ASL-MRI-guided evaluation of multiple burr hole revascularization surgery in Moyamoya disease.

PURPOSE: Moyamoya (MM) disease is characterized by progressive intracranial arterial stenosis. Patients commonly need revascularization surgery to optimize cerebral blood flow (CBF). Estimation of CBF and cerebrovascular reserve (CVR) is therefore necessary before and after surgery. However, assessment of CBF before and after indirect revascularization surgery with the multiple burr hole (MBH) technique in MM has not been studied extensively. In this study, we describe our initial experience using arterial spin labeling magnetic resonance perfusion imaging (ASL-MRI) for CBF and CVR assessment before and after indirect MBH revascularization surgery in MM patients. METHODS: Eleven MM patients (initial age 6-50 years, 1 male/10 female) with 19 affected hemispheres were included. A total of 35 ASL-MRI examinations were performed using a 3D-pCASL acquisition before and after i.v. acetazolamide challenge (1000 mg in adults and 10 mg/kg in children). Twelve MBH procedures were performed in seven patients. The first follow-up ASL-MRI was performed 7-21 (mean 12) months after surgery. RESULTS: Before surgery, CBF was 46 ± 16 (mean ± SD) ml/100 g/min and CVR after acetazolamide challenge was 38.5 ± 9.9 (mean ± SD)% in the most affected territory (middle cerebral artery). In cases in which surgery was not performed, CVR was 56 ± 12 (mean ± SD)% in affected hemispheres. After MBH surgery, there was a relative change in CVR compared to baseline (preop) of + 23.5 ± 23.3% (mean ± SD). There were no new ischemic events. CONCLUSION: Using ASL-MRI we followed changes in CBF and CVR in patients with MM. The technique was encouraging for assessments before and after revascularization surgery.

Chronic cerebral blood flow alterations in traumatic brain injury and sports-related concussions.

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.

Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity.

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 < 0.05) between MET uptake and tumor cell density was demonstrated in all tumors separately. In two tumors, MET correlated with the density of proliferating cells and vessel cell density. There were no significant correlations between MET uptake and rCBV, and between rCBV and histological cell markers. CONCLUSIONS: The MET uptake in hot spots, outside hotspots, and in infiltrating tumor edges unanimously reflects tumor cell density. The correlation between MET uptake and vessel density and density of proliferating cells is less stringent in infiltrating tumor edges and is probably more susceptible to artifacts caused by larger blood vessels surrounding the tumor. Although based on a limited number of samples, this study provides histological proof for MET as an indicator of tumor cell density and for the lack of statistically significant correlations between rCBV and histological cell markers in oligodendrogliomas.

Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation.

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.

Standardized image evaluation in patients with idiopathic normal pressure hydrocephalus: consistency and reproducibility.

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.

Preserved white matter microstructure in adolescent patients with atypical anorexia nervosa.

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.

Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory.

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.

Cerebral Microbleeds: Imaging and Clinical Significance.

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.

Olfactory fMRI: Implications of Stimulation Length and Repetition Time.

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 4 olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex, and the insula. Twenty-two healthy participants with normal olfaction were examined with fMRI, with 2 stimulation lengths (6 s and 15 s) and 2 TRs (0.901 s and 1.34 s). 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 4 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 4 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.

Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. DISCUSSION: 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.

Quantitative and qualitative MRI evaluation of cerebral small vessel disease in an elderly population: a longitudinal study.

