BACKGROUND:Essential tremor (ET) is the most common movement disorder in the elderly. Despite a close relationship between ET onset and age, it remains unclear whether ET reflects accelerated brain ageing or disease-specific structural changes. This study investigated whether ET is associated with accelerated global brain ageing or altered regional ageing patterns. METHODS:We studied 38 ET patients and 37 matched controls using 3 T structural and diffusion MRI alongside clinical assessments. Brain age and brain age gap (BAG; the difference between chronological and brain age) were estimated by a deep learning model. We analyzed group differences in global brain morphometry, and regional correlations between brain age and volumetric data. Regions demonstrating differential ageing in ET were combined into a composite metric to characterize disease-specific effects. RESULTS:Spatial patterns of brain ageing differed between ET and controls despite no evidence of globally accelerated ageing. In controls, brain age was associated with enlarged ventricles and diffuse cortical thinning, consistent with prototypical ageing. In contrast, ET showed strong negative associations between brain age and volumes specifically in the cerebellar cortex, thalami, and cortical tremor network. A composite metric comprising these regions demonstrated a significant interaction with group and predicted brain age, with ET patients showing volume reduction. CONCLUSIONS:ET is characterized by a distinct, disease-specific pattern of brain ageing rather than accelerated global ageing. This suggests that ET al.ters the spatial distribution of age-related structural changes, preferentially affecting the tremor network, and may help explain ET clinical heterogeneity.

OBJECTIVES The splenial angle (SA), measured on axial DTI colour fractional anisotropy MRI, outperformed the callosal angle (CA) in predicting idiopathic normal pressure hydrocephalus (NPH) patients from those with Alzheimer’s dementia, Parkinson’s disease (PD) and healthy controls (HC). We investigated its reliability and classification performance on more commonly acquired T1 MPRAGE and FLAIR images. METHODS SA was measured on axial MPRAGE and FLAIR images in 57 subjects (19 NPH, PD and HC each) by two raters, and compared across groups. Receiver operating characteristics (ROC) analysis was used to assess its classification performance differentiating NPH from non-NPH groups, in comparison to the CA. RESULTS Inter-rater reliability for SA were excellent (intraclass correlation coefficients ≥0.91). SA was effective in differentiating NPH from non-NPH patients on MPRAGE and FLAIR images (p < 0.001). Its ROC curves showed excellent performance classifying NPH from HC (AUC 1) and PD (AUC >0.93) groups, and were highly comparable to those for CA (1; 0.947). Angles wider than 60° and narrower than 45° robustly (100%) excluded and predicted NPH from HC, respectively. The narrower 45° cutoff yielded better sensitivity (84.2–89.5%) in differentiating NPH from PD patients. CONCLUSIONS The SA on MPRAGE/FLAIR images showed excellent inter-rater reliability and classification performance predicting NPH from non-NPH groups, rivalling those of the CA. ADVANCES IN KNOWLEDGE The SA on MPRAGE and FLAIR images is reproducible and shows excellent diagnostic performance differentiating NPH from non-NPH groups, with potential to replace the CA in NPH screening given its accessibility on routine axial neuroimaging.

