Quantitative Susceptibility Mapping Research Articles

Renal ischemia-reperfusion injury in rabbits evaluated with quantitative susceptibility mapping: an animal study.

There were no effective noninvasive methods to diagnose renal ischemia-reperfusion injury (IRI), which is a major clinical problem. The objective of this study was to explore the feasibility of the quantitative susceptibility mapping (QSM) technique in evaluating the dynamic changes in the renal IRI process. A total of 36 New Zealand rabbits were randomly assigned to the IRI group (n=30) and the sham group (n=6). All rabbits underwent magnetic resonance imaging (MRI) examination, including T2-weighted imaging and QSM before the operation (pre-IRI) and 1, 12, 24, and 48 h after the operation (IRI-1h, IRI-12h, IRI-24h, and IRI-48h, respectively). Regions of interest were manually delineated in the outer medulla. All specimens were stained with hematoxylin and eosin (HE) and glutathione peroxidase 4 (GPX4). The pathological score of renal injury and the average optical density value of GPX4 were calculated. The repeated measurement analysis of variance (ANOVA) and Spearman correlation analysis were used to compare the differences between the susceptibility values and determine the correlation. In the IRI group, the susceptibility values of the outer medulla at the pre-IRI, IRI-1h, IRI-12h, IRI-24h, and IRI-48h time points were (42.83±7.83)×10-3, (-5.33±6.28)×10-3, (6.50±3.94)×10-3, (12.00±3.74)×10-3, and (22.00±6.81)×10-3 ppm, respectively. The susceptibility values significantly differed among the different time points (P<0.001). The susceptibility values had a negative correlation with the scores of cell edema (ρ=-0.61; P=0.002) and the average optical density value of GPX4 (ρ=-0.70; P<0.001). The susceptibility values had a positive correlation with iron content (ρ=0.79; P<0.001), the scores of cell necrosis (ρ=0.71; P<0.001), interstitial inflammation (ρ=0.60; P=0.002), cast (ρ=0.75; P<0.001), and the total pathological score of renal injury (ρ=0.51; P=0.01). QSM can be used as a noninvasive method to assess the dynamic changes of the outer medulla in the early stage of renal IRI in rabbits.

PREdiction and Diagnosis using Imaging and Clinical biomarkers Trial in Traumatic Brain Injury (PREDICT-TBI) study protocol: an observational, prospective, multicentre cohort study for the prediction of outcome in moderate-to-severe TBI

IntroductionTraumatic brain injury (TBI) is a heterogeneous condition with a broad spectrum of injury severity, pathophysiological processes and variable outcomes. For moderate-to-severe TBI survivors, recovery is often protracted and outcomes...

Multimodal comparisons of QSM and PET in neurodegeneration and aging

Quantitative susceptibility mapping (QSM) has been used to study susceptibility changes that may occur based on tissue composition and mineral deposition. Iron is a primary contributor to changes in magnetic susceptibility and of particular interest in applications of QSM to neurodegeneration and aging. Iron can contribute to neurodegeneration through inflammatory processes and via interaction with aggregation of disease-related proteins. To better understand the local susceptibility changes observed on QSM, its signal has been studied in association with other imaging metrics such as positron emission tomography (PET). The associations of QSM and PET may provide insight into the pathophysiology of disease processes, such as the role of iron in aging and neurodegeneration, and help to determine the diagnostic utility of QSM as an indirect indicator of disease processes typically evaluated with PET. In this review we discuss the proposed mechanisms and summarize prior studies of the associations of QSM and amyloid PET, tau PET, TSPO PET, FDG-PET, 15O-PET, and F-DOPA PET in evaluation of neurologic diseases with a focus on aging and neurodegeneration.

Cortical iron accumulation in MAPT- and C9orf 72-associated frontotemporal lobar degeneration.

