Quantitative Susceptibility Mapping Values Research Articles

Phase-sensitive deep reconstruction method for rapid multiparametric MR fingerprinting and quantitative susceptibility mapping in the brain

IntroductionThis study explores the potential of Magnetic Resonance Fingerprinting (MRF) with a novel Phase-Sensitivity Deep Reconstruction Network (PS-DRONE) for simultaneous quantification of T1, T2, Proton Density, B1+, phase and quantitative susceptibility mapping (QSM). MethodsData were acquired at 3 T in vitro and in vivo using an optimized EPI-based MRF sequence. Phantom experiments were conducted using a standardized phantom for T1 and T2 maps and a custom-made agar-based gadolinium phantom for B1 and QSM maps. In vivo experiments included five healthy volunteers and one patient diagnosed with brain metastasis. PSDRONE maps were compared to reference maps obtained through standard imaging sequences. ResultsTotal scan time was 2 min for 32 slices and a resolution of [1 mm, 1 mm, 4.5 mm]. The reconstruction of T1, T2, Proton Density, B1+ and phase maps were reconstructed within 1 s. In the phantoms, PS-DRONE analysis presented accurate and strongly correlated T1 and T2 maps (r = 0.99) compared to the reference maps. B1 maps from PS-DRONE showed slightly higher values, though still correlated (r = 0.6) with the reference. QSM values showed a small bias but were strongly correlated (r = 0.99) with reference data. In the in vivo analysis, PS-DRONE-derived T1 and T2 values for gray and white matter matched reference values in healthy volunteers. PS-DRONE B1 and QSM maps showed strong correlations with reference values. ConclusionThe PS-DRONE network enables concurrent acquisition of T1, T2, PD, B1+, phase and QSM maps, within 2 min of acquisition time and 1 s of reconstruction time.

Quantitative susceptibility mapping for iron monitoring of multiple subcortical nuclei in type 2 diabetes mellitus: a systematic review and meta-analysis.

Iron accumulation in the brain has been linked to diabetes, but its role in subcortical structures involved in motor and cognitive functions remains unclear. Quantitative susceptibility mapping (QSM) allows the non-invasive quantification of iron deposition in the brain. This systematic review and meta-analysis examined magnetic susceptibility measured by QSM in the subcortical nuclei of patients with type 2 diabetes mellitus (T2DM) compared with controls. PubMed, Scopus, and Web of Science databases were systematically searched [following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines] for studies reporting QSM values in the deep gray matter (DGM) regions of patients with T2DM and controls. Pooled standardized mean differences (SMDs) for susceptibility were calculated using fixed-effects meta-analysis models, and heterogeneity was assessed using I2. Sensitivity analyses were conducted, and publication bias was evaluated using Begg's and Egger's tests. Six studies including 192 patients with T2DM and 245 controls were included. This study found a significant increase in iron deposition in the subcortical nuclei of patients with T2DM compared to the control group. The study found moderate increases in the putamen (SMD = 0.53, 95% CI 0.33 to 0.72, p = 0.00) and dentate nucleus (SMD = 0.56, 95% CI 0.27 to 0.85, p = 0.00) but weak associations between increased iron levels in the caudate nucleus (SMD = 0.32, 95% CI 0.13 to 0.52, p = 0.00) and red nucleus (SMD = 0.22, 95% CI 0.00 0.44, p = 0.05). No statistical significance was found for iron deposition alterations in the globus pallidus (SMD = 0.19; 95% CI -0.01 to 0.38; p = 0.06) and substantia nigra (SMD = 0.12, 95% CI -0.10, 0.34, p = 0.29). Sensitivity analysis showed that the findings remained unaffected by individual studies, and consistent increases were observed in multiple subcortical areas. QSM revealed an increase in iron in the DGM/subcortical nuclei in T2DM patients versus controls, particularly in the motor and cognitive nuclei, including the putamen, dentate nucleus, caudate nucleus, and red nucleus. Thus, QSM may serve as a potential biomarker for iron accumulation in T2DM patients. However, further research is needed to validate these findings.

Associations of quantitative susceptibility mapping with cortical atrophy and brain connectome in Alzheimer's disease: A multi-parametric study

Aberrant susceptibility due to iron level abnormality and brain network disconnections are observed in Alzheimer's disease (AD), with disrupted iron homeostasis hypothesized to be linked to AD pathology and neuronal loss. However, whether associations exist between abnormal quantitative susceptibility mapping (QSM), brain atrophy, and altered brain connectome in AD remains unclear. Based on multi-parametric brain imaging data from 30 AD patients and 26 healthy controls enrolled at the China-Japan Friendship Hospital, we investigated the abnormality of the QSM signal and volumetric measure across 246 brain regions in AD patients. The structural and functional connectomes were constructed based on diffusion MRI tractography and functional connectivity, respectively. The network topology was quantified using graph theory analyses. We identified seven brain regions with both reduced cortical thickness and abnormal QSM (p < 0.05) in AD, including the right superior frontal gyrus, left superior temporal gyrus, right fusiform gyrus, left superior parietal lobule, right superior parietal lobule, left inferior parietal lobule, and left precuneus. Correlations between cortical thickness and network topology computed across patients in the AD group resulted in statistically significant correlations in five of these regions, with higher correlations in functional compared to structural topology. We computed the correlation between network topological metrics, QSM value and cortical thickness across regions at both individual and group-averaged levels, resulting in a measure we call spatial correlations. We found a decrease in the spatial correlation of QSM and the global efficiency of the structural network in AD patients at the individual level. These findings may provide insights into the complex relationships among QSM, brain atrophy, and brain connectome in AD.