OBJECTIVES:The splenial angle (SA), measured on axial DTI colour fractional anisotropy MRI, outperformed the callosal angle (CA) in predicting idiopathic normal pressure hydrocephalus (NPH) patients from those with Alzheimer's dementia, Parkinson's disease (PD), and healthy controls (HC). We investigated its reliability and classification performance on more commonly acquired T1 magnetization-prepared rapid gradient-echo (MPRAGE) and fluid-attenuated inversion-recovery (FLAIR) images. METHODS:Splenial angle was measured on axial MPRAGE and FLAIR images in 57 subjects (19 NPH, PD and HC each) by 2 raters and compared across groups. Receiver operating characteristics (ROC) analysis was used to assess its classification performance, differentiating NPH from non-NPH groups, in comparison to the CA. RESULTS:Inter-rater reliability for SA was excellent (intraclass correlation coefficients ≥ 0.91). Splenial angle was effective in differentiating NPH from non-NPH patients on MPRAGE and FLAIR images (P < .001). Its ROC curves showed excellent performance classifying NPH from HC (Area under the curve [AUC] 1) and PD (AUC > 0.93) groups and were highly comparable to those for CA (1; 0.947). Angles wider than 60° and narrower than 45° robustly (100%) excluded and predicted NPH from HC, respectively. The narrower 45° cutoff yielded better sensitivity (84.2%-89.5%) in differentiating NPH from PD patients. CONCLUSIONS:The SA on MPRAGE/FLAIR images showed excellent inter-rater reliability and classification performance predicting NPH from non-NPH groups, rivalling those of the CA. ADVANCES IN KNOWLEDGE:The SA on MPRAGE and FLAIR images is reproducible and shows excellent diagnostic performance, differentiating NPH from non-NPH groups, with potential to replace the CA in NPH screening given its accessibility on routine axial neuroimaging.

PurposeSusceptibility map weighted imaging (SMWI), based on quantitative susceptibility mapping (QSM), allows accurate nigrosome-1 (N1) evaluation and has been used to develop Parkinson’s disease (PD) deep learning (DL) classification algorithms. Neuromelanin-sensitive (NMS) MRI could improve automated quantitative N1 analysis by revealing neuromelanin content. This study aimed to compare classification performance of four approaches to PD diagnosis: (1) N1 quantitative “QSM-NMS” composite marker, (2) DL model for N1 morphological abnormality using SMWI (“Heuron IPD”), (3) DL model for N1 volume using SMWI (“Heuron NI”), and (4) N1 SMWI neuroradiological evaluation.MethodPD patients (n = 82; aged 65 ± 9 years; 68% male) and healthy-controls (n = 107; 66 ± 7 years; 48% male) underwent 3 T midbrain MRI with T2*-SWI multi-echo-GRE (for QSM and SMWI), and NMS-MRI. AUC was used to compare diagnostic performance. We tested for correlation of each imaging measure with clinical parameters (severity, duration and levodopa dosing) by Spearman-Rho or Kendall-Tao-Beta correlation.ResultsClassification performance was excellent for the QSM-NMS composite marker (AUC = 0.94), N1 SMWI abnormality (AUC = 0.92), N1 SMWI volume (AUC = 0.90), and neuroradiologist (AUC = 0.98). Reasons for misclassification were right–left asymmetry, through-plane re-slicing, pulsation artefacts, and thin N1. In the two DL models, all 18/189 (9.5%) cases misclassified by Heuron IPD were controls with normal N1 volumes. We found significant correlation of the SN QSM-NMS composite measure with levodopa dosing (rho = −0.303, p = 0.006).ConclusionOur data demonstrate excellent performance of a quantitative QSM-NMS marker and automated DL PD classification algorithms based on midbrain MRI, while suggesting potential further improvements. Clinical utility is supported but requires validation in earlier stage PD cohorts.

RATIONALE AND OBJECTIVES:To evaluate the effect of compressed SENSE (CS) in clinical settings on scan time reduction and image quality. MATERIALS AND METHODS:Ninety-five magnetic resonance imaging (MRI) scans from different anatomical regions were acquired, consisting of a standard protocol sequence (SS) and sequence accelerated with CS. Anonymized paired sequences were randomly displayed and rated by six blinded subspecialty radiologists. Side-by-side evaluation on perceived sharpness, perceived signal-to-noise-ratio (SNR), lesion conspicuity, and artifacts were compared and scored on a five-point Likert scale, and individual image quality was evaluated on a four-point Likert scale. RESULTS:CS reduced overall scan time by 32% while maintaining acceptable MRI quality for all regions. The largest time savings were seen in the spine (mean = 68 seconds, 44% reduction) followed by the brain (mean = 86 seconds, 37% reduction). The sequence with maximum time savings was intracranial 3D-time-of-flight magnetic resonance angiography (202 seconds, 56% reduction). CS was mildly inferior to SS on perceived sharpness, perceived SNR, and lesion conspicuity (mean scores = 2.32-2.96, P < .001 [1: SS superior; 3: equivalent; 5: CS superior]). CS was equivalent to SS for joint and body scans on overall image quality (CS = 3.02-3.37, SS = 3.04-3.68, P > .05, [1: lowest quality and 4: highest quality]). The overall image quality of CS was slightly less for brain and spine scans (mean CS = 2.79-3.05, mean SS = 3.13-3.43, P = .021) but still diagnostic. Good overall clinical acceptance for CS (88%) was noted with full clinical acceptance for body scans (100%) and high acceptance for other regions (68%-95%). CONCLUSION:CS significantly reduced MR acquisition time while maintaining acceptable image quality. The implementation of CS may improve departmental workflows and enhance patient care.

