Validation of quantitative susceptibility mapping with Perls' iron staining for subcortical gray matter

Sun, Hongfu; Walsh, Andrew J.; Lebel, R. Marc; Blevins, Gregg; Catz, Ingrid; Lu, Jian‐Qiang; Johnson, Edward S.; Emery, Derek; Warren, Kenneth G.; Wilman, Alan H.

doi:10.1016/j.neuroimage.2014.11.010

Cited by 143 publications

(129 citation statements)

References 49 publications

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“…QSM provides a quantitative and local anatomical contrast by estimating magnetic susceptibility sources from their signature on the MRI signal phase (de Rochefort et al, 2008). QSM results have shown agreement with both post-mortem iron measurements (Langkammer et al, 2012;Sun et al, 2015;Zheng et al, 2013) and additional iron-sensitive MRI techniques (Bilgic et al, 2012;Poynton et al, 2015). Furthermore, at ultra high-field strength (B0≥7 Tesla), QSM has demonstrated superb anatomical contrast and superior delineation of GM substructures compared to R2* and conventional iron-sensitive measures (Deistung et al, 2013;Lotfipour et al, 2012).…”

Section: Introductionmentioning

confidence: 69%

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

et al. 2016

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Quantitative susceptibility mapping (QSM) has recently emerged as a novel magnetic resonance imaging (MRI) method to detect non-haem iron deposition, calcifications, demyelination and vascular lesions in the brain. It has been suggested that QSM is more sensitive than the more conventional quantifiable MRI measure, namely the transverse relaxation rate, R2*. Here, we conducted the first high-resolution, whole-brain, simultaneously acquired, comparative study of the two techniques using 7 Tesla MRI. We asked which of the two techniques would be more sensitive to explore global differences in tissue composition in elderly adults relative to young subjects. Both QSM and R2* revealed strong agerelated differences in subcortical regions, hippocampus and cortical grey matter, particularly in superior frontal regions, motor/premotor cortices, insula and cerebellar regions. Within the basal ganglia system-but also hippocampus and cerebellar dentate nucleus-, QSM was largely in agreement with R2* with the exception of the globus pallidus. QSM, however, provided superior anatomical contrast and revealed age-related differences in the thalamus and in white matter, which were otherwise largely undetected by R2* measurements. In contrast, in occipital cortex, age-related differences were much greater with R2* compared to QSM. The present study, therefore, demonstrated that in vivo QSM using ultra-high field MRI provides a novel means to characterize age-related differences in the human brain, but also combining QSM and R2* using multigradient recalled echo imaging can potentially provide a more complete picture of mineralization, demyelination and/or vascular alterations in aging and disease.

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Section: Introductionmentioning

confidence: 69%

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

et al. 2016

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“…All scans were performed on a 3T GE LX The 65 Zn experiments were adapted from a previous publication. 59 Briefly, serum-free immunohistochemistry and brain section analysis.…”

Section: Brain Imaging and Sn T 2 Relaxometrymentioning

confidence: 99%

“…Lithium treatment induced a decrease in hippocampal T 2 relaxation time 19 that could not only indicate an improvement in various neuropathologies (for example, edema), but also reflect an increase in tissue iron. 61,62,63,64,65 As iron elevation in the SN could contribute to Parkinson-like side effects such as the commonly observed hand tremor, we revisited this study and measured T 2 relaxation in this region, as well as other comparison regions in the same coronal planes (as marked in Supplementary Figure 1a, with reference to a standard neuroanatomical atlas). We found that the average T 2 relaxation time in the SN of the lithium group at 3 months (scan two) was significantly reduced from baseline (scan one) (−5%, P=0.007), and significantly lower than the Figure 1b).…”

Section: Low-dose Lithium Treatment Induces Reversible T 2 * Changes mentioning

confidence: 99%

Lithium suppression of tau induces brain iron accumulation and neurodegeneration

et al. 2016

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Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T 2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tauand amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer's disease), and may explain lithium-associated motor symptoms in susceptible patients.

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“…5,[7][8][9][10][11] Among the MR imaging measures used, only the gradient-echo transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) have been validated against postmortem iron assessment, both in non-MS 12,13 and in MS populations. 14,15 Three MS studies assessed different aspects of cognition along with R2*. 5,10,11 In Khalil et al, 5 R2* in the basal ganglia (but not in the thalamus) was related to processing speed in patients with clinically isolated syndrome and those with MS.…”

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confidence: 99%

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis

Fujiwara¹,

Kmech²,

Cobzaş³

et al. 2017

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging-based iron-susceptibility measures.

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Validation of quantitative susceptibility mapping with Perls' iron staining for subcortical gray matter

Cited by 143 publications

References 49 publications

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

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

Lithium suppression of tau induces brain iron accumulation and neurodegeneration

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis

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