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Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R1), transverse relaxation (R2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R1-difference-map. The quantitative R1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.

BACKGROUND AND PURPOSE: Arterial spin-labeling-derived CBF values may be affected by arterial transit time artefacts. Thus, our aim was to assess to what extent arterial spin-labeling–derived CBF and cerebrovascular reserve capacity values in major vascular regions are overestimated due to the arterial transit time artifacts in patients with Moyamoya disease. MATERIALS AND METHODS: Eight patients with Moyamoya disease were included before or after revascularization surgery. CBF maps were acquired using a 3D pseudocontinuous arterial spin-labeling sequence, before and 5, 15, and 25 minutes after an IV acetazolamide injection and were registered to each patient’s 3D-T1-weighted images. Vascular regions were defined by spatial normalization to a Montreal Neurological Institute–based vascular regional template. The arterial transit time artifacts were defined as voxels with high signal intensity corresponding to the right tail of the histogram for a given vascular region, with the cutoff selected by visual inspection. Arterial transit time artifact maps were created and applied as masks to exclude arterial transit time artifacts on CBF maps, to create corrected CBF maps. The cerebrovascular reserve capacity was calculated as CBF after acetazolamide injection relative to CBF at baseline for corrected and uncorrected CBF values, respectively. RESULTS: A total of 16 examinations were analyzed. Arterial transit time artifacts were present mostly in the MCA, whereas the posterior cerebral artery was generally unaffected. The largest differences between corrected and uncorrected CBF and cerebrovascular reserve capacity values, reported as patient group average ratio and percentage point difference, respectively, were 0.978 (95% CI, 0.968–0.988) and 1.8 percentage points (95% CI, 0.3–3.2 percentage points). Both were found in the left MCA, 15 and 5 minutes post-acetazolamide injection, respectively. CONCLUSIONS: Arterial transit time artifacts have negligible overestimation effects on calculated vascular region-based CBF and cerebrovascular reserve capacity values derived from single-delay 3D pseudocontinuous arterial spin-labeling.

Traumatic brain injury (TBI) or repeated sport-related concussions (rSRC) may lead to long-term memory impairment. Diffusion tensor imaging (DTI) is helpful to reveal global white matter damage but may underestimate focal abnormalities. We investigated the distribution of post-injury regional white matter changes after TBI and rSRC. Six patients with moderate/severe TBI, and 12 athletes with rSRC were included ≥6 months post-injury, and 10 (age-matched) healthy controls (HC) were analyzed. The Repeatable Battery for the Assessment of Neuropsychological Status was performed at the time of DTI. Major white matter pathways were tracked using q-space diffeomorphic reconstruction and analyzed for global and regional changes with a controlled false discovery rate. TBI patients displayed multiple classic white matter injuries compared with HC (p < 0.01). At the regional white matter analysis, the left frontal aslant tract, anterior thalamic radiation, and the genu of the corpus callosum displayed focal changes in both groups compared with HC but with different trends. Both TBI and rSRC displayed worse memory performance compared with HC (p < 0.05). While global analysis of DTI-based parameters did not reveal common abnormalities in TBI and rSRC, abnormalities to the fronto-thalamic network were observed in both groups using regional analysis of the white matter pathways. These results may be valuable to tailor individualized rehabilitative approaches for post-injury cognitive impairment in both TBI and rSRC patients.

Primary Objective Traumatic brain injury (TBI) and sports-related concussion (SRC) may result in chronic functional and neuroanatomical changes. We tested the hypothesis that neuroimaging findings (cerebral blood flow (CBF), cortical thickness, and 1H-magnetic resonance (MR) spectroscopy (MRS)) were associated to cognitive function, TBI severity, and sex. Research Design Eleven controls, 12 athletes symptomatic following ≥3SRCs and 6 patients with moderate-severe TBI underwent MR scanning for evaluation of cortical thickness, brain metabolites (MRS), and CBF using pseudo-continuous arterial spin labeling (ASL). Cognitive screening was performed using the RBANS cognitive test battery. Main Outcomes and Results RBANS-index was impaired in both injury groups and correlated with the injury severity, although not with any neuroimaging parameter. Cortical thickness correlated with injury severity (p = 0.02), while neuronal density, using the MRS marker ((NAA+NAAG)/Cr, did not. On multivariate analysis, injury severity (p = 0.0003) and sex (p = 0.002) were associated with CBF. Patients with TBI had decreased gray (p = 0.02) and white matter (p = 0.02) CBF compared to controls. CBF was significantly lower in total gray, white matter and in 16 of the 20 gray matter brain regions in female but not male athletes when compared to female and male controls, respectively. Conclusions Injury severity correlated with CBF, cognitive function, and cortical thickness. CBF also correlated with sex and was reduced in female, not male, athletes. Chronic CBF changes may contribute to the persistent injury mechanisms in TBI and rSRC.

Purpose Assess the agreement for two investigators between computed tomography (CT) and magnetic resonance imaging (MRI) for seven imaging features included in the iNPH Radscale, a radiological screening tool. Methods The study included 35 patients with idiopathic normal pressure hydrocephalus (iNPH) who were treated surgically from 2011 to 2015 at Uppsala University Hospital with preoperative CT and MRI performed with maximum 3 months between scans. Seven features were assessed: Evans’ index, temporal horn size, callosal angle, periventricular white matter changes, narrow high convexity sulci, focally enlarged sulci, and enlarged Sylvian fissures. All scans were assessed by two investigators who were blinded to each other’s results and to clinical data. Results The agreement between CT and MRI was almost perfect for Evans’ index, temporal horns, narrow sulci, and Sylvian fissures (kappa and intraclass correlation, 0.84–0.91, p ≤ 0.001). There was substantial to almost perfect agreement for callosal angle and focally enlarged sulci. The concordance between modalities was fair for changes in periventricular white matter. Conclusion CT and MRI are equally good for assessing radiological signs associated with iNPH except for periventricular white matter changes, as MRI has superior soft tissue contrast. The other imaging features can be evaluated consistently, and assessments are reproducible independent of modality. Therefore, the iNPH Radscale is applicable to both CT and MRI and may become an important tool for standardized evaluation in the workup in patients with suspected iNPH. Electronic supplementary material The online version of this article (10.1007/s00234-019-02273-2) contains supplementary material, which is available to authorized users.

OBJECTIVES To determine whether treatment with autologous hematopoietic stem cell transplantation (HSCT) can induce sustained complete remission in patients with multiple sclerosis (MS). MATERIAL AND METHODS Case series of patients with relapsing-remitting MS (n = 10) treated at a single center between 2004 and 2007 and followed up for 10 years. The patients were treated with a BEAM/ATG conditioning regimen (n = 9) or a cyclophosphamide/ATG conditioning regimen (n = 1) followed by infusion of unmanipulated autologous hematopoietic stem cells. The primary endpoint was sustained complete remission. Sustained complete remission was defined as "no evidence of disease activity-4," sustained for a period of at least 5 years without any ongoing disease-modifying treatment. Furthermore, MS was considered as "resolved" if intrathecal IgG production and cerebrospinal fluid neurofilament light levels were normalized as well. RESULTS Five out of 10 patients were in sustained complete remission at the end of the study. In three of them, MS was resolved. CONCLUSIONS Our data demonstrate that sustained complete remission after autologous HSCT for MS is possible.

