Deep Gray Matter Nuclei Research Articles

Associations of Brain Atrophy and Cerebral Iron Accumulation at MRI with Clinical Severity in Wilson Disease.

Background Abnormal findings at brain MRI in patients with neurologic Wilson disease (WD) are characterized by signal intensity changes and cerebral atrophy. T2 signal hypointensities and atrophy are largely irreversible with treatment; their relationship with permanent disability has not been systematically investigated. Purpose To investigate associations of regional brain atrophy and iron accumulation at MRI with clinical severity in participants with neurologic WD who are undergoing long-term anti-copper treatment. Materials and Methods Participants with WD and controls were compared in a prospective study performed from 2015 to 2019. MRI at 3.0 T included three-dimensional T1-weighted and six-echo multigradient-echo pulse sequences for morphometry and quantitative susceptibility mapping, respectively. Neurologic severity was assessed with the Unified WD Rating Scale (UWDRS). Automated multi-atlas segmentation pipeline with dual contrast (susceptibility and T1) was used for the calculation of volumes and mean susceptibilities in deep gray matter nuclei. Additionally, whole-brain analysis using deformation and surface-based morphometry was performed. Least absolute shrinkage and selection operator regression was used to assess the association of regional volumes and susceptibilities with the UWDRS score. Results Twenty-nine participants with WD (mean age, 47 years ± 9 [standard deviation]; 15 women) and 26 controls (mean age, 45 years ± 12; 14 women) were evaluated. Whole-brain analysis demonstrated atrophy of the deep gray matter nuclei, brainstem, internal capsule, motor cortex and corticospinal pathway, and visual cortex and optic radiation in participants with WD (P < .05 at voxel level, corrected for family-wise error). The UWDRS score was negatively correlated with volumes of putamen (r = -0.63, P < .001), red nucleus (r = -0.58, P = .001), globus pallidus (r = -0.53, P = .003), and substantia nigra (r = -0.50, P = .006) but not with susceptibilities. Only the putaminal volume was identified as a stable factor associated with the UWDRS score (R2 = 0.38, P < .001) using least absolute shrinkage and selection operator regression. Conclusion Individuals with Wilson disease (WD) had widespread brain atrophy most pronounced in the central structures. The putaminal volume was associated with the Unified WD Rating Scale score and can be used as a surrogate imaging marker of clinical severity. © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Du and Bydder in this issue.

Clinical analysis of 33 cases with neonatal cerebral infarction.

Objective:To investigate the etiology, clinical manifestations, diagnosis, treatment and prognosis of neonatal cerebral infarction (NCI) to further improve the understanding of the disease.Methods:Clinical data and follow-up results of 33 cases of NCI in neonatal intensive care unit of a first-class hospital from September 2009 to September 2019 were retrospectively analyzed.Results:All 33 patients were diagnosed with NCI by MRI. Among them, 31 cases (93.94%) were full-term infants, 25 cases (75.76%) were mother’s first birth, and 18 (54.55%) cases were males. Pregnancy complications were reported in 18 cases (54.55%), and 19 cases (57.58%) had perinatal hypoxia history. Seizures were the most common first symptom and clinical manifestation in the course of disease (81.8%). There were 27 cases (81.82%) of patent foramen ovale (PFO) among NCI cohort. Ischemic cerebral infarction occurred in 32 cases (96.97%). The middle cerebral artery and its branches were more frequently involved, mainly on the left side. The acute stage of NCI was managed by symptomatic support treatment, and the recovery stage involved mainly rehabilitation treatment. Among the 33 cases, five cases were lost to follow-up, two patients died, 26 patients survived without complications, one case had cerebral palsy, one case had language retardation, and six cases had dyskinesia. Poor prognosis was associated with the involvement of deep gray matter nuclei or multiple lobes, and intrapartum complications. Vaginal mode of delivery and longer hospital stay were associated with better prognosis.Conclusions:Complications leading to placental circulation disorder during pregnancy and perinatal hypoxia are common high-risk factors of NCI. The seizure is the most common clinical manifestation. There is a possible correlation between PFO and NCI. Involvement of deep gray matter or multiple lobes and intrapartum complications may indicate poor prognosis, while vaginal delivery and prolonged hospitalizations are associated with better prognosis of NCI.

Gray Matter Matters: A Longitudinal Magnetic Resonance Voxel-Based Morphometry Study of Primary Progressive Multiple Sclerosis.

