Diffusion tensor imaging of deep gray matter brain structures: Effects of age and iron concentration

Abstract

Diffusion tensor imaging (DTI) of the brain has become a mainstay in the study of normal aging of white matter, and only recently has attention turned to the use of DTI to examine aging effects in gray matter structures. Of the many changes in the brain that occur with advancing age is increased presence of iron, notable in selective deep gray matter structures. In vivo detection and measurement of iron deposition is possible with magnetic resonance imaging (MRI) because of iron's effect on signal intensity. In the process of a DTI study, a series of diffusion-weighted images (DWI) is collected, and while not normally considered as a major dependent variable in research studies, they are used clinically and they reveal striking conspicuity of the globus pallidus and putamen caused by signal loss in these structures, presumably due to iron accumulation with age. These iron deposits may in turn influence DTI metrics, especially of deep gray matter structures. The combined imaging modality approach has not been previously used in the study of normal aging. The present study used legacy DTI data collected in 10 younger (22-37 years) and 10 older (65-79 years) men and women at 3.0 T and fast spin-echo (FSE) data collected at 1.5 T and 3.0 T to derive an estimate of the fielddependent relaxation rate increase (the "FDRI estimate") in the putamen, caudate nucleus, globus pallidus, thalamus, and a frontal white matter sample comparison region. The effect of age on the diffusion measures in the deep gray matter structures was distinctly different from that reported in white matter. In contrast to lower anisotropy and higher diffusivity typical in white matter of older relative to younger adults observed with DTI, both anisotropy and diffusivity were higher in the older than younger group in the caudate nucleus and putamen; the thalamus showed little effect of age on anisotropy or diffusivity. Signal intensity measured with DWI was lower in the putamen of elderly than young adults, whereas the opposite was observed for the white matter region and thalamus. As a retrospective study based on legacy data, the FDRI estimates were based on FSE sequences, which underestimated the classical FDRI index of brain iron. Nonetheless, the differential effects of age on DTI metrics in subcortical gray matter structures compared with white matter tracts appears to be related, at least in part, to local iron content, which in the elderly of the present study was prominent

Longitudinal diffusion tensor and manganese-enhanced MRI detect delayed cerebral gray and white matter injury after hypoxia–ischemia and hyperoxia

“…In preterm infants with diffuse excessive high signal intensity in white matter indicating white matter abnormality, increased axial and radial diffusivity have been found on DTI (33). DTI studies of normal aging subjects have revealed higher FA and axial diffusivity in basal ganglia attributed to tissue degradation and a relatively more compact tissue (34). A restricted volume of basal ganglia has been shown in preterm infants (35), parallel to our findings of lower contralateral brain volume after HI in the long term.…”

Thalamic Fractional Anisotropy Predicts Accrual of Cerebral White Matter Damage in Older Subjects with Small-Vessel Disease

“…Specifically, without a control group or histopathologic data we are unable to assess whether FA values of the deep GM reflected SVD pathology. In addition, because of the reported direct correlation between iron content and FA values, 12,42 age-related iron accumulation in the striatum might have concealed possible associations of FA changes in the caudate and putamen with WMH burden and accrual. There is emerging scientific evidence that the iron content increases with age also within the thalamus.…”

Diffusion Tensor MR Imaging in Children with Pantothenate Kinase−Associated Neurodegeneration with Brain Iron Accumulation and Their Siblings

“…24 It has been reported that iron deposition influences DTI metrics 16,17 by introducing local field gradients that have been shown to increase anisotropy. 25 Pfefferbaum et al 16 reported increased anisotropy in deep gray matter nuclei with age and correlated it with FDRI estimates. A near-perfect correlation between FDRI estimates and brain iron concentration measured postmortem has also been reported.…”

“…A near-perfect correlation between FDRI estimates and brain iron concentration measured postmortem has also been reported. 16,26 It suggests that iron accumulation influences FA values in controls and patients with abnormal iron metabolism. In another DTI study on brain hemorrhage and HBT, increased FA has been reported even in glioma with a chronic stage of bleed.…”

“…15 Recently, high FA has also been reported in the deep gray matter nuclei with advancing age, and the physiologic increase in iron deposition has been implicated as the cause. 16,17 In view of observed increased iron accumulation associated with high FA, [15][16][17] we hypothesized that the increase in iron concentration in the basal ganglia of these children should result in increased anisotropy, because the disorder is known to have abnormal iron metabolism. The study aimed to compare DTI metrics in deep gray matter of patients with PKAN and their siblings with age-matched healthy controls and to see whether these changes indicate abnormal iron metabolism, especially in siblings of patients with PKAN.…”