Search

Background and Objectives: Cerebral small vessel disease (CSVD) is associated to cognitive decline and dementia. Neuroimaging changes of CSVD are highly prevalent above 80 years. Only few studies report on incidence of CSVD in high age. We have investigated the incidence and prevalence of magnetic resonance imaging (MRI) markers of CSVD and risk factors in the general older population., Methods: As part of the general population Good Aging in Skåne cohort study (GÅS), 241 persons (mean age 76.3 years) underwent two brain MRI, 3-T scanner with a mean interval of 5.9 years. The incidence of white matter hyperintensities (WMH), lacunar infarction, cerebral atrophies and cerebral microbleeds (CMB) were calculated and the relationship to risk factors analysed by a multivariate regression analysis. Medial temporal lobe atrophy (MTA) was graded according to Scheltens'18 scale and CMB were defined as having > 1 small (0.2-0.5 cm) hypointense lesion., Results: The 6-year incidence of CMB, WMH and MTA were, 19%, 17% and 13% respectively, corresponding to 170/1,000 py., 172/1,000 py., and respectively 167/1,000 py. The incidence of CSVD according to the modified STRIVE score was 33%, 169/1,000 py and the prevalence at baseline was 73%. Moderate to high intake of alcohol was related to increased incidence of MTA and higher STRIVE score. Exposure to smoking was related to higher incidence of CMB and higher STRIVE score, adjusted for other known risk factors., Conclusion: CSVD is highly prevalent in the general older population and the 6-year incidence of WMH, CMB and MTA ranges from 13 to 19 percent. The modifiable lifestyle factors: smoking, and moderate alcohol intake are related to incident CSVD., (© 2024. The Author(s).)

Background: Early detection of treatment response is important for the management of patients with malignant brain tumors such as glioblastoma to assure good quality of life in relation to therapeutic efficacy., Aim: To investigate whether parametric response mapping (PRM) with diffusion MRI may provide prognostic information at an early stage of standard therapy for glioblastoma., Materials and Methods: This prospective study included 31 patients newly diagnosed with glioblastoma WHO grade IV, planned for primary standard postoperative treatment with radiotherapy 60Gy/30 fractions with concomitant and adjuvant Temozolomide. MRI follow-up including diffusion and perfusion weighting was performed at 3 T at start of postoperative chemoradiotherapy, three weeks into treatment, and then regularly until twelve months postoperatively. Regional mean diffusivity (MD) changes were analyzed voxel-wise using the PRM method (MD-PRM). At eight and twelve months postoperatively, after completion of standard treatment, patients were classified using conventional MRI and clinical evaluation as either having stable disease (SD, including partial response) or progressive disease (PD). It was assessed whether MD-PRM differed between patients having SD versus PD and whether it predicted the risk of disease progression (progression-free survival, PFS) or death (overall survival, OS). A subgroup analysis was performed that compared MD-PRM between SD and PD in patients only undergoing diagnostic biopsy. MGMT-promotor methylation status (O6-methylguanine-DNA methyltransferase) was registered and analyzed with respect to PFS, OS and MD-PRM., Results: Of the 31 patients analyzed: 21 were operated by resection and ten by diagnostic biopsy. At eight months, 19 patients had SD and twelve had PD. At twelve months, ten patients had SD and 20 had PD, out of which ten were deceased within twelve months and one was deceased without known tumor progression. Median PFS was nine months, and median OS was 17 months. Eleven patients had methylated MGMT-promotor, 16 were MGMT unmethylated, and four had unknown MGMT-status. MD-PRM did not significantly predict patients having SD versus PD neither at eight nor at twelve months. Patients with an above median MD-PRM reduction had a slightly longer PFS (P = 0.015) in Kaplan-Maier analysis, as well as a non-significantly longer OS (P = 0.099). In the subgroup of patients only undergoing biopsy, total MD-PRM change at three weeks was generally higher for patients with SD than for patients with PD at eight months, although no tests were performed. MGMT status strongly predicted both PFS and OS but not MD-PRM change., Conclusion: MD-PRM at three weeks was not demonstrated to be predictive of treatment response, disease progression, or survival. Preliminary results suggested a higher predictive value in non-resected patients, although this needs to be evaluated in future studies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Diffusion MRI uses the random displacement of water molecules to sensitize the signal to brain microstructure and to properties such as the density and shape of cells. Microstructure modeling techniques aim to estimate these properties from acquired data by separating the signal between virtual tissue 'compartments' such as the intra-neurite and the extra-cellular space. A key challenge is that the diffusion MRI signal is relatively featureless compared with the complexity of brain tissue. Another challenge is that the tissue microstructure is wildly different within the gray and white matter of the brain. In this review, we use results from multidimensional diffusion encoding techniques to discuss these challenges and their tentative solutions. Multidimensional encoding increases the information content of the data by varying not only the b-value and the encoding direction but also additional experimental parameters such as the shape of the b-tensor and the echo time. Three main insights have emerged from such encoding. First, multidimensional data contradict common model assumptions on diffusion and T 2 relaxation, and illustrates how the use of these assumptions cause erroneous interpretations in both healthy brain and pathology. Second, many model assumptions can be dispensed with if data are acquired with multidimensional encoding. The necessary data can be easily acquired in vivo using protocols optimized to minimize Cramér-Rao lower bounds. Third, microscopic diffusion anisotropy reflects the presence of axons but not dendrites. This insight stands in contrast to current 'neurite models' of brain tissue, which assume that axons in white matter and dendrites in gray matter feature highly similar diffusion. Nevertheless, as an axon-based contrast, microscopic anisotropy can differentiate gray and white matter when myelin alterations confound conventional MRI contrasts., Competing Interests: Declaration of Competing Interest Markus Nilsson and Filip Szczepankiewicz declare ownership interests in Random Walk Imaging, which holds patents pertaining to the methods presented herein. Remaining authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Frontotemporal dementia is the second most common form of early onset dementia (<65 years). Despite this, there are few known disease-modifying factors. The anterior cingulate is a focal point of pathology in behavioural variant frontotemporal dementia. Sulcation of the anterior cingulate is denoted by the presence of a paracingulate sulcus, a tertiary sulcus developing, where present during the third gestational trimester and remaining stable throughout life. This study aims to examine the impact of right paracingulate sulcal presence on the expression and prognosis of behavioural variant frontotemporal dementia. This retrospective analysis drew its population from two clinical samples recruited from memory clinics at university hospitals in the USA and The Netherlands. Individuals with sporadic behavioural variant frontotemporal dementia were enrolled between 2000 and 2022 and followed up for an average of 7.71 years. T 1 -MRI data were evaluated for hemispheric paracingulate sulcal presence in accordance with an established protocol by two blinded raters. Outcome measures included age at onset, survival, cortical thickness and Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating determined clinical disease progression. The study population consisted of 186 individuals with sporadic behavioural variant frontotemporal dementia (113 males and 73 females), mean age 63.28 years (SD 8.32). The mean age at onset was 2.44 years later in individuals possessing a right paracingulate sulcus [60.2 years (8.54)] versus individuals who did not [57.76 (8.05)], 95% confidence interval > 0.41, P = 0.02. Education was not associated with age at onset ( β = -0.05, P = 0.75). The presence of a right paracingulate sulcus was associated with an 83% increased risk of death per year after age at onset (hazard ratio 1.83, confidence interval [1.09-3.07], P < 0.02), whilst the mean age at death was similar for individuals with a present and absent right paracingulate sulcus ( P = 0.7). Right paracingulate sulcal presence was not associated with baseline cortical thickness. Right paracingulate sulcal presence is associated with disease expression and survival in sporadic behavioural variant frontotemporal dementia. Findings provide evidence of neurodevelopmental brain reserve in behavioural variant frontotemporal dementia that may be important in the design of trials for future therapeutic approaches., Competing Interests: O.H. has acquired research support (for the institution) from ADx, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer and Roche. In the past 2 years, he has received consultancy/speaker fees from AC Immune, Amylyx, Alzpath, BioArctic, Biogen, Cerveau, Eisai, Fujirebio, Genentech, Novartis, Novo Nordisk, Roche and Siemens., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Acute ischemic lesions are challenging to detect by conventional computed tomography (CT). Virtual monoenergetic images may improve detection rates by increased tissue contrast., Purpose: To compare the ability to detect ischemic lesions of virtual monoenergetic with conventional images in patients with acute stroke., Material and Methods: We included consecutive patients at our center that underwent brain CT in a spectral scanner for suspicion of acute stroke, onset <12 h, with or without (negative controls) a confirmed cortical ischemic lesion in the initial scan or a follow-up CT or magnetic resonance imaging. Attenuation was measured in predefined areas in ischemic gray (guided by follow-up exams), normal gray, and white matter in conventional images and retrieved in spectral diagrams for the same locations in monoenergetic series at 40-200 keV. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Visual assessment of diagnostic measures was performed by independent review by two neuroradiologists blinded to reconstruction details., Results: In total, 29 patients were included (January 2018 to July 2019). SNR was higher in virtual monoenergetic compared to conventional images, significantly at 60-150 keV. CNR between ischemic gray and normal white matter was higher in monoenergetic images at 40-70 keV compared to conventional images. Virtual monoenergetic images received higher scores in overall image quality. The sensitivity for diagnosing acute ischemia was 93% and 97%, respectively, for the reviewers, compared to 55% of the original report based on conventional images., Conclusion: Virtual monoenergetic reconstructions of spectral CIs may improve image quality and diagnostic ability in stroke assessment.