Background: Multiple Sclerosis (MS) lesions in white matter (WM) are easily detected with conventional MRI which induce inflammation thereby generating contrast. WM lesions do not consistently explain the extent of clinical disability, cognitive impairment, or the source of an exacerbation. Gray matter (GM) structures including the cerebral cortex and various deep nuclei are known to be affected early in Primary Progressive Multiple Sclerosis (PPMS) and drive disease progression, disability, fatigue, and cognitive dysfunction. However, little is known about how rapidly GM lesions develop and accumulate over time.Objective: The purpose of this study is to analyze the degree and rate of progression in 25 patients with PPMS using voxel-based automated volumetric quantitation.Methods: This is a retrospective single-center study which includes a cohort of 25 patients with PPMS scanned utilizing NeuroQuant® 3 dimensional voxel-based morphometry (3D VBM) automated analysis and database and restudied after a period of ~1 year (11–14 months). Comparisons with normative data were acquired for whole brain, forebrain parenchyma, cortical GM, hippocampus, thalamus, superior and inferior lateral ventricles. GM volume changes were correlated with their clinical motor and cognitive scores using Extended Disability Status Scales (EDSS) and Montreal Cognitive Assessments (MoCA).Results: Steep reductions occurred in cerebral cortical GM and deep GM nuclei volumes which correlated with each patient's clinical and cognitive impairment. The median observed percentile volume losses were statistically significant compared with the 50th percentile for each GM component. Longitudinal assessments of an unselected sample of one dozen patients involved in the PPMS study showed prominent losses occurring mainly in cortical GM and hippocampus which were reflected in their EDSS and MoCA. The longitudinal results were compared with a similar sample of patients having Relapsing MS (RMS) whose GM values were largely in normal range, annualized volume GM changes were much less, while WM hyperintensities were in abnormal range in half the unselected cases.Conclusions: Knowledge of the degree and rapidity with which cortical atrophy and deep GM volume loss develops clarifies the source of progressive cognitive and clinical decline in PPMS.

Voxel-Based quantitative MRI reveals spatial patterns of grey matter alteration in multiple sclerosis.

Despite robust postmortem evidence and potential clinical importance of gray matter (GM) pathology in multiple sclerosis (MS), assessing GM damage by conventional magnetic resonance imaging (MRI) remains challenging. This prospective cross‐sectional study aimed at characterizing the topography of GM microstructural and volumetric alteration in MS using, in addition to brain atrophy measures, three quantitative MRI (qMRI) parameters—magnetization transfer (MT) saturation, longitudinal (R1), and effective transverse (R2*) relaxation rates, derived from data acquired during a single scanning session. Our study involved 35 MS patients (14 relapsing–remitting MS; 21 primary or secondary progressive MS) and 36 age‐matched healthy controls (HC). The qMRI maps were computed and segmented in different tissue classes. Voxel‐based quantification (VBQ) and voxel‐based morphometry (VBM) statistical analyses were carried out using multiple linear regression models. In MS patients compared with HC, three configurations of GM microstructural/volumetric alterations were identified. (a) Co‐localization of GM atrophy with significant reduction of MT, R1, and/or R2*, usually observed in primary cortices. (b) Microstructural modifications without significant GM loss: hippocampus and paralimbic cortices, showing reduced MT and/or R1 values without significant atrophy. (c) Atrophy without significant change in microstructure, identified in deep GM nuclei. In conclusion, this quantitative multiparametric voxel‐based approach reveals three different spatially‐segregated combinations of GM microstructural/volumetric alterations in MS that might be associated with different neuropathology.

Different iron deposition patterns in Parkinson's disease subtypes: a quantitative susceptibility mapping study.

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with various subtypes and uncertain pathogenesis. Iron deposition is considered to be involved in the pathological mechanisms of PD. The present study aimed to investigate the iron deposition in deep gray matter in patients with different PD subtypes using quantitative susceptibility mapping (QSM). Forty-six PD patients and 22 healthy controls (HCs) were recruited for the study. PD patients were allocated to the tremor-dominant (TD) group (n=22), postural instability and gait disorder-dominant (PIGD) group (n=19), and intermediate group (n=5). Susceptibility values in deep gray matter nuclei measured by QSM among the PD-TD and PD-PIGD groups and the HCs, as well as the relationship between iron accumulation and clinical motor features, were investigated. Susceptibility values in the dentate nucleus (DN) were greater in the PD-TD (118.73±70.45) group than in the PD-PIGD (72.14±39.85, P=0.02) group and HCs (78.26±41.38, P=0.042). Further, a significant positive correlation was observed between the DN susceptibility values and tremor scores (r=0.324, P=0.028). Compared with the HCs (182.60±85.35), both the PD-TD (282.00±102.49, P=0.006) and PD-PIGD groups (284.91±118.54, P=0.007) exhibited greater susceptibility values in the substantia nigra (SN) pars reticulata. The susceptibility values in the SN pars compacta were also greater in the PD-PIGD group (164.51±89.44) than in the HCs (107.78±63.11, P=0.048). The present study demonstrated various iron deposition patterns in different PD phenotypes. These findings give insight into the pathophysiology underlying different PD phenotypes, and potentially illustrate the involvement of iron deposition in the PD-TD and PD-PIGD subtypes.