Neuroinflammation has been implicated in frontotemporal lobar degeneration (FTLD) pathophysiology, including in genetic forms with microtubule-associated protein tau (MAPT) mutations (FTLD-MAPT) or chromosome 9 open reading frame 72(C9orf72) repeat expansions (FTLD-C9orf72). Iron accumulation as a marker of neuroinflammation has, however, been understudied in genetic FTLD to date. To investigate the occurrence of cortical iron accumulation in FTLD-MAPT and FTLD-C9orf72, iron histopathology was performed on the frontal and temporal cortex of 22 cases (11 FTLD-MAPT and 11 FTLD-C9orf72). We studied patterns of cortical iron accumulation and its colocalization with the corresponding underlying pathologies (tau and TDP-43), brain cells (microglia and astrocytes), and myelination. Further, with ultrahigh field ex vivo MRI on a subset (four FTLD-MAPT and two FTLD-C9orf72), we examined the sensitivity of T2*-weighted MRI for iron in FTLD. Histopathology showed that cortical iron accumulation occurs in both FTLD-MAPT and FTLD-C9orf72 in frontal and temporal cortices, characterized by a diffuse mid-cortical iron-rich band, and by a superficial cortical iron band in some cases. Cortical iron accumulation was associated with the severity of proteinopathy (tau or TDP-43) and neuronal degeneration, in part with clinical severity, and with the presence of activated microglia, reactive astrocytes and myelin loss. Ultra-high field T2*-weighted MRI showed a good correspondence between hypointense changes on MRI and cortical iron observed on histology. We conclude that iron accumulation is a feature of both FTLD-MAPT and FTLD-C9orf72 and is associated with pathological severity. Therefore, in vivo iron imaging using T2*-weighted MRI or quantitative susceptibility mapping may potentially be used as a noninvasive imaging marker to localize pathology in FTLD.

Comparison between Dual-Energy CT and Quantitative Susceptibility Mapping in Assessing Brain Iron Deposition in Parkinson Disease.

Both dual-energy CT and quantitative susceptibility mapping can evaluate iron depositions in the brain. The purpose of this study was to compare these 2 techniques in evaluating brain iron depositions in Parkinson disease. Forty-one patients with Parkinson disease (Parkinson disease group) and 31 age- and sex-matched healthy controls (healthy control group) were included. All participants underwent brain dual-energy CT and quantitative susceptibility mapping. ROIs were set bilaterally in the globus pallidus, substantia nigra, red nucleus, caudate nucleus, and putamen. CT values and magnetic susceptibility values were obtained in each ROI. Differences in CT values and magnetic susceptibility values between the Parkinson disease and healthy control groups were compared, followed by analysis of receiver operating characteristic curves. Correlations between CT values and magnetic susceptibility values were then evaluated. The CT values of the bilateral globus pallidus, substantia nigra, and red nucleus were higher in the Parkinson disease group (P < .05). The magnetic susceptibility values of the bilateral globus pallidus and substantia nigra were higher in the Parkinson disease group (P < .05). The CT value of the right globus pallidus in linear fusion images had the highest diagnostic performance (0.912). Magnetic susceptibility values of the bilateral globus pallidus in the Parkinson disease group were positively correlated with CT values at the level of 80 kV(peak), linear fusion images, and SN150 kV(p) (r = 0.466∼0.617; all, P < .05). Both dual-energy CT and quantitative susceptibility mapping could assess excessive brain iron depositions in Parkinson disease, and we found a positive correlation between CT values and magnetic susceptibility values in the bilateral globus pallidus.

Tilted quantitative susceptibility mapping at oblique MRI (tiltQSM)

ObjectiveIf the phase image matrix was acquired from oblique MRI, it is needed to deal with the oblique effect for quantitative susceptibility mapping (QSM), as addressed in this paper. MethodsWe proposed two methods for QSM reconstruction from slice-tilted MRI phase image (tiltQSM): 1) rotData per anti-tilting phase image rotation back into the B0-upright system, and 2) rotKernel per pro-tilting dipole kernel rotation into the same oblique setting as defined by the tilted phase image. Both matrix methods were implemented in an additional preprocessing subroutine to ensure that the phase image and the dipole kernel were represented in the same coordinate system (either in B0-upright system or in B0-tilted system); thereafter tiltQSM could be completed through a regular QSM procedure. Besides the oblique effect, tiltQSM also suffers from MRI anisotropy. We provided numeric simulations, phantom tests and in vivo brain experiments on tiltQSM with oblique MRI (axial slice tilting at 3T). ResultsThe tiltQSM reconstruction could attain a performance corr > 0.90 (spatial correlation conformance) for small tilting angles <10°. The tiltQSM performance could be further degraded by voxel anisotropy due to image matrix rotation (digital geometry error). ConclusionsTo seek inverse solutions of MRI phase images acquired at oblique MRI (e.g. in axial slice tilting), we proposed tiltQSM to deal with the oblique effect per matrix rotation (either rotData or rotKernel) in a preprocessing subroutine prior to a regular QSM procedure. In practice, it is always recommended to acquire MRI phase images in isotropic matrix at zero obliqueness (or limited to small tilting angles <10°) for maximal (optimal) QSM reconstruction.