Purpose Atrial fibrillation (AF) imposes an inherent risk for stroke and silent cerebral emboli, partly related to left atrial (LA) remodeling and activation of inflammatory and coagulation systems. The aim was to explore the effects of cardioversion (CV) and short-lasting AF on left atrial hemodynamics, inflammatory, coagulative and cardiac biomarkers, and the association between LA functional recovery and the presence of a prior history of AF. Methods Patients referred for CV within 48 h after AF onset were prospectively included. Echocardiography and blood sampling were performed immediately prior, 1–3 h after, and at 7–10 days after CV. The presence of chronic white matter hyperintensities (WMH) on magnetic resonance imaging was related to biomarker levels. Results Forty-three patients (84% males), aged 55±9.6 years, with median CHA2DS2-VASc score 1 (IQR 0–1) were included. The LA emptying fraction (LAEF), LA peak longitudinal strain during reservoir, conduit, and contractile phases improved significantly after CV. Only LAEF normalized within 10 days. Interleukin-6, high-sensitivity cardiac-troponin-T (hs-cTNT), N-terminal-pro-brain-natriuretic peptide, prothrombin-fragment 1+2 (PTf1+2), and fibrinogen decreased significantly after CV. There was a trend towards higher C-reactive protein, hs-cTNT, and PTf1+2 levels in patients with WMH (n=21) compared to those without (n=22). At 7–10 days, the LAEF was significantly lower in patients with a prior history of AF versus those without. Conclusion Although LA stunning resolved within 10 days, LAEF remained significantly lower in patients with a prior history of AF versus those without. Inflammatory and coagulative biomarkers were higher before CV, but subsided after 7–10 days, which altogether might suggest an enhanced thrombogenicity, even in these low-risk patients.

Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.

Graphical abstract, Highlights • Traumatic brain injury (TBI) leads to axonal injury and an inflammatory response. • Repeated sports-related concussions (rSRC) are linked to neurodegeneration. • We studied tau aggregation and neuroinflammation in rSRC and TBI using PET/MRI. • In young rSRC and TBI patients, tau aggregation and neuroinflammation was increased. • PET useful when studying the long-term consequences of rSRC and TBI., Traumatic brain injury (TBI) and repeated sports-related concussions (rSRCs) are associated with an increased risk for neurodegeneration. Autopsy findings of selected cohorts of long-term TBI survivors and rSRC athletes reveal increased tau aggregation and a persistent neuroinflammation. To assess in vivo tau aggregation and neuroinflammation in young adult TBI and rSRC cohorts, we evaluated 9 healthy controls (mean age 26 ± 5 years; 4 males, 5 females), 12 symptomatic athletes (26 ± 7 years; 6 males, 6 females) attaining ≥3 previous SRCs, and 6 moderate-to severe TBI patients (27 ± 7 years; 4 males, 2 females) in a combined positron emission tomography (PET)/magnetic resonance (MR) scanner ≥6 months post-injury. Dual PET tracers, [18F]THK5317 for tau aggregation and [11C]PK11195 for neuroinflammation/microglial activation, were investigated on the same day. The Repeated Battery Assessment of Neurological Status (RBANS) scores, used for cognitive evaluation, were lower in both the rSRC and TBI groups (p

Background White matter hyperintensities (WMH), assessed using Fazekas scale, are more prevalent in patients with atrial fibrillation (AF), although its pathophysiologic mechanism(s) is unclear. Purpose The study objective was to explore the association between cardiac, inflammatory and coagulation biomarkers and white matter hyperintensities in anticoagulant-naïve patients following electrical cardioversion (CV) of recent onset AF. Methods Patients with AF duration Results Forty-three patients (84% males), aged 55±9.6 years, (mean±SD) with median CHA2DS2-VASc score 1 (interquartile range 0–1) were included. Sequential MRI showed no new brain lesions after CV, while WMH were present at baseline in 21/43 (49%) patients. Repeated measure analysis of variance revealed a statistically significant overall change for hs-TNT: F(2,84)=6.056, p=0.03, NT-proBNP: F(2,84)=106.02, p Conclusion Transient activation of inflammatory and coagulation systems during atrial fibrillation subsides within 7–10 days after electric cardioversion of recent onset atrial fibrillation. A tendency of higher degree of activation during atrial fibrillation was observed in patients with white matter hyperintensities. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swedish Heart-Lung Foundation, Swedish Research Council, Correvio International Sárl (Geneva Switzerland), Selanders Stiftelse

Background Atrial fibrillation (AF) results in left atrial electrical, structural and functional remodeling. Restoration of sinus rhythm hallmarks the beginning of reverse remodeling, the extent of which may depend on the type of AF. Purpose The aim of the study was to assess resumption of left atrial function after electric cardioversion in patients with recent onset AF and to explore the association between reverse remodeling and the type of atrial fibrillation. Methods Patients with AF duration Results Forty-three patients (84% males) aged 55±9.6 years, (mean±SD), with median CHA2DS2-VASc score 1 (interquartile range 0–1) were included. Repeated measure analysis of variance revealed a statistically significant overall change for LAGLS-res F(2,78)=55.4, p Conclusion Left atrial functional reverse remodeling occurs within ten days after successful electric cardioversion of patients with recent onset atrial fibrillation. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swedish Heart-Lung Foundation, Correvio International Sárl (Geneva Switzerland), Selanders Stiftelse

Funding Acknowledgements Unrestricted grants from the Swedish Heart-Lung Foundation, the Swedish Research Council, Correvio International Sárl (CH) and Selanders stiftelse Background Patients with atrial fibrillation (AF) have a high incidence of cognitive impairment, which may be related to clinically silent microembolism causing cerebral infarctions. Purpose To explore the occurrence and timing of silent brain lesions following electrical cardioversion (CV) of recent onset AF in anticoagulant-naïve patients and to further study related effects on cognitive function and biomarkers of cerebral damage, S100b. Methods Patients with AF duration < 48 hours were prospectively included. Brain magnetic resonance imaging (MRI) and S100b, were obtained prior, after and 7-10 days following CV. Trail making tests (TMT-A and TMT-B) and their difference, ΔΤΜΤ, were assessed prior to CV, 7-10 days and 30 days after CV. Results Forty-three patients (84% males) with mean CHA2DS2-VASc score 0.6 ± 0.7 were included. Sequential MRI, including diffusion weighted scans, showed no new brain lesions after CV. Chronic white matter hyperintensities (WMH) were present at baseline in 21/43 (49%) patients. By partitioning the study population into four major groups according to the extend of WMH (Fazekas score 0 or ≥ 1) and the presence or absence of TE risk factors (CHA2DS2-VASc score 0 or ≥ 1), the TE risk as defined by CHA2DS2-VASc score ≥ 1, was associated with a higher incidence of WMH, Pearson χ2(1,N = 43)=3.95, p = 0.047. The S100b (µg/l) levels increased significantly from baseline, (mean ± SD) 0.0472 ± 0.0182 to 0.0551 ± 0.0185 after CV, p = 0.001 and then decreased 7-10 days after CV to 0.0450 ± 0.0186, p Consecutive TMT scores improved successively after CV, being statistically and clinically significant for TMT-B (p 1.96). Conclusion New brain lesions could not be detected on MRI after CV, but the high incidence of white matter hyperintensities and the transient increase in S100b may indicate transient or minor brain damage undetectable by MRI thus heightening the need to reevaluate thromboembolic risk prior to CV even in low risk patients. Abstract Figure. S100b_TMT