Iron and inflammation: in vivo and post-mortem studies in Parkinson's disease.

In these present studies, in vivo and and post-mortem studies have investigated the association between iron and inflammation. Early-stage Parkinson's disease (PD) patients, of less than 5years disease duration, showed associations of plasmatic ferritin concentrations with both proinflammatory cytokine interleukin-6 and hepcidin, a regulator of iron metabolism as well as clinical measures. In addition ratios of plasmatic ferritin and iron accumulation in deep grey matter nuclei assessed with relaxometry T2* inversely correlated with disease severity and duration of PD. On the hand, post-mortem material of the substantia nigra compacta (SNc) divided according to Braak and Braak scores, III-IV and V-VI staging, exhibited comparable microgliosis, with a variety of phenotypes present. There was an association between the intensity of microgliosis and iron accumulation as assayed by Perl's staining in the SNc sections. In conclusion, markers of inflammation and iron metabolism in both systemic and brain systems are closely linked in PD, thus offering a potential biomarker for progression of the disease.

Paramagnetic Metal Accumulation in the Deep Gray Matter Nuclei Is Associated With Neurodegeneration in Wilson's Disease.

BackgroundNeuropathological studies have revealed copper and iron accumulation in the deep gray matter (DGM) nuclei of patients with Wilson’s disease (WD). However, the association between metal accumulation and neurodegeneration in WD has not been well studied in vivo. The study was aimed to investigate whether metal accumulation in the DGM was associated with the structural and functional changes of DGM in neurological WD patients.MethodsSeventeen neurological WD patients and 20 healthy controls were recruited for the study. Mean bulk susceptibility values and volumes of DGM were obtained from quantitative susceptibility mapping (QSM). Regions of interest including the head of the caudate nucleus, globus pallidus, putamen, thalamus, substantia nigra, red nucleus, and dentate nucleus were manually segmented. The susceptibility values and volumes of DGM in different groups were compared using a linear regression model. Correlations between susceptibility values and volumes of DGM and Unified Wilson’s Disease Rating Scale (UWDRS) neurological subscores were investigated.ResultsThe susceptibility values of all examined DGM in WD patients were higher than those in healthy controls (P < 0.05). Volume reductions were observed in the head of the caudate nucleus, globus pallidus, putamen, thalamus, and substantia nigra of WD patients (P < 0.001). Susceptibility values were negatively correlated with the volumes of the head of the caudate nucleus (rp = −0.657, P = 0.037), putamen (rp = −0.667, P = 0.037), and thalamus (rp = −0.613, P = 0.046) in WD patients. UWDRS neurological subscores were positively correlated with the susceptibility values of all examined DGM. The susceptibility values of putamen, head of the caudate nucleus, and dentate nucleus could well predict UWDRS neurological subscores.ConclusionOur study provided in vivo evidence that paramagnetic metal accumulation in the DGM was associated with DGM atrophy and neurological impairment. The susceptibility of DGM could be used as a biomarker to assess the severity of neurodegeneration in WD.

Gray Matter Nucleus Hyperintensity After Monthly Triple-Dose Gadopentetate Dimeglumine With Long-term Magnetic Resonance Imaging.