A rapid multi-parametric quantitative MR imaging method to assess Parkinson’s disease: a feasibility study

BackgroundMULTIPLEX is a single-scan three-dimensional multi-parametric MRI technique that provides 1 mm isotropic T1-, T2*-, proton density- and susceptibility-weighted images and the corresponding quantitative maps. This study aimed to investigate its feasibility of clinical application in Parkinson’s disease (PD).Methods27 PD patients and 23 healthy control (HC) were recruited and underwent a MULTIPLEX scanning. All image reconstruction and processing were automatically performed with in-house C + + programs on the Automatic Differentiation using Expression Template platform. According to the HybraPD atlas consisting of 12 human brain subcortical nuclei, the region-of-interest (ROI) based analysis was conducted to extract quantitative parameters, then identify PD-related abnormalities from the T1, T2* and proton density maps and quantitative susceptibility mapping (QSM), by comparing patients and HCs.ResultsThe ROI-based analysis revealed significantly decreased mean T1 values in substantia nigra pars compacta and habenular nuclei, mean T2* value in subthalamic nucleus and increased mean QSM value in subthalamic nucleus in PD patients, compared to HCs (all p values < 0.05 after FDR correction). The receiver operating characteristic analysis showed all these four quantitative parameters significantly contributed to PD diagnosis (all p values < 0.01 after FDR correction). Furthermore, the two quantitative parameters in subthalamic nucleus showed hemicerebral differences in regard to the clinically dominant side among PD patients.ConclusionsMULTIPLEX might be feasible for clinical application to assist in PD diagnosis and provide possible pathological information of PD patients’ subcortical nucleus and dopaminergic midbrain regions.

The Analysis of relation to brain iron deposition of Parkinson’s Disease using Quantitative Susceptibility Mapping

Objectives: This study aimed to investigate the levels of brain iron deposition in Parkinson's disease (PD) patients using Quantitative Susceptibility Mapping (QSM) and to determine whether distinctions compared to the general population exist. Furthermore, we examined potential variations in iron deposition among different PD subtypes.Methods: Structural brain imaging was conducted on 75 participants at Gangdong Kyung Hee University Hospital between August 2017 and May 2020. PD patients were categorized into Tremor Dominant (TD) and Postural Instability and Gait Difficulty (PIGD) subtypes. Voxel-based morphometry and QSM were employed to compare voxel-wise magnetic susceptibility across the entire brain between Normal Controls (NC) and PD groups. Subsequently, QSM values were compared between TD and PIGD groups.Results: QSM values were compared among 46 PD patients and 23 normal controls, as well as between TD (n=22) and PIGD (n=24) groups. Voxel-based QSM analysis revealed no significant differences between groups. Similarly, ROI-based QSM analysis showed no significant distinctions.Conclusions: No significant variations were observed between the PD patient group, NC group, or PD subtypes. This study systematically compared QSM values across a broad range of brain regions potentially linked to PD pathology. Additionally, the subdivision of the PD group into TD and PIGD subtypes for QSM-based iron deposition analysis represents a meaningful and innovative approach.

Increased plasma lipocalin‐2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease

AbstractLipocalin‐2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme‐linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel‐based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

Increased iron in the substantia nigra pars compacta identifies patients with early Parkinson’s disease: A 3T and 7T MRI study