Background and purpose Cerebral blood flow (CBF) has been reported to increase after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). The aims of this study were to investigate if CBF, measured using the noninvasive perfusion MRI method arterial spin labeling (ASL), increased after shunt surgery, if postoperative change in CBF correlated with improvement in symptoms, and if baseline CBF data correlated with postoperative outcome. Methods Twenty-three patients with iNPH were prospectively included and examined with MRI of the brain and clinical tests of symptoms at baseline. Eighteen of the patients were treated with shunt implantation and were reexamined with clinical tests and MRI 3 months postoperatively. The MRI protocol included a pseudo-continuous ASL sequence for perfusion imaging. The perfusion was measured in 12 manually drawn regions of interest (ROIs). Results In the whole sample, CBF did not increase after shunting in any ROI. Preoperative CBF in medial frontal cortex correlated with an improvement in urinary incontinence after shunt surgery, r = .53, P = .022. There were no correlations between change in CBF and change in clinical symptoms postoperatively. Conclusions The clinical value of ASL in the work-up of patients with iNPH is uncertain. In this study, ASL could not predict outcome after shunt surgery and there were no correlations between change in CBF and change in clinical symptoms after shunt surgery.

Background and purposeThe idiopathic normal pressure hydrocephalus (iNPH) Radscale was developed to standardize the evaluation of radiological signs in iNPH. The purpose of this study was to estimate the diagnostic accuracy of the iNPH Radscale in a sample of "true positive" and "true negative" cases.MethodsSeventy-five patients with definite iNPH, i.e. who had improved at clinical follow-up one year after ventriculoperitoneal shunt surgery, were compared with 55 asymptomatic individuals from the general population. A radiologist assessed the seven radiological features of the iNPH Radscale in computed tomography of the brain in the patients (preoperatively) and controls.ResultsThe iNPH Radscale score was significantly higher in the iNPH group (Median = 10, interquartile range 9-11) than in the control group (Median = 1, interquartile range 1-2) (p ConclusionsIn this study, iNPH Radscale could accurately discriminate between patients with definite iNPH and asymptomatic individuals over 65 years old. According to the results, a diagnosis of iNPH is very likely in patients with an iNPH Radscale score above 8 and corresponding clinical symptoms. On the other hand, the diagnosis should be questioned when the iNPH Radscale score is below the cut-off level of 4. We conclude that the iNPH Radscale could work as a diagnostic screening tool to detect iNPH. Whether the scale also can be used to predict shunt outcome needs further studies.

Purpose Oligodendrogliomas are heterogeneous tumors in terms of imaging appearance, and a deeper understanding of the histopathological tumor characteristics in correlation to imaging parameters is needed. We used PET-to-MRI-to-histology co-registration with the aim of studying intra-tumoral 11C-methionine (MET) uptake in relation to tumor perfusion and the protein expression of histological cell markers in corresponding areas. Methods Consecutive histological sections of four tumors covering the entire en bloc-removed tumor were immunostained with antibodies against IDH1-mutated protein (tumor cells), Ki67 (proliferating cells), and CD34 (blood vessels). Software was developed for anatomical landmarks-based co-registration of subsequent histological images, which were overlaid on corresponding MET PET scans and MRI perfusion maps. Regions of interest (ROIs) on PET were selected throughout the entire tumor volume, covering hot spot areas, areas adjacent to hot spots, and tumor borders with infiltrating zone. Tumor-to-normal tissue (T/N) ratios of MET uptake and mean relative cerebral blood volume (rCBV) were measured in the ROIs and protein expression of histological cell markers was quantified in corresponding regions. Statistical correlations were calculated between MET uptake, rCBV, and quantified protein expression. Results A total of 84 ROIs were selected in four oligodendrogliomas. A significant correlation (p

Cerebral microbleeds (CMBs), also referred to as microhemorrhages, appear on magnetic resonance (MR) images as hypointense foci notably at T2*-weighted or susceptibility-weighted (SW) imaging. CMBs are detected with increasing frequency because of the more widespread use of high magnetic field strength and of newer dedicated MR imaging techniques such as three-dimensional gradient-echo T2*-weighted and SW imaging. The imaging appearance of CMBs is mainly because of changes in local magnetic susceptibility and reflects the pathologic iron accumulation, most often in perivascular macrophages, because of vasculopathy. CMBs are depicted with a true-positive rate of 48%-89% at 1.5 T or 3.0 T and T2*-weighted or SW imaging across a wide range of diseases. False-positive "mimics" of CMBs occur at a rate of 11%-24% and include microdissections, microaneurysms, and microcalcifications; the latter can be differentiated by using phase images. Compared with postmortem histopathologic analysis, at least half of CMBs are missed with premortem clinical MR imaging. In general, CMB detection rate increases with field strength, with the use of three-dimensional sequences, and with postprocessing methods that use local perturbations of the MR phase to enhance T2* contrast. Because of the more widespread availability of high-field-strength MR imaging systems and growing use of SW imaging, CMBs are increasingly recognized in normal aging, and are even more common in various disorders such as Alzheimer dementia, cerebral amyloid angiopathy, stroke, and trauma. Rare causes include endocarditis, cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and radiation therapy. The presence of CMBs in patients with stroke is increasingly recognized as a marker of worse outcome. Finally, guidelines for adjustment of anticoagulant therapy in patients with CMBs are under development. © RSNA, 2018.

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 84 years 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. (C) 2017 Elsevier Inc. All rights reserved.

Patients with atypical anorexia nervosa (AN) have many features overlapping with AN in terms of genetic risk, age of onset, psychopathology and prognosis of outcome, although the weight loss may not be a core factor. While brain structural alterations have been reported in AN, there are currently no data regarding atypical AN patients.We investigated brain structure through a voxel-based morphometry analysis in 22 adolescent females newly-diagnosed with atypical AN, and 38 age- and sex-matched healthy controls (HC). ED-related psychopathology, impulsiveness and obsessive-compulsive traits were assessed with the Eating Disorder Examination Questionnaire (EDE-Q), Barratt Impulsiveness Scale (BIS-11) and Obsessive-compulsive Inventory Revised (OCI-R), respectively. Body mass index (BMI) was also calculated.Patients and HC differed significantly on BMI (p .002), EDE-Q total score (p .000) and OCI-R total score (p .000). No differences could be detected in grey matter (GM) regional volume between groups.The ED-related cognitions in atypical AN patients would suggest that atypical AN and AN could be part of the same spectrum of restrictive-ED. However, contrary to previous reports in AN, our atypical AN patients did not show any GM volume reduction. The different degree of weight loss might play a role in determining such discrepancy. Alternatively, the preservation of GM volume might indeed differentiate atypical AN from AN.

The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations.

The inferior longitudinal fascicle (ILF) is one of the major occipital-temporal association pathways. Several studies have mapped its hierarchical segmentation to specific functions. There is, however, no consensus regarding a detailed description of ILF fibre organisation. The aim of this study was to establish whether the ILF has a constant number of subcomponents. A secondary aim was to determine the quantitative diffusion proprieties of each subcomponent and assess their anatomical trajectories and connectivity patterns. A white matter dissection of 14 post-mortem normal human hemispheres was conducted to define the course of the ILF and its subcomponents. These anatomical results were then investigated in 24 right-handed, healthy volunteers using in vivo diffusion tensor imaging (DTI) and streamline tractography. Fractional anisotropy (FA), volume, fibre length and the symmetry coefficient of each fibre group were analysed. In order to show the connectivity pattern of the ILF, we also conducted an analysis of the cortical terminations of each segment. We confirmed that the main structure of the ILF is composed of three constant components reflecting the occipital terminations: the fusiform, the lingual and the dorsolateral-occipital. ILF volume was significantly lateralised to the right. The examined indices of ILF subcomponents did not show any significant difference in lateralisation. The connectivity pattern and the quantitative distribution of ILF subcomponents suggest a pivotal role for this bundle in integrating information from highly specialised modular visual areas with activity in anterior temporal territory, which has been previously shown to be important for memory and emotions.

