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Purpose No consensus exists regarding follow-up recommendations for suspected pituitary microadenoma in children. To address this knowledge gap, we investigated the growth potential of pituitary solid and cystic lesions Methods The children included were Results In total, 74 children, median age 12 years (range 3–17), had a non-functioning microadenoma, probable microadenoma, or cyst. Of these, 55 underwent repeated MRI (median 3, range 2–7) with a median follow-up of 37 months (range 4–189). None of the pituitary lesions without hormonal disturbances increased significantly during follow-up. Two radiologists agreed that no lesion could be identified in 38/269 (14%) MRI examinations, and in 51/231 (22%) they disagreed about lesion location. In 34/460 (7%) MRI measurements size differed >2 mm, which had been considered significant progression. Conclusion Non-functioning pituitary microadenoma in children has small size variations, often below the spatial resolution of the scanners. We suggest lesions

Background: Childhood acute lymphoblastic leukemia (ALL) is associated with cognitive impairment in adulthood. Cognitive interference processing and its correlated functional magnetic resonance imaging (fMRI) activity in the brain have not yet been studied in this patient group.Material: Twenty-six adult childhood ALL survivors (median [interquartile range {IQR}] age, 40.0 [37.0-42.3] years) were investigated at median age (IQR), 35.0 (32.0-37.0) years after treatment with intrathecal and intravenous chemotherapy as well as cranial radiotherapy (24 Gy) and compared with 26 matched controls (median [IQR] age, 37.5 [33.0-41.5] years).Methods: Cognitive interference processing was investigated in terms of behavioral performance (response times [ms] and accuracy performance [%]) and fMRI activity in the cingulo-fronto-parietal (CFP) attention network as well as other parts of the brain using the multisource interference task (MSIT).Results: ALL survivors had longer response times and reduced accuracy performance during cognitive interference processing (median [IQR] interference effect, 371.9 [314.7-453.3] ms and 6.7 [4.2-14.7]%, respectively) comparedwith controls (303.7 [275.0-376.7] ms and 2.3 [1.6-4.3]%, respectively), but did not exhibit altered fMRI activity in the CFP attention network or elsewhere in the brain.Conclusion: Adult childhood ALL survivors demonstrated impaired behavioral performance but no altered fMRI activity when performing cognitive interference processing when compared with controls. The results can be used to better characterize this patient group and to optimize follow-up care and support for these individuals. (Less)

Purpose To assess cognitive interference processing in adults with childhood craniopharyngioma (CP), with and without hypothalamic injury, respectively, in terms of behavioral performance and functional magnetic resonance imaging (fMRI) activity, using the multi-source interference task (MSIT). Methods Twenty-eight CP patients (median age 34.5 [29.0–39.5] years) were investigated at median 20.5 (16.3–28.8) years after treatment with surgical resection and in some cases additional radiotherapy (n = 10) and compared to 29 matched controls (median age 37.0 [32.5–42.0] years). The subjects performed the MSIT during fMRI acquisition and behavioral performance in terms of response times (ms) and accuracy performance (%) were recorded. Results The MSIT activated the cingulo-fronto-parietal (CFP) attention network in both CP patients and controls. No differences were found in behavioral performance nor fMRI activity between CP patients (interference effect 333.9 [287.3–367.1] ms and 3.1 [1.6–5.6]%, respectively) and controls (309.1 [276.4–361.0] ms and 2.6 [1.6–4.9]%). No differences were found in behavioral performance nor fMRI activity between the two subgroups with (332.0 [283.6–353.4] ms and 4.2 [2.3–5.7]%, respectively) and without hypothalamic injury (355.7 [293.7–388.7] ms and 2.1 [1.0–5.2]%, respectively), respectively, and controls. Conclusion Adults with childhood CP performed cognitive interference processing equally well as controls and demonstrated no compensatory fMRI activity in the CFP attention network compared to controls. This was also true for the two subgroups with and without hypothalamic injury. The results can be useful to better characterize this condition, and to optimize treatment and support for these individuals.

Introduction: Cognitive function is an important outcome measure in patients with brain tumor, providing information about the patient’s clinical situation, treatment effects and possible progressi...

