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Diagnosing early stage Parkinson's disease (PD) is still a clinical challenge. Previous studies using iron, neuromelanin (NM) or the Nigrosome-1 (N1) sign in the substantia nigra (SN) by themselves have been unable to provide sufficiently high diagnostic performance for these methods to be adopted clinically. Our goal in this study was to extract the NM complex volume, iron content and volume representing the entire SN, and the N1 sign as potential complementary imaging biomarkers using a single 3D magnetization transfer contrast (MTC) gradient echo sequence and to evaluate their diagnostic performance and clinical correlations in early stage PD. A total of 40 early stage idiopathic PD subjects and 40 age- and sex-matched healthy controls (HCs) were imaged at 3T. NM boundaries (representing the SN pars compacta (SNpc) and parabrachial pigmented nucleus) and iron boundaries representing the total SN (SNpc and SN pars reticulata) were determined semi-automatically using a dynamic programming (DP) boundary detection algorithm. Receiver operating characteristic analyses were performed to evaluate the utility of these imaging biomarkers in diagnosing early stage PD. A correlation analysis was used to study the relationship between these imaging measures and the clinical scales. We also introduced the concept of NM and total iron overlap volumes to demonstrate the loss of NM relative to the iron containing SN. Furthermore, all 80 cases were evaluated for the N1 sign independently. The NM and SN volumes were lower while the iron content was higher in the SN for PD subjects compared to HCs. Interestingly, the PD subjects with bilateral loss of the N1 sign had the highest iron content. The area under the curve (AUC) values for the average of both hemispheres for single measures were: .960 for NM complex volume; .788 for total SN volume; .740 for SN iron content and .891 for the N1 sign. Combining NM complex volume with each of the following measures through binary logistic regression led to AUC values for the averaged right and left sides of: .976 for total iron content; .969 for total SN volume, .965 for overlap volume and .983 for the N1 sign. We found a negative correlation between SN volume and UPDRS-III (R 2  = .22, p = .002). While the N1 sign performed well, it does not contain any information about iron content or NM quantitatively, therefore, marrying this sign with the NM and iron measures provides a better physiological explanation of what is happening when the N1 sign disappears in PD subjects. In summary, the combination of NM complex volume, SN volume, iron content and the N1 sign as derived from a single MTC sequence provides complementary information for understanding and diagnosing early stage PD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Aceruloplasminemia (ACP) is a rare autosomal recessive disorder characterized by intracranial and visceral iron overload. With R2*-based imaging or quantitative susceptibility mapping (QSM), it is feasible to measure iron in the brain quantitatively, although to date this has not yet been done for patients with ACP. The aim of this study was to provide quantitative iron measurements for each affected brain region in an ACP patient with the potential to do so in all future ACP patients. This may shed light on the link between brain iron metabolism and the territories affected by ceruloplasmin function., Methods: We imaged a patient with ACP using a 3T magnetic resonance imaging scanner with a fifteen-channel head coil. We manually demarcated gray matter and white matter on the Strategically Acquired Gradient Echo (STAGE) images, and calculated values for susceptibility and R2* in these regions. Correlation analysis was performed between the R2* values and the susceptibility values., Results: Besides the usual territories affected in ACP, we also discovered that the mammillary bodies and the lateral habenulae had significant increases in iron, and the hippocampus was severely affected both in terms of iron content and abnormal tissue signal. We also noted that the iron in the cortical gray matter appeared to be deposited in the inner layers. Moreover, several pathways between the superior colliculus and the pulvinar thalamus, between the caudate and putamen anteriorly and between the caudate and pulvinar thalamus posteriorly were also evident. Finally, R2* correlated strongly with the QSM data (R 2  = 0.67, t = 6.78, p < 0.001)., Conclusion: QSM and R2* have proven to be sensitive and quantitative means by which to measure iron content in the brain. Our findings included several newly noted affected brain regions of iron overload and provided some new aspects of iron metabolism in ACP that may be further applicable to other pathologic conditions. Furthermore, our study may pave the way for assessing efficacy of iron chelation therapy in these patients and for other common iron related neurodegenerative disorders., Competing Interests: Disclosure This study was sponsored by the Department of Neurology & Institute of Neurology Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine. Dr. Liche Zhou reports no disclosures. Dr. Yan Chen reports no disclosures. Dr. Yan Li reports no disclosures. Mrs. Sara Gharabaghi reports no disclosures. Dr. Yongsheng Chen reports no disclosures. Mr. Sean K. Sethi reports no disclosures. Dr. Yiwen Wu reports no disclosures. Dr. E. M. Haacke reports no disclosures., (Copyright © 2020. Published by Elsevier Inc.)

