High-Resolution Small Animal MRI Provides in vivo Measurements of Eye Dimensions With High Accuracy

Abstract

Purpose: : Significant progress in the mouse genome project and established technology for generation of transgenic mice makes the mouse a very attractive species where to study molecular mechanisms of myopia and roles of various genes in postnatal eye plasticity. However, there is currently a lack of methods to objectively measure small changes in the mouse eye dimensions in vivo. To address this issue we tested the feasibility and applicability of a high-resolution small animal MRI for monitoring small changes in the size of the mouse eye anticipated in experimental mouse myopia.

Methods: : In anesthetized mice, longitudinal high-resolution MRI images(23.4 x 23.4 mm²) were obtained in the same C57BL/6J mice (n = 3) at P17, P23, P31 and P35 using a 4.7T Bruker Avance System using a two-turn transmit/receive surface coil (0.8-cm diameter) placed over the eye. Topical gadopentetate dimeglumine (Magnevist) was administered immediately before the MRI examination to help delineate the contours of the anterior chamber. A derived eye diameter was calculated from the orbital circumference as Derived Diameter=Circumference/π.

Results: : Sequential high-resolution images of the mouse eye in the same C57BL/6J mice (n=3) were obtained at P17, P23, P31 and P35. A variety of ocular parameters can be extracted from such images including minor and major axis length, anterior and posterior chamber depth, as well as derived diameter. We found that a derived diameter is a parameter that is independent of the shape of the eye and, therefore, better reflects changes in eye dimensions compared to the direct measurement of axial length. For the derived diameter, we routinely achieved accuracy of at least ±10 µm. The derived diameter of the eyeball was calculated in a group of littermates at P17, P23, P31 and P35. As expected, the growth rate of the eye began to level off as mice aged. A difference of 40 µm between P31 and P35 (close to the anticipated difference between myopic and non-myopic eye in experimental mouse myopia) could be resolved with high confidence (P < 0.0000002).

Conclusions: : High-resolution small animal MRI has sufficient accuracy to measure the small changes in eye size that are anticipated in the proposed experimental mouse myopia.

Keywords: myopia • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • visual development