Purpose: Conventional computed tomography (CT) images are severely affected by metal artifacts in patients with intracranial coils. Monoenergetic images have been suggested to reduce metal artifacts.The aim of this study was to assess metal artifacts in virtual monoenergetic images (VMIs) reconstructed from spectral brain CT., Methods: Thirty-two consecutive patients with intracranial coils examined by spectral non contrast brain CT (NCCT) at our center between November 2017 and April 2019 were included. Attenuation and standard deviations were measured in regions of interest (ROIs) at predefined areas in artifact-free and artifact-affected areas. Measurements were performed in conventional polyenergetic images (CIs) and the corresponding data for VMIs were retrieved through spectral diagrams for the each ROI. Subjective analysis was performed by visual grading of CIs and specific VMIs by two neuroradiologists, independently., Results: In artefact-affected image areas distal from the metal objects, the attenuation values decreased with higher energy level VMIs. The same effect was not seen for artefact-affected image areas close to the metal.Subjective rating of the artefact severity was significantly better in VMIs at 50 keV for one of the two reviewers compared to the CIs. Overall image quality and tissue differentiation scores were significantly higher for both reviewers in VMIs at 60 and 70 keV compared to CIs., Conclusion: Our quantitative and qualitative image analysis shown that there is a small significant reduction of intracranial coils artifacts severity by all monoenergetic reconstructions from 50 to 200 keV with preserved or increased overall subjective image quality compared to conventional images., Competing Interests: None of the authors have any conflicts of interests related to the study. JW is a founder and shareholder of Uman Sense AB and has received speaker honoraria from Siemens Healthineers, BALT group and Medtronic Inc., (© 2023 The Authors.)

Background: Using multi-block methods we combined multimodal neuroimaging metrics of thalamic morphology, thalamic white matter tract diffusion metrics, and cortical thickness to examine changes in behavioural variant frontotemporal dementia. (bvFTD)., Method: Twenty-three patients with sporadic bvFTD and 24 healthy controls underwent structural and diffusion MRI scans. Clinical severity was assessed using the Clinical Dementia Rating scale and behavioural severity using the Frontal Behaviour Inventory by patient caregivers. Thalamic volumes were manually segmented. Anterior and posterior thalamic radiation fractional anisotropy and mean diffusivity were extracted using Tract-Based Spatial Statistics. Finally, cortical thickness was assessed using Freesurfer. We used shape analyses, diffusion measures, and cortical thickness as features in sparse multi-block partial least squares (PLS) discriminatory analyses to classify participants within bvFTD or healthy control groups. Sparsity was tuned with five-fold cross-validation repeated 10 times. Final model fit was assessed using permutation testing. Additionally, sparse multi-block PLS was used to examine associations between imaging features and measures of dementia severity., Results: Bilateral anterior-dorsal thalamic atrophy, reduction in mean diffusivity of thalamic projections, and frontotemporal cortical thinning, were the main features predicting bvFTD group membership. The model had a sensitivity of 96%, specificity of 68%, and was statistically significant using permutation testing (p = 0.012). For measures of dementia severity, we found similar involvement of regional thalamic and cortical areas as in discrimination analyses, although more extensive thalamo-cortical white matter metric changes., Conclusions: Using multimodal neuroimaging, we demonstrate combined structural network dysfunction of anterior cortical regions, cortical-thalamic projections, and anterior thalamic regions in sporadic bvFTD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: The pathological response to preoperative chemotherapy of colorectal liver metastases (CRLMs) is predictive of long-term prognosis after liver resection. Accurate preoperative assessment of chemotherapy response could enable treatment optimization., Purpose: To investigate whether changes in lesion-apparent diffusion coefficient (ADC) measured with diffusion-weighted magnetic resonance imaging (MRI) can be used to assess pathological treatment response in patients with CRLMs undergoing preoperative chemotherapy., Material and Methods: Patients who underwent liver resection for CRLMs after preoperative chemotherapy between January 2011 and December 2019 were retrospectively included if they had undergone MRI before and after preoperative chemotherapy on the same 1.5-T MRI scanner with diffusion-weighted imaging with b -values 50, 400, and 800 s/mm 2 . The pathological chemotherapy response was assessed using the tumor regression grade (TRG) by AJCC/CAP. Lesions were divided into two groups: pathological responding (TRG 0-2) and non-responding (TRG 3). The change in lesion ADC after preoperative chemotherapy was compared between responding and non-responding lesions., Results: A total of 27 patients with 49 CRLMs were included, and 24/49 lesions showed a pathological chemotherapy response. After chemotherapy, ADC increased in both pathological responding (pretreatment ADC: 1.26 [95% confidence interval (CI)=1.06-1.37] vs. post-treatment ADC: 1.33 [95% CI=1.13-1.56] × 10 -3  mm 2 /s; P  = 0.026) and non-responding lesions (1.12 [95% CI=0.980-1.21] vs. 1.20 [95% CI=1.09-1.43] × 10 -3  mm 2 /s; P  = 0.018). There was no difference in median relative difference in ADC after chemotherapy between pathological responding and non-responding lesions (15.8 [95% CI=1.42-26.3] vs. 7.17 [95% CI=-4.31 to 31.2]%; P  = 0.795)., Conclusion: Changes in CRLM ADCs did not differ between pathological responding and non-responding lesions.