Degeneration in the substantia nigra (SN) pars compacta (SNc) underlies motor symptoms in Parkinson’s disease (PD). Currently, there are no neuroimaging biomarkers that are sufficiently sensitive, specific, reproducible, and accessible for routine diagnosis or staging of PD. Although iron is essential for cellular processes, it also mediates neurodegeneration. MRI can localize and quantify brain iron using magnetic susceptibility, which could potentially provide biomarkers of PD.We measured iron in the SNc, SN pars reticulata (SNr), total SN, and ventral tegmental area (VTA), using quantitative susceptibility mapping (QSM) and R2* relaxometry, in PD patients and age-matched healthy controls (HCs). PD patients, diagnosed within five years of participation and HCs were scanned at 3T (22 PD and 23 HCs) and 7T (17 PD and 21 HCs) MRI. Midbrain nuclei were segmented using a probabilistic subcortical atlas. QSM and R2* values were measured in midbrain subregions. For each measure, groups were contrasted, with Age and Sex as covariates, and receiver operating characteristic (ROC) curve analyses were performed with repeated k-fold cross-validation to test the potential of our measures to classify PD patients and HCs. Statistical differences of area under the curves (AUCs) were compared using the Hanley-MacNeil method (QSM versus R2*; 3T versus 7T MRI).PD patients had higher QSM values in the SNc at both 3T (padj = 0.001) and 7T (padj = 0.01), but not in SNr, total SN, or VTA, at either field strength. No significant group differences were revealed using R2* in any midbrain region at 3T, though increased R2* values in SNc at 7T MRI were marginally significant in PDs compared to HCs (padj = 0.052). ROC curve analyses showed that SNc iron measured with QSM, distinguished early PD patients from HCs at the single-subject level with good diagnostic accuracy, using 3T (mean AUC = 0.83, 95 % CI = 0.82–0.84) and 7T (mean AUC = 0.80, 95 % CI = 0.79–0.81) MRI. Mean AUCs reported here are from averages of tests in the hold-out fold of cross-validated samples. The Hanley-MacNeil method demonstrated that QSM outperforms R2* in discriminating PD patients from HCs at 3T, but not 7T. There were no significant differences between 3T and 7T in diagnostic accuracy of QSM values in SNc.This study highlights the importance of segmenting midbrain subregions, performed here using a standardized atlas, and demonstrates high accuracy of SNc iron measured with QSM at 3T MRI in identifying early PD patients. QSM measures of SNc show potential for inclusion in neuroimaging diagnostic biomarkers of early PD. An MRI diagnostic biomarker of PD would represent a significant clinical advance.

Increased brain iron in patients with thyroid-associated ophthalmopathy: a whole-brain analysis.

To investigate the whole-brain iron deposition alternations in patients with thyroid-associated ophthalmopathy (TAO) using quantitative susceptibility mapping (QSM). Forty-eight patients with TAO and 33 healthy controls (HCs) were enrolled. All participants underwent brain magnetic resonance imaging scans and clinical scale assessments. QSM values were calculated and compared between TAO and HCs groups using a voxel-based analysis. A support vector machine (SVM) analysis was performed to evaluate the performance of QSM values in differentiating patients with TAO from HCs. Compared with HCs, patients with TAO showed significantly increased QSM values in the bilateral caudate nucleus (CN), left thalamus (TH), left cuneus, left precuneus, right insula and right middle frontal gyrus. In TAO group, QSM values in left TH were positively correlated with Hamilton Depression Rating Scale (HDRS) scores (r = 0.414, p = 0.005). The QSM values in right CN were negatively correlated with Montreal Cognitive Assessment (MoCA) scores (r = -0.342, p = 0.021). Besides that, a nearly negative correlation was found between QSM values in left CN and MoCA scores (r = -0.286, p = 0.057). The SVM model showed a good performance in distinguishing patients with TAO from the HCs (area under the curve, 0.958; average accuracy, 90.1%). Patients with TAO had significantly increased iron deposition in brain regions corresponding to known visual, emotional and cognitive deficits. QSM values could serve as potential neuroimaging markers of TAO.

Detection of brown adipose tissue in rats with acute cold stimulation using quantitative susceptibility mapping.