Brain iron deposition is positively correlated with cognitive impairment in patients with chronic cerebral hypoperfusion: a MRI susceptibility mapping study

To investigate the relationship of brain iron deposition with cognitive impairment in patients with chronic cerebral hypoperfusion (CHP). Brain iron deposition was detected using quantitative susceptibility mapping (QSM), and cognitive function by neuropsychological tests including the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADLs), and verbal fluency tests in a total of 40 participants, 23 with CHP and 17 age- and sex-matched healthy participants without CHP (controls). The neuropsychological tests revealed that cognitive impairment (p<0.05) and susceptibility values (p<0.05) of the bilateral hippocampus (HP) and substantia nigra (SN) in CHP patients were significantly higher than those of the controls. The susceptibility values of bilateral HP and left putamen correlated closely with the scores of neuropsychological tests in the CHP patients (p<0.05, r2>0.1). The susceptibility values in the left putamen and bilateral HP were significantly higher in CHP patients with mild cognitive impairment (MCI; n=8) than those of CHP patients without MCI (n=15; p<0.05). The present findings indicated that brain iron deposition in specific areas may be responsible for the cognitive impairment in CHP patients, and that QSM is a useful tool to determine brain iron, predicting cognitive impairment in CHP patients.

Data adaptive regularization with reference tissue constraints for liver quantitative susceptibility mapping.

To improve repeatability and reproducibility across acquisition parameters and reduce bias in quantitative susceptibility mapping (QSM) of the liver, through development of an optimized regularized reconstruction algorithm for abdominal QSM. An optimized approach to estimation of magnetic susceptibility distribution is formulated as a constrained reconstruction problem that incorporates estimates of the input data reliability and anatomical priors available from chemical shift-encoded imaging. The proposed data-adaptive method was evaluated with respect to bias, repeatability, and reproducibility in a patient population with a wide range of liver iron concentration (LIC). The proposed method was compared to the previously proposed and validated approach in liver QSM for two multi-echo spoiled gradient-recalled echo protocols with different acquisition parameters at 3T. Linear regression was used for evaluation of QSM methods against a reference FDA-approved -based LIC measure and measurements; repeatability/reproducibility were assessed by Bland-Altman analysis. The data-adaptive method produced susceptibility maps with higher subjective quality due to reduced shading artifacts. For both acquisition protocols, higher linear correlation with both - and -based measurements were observed for the data-adaptive method ( for , for ) than the standard method ( and ). For both protocols, the data-adaptive method enabled better test-retest repeatability (repeatability coefficients 0.19/0.30 ppm for the data-adaptive method, 0.38/0.47 ppm for the standard method) and reproducibility across protocols (reproducibility coefficient 0.28 vs. 0.53ppm) than the standard method. The proposed data-adaptive QSM algorithm may enable quantification of LIC with improved repeatability/reproducibility across different acquisition parameters as 3T.

Implications of quantitative susceptibility mapping at 7 Tesla MRI for microbleeds detection in cerebral small vessel disease.

Cerebral microbleeds (MBs) are a hallmark of cerebral small vessel disease (CSVD) and can be found on T2*-weighted sequences on MRI. Quantitative susceptibility mapping (QSM) is a postprocessing method that also enables MBs identification and furthermore allows to differentiate them from calcifications. We explored the implications of using QSM at submillimeter resolution for MBs detection in CSVD. Both 3 and 7 Tesla (T) MRI were performed in elderly participants without MBs and patients with CSVD. MBs were quantified on T2*-weighted imaging and QSM. Differences in the number of MBs were assessed, and subjects were classified in CSVD subgroups or controls both on 3T T2*-weighted imaging and 7T QSM. 48 participants [mean age (SD) 70.9 (8.8) years, 48% females] were included: 31 were healthy controls, 6 probable cerebral amyloid angiopathy (CAA), 9 mixed CSVD, and 2 were hypertensive arteriopathy [HA] patients. After accounting for the higher number of MBs detected at 7T QSM (Median = Mdn; Mdn7T-QSM = 2.5; Mdn3T-T2 = 0; z = 4.90; p < 0.001) and false positive MBs (6.1% calcifications), most healthy controls (80.6%) demonstrated at least one MB and more MBs were discovered in the CSVD group. Our observations suggest that QSM at submillimeter resolution improves the detection of MBs in the elderly human brain. A higher prevalence of MBs than so far known in healthy elderly was revealed.

