In vivo MR evaluation of age-related increases in brain iron.

PURPOSE: To assess the validity of an MR method of evaluating tissue iron. METHODS: The difference between the transverse relaxation rate (R2) measured with a high-field MR instrument and the R2 measured with a lower field instrument defines a measure termed the field-dependent R2 increase (FDRI). Previous in vivo and in vitro studies indicated that FDRI is a specific measure of tissue iron stores (ferritin). T2 relaxation times were obtained using two clinical MR instruments operating at 0.5 T and 1.5 T. T2 relaxation times were measured in the frontal white matter, caudate nucleus, putamen, and globus pallidus of 20 healthy adult male volunteers with an age range of 20 to 81 years. R2 was calculated as the reciprocal of T2 relaxation time. These in vivo MR results were correlated with previously published postmortem data on age-related increases of nonheme iron levels. RESULTS: The FDRI was very highly correlated with published brain iron levels for the four regions examined. In the age range examined, robust and highly significant age-related increases in FDRI were observed in the caudate and putamen. The correlations of age and FDRI in the globus pallidus and white matter were significantly lower and did not have statistical significance. CONCLUSIONS: The data provide additional evidence that FDRI is a specific measure of tissue iron stores. The data also show that age-related increases in tissue iron stores can be quantified in vivo despite significant age-related processes that oppose the increase in R2 caused by iron. These results are relevant to the investigation of neurodegenerative processes in which iron may catalyze toxic free-radical reactions.

In vivo evaluation of brain iron in Alzheimer's disease and normal subjects using MRI.

Magnetic resonance imaging (MRI) can measure transverse relaxation rate (R2) of tissues. Although R2 is increased by tissue iron levels, R2 is not a specific measure of iron. A new method, based on the fact that ferritin (the primary tissue iron storage protein) affects R2 in a field-dependent manner, can quantify tissue iron with specificity by measuring the Field Dependent R2 Increase (FDRI). Using the FDRI method, we compared brain iron stores in frontal white matter, caudate nucleus, putamen, and globus pallidus of five male patients with Alzheimer disease (AD) and eight age and gender-matched normal controls. FDRI values were significantly higher among AD patients in the caudate and globus pallidus. The data suggest that AD may involve disturbances in brain iron metabolism and that the involvement of iron in the pathophysiology of age-related neurodegenerative disorders can be investigated in vivo using MRI.

Reliability of in vivo volume measures of hippocampus and other brain structures using MRI.

Volume reductions of the hippocampus are associated with Alzheimer's disease, schizophrenia, and epilepsy. We used clinically available MRI methods (2D acquisition; inversion recovery and calculated T2 images; 3 mm contiguous slices) that optimize image contrast, quality, and resolution and standardized positioning protocols to maximize the in vivo accuracy (test-retest reliability) of brain volume measurements in volunteers who were scanned two or three times. Volunteers were scanned in the same MRI instrument (intrascanner reliability) as well as in two different instruments (interscanner reliability). A single rater obtained brain volume measures of seven contiguous slices centered on the anterior commissure. The in vivo intrascanner reliability for measures of anterior hippocampus and ventricular volumes was very good, with reliability coefficients [intraclass r (rxx)] ranging between .855 and .997, and a median coefficient of variation (CV) of 6.4%. Reliability was good for amygdala (rxx of .740 and .764) and for total frontal and temporal lobe volumes and white matter volume measures (rxx ranging between .640 and .823, median coefficient of variation was 3.2%). Overall, interscanner reliability was also good. We discuss the implications of our results relative to the possible clinical utility of hippocampal quantification and the feasibility of prospective studies aimed at quantifying progressive neurodegeneration.