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

Abstract

Purpose: To estimate the relationship between R 2 ϭ 1/T 2 as measured with a double echo spin echo sequence and total iron concentration in gray matter structures in the brains of aging rhesus monkeys. Materials and Methods: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 R 2 ϭ 1/T 2 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. Results:The range of tissue iron concentration spanned from 15 to 450 g/g wet weight, with the highest levels in the globus pallidus and the lowest levels in the cerebellum. The results show that R 2 was highly correlated with the total iron concentration and that the relationship between R 2 and tissue iron concentration appeared to depend upon the iron concentration. For concentrations above approximately 150 g/g wet weight, R 2 increased with a sensitivity of 0.0484 Ϯ 0.0023 second -1 ( g/g) -1 . In contrast, where the iron concentration was below 150 g/g, R 2 increased at 0.0013 Ϯ 0.0073 second -1 ( g/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. Conclusion:This study reaffirms the value of measuring the MR relaxation rate R 2 for a noninvasive estimate of iron content in the brain and identified limitations in the relationship at low tissue iron concentrations.

Differentiation of Typical and Atypical Parkinson Syndromes by Quantitative MR Imaging

“…An increase in R2, and especially R2*, can, therefore, be regarded as a marker for iron accumulation, and several studies have provided neuropathologic evidence for this view. [16][17][18] Our results indicate that the higher iron sensitivity of R2* is a key factor in detecting patients with MSA-type Parkinson. The other parameters in our study were clearly less useful in differentiating patients with MSA-type Parkinson from those with IPS or controls.…”

Effect of Age on MRI Phase Behavior in the Subcortical Deep Gray Matter of Healthy Individuals

“…1 Brain iron has been investigated in healthy individuals in both postmortem 1,2 and, more recently, in vivo studies with the use of different MR-based techniques. [3][4][5][6][7][8][9][10][11] Increased iron levels predominantly occur in brain subcortical deep gray matter (SDGM) structures such as the caudate, putamen, thalamus, red nucleus, and substantia nigra. Furthermore, it has been found that brain iron accumulation is influenced by sex.…”

Measurement of brain iron distribution in Hallevorden‐Spatz syndrome

“…Quantitative methods that have been promoted as measures of iron accumulation in the brain are based on relaxation times T1, T2, T2*, and T2' or equivalent relaxation rates R1, R2, R2*, and R2' measurements. It has been shown that these, to a certain degree, are correlated with tissue iron content in the elderly human subjects and in animal models (34). Recent results in nine normal subjects demonstrate a linear relationship between R2* measures and literature-derived iron concentration in four iron-rich areas of the brain: putamen, caudate nucleus, globus pallidus, and thalamus (35).…”