Iron quantification in Parkinson's disease using an age-based threshold on susceptibility maps: The advantage of local versus entire structure iron content measurements

Sethi, Sajiv; Kisch, Shawn J.; Ghassaban, Kiarash; Rajput, Ali H.; Rajput, Alex; Babyn, Paul; Liu, Saifeng; Szkup, Peter; Haacke, E. Mark

doi:10.1016/j.mri.2018.10.001

Cited by 17 publications

(7 citation statements)

References 44 publications

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“…The age related data generated for each structure including susceptibility, volume, or total iron content for both the global and regional analysis can be used to correct for age dependence of each of these measures for monitoring abnormal global and regional iron deposition. The literature and data for RII is scant as it is a relatively new technique for measuring iron on QSM (Habib et al, 2012;Ghassaban et al, 2019;Sethi et al, 2019). As for the RII analysis findings, the correlations of iron with age are moderate to strong in almost all structures other than the THA, which is consistent with the work of Liu et al (2016).…”

Section: Discussionsupporting

confidence: 64%

Iron Content in Deep Gray Matter as a Function of Age Using Quantitative Susceptibility Mapping: A Multicenter Study

Sethi

Miao

et al. 2021

Front. Neurosci.

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PurposeTo evaluate the effect of resolution on iron content using quantitative susceptibility mapping (QSM); to verify the consistency of QSM across field strengths and manufacturers in evaluating the iron content of deep gray matter (DGM) of the human brain using subjects from multiple sites; and to establish a susceptibility baseline as a function of age for each DGM structure using both a global and regional iron analysis.MethodsData from 623 healthy adults, ranging from 20 to 90 years old, were collected across 3 sites using gradient echo imaging on one 1.5 Tesla and two 3.0 Tesla MR scanners. Eight subcortical gray matter nuclei were semi-automatically segmented using a full-width half maximum threshold-based analysis of the QSM data. Mean susceptibility, volume and total iron content with age correlations were evaluated for each measured structure for both the whole-region and RII (high iron content regions) analysis. For the purpose of studying the effect of resolution on QSM, a digitized model of the brain was applied.ResultsThe mean susceptibilities of the caudate nucleus (CN), globus pallidus (GP) and putamen (PUT) were not significantly affected by changing the slice thickness from 0.5 to 3 mm. But for small structures, the susceptibility was reduced by 10% for 2 mm thick slices. For global analysis, the mean susceptibility correlated positively with age for the CN, PUT, red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). There was a negative correlation with age in the thalamus (THA). The volumes of most nuclei were negatively correlated with age. Apart from the GP, THA, and pulvinar thalamus (PT), all the other structures showed an increasing total iron content despite the reductions in volume with age. For the RII regional high iron content analysis, mean susceptibility in most of the structures was moderately to strongly correlated with age. Similar to the global analysis, apart from the GP, THA, and PT, all structures showed an increasing total iron content.ConclusionA reasonable estimate for age-related iron behavior can be obtained from a large cross site, cross manufacturer set of data when high enough resolutions are used. These estimates can be used for correcting for age related iron changes when studying diseases like Parkinson’s disease, Alzheimer’s disease, and other iron related neurodegenerative diseases.

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Section: Discussionsupporting

confidence: 64%

Iron Content in Deep Gray Matter as a Function of Age Using Quantitative Susceptibility Mapping: A Multicenter Study

Sethi

Miao

et al. 2021

Front. Neurosci.

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“…The global and regional analyses in the SN of PD patients has previously been evaluated in Ghassaban et al (2018) and Sethi et al (2018) in which similar QSM reconstruction techniques were adopted using different scanners and field strengths. The regional analysis being more sensitive to local high iron content changes seen in the SN in this study is in accordance with their findings.…”

Section: Discussionmentioning

confidence: 99%

Regional High Iron in the Substantia Nigra Differentiates Parkinson’s Disease Patients From Healthy Controls

Ghassaban

Sethi

et al. 2019

Front. Aging Neurosci.

