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Transcranial direct current stimulation (tDCS) is a widely used non-invasive brain stimulation technique by applying low-frequency weak direct current via electrodes attached on the head. The tDCS using a fixed current between 1 and 2 mA has relied on computational modelings to achieve optimal stimulation effects. Recently, by measuring the tDCS current induced magnetic field using an MRI scanner, the internal current pathway has been successfully recovered. However, up to now, there is no technique to visualize electrical properties including the electrical anisotropic conductivity, effective extracellular ion-concentration, and electric field using only the tDCS current in-vivo. By measuring the apparent diffusion coefficient (ADC) and the magnetic flux density induced by the tDCS, we propose a method to visualize the electrical properties. We reconstruct the scale parameter, which connects the anisotropic conductivity tensor to the diffusion tensor of water molecules, by introducing a repetitive scheme called the diffusion tensor J-substitution algorithm using the recovered current density and the measured ADCs. We investigate the proposed method to explain why the iterative scheme converges to the internal conductivity. We verified the proposed method with an anesthetized canine brain to visualize electrical properties including the electrical properties by tDCS current. [ABSTRACT FROM AUTHOR]

Objectives: Apparent diffusion coefficient (ADC) has been suggested to reflect the tumor grades of hepatocellular carcinomas (HCCs); i.e., it can be used as a biomarker to predict the patients’ prognosis. To verify its feasibility as a biomarker, the present study sought to determine how the ADC values of HCC are affected by a tumor’s histopathologic grade and arterial vascularity. Materials and methods: From 131 consecutive patients, 141 surgically resected HCCs (16 well-differentiated [wd-HCCs], 83 moderately-differentiated [md-HCCs], and 42 poorly-differentiated HCCs [pd-HCCs]) were subjected to a comparison of the tumors’ arterial vascularity (non-, slightly-, or markedly-hypervascular) determined on dynamic magnetic resonance imaging (MRI) and the ADC was measured retrospectively. Results: The pd-HCCs (1.05±0.16 × 10−3 mm2/s) had a significantly lower ADC than md-HCCs (1.16±0.21 × 10−3 mm2/s; p = 0.010), but there was no significant difference compared to wd-HCCs (1.11±0.18 × 10−3 mm2/s; p = 0.968). The mean ADC was significantly higher in markedly hypervascular lesions (1.20±0.20 × 10−3 mm2/s) than in nonhypervascular lesions (0.95±0.14 × 10−3mm2/s; p<0.001) or slightly hypervascular lesions (1.04±0.15 × 10−3mm2/s; p<0.001). The ADC values and arterial vascularity were significantly correlated in wd-HCCs (p = 0.005) and md-HCCs (p<0.001). The mean ADC of pd-HCCs was significantly lower than those of other lesions, even in the markedly hypervascular lesion subgroup (p = 0.020). Conclusion: Although pd-HCC constantly shows low ADCs regardless of arterial vascularities, ADCs cannot stably stratify histopathologic tumor grades due to the variable features of wd-HCCs; and the ADC should be used with caution as a tumor biomarker of HCC. [ABSTRACT FROM AUTHOR]

Purpose: Peritumoral edema impedes the full delineation of fiber tracts due to partial volume effects in image voxels that contain a mixture of cerebral parenchyma and extracellular water. The purpose of this study is to investigate the effect of incorporating a free water (FW) model of edema for white matter tractography in the presence of edema. Materials and methods: We retrospectively evaluated 26 consecutive brain tumor patients with diffusion MRI and T2-weighted images acquired presurgically. Tractography of the arcuate fasciculus (AF) was performed using the two-tensor unscented Kalman filter tractography (UKFt) method, the UKFt method with a reduced fiber tracking stopping fractional anisotropy (FA) threshold (UKFt+rFA), and the UKFt method with the addition of a FW compartment (UKFt+FW). An automated white matter fiber tract identification approach was applied to delineate the AF. Quantitative measurements included tract volume, edema volume, and mean FW fraction. Visual comparisons were performed by three experts to evaluate the quality of the detected AF tracts. Results: The AF volume in edematous brain hemispheres was significantly larger using the UKFt+FW method (p<0.0001) compared to UKFt, but not significantly larger (p = 0.0996) in hemispheres without edema. The AF size increase depended on the volume of edema: a significant correlation was found between AF volume affected by (intersecting) edema and AF volume change with the FW model (Pearson r = 0.806, p<0.0001). The mean FW fraction was significantly larger in tracts intersecting edema (p = 0.0271). Compared to the UKFt+rFA method, there was a significant increase of the volume of the AF tract that intersected the edema using the UKFt+FW method, while the whole AF volumes were similar. Expert judgment results, based on the five patients with the smallest AF volumes, indicated that the expert readers generally preferred the AF tract obtained by using the FW model, according to their anatomical knowledge and considering the potential influence of the final results on the surgical route. Conclusion: Our results indicate that incorporating biophysical models of edema can increase the sensitivity of tractography in regions of peritumoral edema, allowing better tract visualization in patients with high grade gliomas and metastases. [ABSTRACT FROM AUTHOR]

Introduction: Diffusion Tensor MRI (DT-MRI) is a promising tool for the evaluation of brachial plexus pathology. Therefore, we introduce and evaluate a fast DT-MRI protocol (8min33s scanning with 5–10 min postprocessing time) for the brachial plexus. Materials and methods: Thirty healthy volunteers within three age-groups (18–35, 36–55, and > 56) received DT-MRI of the brachial-plexus twice. Means of fractional-anisotropy (FA), mean-diffusivity (MD), axial-diffusivity (AD), and radial-diffusivity (RD) for the individual roots and trunks were evaluated. A stepwise forward approach was applied to test for correlations with age, sex, body-mass-index (BMI), bodysurface, height, and bodyweight. Within-subject, intra-rater, and inter-rater repeatability were assessed using Bland-Altman analysis, coefficient of variation (CV), intraclass-correlation (ICC), and minimal detectable difference (MDD). Results: No differences between sides and root levels were found. MD, AD, and RD correlated (P < 0.05) with bodyweight. Within-subject quantification proved repeatable with CVs for FA, MD, AD, and RD of 16%, 12%, 11%, and 14%, respectively. Discussion: The DT-MRI protocol was fast and repeatable. Found correlations should be considered in future studies of brachial plexus pathology. [ABSTRACT FROM AUTHOR]

Background: Developing more effective strategies to prevent relapse remains one of the major challenges of treating substance dependence. Previous studies have identified brain abnormalities in abstinent alcoholics. However, whether these persistent brain deficits in abstinence could predict early relapse to alcohol use has not been well established. This study aimed to identify biomarkers of relapse vulnerability by investigating persistent brain abnormalities in abstinent alcohol-dependent patients. Methods: Brain imaging and impulsive behavior data were collected from 56 abstinent alcohol-dependent male inpatients and 33 age-matched male healthy controls. Voxel-based morphometry was used to investigate the differences of grey matter volume between the groups. The resting-state functional connectivity was examined using brain areas with gray matter deficits as seed regions. A preliminary prospective study design was used to classify patients into abstainers and relapsers after a 62-day average abstinence period. Results: Compared with healthy controls, both relapsers and abstainers exhibited significantly reduced gray matter volume in the cuneus. Functional connectivity analysis revealed that relapsers relative to abstainers demonstrated increased cuneus-centered negative functional connectivity within a network of brain regions which are involved in executive control and salience. Abnormal gray matter volume in the left cuneus and the functional connectivity between the right cuneus and bilateral dorsolateral prefrontal cortex could successfully predict relapse during the 3-month follow-up period. Conclusions: Findings suggest that the abnormal gray matter volume in the cuneus and resting-state cuneus-prefrontal functional connectivity may play an important role in poor treatment outcomes in alcoholics and serve as useful neural markers of relapse vulnerability. [ABSTRACT FROM AUTHOR]

Diffusion kurtosis imaging (DKI) is a new promising MRI technique with microstructural sensitivity superior to conventional diffusion tensor (DTI) based methods. In stroke, considerable mismatch exists between the infarct lesion outline obtained from the two methods, kurtosis and diffusion tensor derived metrics. We aim to investigate if this mismatch can be examined in fixed tissue. Our investigation is based on estimates of mean diffusivity (MD) and mean (of the) kurtosis tensor (MKT) obtained using recent fast DKI methods requiring only 19 images. At 24 hours post stroke, rat brains were fixed and prepared. The infarct was clearly visible in both MD and MKT maps. The MKT lesion volume was roughly 31% larger than the MD lesion volume. Subsequent histological analysis (hematoxylin) revealed similar lesion volumes to MD. Our study shows that structural components underlying the MD/MKT mismatch can be investigated in fixed tissue and therefore allows a more direct comparison between lesion volumes from MRI and histology. Additionally, the larger MKT infarct lesion indicates that MKT do provide increased sensitivity to microstructural changes in the lesion area compared to MD. [ABSTRACT FROM AUTHOR]