Diagnostic Radiography encompasses both theoretical and clinical skills. Diagnostic radiographers are required to undergo stipulated years of education to satisfactorily complete their training curriculum to the required depth and breadth. At the completion of this training, the newly qualified radiographer is expected to be independent, safe and competent in providing quality care to the patients.

BACKGROUND:Diffusion kurtosis imaging provides in vivo measurement of microstructural tissue characteristics and could help guide management of Parkinson's disease. OBJECTIVE:To investigate longitudinal diffusion kurtosis imaging changes on magnetic resonance imaging in the deep grey nuclei in people with early Parkinson's disease over two years, and whether they correlate with disease progression. METHODS:We conducted a longitudinal case-control study of early Parkinson's disease. 262 people (Parkinson's disease: n = 185, aged 67.5±9.1 years; 43% female; healthy controls: n = 77, aged 66.6±8.1 years; 53% female) underwent diffusion kurtosis imaging and clinical assessment at baseline and two-year timepoints. We automatically segmented five nuclei, comparing the mean kurtosis and other diffusion kurtosis imaging indices between groups and over time using repeated-measures analysis of variance, and Pearson correlation with the two-year change in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III. RESULTS:At baseline, mean kurtosis was higher in Parkinson's disease than controls in the substantia nigra, putamen, thalamus and globus pallidus when adjusting for age, sex, and levodopa equivalent daily dose (p < 0.027). These differences grew over two years, with mean kurtosis increasing for the Parkinson's disease group while remaining stable for the control group; evident in significant "group ×time" interaction effects for the putamen, thalamus and globus pallidus (ηp2= 0.08-0.11, p < 0.015). However, we did not detect significant correlations between increasing mean kurtosis and declining motor function in the Parkinson's disease group. CONCLUSION:Diffusion kurtosis imaging of specific grey matter structures shows abnormal microstructure in PD at baseline and abnormal progression in PD over two years.

Background Neuromelanin- and iron-sensitive MRI studies in Parkinson's disease (PD) are limited by small sample sizes and lack detailed clinical correlation. In a large case–control PD cohort, we evaluated the diagnostic accuracy of quantitative iron–neuromelanin MRI parameters from the substantia nigra (SN), their radiological utility, and clinical association. Methods PD patients and age-matched controls were prospectively recruited for motor assessment and midbrain neuromelanin- and iron-sensitive [quantitative susceptibility mapping (QSM) and susceptibility map-weighted imaging (SMWI)] MRI. Quantitative neuromelanin–iron parameters from the SN were assessed for their discriminatory performance in PD classification using ROC analysis compared to those of qualitative visual classification by radiological readers of differential experience and used to predict motor severity. Results In total, 191 subjects (80 PD, mean age 65.0 years; 111 controls, 65.6) were included. SN masks showed (a) higher mean susceptibility ( p < 0.0001) and smaller sizes after thresholding for low susceptibility ( p < 0.0001) on QSM and (b) lower contrast range ( p < 0.0001) and smaller sizes after thresholding for high-signal voxels ( p < 0.0001) on neuromelanin-sensitive MRI in patients than in controls. Quantitative iron and neuromelanin parameters showed a moderate correlation with motor dysfunction (87.5%: 0.4< | r | <0.6, p < 0.0001), respectively. A composite quantitative neuromelanin–iron marker differentiated the groups with excellent performance (AUC 0.94), matching the diagnostic accuracy of the best-performing reader (accuracy 97%) using SMWI. Conclusion Quantitative neuromelanin–iron MRI is associated with PD motor severity and matched best-performing radiological PD classification using SMWI, with the potential to improve diagnostic confidence in the clinics and track disease progression and response to neuroprotective therapies.