Background Cerebral white matter hyperintensities (WMHs), lacunes, and microbleeds are seen on magnetic resonance imaging (MRI) in small vessel disease (SVD). Purpose To assess SVD on MRI and its evolution over five years in an elderly population and to investigate whether relative cerebral blood flow (rCBF) at baseline was related to the progression of white matter (WM) lesions. Material and Methods In a population-based study, 406 participants aged 75 years underwent morphological MRI of the brain and 252 of them again at age 80 years. At age 75 years, a perfusion scan was also done. WMHs were evaluated qualitatively (visual scoring) and quantitatively (CASCADE software). Lacunes and microbleeds were counted. Results A significant progression of the WMH score and WMH volume occurred over five years ( P < 0.0001). New lacunes were seen in 10%. Participants with new lacunes at age 80 years showed a more pronounced increase in WMHs (P < 0.0001). Microbleeds were present in 14% at age 75 years. The visual WMH score was significantly associated with the presence of microbleeds ( P < 0.0001). There was no relationship between total WM rCBF and WMH volume at age 75 years, and no significant associations between regional or total rCBF at age 75 years and changes in WMH volume over five years. The total WM and GM volume decreased significantly between the ages of 75 and 80 years ( P < 0.0001). Conclusion MRI manifestations of SVD progressed over five years in an elderly population (age range = 75-80 years). rCBF was not associated with WMH volume or progression of WMH volume.

Perfusion Magnetic Resonance Imaging Changes in Normal Appearing Brain Tissue after Radiotherapy in Glioblastoma Patients may Confound Longitudinal Evaluation of Treatment Response.

BACKGROUND: The aim of this study was assess acute and early delayed radiation-induced changes in normal-appearing brain tissue perfusion as measured with perfusion magnetic resonance imaging (MRI) and the dependence of these changes on the fractionated radiotherapy (FRT) dose level. PATIENTS AND METHODS: Seventeen patients with glioma WHO grade III-IV treated with FRT were included in this prospective study, seven were excluded because of inconsistent FRT protocol or missing examinations. Dynamic susceptibility contrast MRI and contrast-enhanced 3D-T1-weighted (3D-T1w) images were acquired prior to and in average (standard deviation): 3.1 (3.3), 34.4 (9.5) and 103.3 (12.9) days after FRT. Pre-FRT 3D-T1w images were segmented into white- and grey matter. Cerebral blood volume (CBV) and cerebral blood flow (CBF) maps were calculated and co-registered patient-wise to pre-FRT 3D-T1w images. Seven radiation dose regions were created for each tissue type: 0-5 Gy, 5-10 Gy, 10-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy and 50-60 Gy. Mean CBV and CBF were calculated in each dose region and normalised (nCBV and nCBF) to the mean CBV and CBF in 0-5 Gy white- and grey matter reference regions, respectively. RESULTS: Regional and global nCBV and nCBF in white- and grey matter decreased after FRT, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in grey matter. CONCLUSIONS: Our data suggest that radiation-induced perfusion changes occur in normal-appearing brain tissue after FRT. This can cause an overestimation of relative tumour perfusion using dynamic susceptibility contrast MRI, and can thus confound tumour treatment evaluation.

The interactive effect of demographic and clinical factors on hippocampal volume: A multicohort study on 1958 cognitively normal individuals.

Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.

A resting-state fMRI study of obese females between pre- and postprandial states before and after bariatric surgery.

Past studies utilizing resting-state functional MRI (rsfMRI), have shown that obese humans exhibit altered activity in brain areas related to reward compared to normal-weight controls. However, to what extent bariatric surgery-induced weight loss alters resting-state brain activity in obese humans is less well-studied. Thus, we measured the fractional amplitude of low-frequency fluctuations from eyes-closed, rsfMRI in obese females (n = 11, mean age = 42 years, mean BMI = 41 kg/m2 ) in both a pre- and postprandial state at two time points: four weeks before, and four weeks after bariatric surgery. Several brain areas showed altered resting-state activity following bariatric surgery, including the putamen, insula, cingulate, thalamus and frontal regions. Activity augmented by surgery was also dependent on prandial state. For example, in the fasted state, activity in the middle frontal and pre- and postcentral gyri was found to be decreased after surgery. In the sated state, activity within the insula was increased before, but not after surgery. Collectively, our results suggest that resting-state neural functions are rapidly affected following bariatric surgery and the associated weight loss and change in diet.

Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.

OBJECTIVE: Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET. METHODS: Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis. RESULTS: Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168). CONCLUSION: ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET. KEY POINTS: • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.