OBJECTIVES: To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort. METHODS: Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0-4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile. RESULTS: Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline. CONCLUSION: At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later. KEY POINTS: • Gender and education are confounders for MTA grading. • We suggest cut-off values for 75-year-olds, taking gender and education into account. • Males have higher MTA scores than women. • Higher MTA scores are associated with worse cognitive performance.

Background Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD). Methods We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18 years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram (20 mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605. Findings Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n = 24) as compared to covert (n = 22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69–31.65, p, Highlights • Overt surpassed covert SSRI treatment with doubled effect size and tripled response rate on the main social anxiety outcome. • Overt vs. covert SSRI treatment yielded different neural changes in brain areas involved in emotion-cognition interactions. • This study suggests that the presentation of a treatment may be as important as the treatment itself. Using truthful or deceiving verbal instructions, we tested how expectancies influence SSRI efficacy in social anxiety disorder. The number of responders was more than three times higher after open administration of escitalopram 20 mg compared to covert administration of the drug presented as “active placebo” in a cover story. Correct vs. incorrect information about the SSRI also yielded different neural changes in brain areas involved in emotion-cognition interactions. The benefit of SSRI medication seems to be highly affected by psychological factors like positive expectancies traditionally associated with placebo. Our results favor a biopsychosocial over a biomedical explanatory model for SSRI efficacy.

BACKGROUND AND PURPOSE: There are, to date, no MR imaging diagnostic markers for Lewy body dementia. Nigrosome 1, containing dopaminergic cells, in the substantia nigra pars compacta is hyperintense on SWI and has been called the swallow tail sign, disappearing with Parkinson disease. We aimed to study the swallow tail sign and its clinical applicability in Lewy body dementia and hypothesized that the sign would be likewise applicable in Lewy body dementia. MATERIALS AND METHODS: This was a retrospective cross-sectional multicenter study including 97 patients (mean age, 65 ± 10 years; 46% women), consisting of the following: controls (n = 21) and those with Lewy body dementia (n = 19), Alzheimer disease (n = 20), frontotemporal lobe dementia (n = 20), and mild cognitive impairment (n = 17). All patients underwent brain MR imaging, with susceptibility-weighted imaging at 1.5T (n = 46) and 3T (n = 51). The swallow tail sign was assessed independently by 2 neuroradiologists. RESULTS: Interrater agreement was moderate (κ = 0.4) between raters. An abnormal swallow tail sign was most common in Lewy body dementia (63%; 95% CI, 41%–85%; P < .001) and had a predictive value only in Lewy body dementia with an odds ratio of 9 (95% CI, 3–28; P < .001). The consensus rating for Lewy body dementia showed a sensitivity of 63%, a specificity of 79%, a negative predictive value of 89%, and an accuracy of 76%; values were higher on 3T compared with 1.5T. The usefulness of the swallow tail sign was rater-dependent with the highest sensitivity equaling 100%. CONCLUSIONS: The swallow tail sign has diagnostic potential in Lewy body dementia and may be a complement in the diagnostic work-up of this condition.

Bariatric surgery is an effective method to rapidly induce weight loss in severely obese people, however its impact on brain functional connectivity after longer periods of follow-up is yet to be assessed. We investigated changes in connectivity in 16 severely obese women one month before, one month after and one year after Roux-en-Y gastric bypass surgery (RYGB). 12 lean controls were also enrolled. Resting-state fMRI was acquired for all participants following an overnight fast and after a 260 kcal load. Connectivity between regions involved in food-related saliency attribution and reward-driven eating behavior was stronger in presurgery patients compared to controls, but progressively weakened after follow-up. At one year, changes in networks related to cognitive control over eating and bodily perception also occurred. Connectivity between regions involved in emotional control and social cognition had a temporary reduction early after treatment but had increased again after one year of follow-up. Furthermore, we could predict the BMI loss by presurgery connectivity in areas linked to emotional control and social interaction. RYGBP seems to reshape brain functional connectivity, early affecting cognitive control over eating, and these changes could be an important part of the therapeutic effect of bariatric surgery.

Title:A functional (f) MRI-based model for individual memory assessment in patients eligible for temporal lobe resection.Aim:To investigate if pre-operative fMRI memory paradigms, add predictive information with regard to post-surgical memory deficits.Methods:Fourteen pharmacoresistant Temporal Lobe Epilepsy (TLE) patients accepted for Anterior Temporal Lobe Resection (ATLR) were included. A clinical risk assessment score (RAS 0-3) was constructed from structural MRI, neuropsychological testing and hemisphere dominance. fMRI lateralization indices (LIs) over frontal language and medial temporal regions were calculated. Predictive value from clinical risk scoring and added value from fMRI LIs were correlated to post-surgical memory change scores (significant decline -1 SD). Verbal memory outcome was classified either as expected (RAS 2-3 and post-operative decline; RAS 0-1 and intact post-operative verbal memory) or as unexpected (RAS 2-3 and intact post-operative verbal memory post-surgery; RAS 0-1 and post-operative decline).Results:RAS for verbal memory decline exhibited a specificity of 67% and a sensitivity of 75%. Significant correlations were found between frontal language LIs and post-operative verbal memory (r = -0.802; p = 0.017) for left (L) TLE and between medial temporal lobe LIs and visuospatial memory (r = 0.829; p = 0.021), as well as verbal memory (r = 0.714; p = 0.055) for right (R) TLE. Ten patients had expected outcome and four patients had an unexpected outcome. In two MRI-negative RTLE patients that suffered significant verbal memory decline post-operatively, fMRI identified bilateral language and right lateralized medial temporal verbal encoding. In two LTLE patients with MRI pathology and verbal memory dysfunction, neither RAS nor fMRI identified the risk for aggravated verbal memory decline following ATLR.Conclusion:fMRI visualization of temporal-frontal network activation may add value to the pre-surgical work-up in epilepsy patients eligible for ATLR. Frontal language patterns are important for prediction in both L and RTLE. Strong left lateralized language in LTLE, as well as bilateral language combined with right lateralized encoding in RTLE, seems to indicate an increased risk for post-operative verbal memory decline.