Iron accumulation and axonal damage of cerebellum in idiopathic cervical dystonia.

Postmortem brain study indicated that cerebellar Purkinje cell (PC) loss might be a pathological finding in patients with inherited and idiopathic cervical dystonia (ICD). The analysis of conventional magnetic resonance imaging brain scans failed to yield support for this finding. Previous studies have identified that iron overload can be the consequence of neuron death. The objectives of this study were to investigate iron distribution and demonstrate changes in axons in the cerebellum, providing evidence for PC loss in patients with ICD. Twenty-eight patients with ICD (20 females) and 28 age- and sex-matched healthy controls were recruited. A spatially unbiased infratentorial template was applied to perform cerebellum optimized quantitative susceptibility mapping and diffusion tensor analysis based on magnetic resonance imaging. Voxel-wise analysis was performed to assess cerebellar tissue magnetic susceptibility and fractional anisotropy (FA) alterations, and the clinical relevance of these findings was investigated in the patients with ICD. Increased susceptibility values revealed by quantitative susceptibility mapping in the right lobule CrusI, CrusII, VIIb, VIIIa, VIIIb and IX were found in the patients with ICD. A reduced FA value was found across almost all the cerebellum; an FA value of the significant clusters within the right lobule VIIIa significantly correlated with the motor severity of patients with ICD (r=-0.575, p=0.002). Our study provided evidence for cerebellar iron overload and axonal damage in patients with ICD, which may indicate PC loss and related axonal changes. These results provide evidence for the neuropathological findings in patients with ICD and further highlight the cerebellar involvement in the pathophysiology of dystonia.

Frameless Robot-Assisted Asleep Centromedian Thalamic Nucleus Deep Brain Stimulation Surgery in Patients with Drug-Resistant Epilepsy: Technical Description and Short-Term Clinical Results.

This purpose of this work is to give a detailed description of a surgical technique for frameless robot-assisted asleep deep brain stimulation (DBS) of the centromedian thalamic nucleus (CMT) in drug-resistant epilepsy (DRE). Ten consecutively enrolled patients who underwent CMT-DBS were included in the study. The FreeSurfer "Thalamic Kernel Segmentation" module and experience target coordinates were used for locating the CMT, and quantitative susceptibility mapping (QSM) images were used to check the target. The patient's head was secured with a head clip, and electrode implantation was performed with the assistance of the neurosurgical robot Sinovation®. After opening the dura, the burr hole was continuously flushed with physiological saline to stop air from entering the skull. All procedures were performed under general anesthesia without intraoperative microelectrode recording (MER). The mean age of the patients at surgery and onset of seizures was 22years (range 11-41years) and 11years (range 1-21years), respectively. The median duration of seizures before CMT-DBS surgery was 10years (2-26years). CMT was successfully segmented, and its position was verified by experience target coordinates and QSM images in all ten patients. The mean surgical time for bilateral CMT-DBS in this cohort was 165 ± 18min. The mean pneumocephalus volume was 2 cm3. The median absolute errors in the x-, y-, and z-axes were 0.7mm, 0.5mm, and 0.9mm, respectively. The median Euclidean distance (ED) and radial error (RE) was 1.3 ± 0.5mm and 1.0 ± 0.3mm, respectively. No significant difference was found between right- and left-sided electrodes regarding the RE nor the ED. After a mean 12-month follow-up, the average reduction in seizures was 61%, and six patients experienced a ≥ 50% reduction in seizures, including one patient who had no seizures after the operation. All patients tolerated the anesthesia operation, and no permanent or serious complications were reported. Frameless robot-assisted asleep surgery is a precise and safe approach for placing CMT electrodes in patients with DRE, shortening the surgery time. The segmentation of the thalamic nuclei enables the precise location of the CMT, and the flow of physiological saline to seal the burr holes is a good way to reduce the influx of air. CMT-DBS is an effective method to reduce seizures.