Gadolinium deposition is widely believed to occur, but questions regarding accumulation pattern and permanence remain. We conducted a retrospective study of intracranial signal changes on monthly triple-dose contrast-enhanced magnetic resonance imaging (MRI) examinations from the previously published Betaseron vs. Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints Trial (N = 67) to characterize the dynamics of gadolinium deposition in several deep brain nuclei and track persistence versus washout of gadolinium deposition on long-term follow-up (LTFU) examinations (N = 28) obtained approximately 10 years after enrollment in the Betaseron vs. Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints Trial. Using T2 and proton density images and using image analysis software (ITK-SNAP), manual regions of interest were created ascribing boundaries of the caudate nucleus, dentate nucleus, globus pallidus, pulvinar, putamen, white matter, and air. Intensity analysis was conducted on T1-weighted fat-saturated (fat-sat) images using the FSL package. A linear rigid-body transform was calculated from the fat-sat image at each target time point to the region of interest segmentation reference time point fat-sat image. Serial MRI signal was analyzed using linear mixed regression modeling with random intercept. Annual MRI signal changes including LTFU scans were assessed with t test. During monthly scanning, all gray matter structures demonstrated a significant (P < 0.0001) increase in contrast-to-noise ratio. Yearly changes in deposition showed distinctive patterns for the specific nucleus: globus pallidus showed complete retention, pulvinar showed partial washout, while dentate, caudate, and putamen returned to baseline (ie, complete washout). Monthly increased contrast-to-noise ratio in gray matter nuclei is consistent with gadolinium deposition over time. The study also suggests that some deep gray matter nuclei permanently retain gadolinium, whereas others demonstrate washout of soluble gadolinium.

Quantitative Measurement of Metal Accumulation in Brain of Patients With Wilson's Disease.

Currently, no study has evaluated metal accumulation in the brains of patients with Wilson's disease by using quantitative susceptibility mapping at 3T MRI. The objectives of this study were to qualitatively and quantitatively evaluate changes in magnetic susceptibility and R2* maps in deep gray matter nuclei to discriminate Wilson's disease patients from healthy controls and to evaluate their sensitivities in diagnosing Wilson's disease. Magnetic susceptibility and R2* maps and conventional T1-weighted, T2-weighted, and T2-weighted fluid-attenuated inversion recovery images were obtained from 17 Wilson's disease patients and 14 age-matched healthy controls on a 3T MRI scanner. Differences between Wilson's disease and healthy control groups in susceptibility and R2* values in multiple deep nuclei were evaluated using a Mann-Whitney U test and receiver operating characteristic curves. The correlations of susceptibility and R2* values with Unified Wilson's Disease Rating Scale score were also performed. Magnetic susceptibility and R2* can effectively distinguish different types of signal abnormalities. Magnetic susceptibility and R2* values in multiple deep nuclei of Wilson's disease patients were significantly higher than those in healthy controls. Magnetic susceptibility value in the substantia nigra had the highest area under the curve (0.888). There were positive correlations of the Unified Wilson's Disease Rating Scale score with susceptibility values in the caudate nucleus (r = 0.757, P = 0.011), putamen (r = 0.679, P = 0.031), and red nucleus (r = 0.638, P = 0.047), as well as R2* values in the caudate nucleus (r = 0.754, P = 0.012). Quantitative susceptibility mapping at 3T could be a useful tool to evaluate metal accumulation in deep gray matter nuclei of Wilson's disease patients. © 2020 International Parkinson and Movement Disorder Society.

Evaluation of abnormal iron distribution in specific regions in the brains of patients with Parkinson's disease using quantitative susceptibility mapping and R2* mapping

The primary aim of the present study was to evaluate abnormal iron distribution in specific regions of the brains in patients with Parkinson's disease (PD) using quantitative susceptibility mapping (QSM) and R2* mapping, and to compare the diagnostic performances of QSM and R2* mapping in differentiating patients with PD with that in normal controls. A total of 25 patients with idiopathic PD and 28 sex-and age-matched normal controls were included in the present study and their brains investigated using a 3T scanner. Magnetic resonance imaging techniques, namely, QSM and R2* mapping, were applied to generate susceptibility and R2* values. The differences in susceptibility and R2* values in deep grey matter nuclei between patients with PD and the normal controls were compared using independent samples t-tests. The abilities of QSM and R2* mapping to classify patients with PD and normal controls were analyzed using receiver operating characteristic curves. Correlation analyses between imaging parameters (e.g. susceptibility and R2* values) and clinical feature (disease severity assessed using the Hoehn and Yahr score) were performed. The intra-class correlation coefficient (ICC) for susceptibility (ICC=0.977; P<0.001) and R2* (ICC=0.945; P<0.001) values between two neuro-radiologists were >0.81, showing excellent inter-rater agreement. The susceptibility values were significantly increased in the substantia nigra (SN) and red nucleus, but were decreased in the putamen of patients with PD compared with that in the corresponding brain regions of normal controls. However, increased R2* values were observed only in the SN in patients with PD. QSM showed higher sensitivity and specificity compared with R2* mapping to separate the patients with PD from the normal controls. There were no significant correlations between the susceptibility/R2* values and clinical features in all targeted regions of the brains in patients with PD. In conclusion, both QSM and R2* mapping are feasible to calculate the iron levels in human brains, and QSM provides a more sensitive and accurate method to assess regional abnormal iron distribution in patients with PD.