To the Editor: Adipose tissue occurs in at least two different entities in mammals and humans: brown adipose tissue (BAT) and white adipose tissue (WAT). BAT is characterized by a unique uncoupling protein 1 (UCP1) in the mitochondria that enables the uncoupling of the respiratory chain from adenosine triphosphate synthesis. Thus, energy is dissipated as heat to reduce fat accumulation. BAT is also considered a highly heterogeneous tissue with abundant oxygen, blood supply, and iron-rich mitochondria.[1,2] Activation of BAT via exposure to a cold environment is considered to be a means of reducing triglycerides to fight obesity.[3] The alterations in cells and tissues of activated BAT include increased iron content and UCP1 expression in mitochondrial, blood perfusion, and lipid utilization.[4] Therefore, accurate identification and quantitative analysis of inactive and activated BAT are of great significance for the treatment of metabolic diseases that target BAT, such as obesity. Owing to the iron-rich mitochondria in BAT,[5] we tested our hypothesis that quantitative susceptibility mapping (QSM) could be a promising method for monitoring BAT activation in the interscapular region and showing significant differences in magnetic susceptibility in WAT from BAT. In the present study, we aimed to investigate the feasibility of QSM for differentiating BAT from WAT and detecting activated BAT in the interscapular region of rats, with comparisons to fat fraction (FF) and R2*. All animal experiments were conducted in accordance with the Southern Medical University Animal Care and Use Committee guidelines. Sprague–Dawley male rats (5 weeks old, 150–200 g) were acclimated to our animal facility maintained at 22°C with 12 h light and dark cycles for one week. The rats were subsequently divided into three groups: control group (Control), cold-stimulated group for 12 h (Cold 12 h), and cold-stimulated group for 24 h (Cold 24 h). The rats in the control group were exposed to room temperature. Those in the Cold 12 h and Cold 24 h groups were exposed to cold at 4°C for 12 h and 24 h, respectively. After the cold stimulation, a three-dimensional multi-echo gradient-echo sequence was performed on a 7T MR system (Bruker, Bremen, Germany). The animals were placed in the coil headfirst in the supine position for the interscapular region scanning. All animals were sacrificed immediately after magnetic resonance imaging (MRI) experiments. BAT and WAT depots were excised from the scanning region for histological analysis and the special protein expression quantification. The experimental design is shown in Supplementary Figure 1 (https://links.lww.com/CM9/B184). The MRI scan parameters and data analysis are shown in the Supplementary Materials (https://links.lww.com/CM9/B184). MRI maps highlight the unique wings shape of BAT and a triangular sheet of WAT [Figure 1A]. Hematoxylin-eosin staining showed the number of lipid vacuoles decreased in the activated BAT with cold stimulation for 12 and 24 h. In addition, high-density cells with plenty of cytoplasm were observed in BAT after cold stimulation. However, no obvious change in lipid vacuoles was observed in WAT after cold stimulation [Figure 1B]. By contrast, the small vessels in WAT were dilatated and proliferated after cold stimulation. Immunohistochemical staining showed a large amount of positive expression of UCP1 in BAT, which indicates that BAT was activated effectively, but without positive expression in WAT [Figure 1B]. Western blotting analysis revealed that UCP1 of BAT expressed continuously in the three groups, and the expressions were more statistically significantly upregulated in both cold 12 h and 24 h than those in the control group [Figure 1D].Figure 1: (A) Axial slices of the reconstructed FF, QSM, and R2* maps of interscapular BAT and WAT in the different groups. FF, QSM, and R2* maps of a normal male rat without cold exposure (top), cold stimulated male rats with 12 h (middle) and 24 h (bottom). White long and short arrows indicated the contour of BAT and WAT, respectively. (B) Representative histology of H&E and immunohistochemistry of UCP1 in BAT (left) and WAT (right) (original magnification × 100). (C) Column diagram analysis of FF, QSM, and R2* between WAT and BAT in three groups (Control, Cold 12 h, and Cold 24 h). Column diagram analysis of FF, QSM, and R2* of BAT or WAT in different groups. ∗ P < 0.05; ∗∗ P < 0.01; ∗∗∗ P < 0.001. (D) Western blotting showed that UCP1 expressions at 4°C exposed in interscapular BAT were statistically significantly higher than those of the control group. Interscapular BAT UCP1 expression increased in sequence in the groups of Control, Cold 12 h, and Cold 24 h. BAT: Brown adipose tissue; FF: Fat fraction; H&E: Hematoxylin-eosin; QSM: Quantitative susceptibility mapping; UCP1: Unique uncoupling protein 1; WAT: White adipose tissue.Our results showed significant differences in QSM, FF, and R2* between BAT and WAT whether in room temperature (inactive) or cold exposure (activated) (P < 0.05). In line with previous studies,[6,7] FF decreased significantly in inactive or activated BAT compared with WAT. Our study additionally found that BAT had a statistically significantly lower QSM in contrast to WAT. Therefore, the QSM value can effectively identify BAT from WAT under room temperature or cold exposure. By contrast, QSM, FF, and R2* of cold-stimulation activated BAT (Cold 12 h or 24 h groups) were all significantly lower than inactive BAT (control group), and QSM was further significantly reduced after cold stimulation for 12 h or 24 h [Figure 1C]. The change in QSM value could be attributable to the comprehensive influence of iron content in mitochondria and fat content of BAT after acute cold stimulation. The increasing iron content and the decreasing fat content have opposite effects on the change of susceptibility because they are all paramagnetic substances. If the increasing iron content is not enough to compensate for the decreasing fat content in tissue, the total susceptibility will decrease. This final analysis indicated that the change of fat content in BAT after cold stimulation could play a dominant role in total magnetic susceptibility rather than the iron content in mitochondria. Histologically, the number of adipose vacuoles was confirmed to decrease significantly in BAT under cold exposure. As a consequence, the QSM value can distinguish between activated and inactive BAT. We also found that the cold stimulation groups, regardless of 12 h or 24 h, induced a significantly decreased QSM in WAT compared with the control group (0.19 ± 0.12 ppm vs. 0.55 ± 0.09 ppm, 0.21 ± 0.13 ppm vs. 0.55 ± 0.09 ppm), while no significant changes of FF and R2* were observed. We speculated that the change of QSM in WAT might be related to the dilatation or proliferation of small vessels in WAT after cold stimulation. Further pathologic or histologic validation may prove QSM to be useful in the detection of tiny change of cell structure while FF and R2* do not reach the detection in WAT. A best linear relationship between FF and UCP1 expression was found (r = −0.7930), followed by QSM, suggesting that FF may correlate well with the activated state of BAT with consistent to the previous study [Supplementary Figure 2, https://links.lww.com/CM9/B184].[8] To our knowledge, magnetic susceptibility is not only affected by the changes of iron in mitochondria but also the content of fat in BAT. Although FF has a higher correlation with UCP1 expression than QSM and R2*, the limitation is the observed change of FF only based on fat utilization rather than additional BAT microstructure. Using FF as an absolute or single indicator to detect activated BAT from inactive BAT may not be accurate. The values of QSM and FF together may be a better choice to identify activated BAT from inactive BAT. In conclusion, our study found that the inactive or activated BAT has a lower QSM and FF and a higher R2* compared with WAT. Additionally, the activated BAT induced by acute cold stimulation has lower QSM, FF, and R2* than inactive BAT. All the MRI biomarkers mentioned above are confirmed with a good linear correlation with UCP1 expression of BAT. To our knowledge, QSM is highly sensitive for iron and fat content detection and susceptibility contrast directly reflects subtle variations in tissue composition consistent with histological changes. QSM provides more details about the identification of substructures of BAT and WAT, compared with the other MRI biomarkers such as FF and R2*. QSM could be a new quantitative biomarker for identifying and detecting BAT. Funding This study was supported by a grant from the National Natural Science Foundation of China (No. 81801653). Conflicts of interest None.