The Extracorporeal Life Support Organisation accepts permissive hypoxaemia in adult patients during extracorporeal membrane oxygenation (ECMO). The neurological long-term outcome of this approach has not yet been studied.We investigated the prevalence of brain lesions and cognitive dysfunction in survivors from the Influenza A/H1N1 2009 pandemic treated with permissive hypoxaemia during ECMO for severe acute respiratory distress syndrome (ARDS). Our hypothesis was that this method is reasonable if tissue hypoxia is avoided.Long-term follow-up study after ECMO.Karolinska University Hospital, Sweden, from October 2012 to July 2013.Seven patients treated with ECMO for severe influenza A/H1N1-induced ARDS were studied 3.2 years after treatment. Blood lactate concentrations were used as a surrogate for tissue oxygenation.Neurocognitive outcome was studied with standardised cognitive tests and MRI of the brain.Cognitive functioning and hypoxic brain lesions after permissive hypoxaemia during ECMO. The observation period was the first 10 days of ECMO or the entire treatment period if shorter than 10 days.Eleven of 13 patients were still alive 3 years after ECMO. We were able to contact seven of these patients (mean age 31 years), who all agreed to participate in this study. Mean ± SD peripherally measured arterial saturation during the observation period was 79 ± 10%. Full-scale Intelligence Quotient was within one standard deviation or above from the mean of a healthy population in five patients, and was 1.5 SD below the mean in one patient. In one other patient, it could not be determined because of a lack of formal education. Memory functioning was normal in all patients. MRI showed no changes related to cerebral hypoxia.Permissive hypoxaemia during ECMO might not negatively affect long-term cognitive outcome if adequate organ perfusion is maintained.at Clinicaltrials.gov NCT01763060.

The anterior hippocampus has been implicated in associative memory, and along with hippocampal volume, this type of memory declines with age. However, few cross-sectional studies include middle-aged samples, making it unclear at what point these age-related changes occur. In addition, although men and women have been shown to differ in associative memory and rates of age-related hippocampal atrophy, sex-differences in aging are rarely studied. To address these issues, we assessed memory for word-pairs, hippocampal volume and activation during encoding and retrieval, across middle-aged (n=39) and older (n=44) participants, specifically in relation to sex. Older adults showed significantly poorer associative memory compared to middle-aged adults, paralleled by smaller anterior hippocampi and less activation during successful retrieval. The age-by-sex interaction observed in memory performance was also mirrored in the volume and activation of the hippocampus, indicating more pronounced age-effects in men as compared to women. These results indicate a specific role of the anterior hippocampus in verbal associative memory and suggest they both decline between middle-age and older age.

Background Deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) is an evolving treatment option in refractory focal epilepsy. Due to poor visualization of ANT in traditional MRI sequences used for movement disorder surgery, targeting of ANT is mainly based on stereotactic atlas information. Sophisticated 3T MRI methods enable visualization of ANT, but 1.5T MRI is still preferred or more readily available in a large number of centers performing DBS. Objective In the present study, we sought to determine whether ANT could be adequately visualized at 1.5T MRI pre- and postoperatively using imaging techniques similar to the ones visualizing ANT in 3T MRI. A total of 15 MRI examinations with short tau inversion recovery (STIR) and T1-weighted magnetization prepared gradient echo (MPRAGE) images were performed to visualize ANT in nonepileptic subjects (n = 2), patients with vagus nerve stimulator (VNS) (n = 3), stereotactic MRI (n = 3), patients with ANT-DBS (n = 7). Results ANT was distinctly visualized in STIR and T1-weighted MPRAGE images in patients without implanted stimulators, with Leksell stereotactic frame and with fully implanted VNS. Postoperative 1.5T MRI was able to demonstrate some of the anatomical landmarks around ANT enabling assessment of electrode contact locations. Conclusions The visualization of ANT is possible in preoperative 1.5T MRI enabling direct targeting of ANT all examined situations. The use of indirect targeting and its inherent potential for lead misplacement due to anatomical variation may be avoided using these MRI methods. Furthermore, postoperative MRI with STIR and T1-weighted MPRAGE images enable detailed postoperative assessment of contact locations.

Correct prediction of treatment response is a central goal of precision psychiatry. Here, we tested the predictive accuracy of a variety of pre-treatment patient characteristics, including clinical, demographic, molecular genetic, and neuroimaging markers, for treatment response in patients with social anxiety disorder (SAD).Forty-seven SAD patients (mean±SD age 33.9 ± 9.4 years, 24 women) were randomized and commenced 9 weeks' Internet-delivered cognitive behavior therapy (CBT) combined either with the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg daily [10 mg first week], SSRI+CBT, n = 24) or placebo (placebo+CBT, n = 23). Treatment responders were defined from the Clinical Global Impression-Improvement scale (CGI-I ≤ 2). Before treatment, patients underwent functional magnetic resonance imaging and the Multi-Source Interference Task taxing cognitive interference. Support vector machines (SVMs) were trained to separate responders from nonresponders based on pre-treatment neural reactivity in the dorsal anterior cingulate cortex (dACC), amygdala, and occipital cortex, as well as molecular genetic, demographic, and clinical data. SVM models were tested using leave-one-subject-out cross-validation.The best model separated treatment responders (n = 24) from nonresponders based on pre-treatment dACC reactivity (83% accuracy, P = 0.001). Responders had greater pre-treatment dACC reactivity than nonresponders especially in the SSRI+CBT group. No other variable was associated with clinical response or added predictive accuracy to the dACC SVM model.Small sample size, especially for genetic analyses. No replication or validation samples were available.The findings demonstrate that treatment outcome predictions based on neural cingulate activity, at the individual level, outperform genetic, demographic, and clinical variables for medication-assisted Internet-delivered CBT, supporting the use of neuroimaging in precision psychiatry.

Gadolinium-based contrast agents (GBCAs) increase lesion detection and improve disease characterization for many cerebral pathologies investigated with MRI. These agents, introduced in the late 1980s, are in wide use today. However, some non-ionic linear GBCAs have been associated with the development of nephrogenic systemic fibrosis in patients with kidney failure. Gadolinium deposition has also been found in deep brain structures, although it is of unclear clinical relevance. Hence, new guidelines from the International Society for Magnetic Resonance in Medicine advocate cautious use of GBCA in clinical and research practice. Some linear GBCAs were restricted from use by the European Medicines Agency (EMA) in 2017. This review focuses on non-contrast-enhanced MRI techniques that can serve as alternatives for the use of GBCAs. Clinical studies on the diagnostic performance of non-contrast-enhanced as well as contrast-enhanced MRI methods, both well established and newly proposed, were included. Advantages and disadvantages together with the diagnostic performance of each method are detailed. Non-contrast-enhanced MRIs discussed in this review are arterial spin labeling (ASL), time of flight (TOF), phase contrast (PC), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), susceptibility weighted imaging (SWI), and amide proton transfer (APT) imaging. Ten common diseases were identified for which studies reported comparisons of non-contrast-enhanced and contrast-enhanced MRI. These specific diseases include primary brain tumors, metastases, abscess, multiple sclerosis, and vascular conditions such as aneurysm, arteriovenous malformation, arteriovenous fistula, intracranial carotid artery occlusive disease, hemorrhagic, and ischemic stroke. In general, non-contrast-enhanced techniques showed comparable diagnostic performance to contrast-enhanced MRI for specific diagnostic questions. However, some diagnoses still require contrast-enhanced imaging for a complete examination.