Two-year regional grey and white matter volume changes with natalizumab and fingolimod

ObjectiveTo compare the efficacy of fingolimod and natalizumab in preventing regional grey matter (GM) and white matter (WM) atrophy in relapsing-remitting multiple sclerosis (RRMS) over 2 years.MethodsPatients with RRMS starting...

Characterization of Iron Accumulation in Deep Gray Matter in Myotonic Dystrophy Type 1 and 2 Using Quantitative Susceptibility Mapping and R2* Relaxometry: A Magnetic Resonance Imaging Study at 3 Tesla

Quantitative mapping of the magnetic susceptibility and the effective transverse relaxation rate (R2*) are suitable to assess the iron content in distinct brain regions. In this prospective, explorative study the iron accumulation in deep gray matter nuclei (DGM) in myotonic dystrophy type 1 (DM1) and 2 (DM2) and its clinical and neuro-cognitive relevance using susceptibility and R2* mapping was examined. Twelve classical DM1, four childhood-onset DM1 (DM1c.o.), twelve DM2 patients and twenty-nine matched healthy controls underwent MRI at 3 Tesla, neurological and neuro-cognitive tests. Susceptibility, R2* and volumes were determined for eleven DGM structures and compared between patients and controls. Twelve classical DM1, four childhood-onset DM1, and 12 DM2 patients as well as 29 matched healthy controls underwent MRI at 3 Tesla, and neurological and neuro-cognitive tests. Susceptibility, R2* and volumes were determined for 11 DGM structures and compared between patients and controls. Iron accumulation in DGM reflected by R2* or susceptibility was found in the putamen and accumbens of DM1 and in DM2, but was more widespread in DM1 (caudate, pallidum, hippocampus, subthalamic nucleus, thalamus, and substantia nigra). Opposed changes of R2* or susceptibility were detected in caudate, putamen and accumbens in the childhood-onset DM1 patients compared to classical DM1. R2* or susceptibility alterations in DGM were significantly associated with clinical symptoms including muscular weakness (DM1), daytime sleepiness (DM1), depression (DM2), and with specific cognitive deficits in DM1 and DM2.

Sensorimotor and pain-related alterations of the gray matter and white matter in Type 2 diabetic patients with peripheral neuropathy.

Although diabetic peripheral neuropathy (DPN) has long been considered a disease of the peripheral nervous system, recent neuroimaging studies have shown that alterations in the central nervous system may play a crucial role in its pathogenesis. Here, we used surface‐based morphometry (SBM) and tract‐based spatial statistics (TBSS) to investigate gray matter (GM) and white matter (WM) differences between patients with DPN (n = 67, 44 painless and 23 painful) and healthy controls (HCs; n = 88). Compared with HCs, patients with DPN exhibited GM abnormalities in the pre‐ and postcentral gyrus and in several deep GM nuclei (caudate, putamen, medial pallidum, thalamus, and ventral nuclear). They also exhibited altered WM tracts (corticospinal tract, spinothalamic tract, and thalamocortical projecting fibers). These findings suggest impaired motor and somatosensory pathways in DPN. Further, patients with DPN (particularly painful DPN) exhibited morphological differences in the cingulate, insula, prefrontal cortex, and thalamus, as well as impaired WM integrity in periaqueductal WM and internal and external capsules. This suggests pain‐perception/modulation pathways are altered in painful DPN. Intermodal correlation analyses found that the morphological indices of the brain regions identified by the SBM analysis were significantly correlated with the fractional anisotropy of brain regions identified by the TBSS analysis, suggesting that the GM and WM alterations were tightly coupled. Overall, our study showed sensorimotor and pain‐related GM and WM alterations in patients with DPN, which might be involved in the development of DPN.

Detection of occult abnormalities in the deep gray matter nuclei of neonates with punctate white matter lesions by magnetic resonance spectroscopy.