Over the past several years, significant efforts have been made to improve the spatial resolution of diffusion-weighted imaging (DWI), aiming at better detecting subtle lesions and more reliably resolving white-matter fiber tracts. A major concern with high-resolution DWI is the limited signal-to-noise ratio (SNR), which may significantly offset the advantages of high spatial resolution. Although the SNR of DWI data can be improved by denoising in post-processing, existing denoising procedures may potentially reduce the anatomic resolvability of high-resolution imaging data. Additionally, non-Gaussian noise induced signal bias in low-SNR DWI data may not always be corrected with existing denoising approaches. Here we report an improved denoising procedure, termed diffusion-matched principal component analysis (DM-PCA), which comprises 1) identifying a group of (not necessarily neighboring) voxels that demonstrate very similar magnitude signal variation patterns along the diffusion dimension, 2) correcting low-frequency phase variations in complex-valued DWI data, 3) performing PCA along the diffusion dimension for real- and imaginary-components (in two separate channels) of phase-corrected DWI voxels with matched diffusion properties, 4) suppressing the noisy PCA components in real- and imaginary-components, separately, of phase-corrected DWI data, and 5) combining real- and imaginary-components of denoised DWI data. Our data show that the new two-channel (i.e., for real- and imaginary-components) DM-PCA denoising procedure performs reliably without noticeably compromising anatomic resolvability. Non-Gaussian noise induced signal bias could also be reduced with the new denoising method. The DM-PCA based denoising procedure should prove highly valuable for high-resolution DWI studies in research and clinical uses. [ABSTRACT FROM AUTHOR]

Background: Diffusion tensor imaging (DTI) has been suggested as a potential biomarker of disease progression, neurodegeneration and de/remyelination in MS. However, the pathological substrates that underpin alterations in brain diffusivity are not yet fully delineated. We propose that in highly cohesive fiber tracts: 1) a relative increase in parallel (axial) diffusivity (AD) may serve as a measure of increased extra-cellular space (ESC) within the core of chronic MS lesions and, as a result, may provide an estimate of the degree of tissue destruction, and 2) the contribution of the increased extra-cellular water to perpendicular (radial) diffusivity (RD) can be eliminated to provide a more accurate assessment of membranal (myelin) loss. Objective: The purpose of this study was to isolate the contribution of extra-cellular water and demyelination to observed DTI indices in the core of chronic MS lesions, using the OR as an anatomically cohesive tract. Method: Pre- and post-gadolinium (Gd) enhanced T1, T2 and DTI images were acquired from 75 consecutive RRMS patients. In addition, 25 age and gender matched normal controls were imaged using an identical MRI protocol (excluding Gd). The optic radiation (OR) was identified in individual patients using probabilistic tractography. The T2 lesions were segmented and intersected with the OR. Average eigenvalues were calculated within the core of OR lesions mask. The proportion of extra-cellular space (ECS) within the lesional core was calculated based on relative increase of AD, which was then used to normalise the perpendicular eigenvalues to eliminate the effect of the expanded ECS. In addition, modelling was implemented to simulate potential effect of various factors on lesional anisotropy. Results: Of 75 patients, 41 (55%) demonstrated sizable T2 lesion volume within the ORs. All lesional eigenvalues were significantly higher compared to NAWM and controls. There was a strong correlation between AD and RD within the core of OR lesions, which was, however, not seen in OR NAWM of MS patients or normal controls. In addition, lesional anisotropy (FA) was predominantly driven by the perpendicular diffusivity, while in NAWM and in OR of normal controls all eigenvectors contributed to variation in FA. Estimated volume of ECS component constituted significant proportion of OR lesional volume and correlated significantly with lesional T1 hypointensity. While perpendicular diffusivity dropped significantly following normalisation, it still remained higher compared with diffusivity in OR NAWM. The “residual” perpendicular diffusivity also showed a substantial reduction of inter-subject variability. Both observed and modelled diffusion data suggested anisotropic nature of water diffusion in ESC. In addition, the simulation procedure offered a possible explanation for the discrepancy in relationship between eigenvalues and anisotropy in lesional tissue and NAWM. Conclusion: This paper presents a potential technique for more reliably quantifying the effects of neurodegeneration (tissue loss) versus demyelination in OR MS lesions. This may provide a simple and effective way for applying single tract diffusion analysis in MS clinical trials, with particular relevance to pro-remyelinating and neuroprotective therapeutics. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that structural brain abnormalities may play a role in the pathophysiology of melancholic depression. We set out to test whether diffusion-derived estimates of white matter structure were disrupted in melancholia in regions underpinning psychomotor function. We hypothesized that those with melancholia (and evidencing impaired psychomotor function) would show disrupted white matter organization in internal capsule subdivisions. Diffusion magnetic resonance imaging (dMRI) data were acquired from 22 melancholic depressed, 23 non-melancholic depressed, and 29 healthy control participants. Voxel-wise fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) values were derived for anterior, posterior, and retrolenticular limbs of the internal capsule and compared between groups. Neuropsychological (reaction time) and psychomotor functioning were assessed and correlated against FA. Fractional anisotropy was distinctly increased, whilst RD was decreased, in the right anterior internal capsule in those with melancholia, compared to controls. The right anterior limb of the internal capsule correlated with clinical ratings of psychomotor disturbance, and reduced psychomotor speed was associated with increased FA values in the right retrolenticular limb in those with melancholia. Our findings highlight a distinct disturbance in the local white matter arrangement in specific regions of the internal capsule in melancholia, which in turn is associated with psychomotor dysfunction. This study clarifies the contribution of structural brain integrity to the phenomenology of melancholia, and may assist future efforts seeking to integrate neurobiological markers into depression subtyping. [ABSTRACT FROM AUTHOR]

The aim of the present study is to differentiate subtypes of hippocampal sclerosis (HS) using ex vivo ultra-high field magnetic resonance imaging (MRI). Included were 14 surgically resected hippocampi of patients with medically intractable temporal lobe epilepsy. The resected hippocampi were histologically categorized into subtypes of hippocampal sclerosis (HS type 1 (n = 10), HS type 2 (n = 2) and no-HS (n = 2)) and subsequently scanned on a preclinical 7T MRI acquiring T2-weighted morphology, relaxometry and diffusion tensor imaging. On the morphological images, the pyramidal cell layer (PCL) of the hippocampus was segmented and the following parameters were derived: T2 signal intensity, T1-, T2- and T2*-relaxation times, apparent diffusion coefficient (ADC), fractional anisotropy (FA) and mean diffusivity (MD). Furthermore, the area of the PCL was determined, as well as the parameter product which refers to the widths of the PCL parallel and perpendicular to the stratum moleculare. Spearman correlation coefficient was used to demonstrate relationships between MR-parameters and type of sclerosis. In comparison to no-HS specimens, the PCL was significantly narrower in HS type 1 and HS type 2 hippocampi. This narrowing affected the entire cornu ammonis sector (CA) 1 in HS type 1, while it was limited to the upper half of CA1 in direction to CA2 in HS type 2. The parameter product median increased from 0.43 to 1.67 and 2.91 mm2 for HS type 1, HS type 2 and no-HS, respectively. Correlation coefficients were significant for the PCL parameters product (0.73), area (0.71), T2*-time (-0.67), FA (0.65) and ADC (0.55). Our initial results suggest that HS type 1, HS type 2 and no-HS subtypes can be distinguished from each other using ex vivo UHF MRI based on T2-weighted morphologic images and the assessment of the parameter product. Upon clinical translation, UHF-MRI may provide a promising technique for the preoperative differentiation of HS subtypes in patients. [ABSTRACT FROM AUTHOR]

