Understanding microscale physiology and microstructural cellular features of the brain is key to understanding mechanisms of neurodegenerative diseases and injury, as well as prominent changes undergone in development and aging. Non-invasive imaging modalities sensitive to the microscale, especially diffusion magnetic resonance imaging (dMRI), are promising for mapping of cellular microstructure of brain tissues; however, there is a need for robust validation techniques to verify and improve the biological accuracy of information derived. Recent advances in dMRI have moved toward probing of the more complex grey matter architecture, challenging current validation techniques, which are largely based on ex vivo staining and microscopy focusing on white matter. Polarized light imaging (PLI) has been shown to be successful for high resolution, direct, microstructural imaging and has been applied to dMRI validation with clear advantages over staining and microscopy techniques. Conventionally, PLI is applied to thin, sectioned samples in transmission mode, but PLI has also been extended to operate in reflectance mode to bridge the gap toward in vivo measurements of the brain. In this report we investigate the use of backscattering Mueller Matrix polarimetry to characterize the microstructural content of intact ferret brain specimens. The results show that backscattering polarimetry can probe white matter fiber coherence and fiber orientation, and show promise for probing grey matter microstructure. Ultimately, this motivates further study to fully understand how best to implement backscattering polarimetry for in vivo microstructural imaging of the brain.

Knowledge of fiber microstructure and orientation in the brain is critical for understanding the pathogenesis and progression of neurodegenerative diseases such as Alzheimer’s disease. Diffusion magnetic resonance imaging (dMRI) is a noninvasive imaging modality that can generate mappings of nerve fiber orientation. Due to rigorous levels of mathematical modeling involved in reconstructing dMRI data; and limited spatial resolution, there arises a need to validate the biological accuracy of collected dMRI data. Polarized light imaging (PLI) has been shown to have potential for microstructural validation due to the anisotropy in many biological tissues, particularly in myelin sheaths surrounding nerve fibers in the brain. Using PLI for this purpose is appealing because it is directly sensitive to tissue structure and can be done at high resolution. While several studies have had success using PLI for fiber mapping, continuing to advance this modality, particularly reflectance based PLI systems, could provide a valuable avenue for in vivo neural imaging. In order to reach the full potential of reflectance PLI systems, some key questions remain such as the ability of PLI to resolve crossing fibers, and the sensitivity of reflectance PLI to fiber inclination. Tissue phantoms are one potential method to isolate these issues in order to investigate them. In this proceeding, a five-wavelength reflectance Mueller matrix polarimeter is used for imaging of promising PLI tissue phantoms as well as regions of interest in fixed ferret brain samples. The retardance, diattenuation and depolarization mappings are derived from the Mueller matrix and studied in order to assess the sensitivity of this polarimeter configuration to different fiber orientations.

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Gastrinomas are gastrin-producing neuroendocrine tumors (NETs) located in the gastroenteropancreatic system. Gastrinomas are often small, multifocal, and found at late stages. Their unpredictable behavior and metastatic potential make it extremely challenging to develop therapeutic strategies. Surgery is the only potentially curative treatment for gastrinoma, but current tumor localization techniques such as intraoperative ultrasound and manual palpitation have poor sensitivity for small tumors, resulting in higher rates of recurrence and metastasis. Therefore, there is a strong clinical need for developing advanced intraoperative imaging technologies for tumor localization in treating gastrinoma. Polarized light imaging (PLI) is a promising method for label-free tissue characterization due to its sensitivity to micro and nanoscale structures, which are often influenced with the onset of cancer, but no works have yet investigated the application of PLI for gastrinoma localization.To assess the suitability of PLI for gastrinoma localization, we imaged 11 formalin-fixed paraffin embedded (FFPE) specimens of gastrinoma using a five-wavelength Mueller Matrix Polarization Microscope. The Lu-Chipman decomposition was applied to spatial maps of the sixteen Mueller matrix parameters. Values for depolarization, diattenuation, and retardance were compared for regions of interest corresponding to tumor and adjacent tissues. There was significant difference between the average depolarization of the Brunner's gland and tumors when imaged with light at 442, 543, and 632nm (p<0.05), and the average diattenuation values of the two at 405nm (p<0.05), suggesting that these properties could be used for label-free localization. These results motivate further study of the use of PLI for NET localization. Future steps include broadening the sample pool to other NETs and validating results in fresh tissue studies.