In vivo multi-parameter mapping of the habenula using MRI

The habenula is a small, epithalamic brain structure situated between the mediodorsal thalamus and the third ventricle. It plays an important role in the reward circuitry of the brain and is implicated in psychiatric conditions, such as depression. The importance of the habenula for human cognition and mental health make it a key structure of interest for neuroimaging studies. However, few studies have characterised the physical properties of the human habenula using magnetic resonance imaging because its challenging visualisation in vivo, primarily due to its subcortical location and small size. To date, microstructural characterization of the habenula has focused on quantitative susceptibility mapping. In this work, we complement this previous characterisation with measures of longitudinal and effective transverse relaxation rates, proton density and magnetisation transfer saturation using a high-resolution quantitative multi-parametric mapping protocol at 3T, in a cohort of 26 healthy participants. The habenula had consistent boundaries across the various parameter maps and was most clearly visualised on the longitudinal relaxation rate maps. We have provided a quantitative multi-parametric characterisation that may be useful for future sequence optimisation to enhance visualisation of the habenula, and additionally provides reference values for future studies investigating pathological differences in habenula microstructure.

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.

New 3D phase-unwrapping method based on voxel clustering and local polynomial modeling: application to quantitative susceptibility mapping.

To develop an accurate and robust 3-dimensional (3D) phase-unwrapping method that works effectively in the presence of severe noise, disconnected regions, rapid phase changes, and open-ended lines for quantitative susceptibility mapping (QSM). We developed a 3D phase-unwrapping method based on voxel clustering and local polynomial modeling named CLOSE3D, which firstly explores the 26-neighborhood to calculate local variation of the phasor and the phase, and then according to the local variation of the phasor, clusters the phase data into easy-to-unwrap blocks and difficult-to-unwrap residual voxels. Next, CLOSE3D sequentially performs intrablock, interblock, and residual-voxel unwrapping by using the region-growing local polynomial modeling method. CLOSED3D was evaluated in simulation and using in vivo brain QSM data, and was compared with classical region-growing and region-expanding labeling for unwrapping estimates methods. The simulation experiments showed that CLOSE3D achieved accurate phase-unwrapping results with a mean error ratio <0.39%, even in the presence of serious noise, disconnected regions, and rapid phase changes. The error ratios of region-growing (P=0.000 and P=0.000) and region-expanding labeling for unwrapping estimates (P=0.007, P=0.014) methods were both significantly higher than that of CLOSE3D, when the noise level was ≥60%. The results of the in vivo brain QSM experiments showed that CLOSE3D unwrapped the phase data and accurately reconstructed quantitative susceptibility data, even with serious noise, rapid-varying phase, or an open-ended cutline. CLOSE3D achieves phase unwrapping with high accuracy and robustness, which will help phase-related 3D magnetic resonance imaging (MRI) applications such as QSM and susceptibility weighted imaging.

Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study.

Dysfunction of iron metabolism, especially in substantia nigra (SN), is widely acknowledged in Parkinson's disease (PD), but the genetic influence on iron deposition remains largely unknown. Thus, in this study, we aimed to investigate potential genetic impacts on iron deposition in PD. Seventy-four subjects, including 38 patients with PD and 36 age-matched normal controls, participated in this study. Imaging genetic association analysis was used to identify the specific influence of single nucleotide polymorphism (SNP) on iron-related quantitative traits (QT). Genetic effects on iron deposition at the disease level, SNP level, and their interactive effect were highlighted. Four strong SNP-QT associations were detected: rs602201-susceptibility of bilateral SN, rs198440-susceptibility of left SN, and rs7895403-susceptibility of left caudate head. Detailed analyses showed that: (1) significant iron deposition was exclusively found in bilateral SN in PD; (2) altered polymorphisms of the A allele/A- genotype of rs602201 and G allele/G- genotype of rs198440 and rs7895403 were more frequently observed in PD; (3) for rs602201, among all subjects, A- genotype carriers showed significantly increased iron content than TT genotype in bilateral SN; for rs198440 and rs7895403, G- carriers showed increased iron content than AA genotype in left SN and left caudate head, respectively; and (4) rs602201 exhibited significant SNP-by-disease interaction in bilateral SN. This study shows that rs602201 and rs198440 have a stimulative impact on nigral iron deposition in PD, which provides improved understanding of iron-related pathogenesis in PD, and specifically, that vulnerability to iron deposition in SN is genetic-based.