Objective: Dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) has previously shown alterations in cerebral perfusion in patients with systemic lupus erythematosus (SLE). However, the results have been inconsistent, in particular regarding neuropsychiatric (NP) SLE. Thus, we investigated perfusion-based measures in different brain regions in SLE patients with and without NP involvement, and additionally, in white matter hyperintensities (WMHs), the most common MRI pathology in SLE patients., Materials and Methods: We included 3 T MRI images (conventional and DSC) from 64 female SLE patients and 19 healthy controls (HC). Three different NPSLE attribution models were used: the Systemic Lupus International Collaborating Clinics (SLICC) A model (13 patients), the SLICC B model (19 patients), and the American College of Rheumatology (ACR) case definitions for NPSLE (38 patients). Normalized cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were calculated in 26 manually drawn regions of interest and compared between SLE patients and HC, and between NPSLE and non-NPSLE patients. Additionally, normalized CBF, CBV and MTT, as well as absolute values of the blood-brain barrier leakage parameter (K 2 ) were investigated in WMHs compared to normal appearing white matter (NAWM) in the SLE patients., Results: After correction for multiple comparisons, the most prevalent finding was a bilateral significant decrease in MTT in SLE patients compared to HC in the hypothalamus, putamen, right posterior thalamus and right anterior insula. Significant decreases in SLE compared to HC were also found for CBF in the pons, and for CBV in the bilateral putamen and posterior thalamus. Significant increases were found for CBF in the posterior corpus callosum and for CBV in the anterior corpus callosum. Similar patterns were found for both NPSLE and non-NPSLE patients for all attributional models compared to HC. However, no significant perfusion differences were revealed between NPSLE and non-NPSLE patients regardless of attribution model. The WMHs in SLE patients showed a significant increase in all perfusion-based metrics (CBF, CBV, MTT and K 2 ) compared to NAWM., Conclusion: Our study revealed perfusion differences in several brain regions in SLE patients compared to HC, independently of NP involvement. Furthermore, increased K 2 in WMHs compared to NAWM may indicate blood-brain barrier dysfunction in SLE patients. We conclude that our results show a robust cerebral perfusion, independent from the different NP attribution models, and provide insight into potential BBB dysfunction and altered vascular properties of WMHs in female SLE patients. Despite SLE being most prevalent in females, a generalization of our conclusions should be avoided, and future studies including all sexes are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Currently, little is known about the spatial distribution of white matter hyperintensities (WMH) in the brain of patients with Systemic Lupus erythematosus (SLE). Previous lesion markers, such as number and volume, ignore the strategic location of WMH. The goal of this work was to develop a fully-automated method to identify predominant patterns of WMH across WM tracts based on cluster analysis. A total of 221 SLE patients with and without neuropsychiatric symptoms from two different sites were included in this study. WMH segmentations and lesion locations were acquired automatically. Cluster analysis was performed on the WMH distribution in 20 WM tracts. Our pipeline identified five distinct clusters with predominant involvement of the forceps major, forceps minor, as well as right and left anterior thalamic radiations and the right inferior fronto-occipital fasciculus. The patterns of the affected WM tracts were consistent over the SLE subtypes and sites. Our approach revealed distinct and robust tract-based WMH patterns within SLE patients. This method could provide a basis, to link the location of WMH with clinical symptoms. Furthermore, it could be used for other diseases characterized by presence of WMH to investigate both the clinical relevance of WMH and underlying pathomechanism in the brain., (© 2022. The Author(s).)

The transport of platelets in blood is commonly assumed to obey an advection-diffusion equation with a diffusion constant given by the so-called Zydney-Colton theory. Here we reconsider this hypothesis based on experimental observations and numerical simulations including a fully resolved suspension of red blood cells and platelets subject to a shear. We observe that the transport of platelets perpendicular to the flow can be characterized by a non-trivial distribution of velocities with and exponential decreasing bulk, followed by a power law tail. We conclude that such distribution of velocities leads to diffusion of platelets about two orders of magnitude higher than predicted by Zydney-Colton theory. We tested this distribution with a minimal stochastic model of platelets deposition to cover space and time scales similar to our experimental results, and confirm that the exponential-powerlaw distribution of velocities results in a coefficient of diffusion significantly larger than predicted by the Zydney-Colton theory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kotsalos, Raynaud, Lätt, Dutta, Dubois, Zouaoui Boudjeltia and Chopard.)

Background: Chemo- and radiotherapy (RT) is standard treatment for patients with high-grade glioma, but may cause side-effects on the patient's cognitive function., Aim: Use of diffusion tensor imaging (DTI) to investigate the longitudinal changes in normal-appearing brain tissue in glioblastoma patients undergoing modern arc-based RT with volumetric modulated arc therapy (VMAT) or helical tomotherapy., Materials and Methods: The study included 27 patients newly diagnosed with glioblastoma and planned for VMAT or tomotherapy. All subjects underwent magnetic resonance imaging at the start of RT and at week 3, 6, 15, and 26. Fourteen subjects were additionally imaged at week 52. The DTI data were co-registered to the dose distribution maps. Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were assessed in the corpus callosum, the centrum semiovale, the hippocampus, and the amygdala., Results: Significant longitudinal changes in FA, MD, and RD were mainly found in the corpus callosum. In the other examined brain structures, only sparse and transient changes were seen. No consistent correlations were found between biodose, age, or gender and changes in DTI parameters., Conclusion: Longitudinal changes in MD, FA, and RD were observed but only in a limited number of brain structures and the changes were smaller than expected from literature. The results suggest that modern, arc-based RT may have less negative effect on normal-appearing parts of the brain tissue up to 12 months after radiotherapy.

Background: Previous research has provided evidence for cognitive dysfunction as a common symptom of systemic lupus erythematosus (SLE). In light of this, the primary goal of this study was to investigate how cognitive impairment in this patient group develops over time. In addition, the present dataset contributes to delineating the specific abilities that are impaired in SLE patients as well as answering the question whether the disease affects the cognition of SLE patients with neuropsychiatric manifestations (NPSLE) and without (non-NPSLE) in distinct ways., Methods: 91 female participants (33 NPSLE, 29 non-NPSLE, 29 healthy controls (HC)) underwent standardized neurocognitive testing. A total of ten different cognitive abilities were assessed, among others executive function, memory, and attention. Some of the participants (30 NPSLE patients, 22 non-NPSLE, 13 HC) were tested twice (mean time between testing sessions: 50 months) to enable longitudinal tracking of cognitive abilities. Analyses of Variance (ANOVA) were conducted to determine whether cognitive performance differed cross-sectionally between the groups. Linear mixed effects models were fit to investigate performance differences between the groups over time., Results: Cross-sectional analysis at follow-up demonstrated that the cognitive performance of both NPSLE and non-NPSLE was significantly lower than that of HC for the motor speed and the psychomotor speed domain. Additionally, NPSLE patients performed significantly weaker than HC in the complex attention domain. At the same time, the cross-sectional data did not yield any support for performance differences between NPSLE and non-NPSLE patients. Weak positive correlations between disease duration and psychomotor speed, motor speed and reaction time emerged. A temporal progression of cognitive dysfunction in SLE patients was not confirmed., Conclusions: Cognitive performance is affected in both non-NPSLE and NPSLE patients. However, a linear decline in performance over time could not be verified. More in-depth longitudinal assessments of cognition in SLE patients are needed to establish how cognitive abilities in this patient population develop over time., (© 2022. The Author(s).)

At field strengths of 7 T and above, T 1 -weighted imaging of human brain suffers increasingly from radiofrequency (RF) B 1 inhomogeneities. The well-known MP2RAGE (magnetization prepared two rapid acquisition gradient echoes) sequence provides a solution but may not be readily available for all MR systems. Here, we describe the implementation and evaluation of a sequential protocol to obtain normalized magnetization prepared rapid gradient echo (MPRAGE) images at 0.7, 0.8, or 0.9-mm isotropic spatial resolution. Optimization focused on the reference gradient-recalled echo (GRE) that was used for normalization of the MPRAGE. A good compromise between white-gray matter contrast and the signal-to-noise ratio (SNR) was reached at a flip angle of 3° and total scan time was reduced by increasing the reference voxel size by a factor of 8 relative to the MPRAGE resolution. The average intra-subject coefficient-of-variation ( CV ) in segmented white matter (WM) was 7.9 ± 3.3% after normalization, compared to 20 ± 8.4% before. The corresponding inter-subject average CV in WM was 7.6 ± 7.6% and 13 ± 7.8%. Maps of T 1 derived from forward signal modelling showed no obvious bias after correction by a separately acquired flip angle map. To conclude, a non-interleaved acquisition for normalization of MPRAGE offers a simple alternative to MP2RAGE to obtain semi-quantitative purely T 1 -weighted images. These images can be converted to T 1 maps, analogously to the established MP2RAGE approach. Scan time can be reduced by increasing the reference voxel size which has only a miniscule effect on image quality.

Background: Carotid atherosclerotic plaques with intraplaque hemorrhage (IPH) are associated with elevated stroke risk. IPH is predominantly imaged based on paramagnetic properties of the upstream hemoglobin degradation product methemoglobin. This is an explorative observational study to test the feasibility of a spoiled gradient echo based T2* weighted MRI sequence (3D MEDIC) for carotid plaque imaging, and to compare signs suggestive of the downstream degradation product hemosiderin on 3D MEDIC with signs of methemoglobin on a T1wBB sequence., Methods: Patients with recent TIA or stroke were selected based on the presence on non-calcified plaque components on CTA to promote an enriched prevalence of IPH in the material. Patients (n = 42) underwent 3T MRI with 3D MEDIC and 2D turbo spin echo T1w black blood (T1wBB). Images were independently evaluated by two neuroradiologists and Cohens Kappa was used for inter-reader agreement for each sequence., Results: The technical feasibility for 3D MEDIC, was 34/42 patients (81%). Non-calcified plaque components with susceptibility effect without simultaneous T1-shortening-a combination suggestive of hemosiderin, was seen in 13/34 of the plaques. An equally large group display elevated T1w signal in combination with signal loss on 3D MEDIC, a combination suggestive of both hemosiderin and methemoglobin. Cohen's kappa for inter-reader agreement was 0.64 (CI 0.345-0.925) for 3D MEDIC and 0.94 (CI 0.81-1.00) for T1wBB., Conclusions: 3D MEDIC shows signal loss, without elevated T1w signal on T1wBB, in non-calcified tissue in many plaques in this group of patients. If further studies, including histological verification, confirm that the 3D MEDIC susceptibility effect is indeed caused by hemosiderin, 3D MEDIC could aid in the detection of IPH, beyond elevation of T1w signal., (© 2021. The Author(s).)

