Assessment of brain iron and neuronal integrity in patients with Parkinson's disease using novel MRI contrasts

Abstract

Postmortem demonstration of increased iron in the substantia nigra (SN) is a well-appreciated finding in Parkinson's disease (PD). Iron facilitates generation of free radicals, which are thought to play a role in dopamine neuronal loss. To date, however, magnetic resonance imaging (MRI) has failed to show significant in vivo differences in SN iron levels in subjects with PD versus control subjects. This finding may be due to the limitations in tissue contrasts achievable with conventional T(1)- and T(2)-weighted MRI sequences that have been used. With the recent development of novel rotating frame transverse (T(2rho)) and longitudinal (T(1rho)) relaxation MRI methods that appear to be sensitive to iron and neuronal loss, respectively, we embarked on a study of 8 individuals with PD (Hoehn & Yahr, Stage II) and 8 age-matched control subjects. Using these techniques with a 4T MRI magnet, we assessed iron deposits and neuronal integrity in the SN. First, T(2rho) MRI, which is reflective of iron-related dynamic dephasing mechanisms (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities), demonstrated a statistically significant difference between the PD and control group, while routine T(2) MRI did not. Second, T(1rho) measurements, which appear to reflect upon neuronal count, indicated neuronal loss in the SN in PD. We show here that sub-millimeter resolution T(1rho) and T(2rho) MRI relaxation methods can provide a noninvasive measure of iron content as well as evidence of neuronal loss in the midbrain of patients with PD.

Different Iron-Deposition Patterns of Multiple System Atrophy with Predominant Parkinsonism and Idiopathetic Parkinson Diseases Demonstrated by Phase-Corrected Susceptibility-Weighted Imaging

“…Our results are in concordance with several previous studies reporting increased iron depositions in the SN of patients with multiple system atrophy and IPD. 15,[42][43][44][45][46][47] A few studies [48][49][50] used SWI images to detect putative iron content in the brain as a tool to differentiate MSA-P from IPD. Gupta et al 49 investigated SWI for patterns of mineralization to differentiate progressive supranuclear palsy, IPD, and multiple system atrophy; minimum-intensity-projection images of SWI were used to obtain signal intensities of each nucleus, which did not demonstrate a significant difference between IPD and multiple system atrophy, though higher putaminal hypointensity scores were found in patients with multiple system atrophy compared with those with IPD.…”

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

“…The thalamus and white matter contain little to no iron (Hallgren and Sourander, 1958) and therefore exhibit no T 2 * effect from iron (Bartzokis et al, 1993). Other structures, including the putamen and caudate, however, are vulnerable to further accumulation of iron with advancing age (Bartzokis et al, 1994(Bartzokis et al, , 2007b, and the iron accumulation is abnormally high in diseases of the basal ganglia, such as Parkinson's disease (Bartzokis et al, 1999;Michaeli et al, 2007;Pujol et al, 1992), striatonigral degeneration , and Huntington's disease (Bartzokis et al, 2007a).…”

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

“…However, R2' and R2* did not correlate with clinical impairment. In another study, using the T2 rho MRI method, Michaeli et al 50 showed increased substantia nigra iron levels in patients with PD versus normal controls. Kosta et al 100 compared T2 intensity in the substantia nigra pars compacta and subthalamic nucleus in 40 patients with PD and 40 normal controls.…”

“…Wheaton et al 49 demonstrated an increase in iron-related contrast when comparing images created with T2 rho to conventional T2 in the normal human brain. Using a 4T magnet with a rotating frame and applying adiabatic pulses, Michaeli et al 50 demonstrated a statistically significant shortening of relaxation times in substantia nigra tissue in patients with PD compared to normal controls with T2 rho but not with routine T2. This correlates with postmortem observations of excessive iron deposition associated with the disease and suggests that this novel technique generates better iron-related contrast than conventional T2 methodology.…”