Background: Patients with mild degenerative cervical myelopathy (DCM) are often managed non-operatively, and surgery is recommended if neurological progression occurs. However, detection of progression is often subjective. Quantitative MRI (qMRI) directly measures spinal cord (SC) tissue changes, detecting axonal injury, demyelination, and atrophy. This longitudinal study compared multiparametric qMRI with clinical measures of progression in non-operative DCM patients. Methods: 26 DCM patients were followed. Clinical data included modified Japanese Orthopedic Association (mJOA) and additional assessments. 3T qMRI data included cross sectional area, diffusion fractional anisotropy, magnetization transfer ratio, and T2*-weighted white/grey matter signal ratio, extracted from the compressed SC and above/below. Progression was defined as 1) patients’ subjective impression, 2) 2-point mJOA decrease, 3) ≥3 clinical measures worsening ≥5%, 4) increased compression on MRI, or 5) ≥1 of 10 qMRI measures or composite score worsening (p < 0.004, corrected). Results: Follow-up (13.5 ± 4.9 months) included mJOA in all 26 patients, MRI in 25, and clinical/qMRI in 22. 42.3% reported subjective worsening, compared with mJOA (11.5%), MRI (20%), comprehensive assessments (54.6%), and qMRI (68.2%). Relative to subjective worsening, qMRI showed 100% sensitivity and 53.3% specificity compared with comprehensive assessments (75%, 60%), mJOA (27.3%, 100%), and MRI (18.2%, 81.3%). A decision-making algorithm incorporating qMRI identified progression and recommended surgery for 11 subjects (42.3%). Conclusions: Quantitative MRI shows high sensitivity to detect myelopathic progression. Our results suggest that neuroplasticity and behavioural adaptation may mask progressive SC tissue injury. qMRI appears to be a useful method to confirm subtle myelopathic progression in individual patients, representing an advance toward clinical translation of qMRI. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the predictive factors for lateral pelvic lymph node (LPLN) metastasis in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy (CRT). Materials and methods: Fifty-seven patients with locally advanced rectal cancer and LPLNs larger than 5 mm underwent LPLN dissection (LPLD) after preoperative CRT. The MRI findings, including the apparent diffusion coefficient value and LPLN size reduction rate before/after CRT; clinical factors; and pathologic results were evaluated to identify the predictive factors associated with LPLN metastasis. Results: LPLN metastasis was confirmed in 23 patients (40.4%). Metastasis was significantly higher in LPLNs with multiplicity, short-axis diameter ≥8 mm before CRT, short-axis diameter >5 mm after CRT, size reduction rate ≤33.3%, heterogeneous signal intensity, and irregular margin (P<0.05) on MR. Multivariable analysis showed that pre-CRT short-axis diameter of LPLNs ≥8 mm, size reduction rate ≤33.3%, and heterogeneous signal intensity were independently associated with LPLN metastasis. Conclusions: The size and signal intensity of LPLN before and after CRT are useful MRI findings to predict LPLN metastasis and are helpful to determine the indications for LPLD. [ABSTRACT FROM AUTHOR]

Object conceptual processing has been localized to distributed cortical regions that represent specific attributes. A challenging question is how object semantic space is formed. We tested a novel framework of representing semantic space in the pattern of white matter (WM) connections by extending the representational similarity analysis (RSA) to structural lesion pattern and behavioral data in 80 brain-damaged patients. For each WM connection, a neural representational dissimilarity matrix (RDM) was computed by first building machine-learning models with the voxel-wise WM lesion patterns as features to predict naming performance of a particular item and then computing the correlation between the predicted naming score and the actual naming score of another item in the testing patients. This correlation was used to build the neural RDM based on the assumption that if the connection pattern contains certain aspects of information shared by the naming processes of these two items, models trained with one item should also predict naming accuracy of the other. Correlating the neural RDM with various cognitive RDMs revealed that neural patterns in several WM connections that connect left occipital/middle temporal regions and anterior temporal regions associated with the object semantic space. Such associations were not attributable to modality-specific attributes (shape, manipulation, color, and motion), to peripheral picture-naming processes (picture visual similarity, phonological similarity), to broad semantic categories, or to the properties of the cortical regions that they connected, which tended to represent multiple modality-specific attributes. That is, the semantic space could be represented through WM connection patterns across cortical regions representing modality-specific attributes. [ABSTRACT FROM AUTHOR]

Background and purpose: T2*-weighted magnetic resonance angiography (SWAN) detects hemodynamic insufficiency as hypointense areas in medullary or cortical veins. We therefore investigated whether SWAN can help predict ischemic penumbra-like lesions in patients with acute ischemic stroke (AIS). Materials and methods: Magnetic resonance imaging (MRI) records—including SWAN, diffusion-weighted imaging (DWI), and magnetic resonance angiography (MRA)—of consecutive patients with major vessel occlusion within 6 h from AIS onset were analyzed. Acute recanalization was defined as an arterial occlusive lesion score of 2–3. A modified Alberta Stroke Program Early CT Score (mASPECTS) was used to evaluate ischemic areas revealed by SWAN and DWI. SWAN- and DWI-based mASPECTSs were calculated, and correlations between DWI-SWAN mismatches with final infarct lesions or clinical outcomes were evaluated. Results: Among the 35 patients included in this study, we confirmed cardioembolic stroke in 26, atherothrombotic stroke in 4, and unknown stroke etiology in 5. Overall, recanalization was achieved in 23 patients, who showed a higher follow-up DWI-based mASPECTS and lower modified Rankin Scale (mRS) score at 90 days than patients without recanalization. Initial SWAN- and follow-up DWI-based mASPECTSs were significantly higher for atherothrombotic stroke than for cardioembolic stroke. Of 12 patients without recanalization, DWI-SWAN mismatch was significantly correlated with infarct growth. Patients with recanalization showed no such correlation. In the assessment of clinical outcome, follow-up DWI-based mASPECTS and patient's age were significantly correlated with mRS at 90 days after stroke. A multivariate logistic regression analysis revealed that the follow-up DWI-based mASPECTS was independently associated with a favorable outcome 90 days after stroke. Conclusions: For patients with AIS, DWI-SWAN mismatch might show penumbra-like lesions that would predict infarct growth without acute recanalization. Assessment of ischemic lesions from the venous side appears to be useful for considering the etiology and revascularization therapy. [ABSTRACT FROM AUTHOR]

The intravoxel incoherent motion (IVIM) model for diffusion-weighted imaging (DWI) MRI data bears much promise as a tool for visualizing tumours and monitoring treatment response. To improve the currently poor precision of IVIM, several fit algorithms have been suggested. In this work, we compared the performance of two Bayesian IVIM fit algorithms and four other IVIM fit algorithms for pancreatic cancer imaging. DWI data were acquired in 14 pancreatic cancer patients during two MRI examinations. Three different measures of performance of the fitting algorithms were assessed: (i) uniqueness of fit parameters (Spearman’s rho); (ii) precision (within-subject coefficient of variation, wCV); and (iii) contrast between tumour and normal-appearing pancreatic tissue. For the diffusivity D and perfusion fraction f, a Bayesian fit (IVIM-Bayesian-lin) offered the best trade-off between tumour contrast and precision. With the exception for IVIM-Bayesian-lin, all algorithms resulted in a very poor precision of the pseudo-diffusion coefficient D* with a wCV of more than 50%. The pseudo-diffusion coefficient D* of the Bayesian approaches were, however, significantly correlated with D and f. Therefore, the added value of fitting D* was considered limited in pancreatic cancer patients. The easier implemented least squares fit with fixed D* (IVIM-fixed) performed similar to IVIM-Bayesian-lin for f and D. In conclusion, the best performing IVIM fit algorithm was IVM-Bayesian-lin, but an easier to implement least squares fit with fixed D* performs similarly in pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Several publications have reported structural changes in the brain of synesthetes compared to controls, either local differences or differences in connectivity. In the present study, we pursued this quest for structural brain differences that might support the subjective experience of synesthesia. In particular, for the first time in this field, we investigated brain folding in comparing 45 sulcal shapes in each hemisphere of control and grapheme-color synesthete populations. To overcome flaws relative to data interpretation based only on p-values, common in the synesthesia literature, we report confidence intervals of effect sizes. Moreover, our statistical maps are displayed without introducing the classical, but misleading, p-value level threshold. We adopt such a methodological procedure to facilitate appropriate data interpretation and promote the “New Statistics” approach. Based on structural or diffusion magnetic resonance imaging data, we did not find any strong cerebral anomaly, in sulci, tissue volume, tissue density or fiber organization that could support synesthetic color experience. Finally, by sharing our complete datasets, we strongly support the multi-center construction of a sufficient large dataset repository for detecting, if any, subtle brain differences that may help understanding how a subjective experience, such as synesthesia, is mentally constructed. [ABSTRACT FROM AUTHOR]

Background: After the emergence of new MRI techniques such as susceptibility- and diffusion-weighted imaging (SWI and DWI) and because of specific imaging characteristics of melanoma brain metastases (MBM), it is unclear which MRI sequences are most beneficial for detection of MBM. This study was performed to investigate the sensitivity of six clinical MRI sequences in the early detection of MBM. Methods: Medical records of all melanoma patients referred to our center between November 2005 and December 2016 were reviewed for presence of MBM. Analysis encompassed six MRI sequences at the time of initial diagnosis of first or new MBM, including non-enhanced T1-weighted (T1w), contrast-enhanced T1w (ceT1w), T2-weighted (T2w), T2w-FLAIR, susceptibility-weighted (SWI) and diffusion-weighted (DWI) MRI. Each lesion was rated with respect to its conspicuity (score from 0—not detectable to 3—clearly visible). Results: Of 1210 patients, 217 with MBM were included in the analysis and up to 5 lesions per patient were evaluated. A total of 720 metastases were assessed and all six sequences were available for 425 MBM. Sensitivity (conspicuity ≥2) was 99.7% for ceT1w, 77.0% for FLAIR, 64.7% for SWI, 61.0% for T2w, 56.7% for T1w, and 48.4% for DWI. Thirty-one (7.3%) of 425 lesions were only detectable by ceT1w but no other sequence. Conclusions: Contrast-enhanced T1-weighting is more sensitive than all other sequences for detection of MBM. Disruption of the blood-brain-barrier is consistently an earlier sign in MBM than perifocal edema, signal loss on SWI or diffusion restriction. [ABSTRACT FROM AUTHOR]