Striatal Iron Deposition in Recreational MDMA (Ecstasy) Users

BackgroundThe common club drug MDMA (also known as ecstasy) enhances mood, sensory perception, energy, sociability, and euphoria. While MDMA has been shown to produce neurotoxicity in animal models, research on its potential neurotoxic effects in humans is inconclusive and has focused primarily on the serotonin system. MethodsWe investigated 34 regular, largely pure MDMA users for signs of premature neurodegenerative processes in the form of increased iron load in comparison to a group of 36 age-, sex-, and education-matched MDMA-naïve control subjects. We used quantitative susceptibility mapping, a novel tool able to detect even small tissue (nonheme) iron accumulations. Cortical and relevant subcortical gray matter structures were grouped into 8 regions of interest and analyzed. ResultsSignificantly increased iron deposition in the striatum was evident in the MDMA user group. The effect survived correction for multiple comparisons and remained after controlling for relevant confounding factors, including age, smoking, and stimulant co-use. Although no significant linear relationship between measurements of the amounts of MDMA intake (hair analysis and self-reports) and quantitative susceptibility mapping values was observed, increased striatal iron deposition might nevertheless point to MDMA-induced neurotoxic processes. Additional factors (hyperthermia and simultaneous co-use of other substances) that possibly amplify neurotoxic effects of MDMA during the state of acute intoxication are discussed. ConclusionsThe demonstrated increased striatal iron accumulation may indicate that regular MDMA users have an increased risk potential for neurodegenerative diseases with progressing age.

Peripheral and Central Iron Measures in Alcohol Use Disorder and Aging: A Quantitative Susceptibility Mapping Pilot Study.

Chronic excessive alcohol use has neurotoxic effects, which may contribute to cognitive decline and the risk of early-onset dementia. Elevated peripheral iron levels have been reported in individuals with alcohol use disorder (AUD), but its association with brain iron loading has not been explored. We evaluated whether (1) serum and brain iron loading are higher in individuals with AUD than non-dependent healthy controls and (2) serum and brain iron loading increase with age. A fasting serum iron panel was obtained and a magnetic resonance imaging scan with quantitative susceptibility mapping (QSM) was used to quantify brain iron concentrations. Although serum ferritin levels were higher in the AUD group than in controls, whole-brain iron susceptibility did not differ between groups. Voxel-wise QSM analyses revealed higher susceptibility in a cluster in the left globus pallidus in individuals with AUD than controls. Whole-brain iron increased with age and voxel-wise QSM indicated higher susceptibility with age in various brain areas including the basal ganglia. This is the first study to analyze both serum and brain iron loading in individuals with AUD. Larger studies are needed to examine the effects of alcohol use on iron loading and its associations with alcohol use severity, structural and functional brain changes, and alcohol-induced cognitive impairments.

Age-related differences of cerebellar cortex and nuclei: MRI findings in healthy controls and its application to spinocerebellar ataxia (SCA6) patients

Understanding cerebellar alterations due to healthy aging provides a reference point against which pathological findings in late-onset disease, for example spinocerebellar ataxia type 6 (SCA6), can be contrasted. In the present study, we investigated the impact of aging on the cerebellar nuclei and cerebellar cortex in 109 healthy controls (age range: 16 – 78 years) using 3 Tesla magnetic resonance imaging (MRI). Findings were compared with 25 SCA6 patients (age range: 38 – 78 years). A subset of 16 SCA6 (included: 14) patients and 50 controls (included: 45) received an additional MRI scan at 7 Tesla and were re-scanned after one year. MRI included T1-weighted, T2-weighted FLAIR, and multi-echo T2*-weighted imaging. The T2*-weighted phase images were converted to quantitative susceptibility maps (QSM). Since the cerebellar nuclei are characterized by elevated iron content with respect to their surroundings, two independent raters manually outlined them on the susceptibility maps. T1-weighted images acquired at 3T were utilized to automatically identify the cerebellar gray matter (GM) volume. Linear correlations revealed significant atrophy of the cerebellum due to tissue loss of cerebellar cortical GM in healthy controls with increasing age. Reduction of the cerebellar GM was substantially stronger in SCA6 patients. The volume of the dentate nuclei did not exhibit a significant relationship with age, at least in the age range between 18 and 78 years, whereas mean susceptibilities of the dentate nuclei increased with age. As previously shown, the dentate nuclei volumes were smaller and magnetic susceptibilities were lower in SCA6 patients compared to age- and sex-matched controls. The significant dentate volume loss in SCA6 patients could also be confirmed with 7T MRI. Linear mixed effects models and individual paired t-tests accounting for multiple comparisons revealed no statistical significant change in volume and susceptibility of the dentate nuclei after one year in neither patients nor controls. Importantly, dentate volumes were more sensitive to differentiate between SCA6 (Cohen's d = 3.02) and matched controls than the cerebellar cortex volume (d = 2.04). In addition to age-related decline of the cerebellar cortex and atrophy in SCA6 patients, age-related increase of susceptibility of the dentate nuclei was found in controls, whereas dentate volume and susceptibility was significantly decreased in SCA6 patients. Because no significant changes of any of these parameters was found at follow-up, these measures do not allow to monitor disease progression at short intervals.