Free water and iron content in the substantia nigra at different stages of Parkinson's disease

PurposeAbnormalities in free water (FW) and susceptibility values exist in the substantia nigra (SN) of patients with Parkinson’s disease (PD), but their role in characterizing the disease processes remains uncertain. This study investigated these values at various SN locations and stages of PD, and their relationship with clinical symptoms. MethodFW and quantitative susceptibility mapping (QSM) values were evaluated in the anterior and posterior SN, along with swallow-tail-sign (STS) ratings, in patients with PD (early-stage: n = 39; middle-to-advanced-stage: n = 97) and healthy controls (n = 82). The correlation between these indices and motor and non-motor symptoms, and their capability to distinguish PD from healthy controls, were also examined. ResultsIncreased FW in the anterior and posterior SN and increased QSM values in the posterior SN were observed in both early-stage and middle-to-advanced-stage PD patients (p < 0.05). However, there was no significant difference in FW, QSM values, or STS ratings among patients at different stages. FW and QSM values correlated with motor symptoms in middle-to-advanced-stage patients (p < 0.05), while STS ratings were associated with non-motor symptoms (p < 0.05). Additionally, combining FW and QSM values in the posterior SN with STS ratings in logistic regression showed better performance in distinguishing PD (area under curve = 0.931) compared to using STS ratings alone (area under curve = 0.880). ConclusionsFindings suggest elevated FW and iron content in PD at different stages, with dissociation in SN location between the two indices. Elevated signals are related to the motor symptom severity in middle-to-advanced-stage patients, and may have the potential for PD diagnosis and symptom assessment.

Epileptogenic Tubers Are Associated with Increased Kurtosis of Susceptibility Values: A Combined Quantitative Susceptibility Mapping and Stereoelectroencephalography Pilot Study.

Prior studies have found an association between calcification and the epileptogenicity of tubers in tuberous sclerosis complex. Quantitative susceptibility mapping is a novel tool sensitive to magnetic susceptibility alterations due to tissue calcification. We assessed the utility of quantitative susceptibility mapping in identifying putative epileptogenic tubers in tuberous sclerosis complex using stereoelectroencephalography data as ground truth. We studied patients with tuberous sclerosis complex undergoing stereoelectroencephalography at a single center who had multiecho gradient-echo sequences available. Quantitative susceptibility mapping and R2* values were extracted for all tubers on the basis of manually drawn 3D ROIs using T1- and T2-FLAIR sequences. Characteristics of quantitative susceptibility mapping and R2* distributions from implanted tubers were compared using binary logistic generalized estimating equation models designed to identify ictal (involved in seizure onset) and interictal (persistent interictal epileptiform activity) tubers. These models were then applied to the unimplanted tubers to identify potential ictal and interictal tubers that were not sampled by stereoelectroencephalography. A total of 146 tubers were identified in 10 patients, 76 of which were sampled using stereoelectroencephalography. Increased kurtosis of the tuber quantitative susceptibility mapping values was associated with epileptogenicity (P = .04 for the ictal group and P = .005 for the interictal group) by the generalized estimating equation model. Both groups had poor sensitivity (35.0% and 44.1%, respectively) but high specificity (94.6% and 78.6%, respectively). Our finding of increased kurtosis of quantitative susceptibility mapping values (heavy-tailed distribution) was highly specific, suggesting that it may be a useful biomarker to identify putative epileptogenic tubers in tuberous sclerosis complex. This finding motivates the investigation of underlying tuber mineralization and other properties driving kurtosis changes in quantitative susceptibility mapping values.

Iron accumulation in the ventral tegmental area in Parkinson's disease.

The ventral tegmental area (VTA) is less affected compared to substantia nigra pars compacta (SNc) in Parkinson's disease (PD). This study aimed to quantitatively evaluate iron content in the VTA across different stages of PD in order to help explain the selective loss of dopamine neurons in PD. Quantitative susceptibility mapping (QSM) data were obtained from 101 PD patients, 35 idiopathic rapid eye movement sleep behavior disorder (RBD) patients, and 62 healthy controls (HCs). The mean QSM values in the VTA and SNc were calculated and compared among the groups. Both RBD and PD patients had increased iron values in the bilateral SNc compared with HCs. RBD and PD patients in the Hoehn-Yahr (H & Y) stage 1 did not show elevated iron values in the VTA, while PD patients with more than 1.5 H & Y staging had increased iron values in bilateral VTA compared to HCs. This study shows that there is no increased iron accumulation in the VTA during the prodromal and early clinical stages of PD, but iron deposition increases significantly as the disease becomes more severe.