Mobility impairment in older persons is associated with brain white matter hyperintensities (WMH), a common finding in magnetic resonance images and one established imaging biomarker of small vessel disease. The contribution of possible microstructural abnormalities within normal-appearing white matter (NAWM) to mobility, however, remains unclear. We used diffusion tensor imaging (DTI) measures, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), to assess microstructural changes within supratentorial NAWM and WMH sub-compartments, and to investigate their association with changes in mobility performance, i.e. Tinetti assessment and the 2.5-meters walk time test. We analyzed baseline (N = 86, age ≥75 years) and 4-year (N = 41) follow-up data. Results from cross-sectional analysis on baseline data showed significant correlation between WMH volume and NAWM-FA (r = -0.33, p = 0.002), NAWM-AD (r = 0.32, p = 0.003) and NAWM-RD (r = 0.39, p = 0.0002). Our longitudinal analysis showed that after 4-years, FA and AD decreased and RD increased within NAWM. In regional tract-based analysis decrease in NAWM-FA and increase in NAWM-RD within the genu of the corpus callosum correlated with slower walk time independent of age, gender and WMH burden. In conclusion, global DTI indices of microstructural integrity indicate that significant changes occur in the supratentorial NAWM over four years. The observed changes likely reflect white matter deterioration resulting from aging as well as accrual of cerebrovascular injury associated with small vessel disease. The observed association between mobility scores and regional measures of NAWM microstructural integrity within the corpus callosum suggests that subtle changes within this structure may contribute to mobility impairment. [ABSTRACT FROM AUTHOR]

Subject-specific computer models (male and female) of the human head were used to investigate the possible axonal deformation resulting from the primary phase blast-induced skull flexures. The corresponding axonal tractography was explicitly incorporated into these finite element models using a recently developed technique based on the embedded finite element method. These models were subjected to extensive verification against experimental studies which examined their pressure and displacement response under a wide range of loading conditions. Once verified, a parametric study was developed to investigate the axonal deformation for a wide range of loading overpressures and directions as well as varying cerebrospinal fluid (CSF) material models. This study focuses on early times during a blast event, just as the shock transverses the skull (< 5 milliseconds). Corresponding boundary conditions were applied to eliminate the rotation effects and the resulting axonal deformation. A total of 138 simulations were developed– 128 simulations for studying the different loading scenarios and 10 simulations for studying the effects of CSF material model variance–leading to a total of 10,702 simulation core hours. Extreme strains and strain rates along each of the fiber tracts in each of these scenarios were documented and presented here. The results suggest that the blast-induced skull flexures result in strain rates as high as 150–378 s-1. These high-strain rates of the axonal fiber tracts, caused by flexural displacement of the skull, could lead to a rate dependent micro-structural axonal damage, as pointed by other researchers. [ABSTRACT FROM AUTHOR]

We prospectively examined the variability of non-Gaussian diffusion magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) measurements with different numbers of b-values and excitations in normal breast tissue and breast lesions. Thirteen volunteers and fourteen patients with breast lesions (seven malignant, eight benign; one patient had bilateral lesions) were recruited in this prospective study (approved by the Internal Review Board). Diffusion-weighted MRI was performed with 16 b-values (0–2500 s/mm2 with one number of excitations [NEX]) and five b-values (0–2500 s/mm2, 3 NEX), using a 3T breast MRI. Intravoxel incoherent motion (flowing blood volume fraction [fIVIM] and pseudodiffusion coefficient [D*]) and non-Gaussian diffusion (theoretical apparent diffusion coefficient [ADC] at b value of 0 sec/mm2 [ADC0] and kurtosis [K]) parameters were estimated from IVIM and Kurtosis models using 16 b-values, and synthetic apparent diffusion coefficient (sADC) values were obtained from two key b-values. The variabilities between and within subjects and between different diffusion acquisition methods were estimated. There were no statistical differences in ADC0, K, or sADC values between the different b-values or NEX. A good agreement of diffusion parameters was observed between 16 b-values (one NEX), five b-values (one NEX), and five b-values (three NEX) in normal breast tissue or breast lesions. Insufficient agreement was observed for IVIM parameters. There were no statistical differences in the non-Gaussian diffusion MRI estimated values obtained from a different number of b-values or excitations in normal breast tissue or breast lesions. These data suggest that a limited MRI protocol using a few b-values might be relevant in a clinical setting for the estimation of non-Gaussian diffusion MRI parameters in normal breast tissue and breast lesions. [ABSTRACT FROM AUTHOR]

Neuroeconomics is providing insights into the neural bases of decision-making in normal and pathological conditions. In the neuropsychiatric domain, this discipline investigates how abnormal functioning of neural systems associated with reward processing and cognitive control promotes different disorders, and whether such evidence may inform treatments. This endeavor is crucial when studying different types of addiction, which share a core promoting mechanism in the imbalance between impulsive subcortical neural signals associated with immediate pleasurable outcomes and inhibitory signals mediated by a prefrontal reflective system. The resulting impairment in behavioral control represents a hallmark of alcohol use disorders (AUDs), a chronic relapsing disorder characterized by excessive alcohol consumption despite devastating consequences. This review aims to summarize available magnetic resonance imaging (MRI) evidence on reward-related decision-making alterations in AUDs, and to envision possible future research directions. We review functional MRI (fMRI) studies using tasks involving monetary rewards, as well as MRI studies relating decision-making parameters to neurostructural gray- or white-matter metrics. The available data suggest that excessive alcohol exposure affects neural signaling within brain networks underlying adaptive behavioral learning via the implementation of prediction errors. Namely, weaker ventromedial prefrontal cortex activity and altered connectivity between ventral striatum and dorsolateral prefrontal cortex likely underpin a shift from goal-directed to habitual actions which, in turn, might underpin compulsive alcohol consumption and relapsing episodes despite adverse consequences. Overall, these data highlight abnormal fronto-striatal connectivity as a candidate neurobiological marker of impaired choice in AUDs. Further studies are needed, however, to unveil its implications in the multiple facets of decision-making. [ABSTRACT FROM AUTHOR]

Pain remains highly prevalent in HIV-seropositive (HIV+) patients despite their well-suppressed viremia with combined antiretroviral therapy. Investigating brain abnormalities within the pain matrix, and in relation to pain symptoms, in HIV+ participants may provide objective biomarkers and insights regarding their pain symptoms. We used Patient-Reported Outcome Measurement Information System (PROMIS®) pain questionnaire to evaluate pain symptoms (pain intensity, pain interference and pain behavior), and structural MRI to assess brain morphometry using FreeSurfer (cortical area, cortical thickness and subcortical volumes were evaluated in 12 regions within the pain matrix). Compared to seronegative (SN) controls, HIV+ participants had smaller surface areas in prefrontal pars triangularis (right: p = 0.04, left: p = 0.007) and right anterior cingulate cortex (p = 0.03) and smaller subcortical regions (thalamus: p ≤ 0.003 bilaterally; right putamen: p = 0.01), as well as higher pain scores (pain intensity-p = 0.005; pain interference-p = 0.008; pain-behavior-p = 0.04). Furthermore, higher pain scores were associated with larger cortical areas, thinner cortices and larger subcortical volumes in HIV+ participants; but smaller cortical areas, thicker cortices and smaller subcortical volumes in SN controls (interaction-p = 0.009 to p = 0.04). These group differences in the pain-associated brain abnormalities suggest that HIV+ individuals have abnormal pain responses. Since these abnormal pain-associated brain regions belong to the affective component of the pain matrix, affective symptoms may influence pain perception in HIV+ patients and should be treated along with their physical pain symptoms. Lastly, associations of lower pain scores with better physical or mental health scores, regardless of HIV-serostatus (p < 0.001), suggest adequate pain treatment would lead to better quality of life in all participants. [ABSTRACT FROM AUTHOR]

Patients with complex regional pain syndrome (CRPS) exhibit diverse symptoms, such as neuropathic pain, allodynia, local edema and skin color changes in the affected lesion. Although nerve injury may cause CRPS, pathophysiological mechanisms underlying the syndrome are unclear, and local edema, a characteristic of CRPS, has not been evaluated quantitatively for technical reasons. Here, using a rat spinal nerve ligation-induced CRPS model, we show that edematous changes in gastrocnemius muscle can be detected quantitatively by diffusion magnetic resonance imaging (MRI). Using the line-scan diffusion spectrum on a 1.5 T clinical MR imager, we demonstrate significant elevation of the apparent diffusion coefficient (ADC) ratios in gastrocnemius muscle on the ligated versus the sham-operated rats by one day after surgery, those ratios gradually decreased over time. Meanwhile, T2 ratios in gastrocnemius muscle on the ligated rats increased gradually and significantly, peaking two weeks after surgery, and those ratios remained high and were consistent with edema. Expression of vascular endothelial growth factor (VEGF), a key regulator of blood vessel formation and function, was significantly lower in gastrocnemius muscle on the ligated versus non-ligated side, suggesting that nerve ligation promotes edematous changes and perturbs VEGF expression in target muscle. [ABSTRACT FROM AUTHOR]

