In VivoMRI Mapping of Brain Iron Deposition across the Adult Lifespan

Abstract

Disruption of iron homeostasis as a consequence of aging is thought to cause iron levels to increase, potentially promoting oxidative cellular damage. Therefore, understanding how this process evolves through the lifespan could offer insights into both the aging process and the development of aging-related neurodegenerative brain diseases. This work aimed to map, in vivo for the first time with an unbiased whole-brain approach, age-related iron changes using quantitative susceptibility mapping (QSM)-a new postprocessed MRI contrast mechanism. To this end, a full QSM standardization routine was devised and a cohort of N ϭ 116 healthy adults (20 -79 years of age) was studied. The whole-brain and ROI analyses confirmed that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their exact anatomical location. Whereas only patchy signs of iron scavenging were observed in white matter, strong, bilateral, and confluent QSM-age associations were identified in several deep-brain nuclei-chiefly the striatum and midbrain-and across motor, premotor, posterior insular, superior prefrontal, and cerebellar cortices. The validity of QSM as a suitable in vivo imaging technique with which to monitor iron dysregulation in the human brain was demonstrated by confirming age-related increases in several subcortical nuclei that are known to accumulate iron with age. The study indicated that, in addition to these structures, there is a predilection for iron accumulation in the frontal lobes, which when combined with the subcortical findings, suggests that iron accumulation with age predominantly affects brain regions concerned with motor/output functions.

High-resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7 T

“…The study received ethical approval from the Faculty of Medicine at the University of Magdeburg. All older adults were a subset of a larger cohort previously screened to ensure intact global cognitive performance using a brief neuropsychological battery, exclude neurological or major psychiatric illness and cases of white matter (WM) ischaemia (Acosta-Cabronero et al, 2016). Prior to recruitment into this study, T2-weighted images acquired with 3T MRI were visually inspected to exclude severe brain abnormalities.…”

“…The regularisation parameter (λ=1,000) was the median resulting from five randomly selected datasets, where-using λ=500 steps-the consistency-term residual was matched to an estimate of the foreground field noise level (Morozov, 1966). Note that with the exception of the initial multi-echo combination step, the reconstruction pipeline is essentially the same as that described in a recent 3T study (Acosta-Cabronero et al, 2016).…”

“…Previous studies using either post mortem (Hallgren and Sourander, 1958) or in vivo iron-sensitive MRI techniques (Acosta-Cabronero et al, 2016;Bartzokis et al, 2007;Haacke et al, 2007;Hasan et al, 2012;Pfefferbaum et al, 2009;Raz et al, 2007) have revealed that iron levels and its rate of accumulation are heterogeneous in the human brain. Furthermore, iron deposition may correlate with cognitive impairment (Daugherty et al, 2015;Ghadery et al, 2015;Penke et al, 2012) and slowing of motor performance (Cass et al, 2007;Li et al, 2015;Sullivan et al, 2009), though it is unclear whether this is cause or consequence.…”

“…Furthermore both aforementioned studies were limited to regions-of-interest (ROI) analyses. Yet, recent aging lifespan studies using quantitative multimodal MRI (Callaghan et al, 2014) and QSM (Acosta-Cabronero et al, 2016) have shown whole-brain analyses may be used to reveal global patterns of iron distribution that may otherwise be missed in pre-defined ROI analyses.…”

Feasibility of a Direct-Conversion Method from Magnetic Susceptibility to Relative Electron Density for Radiation Therapy Treatment Planning

“…On the other hand, a new quantitative value, magnetic susceptibility, has been utilized in clinical research in addition to the T 1 , T 2 , and ADC values [18] [19] [20] [21]. Magnetic susceptibility is a physical property of a material that may assist with the detection and quantification of specific biomarkers such as gadolinium, calcium, and iron to assess brain physiology and pathology.…”