Punctate white matter lesions (PWML) are common in preterm neonates and have also been reported in the full term. While most studies focus on white matter abnormalities, gray matter (GM) alterations are generally ignored due to thelack of abnormalities on conventional MRI. This study aims to investigate whether magnetic resonance spectroscopy is a sensitive and practical method to detect occult alterations of deep GM nuclei in these neonates. Neonates with PWML and controls with no MRI abnormalities were retrospectively studied. Apparent diffusion coefficient values and metabolic ratios (Cho/Cr, NAA/Cho, and NAA/Cr) in the lenticular nucleus and the thalamus were compared between the PWML and control groups. Forty-two neonates with PWML (grades I, II, and III contained 14, 21, and 7 subjects, respectively) and 50 controls were enrolled. Apparent diffusion coefficient values in the lenticular nucleus and the thalamus were not significantly different between the PWML and the control groups. The NAA/Cho ratio was significantly lower in the PWML group than in the control group in both regions, whereas a lower NAA/Cr ratio was only observed in the thalamus. Significantly lower ratios of NAA/Cho in both regions and NAA/Cr in the thalamus were detected in the grade II and III subgroup, whereas the thalamic NAA/Cho ratio was decreased in the grade I group compared with controls. Magnetic resonance spectroscopy is a sensitive method for detecting the occult deep GM abnormalities for the study cohort of neonates with PWML when compared with subjects without PWML.

Automated Steerable Path Planning for Deep Brain Stimulation Safeguarding Fiber Tracts and Deep Gray Matter Nuclei.

Deep Brain Stimulation (DBS) is a neurosurgical procedure consisting in the stereotactic implantation of stimulation electrodes to specific brain targets, such as deep gray matter nuclei. Current solutions to place the electrodes rely on rectilinear stereotactic trajectories (RTs) manually defined by surgeons, based on pre-operative images. An automatic path planner that accurately targets subthalamic nuclei (STN) and safeguards critical surrounding structures is still lacking. Also, robotically-driven curvilinear trajectories (CTs) computed on the basis of state-of-the-art neuroimaging would decrease DBS invasiveness, circumventing patient-specific obstacles. This work presents a new algorithm able to estimate a pool of DBS curvilinear trajectories for reaching a given deep target in the brain, in the context of the EU's Horizon EDEN2020 project. The prospect of automatically computing trajectory plans relying on sophisticated newly engineered steerable devices represents a breakthrough in the field of microsurgical robotics. By tailoring the paths according to single-patient anatomical constraints, as defined by advanced preoperative neuroimaging including diffusion MR tractography, this planner ensures a higher level of safety than the standard rectilinear approach. Ten healthy controls underwent Magnetic Resonance Imaging (MRI) on 3T scanner, including 3DT1-weighted sequences, 3Dhigh-resolution time-of-flight MR angiography (TOF-MRA) and high angular resolution diffusion MR sequences. A probabilistic q-ball residual-bootstrap MR tractography algorithm was used to reconstruct motor fibers, while the other deep gray matter nuclei surrounding STN and vessels were segmented on T1 and TOF-MRA images, respectively. These structures were labeled as obstacles. The reliability of the automated planner was evaluated; CTs were compared to RTs in terms of efficacy and safety. Targeting the anterior STN, CTs performed significantly better in maximizing the minimal distance from critical structures, by finding a tuned balance between all obstacles. Moreover, CTs resulted superior in reaching the center of mass (COM) of STN, as well as in optimizing the entry angle in STN and in the skull surface.

Iron deposition in Parkinson\u2019s disease by quantitative susceptibility mapping

BackgroundPatients with Parkinson’s disease (PD) have elevated levels of brain iron, especially in the nigrostriatal dopaminergic system. The purpose of this study was to evaluate the iron deposition in the substantia nigra (SN) and other deep gray matter nuclei of PD patients using quantitative susceptibility mapping (QSM) and its clinical relationship, and to explore whether there is a gradient of iron deposition pattern in globus pallidus (GP)–fascicula nigrale (FN)–SN pathway.MethodsThirty-three PD patients and 26 age- and sex-matched healthy volunteers (HVs) were included in this study. Subjects underwent brain MRI and constructed QSM data. The differences in iron accumulation in the deep gray matter nuclei of the subjects were compared, including the PD group and the control group, the early-stage PD (EPD) group and the late-stage PD (LPD) group. The iron deposition pattern of the GP–FN–SN pathway was analyzed.ResultsThe PD group showed increased susceptibility values in the FN, substantia nigra pars compacta (SNc), internal globus pallidus (GPi), red nucleus (RN), putamen and caudate nucleus compared with the HV group (P < 0.05). In both PD and HV group, iron deposition along the GP–FN–SN pathway did not show an increasing gradient pattern. The SNc, substantia nigra pars reticulata (SNr) and RN showed significantly increased susceptibility values in the LPD patients compared with the EPD patients.ConclusionPD is closely related to iron deposition in the SNc. The condition of PD patients is related to the SNc and the SNr. There is not an increasing iron deposition gradient along the GP–FN–SN pathway. The source and mechanism of iron deposition in the SN need to be further explored, as does the relationship between the iron deposition in the RN and PD.