Background: Structural imaging studies of borderline personality disorder (BPD) have found regions of reduced cortical volume, but these have varied considerably across studies. Reduced hippocampus and amygdala volume have also been a regular finding in studies using conventional volumetric measurement. How far comorbid major depression, which is common in BPD and can also affect in brain structure, influences the findings is not clear. Methods: Seventy-six women with BPD and 76 matched controls were examined using whole-brain voxel-based morphometry (VBM). The hippocampus and amygdala were also measured, using both conventional volume measurement and VBM within a mask restricted to these two subcortical structures. Lifetime history of major depression was assessed using structured psychiatric interview. Results: At a threshold of p = 0.05 corrected, the BPD patients showed clusters of volume reduction in the dorsolateral prefrontal cortex bilaterally and in the pregenual/subgenual medial frontal cortex. There was no evidence of volume reductions in the hippocampus or amygdala, either on conventional volumetry or using VBM masked to these regions. Instead there was evidence of right-sided enlargement of these structures. No significant structural differences were found between patients with and without lifetime major depression. Conclusions: According to this study, BPD is characterized by a restricted pattern of cortical volume reduction involving the dorsolateral frontal cortex and the medial frontal cortex, both areas of potential relevance for the clinical features of the disorder. Previous findings concerning reduced hippocampus and amygdala volume in the disorder are not supported. Brain structural findings in BPD do not appear to be explainable on the basis of history of associated lifetime major depression. [ABSTRACT FROM AUTHOR]

Accumulation of amyloid-β (Aβ) peptides in the brain is a critical early event in the pathogenesis of Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. There is increasing interest in measuring levels of plasma Aβ since this could help in diagnosis of brain pathology. However, the value of plasma Aβ in such a diagnosis is still controversial and factors modulating its levels are still poorly understood. The mouse lemur (Microcebus murinus) is a primate model of cerebral aging which can also present with amyloid plaques and whose Aβ is highly homologous to humans'. In an attempt to characterize this primatemodel and to evaluate the potential of plasma Aβ as a biomarker for brain alterations, we measured plasma Aβ40 concentration in 21 animals aged from 5 to 9.5 years. We observed an age-related increase in plasma Aβ40 levels. We then evaluated the relationships between plasma Aβ40 levels and cerebral atrophy in these mouse lemurs. Voxel-βased analysis of cerebral MR images (adjusted for the age/sex/brain size of the animals), showed that low Aβ40 levels are associated with atrophy of several white matter and subcortical brain regions. These results suggest that low Aβ40 levels in middle-aged/old animals are associated with brain deterioration. One special feature of mouse lemurs is that their metabolic and physiological parameters follow seasonal changes strictly controlled by illumination. We evaluated seasonal-related variations of plasma Aβ40 levels and found a strong effect, with higher plasma A&#94640 concentrations in winter conditions compared to summer. This question of seasonal modulation of Ab plasma levels should be addressed in clinical studies. We also focused on the amplitude of the difference between plasma Ab40 levels during the two seasons and found that this amplitude increases with age. Possible mechanisms leading to these seasonal changes are discussed. [ABSTRACT FROM AUTHOR]

Identification of imaging biomarkers for schizophrenia is an important but still challenging problem. Even though considerable efforts have been made over the past decades, quantitative alterations between patients and healthy subjects have not yet provided a diagnostic measure with sufficient high sensitivity and specificity. One of the most important reasons is the lack of consistent findings, which is in part due to single-mode study, which only detects single dimensional information by each modality, and thus misses the most crucial differences between groups. Here, we hypothesize that multimodal integration of functional MRI (fMRI), structural MRI (sMRI), and diffusion tensor imaging (DTI) might yield more power for the diagnosis of schizophrenia. A novel multivariate data fusion method for combining these modalities is introduced without reducing the dimension or using the priors from 161 schizophrenia patients and 168 matched healthy controls. The multi-index feature for each ROI is constructed and summarized with Wilk's lambda by performing multivariate analysis of variance to calculate the significant difference between different groups. Our results show that, among these modalities, fMRI has the most significant featureby calculating the Jaccard similarity coefficient (0.7416) and Kappa index (0.4833). Furthermore, fusion of these modalities provides the most plentiful information and the highest predictive accuracy of 86.52%. This work indicates that multimodal integration can improve the ability of distinguishing differences between groups and might be assisting in further diagnosis of schizophrenia. [ABSTRACT FROM AUTHOR]

Dynamic magnetic resonance imaging (DMRI) is used to noninvasively trace the movements of organs and the process of drug delivery. The results can provide quantitative or semiquantitative pathology-related parameters, thus giving DMRI great potential for clinical applications. However, conventional DMRI techniques suffer from low temporal resolution and long scan time owing to the limitations of the k-space sampling scheme and image reconstruction algorithm. In this paper, we propose a novel DMRI sampling scheme based on a golden-ratio Cartesian trajectory in combination with a compressed sensing reconstruction algorithm. The results of two simulation experiments, designed according to the two major DMRI techniques, showed that the proposed method can improve the temporal resolution and shorten the scan time and provide high-quality reconstructed images. [ABSTRACT FROM AUTHOR]

Introduction: Low-back pain (LBP) has been correlated to the presence of intervertebral disc (IVD) degeneration on T2-weighted (T2w) MRI. It remains challenging, however, to accurately stage degenerative disc disease (DDD) based on T2w MRI and measurements of IVD height, particularly for early DDD. Several quantitative MRI techniques have been introduced to detect changes in matrix composition signifying early DDD. In this study, we correlated quantitative T2, T1rho and Apparent Diffusion Coefficient (ADC) values to disc mechanical behavior and gold standard early DDD markers in a graded degenerated lumbar IVD caprine model, to assess their potential for early DDD detection. Methods: Lumbar caprine IVDs were injected with either 0.25 U/ml or 0.5 U/ml Chondroïtinase ABC (Cabc) to trigger early DDD-like degeneration. Injection with phosphate-buffered saline (PBS) served as control. IVDs were cultured in a bioreactor for 20 days under axial physiological loading. High-resolution 9.4 T MR images were obtained prior to intervention and after culture. Quantitative MR results were correlated to recovery behavior, histological degeneration grading, and the content of glycosaminoglycans (GAGs) and water. Results: Cabc-injected IVDs showed aberrancies in biomechanics and loss of GAGs without changes in water-content. All MR sequences detected changes in matrix composition, with T1rho showing largest changes pre-to-post in the nucleus, and significantly more than T2 and ADC. Histologically, degeneration due to Cabc injection was mild. T1rho nucleus values correlated strongest with altered biomechanics, histological degeneration score, and loss of GAGs. Conclusions: T2- and T1rho quantitative MR-mapping detected early DDD changes. T1rho nucleus values correlated better than T2 and ADC with biomechanical, histological, and GAG changes. Clinical implementation of quantitative MRI, T1rho particularly, could aid in distinguishing DDD more reliably at an earlier stage in the degenerative process. [ABSTRACT FROM AUTHOR]

Background: In acute ischemic stroke the status of collateral circulation is a critical factor in determining outcome. We propose a less invasive alternative to digital subtraction angiography for evaluating collaterals based on dynamic-susceptibility contrast magnetic resonance imaging. Methods: Perfusion maps of Tmax and cerebral blood flow (CBF) were created for 35 patients with baseline occlusion of a major cerebral artery. Volumes of hypoperfusion were defined as having a Tmax delay of > 4 seconds (Tmax4s) and > 6 seconds (Tmax6s) and a CBF drop below 80% of healthy, contralateral tissue. For each patient a ratio between the volume of the CBF and the Tmax based perfusion deficit was calculated. Associations with collateral status and radiological outcome were assessed with the Mann-Whitney-U test, uni- and multivariable logistic regression analyses as well as area under the receiver-operator-characteristic (ROC) curve. Results: The CBF/Tmax volume ratios were significantly associated with bad collateral status in crude logistic regression analysis as well as with adjustment for NIHSS at admission and baseline infarct volume (OR = 2.5 95% CI[1.2–5.4] p = 0.020 for CBF/Tmax 4s volume ratio and OR = 1.6 95% CI[1.0–2.6] p = 0.031 for CBF/Tmax6s volume ratio). Moreover, the ratios were significantly correlated to final infarct size (Spearman’s rho = 0.711 and 0.619, respectively for the CBF/Tmax4s volume ratio and CBF/Tmax6s volume ration, all p<0.001). The ratios also had a high area under the ROC curve of 0.93 95%CI[0.86–1.00]) and 0.90 95%CI[0.80–1.00]respectively for predicting poor radiological outcome. Conclusions: In the setting of acute ischemic stroke the CBF/Tmax volume ratio can be used to differentiate between good and insufficient collateral circulation without the need for invasive procedures like conventional angiography. [ABSTRACT FROM AUTHOR]

