Quantitative MR Imaging of Brain Iron: A Postmortem Validation Study

Langkammer, Christian; Krebs, Nikolaus; Goessler, Walter; Scheurer, Eva; Ebner, Franz; Yen, Kathrin; Fazekas, Franz; Ropele, Stefan

doi:10.1148/radiol.10100495

Cited by 452 publications

(493 citation statements)

References 39 publications

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“…The location of iron accumulation was further associated with microstructural axonal damage. Recently, several studies reported a linear relationship between transverse magnetic resonance relaxation rates and iron content in healthy subjects and postmortem tissue, indicating that R2* imaging is a good surrogate for detecting cerebral iron accumulations 25, 26, 27. By a rater‐driven approach, T2*‐weighted imaging of SAH patients in their chronic stage allowed to identify signal alterations within the subarachnoid space even years after the onset 28, 29, 30.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal profile of iron accumulation in good‐grade subarachnoid hemorrhage

Scherfler

Schiefecker

Delazer

et al. 2016

Ann Clin Transl Neurol

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Objective MRI parameters of iron concentration (R2*, transverse relaxation rate), microstructural integrity (mean diffusivity and fractional anisotropy), as well as gray and white matter volumes were analyzed in patients with subarachnoid hemorrhage (SAH) and uncomplicated clinical course to detect the evolution of brain tissue changes 3 weeks and 12 months after ictus.Methods MRI scans of 14 SAH patients (aneurysm of the anterior communicating artery, n = 5; no aneurysm n = 9) were compared with 14 age‐matched healthy control subjects. Statistical parametric mapping (SPM) was applied to objectively identify focal changes of MRI parameters throughout the entire brain and to correlate image parameters with neuropsychological measures.Results SPM localized significant bilateral increases in R2* signal within the white matter compartment of the temporal and parietal lobe and the cingulate gyrus (P < 0.001) which did not change significantly at 12 months. Significant gray matter volume reduction of the left insula and superior temporal gyrus (P < 0.001), as well as decreases in fractional anisotropy of the cingulate gyrus (P < 0.01) were also evident at 12 months. Significant correlations were found between fractional anisotropy signal alterations adjacent to the left middle and superior frontal gyrus and cognitive parameters of executive dysfunction (P < 0.001).InterpretationThe study indicates that iron is trapped predominantly throughout large portions of the white matter compartment in SAH patients at 12 months postbleeding. Increased disintegration of fiber tracts colocalizing with iron overload and correlating with lower executive function performance suggests that the white matter compartment is primarily susceptible toward long‐term damage in patients with good clinical grade SAH.

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Section: Discussionmentioning

confidence: 99%

Longitudinal profile of iron accumulation in good‐grade subarachnoid hemorrhage

Scherfler

Schiefecker

Delazer

et al. 2016

Ann Clin Transl Neurol

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“…54 Proton magnetic resonance spectroscopy ( 1 H MRS) can add information on the biochemical nature of MS related abnormalities, by quantifying several CNS metabo lites. 55 T2 hypointense areas and reduced T2* relaxation time (or its reciprocal R2*) are thought to be associated with iron deposition, which is believed to be a sign of neurodegeneration in patients with MS. 56 Application of these techniques to characterize the extent and distribution of MS related damage within focal lesions or in normal appearing white and grey matter has shown that tissue disruption in patients with progressive disease is more severe and more widely distributed than in patients with relapsing forms of MS. 57 Additionally, struc tural CNS damage has been shown to progress at different rates across the major clinical pheno types of MS. Global and regional quantitative MRI abnormalities corre late with the severity of clinical and cognitive impairment, and advanced and quantitative MRI techniques seem to be useful for predicting subsequent accumulation of clinical disability and cognitive impairment.…”

Section: Focal Lesionsmentioning

confidence: 99%

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

2015

Nat Rev Neurol

413

147

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“…In fact, several studies report a linear relationship between iron content and T 2 in brain tissue. [23][24][25] …”

Section: Endogenous T 2 Contrastmentioning

confidence: 99%

“…63 Most iron is chelated and stored in the protein ferritin as Fe 3+ , 23,63 which shortens water proton T 1 and T 2 relaxation times. 23,64 Accordingly, several studies reported T 1 and T 2 effects as a function of iron content 10,[23][24][25]65 in the human brain, with concentration in the globus pallidus (GP) among the highest. Though T 2 W MR imaging shows a similar pattern of signal reduction around the GP (white arrows in Fig.…”

Section: Nerve Cellsmentioning

confidence: 99%

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

2016

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This article provides an overview of in vivo magnetic resonance (MR) imaging contrasts obtained for mammalian brain in relation to histological knowledge. Emphasis is paid to the (1) significance of high spatial resolution for the optimization of T 1 , T 2 , and magnetization transfer contrast, (2) use of exogenous extra-and intracellular contrast agents for validating endogenous contrast sources, and (3) histological structures and biochemical compounds underlying these contrasts and (4) their relevance to neuroradiology. Comparisons between MR imaging at subnanoliter resolution and histological data indicate that (a) myelin sheaths, (b) nerve cells, and (c) the neuropil are most responsible for observed MR imaging contrasts, while (a) diamagnetic macromolecules, (b) intracellular paramagnetic ions, and (c) extracellular free water, respectively, emerge as the dominant factors. Enhanced relaxation rates due to paramagnetic ions, such as iron and manganese, have been observed for oligodendrocytes, astrocytes, microglia, and blood cells in the brain as well as for nerve cells. Taken together, a plethora of observations suggests that the delineation of specific structures in high-resolution MR imaging of mammalian brain and the absence of corresponding contrasts in MR imaging of the human brain do not necessarily indicate differences between species but may be explained by partial volume effects. Second, paramagnetic ions are required in active cells in vivo which may reduce the magnetization transfer ratio in the brain through accelerated T 1 recovery. Third, reductions of the magnetization transfer ratio may be more sensitive to a particular pathological condition, such as astrocytosis, microglial activation, inflammation, and demyelination, than changes in relaxation. This is because the simultaneous occurrence of increased paramagnetic ions (i.e., shorter relaxation times) and increased free water (i.e., longer relaxation times) may cancel T 1 or T 2 effects, whereas both processes reduce the magnetization transfer ratio.

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Quantitative MR Imaging of Brain Iron: A Postmortem Validation Study

Cited by 452 publications

References 39 publications

Longitudinal profile of iron accumulation in good‐grade subarachnoid hemorrhage

Longitudinal profile of iron accumulation in good‐grade subarachnoid hemorrhage

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

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