Investigation of Brain Iron in Niemann-Pick Type C: A 7T Quantitative Susceptibility Mapping Study.

While brain iron dysregulation has been observed in several neurodegenerative disorders, its association with the progressive neurodegeneration in Niemann-Pick type C is unknown. Systemic iron abnormalities have been reported in patients with Niemann-Pick type C and in animal models of Niemann-Pick type C. In this study, we examined brain iron using quantitative susceptibility mapping MR imaging in individuals with Niemann-Pick type C compared with healthy controls. A cohort of 10 patients with adolescent- and adult-onset Niemann-Pick type C and 14 age- and sex-matched healthy controls underwent 7T brain MR imaging with T1 and quantitative susceptibility mapping acquisitions. A probing whole-brain voxelwise comparison of quantitative susceptibility mapping between groups was conducted. Mean quantitative susceptibility mapping in the ROIs (thalamus, hippocampus, putamen, caudate nucleus, and globus pallidus) was further compared. The correlations between regional volume, quantitative susceptibility mapping values, and clinical features, which included disease severity on the Iturriaga scale, cognitive function, and the Social and Occupational Functioning Assessment Scale, were explored as secondary analyses. We observed lower volume in the thalamus and voxel clusters of higher quantitative susceptibility mapping in the pulvinar nuclei bilaterally in patients with Niemann-Pick type C compared with the control group. In patients with Niemann-Pick type C, higher quantitative susceptibility mapping in the pulvinar nucleus clusters correlated with lower volume of the thalamus on both sides. Moreover, higher quantitative susceptibility mapping in the right pulvinar cluster was associated with greater disease severity. Our findings suggest iron deposition in the pulvinar nucleus in Niemann-Pick type C disease, which is associated with thalamic atrophy and disease severity. This preliminary evidence supports the link between iron and neurodegeneration in Niemann-Pick type C, in line with existing literature on other neurodegenerative disorders.

Change of iron content in brain regions after intravenous iron therapy in restless legs syndrome: quantitative susceptibility mapping study.

The pathomechanism of restless legs syndrome (RLS) is related to brain iron deficiency and iron therapy is effective for RLS; however, the effect of iron therapy on human brain iron state has never been studied with magnetic resonance imaging. This study aimed to investigate the change of brain iron concentrations in patients with RLS after intravenous iron therapy using quantitative susceptibility mapping (QSM). We enrolled 31 RLS patients and 20 healthy controls. All participants underwent initial baseline (t0) assessment using brain magnetic resonance imaging, serum iron status, and sleep questionnaires including international RLS Study Group rating scale (IRLS). RLS patients underwent follow-up tests at 6 and 24 weeks (t1 and t2) after receiving 1000 mg ferric carboxymaltose. Iron content of region-of-interest on QSM images was measured for 13 neural substrates using the fixed-shaped method. RLS symptoms evaluated using IRLS were significantly improved after iron treatment (t0: 29.7 ± 6.5, t1: 19.5 ± 8.5, t2: 21.3 ± 10.1; p < .001). There was no significant difference in susceptibility values between the controls and RLS patients at t0. In the caudate nucleus, putamen, and pulvinar thalamus of RLS patients, the QSM values differed significantly for three timepoints (p = .035, .048, and .032, respectively). The post-hoc analysis revealed that the QSM values increased at t1 in the caudate nucleus (66.8 ± 18.0 vs 76.4 ± 16.6, p = .037) and decreased from t1 to t2 in the putamen (69.4 ± 16.3 vs 62.5 ± 13.6, p = .025). Changes in the QSM values for the pulvinar and caudate nuclei at t1 were positively and negatively correlated with symptomatic improvement, respectively (r = 0.361 and -0.466, respectively). Intravenous iron treatment results in changes in brain iron content which correlate to reductions in RLS severity. This suggests a connection between symptom improvement and the associated specific brain regions constituting the sensorimotor network.

Banks of the Superior Temporal Sulcus in Alzheimer's Disease: A Pilot Quantitative Susceptibility Mapping Study.