Objective: To evaluate intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) sequences for quantitative characterization of anal fistula activity. Methods: This retrospective study was approved by the institutional review board. One hundred and two patients underwent MRI for clinical suspicion of anal fistula. Forty-three patients with demonstrable anal fistulas met the inclusion criteria. Quantitative analysis included measurement of DCE and IVIM parameters. The reference standard was clinical activity based on medical records. Statistical analyses included Bayesian analysis with Markov Chain Monte Carlo, multivariable logistic regression, and receiver operating characteristic analyses. Results: Brevity of enhancement, defined as the time difference between the wash-in and wash-out, was longer in active than inactive fistulas (p = 0.02). Regression coefficients of multivariable logistic regression analysis revealed that brevity of enhancement increased and normalized perfusion area under curve decreased with presence of active fistulas (p = 0.03 and p = 0.04, respectively). By cross-validation, a logistic regression model that included quantitative perfusion parameters (DCE and IVIM) performed significantly better than IVIM only (p < 0.001). Area under the curves for distinguishing patients with active from those with inactive fistulas were 0.669 (95% confidence interval [CI]: 0.500, 0.838) for a model with IVIM only, 0.860 (95% CI: 0.742, 0.977) for a model with IVIM and brevity of enhancement, and 0.921 (95% CI: 0.846, 0.997) for a model with IVIM and all DCE parameters. Conclusion: The inclusion of brevity of enhancement measured by DCE-MRI improved assessment of anal fistula activity over IVIM-DWI only. [ABSTRACT FROM AUTHOR]

Introduction: In conventional MR examinations glioblastomas multiforme (GBMs), metastases and primary CNS lymphomas (PCNSLs) may show very similar appearance. The aim of the study was to evaluate usefulness of multiparametric T2*DSC perfusion and diffusion MR imaging in the preoperative differentiation of these tumors. Material and methods: Seventy four solitary enhancing tumors (27 GBMs, 30 metastases, 17 PCNSLs) were enrolled in the study. Parameters of cerebral blood volume (rCBV), peak height (rPH), percentage of signal recovery (rPSR) and apparent diffusion coefficient (ADC) were assessed from the tumor core and the peritumoral non-enhancing T2-hyperintense zone. Results: Within the tumor core there were no differences in perfusion and diffusion parameters between GBMs and metastases. Compared to GBMs and metastases, PCNSLs showed significantly lower rCBV and rPH, ADC as well as higher rPSR values. Max rCBV with a cut-off value of 2.18 demonstrated the highest accuracy of 0.98 in differentiating PCNSLs from other tumors. To distinguish GBMs from metastases analysis of the peritumoral zone was performed showing significantly higher rCBV, rPH and lower ADC values in GBMs with the highest accuracy of 0.94 found for max rCBV at a cut-off value of 0.98. Conclusions: Max rCBV seems to be the most important parameter to differentiate GBMs, metastases and PCNSLs. Analysis of max rCBV within the tumor core enables to distinguish hypoperfused PCNSLs from hyperperfused GBMs and metastases while evaluation of max rCBV within the peritumoral zone is helpful to distinguish GBMs showing peritumoral infiltration from metastases surrounded by pure edema. [ABSTRACT FROM AUTHOR]

The posterior visual pathway is commonly affected by multiple sclerosis (MS) pathology that results in measurable clinical and electrophysiological impairment. Due to its highly structured retinotopic mapping, the visual pathway represents an ideal substrate for investigating patho-mechanisms in MS. Therefore, a reliable and robust imaging segmentation method for in-vivo delineation of the optic radiations (OR) is needed. However, diffusion-based tractography approaches, which are typically used for OR segmentation are confounded by the presence of focal white matter lesions. Current solutions require complex acquisition paradigms and demand expert image analysis, limiting application in both clinical trials and clinical practice. In the current study, using data acquired in a clinical setting on a 3T scanner, we optimised and compared two approaches for optic radiation (OR) reconstruction: individual probabilistic tractography-based and template-based methods. OR segmentation results were applied to subjects with MS and volumetric and diffusivity parameters were compared between OR segmentation techniques. Despite differences in reconstructed OR volumes, both OR lesion volume and OR diffusivity measurements in MS subjects were highly comparable using optimised probabilistic tractography-based, and template-based, methods. The choice of OR reconstruction technique should be determined primarily by the research question and the nature of the available dataset. Template-based approaches are particularly suited to the semi-automated analysis of large image datasets and have utility even in the absence of dMRI acquisitions. Individual tractography methods, while more complex than template based OR reconstruction, permit measurement of diffusivity changes along fibre bundles that are affected by specific MS lesions or other focal pathologies. [ABSTRACT FROM AUTHOR]

In animal models of Parkinson's disease (PD), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. However, brain structural changes in response to MPTP remain unclear. This study aimed to investigate in vivo longitudinal changes in gray matter (GM) volume and white matter (WM) microstructure in primate models administered with MPTP. In six cynomolgus monkeys, high-resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) scans were acquired 7 times over 32 weeks, and assessments of motor symptoms were conducted over 15 months, before and after the MPTP injection. Changes in GM volume and WM microstructure were estimated on a voxel-by-voxel basis. Mixed-effects regression models were used to examine the trajectories of these structural changes. GM volume initially increased after the MPTP injection and gradually decreased in the striatum, midbrain, and other dopaminergic areas. The cerebellar volume temporarily decreased and returned to its baseline level. The rate of midbrain volume increase was positively correlated with the increase rate of motor symptom severity (Spearman rho = 0.93, p = 0.008). Mean, axial, and radial diffusivity in the striatum and frontal areas demonstrated initial increases and subsequent decreases. The current multi-modal imaging study of MPTP-administered monkeys revealed widespread and dynamic structural changes not only in the nigrostriatal pathway but also in other cortical, subcortical, and cerebellar areas. Our findings may suggest the need to further investigate the roles of inflammatory reactions and glial activation as potential underlying mechanisms of these structural changes. [ABSTRACT FROM AUTHOR]

Background: In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance. Methods: 20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance. Results: Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance. Conclusions: Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes underlie fatigue in PBC. [ABSTRACT FROM AUTHOR]

Introduction: While progressive MRI brain changes characterize advanced Parkinson’s disease (PD), little has been discovered about structural alterations in the earliest phase of the disease, i.e. in patients with motor symptoms and with normal cognition. Our study aimed to detect grey matter (GM) and white matter (WM) changes in PD patients without cognitive impairment. Methods: Twenty PD patients and twenty-one healthy controls (HC) were tested for attention, executive function, working memory, and visuospatial and language domains. High-resolution T1-weighted and 60 directional diffusion-weighted 3T MRI images were acquired. The cortical, deep GM and WM volumes and density, as well as the diffusion properties of WM, were calculated. Analyses were repeated on data flipped to the side of the disease origin. Results: PD patients did not show any significant differences from HC in cognitive functioning or in brain volumes. Decreased GM intensity was found in the left superior parietal lobe in the right (p<0.02) and left (p<0.01) flipped data. The analysis of original, un-flipped data demonstrated elevated axial diffusivity (p<0.01) in the superior and anterior corona radiata, internal capsule, and external capsule in the left hemisphere of PD relative to HC, while higher mean and radial diffusivity were discovered in the right (p<0.02 and p<0.03, respectively) and left (p<0.02 and p<0.02, respectively) in the fronto-temporal WM utilizing flipped data. Conclusions: PD patients without cognitive impairment and GM atrophy demonstrated widespread alterations of WM microstructure. Thus, WM impairment in PD might be a sensitive sign preceding the neuronal loss in associated GM regions. [ABSTRACT FROM AUTHOR]

Background and Purpose: A pipeline for fully automated segmentation of 3T brain MRI scans in multiple sclerosis (MS) is presented. This 3T morphometry (3TM) pipeline provides indicators of MS disease progression from multichannel datasets with high-resolution 3-dimensional T1-weighted, T2-weighted, and fluid-attenuated inversion-recovery (FLAIR) contrast. 3TM segments white (WM) and gray matter (GM) and cerebrospinal fluid (CSF) to assess atrophy and provides WM lesion (WML) volume.Methods: To address nonuniform distribution of noise/contrast (eg, posterior fossa in 3D-FLAIR) of 3T magnetic resonance imaging, the method employs dual sensitivity (different sensitivities for lesion detection in predefined regions). We tested this approach by assigning different sensitivities to supratentorial and infratentorial regions, and validated the segmentation for accuracy against manual delineation, and for precision in scan-rescans.Results: Intraclass correlation coefficients of .95, .91, and .86 were observed for WML and CSF segmentation accuracy and brain parenchymal fraction (BPF). Dual sensitivity significantly reduced infratentorial false-positive WMLs, affording increases in global sensitivity without decreasing specificity. Scan-rescan yielded coefficients of variation (COVs) of 8% and .4% for WMLs and BPF and COVs of .8%, 1%, and 2% for GM, WM, and CSF volumes. WML volume difference/precision was .49 ± .72 mL over a range of 0-24 mL. Correlation between BPF and age was r = .62 (P = .0004), and effect size for detecting brain atrophy was Cohen's d = 1.26 (standardized mean difference vs. healthy controls).Conclusions: This pipeline produces probability maps for brain lesions and tissue classes, facilitating expert review/correction and may provide high throughput, efficient characterization of MS in large datasets. [ABSTRACT FROM AUTHOR]

