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  • White Matter Tracts Fractional Anisotropy and Mean Diffusivity Changes Over Time in A Rodent Model of Chronic Communicating Hydrocephalus

    Final Number:

    Tito G.M. Vivas-Buitrago MD; Gabriel David Pinilla-Monsalve ASc, MD; Ignacio Jusue-Torres; Jamie Robison RN; Alfredo Quiñones-Hinojosa MD; Susumu Mori; Daniele Rigamonti MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2018 Annual Meeting

    Introduction: The pathogenesis of idiopathic normal pressure hydrocephalus (NPH) still unclear, although, alterations in the white matter secondary to mechanical forces due to the ventricular dilatation is believed to contribute to the patient’s symptomatology. Diffusion tensor imaging (DTI) has been used to characterize microstructural alterations of the brain parenchyma. Given the difficulty to identify iNPH patients before their symptoms onset, we aim, in this study, to explore the fractional anisotropy (FA) and mean diffusivity (MD) in the white matter tracks (WM) during the development of communicating chronic hydrocephalus in a rodent model.

    Methods: Communicating chronic hydrocephalus was induced in five adults Sprague-Dawley rats weighing 250g by a bilateral kaolin injection into the subarachnoid space over the convexities. Five additional animals were used as a control. DTI data acquisition was obtained with a Bruker 11.7-Tscan. Regional FA and MD were measured at the corpus callosum (CC) and cortical-spinal tracts (CST) at days 15,60,90 and, 120 after injection. Statistical analysis was performed using Mann-Withney’s-U, Spearman and Friedman’s tests.

    Results: Progressive ventricular enlargement was demonstrated in the injected group at all four-time points (p<0.050) when compared with control animals. MD at the corpus-callosum was significantly higher in animals with hydrocephalus: 14(p=0.0278), 60(p=0.0143), 90(p=0.009), and 120 days (p=0.0139). CC-MD shows a positive correlation with the ventricular volume (p=0.013), as well as a significant progressive increase in value over time (p=0.0070). CC-FA was decreased in the hydrocephalic animals only at 90 days (p=0.0150). There were no significant differences CP-FA at any time point between groups.

    Conclusions: Mean Diffusivity measurements at the corpus-callosum were significantly higher at all time points in the hydrocephalic animals. These values should be further studied and correlated with behavioral changes as well as its variations/recovery when treated the animals with CSF diversion at different time points.

    Patient Care: With this study, we aim to identify DTI values and in animals induced with chronic hydrocephalus closely resembling the human condition in iNPH like no other animal study. Previously published studies using this animal model have shown an initial asymptomatic ventricular enlargement for the first 60 days. By identifying these diffusion values, we can compare them with the behavioral changes onset and intensity and establish thresholds that can later be translated and validated in a human population for early diagnosis, and prognosis, as well as serve as a potential surgical shunting indication.

    Learning Objectives: To identify the diffusion properties and dynamics in the brain parenchyma during the development of chronic communicating hydrocephalus.

    References: 1. Hoza, D., Vlasák, A., Horínek, D., Sameš, M., & Alfieri, A. (2015). DTI-MRI biomarkers in the search for normal pressure hydrocephalus etiology: a review. Neurosurgical review, 38(2), 239-244. 2. Rumple, A., McMurray, M., Johns, J., Lauder, J., Makam, P., Radcliffe, M., & Oguz, I. (2013). 3-dimensional diffusion tensor imaging (DTI) atlas of the rat brain. PLoS One, 8(7), e67334. 3. Jugé, L., Pong, A. C., Bongers, A., Sinkus, R., Bilston, L. E., & Cheng, S. (2016). Changes in rat brain tissue microstructure and stiffness during the development of experimental obstructive hydrocephalus. PloS one, 11(2), e0148652. 4- Jusué-Torres, I., Jeon, L. H., Sankey, E. W., Lu, J., Vivas-Buitrago, T., Crawford, J. A., ... & Crain, B. (2016). A novel experimental animal model of adult chronic hydrocephalus. Neurosurgery, 79(5), 746-756.

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