Atypical anorexia nervosa (AN) usually occurs during adolescence. Patients are often in the normal-weight range at diagnosis; however, they often present with signs of medical complications and severe restraint over eating, body dissatisfaction, and low self-esteem. We investigated functional circuitry underlying the hedonic response in 28 female adolescent patients diagnosed with atypical AN and 33 healthy controls. Participants were shown images of food with high (HC) or low (LC) caloric content in alternating blocks during functional MRI. The HC > LC contrast was calculated. Based on the previous literature on full-threshold AN, we hypothesized that patients would exhibit increased connectivity in areas involved in sensory processing and bottom-up responses, coupled to increased connectivity from areas related to top-down inhibitory control, compared with controls. Patients showed increased connectivity in pathways related to multimodal somatosensory processing and memory retrieval. The connectivity was on the other hand decreased in patients in salience and attentional networks, and in a wide cerebello-occipital network. Our study was the first investigation of food-related neural response in atypical AN. Our findings support higher somatosensory processing in patients in response to HC food images compared with controls, however HC food was less efficient than LC food in engaging patients’ bottom-up salient responses, and was not associated with connectivity increases in inhibitory control regions. These findings suggest that the psychopathological mechanisms underlying food restriction in atypical AN differ from full-threshold AN. Elucidating the mechanisms underlying the development and maintenance of eating behavior in atypical AN might help designing specific treatment strategies.

Accurate volumetric change estimation of glioblastoma is very important for post-surgical treatment follow-up. In this paper, an interactive segmentation method was developed and evaluated with the aim to guide volumetric estimation of glioblastoma. U-Net based fully convolutional network is used for initial segmentation of glioblastoma from post contrast MR images. The max flow algorithm is applied on the probability map of U-Net to update the initial segmentation and the result is displayed to the user for interactive refinement. Network update is performed based on the corrected contour by considering patient specific learning to deal with large context variations among different images. The proposed method is evaluated on a clinical MR image database of 15 glioblastoma patients with longitudinal scan data. The experimental results depict an improvement of segmentation performance due to patient specific fine-tuning. The proposed method is computationally fast and efficient as compared to state-of-the-art interactive segmentation tools. This tool could be useful for post-surgical treatment follow-up with minimal user intervention.

Olfactory dysfunction is an early manifestation of Parkinson's disease (PD). The present study aimed to illustrate potential differences between PD patients and healthy controls in terms of neural activity and functional connectivity within the olfactory brain network. Twenty PD patients and twenty healthy controls were examined with olfactory fMRI and resting-state fMRI. Data analysis of olfactory fMRI included data-driven tensorial independent component (ICA) and task-driven general linear model (GLM) analyses. Data analysis of resting-state fMRI included probabilistic ICA based on temporal concatenation and functional connectivity analysis within the olfactory network. ICA of olfactory fMRI identified an olfactory network consisting of the posterior piriform cortex, insula, right orbitofrontal cortex and thalamus. Recruitment of this network was less significant for PD patients. GLM analysis revealed significantly lower activity in the insula bilaterally and the right orbitofrontal cortex in PD compared to healthy controls but no significant differences in the olfactory cortex itself. Analysis of resting-state fMRI did not reveal any differences in the functional connectivity within the olfactory, default mode, salience or central executive networks between the two groups. In conclusion, olfactory dysfunction in PD is associated with less significant recruitment of the olfactory brain network. ICA could demonstrate differences in both the olfactory cortex and its main projections, compared to GLM that revealed differences only on the latter. Resting-state fMRI did not reveal any significant differences in functional connectivity within the olfactory, default mode, salience and central executive networks in this cohort., Highlights • Less significant recruitment of the olfactory brain network was found in Parkinson's disease. • Independent component analysis reveals differences in both olfactory cortex and its projections. • Differences in functional connectivity within the olfactory network were not significant.

Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET. Authors and title in thesis list of papers: Fahlström, M., Appel, L., Danfors, T., Engström, M., Antoni, G., Kumlien, E., Wikström, J., Larsson, E-M., Lubberink, M. Evaluation of pseudo-continuous arterial spin labeling MRI – agreement with 15O-water PET with arterial input function and use of integrated PET/MR

Memories become labile and malleable to modification when recalled [1]. Fear-conditioning experiments in both rodents and humans indicate that amygdala-localized short-term fear memories can be attenuated by disruption of their reconsolidation with extinction training soon after memory activation [2-7]. However, this may not be true for natural long-term fears. Studies in rodents indicate that although it is possible to disrupt the reconsolidation of older memories [8-11], they appear to be more resistant [1, 3, 9, 12, 13]. In humans, 1-week-old conditioned fear memories have been attenuated by behaviorally induced disruption of reconsolidation [14], but it remains to be seen whether this is possible for naturally occurring long-term fears and whether the underlying neural mechanisms are similar to those found in experimental fear-conditioning paradigms. Using functional brain imaging in individuals with a lifelong fear of spiders, we show that fear memory activation followed by repeated exposure to feared cues after 10 min, which disrupts reconsolidation, attenuates activity in the basolateral amygdala at re-exposure 24 hr later. In contrast, repeated exposure 6 hr after fear memory activation, which allows for reconsolidation, did not attenuate amygdala activity. Disrupted, but not undisrupted, reconsolidation facilitated approach behavior to feared cues, and approach behavior was inversely related to amygdala activity during re-exposure. We conclude that memory activation immediately preceding exposure attenuates the neural and behavioral expression of decades-old fear memories and that, similar to experimentally induced fear memories, the basolateral amygdala is crucially involved in this process.

BACKGROUND: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. OBJECTIVE: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). METHODS: Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m(-)(2)) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m(-)(2)), both before and 30 min after consumption of a standardized meal (~260 kcal). RESULTS: Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (PDe tre första författarna delar förstaförfattarskapet.

Objective: MR-perfusion post-processing still lacks standardization. This study evaluates the results of perfusion analysis with two established software solutions in a large series of patients with different diseases when a highly standardized processing workflow is ensured. Methods: Multicenter data of 260 patients (80 with brain tumors, 124 with cerebrovascular disease and 56 with dementia examined with the same MR protocol) were analyzed. Raw data sets were processed with two software suites: Olea sphere and NordicICE. Group differences were analyzed with paired t-tests and one-way ANOVA. Results: Perfusion metrics were significantly different for all examined diseases in the unaffected brain for both software suites [ratio cortex/white matter left hemisphere: mean transit time (MTT) 0.991 vs 0.847, p < 0.05; relative cerebral bloodflow (rBF) 3.23 vs 4.418, p < 0.001; relative cerebral bloodvolume (rBVc) 2.813 vs 3.884, p < 0.001; right hemisphere: MTT 1.079 vs 0.854, p < 0.05; rBF 3.262 vs 4.378, p < 0.001; rBVc 2.762 vs 3.935, p < 0.001)]. Perfusion results were also significantly different in patients with stroke (ratio cortex/white matter affected hemisphere: MTT 1.058 vs 0.784; p < 0.001), dementia (ratio cortex/white matter left hemisphere: rBVc 1.152 vs 1.795, p < 0.001; right hemisphere: rBVc 1.396 vs 1.662, p < 0.05) and brain tumors (ratio cortex/whole tumor rBVc: 0.778 vs 0.919, p < 0.001 and ratio cortex/tumor hotspot rBVc: 0.529 vs 0.512, p < 0.05). Conclusion: Despite a highly standardized workflow, parametric perfusion maps are depended on the chosen software. Radiologists should consider software related variances when using dynamic susceptibility contrast perfusion for clinical imaging and research. Advances in knowledge: This multicenter study compared perfusion parameters calculated by two commercial dynamic susceptibility contrast perfusion post-processing software solutions in different central nervous system disorders with a large sample size and a highly standardized processing workflow. Despite, parametric perfusion maps are depended on the chosen software which impacts clinical imaging and research.