We found associations between tract-specific myelin water fraction and cognitive decline, and motor dysfunction in patients with Parkinson’s disease (PD). Myelin water fractions (MWF) in the anterior corona radiata and posterior thalamic radiations were associated with cognitive decline in PD whilst those in the superior and posterior corona radiata, posterior limb of internal capsule and corticospinal tract were associated with moderate to severe motor dysfunction in PD. Our results suggest that MWF has potential utility as an objective imaging biomarker to monitor longitudinal changes in target WM tracts relevant to motor and cognitive dysfunction in PD neurodegeneration.

Parkinson’s disease (PD) is a common neurodegenerative disease. Besides motor deficits, autonomic and cognitive dysfunctions might be caused by global abnormalities beyond the dopaminergic system. We performed resting-state fMRI to measure functional connectivity between the central autonomic network and eight other critical resting networks in both early PD and healthy control groups. Using general linear models, we identified functional impairments in the inter- and intra-network connections in relation to various brain functions. These findings could shed light on the neural mechanisms behind the complex clinical manifestations evident even in the early stages of PD.

Background: Neurofilament light is a marker of axonal degeneration, whose measurement from peripheral blood was recently made possible by new assays. Objective: We aimed to determine whether plasma neurofilament light chain (NfL) concentration reflects brain white matter integrity in patients with early Parkinson's disease (PD). Methods: 137 early PD patients and 51 healthy controls were included. Plasma NfL levels were measured using ultrasensitive single molecule array. 3T MRI including diffusion tensor imaging was acquired for voxelwise analysis of association between NfL and both fractional anisotropy (FA) and mean diffusivity (MD) in white matter tracts and subcortical nuclei. Results: A pattern of brain microstructural changes consistent with neurodegeneration was associated with increased plasma NfL in most of the frontal lobe and right internal capsule, with decreased FA and increased MD. The same clusters were also associated with poorer global cognition. A significant cluster in the left putamen was associated with increased NfL, with a significantly greater effect in PD than controls. Conclusion: Plasma NfL may be associated with brain microstructure, as measured using diffusion tensor imaging, in patients with early PD. Higher plasma NfL was associated with a frontal pattern of neurodegeneration that also correlates with cognitive performance in our cohort. This may support a future role for plasma NfL as an accessible biomarker for neurodegeneration and cognitive dysfunction in PD.

Synopsis:Developments in Magnetic Resonance Imaging (MRI) techniques offers opportunities to visualize in vivo substantia nigra pathology in Idiopathic Parkinson's disease (IPD). Nigrosome abnormalities are studied using susceptibility map-weighted imaging (SMWI). Nigrosome abnormalities have been demonstrated in IPD patients, raising the possibility of using it as an imaging marker of disease progression. Synopsis: Developments in Magnetic Resonance Imaging (MRI) techniques offers opportunities to visualize in vivo substantia nigra pathology in Idiopathic Parkinson's disease (IPD). Nigrosome abnormalities are studied using susceptibility map-weighted imaging (SMWI). Nigrosome abnormalities have been demonstrated in IPD patients, raising the possibility of using it as an imaging marker of disease progression.