Objective: Subclinical obsessive-compulsive (OC) symptoms are frequently observed in children and have been reported to predict a subsequent diagnosis of OC disorder (OCD). Therefore, identifying the putative neurobiological signatures of such risk is crucial, because it would allow for the characterization of the underpinnings of OCD without the interfering effects of chronicity, medication, or comorbidities, especially when interpreted within the context of OCD clinical heterogeneity and taking into account normal neurodevelopmental changes. The present study aimed to identify the brain volumetric features associated with subclinical OC symptoms and the potential modulatory effects of sex and age in a large sample of healthy children.Method: Two hundred fifty-five healthy children were assessed using the Obsessive-Compulsive Inventory-Child Version and underwent a brain structural magnetic resonance examination. The relation between total and symptom-specific scores and regional gray and white matter (GM and WM) volumes was evaluated. Participants were grouped according to sex and age (younger versus older) to assess the effect of these factors on symptom-brain morphometry associations.Results: Ordering symptoms were negatively related to GM volumes in the ventral caudate. Hoarding symptoms were positively associated with GM and WM volumes in the left inferior frontal gyrus, and obsessing symptoms correlated negatively with GM and WM volumes in the right temporal pole. Doubt-checking symptoms correlated positively with WM volumes in the right inferior fronto-occipital fasciculus and the corpus callosum. Sex and age modulated some of these associations.Conclusion: Subclinical OC symptoms are associated with specific brain volumetric features, which could be considered potential neural signatures of increased risk for OCD. [ABSTRACT FROM AUTHOR]

One clinical dimension often cited as a hallmark of schizophrenia is thought disorder (TD). The aim of the current systematic review was to summarise our current understanding of the neurobiology of TD that has been investigated with structural neuroimaging techniques. Ninety-seven relevant studies were identified from January 1990 to August 2016, 26 of which had TD-motivated research questions or hypotheses. The remaining 71 studies conducted exploratory clinical analyses that included TD amongst a number of psychotic symptoms. These studies implicate the left superior temporal gyrus in TD. There was also evidence to suggest associations between TD and structural measures within the orbitofrontal cortex, cerebellum, nucleus accumbens, and amygdala-hippocampal region. However, there is a dearth of structural neuroimaging research driven by TD-motivated hypotheses. Furthermore, few studies have explored specific TD symptoms or subgroups, or surface-based morphometric measures of cortical structure, despite theoretical and practical reasons for doing so. It is hoped that the current review will assist in the augmentation of diverse hypothesis-driven research into the aetiology of TD. [ABSTRACT FROM AUTHOR]

Purpose: To implement a statistical framework for assessing the precision of several quantitative MRI metrics sensitive to myelin in the human spinal cord: T1, Magnetization Transfer Ratio (MTR), saturation imposed by an off-resonance pulse (MTsat) and Macromolecular Tissue Volume (MTV). Methods: Thirty-three healthy subjects within two age groups (young, elderly) were scanned at 3T. Among them, 16 underwent the protocol twice to assess repeatability. Statistical reliability indexes such as the Minimal Detectable Change (MDC) were compared across metrics quantified within different cervical levels and white matter (WM) sub-regions. The differences between pathways and age groups were quantified and interpreted in context of the test-retest repeatability of the measurements. Results: The MDC was respectively 105.7ms, 2.77%, 0.37% and 4.08% for T1, MTR, MTsat and MTV when quantified over all WM, while the standard-deviation across subjects was 70.5ms, 1.34%, 0.20% and 2.44%. Even though particular WM regions did exhibit significant differences, these differences were on the same order as test-retest errors. No significant difference was found between age groups for all metrics. Conclusion: While T1-based metrics (T1 and MTV) exhibited better reliability than MT-based measurements (MTR and MTsat), the observed differences between subjects or WM regions were comparable to (and often smaller than) the MDC. This makes it difficult to determine if observed changes are due to variations in myelin content, or simply due to measurement error. Measurement error remains a challenge in spinal cord myelin imaging, but this study provides statistical guidelines to standardize the field and make it possible to conduct large-scale multi-center studies. [ABSTRACT FROM AUTHOR]

Background: Putaminal diffusivity in brain magnetic resonance diffusion-weighted imaging (DWI) is increased in patients with the parkinsonian variant of multiple system atrophy (MSA-P) compared to Parkinson disease (PD) patients. Purpose: We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of DWI to distinguish MSA-P from PD. Methods: Studies on DWI were identified through a systematic PubMed and Clarivate Analytics® Web of Science® Core Collection search. Papers were selected based on stringent inclusion criteria; minimum requirement was the inclusion of MSA-P and PD patients and documented true positive, true negative, false positive and false negative rates or overall sample size and reported sensitivity and specificity. Meta-analysis was performed using the hierarchical summary receiver operating characteristics curve approach. Results: The database search yielded 1678 results of which 9 studies were deemed relevant. Diagnostic accuracy of putaminal diffusivity measurements were reported in all of these 9 studies, whereas results of other regions of interest were only reported irregularly. Therefore, a meta-analysis could only be performed for putaminal diffusivity measurements: 127 patients with MSA-P, 262 patients with PD and 70 healthy controls were included in the quantitative synthesis. The meta-analysis showed an overall sensitivity of 90% (95% confidence interval (CI): 76.7%-95.8%) and an overall specificity of 93% (95% CI: 80.0%-97.7%) to distinguish MSA-P from PD based on putaminal diffusivity. Conclusion: Putaminal diffusivity yields high sensitivity and specificity to distinguish clinically diagnosed patients with MSA-P from PD. The confidence intervals indicate substantial variability. Further multicenter studies with harmonized protocols are warranted particularly in early disease stages when clinical diagnosis is less certain. [ABSTRACT FROM AUTHOR]

We used a robotic exoskeleton to quantify specific patterns of abnormal upper limb motor behaviour in people who have had transient ischemic attack (TIA). A cohort of people with TIA was recruited within two weeks of symptom onset. All individuals completed a robotic-based assessment of 8 behavioural tasks related to upper limb motor and proprioceptive function, as well as cognitive function. Robotic task performance was compared to a large cohort of controls without neurological impairments corrected for the influence of age. Impairment in people with TIA was defined as performance below the 5th percentile of controls. Participants with TIA were also assessed with the National Institutes of Health Stroke Scale (NIHSS) score, Chedoke-McMaster Stroke Assessment (CMSA) of the arm, the Behavioural Inattention Test (BIT), the Purdue pegboard test (PPB), and the Montreal Cognitive Assessment (MoCA). Age-related white matter change (ARWMC), prior infarction and cella-media index (CMI) were assessed from baseline CT scan that was performed within 24 hours of TIA. Acute infarction was assessed from diffusion-weighted imaging in a subset of people with TIA. Twenty-two people with TIA were assessed. Robotic assessment showed impaired upper limb motor function in 7/22 people with TIA patients and upper limb sensory impairment in 4/22 individuals. Cognitive tasks involving robotic assessment of the upper limb were completed in 13 participants, of whom 8 (61.5%) showed significant impairment. Abnormal performance in the CMSA arm inventory was present in 12/22 (54.5%) participants. ARWMC was 11.8 ± 6.4 and CMI was 5.4 ± 1.5. DWI was positive in 0 participants. Quantitative robotic assessment showed that people who have had a TIA display a spectrum of upper limb motor and sensory performance deficits as well as cognitive function deficits despite resolution of symptoms and no evidence of tissue infarction. [ABSTRACT FROM AUTHOR]