BACKGROUND AND PURPOSE: Increased CSF stroke volume through the cerebral aqueduct has been proposed as a possible indicator of positive surgical outcome in patients with idiopathic normal pressure hydrocephalus; however, consensus is lacking. In this prospective study, we aimed to compare CSF flow parameters in patients with idiopathic normal pressure hydrocephalus with those in healthy controls and change after shunt surgery and to investigate whether any parameter could predict surgical outcome. MATERIALS AND METHODS: Twenty-one patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched healthy controls were prospectively included and examined clinically and with MR imaging of the brain. Eighteen patients were treated with shunt implantation and were re-examined clinically and with MR imaging the day before the operation and 3 months postoperatively. All MR imaging scans included a phase-contrast sequence. RESULTS: The median aqueductal CSF stroke volume was significantly larger in patients compared with healthy controls (103.5 μL; interquartile range, 69.8–142.8 μL) compared with 62.5 μL (interquartile range, 58.3–73.8 μL; P < .01) and was significantly reduced 3 months after shunt surgery from 94.8 μL (interquartile range, 81–241 μL) to 88 μL (interquartile range, 51.8–173.3 μL; P < .05). Net flow in the caudocranial direction (retrograde) was present in 11/21 patients and in 10/21 controls. Peak flow and net flow did not differ between patients and controls. There were no correlations between any CSF flow parameters and surgical outcomes. CONCLUSIONS: Aqueductal CSF stroke volume was increased in patients with idiopathic normal pressure hydrocephalus and decreased after shunt surgery, whereas retrograde aqueductal net flow did not seem to be specific for patients with idiopathic normal pressure hydrocephalus. On the basis of the results, the usefulness of CSF flow parameters to predict outcome after shunt surgery seem to be limited.

INTRODUCTION: Previous studies have demonstrated a survival benefit with increasing extent of resection (EOR) for patients with glioblastoma. However, EOR is a relative measurement making it difficult to determine the significance of residual tumor size in clinical practice. Our aim is to determine whether absolute postoperative volume affects survival similarly. Moreover, despite that methylation of the enzyme MGMT is associated with a better prognosis in glioblastoma, it is still unknown whether the survival benefit of increasing surgical resection differs between patients with different MGMT-methylation status. MATERIALS AND METHODS: In total 286 patients with newly diagnosed supratentorial glioblastoma that underwent cytoreductive surgery between 2010 and 2016 were identified in a regional cancer registry. Pre- and postoperative 3D volumetric measurements were performed retrospectively. Information about age at surgery, pre- and postoperative WHO performance status, oncological treatment and histopathological data including result of MGMT-methylation status analysis were collected. RESULTS: The median age of patients was 65 years. The median postoperative volume was 0.513 cm(3) and median EOR was 98,7%. Median overall survival time was 13 months and for patients with gross total resection 15.3 months. Age, pre- and postoperative performance status and oncological treatment were included in a multivariate Cox proportional hazards analysis. Postoperative volume and EOR were both predictive of survival at p=0.0090 with a concordance index of 0.71. In a separate multivariate interaction analysis including the 151 patients with known MGMT-methylation status the p-value for interaction between MGMT-methylation and EOR was 0.60 and respectively for postoperative volume 0.54. CONCLUSIONS: Postoperative volume affects survival in patients with newly diagnosed glioblastoma with similar descriptive abilities as EOR. In considering risk of neurological morbidity no significant differences in postoperative performance status were seen between patients with different EOR or postoperative volume. MGMT-methylation status seems to not significantly affect survival in relation to EOR or postoperative volume, although a slight trend was observed towards a greater benefit for patients with methylated MGMT. Further studies will clarify whether MGMT or other molecular pathological properties in glioblastoma affects benefit of EOR.

Objective Patients with atypical anorexia nervosa (AN) are often in the normal‐weight range at presentation; however, signs of starvation and medical instability are not rare. White matter (WM) microstructural correlates of atypical AN have not yet been investigated, leaving an important gap in our knowledge regarding the neural pathogenesis of this disorder. Method We investigated WM microstructural integrity in 25 drug‐naïve adolescent patients with atypical AN and 25 healthy controls, using diffusion tensor imaging (DTI) with a tract‐based spatial statistics (TBSS) approach. Psychological variables related to the eating disorder and depressive symptoms were also evaluated by administering the eating disorder examination questionnaire (EDE‐Q) and the Montgomery–Åsberg depression rating scale (MADRS‐S) respectively, to all participants. Results Patients and controls were in the normal‐weight range and did not differ from the body mass index standard deviations for their age. No between groups difference in WM microstructure could be detected. Discussion Our findings support the hypothesis that brain structural alterations may not be associated to early‐stage atypical AN. These findings also suggest that previous observations of alterations in WM microstructure in full syndrome AN may constitute state‐related consequences of severe weight loss. Whether the preservation of WM structure is a pathogenetically discriminant feature of atypical AN or only an effect of a less severe nutritional disturbance, will have to be verified by future studies on larger samples, possibly directly comparing AN and atypical AN.

Neuroimaging is a central part of diagnostic work-up of patients with suspected neurodegenerative disease. FDG-PET can reveal pathological changes earlier and more reliably than morphological imaging. Diagnostic accuracy can be improved by constructing 3D SSP Z-score maps, showing patterns of significant deficits. During FDG-PET, the subject receives a moderate but not insignificant dose of ionizing radiation, and a dose reduction with retained image quality is desirable. With lower dose, repeated examinations can become a useful tool for monitoring disease progress and potential effects of disease-modifying interventions. The aim of this study was to evaluate Z-maps created from low-dose and normal-dose FDG-PET of the brain, with quantitative and qualitative methods. Nine patients with neurodegenerative disorders were prospectively enrolled and nine age-matched controls were recruited through advertising. All subjects (n=18) underwent two FDG-PET scans on separate occasions; a routine and a low-dose scan. The routine dosage of FDG was 3 MBq/kg, and low dosage was 0.75 MBq/kg. 3D-SSP images showing Z-scores of < -1.96 were created from 10-minute summations. The study was comprised of a quantitative part comparing the Z-scores, and a qualitative part where experienced nuclear medicine specialists visually assessed the images. Regarding the quantitative part, Bland-Altman analysis showed a slight constant bias (0.206). Regarding qualitative discrimination between patients and controls, the performance between normal- and low-dose were equal, both showing 72% sensitivity, 83% specificity and 78% accuracy. In this study, visual assessment of 3D-SSP Z-score maps from low-dose FDG-PET provided diagnostic information highly comparable to normal-dose, with minor quantitative discrepancies.

BACKGROUND AND PURPOSE: Administration of a gadolinium-based contrast agent is an important diagnostic biomarker for blood-brain barrier damage. In clinical use, detection is based on subjective comparison of native and postgadolinium-based contrast agent T1-weighted images. Quantitative MR imaging studies have suggested a relation between the longitudinal relaxation rate and proton-density in the brain parenchyma, which is disturbed by gadolinium-based contrast agents. This discrepancy can be used to synthesize a contrast-enhancement map based solely on the postgadolinium-based contrast agent acquisition. The aim of this study was to compare synthetic enhancement maps with subtraction maps of native and postgadolinium-based contrast agent images. MATERIALS AND METHODS: For 14 patients with high-grade gliomas, quantitative MR imaging was performed before and after gadolinium-based contrast agent administration. The quantification sequence was multidynamic and multiecho, with a scan time of 6 minutes. The 2 image stacks were coregistered using in-plane transformation. The longitudinal relaxation maps were subtracted and correlated with the synthetic longitudinal relaxation enhancement maps on the basis of the postgadolinium-based contrast agent images only. ROIs were drawn for tumor delineation. RESULTS: Linear regression of the subtraction and synthetic longitudinal relaxation enhancement maps showed a slope of 1.02 ± 0.19 and an intercept of 0.05 ± 0.12. The Pearson correlation coefficient was 0.861 ± 0.059, and the coefficient of variation was 0.18 ± 0.04. On average, a volume of 1.71 ± 1.28 mL of low-intensity enhancement was detected in the synthetic enhancement maps outside the borders of the drawn ROI. CONCLUSIONS: The study shows that there was a good correlation between subtraction longitudinal relaxation enhancement maps and synthetic longitudinal relaxation enhancement maps in patients with high-grade gliomas. The method may improve the sensitivity and objectivity for the detection of gadolinium-based contrast agent enhancement.