Multimodal Imaging of Substantia Nigra in Parkinson's Disease with Levodopa-Induced Dyskinesia.

Degeneration of the substantia nigra (SN) may contribute to levodopa-induced dyskinesia (LID) in Parkinson's disease (PD), but the exact characteristics of SN in LID remain unclear. To further understand the pathogenesis of patients with PD with LID (PD-LID), we explored the structural and functional characteristics of SN in PD-LID using multimodal magnetic resonance imaging (MRI). Twenty-nine patients with PD-LID, 37 patients with PD without LID (PD-nLID), and 28 healthy control subjects underwent T1-weighted MRI, quantitative susceptibility mapping, neuromelanin-sensitive MRI, multishell diffusion MRI, and resting-state functional MRI. Different measures characterizing the SN were obtained using a region of interest-based approach. Compared with patients with PD-nLID and healthy control subjects, the quantitative susceptibility mapping values of SN pars compacta (SNpc) were significantly higher (P= 0.049 and P= 0.00002), and the neuromelanin contrast-to-noise ratio values in SNpc were significantly lower (P= 0.012 and P= 0.000002) in PD-LID. The intracellular volume fraction of the posterior SN in PD-LID was significantly higher compared with PD-nLID (P= 0.037). Resting-state fMRI indicated that PD-LID in the medication off state showed higher functional connectivity between the SNpc and putamen compared with PD-nLID (P= 0.031), and the functional connectivity changes in PD-LID were positively correlated with Unified Dyskinesia Rating Scale total scores (R= 0.427, P=0.042). Our multimodal imaging findings highlight greater neurodegeneration in SN and the altered nigrostriatal connectivity in PD-LID. These characteristics provide a new perspective into the role of SN in the pathophysiological mechanisms underlying PD-LID. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The impact of iron deposition on the fear circuit of the brain in patients with Parkinson's disease and anxiety.

Anxiety is one of the most common psychiatric symptoms of Parkinson's disease (PD), and brain iron deposition is considered to be one of the pathological mechanisms of PD. The objective of this study was to explore alterations in brain iron deposition in PD patients with anxiety compared to PD patients without anxiety, especially in the fear circuit. Sixteen PD patients with anxiety, 23 PD patients without anxiety, and 26 healthy elderly controls were enrolled prospectively. All subjects underwent neuropsychological assessments and brain magnetic resonance imaging (MRI) examinations. Voxel-based morphometry (VBM) was used to study morphological brain differences between the groups. Quantitative susceptibility mapping (QSM), an MRI technique capable of quantifying susceptibility changes in brain tissue, was used to compare susceptibility changes in the whole brain among the three groups. The correlations between brain susceptibility changes and anxiety scores quantified using the Hamilton Anxiety Rating Scale (HAMA) were compared and analyzed. PD patients with anxiety had a longer duration of PD and higher HAMA scores than PD patients without anxiety. No morphological brain differences were observed between the groups. In contrast, voxel-based and ROI-based QSM analyses showed that PD patients with anxiety had significantly increased QSM values in the medial prefrontal cortex, anterior cingulate cortex, hippocampus, precuneus, and angular cortex. Furthermore, the QSM values of some of these brain regions were positively correlated with the HAMA scores (medial prefrontal cortex: r = 0.255, p = 0.04; anterior cingulate cortex: r = 0.381, p < 0.01; hippocampus: r = 0.496, p < 0.01). Our findings support the idea that anxiety in PD is associated with iron burden in the brain fear circuit, providing a possible new approach to explaining the potential neural mechanism of anxiety in PD.