Purpose: Reperfusion therapy enables effective treatment of ischemic stroke presenting within 4-6 hours. However, tissue progression from ischemia to infarction is variable, and some patients benefit from treatment up until 24 hours. Improved imaging techniques are needed to identify these patients. Here, it was hypothesized that time dependence in diffusion MRI may predict tissue outcome in ischemic stroke., Methods: Diffusion MRI data were acquired with multiple diffusion times in five non-reperfused patients at 2, 9, and 100 days after stroke onset. Maps of "rate of kurtosis change" (k), mean kurtosis, ADC, and fractional anisotropy were derived. The ADC maps defined lesions, normal-appearing tissue, and the lesion tissue that would either be infarcted or remain viable by day 100. Diffusion parameters were compared (1) between lesions and normal-appearing tissue, and (2) between lesion tissue that would be infarcted or remain viable., Results: Positive values of k were observed within stroke lesions on day 2 (P = .001) and on day 9 (P = .023), indicating diffusional exchange. On day 100, high ADC values indicated infarction of 50 ± 20% of the lesion volumes. Tissue infarction was predicted by high k values both on day 2 (P = .026) and on day 9 (P = .046), by low mean kurtosis values on day 2 (P = .043), and by low fractional anisotropy values on day 9 (P = .029), but not by low ADC values., Conclusions: Diffusion time dependence predicted tissue outcome in ischemic stroke more accurately than the ADC, and may be useful for predicting reperfusion benefit., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

The purpose of this study is to investigate possible differences in brain structure, as measured by T1-weighted MRI, between patients with systemic lupus erythematosus (SLE) and healthy controls (HC), and whether any observed differences were in turn more severe in SLE patients with neuropsychiatric manifestations (NPSLE) than those without (non-NPSLE). Structural T1-weighted MRI was performed on 69 female SLE patients (mean age = 35.8 years, range = 18-51 years) and 24 age-matched female HC (mean age = 36.8 years, range = 23-52 years) in conjunction with neuropsychological assessment using the CNS Vital Signs test battery. T1-weighted images were preprocessed and analyzed by FSL-VBM. The results show that SLE patients had lower grey matter probability values than the control group in the VIIIa of the cerebellum bilaterally, a region that has previously been implied in sensorimotor processing in human and non-human primates. No structural differences for this region were found between NPSLE and non-NPSLE patients. VBM values from the VIIIa region showed a weak positive correlation with the psychomotor speed domain from CNS Vital Signs ( p = 0.05, r = 0.21), which is in line with its presumed role as a sensorimotor processing area.

•A detailed, practical description of a 2D lattice Boltzmann (LB) free-surface model and its coupling with a 1D LB shallow water model is provided.•A Python code is provided, that implements the Gaussian droplet benchmark of the research article (Thorimbert et al., 2019) corresponding to this method article.•Particular attention is given to the details of the free-surface implementation which, in the literature, vary among authors. These ambiguities must be addressed in order to build a reproducible scheme, as well as the exact implementation and parameters of the coupling model proposed in the associated research article., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Purpose: Radiological assessment of primary brain neoplasms, both high (HGG) and low grade tumors (LGG), based on contrast-enhancement alone can be inaccurate. We evaluated the radiological value of amide proton transfer weighted (APTw) MRI as an imaging complement for pre-surgical radiological diagnosis of brain tumors., Methods: Twenty-six patients were evaluated prospectively; (22 males, 4 females, mean age 55 years, range 26-76 years) underwent MRI at 3T using T1-MPRAGE pre- and post-contrast administration, conventional T2w, FLAIR, and APTw imaging pre-surgically for suspected primary/secondary brain tumor. Assessment of the additional value of APTw imaging compared to conventional MRI for correct pre-surgical brain tumor diagnosis. The initial radiological pre-operative diagnosis was based on the conventional contrast-enhanced MR images. The range, minimum, maximum, and mean APTw signals were evaluated. Conventional normality testing was performed; with boxplots/outliers/skewness/kurtosis and a Shapiro-Wilk's test. Mann-Whitney U for analysis of significance for mean/max/min and range APTw signal. A logistic regression model was constructed for mean, max, range and Receiver Operating Characteristic (ROC) curves calculated for individual and combined APTw signals., Results: Conventional radiological diagnosis prior to surgery/biopsy was HGG (8 patients), LGG (12 patients), and metastasis (6 patients). Using the mean and maximum: APTw signal would have changed the pre-operative evaluation the diagnosis in 8 of 22 patients (two LGGs excluded, two METs excluded). Using a cut off value of >2.0% for mean APTw signal integral, 4 of the 12 radiologically suspected LGG would have been diagnosed as high grade glioma, which was confirmed by histopathological diagnosis. APTw mean of >2.0% and max >2.48% outperformed four separate clinical radiological assessments of tumor type, P-values = .004 and = .002, respectively., Conclusions: Using APTw-images as part of the daily clinical pre-operative radiological evaluation may improve diagnostic precision in differentiating LGGs from HGGs, with potential improvement of patient management and treatment., Competing Interests: PvZ acknowledges research support from Philips Healthcare, travel support from Philips Healthcare, paid lectures for Philips Healthcare. Also, APT technology is licensed to Philips Healthcare. The commercial vendor Siemens Healthcare provided support in the form of salaries for authors FT and BS, but did not have any additional role in the study. The specific roles of these authors are articulated in the ‘author contributions’ section. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo, especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process., Competing Interests: HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is also a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS). These do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Ultrahigh-field (UHF) MRI advances towards clinical use. Patient compliance is generally high, but few large-scale studies have investigated the effects experienced in 7T MRI systems, especially considering peripheral nerve stimulation (PNS) and caregiving., Purpose: To evaluate the quantity, the intensity, and subjective experiences from short-term effects, focusing on the levels of comfort and compliance of subjects., Study Type: Prospective., Population: In all, 954 consecutive MRIs in 801 subjects for 3 years., Field Strength: 7T., Assessment: After the 7T examination, a questionnaire was used to collect data., Statistical Tests: Descriptive statistics, Spearman's rank correlation, Mann-Whitney U-test, and t-test., Results: The majority (63%) of subjects agreed that the MRI experience was comfortable and 93% would be willing to undergo future 7T MRI as a patient (5% undecided) and 82% for research purposes (12% undecided). The most common short-term effects experienced were dizziness (81%), inconsistent movement (68%), PNS (63%), headache (40%), nausea (32%), metallic taste (12%), and light flashes (8%). Of the subjects who reported having PNS (n = 603), 44% experienced PNS as "not uncomfortable at all," 45% as "little or very little uncomfortable," and 11% as "moderate to very much uncomfortable." Scanner room temperature was experienced more comfortable before (78%) than during (58%) examinations, and the noise level was acceptable by 90% of subjects. Anxiety before the examination was reported by 43%. Patients differed from healthy volunteers regarding an experience of headache, metallic taste, dizziness, or anxiety. Room for improvement was pointed out after 117 examinations concerning given information (n = 73), communication and sound system (n = 35), or nursing care (n = 15)., Data Conclusion: Subjectively reported effects occur in actively shielded 7T MRI and include physiological responses and individual psychological issues. Although leaving room for improvement, few subjects experienced these effects being so uncomfortable that they would lead to aversion to future UHF examinations., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 5 J. Magn. Reson. Imaging 2020;52:1265-1276., (© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Introduction : Cognitive function is an important outcome measure in patients with brain tumor, providing information about the patient's clinical situation, treatment effects and possible progressive disease. The aim of this longitudinal study was to evaluate effects of the currently used radiation and chemotherapy treatment on cognitive function and to investigate associations between cognitive function at baseline and progression as well as overall survival. Methods : 32 patients newly diagnosed with malignant glioma were evaluated at baseline with CNS Vital Signs (CNS-VS), a computerized standardized neuropsychological test battery, prior to arc-based radiotherapy and concomitant chemotherapy with Temozolomide. CNS-VS measures the cognitive functions known to be affected in patients with brain tumor, covering nine cognitive domains. Follow-up cognitive evaluations were performed in 26 patients after 3.5 months and in 13 patients 1 year after treatment start. Results : Overall cognitive scores were lower in the studied patient cohort at baseline compared to standardized domain scores. At 3.5 months follow-up cognitive functioning was slightly decreased, but only in 1/9 cognitive domains - visual memory - where significant changes were found compared to baseline test results. Similarly, at 12 months follow-up no significant changes in cognitive test results were seen compared to baseline examination, except for a decrease in the visual memory domain. In relation to early progression, the most significant cognitive deficits were dysfunctional visual memory and low executive functioning at baseline. Low executive function at baseline correlated most significantly with shorter overall survival. Conclusion : The present study suggests that the currently used arc-based radiotherapy and chemotherapy might affect cognitive function less negatively than previously described during treatment and in the first year after treatment in malignant glioma patients. In general, a high cognitive test score at baseline was associated with longer time to progression and with longer survival.