Are There Differences in Brain Morphology in Patients with Lifelong Premature Ejaculation?

IntroductionEven though lifelong premature ejaculation (PE) is highly prevalent, few studies have investigated the neural mechanisms underlying PE. AimThis study aimed to investigate whether patients with lifelong PE exhibit macrostructural or microstructural alterations of the parts of the brain involved in the male sexual response. Materials and MethodsWe enrolled 42 healthy participants and 54 lifelong PE patients. Lifelong PE was diagnosed according to the Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT). We compared measures of cortical morphology, such as volumes of gray matter, white matter, cerebellum volumes, and subcortical structures (ie, amygdala, caudate, hippocampus, globus pallidus, putamen, and thalamus) between the groups using a voxel-based morphometry method from whole-brain T1-weighted magnetic resonance imaging. Moreover, we evaluated the relationships between the relevant cerebral alterations and the severity of symptoms obtained from participants via self-reported questionnaires. Main Outcome MeasuresCerebral macrostructural and microstructural alterations were assessed in PE patients and controls, along with the correlation of caudate nucleus changes in PE patients with clinical data (including the PEDT and the IELT). ResultsThe mean volume of the caudate nucleus was significantly larger in the lifelong PE patients compared with healthy controls (P = .048). Moreover, caudate nucleus volume was positively correlated with PEDT score (r = 0.621; P = .0179) and negatively correlated with the IELT (r = −0.592; P = .0101). However, cortex morphology and the other subcortical volumes were not significantly different between the 2 groups (P > .05). Clinical ImplicationsMicrostructural alterations in deep gray matter nuclei might be a useful parameter for studying the mechanism of the neurobiology underlying PE. Strengths and LimitationsThere are few studies examining microstructural changes in PE patients. This study furthers our understanding of the etiology of PE. Limitations include the small sample, which limits our ability to make an absolute determination as to whether such subcortical changes are the cause or the consequence of lifelong PE. ConclusionsWe found a significant difference in caudate nucleus volume between patients with PE and healthy controls. In addition, the caudate nucleus volume was positively associated with the severity of PE symptoms. More extensive and possibly longitudinal studies are needed to improve our understanding of the mechanism of the neurobiology underlying PE.Atalay HA, Sonkaya AR, Ozbir S, et al. Are There Differences in Brain Morphology in Patients with Lifelong Premature Ejaculation? J Sex Med 2019;16:992–998.

Automated quantitative evaluation of brain MRI may be more accurate for discriminating preterm born adults.

To investigate the structural brain abnormalities and their diagnostic accuracy through qualitative and quantitative analysis in term born and very preterm birth or with very low birth weight (VP/VLBW) adults. We analyzed 3-T MRIs acquired in 2011-2013 from 67 adults (27 term born controls, mean age 26.4years, 8 females; 40 VP/VLBWs, mean age 26.6years, 16 females). We compared automatic segmentations of the white matter, deep gray matter and cortical gray matter, manual corpus callosum measurements and visual ratings of the ventricles and white matter with t tests, logistic regression, and receiver operator characteristic (ROC) curves. Automatic segmentation correctly classified 84% of cases; visual ratings correctly classified 63%. Quantitative volumetry based on automatic segmentation revealed higher ventricular volume, lower posterior corpus callosum, and deep gray matter volumes in VP/VLBW subjects compared to controls (p < 0.01). Visual rating and manual measurement revealed a thinner corpus callosum in VP/VLBW adults (p = 0.04) and deformed lateral ventricles (p = 0.03) and tendency towards more "dirty" white matter (p = 0.06). Automatic/manual measures combined with visual ratings correctly classified 87% of cases. Stepwise logistic regression identified three independent features that correctly classify 81% of cases: ventricular volume, deep gray matter volume, and white matter aspect. Enlarged and deformed lateral ventricles, thinner corpus callosum, and "dirty" white matter are prevalent in preterm born adults. Their visual evaluation has low diagnostic accuracy. Automatic volume quantification is more accurate but time consuming. It may be useful to ask for prematurity before initiating further diagnostics in subjects with these alterations. • Our study confirms prior reports showing that structural brain abnormalities related to preterm birth persist into adulthood. • In the clinical practice, if large and deformed lateral ventricles, small and thin corpus callosum, and "dirty" white matter are visible on MRI, ask for prematurity before considering other diagnoses. • Although prevalent, visual findings have low accuracy; adding automatic segmentation of lateral ventricles and deep gray matter nuclei improves the diagnostic accuracy.