Background: Reduced flow into the brain or decreased jugular venous outflow from the brain may serve as a potential biomarker for Parkinson's disease (PD). Our goal was to compare the presence of vascular abnormalities, flow, and increases in midbrain iron content (a hallmark of the disease) in patients with PD., Methods: A total of 85 PD patients and 85 healthy controls (HCs) were imaged at 3T. We assessed vascular abnormalities using magnetic resonance (MR) venography, average cerebral blood flow using 2D flow quantification, and substantia nigra iron content using susceptibility mapping., Results: Fifty-two percent (52%) of the PD subjects showed venous structural and functional abnormalities in the two most severe categories, while ony 14% of the HC group showed these abnormalities. Total arterial flow (tA) was significantly lower for the PD group (10.9 ± 1.8 ml/s) compared to the HCs (11.6 ± 2.1 ml/s) (t = 2.28, p = 0.02). Of the PD patients (HCs), 42% (14%) had little flow on the left side. PD patients had higher heart rates and lower perfusion and the lower perfusion correlated with increased iron content in the substantia nigra., Conclusion: Some PD patients showed abnormal left internal jugular veins, lower tA, higher heart rates, and lower perfusion relative to HCs. These indicators could serve as early biomarkers for PD and create new avenues for future studies regarding the etiology of PD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Elevated brain iron has been observed in Idiopathic Parkinson's disease (IPD) within the deep gray matter. Using quantitative susceptibility mapping (QSM) and a thresholded high-iron region, we quantified iron content in the midbrain of patients with Parkinson's disease as a function of age., Methods: We used MRI to scan 24 IPD patients at 3-Tesla. Susceptibility-weighted images were collected with the following parameters, TE: 6 and 20 ms, TR: 30 ms, FA: 15°, and resolution: 0.5 × 0.5 × 2.0 mm 3 . QSM images were reconstructed from the source phase images. Whole-region and thresholded high-iron (RII) region boundaries for the Substantia Nigra (SN) and Red Nucleus (RN) were traced. Iron content was measured via mean susceptibilities and volumes, which were compared between the groups, as well as between right and left side of the structures within groups., Results: Twenty patients with mild to moderate IPD were used in this study. For the SN, mean RII and whole-region iron and volumes were higher in the IPD group compared to HC, as well as mean RII for the RN, while no differences were seen between the groups when considering whole-region mean susceptibility bilaterally for the RN., Conclusion: Using a two-region of interest analysis on QSM, we showed that abnormal iron occurs in IPD patients in the SN and with greater volumes compared to HC. This method may have application as a biomarker for disease diagnosis and early intervention., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Venous vascular contributing factors to multiple sclerosis (MS) have been known for some time. Only recently has the scope of their potential role become more apparent with the theory of chronic cerebrospinal venous insufficiency (CCSVI). As research expands to further explore the role of vascular pathology in the MS population, it is expedient to review the evidence from an imaging perspective. In this paper, we review the current state-of-the-art methods using magnetic resonance imaging (MRI) as applied to imaging MS patients and CCSVI. This includes evaluating imaging signatures of vascular structure and flow as well as brain iron content. Upon review of the literature, we find that extracranial venous anomalies including stenosis, venous malformations, and collateralization of flow in the major veins of the neck have been observed to be prevalent in the MS population. Abnormal flow has been reported in MS patients both in major vessels using phase-contrast flow quantification and in the brain using perfusion-weighted imaging. We discuss the role of quantitative flow imaging and its potential in assessing possible biomarkers for abnormal flow. Finally, it has been suggested that the presence of high iron content may indirectly indicate progression of existing vascular pathology. To that end, we review the use of susceptibility-weighted imaging in monitoring iron in the thalamus, basal ganglia, and MS lesions.

Background and purpose: Hereditary haemochromatosis (HH) is the most common inherited disorder of systemic iron excess in Northern Europeans. Emerging evidence indicates that brain iron overload occurs in HH. Despite this observation, there is a paucity of literature regarding central neurological manifestations, in particular movement disorders, in HH. The current study documents deep gray matter (DGM) nuclei iron deposition, movement disorders, and clinicoradiological correlations in HH without liver failure. Methods: This is a cross‐sectional study. Consecutive subjects with HFE‐haemochromatosis without liver disease were recruited from an outpatient gastroenterology clinic. Age‐ and sex‐matched healthy controls (HCs) were enrolled. Iron content in individual DGM nuclei was measured as mean susceptibility on magnetic resonance imaging using quantitative susceptibility mapping‐based regions of interest analysis. Occurrence and phenotype of movement disorders were documented and correlated with patterns of DGM nuclei iron deposition in subjects with HH. Results: Fifty‐two subjects with HH and 47 HCs were recruited. High magnetic susceptibility was demonstrated in several DGM nuclei in all HH subjects compared to HCs. Thirty‐five subjects with HH had movement disorders. Magnetic susceptibility in specific DGM nuclei correlated with individual movement disorder phenotypes. Serum ferritin, phlebotomy frequency, and duration were poor predictors of brain iron deposition. Conclusions: Abnormal brain iron deposition can be demonstrated on imaging in all subjects with HH without liver failure. A significant proportion of these subjects manifest movement disorders. Peripheral iron measurements appear not to correlate with brain iron deposition. Therefore, routine neurological examination and quantitative brain iron imaging are recommended in all subjects with HH. [ABSTRACT FROM AUTHOR]

Purpose: To 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. Methods: Data 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. Results: The 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. Conclusion: A 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]