Purpose: To address the systematic bias in whole-brain dual flip angle (DFA) T 1 -mapping at 7T by optimizing the flip angle pair and carefully selecting radiofrequency (RF) pulse shape and duration., Theory and Methods: Spoiled gradient echoes can be used to estimate whole-brain maps of T 1 . This can be accomplished by using only two acquisitions with different flip angles, that is, a DFA-based approach. Although DFA-based T 1 -mapping is seemingly straightforward to implement, it is sensitive to bias caused by incomplete spoiling and incidental magnetization transfer effects. Further bias is introduced by the increased B 0 and B 1 + inhomogeneities at 7T. Experiments were performed to determine the optimal flip angle pair and appropriate RF pulse shape and duration. Obtained T 1 estimates were validated using inversion recovery prepared echo planar imaging and compared to literature values. A multi-echo readout was used to increase signal-to-noise ratio, enabling quantification of R 2 ∗ and susceptibility, χ., Results: Incomplete spoiling was observed above a local flip angle of approximately 20°. An asymmetric gauss-filtered sinc pulse with a constant duration of 700 μs showed a sufficiently flat frequency response profile to avoid incomplete excitation in areas with high B 0 offsets. A pulse duration of 700 μs minimized effects from incidental magnetization transfer., Conclusion: When performing DFA-based T 1 -mapping one should (a) limit the higher flip angle to avoid incomplete spoiling, (b) use a RF pulse shape insensitive to B 0 inhomogeneities and (c) apply a constant RF pulse duration, balanced to minimize incidental magnetization transfer., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Differentiation between glioblastoma and brain metastasis may be challenging in conventional contrast-enhanced MRI., Purpose: To investigate if perfusion-weighted MRI is able to differentiate glioblastoma from metastasis and, as a second aim was to see if it was possible in the latter group, to predict the primary site of neoplasm., Material and Methods: Hundred and fourteen patients with newly discovered tumor lesion (76 metastases and 38 glioblastomas) underwent conventional contrast-enhanced MRI including dynamic susceptibility contrast perfusion sequence. The calculated relative cerebral blood volumes were analyzed in the solid tumor area, peritumoral area, area adjacent to peritumoral area, and normal appearing white matter in contralateral semioval center. The Student t-test was used to detect statistically significant differences in relative cerebral blood volume between glioblastomas and metastases in the aforementioned areas. Furthermore, the metastasis group was divided in four sub groups (lung-, breast-, melanoma-, and gastrointestinal origin) and using one-way ANOVA test. P-values < 0.05 were considered significant., Results: Relative cerebral blood volume (rCBV) in the peritumoral edema was significantly higher in glioblastomas than in metastases (mean 3.2 ± 1.4 and mean 0.9 ± 0.7), respectively, (P < 0.0001). No significant differences in the solid tumor area or the area adjacent to edema were found, (P = 0.28 and 0.21 respectively). There were no significant differences among metastases in the four groups., Conclusion: It is possible to differentiate glioblastomas from metastases by measuring the CBV in the peritumoral edema. It is not possible to differentiate between brain metastases from different primaries (lung-, breast-, melanoma or gastrointestinal) using CBV-measurements in the solid tumor area, peritumoral edema or area adjacent to edema., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Material and methods: Thirty-eight (21 women) ALL survivors, median age 38 (27-46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. Results: ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention ( p  < .001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all p  < .05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum ( p  < .05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory ( r = -0.40, p  < .04). The left and right uncinate fasciculus ( r  = 0.6, p  < .001), ( r = -0.5, p  < .02) as well as the right ventral cingulum ( r  = 0.5, p  < .007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus ( r  = 0.3, r  = 0.05, p  = .02), and ventral cingulum ( r  = 0.3, p  = .02) were associated with impaired results of episodic visual memory. Conclusion: ALL survivors with cognitive deficits demonstrated microstructural damage in several WM tracts that were more extensive with DKI as compared to DTI; this might be a marker of radiation and chemotherapy neurotoxicity underlying cognitive dysfunction.

Background: Residual tumor volume (RTV) and extent of resection (EOR) have previously been shown to affect survival in glioblastoma (GB) patients. Quantitative radiological assessment (QRA) of these factors could potentially affect clinical decision-making in the postoperative period., Purpose: The first aim was to evaluate the reproducibility of different volume estimation methods of RTV and EOR by comparing QRA with subjective visual estimation and with objective volume estimations. The second aim was to clarify whether QRA of RTV and EOR would provide accuracy in predicting progression-free survival (PFS) and overall survival (OS) in GB patients., Material and Methods: Seventy GB patients were studied retrospectively. Reproducibility of QRA was compared to conventional visual analysis. Intra-rater agreement between two repeated measurements of 25 patients was calculated. QRA for RTV and EOR was made for the entire study population. Survival analysis was performed by multivariate cox-regression analysis., Results: QRA of RTV and EOR gave superior intra-rater agreement compared to subjective evaluation. Multivariate survival analysis showed prognostic significance on 18 months PFS (hazard ratio [HR] = 0.44, P = 0.003) and OS (HR = 0.42, P = 0.012) at RTV < 1.6 mL and with EOR > 96% on PFS (HR = 2.152, P = 0.005) but not on OS (HR = 1.92, P = 0.053)., Conclusion: QRA of tumor volumes is more robust compared to standard evaluation methods. Since EOR and RTV are correlated to the prognosis in GB, quantitative analysis of tumor volumes could aid decision-making and patient management postoperatively.

Microstructure imaging techniques based on tensor-valued diffusion encoding have gained popularity within the MRI research community. Unlike conventional diffusion encoding-applied along a single direction in each shot-tensor-valued encoding employs diffusion encoding along multiple directions within a single preparation of the signal. The benefit is that such encoding may probe tissue features that are not accessible by conventional encoding. For example, diffusional variance decomposition (DIVIDE) takes advantage of tensor-valued encoding to probe microscopic diffusion anisotropy independent of orientation coherence. The drawback is that tensor-valued encoding generally requires gradient waveforms that are more demanding on hardware; it has therefore been used primarily in MRI systems with relatively high performance. The purpose of this work was to explore tensor-valued diffusion encoding on clinical MRI systems with varying performance to test its technical feasibility within the context of DIVIDE. We performed whole-brain imaging with linear and spherical b-tensor encoding at field strengths between 1.5 and 7 T, and at maximal gradient amplitudes between 45 and 80 mT/m. Asymmetric gradient waveforms were optimized numerically to yield b-values up to 2 ms/μm2. Technical feasibility was assessed in terms of the repeatability, SNR, and quality of DIVIDE parameter maps. Variable system performance resulted in echo times between 83 to 115 ms and total acquisition times of 6 to 9 minutes when using 80 signal samples and resolution 2×2×4 mm3. As expected, the repeatability, signal-to-noise ratio and parameter map quality depended on hardware performance. We conclude that tensor-valued encoding is feasible for a wide range of MRI systems-even at 1.5 T with maximal gradient waveform amplitudes of 33 mT/m-and baseline experimental design and quality parameters for all included configurations. This demonstrates that tissue features, beyond those accessible by conventional diffusion encoding, can be explored on a wide range of MRI systems., Competing Interests: MN declares research support from, and ownership interests in, Colloidal Resource and it subsidiary Random Walk Imaging AB. FSz is a former employee of Random Walk Imaging AB. Remaining authors declare no conflict of interest.