Brain iron homeostasis is disrupted in neurodegeneration and areas of iron overload partially overlap with regions of amyloid and tau burden in Alzheimer's disease (AD). Previous studies demonstrated alterations in brain iron accumulation in AD using quantitative susceptibility mapping (QSM). Here, we investigate brain alterations of QSM values in AD and non-AD patients as compared to healthy controls (HC) in the superior temporal sulcus and its banks (BANKSSTS), one of the top AD-affected regions. Thirty-four patients who underwent brain MRI including a multi-echo gradient-echo sequence were subdivided into AD (n = 19) and non-AD (n = 15) groups according to their clinical profile, CSF (Aβ42/40) and/or amyloid-PET status. Ten HC were also included. QSM values were extracted from left and right BANKSSTS and compared among groups. Correlation and binomial regression analyses between QSM values and CSF-AD biomarkers were conducted. QSM in left BANKSSTS was significantly different among groups (p = 0.003, H = 11.40), being higher in AD. QSM values in left BANKSSTS were correlated with Aβ42 (rho -0.55, p = 0.005), Aβ42/40 (rho -0.66, p < 0.001), pTau (rho 0.63, p < 0.001), tTau (rho 0.56, p = 0.005), tTau/Aβ42 (rho 0.68, p < 0.001) and pTau/Aβ42 (rho 0.71, p < 0.001). No correlations between QSM values and amyloid-PET SUVR in the left BANKSSTS were found. QSM values in left BANKSSTS showed good accuracy in discriminating AD (AUC = 0.80, CI95% [0.66-0.93]). Higher QSM values were independent predictors of Aβ42 (B = 0.63, p = 0.032), Aβ42/40 (B = 0.81, p = 0.028), pTau (B = 0.96, p = 0.046), tTau (B = 0.55, p = 0.027), and tTau/Aβ42 (B = 1.13, p = 0.042) positivity. Our preliminary data support the potential role of increased QSM values in the left BANKSSTS as an auxiliary imaging biomarker in AD diagnosis.

Unraveling the heterogeneous pathological substrates of relapse-onset multiple sclerosis: a multiparametric voxel-wise 3T MRI study.

In multiple sclerosis (MS), pathological processes affecting brain gray (GM) and white matter (WM) are heterogeneous. To apply a multimodal MRI approach to investigate the regional distribution of the different pathological processes occurring in the brain WM and GM of relapse-onset MS patients. Fifty-seven MS patients (forty-two relapsing remitting [RR], fifteen secondary progressive [SP]) and forty-seven age- and sex-matched healthy controls (HC) underwent a multimodal 3T MRI acquisition. Between-group voxel-wise differences of brain WM and GM volumes, magnetization transfer ratio (MTR), T1-weighted(w)/T2w ratio, intracellular volume fraction (ICV_f), and quantitative susceptibility mapping (QSM) maps were investigated. Compared to HC, RRMS showed significant WM, deep GM and cortical atrophy, significantly lower MTR and T1w/T2w ratio of periventricular and infratentorial WM, deep GM and several cortical areas, lower ICV_f in supratentorial and cerebellar WM and in some cortical areas, and lower QSM values in bilateral periventricular WM (p < 0.001). Compared to RRMS, SPMS patients showed significant deep GM and widespread cortical atrophy, significantly lower MTR of periventricular WM, deep GM and cerebellum, lower T1w/T2w ratio of fronto-temporal WM regions, lower ICV_f of some fronto-tempo-occipital WM and cortical areas. They also had increased QSM and T1w/T2w ratio in the pallidum, bilaterally (p < 0.001). A periventricular pattern of demyelination and widespread GM and WM neuro-axonal loss are detectable in RRMS and are more severe in SPMS. Higher T1w/T2w ratio and QSM in the pallidum, possibly reflecting iron accumulation and neurodegeneration, may represent a relevant MRI marker to differentiate SPMS from RRMS.

Application of Nobel QSM technique in MRI for diagnosis of Alzheimer's disease: What is the relationship between iron deposits in brain nuclei with age and severity of disorders?

Background. Iron deposits impair neurons and cause cognitive disorders through different pathways. Today, with the help of quantitative susceptibility mapping (QSM), iron accumulations in different brain areas can be evaluated and measured.This research aims to identify the changes of iron deposits in the brain nuclei in different stages of cognitive disorders using the QSM technique and introduces biomarkers for the early diagnosis of these disorders. Methods. The data of thirty-five participants with normal cognitive conditions and forty six patients with cognitive disorders, classified into four different groups based on the severity of the disorder, were downloaded from the ADNI database. After determining the regions (ROIs) with the FSL automatic segmentation tool, the mean QSM values of twelve brain nuclei were determined with the help of Slicer software, and SPSS software was used for statistical analysis. Results. There was an inverse correlation in the left putamen nucleus of LMCI group (P=0.041). Direct correlation between age variable and QSM values of the left putamen nucleus (P=0.000078) and right putamen nucleus (P=0.000017) of the control group were reported. Conclusion. As the severity of disorders increases in the LMCI group, the number of paramagnetic deposits, such as iron, in the left putamen nucleus increases. Therefore, the QSM values of the left putamen nucleus can be used as an indicator of the severity of the disorder in the advanced stages of cognitive disorders. Practical Implications. Iron deposits cause damage to neurons and cause cognitive disorders through various pathways. Today, with the help of the quantitative susceptibility mapping technique, the numeral of iron accumulations in different brain areas can be evaluated and measured. This research aims to identify the changes of iron deposits in the brain nuclei in different stages of cognitive disorders by using the Quantitative susceptibility mapping (QSM) technique to introduce biomarkers for early diagnosis of these disorders.

