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Anita Nikolova Penkova, Komsan Rattanakijsuntorn, Anahid Khoobyar, Rex Moats, Scott Fraser, Mark S. Humayun, Satwindar Singh Sadhal; GADOLINIUM-IMMUNOGLOBILIN STUDY FOR DIFFUSION COEFFICIENT MEASUREMENT OF BOVINE VITREOUS HUMOR FOR DRUG DELIVERY MODELING. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4457. doi: https://doi.org/.
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The main purpose of this work is to measure the diffusion coefficient (D) of the bovine vitreous humor for a macromolecule (gadolinium-immunoglobulin, Gd-IgG) using MRI visualization combined with numerical modeling of the diffusion process.
The method consists of intravitreally injecting a solution (30 μl, 25 mg/ml) of Gd-lgG (Biopal, Inc.) into fresh bovine eyes (Manning Beef, Pico Rivera, CA) and allowing it to diffuse. Concentration contours were tracked by MRI at different time points, approximately 30 min apart. At the same time, these contours are predicted by a numerical solution of the diffusion equation. The theoretical prediction and the experimental contours are least-squares fitted to minimize the deviation from each other while floating the unknown value of D.Imaging was carried out at 4 or 5 time-points within a 2.5-hour period, giving a snapshot of the concentration profile at each time point. Calibration of the MRI signal for conversion to concentration was carried out by means of phantoms of measured concentrations of Gd-IgG that were included with the eye.
Using the technique developed earlier , constant concentration contours were acquired for each eye at various time points as diffusion of Gd-IgG progressed. Data-fitting of these contours with the theoretical prediction of the concentration distribution for the same initial conditions gave the D values with a standard deviation of 25%. The average value of D for this molecule (160 kDa) was found to be (2.13±0.51)×10-7 cm2/s. This is considerably lower than the value for Gd-DTPA (938 Da), (3.04±0.27)×10-6 cm2/s .
As expected, the diffusion of the larger molecule, Gd-IgG, is considerably lower than that for Gd-DTPA, owing to the substantially larger molecular mass of the former. While in the earlier work  the fully-analytical solution of the diffusion equation relied considerably on near-spherical symmetry of the injected bolus, this does not seem feasible for the bolus with larger molecules that tends distort substantially at injection. Therefore, a finite-element code was employed allowing for greater geometrical flexibility for the current theoretical prediction. These experimental results are useful for the longer term goal of developing a comprehensive model for drug transport in the eye. A. Penkova et al, Int J. Heat Mass Trans, 70: 504-514, 2014
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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