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Background: Iron is important in the pathophysiology of Parkinson’s disease (PD) specifically related to degeneration of the substantia nigra (SN). Magnetic resonance imaging (MRI) can be used to measure brain iron in the entire structure but this approach is insensitive to regional changes in iron content. Objective: The goal of this work was to use quantitative susceptibility mapping (QSM) and R2 ∗ to quantify both global and regional brain iron in PD patients and healthy controls (HC) to ascertain if regional changes correlate with clinical conditions and can be used to discriminate patients from controls. Methods: Susceptibility and R2 ∗ maps of 25 PD and 24 HC subjects were reconstructed from data collected on a 3T GE scanner. For the susceptibility maps, three-dimensional regions-of-interest (ROIs) were traced on eight deep gray matter (DGM) structures and an age-based threshold was applied to define regions of high iron content. The same multi-slice ROIs were duplicated on the R2 ∗ maps as well. Mean susceptibility values of both global and regional high iron (RII) content along with global R2 ∗ values were measured and compared not only between the two cohorts, but also to susceptibility and R2 ∗ baselines as a function of age. Finally, clinical features were compared for those PD patients lying above and below the upper 95% regional susceptibility-age prediction intervals. Results: The SN was the only structure showing significantly higher susceptibility in PD patients compared to controls globally ( p < 0.01) and regionally ( p < 0.001). The R2 ∗ values were also higher only in the SN of PD patients compared to the healthy cohort ( p < 0.05). Furthermore, those patients with abnormal susceptibility values lying above the upper 95% prediction intervals had significantly higher united Parkinson’s diagnostic rating scores. R2 ∗ values had larger errors and showed larger dispersion as a function of age than QSM data for global analysis while the dispersion was significantly less for QSM using the RII iron content. Conclusion: Abnormal iron deposition in the SN, especially in RII areas, could serve as a biomarker to distinguish PD patients from HC and to assess disease severity.

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“…In relation to the development of neurodegenerative diseases, transition metals are involved in the formation of cytotoxic protein aggregates from misfolded proteins as shown for PD, AD, HD, and ALS 67–72 . Moreover, transition metal accumulation and metal metabolism dysfunction have been shown for postmortem brain tissue of PD and AD patients 73–75 .…”

Section: Novel Approaches For Neurodegenerative Disease Treatmentmentioning

confidence: 99%

Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: Finding ways for prevention

Angelova

Esteras

Abramov

2020

Medicinal Research Reviews

176

119

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The world's population aging progression renders age‐related neurodegenerative diseases to be one of the biggest unsolved problems of modern society. Despite the progress in studying the development of pathology, finding ways for modifying neurodegenerative disorders remains a high priority. One common feature of neurodegenerative diseases is mitochondrial dysfunction and overproduction of reactive oxygen species, resulting in oxidative stress. Although lipid peroxidation is one of the markers for oxidative stress, it also plays an important role in cell physiology, including activation of phospholipases and stimulation of signaling cascades. Excessive lipid peroxidation is a hallmark for most neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and many other neurological conditions. The products of lipid peroxidation have been shown to be the trigger for necrotic, apoptotic, and more specifically for oxidative stress‐related, that is, ferroptosis and neuronal cell death. Here we discuss the involvement of lipid peroxidation in the mechanism of neuronal loss and some novel therapeutic directions to oppose it.

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Iron quantification in Parkinson's disease using an age-based threshold on susceptibility maps: The advantage of local versus entire structure iron content measurements

Cited by 17 publications

References 44 publications

Iron Content in Deep Gray Matter as a Function of Age Using Quantitative Susceptibility Mapping: A Multicenter Study

Iron Content in Deep Gray Matter as a Function of Age Using Quantitative Susceptibility Mapping: A Multicenter Study

Regional High Iron in the Substantia Nigra Differentiates Parkinson’s Disease Patients From Healthy Controls

Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: Finding ways for prevention

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