Background and Purpose: Signs of small vessel disease (SVD) are commonly seen on magnetic resonance imaging (MRI) of the brain in cognitively healthy elderly individuals, and the clinical relevance of these are often unclear. We have previously described three different MRI manifestations of SVD as well as cerebral perfusion in a longitudinal study of non-demented 75-year-old subjects. The purpose of the present study was to evaluate the relationship of these findings to cognition and executive function at age 75 and changes after 5 years. Methods: In all, 406 subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study were examined with MRI of the brain at age 75 years. Two-hundred and fifty of the subjects were re-examined 5 years later. White matter hyperintensities (WMHs) and lacunar infarcts (LIs) were assessed on both occasions, but microbleeds (MBs) and perfusion only at age 75. Cognitive function was screened by the Mini Mental State Examination (MMSE). Trail Making Test A and B (TMT-A and TMT-B) were performed at baseline and at follow-up at age 80. Results: At baseline, 93% performed >27 points in the MMSE. The TMT-B at age 75 was significantly related to WMH visual scoring after adjustment for sex, education and cerebrovascular disease risk factors (+80 s (95% CI 0.3-161 s), P < 0.05 for grade 2-3 vs. grade 0). Neither MMSE nor TMT-A was significantly related to WMH scoring. There was no relation between any test performance and WMH volume, white matter volume, number of MBs or brain perfusion at age 75. Subjects who had sustained a new LI (n = 26) showed a greater increase of the time to perform TMT-A at the 5-year follow-up (+25 s vs. +4 s in LI-free subjects, P = 0.003). Changes in MMSE or TMT-A and -B test performance between ages 75 and 80 were not related to changes in WMH scoring or volume during the 5 years follow-up, or to brain perfusion at age 75. Conclusion: In this cognitively healthy community-based population, moderate-severe WMHs and incident LIs on brain MRI in individuals aged 75-80 years were associated with a mild impairment of processing speed and executive function.

Studying olfaction with functional Magnetic Resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of four olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex and the insula. 22 healthy participants with normal olfaction were examined with fMRI, with two stimulation lengths (6 seconds and 15 seconds) and two TRs (0.901 seconds and 1.34 seconds). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA) and by plotting the event related time course of brain activation in the four olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all four olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

Neuroradiology with computed tomography (CT) and magnetic resonance imaging (MRI) is essential for the initial evaluation of patients with a clinical suspicion of brain and spine disorders. Morphologic imaging is required to obtain a probable diagnosis to support the treatment decisions in pre- and perinatal disorders, vascular diseases, traumatic injuries, metabolic disorders, epilepsy, infection/inflammation, neurodegenerative disorders, degenerative spinal disease, and tumors of the central nervous system. Different postprocessing tools are increasingly used for three-dimensional visualization and quantification of lesions. Additional information is provided by angiographic methods and physiologic CT and MRI techniques, such as diffusion MRI, perfusion CT/MRI, MR spectroscopy, functional MRI, tractography, and nuclear medicine imaging methods. Positron emission tomography (PET) is now integrated with CT (PET/CT), and PET/MR scanners have recently also been introduced. These hybrid techniques facilitate the co-registration of lesions with different modalities, and give new possibilites for functional imaging. Repeated imaging is increasingly performed for treatment monitoring. The improved imaging techniques together with the neuropathologic diagnosis after biopsy or surgery allow more personalized treatment of the patient. Neuroradiology also includes endovascular treatment of aneurysms and arteriovenous malformations as well as thrombectomy in acute stroke. This catheter-based treatment has replaced invasive neurosurgery in many cases.

Effects of rescaling atlas and ZTE-AC maps to 68Ge-AC values. (DOCX 336 kb)

BACKGROUND AND PURPOSE: Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions. MATERIALS AND METHODS: Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis. RESULTS: Enhancing lesions had a significantly (P < .001) higher mean longitudinal relaxation rate (1.22 ± 0.36 versus 0.89 ± 0.24), a higher mean transverse relaxation rate (9.8 ± 2.6 versus 7.4 ± 1.9), and a lower mean proton density (77 ± 11.2 versus 90 ± 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained. CONCLUSIONS: Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions.

Functional imaging is becoming increasingly important for the detection of neurodegenerative disorders. Perfusion MRI with arterial spin labeling (ASL) has been reported to provide promising diagnostic possibilities but is not yet widely used in routine clinical work. The aim of this study was to compare, in a clinical setting, the visual assessment of subtracted ASL CBF maps with and without additional smoothing, to FDG-PET data.

Summary Background Infarcts in the brain can be divided into larger cortical and smaller deep lacunar infarcts. The pathogenesis differs between these two types of infarctions. Objective This study aims to investigate the relationship between measures of endothelium-dependent vasodilation (EDV) and occurrence of cortical and lacunar infarcts in a population-based sample. Methods In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV) and brachial artery ultrasound to assess flow-mediated vasodilation (FMD). Six to seven years later MRI of the brain was performed, and the prevalence of cortical and lacunar infarcts was visually assessed in 407 randomly selected subjects. Results Lacunar infarcts were found in 22% and cortical infarcts in 5·9% of the subjects. EDV and FMD were both significantly related to the occurrence of cortical, but not lacunar infarcts. In a model adjusting for gender, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, HDL and LDL cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use, both EDV and FMD were independent predictors of cortical infarcts (P = 0·035 and P = 0·008, respectively). Conclusions Endothelium-dependent vasodilation in both forearm resistance vessels and the brachial artery was related to the occurrence of cortical, but not lacunar, infarcts at MRI in a population-based sample independently of traditional risk factors.

To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images. Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI). The algorithm combines morphological operations, intensity thresholding and mixture modelling. The method was validated against manual delineation and its robustness assessed from repeated imaging examinations. Using automated MRI software, the comparability with MRI was investigated. Volumes were compared based on average relative volume differences and their magnitudes; agreement was shown by a Bland-Altman analysis graph. We observed good agreement between our algorithm and manual delineation of a trained radiologist: the Pearson’s correlation coefficient was r = 0.94, tICVml[manual] = 1.05 × tICVml[automated] - 33.78 (R2 = 0.88). Bland-Altman analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of 1265 to 1526 mL. tICV measurements derived from CT using our proposed algorithm have shown to be reliable and consistent compared to manual delineation. However, it appears difficult to directly compare tICV measures between CT and MRI. • Automated estimation of tICV is in good agreement with manual tracing. • Consistent tICV estimations from repeated measurements demonstrate the robustness of the algorithm. • Automatically segmented volumes seem less variable than those from manual tracing. • Unbiased and automated tlCV estimation is possible from CT.