Background/objectives: Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat., Subjects/methods: A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17-56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage., Results: Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35-1168) mm 3 vs. 879 (775-1086) mm 3 ; P < 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (r s  = -0.67; P < .001; r s  = -0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm 3 increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5-3.9; P < 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records., Conclusions: A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.

We investigated multivoxel proton magnetic resonance spectroscopy ( 1 H-MRS) biometrics for preoperative differentiation and prognosis of patients with brain metastases (MET), low-grade glioma (LGG) and high-grade glioma (HGG). In total, 33 patients (HGG, 14; LGG, 9; and 10 MET) were included. 1 H-MRS imaging (MRSI) data were assessed and neurochemical profiles for metabolites N-acetyl aspartate (NAA) + NAAG(NAA), Cr + PCr(total creatine, tCr), Glu + Gln(Glx), lactate (Lac), myo-inositol(Ins), GPC + PCho(total choline, tCho), and total lipids, and macromolecule (tMM) signals were estimated. Metabolites were reported as absolute concentrations or ratios to tCho or tCr levels. Voxels of interest in an MRSI matrix were labeled according to tissue. Logistic regression, receiver operating characteristic, and Kaplan-Meier survival analysis was performed. Across HGG, LGG, and MET, average Ins/tCho was shown to be prognostic for overall survival (OS): low values (≤1.29) in affected hemisphere predicting worse OS than high values (>1.29), (log rank < 0.007). Lip/tCho and Ins/tCho combined showed 100% sensitivity and specificity for both HGG/LGG ( P < .001) and LGG/MET ( P < .001) measured in nonenhancing/contrast-enhancing lesional tissue. Combining tCr/tCho in perilesional edema with tCho/tCr and NAA/tCho from ipsilateral normal- appearing tissue yielded 100% sensitivity and 81.8% specificity ( P < .002) for HGG/MET. Best single biomarker: Ins/tCho for HGG/LGG and total lipid/tCho for LGG/MET showed 100% sensitivity and 75% and 100% specificity, respectively. HGG/MET; NAA/tCho showed 75% sensitivity and 84.6% specificity. Multivoxel 1H-MRSI provides prognostic information for OS for HGG/LGG/MET and a multibiometric approach for differentiation may equal or outperform single biometrics., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare

Background: Children born very preterm (PT) after fetal growth restriction (FGR) exhibit cognitive impairment at early school age. The relationship between neurodevelopmental impairment and attained regional brain volumes is unknown. Methods: We studied 23 preterm children with FGR (PT-FGR), 24 matched preterm children AGA (PT-AGA), and 27 matched term AGA children (T-AGA) by measuring brain volumes with magnetic resonance imaging at early school age. Cognitive and motor functions were assessed by the Wechsler Intelligence Scales for Children and the ABC-Movement score. Results: The mean ( SD ) full-scale IQ was 80 (17) in the PT-FGR group and 103 (12) in the PT-AGA group ( p < 0.001). The PT-FGR group had lower mean total, gray matter, white matter, thalamic, cerebellar white matter, and hippocampal volumes as compared to the T-AGA group ( p = 0.01, 0.04, 0.003, 0.002, 0.001, and 0.009, respectively). Brain volumes did not differ significantly between the PT groups. Reduction of hippocampal volume correlated with degree of growth restriction at birth ( r = 0.46, p = 0.05). Neither the full-scale IQ nor the ABC movement score <5th percentile were related to brain volumes. Conclusion: Brain volumes as determined by MRI at early school age were primarily associated with degree of prematurity at birth and less with FGR. Regional brain volumes did not discriminate cognitive and motor function beyond that predicted by gestational age at birth.

Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal-subcortical connections. We aim to characterize the grey and white matter components of frontal-thalamic and frontal-striatal circuits in bvFTD. Twenty-four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal-striatal-thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p = .032, and 217% in the thalamus, p = .004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p = .002, and 65% in the thalamus, p = .020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal-subcortical networks; however, longitudinal studies are necessary to test this hypothesis., (© 2018 Wiley Periodicals, Inc.)

Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. Recent studies show the existing clinical tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions. Further they are also incapable to consider inter-individual variability. A physical description of platelets deposition was introduced recently in Chopard et al. (2017), by integrating fundamental understandings of how platelets interact in a numerical model, parameterized by five parameters. These parameters specify the deposition process and are relevant for a biomedical understanding of the phenomena. One of the main intuition is that these parameters are precisely the information needed for a pathological test identifying CVD captured and that they capture the inter-individual variability. Following this intuition, here we devise a Bayesian inferential scheme for estimation of these parameters, using experimental observations, at different time intervals, on the average size of the aggregation clusters, their number per mm 2 , the number of platelets, and the ones activated per μℓ still in suspension. As the likelihood function of the numerical model is intractable due to the complex stochastic nature of the model, we use a likelihood-free inference scheme approximate Bayesian computation (ABC) to calibrate the parameters in a data-driven manner. As ABC requires the generation of many pseudo-data by expensive simulation runs, we use a high performance computing (HPC) framework for ABC to make the inference possible for this model. We consider a collective dataset of seven volunteers and use this inference scheme to get an approximate posterior distribution and the Bayes estimate of these five parameters. The mean posterior prediction of platelet deposition pattern matches the experimental dataset closely with a tight posterior prediction error margin, justifying our main intuition and providing a methodology to infer these parameters given patient data. The present approach can be used to build a new generation of personalized platelet functionality tests for CVD detection, using numerical modeling of platelet deposition, Bayesian uncertainty quantification, and High performance computing.

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

Context: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown., Objective: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP., Design: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation., Setting: The South Medical Region of Sweden (2.5 million inhabitants)., Participants: Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients., Main Outcome Measures: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry., Results: Right uncinate fasciculus was significantly altered ( P  ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge ( P  = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory., Conclusions: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP., (© 2018 The authors.)

The aim was to evaluate volume, diffusion, and perfusion metrics for better presurgical differentiation between high-grade gliomas (HGG), low-grade gliomas (LGG), and metastases (MET). For this retrospective study, 43 patients with histologically verified intracranial HGG (n = 18), LGG (n = 10), and MET (n = 15) were chosen. Preoperative magnetic resonance data included pre- and post-gadolinium contrast-enhanced T1-weighted fluid-attenuated inversion recover, cerebral blood flow (CBF), cerebral blood volume (CBV), fractional anisotropy, and apparent diffusion coefficient maps used for quantification of magnetic resonance biometrics by manual delineation of regions of interest. A binary logistic regression model was applied for multiparametric analysis and receiver operating characteristic (ROC) analysis. Statistically significant differences were found for normalized-ADC-tumor (nADC-T), normalized-CBF-tumor (nCBF-T), normalized-CBV-tumor (nCBV-T), and normalized-CBF-edema (nCBF-E) between LGG and HGG, and when these metrics were combined, HGG could be distinguished from LGG with a sensitivity and specificity of 100%. The only metric to distinguish HGG from MET was the normalized-ADC-E with a sensitivity of 68.8% and a specificity of 80%. LGG can be distinguished from MET by combining edema volume (Vol-E), Vol-E/tumor volume (Vol-T), nADC-T, nCBF-T, nCBV-T, and nADC-E with a sensitivity of 93.3% and a specificity of 100%. The present study confirms the usability of a multibiometric approach including volume, perfusion, and diffusion metrics in differentially diagnosing brain tumors in preoperative patients and adds to the growing body of evidence in the clinical field in need of validation and standardization.