OBJECTIVES:To evaluate the utility of the splenial angle (SA), an axial angular index of lateral ventriculomegaly measured on diffusion tensor MRI color fractional anisotropy maps, in differentiating NPH from Alzheimer's disease (AD), Parkinson's disease (PD), and healthy controls (HC), and post-shunt changes in NPH, compared to Evans' index and callosal angle. METHODS:Evans' index, callosal angle, and SA were measured on brain MRI of 76 subjects comprising equal numbers of age- and sex-matched subjects from each cohort of NPH, AD, PD, and HC by two raters. Receiver operating characteristics (ROC) and multivariable analysis were used to assess the screening performance of each measure in differentiating and predicting NPH from non-NPH groups respectively. Temporal changes in the measures on 1-year follow-up MRI in 11 NPH patients (with or without ventriculoperitoneal shunting) were also assessed. RESULTS:Inter-rater and intra-rater reliability were excellent for all measurements (intraclass correlation coefficients > 0.9). Pairwise comparison showed that SA was statistically different between NPH and AD/PD/HC subjects (p < 0.0001). SA performed the best in predicting NPH, with an area under the ROC curve of > 0.98, and was the only measure left in the final model of the multivariable analysis. Significant (p < 0.01) change in SA was seen at follow-up MRI of NPH patients who were shunted compared to those who were not. CONCLUSIONS:The SA is readily measured on axial DTI color FA maps compared to the callosal angle and shows superior performance differentiating NPH from neurodegenerative disorders and sensitivity to ventricular changes in NPH after surgical intervention. KEY POINTS:• The splenial angle is a novel simple angular radiological index proposed for idiopathic normal pressure hydrocephalus, measured in the ubiquitous axial plane on DTI color fractional anisotropy maps. • The splenial angle quantitates the compression and stretching of the posterior callosal commissural fibers alongside the distended lateral ventricles in idiopathic normal pressure hydrocephalus (NPH) using tools readily accessible in clinical practice and shows excellent test-retest reliability. • Splenial angle outperforms Evans' index and callosal angle in predicting NPH from healthy, Parkinson's disease, and Alzheimer's disease subjects on ROC analysis with an area under the curve of > 0.98 and is sensitive to morphological ventricular changes in NPH patients after ventricular shunting.

The callosal angle (CA) is a useful biomarker in the diagnosis and management of idiopathic normal pressure hydrocephalus (NPH). Used incorrectly, CA measurements are variable, affecting its reliability as a clinical tool. Our objectives are to evaluate (i) reproducibility of established CA measurements between trained raters and (ii) impact of minor angular mal-rotations of the true coronal plane on CA measurements. CAs were measured by two independent raters on three-dimensional isovolumetric T1-weighted brain MRI of NPH patients and healthy controls using the established true coronal plane reformatted orthogonal to the plane containing the anterior-posterior commissural (AC-PC) line at the level of the posterior commissure. CA changes were subsequently evaluated when the coronal plane was mal-rotated by ± 5° and ± 10° in anterior-posterior and clockwise-anticlockwise directions. Inter-rater reliability of CA measurements was assessed using the intraclass correlation coefficient (ICC). On the true coronal plane, inter-rater ICC was excellent (0.973) for NPH patients and good (0.875) for controls. On mal-rotated coronal plane setups, ICC for CA was worse in controls (0.484–0.886) than NPH (0.879–0.981) groups and in clockwise-anticlockwise (0.484–0.956) than anterior-posterior (0.503–0.981) mal-rotations. CA changes secondary to mal-rotations from the true coronal plane were significant in NPH patients (P < 0.0001 to 0.0378) but not in controls (P > 0.1). This is the first demonstration of how small angular mal-rotations of the coronal plane used for CA measurement affect its value and inter-rater reliability, highlighting the importance of a standardized protocol when measuring the CA in NPH workup.

[This corrects the article DOI: 10.3389/fnins.2019.01334.].

