Correlation of R2 with total iron concentration in the brains of rhesus monkeys

To estimate the relationship between R2 = 1/T2 as measured with a double echo spin echo sequence and total iron concentration in gray matter structures in the brains of aging rhesus monkeys.

Using a 1.5-T magnetic resonance (MR) imager, we collected double echo spin echo images of the brains of 12 female rhesus monkeys aged between 9 and 23 years. From the double echo images, the transverse relaxation rate R2 = 1/T2 was calculated in selected gray matter regions. After the animals were euthanized, their brains were excised and tissue punches were taken of the substantia nigra, globus pallidus, and gray matter regions of the cerebellum. Some of the tissue punches were assayed for total iron using atomic absorption spectroscopy.

The range of tissue iron concentration spanned from 15 to 450 microg/g wet weight, with the highest levels in the globus pallidus and the lowest levels in the cerebellum. The results show that R2 was highly correlated with the total iron concentration and that the relationship between R2 and tissue iron concentration appeared to depend upon the iron concentration. For concentrations above approximately 150 microg/g wet weight, R2 increased with a sensitivity of 0.0484 +/- 0.0023 second(-1)(microg/g)(-1). In contrast, where the iron concentration was below 150 microg/g, R2 increased at 0.0013 +/- 0.0073 second(-1)(microg/g)(-1). The bilinear behavior may reflect changes with age in the relative amounts of iron distributed diffusely and in granular form in the globus pallidus and substantia nigra. Histological sections of the tissues stained for iron and ferritin support this hypothesis and indicate that the distribution of ferritin is similar to the distribution of iron.

This study reaffirms the value of measuring the MR relaxation rate R2 for a noninvasive estimate of iron content in the brain and identified limitations in the relationship at low tissue iron concentrations.