Purpose: In Parkinson's disease (PD), pathological microstructural changes occur that may be detected using diffusion magnetic resonance imaging (dMRI). However, there are few longitudinal studies that explore the effect of disease progression on diffusion indices., Methods: We prospectively included 76 patients with PD and 38 healthy controls (HC), all of whom underwent diffusion kurtosis imaging (DKI) as part of the prospective Swedish BioFINDER study at baseline and 2 years later. Annualized rates of change in DKI parameters, including fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK), were estimated in the gray matter (GM) by placing regions of interest (ROIs) in the basal ganglia and the thalamus, and in the white matter (WM) by tract-based spatial statistics (TBSS) analysis., Results: When adjusting for potential confounding factors (age, gender, baseline-follow-up interval, and software upgrade of MRI scanner), only a decrease in FA in the putamen of PD patients (β = - 0.248, P < .01) over 2 years was significantly different from the changes observed in HC over the same time period. This 2-year decrease in FA in the putamen in PD correlated with higher L-dopa equivalent dose at baseline (Spearman's rho = .399, P < .0001)., Conclusion: The study indicates that in PD microstructural changes in the putamen occur selectively over a 2-year period and can be detected with DKI.

Background: The purpose of this study was to investigate whether white matter microstructure is altered in patients suffering from systemic lupus erythematosus (SLE), and if so, whether such alterations differed between patients with and without neuropsychiatric symptoms., Methods: Structural MRI and diffusion tensor imaging (DTI) were performed in 64 female SLE patients (mean age 36.9 years, range 18.2-52.2 years) and 21 healthy controls (mean age 36.7 years, range 23.3-51.2 years) in conjunction with clinical examination, laboratory tests, cognitive evaluation, and self-assessment questionnaires. The patients were subgrouped according to the American College of Rheumatology Neuropsychiatric Systemic Lupus Erythematosus case definitions into non-neuropsychiatric SLE (nonNPSLE) and neuropsychiatric SLE (NPSLE)., Results: Comparisons between the SLE group and healthy controls showed that the mean fractional anisotropy (FA) was significantly reduced in the right rostral cingulum (p = 0.038), the mid-sagittal corpus callosum (CC) (p = 0.050), and the forceps minor of the CC (p = 0.015). The mean diffusivity (MD) was significantly increased in the left hippocampal cingulum (p = 0.017). No significant differences in MD or FA values were identified between NPSLE and nonNPSLE patients. Disease duration among all SLE patients correlated significantly with reduced FA in the CC (p < 0.05). No correlations were found between DTI parameters and white matter hyperintensities, SLE Disease Activity Index-2000, Systemic Lupus International Collaborating Clinical/ACR Organ Damage Index, or Montgomery Asberg Depression Rate Score Self-report., Conclusions: We found alterations of white matter microstructure in SLE patients that were related to disease duration and fatigue. Our results indicate that cerebral involvement in SLE is not isolated to the NPSLE subgroup.

Knowledge concerning the normal aging of cerebral white matter will improve our understanding of abnormal changes in neurodegenerative diseases. The microstructural basis of white matter maturation and aging can be investigated using diffusion tensor imaging (DTI). Generally, diffusion anisotropy increases during childhood and adolescence followed by a decline in middle age. However, this process is subject to spatial variations between tracts. The aim of this study was to investigate to what extent age-related variations also occur within tracts. DTI parameters were compared between segments of two white matter tracts, the cingulate bundle (CB) and the inferior fronto-occipital fasciculus (IFO), in 257 healthy individuals between 13 and 84years of age. Segments of the CB and the IFO were extracted and parameters for each segment were averaged across the hemispheres. The data was analysed as a function of age. Results show that age-related changes differ both between and within individual tracts. Different age trajectories were observed in all segments of the analysed tracts for all DTI parameters. In conclusion, aging does not affect white matter tracts uniformly but is regionally specific; both between and within white matter tracts., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Metabolic complications are frequent in childhood leukaemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors., Design: Case-control study., Patients: Three groups were included: (i) 27 CRT treated ALL survivors on hormone supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without HT involvement and (iii) 27 matched controls., Measurements: DTI parameters of the HT were measured and body composition., Results: Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥25 than with BMI <25. Compared to controls, ALL survivors had reduced FA (P=.04), increased MD (P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT, ALL survivors with a BMI ≥25 showed elevated MD (P=.03) and AD (P=.02) compared to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between CP survivors and controls., Conclusions: Long-term follow-up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT., (© 2017 John Wiley & Sons Ltd.)

Diffusion tensor imaging (DTI) has been used to study microstructural white matter alterations in a variety of conditions including normal aging and Alzheimer's disease (AD). White matter hyperintensities (WMH) are common in cognitively healthy elderly as well as in AD and exhibit elevated mean diffusivity (MD) and reduced fractional anisotropy (FA). However, the effect of WMH on statistical analysis of DTI estimates has not been thoroughly studied. In the present study we address this in two ways. First, we investigate the effect of WMH on MD and FA in the dorsal and ventral cingulum, the superior longitudinal fasciculus, and the corticospinal tract, by comparing two matched groups of cognitively healthy elderly (n = 21 + 21) with unequal WMH load. Second, we assess the effects of adjusting for WMH load when comparing MD and FA in prodromal AD subjects (n = 83) to cognitively healthy elderly (n = 132) in the abovementioned white matter tracts. Results showed the WMH in cognitively healthy elderly to have a generally large effect on DTI estimates (Cohen's d = 0.63 to 1.27 for significant differences in MD and -1.06 to -0.69 for FA). These effect sizes were comparable to those of various neurological and psychiatric diseases (Cohen's d = 0.57 to 2.20 for differences in MD and -1.76 to -0.61 for FA). Adjusting for WMH when comparing DTI estimates in prodromal AD subjects to cognitively healthy elderly improved the explanatory power as well as the outcome of the analysis, indicating that some of the differences in MD and FA were largely driven by unequal WMH load between the groups rather than alterations in normal-appearing white matter (NAWM). Thus, our findings suggest that if the purpose of a study is to compare alterations in NAWM between two groups using DTI it may be necessary to adjust the statistical analysis for WMH.

The early stages of clot formation in blood vessels involve platelet adhesion-aggregation. Although these mechanisms have been extensively studied, gaps in their understanding still persist. We have performed detailed in vitro experiments, using the well-known Impact-R device, and developed a numerical model to better describe and understand this phenomenon. Unlike previous studies, we took into account the differential role of pre-activated and non-activated platelets, as well as the three-dimensional nature of the aggregation process. Our investigation reveals that blood albumin is a major parameter limiting platelet aggregate formation in our experiment. Simulations are in very good agreement with observations and provide quantitative estimates of the adhesion and aggregation rates that are hard to measure experimentally. They also provide a value of the effective diffusion of platelets in blood subject to the shear rate produced by the Impact-R., Competing Interests: We declare we have no competing interests.

Purpose: Filter exchange imaging (FEXI) is sensitive to the rate of diffusional water exchange, which depends, eg, on the cell membrane permeability. The aim was to optimize and analyze the ability of FEXI to infer differences in the apparent exchange rate (AXR) in the brain between two populations., Methods: A FEXI protocol was optimized for minimal measurement variance in the AXR. The AXR variance was investigated by test-retest acquisitions in six brain regions in 18 healthy volunteers. Preoperative FEXI data and postoperative microphotos were obtained in six meningiomas and five astrocytomas., Results: Protocol optimization reduced the coefficient of variation of AXR by approximately 40%. Test-retest AXR values were heterogeneous across normal brain regions, from 0.3 ± 0.2 s -1 in the corpus callosum to 1.8 ± 0.3 s -1 in the frontal white matter. According to analysis of statistical power, in all brain regions except one, group differences of 0.3-0.5 s -1 in the AXR can be inferred using 5 to 10 subjects per group. An AXR difference of this magnitude was observed between meningiomas (0.6 ± 0.1 s -1 ) and astrocytomas (1.0 ± 0.3 s -1 )., Conclusions: With the optimized protocol, FEXI has the ability to infer relevant differences in the AXR between two populations for small group sizes. Magn Reson Med 77:1104-1114, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., (© 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas)., Patients and Methods: Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t -test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves., Results: There were significant differences in all mean DKI variables between perilesional and contralesional NAWM ( p =<0.000), except for axial kurtosis ( p =0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) ( p =0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815., Conclusions: Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes., Competing Interests: Disclosure: No potential conflicts of interest were disclosed.

