intra-/extra-axonal compartment has any significant effect on Myelin Water Fraction values acquired with our MWI technique from rat spinal cords. We will establish the dependence of MWF values in excised rat spinal cords on the cord temperature. We will also study the effect of tissue fixation on MWF and T2 values by varying the fixation time and phosphate buffer concentration. Finally, we will study the effect of myelin compaction on MWI. We will carry out MWI measurements in PLP-null transgenic mouse model characterized by widening and irregularities of the spaces in between the myelin sheaths: similar pattern to myelin debris. We will compare the MWF values and T2 distributions from the PLP-null cords to the ones obtained from the control cords and cords with myelin debris present.*3. To characterize differences between functional myelin and myelin debris.*We will study correlation between ultra-structure of myelin bi-layers measured with electron microscopy (EM) and MWI. Specifically we will compare T2 distributions in functional myelin vs. myelin debris and study how they correspond to morphological features measured with EM. *4. To compare phase MRI and MWI in characterizing biophysical properties of rodent CNS tissue*We will compare phase MRI and MWI in their respective abilities to distinguish between myelin debris and functional myelin. Since phase MRI is sensitive to presence of both myelin and axons, its ability to distinguish between functional myelin and myelin debris may be superior to that of the MWI technique. We will verify this through a number of in vivo and ex vivo experiments involving normal and abnormal rat spinal cords. *Significance of the proposed research:*The proposed program will further expand research capabilities in the area of non-invasive studies of CNS tissue and will help to broaden our understanding of animal CNS biology and physiology. This programme will also provide excellent opportunities for training graduate students in an interdisciplinary environment.