Sex differences have been widely observed in clinical presentation, functional outcome and neuroanatomy in individuals with a first-episode of psychosis, and chronic patients suffering from schizophrenia. However, little is known about sex differences in the highrisk stages for psychosis. The present study investigated sex differences in cortical and subcortical neuroanatomy in individuals at clinical high risk (CHR) for psychosis and healthy controls (CTL), and the relationship between anatomy and clinical symptoms in males at CHR. Magnetic resonance images were collected in 26 individuals at CHR (13 men) and 29 CTLs (15 men) to determine total and regional brain volumes and morphology, cortical thickness, and surface area (SA). Clinical symptoms were assessed with the brief psychiatric rating scale. Significant sex-by-diagnosis interactions were observed with opposite directions of effect in male and female CHR subjects relative to their same-sex controls in multiple cortical and subcortical areas. The right postcentral, left superior parietal, inferior parietal supramarginal, and angular gyri [<5% false discovery rate (FDR)] were thicker in male and thinner in female CHR subjects compared with their same-sex CTLs. The same pattern was observed in the right superior parietal gyrus SA at the regional and vertex level. Using a recently developed surface-based morphology pipeline, we observed sex-specific shape differences in the left hippocampus (<5% FDR) and amygdala (<10% FDR). Negative symptom burden was significantly higher in male compared with female CHR subjects (p = 0.04) and was positively associated with areal expansion of the left amygdala in males (<5% FDR). Some limitations of the study include the sample size, and data acquisition at 1.5 T. This study demonstrates neuroanatomical sex differences in CHR subjects, which may be associated with variations in symptomatology in men and women with psychotic symptoms. [ABSTRACT FROM AUTHOR]

Background and purpose: Inference of etiology from lesion pattern in acute magnetic resonance imaging is valuable for management and prognosis of acute stroke patients. This study aims to assess the value of three-dimensional geometrical lesion-shape descriptors for stroke-subtype classification, specifically regarding stroke of cardioembolic origin. Methods: Stroke Etiology was classified according to ASCOD in retrospectively selected patients with acute stroke. Lesions were segmented on diffusion-weighed datasets, and descriptors of lesion shape quantified: surface area, sphericity, bounding box volume, and ratio between bounding box and lesion volume. Morphological measures were compared between stroke subtypes classified by ASCOD and between patients with embolic stroke of cardiac and non-cardiac source. Results: 150 patients (mean age 77 years; 95% CI, 65–80 years; median NIHSS 6, range 0–22) were included. Group comparison of lesion shape measures demonstrated that lesions caused by small-vessel disease were smaller and more spherical compared to other stroke subtypes. No significant differences of morphological measures were detected between patients with cardioembolic and non-cardioembolic stroke. Conclusion: Stroke lesions caused by small vessel disease can be distinguished from other stroke lesions based on distinctive morphological properties. However, within the group of embolic strokes, etiology could not be inferred from the morphology measures studied in our analysis. [ABSTRACT FROM AUTHOR]

Purpose: Injurious mechanical ventilation causes white matter (WM) injury in preterm infants through inflammatory and haemodynamic pathways. The relative contribution of each of these pathways is not known. We hypothesised that in vivo magnetic resonance imaging (MRI) can detect WM brain injury resulting from mechanical ventilation 24 h after preterm delivery. Further we hypothesised that the combination of inflammatory and haemodynamic pathways, induced by umbilical cord occlusion (UCO) increases brain injury at 24 h. Methods: Fetuses at 124±2 days gestation were exposed, instrumented and either ventilated for 15 min using a high tidal-volume (VT) injurious strategy with the umbilical cord intact (INJ; inflammatory pathway only), or occluded (INJ+UCO; inflammatory and haemodynamic pathway). The ventilation groups were compared to lambs that underwent surgery but were not ventilated (Sham), and lambs that did not undergo surgery (unoperated control; Cont). Fetuses were placed back in utero after the 15 min intervention and ewes recovered. Twenty-four hours later, lambs were delivered, placed on a protective ventilation strategy, and underwent MRI of the brain using structural, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) techniques. Results: Absolute MRS concentrations of creatine and choline were significantly decreased in INJ+UCO compared to Cont lambs (P = 0.03, P = 0.009, respectively); no significant differences were detected between the INJ or Sham groups and the Cont group. Axial diffusivities in the internal capsule and frontal WM were lower in INJ and INJ+UCO compared to Cont lambs (P = 0.05, P = 0.04, respectively). Lambs in the INJ and INJ+UCO groups had lower mean diffusivities in the frontal WM compared to Cont group (P = 0.04). DTI colour mapping revealed lower diffusivity in specific WM regions in the Sham, INJ, and INJ+UCO groups compared to the Cont group, but the differences did not reach significance. INJ+UCO lambs more likely to exhibit lower WM diffusivity than INJ lambs. Conclusions: Twenty-four hours after injurious ventilation, DTI and MRS showed increased brain injury in the injuriously ventilated lambs compared to controls. DTI colour mapping threshold approach provides evidence that the haemodynamic and inflammatory pathways have additive effects on the progression of brain injury compared to the inflammatory pathway alone. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether elevated glucose metabolism in neurofibroma, determined by [F18]-FDG-PET, is correlated with cell density in MRI, as expressed through the apparent diffusion coefficient. Materials and methods: Patients diagnosed with neurofibromatosis type 1 and peripheral nerve sheath tumors (PNST) were enrolled in this prospective, IRB-approved study. After a single [F18]-FDG injection, patients consecutively underwent [F18]-FDG-PET/CT and [F18]-FDG-PET/MRI on the same day. Maximum and mean standardized uptake values (SUVmax, SUVmean) on [F18]-FDG-PET/CT and [F18]-FDG-PET/MRI were compared, and correlated with minimum and mean apparent diffusion coefficients (ADCmean, ADCmin). Results: A total of 12 (6 male/6 female, mean age was 16.2 ± 5.2 years) patients were prospectively included and analyzed on a per-lesion (n = 39) basis. The SUVmean of examined PNST showed a moderate negative correlation with the ADCmean (r = -.441) and ADCmin (r = -.477), which proved to be statistically significant (p = .005 and p = .002). The SUVmax of the respective lesions, however, showed a weaker negative correlation for ADCmean (r: -.311) and ADCmin (r: -.300) and did not reach statistical significance (p = .054 and p = .057). Lesion-based correlation between [F18]-FDG-PET/MRI and [F18]-FDG-PET/CT showed a moderate correlation for SUVmax (r = .353; p = .027) and a strong one for SUVmean (r = .879; p = .001)). Patient-based liver uptake (SUVmax and mean) of [F18]-FDG-PET/MRI and [F18]-FDG-PET/CT were strongly positively correlated (r = .827; p < .001 and r = .721; p < .001) but differed significantly (p < .001). Conclusions: We found a statistically significant, negative correlation between glucose metabolism and cell density in PNST. Thus, ADCmean and ADCmin could possibly add complimentary information to the SUVmax and SUVmean and may serve as a potential determinant of malignant transformation of PNST. [ABSTRACT FROM AUTHOR]

Recent studies suggest that longstanding findings of abnormal amygdala morphology in ASD may be related to symptoms of anxiety. To test this hypothesis, fifty-three children with ASD (mean age = 11.9) underwent structural MRI and were divided into subgroups to compare those with at least one anxiety disorder diagnosis ( n = 29) to those without ( n = 24) and to a typically developing control group (TDC; n = 37). Groups were matched on age and intellectual level. The ASD and anxiety group showed decreased right amygdala volume (controlled for total brain volume) relative to ASD without anxiety ( p = .04) and TDCs ( p = .068). Results suggest that youth with ASD and co-occurring anxiety have a distinct neurodevelopmental trajectory. [ABSTRACT FROM AUTHOR]

Purpose Rolandic epilepsy (RE), also called benign epilepsy with centrotemporal spikes (BECTS) is the most common childhood epilepsy syndrome. RE is associated with cognitive difficulties, which can affect children's quality of life. The underlying causes of these cognitive impairments are unclear. The objective of this prospective study is to investigate sub-cortical morphological alterations in RE children with left, right, or bilateral hemispheric focus and its association with cognition. Methods Participants include 41 children with rolandic epilepsy and 38 healthy controls (age 8–14 years), recruited from CHU Sainte-Justine Montreal Children Hospital ( N = 40) and Basel's Children Hospital ( N = 39). Quantitative volumetric assessment of putamen and caudate structures was performed on T1-weighted MR scans along with the morphological analysis to test for differences between patients and controls. These analyses were performed considering the side of epilepsy focus in all participants. Correlations were investigated between the sub-cortical morphometry and cognitive indices such as intelligence quotient (IQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI). Results Children with bilateral BECTS showed statistically significant volume reduction in right caudate ( p < .05), while no statistically significant putamen volumetric changes were detected in BECTS participants compared to normal controls. According to a spectral-based groupwise shape analysis, regional alterations were found in both putamen and caudate structures of children with BECTS. In particular, children with left BECTS showed significant outward local deformity in left putamen and individuals with bilateral BECTS showed inward local group differences in both right putamen and right caudate. The correlation assessment showed positive association between the volume of the left caudate and cognitive indices in the group containing all BECTS participants. Negative correlation was found between putamen sub-regional shape alterations and cognition in individuals with right BECTS and in all BECTS participants. Negative associations between caudate sub-regional morphologies and cognitive indices were detected in left cohort. Significance We have confirmed putamen and caudate shape alterations in children with BECTS. However, our results further suggest that variations in sub-cortical shape affect cognitive functions. Importantly, we have demonstrated that shape alterations and their relation with cognition depend on the side of epilepsy focus. Our results point to different syndromic entities in the BECTS population. [ABSTRACT FROM AUTHOR]