Distribution pattern of iron deposition in the basal ganglia of different motor subtypes of Parkinson's disease

ObjectiveThe quantitative susceptibility mapping (QSM) technique was used to analyze the distribution pattern of iron deposition in the basal ganglia region of patients with motor subtypes of Parkinson’s disease (PD) and to explore the difference in iron content in the basal ganglia region of PD motor subtypes on the major motor symptomatic side. MethodsThe study included 76 patients with PD and 37 healthy controls (HC). Patients with PD were divided into two groups: postural instability/gait disorder (PIGD)(n = 48), and tremor dominance (TD)(n = 28). We classified patients with PD according to the side of the major motor symptoms as left PIGD (n = 23), left TD (n = 14), right PIGD (n = 25), and right TD (n = 14). All subjects underwent brain magnetic resonance scanning to obtain QSM and susceptibility values in the corresponding regions of interest (ROI). Results(1) Compared with the HC, the bilateral SN in the PD-PIGD and TD group showed greater susceptibility values. The susceptibility values in the left CN, bilateral PUT were also greater in the PD-PIGD group than the HC. (2) Compared with the TD, the left PUT susceptibility values were greater in the PIGD group, especially in patients whose major symptomatic side were on the right limb. (3) Correlation analysis showed that in the PD group, bilateral SN was positively correlated with the unified Parkinson's disease rating scale III part scores of the Movement Disorder Society (MDS-UPDRS III) and the Hoehn-Yahr stage. Bilateral dentate nucleus (DN) susceptibility values were significantly positively correlated with TD scores, and left PUT susceptibility values were positively correlated with PIGD scores. The left SN within the PIGD group was positively correlated with the PIGD score. ConclusionThere were different iron deposition patterns in the basal ganglia between the PD-PIGD and TD groups. There also seems to be a difference in iron deposition in PD motor subtypes on different major motor symptom sides.

394 R2* and QSM Reliability for Measuring Brain Tissue Iron Concentrations

INTRODUCTION: Pathologic levels of iron have been implicated in various neurological disease states, such as Parkinson’s, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Stroke (hemorrhagic &amp; ischemic). Using brain tissue iron concentration as a biomarker for disease progression has great potential for clinical translation; however, measuring iron concentrations non-invasively remains challenging. MRI based R2* and quantitative susceptibility mapping (QSM) values have been shown to correlate with iron levels in previous cadaveric studies. METHODS: Ten normal human subjects (ages 35-73) underwent test and retest MRI scans approximately 10 minutes apart. T1 and gradient-echo images were used to segment 7 regions of the brain bilaterally. The gradient-echo sequences were used to calculate the R2* and QSM for each region of interest. Iron concentrations were calculated from the R2* values based on R2* calibrated with a phantom. RESULTS: R2* values ranged from 19.45 Hz in the hand homunculus to 38.81 Hz in the substantia nigra and were consistent across 8-echo and 6-echo sequences. Mean QSM values ranged from -0.041 in the internal capsule to 0.046 in the globus pallidus. Calculated iron concentrations ranged from 52.1 mg/kg in the centrum semiovale to 104.6 mg/kg in the substantia nigra. Test and retest values showed consistency across brain regions for R2* with weighted coefficient variation percent of 3.9-9.6%. White matter iron concentrations ranged from 52.1-59.5 mg/kg, while deep grey nuclei iron concentrations ranged from 72.5-104.6 mg/kg. CONCLUSIONS: Our study demonstrates the ability of gradient-echo MRI to reliably measure tissue iron levels in non-disease states in healthy human subjects. Further research is needed to validate the ability of specific MRI sequences to be a surrogate biomarker in disease states.

Feasibility and intra-and interobserver reproducibility of quantitative susceptibility mapping with radiomic features for intracranial dissecting intramural hematomas and atherosclerotic calcifications

Quantitative susceptibility mapping (QSM) for 61 patients with dissecting intramural hematomas (n = 36) or atherosclerotic calcifications (n = 25) in intracranial vertebral arteries were collected to assess intra- and interobserver reproducibility in a 3.0-T MR system between January 2015 and December 2017. Two independent observers each segmented regions of interest for lesions twice. The reproducibility was evaluated using intra-class correlation coefficients (ICC) and within-subject coefficients of variation (wCV) for means and concordance correlation coefficients (CCC) and ICC for radiomic features (CCC and ICC > 0.85) were used. Mean QSM values were 0.277 ± 0.092 ppm for dissecting intramural hematomas and − 0.208 ± 0.078 ppm for atherosclerotic calcifications. ICCs and wCVs were 0.885–0.969 and 6.5–13.7% in atherosclerotic calcifications and 0.712–0.865 and 12.4–18.7% in dissecting intramural hematomas, respectively. A total of 9 and 19 reproducible radiomic features were observed in dissecting intramural hematomas and atherosclerotic calcifications, respectively. QSM measurements in dissecting intramural hematomas and atherosclerotic calcifications were feasible and reproducible between intra- and interobserver comparisons, and some reproducible radiomic features were demonstrated.