Background and objectives: It is estimated that 60 million magnetic resonance imaging (MRI) scans are performed annually around the world. Of these, 25% of patients experienced moderate to severe claustrophobia during the procedure. The aim of this study was to determine the prevalence and interethnic variations of patients requiring sedation due to claustrophobia. Another aim was to determine if a wider bore MR scanner was helpful in reducing the incidence of claustrophobia. Methodology: This was an institutional review board-approved study. We retrieved records for 11,813 adult outpatients from the hospital radiological system from 1 January 2012 to 31 December 2012. The data collected included patients’ gender, age, ethnicity, body region scanned, body orientation with respect to the scanner, the types of scanners used, and the need for sedation. Statistical analysis was performed using R 3.0.1. Results: The prevalence of claustrophobic patients requiring sedation was 0.45%, i.e. 53. Of these, 55% were females and 45% males. Among these, 64% were Chinese, 15% Malays, 15% Indians, and 6% were other races. 74% experienced claustrophobia at the 60 cm-wide bore scanners and 26% at 70 cm-wider bore scanners. Referring to Chinese, multivariable regression showed Malays and the Indians were six times and other ethnic groups were 12 times more likely to develop claustrophobia. The incidence of claustrophobia could be reduced by a factor of 2.95 with wider bore scanners. Conclusions: The MR environment is still disturbing to some patients. Feet-in positioning does not significantly minimize claustrophobia. Gender and age had no bearing on claustrophobia. Wider bore MR scanners with a bore size of 70 cm are an obvious choice toward more patient-friendly MR scanners.

The rare variant A673T in the amyloid-β precursor protein (APP) gene has been shown to reduce the risk of cognitive impairment. We genotyped the variant in 8721 Asian individuals comprising 552 with Alzheimer's disease and vascular dementia, 790 with Parkinson's disease, and 7379 controls. The A673T variant was absent in all of the subjects. Our finding suggests that the A673T protective variant is not relevant in our Asian population. Studies in other ethnic populations would clarify whether this variant is specific to specific races/ethnicities.

Neuropsychiatry is an emerging field at the intersection of neurology and psychiatry, driven by the unprecedented advances in neuroscience. The arbitrary demarcation between neurology and psychiatry, which largely existed only in the last century and a half, has become less tenable. We discuss the definition and scope of this emerging field. We also review the development of clinical neuropsychiatry in Singapore in the context of historical developments and recent changes in the field from other countries. At a more practical level, we discuss a few of the clinical settings in which neuropsychiatry operates, in particular, the stigma associated with psychiatric disorders locally, and the significant number of patients with psychiatric or psychosomatic symptoms presenting to neurology and general practice clinics. The stigma may be ameliorated by better understanding of the neurobiological basis of psychiatry. We see the future of neuropsychiatry in Singapore, as in other developed countries, as one approach to understand and manage complex brain disorders. We advocate training for both psychiatry and neurology residents in their counterpart fields, which will lead to greater understanding of both fields, and enhance collaboration in clinical care and research.

This study aimed to demonstrate that afebrile seizures provoked by minor infections constitute a distinct epilepsy syndrome different from febrile seizures and unprovoked afebrile seizures. Of the children who were admitted to hospitals for their first seizure, 1170 had febrile seizures, 286 had provoked seizures, and 125 had unprovoked afebrile seizures. Children with provoked seizures were afebrile at the time of seizure but manifested definite symptoms or signs of minor infection, for example, cough, coryza, vomiting or diarrhea, normal metabolic and cerebrospinal fluid investigations, and no obvious cause for their seizures. The average follow-up was 6.1 years. The Kaplan-Meier estimate of risk at 5 years for subsequent unprovoked afebrile seizures after a first febrile seizure, provoked seizure, or unprovoked afebrile seizure was 1.6%, 5.7%, and 65.7% respectively. All differences were statistically significant (P < 0.0014). In conclusion, afebrile seizures provoked by minor illnesses constitute a distinct type of situation-related seizures, which have not been previously described. Children with provoked seizures have a much lower risk of subsequent unprovoked afebrile seizures than patients with the first afebrile seizure. Careful inquiry for symptoms of minor infections when children present with their first afebrile seizure will help determine the risk for subsequent seizures and the need for antiepileptic drugs.