The structural heterogeneity of tumor tissue can be probed by diffusion MRI (dMRI) in terms of the variance of apparent diffusivities within a voxel. However, the link between the diffusional variance and the tissue heterogeneity is not well-established. To investigate this link we test the hypothesis that diffusional variance, caused by microscopic anisotropy and isotropic heterogeneity, is associated with variable cell eccentricity and cell density in brain tumors. We performed dMRI using a novel encoding scheme for diffusional variance decomposition (DIVIDE) in 7 meningiomas and 8 gliomas prior to surgery. The diffusional variance was quantified from dMRI in terms of the total mean kurtosis (MK T ), and DIVIDE was used to decompose MK T into components caused by microscopic anisotropy (MK A ) and isotropic heterogeneity (MK I ). Diffusion anisotropy was evaluated in terms of the fractional anisotropy (FA) and microscopic fractional anisotropy (μFA). Quantitative microscopy was performed on the excised tumor tissue, where structural anisotropy and cell density were quantified by structure tensor analysis and cell nuclei segmentation, respectively. In order to validate the DIVIDE parameters they were correlated to the corresponding parameters derived from microscopy. We found an excellent agreement between the DIVIDE parameters and corresponding microscopy parameters; MK A correlated with cell eccentricity (r=0.95, p<10 -7 ) and MK I with the cell density variance (r=0.83, p<10 -3 ). The diffusion anisotropy correlated with structure tensor anisotropy on the voxel-scale (FA, r=0.80, p<10 -3 ) and microscopic scale (μFA, r=0.93, p<10 -6 ). A multiple regression analysis showed that the conventional MK T parameter reflects both variable cell eccentricity and cell density, and therefore lacks specificity in terms of microstructure characteristics. However, specificity was obtained by decomposing the two contributions; MK A was associated only to cell eccentricity, and MK I only to cell density variance. The variance in meningiomas was caused primarily by microscopic anisotropy (mean±s.d.) MK A =1.11±0.33 vs MK I =0.44±0.20 (p<10 -3 ), whereas in the gliomas, it was mostly caused by isotropic heterogeneity MK I =0.57±0.30 vs MK A =0.26±0.11 (p<0.05). In conclusion, DIVIDE allows non-invasive mapping of parameters that reflect variable cell eccentricity and density. These results constitute convincing evidence that a link exists between specific aspects of tissue heterogeneity and parameters from dMRI. Decomposing effects of microscopic anisotropy and isotropic heterogeneity facilitates an improved interpretation of tumor heterogeneity as well as diffusion anisotropy on both the microscopic and macroscopic scale., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27-46) years. All were treated with a CRT dose of 24Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p<0.001), memory (p<0.001), learning capacity (p<0.001), spatial ability (p<0.001), executive functions and attention (p<0.001) 34 years after ALL treatment. Compared to controls ALL survivors had reduced white matter (WM) (492 vs 536cm 3 , p<0.001) and grey matter (GM) volumes (525 vs 555cm 3 , p=0.001). ALL survivors had lower levels of WM N-acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p=0.004), WM NAA+NAAG (N-acetylaspartylglutamate)/Cr (1.61 vs 1.85, p<0.001) and lower levels of GM NAA/Cr (1.18 vs 1.30, p=0.001) and GM NAA+NAAG/Cr (1.28 vs 1.34, p=0.01) compared to controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs 0.56, p=0.01) concentrations compared to controls. There was a significantly negative correlation of years since ALL diagnosis to WM NAA+NAAG/Cr (r=-0.4, p=0.04) in ALL survivors. The present study shows impaired brain metabolism detected by MRS, reduced brain volumes and neurocognitive impairment in childhood ALL survivors treated with cranial radiotherapy and chemotherapy, despite complete hormone substitution. We also report an impairment of metabolites correlated to time since treatment and a progressive impairment in sustained attention, suggesting an accelerated aging in the irradiated brain. Following these survivors many decades, or throughout life, after treatment with cranial radiotherapy and chemotherapy is highly warranted for a broader understanding of long-term outcome in this patient group., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the "prefrontal" syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control., Competing Interests: The authors have declared that no competing interests exist.

In Parkinson's disease (PD), pathological microstructural changes occur and such changes might be detected using diffusion magnetic resonance imaging (dMRI). However, it is unclear whether dMRI improves PD diagnosis or helps differentiating between phenotypes, such as postural instability gait difficulty (PIGD) and tremor dominant (TD) PD. We included 105 patients with PD and 44 healthy controls (HC), all of whom underwent dMRI as part of the prospective Swedish BioFINDER study. Diffusion kurtosis imaging (DKI) and neurite density imaging (NDI) analyses were performed using regions of interest in the basal ganglia, the thalamus, the pons and the midbrain as well as tractography of selected white matter tracts. In the putamen, the PD group showed increased mean diffusivity (MD) (p = .003), decreased fractional anisotropy (FA) (p = .001) and decreased mean kurtosis (MK), compared to HC (p = .024). High MD and a low MK in the putamen were associated with more severe motor and cognitive symptomatology (p < .05). Also, patients with PIGD exhibited increased MD in the putamen compared to the TD patients (p = .009). In the thalamus, MD was increased (p = .001) and FA was decreased (p = .032) in PD compared to HC. Increased MD and decreased FA correlated negatively with motor speed and balance (p < .05). In the superior longitudinal fasciculus (SLF), MD (p = .019) and fiso were increased in PD compared to HC (p = .03). These changes correlated negatively with motor speed (p < .002) and balance (p < .037). However, most of the observed changes in PD were also present in cases with either multiple system atrophy (n = 11) or progressive supranuclear palsy (n = 10). In conclusion, PD patients exhibit microstructural changes in the putamen, the thalamus, and the SLF, which are associated with worse disease severity. However, the dMRI changes are not sufficiently specific to improve the diagnostic work-up of PD. Longitudinal studies should evaluate whether dMRI measures can be used to track disease progression.

Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using (18)F-fluorodopa and (11)C-raclopride positron emission tomography. Here we report the postmortem analysis of a patient with Parkinson's disease who 24 y earlier underwent unilateral transplantation of embryonic dopaminergic neurons in the putamen and subsequently exhibited major motor improvement and recovery of striatal dopaminergic function. Histopathological analysis showed that a dense, near-normal graft-derived dopaminergic reinnervation of the putamen can be maintained for a quarter of a century despite severe host brain pathology and with no evidence of immune response. In addition, ubiquitin- and α-synuclein-positive inclusions were seen, some with the appearance of typical Lewy bodies, in 11-12% of the grafted dopaminergic neurons, reflecting the spread of pathology from the host brain to the transplants. Because the clinical benefits induced by transplantation in this patient were gradually lost after 14 y posttransplantation, our findings provide the first reported evidence, to our knowledge, that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain.

Metabolic complications are prevalent in individuals treated with cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia (ALL). The hypothalamus is a master regulator of endocrine and metabolic control. The aim of this study was to investigate whether the hypothalamic volume would be associated to metabolic parameters in ALL survivors. Thirty-eight (21 women) survivors participated in this study 34 years after diagnosis and with a median age of 38 (27-46) years. All were treated with a median CRT dose of 24 Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 31 matched controls. We performed analyses of fat mass, fat free mass, plasma (p)-glucose, p-insulin, Homa-Index (a measure of insulin resistance), serum (s)-leptin, s-ghrelin and of the hypothalamic volume in scans obtained by magnetic resonance imaging (MRI) at 3 Tesla. Serum leptin/kg fat mass (r = -0.4, P = 0.04) and fat mass (r = -0.4, P = 0.01) were negatively correlated with the HT volume among ALL survivors, but not among controls. We also detected significantly higher BMI, waist, fat mass, p-insulin, Homa-Index, leptin/kg fat mass and s-ghrelin and significantly lower fat free mass specifically among female ALL survivors (all P<0.01). Interestingly, s-ghrelin levels increased with time since diagnosis and with low age at diagnosis for childhood ALL. Our results showed that leptin/kg fat mass and fat mass were associated with a reduced HT volume 34 years after ALL diagnosis and that women treated with CRT after ALL are at high risk of metabolic abnormalities. Taken together our data suggest that the hypothalamus is involved in the metabolic consequences after CRT in ALL survivors.