Olfactory testing in consecutive patients referred with suspected dementia.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and early and accurate diagnosis is important. Olfactory dysfunction is an early sign of AD. The contribution by test of olfactory function has been surveyed in AD vs a line of conditions but remains to be settled in the workup of unselected patients referred with suspected dementia. METHODS: We performed a two-step investigation: first, a comparative study of healthy controls and probable AD patients to test the applicability of the chosen scents (cuisine study); second, a study of consecutive patients referred to our geriatric outpatient clinic for suspected dementia with the investigating personnel blinded to the results of the Olfactory Test (blinded study). RESULTS: The sum of scents detected discriminated patients with probable AD from controls in the cuisine study (n = 40; p < 0.001; area under ROC curve 0.94). In the blinded study (n = 50) the diagnosis was probable AD in 48%, minimal cognitive impairment in 24%, vascular dementia in 8%, alcohol induced impairment in 12%, depression in 4%, and Parkinson's disease and Lewy body dementia in 2%. Area under the ROC-curve was 0.67. The odds ratio for probable AD with 2+ smell errors was 12 (95%-CI: 1.3-101; p = 0.026 (reference 0-1 smell errors)) age adjusted. None in the AD group had zero smell errors (Negative Predictive Value 100%). CONCLUSION: Olfactory testing may support to dismiss the diagnosis of probable AD in the workup of a mixed group of patients referred with cognitive impairment. Still, it had a low sensitivity for probable AD.

Does permissive hypoxaemia during extracorporeal membrane oxygenation cause long-term neurological impairment?: A study in patients with H1N1-induced severe respiratory failure.

BACKGROUND: 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. OBJECTIVES: 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. DESIGN: Long-term follow-up study after ECMO. SETTING: Karolinska University Hospital, Sweden, from October 2012 to July 2013. PATIENTS: 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. INTERVENTIONS: Neurocognitive outcome was studied with standardised cognitive tests and MRI of the brain. MAIN OUTCOME MEASURES: 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. RESULTS: 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 ±â€ŠSD peripherally measured arterial saturation during the observation period was 79 ±â€Š10%. 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. CONCLUSIONS: Permissive hypoxaemia during ECMO might not negatively affect long-term cognitive outcome if adequate organ perfusion is maintained. TRIAL REGISTRATION: at Clinicaltrials.gov NCT01763060.

Adolescents newly diagnosed with eating disorders have structural differences in brain regions linked with eating disorder symptoms.

BACKGROUND: Adults with eating disorders (ED) show brain volume reductions in the frontal, insular, cingulate, and parietal cortices, as well as differences in subcortical regions associated with reward processing. However, little is known about the structural differences in adolescents with behavioural indications of early stage ED. AIM: This is the first study to investigate structural brain changes in adolescents newly diagnosed with ED compared to healthy controls (HC), and to study whether ED cognitions correlate with structural changes in adolescents with ED of short duration. METHODS: Fifteen adolescent females recently diagnosed with ED, and 28 age-matched HC individuals, were scanned with structural magnetic resonance imaging (MRI). Whole-brain and region-of-interest analyses were conducted using voxel-based morphometry (VBM). ED cognitions were measured with self-report questionnaires and working memory performance was measured with a neuropsychological computerized test. RESULTS AND CONCLUSIONS: The left superior temporal gyrus had a smaller volume in adolescents with ED than in HC, which correlated with ED cognitions (concerns about eating, weight, and shape). Working memory reaction time correlated positively with insula volumes in ED participants, but not HC. In ED, measurements of restraint and obsession was negatively correlated with temporal gyrus volumes, and positively correlated with cerebellar and striatal volumes. Thus, adolescents with a recent diagnosis of ED had volumetric variations in brain areas linked to ED cognitions, obsessions, and working memory. The findings emphasize the importance of early identification of illness, before potential long-term effects on structure and behaviour occur.

Diffusion Kurtosis Imaging of Gliomas Grades II and III - A Study of Perilesional Tumor Infiltration, Tumor Grades and Subtypes at Clinical Presentation.

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.

An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images.

Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.