Multi-atlas tool for automated segmentation of brain gray matter nuclei and quantification of their magnetic susceptibility

Quantification of tissue magnetic susceptibility using MRI offers a non-invasive measure of important tissue components in the brain, such as iron and myelin, potentially providing valuable information about normal and pathological conditions during aging. Despite many advances made in recent years on imaging techniques of quantitative susceptibility mapping (QSM), accurate and robust automated segmentation tools for QSM images that can help generate universal and sharable susceptibility measures in a biologically meaningful set of structures are still not widely available. In the present study, we developed an automated process to segment brain nuclei and quantify tissue susceptibility in these regions based on a susceptibility multi-atlas library, consisting of 10 atlases with T1-weighted images, gradient echo (GRE) magnitude images and QSM images of brains with different anatomic patterns. For each atlas in this library, 10 regions of interest in iron-rich deep gray matter structures that are better defined by QSM contrast were manually labeled, including caudate, putamen, globus pallidus internal/external, thalamus, pulvinar, subthalamic nucleus, substantia nigra, red nucleus and dentate nucleus in both left and right hemispheres. We then tested different pipelines using different combinations of contrast channels to bring the set of labels from the multi-atlases to each target brain and compared them with the gold standard manual delineation. The results showed that the segmentation accuracy using dual contrasts QSM/T1 pipeline outperformed other dual-contrast or single-contrast pipelines. The dice values of 0.77 ± 0.09 using the QSM/T1 multi-atlas pipeline rivaled with the segmentation reliability obtained from multiple evaluators with dice values of 0.79 ± 0.07 and gave comparable or superior performance in segmenting subcortical nuclei in comparison with standard FSL FIRST or recent multi-atlas package of volBrain. The segmentation performance of the QSM/T1 multi-atlas was further tested on QSM images acquired using different acquisition protocols and platforms and showed good reliability and reproducibility with average dice of 0.79 ± 0.08 to manual labels and 0.89 ± 0.04 in an inter-protocol manner. The extracted quantitative magnetic susceptibility values in the deep gray matter nuclei also correlated well between different protocols with inter-protocol correlation constants all larger than 0.97. Such reliability and performance was ultimately validated in an external dataset acquired at another study site with consistent susceptibility measures obtained using the QSM/T1 multi-atlas approach in comparison to those using manual delineation. In summary, we designed a susceptibility multi-atlas tool for automated and reliable segmentation of QSM images and for quantification of magnetic susceptibilities. It is publicly available through our cloud-based platform (www.mricloud.org). Further improvement on the performance of this multi-atlas tool is expected by increasing the number of atlases in the future.

Segmented Echo Planar Imaging Improves Detection of Subcortical Functional Connectivity Networks in the Rat Brain

Susceptibility artifacts in the vicinity of aural and nasal cavities result in significant signal drop-out and image distortion in echo planar imaging of the rat brain. These effects may limit the study of resting state functional connectivity in deep brain regions. Here, we explore the use of segmented EPI for resting state fMRI studies in the rat, and assess the relative merits of this method compared to single shot EPI. Sequences were evaluated in terms of signal-to-noise ratio, geometric distortions, data driven detection of resting state networks and group level correlations of time series. Multishot imaging provided improved SNR, temporal SNR and reduced geometric distortion in deep areas, while maintaining acceptable overall image quality in cortical regions. Resting state networks identified by independent component analysis were consistent across methods, but multishot EPI provided a more robust and accurate delineation of connectivity patterns involving deep regions typically affected by susceptibility artifacts. Importantly, segmented EPI showed reduced between-subject variability and stronger statistical significance of pairwise correlations at group level over the whole brain and in particular in subcortical regions. Multishot EPI may represent a valid alternative to snapshot methods in functional connectivity studies, particularly for the investigation of subcortical regions and deep gray matter nuclei.