Background Neuronal damage in systemic lupus erythematosus (SLE) is common, but the extent and mechanisms are unclear. Neurofilament light (NfL) concentrations rise in plasma and cerebrospinal fluid (CSF) during neuronal damage in various neurological disorders. In this cross-sectional study, plasma and CSF concentrations of NfL were explored as a marker of neuronal damage in SLE. Methods Seventy-two consecutive SLE out-patients and 26 healthy controls, all female, aged Results Plasma and CSF NfL concentrations correlated strongly (r = 0.72, p p = 0.003), non-NPSLE (0.83 (0.18), p = 0.005); SLICC B model: NPSLE (0.87 (0.14), p = 0.001), non-NPSLE (0.83 (0.18), p = 0.008); ACR model: NPSLE (0.86 (0.16), p p = 0.044)). Plasma and CSF NfL concentrations did not differ between NPSLE and non-NPSLE patients. Higher plasma NfL concentrations correlated with larger CSF volumes on MRI (r = 0.34, p = 0.005), and was associated with poorer cognitive performance in the domains of simple attention, psychomotor speed and verbal memory. SLICC/ACR-Damage Index ≥1 was independently associated with higher plasma NfL concentrations (β = 0.074, p = 0.038). Higher plasma creatinine concentrations, anti-dsDNA-positivity, low complement C3 levels, or a history of renal involvement were associated with higher plasma NfL concentrations (β = 0.003, p = 0.009; β = 0.072, p = 0.031; β = 0.077, p = 0.027; β = 0.069, p = 0.047, respectively). Conclusions Higher plasma NfL concentrations in NPSLE and non-NPSLE patients may indicate a higher degree of neuronal damage in SLE in general, corresponding to cognitive impairment and organ damage development. Furthermore, our results may indicate a higher degree of neuronal breakdown in patients with active SLE, also without overt clinical symptoms. NfL may serve as an indicator of neuronal damage in SLE in further studies.

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

Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use.

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

Dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) has shown potential for tumor imaging using D-glucose as a biodegradable contrast agent. The DGE signal change is small at 3 T (around 1%) and accurate detection is hampered by motion. The intravenous D-glucose injection is associated with transient side effects that can indirectly generate subject movements. In this study, the aim was to study DGE arterial input functions (AIFs) in healthy volunteers at 3 T for different scanning protocols, as a step towards making the D-glucose weighted chemical exchange saturation transfer (glucoCEST) protocol more robust. Two different infusion durations (1.5 and 4.0 minutes) and saturation frequency offsets (1.2 and 2.0 ppm) were used. The effect of subject motion on the DGE signal was studied by using motion estimates retrieved from standard retrospective motion correction to create pseudo-DGE maps, where the apparent DGE signal changes were entirely caused by motion. Furthermore, the DGE AIFs were compared to venous blood glucose levels. A significant difference (p=0.03) between arterial baseline and post-infusion DGE signal was found after D-glucose infusion. The results indicate that the measured DGE AIF signal change depends on both motion and blood glucose concentration change, emphasizing the need for sufficient motion correction in glucoCEST imaging. Finally, we conclude that a longer infusion duration (e.g. 3-4 minutes) should preferably be used in glucoCEST experiments, since it can minimize the glucose infusion side effects without negatively affecting the DGE signal change.

Highlights • Tensor-valued dMRI facilitates prediction of meningioma consistency, grade and type. • Tensor-valued dMRI corroborates findings of diffusion tensor and kurtosis imaging. • MK and MKA is associated with firm and MD with variable meningioma consistency. • Variability of MKI in the vicinity of the tumor is associated with meningioma grade. • MKA 50 and MKI 50 separates psammomatous meningiomas from other meningioma types., Background Preoperative radiological assessment of meningioma characteristics is of value for pre- and post-operative patient management, counselling, and surgical approach. Purpose To investigate whether tensor-valued diffusion MRI can add to the preoperative prediction of meningioma consistency, grade and type. Materials and methods 30 patients with intracranial meningiomas (22 WHO grade I, 8 WHO grade II) underwent MRI prior to surgery. Diffusion MRI was performed with linear and spherical b-tensors with b-values up to 2000 s/mm2. The data were used to estimate mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and its components—the anisotropic and isotropic kurtoses (MKA and MKI). Meningioma consistency was estimated for 16 patients during resection based on ultrasonic aspiration intensity, ease of resection with instrumentation or suction. Grade and type were determined by histopathological analysis. The relation between consistency, grade and type and dMRI parameters was analyzed inside the tumor (“whole-tumor”) and within brain tissue in the immediate periphery outside the tumor (“rim”) by histogram analysis. Results Lower 10th percentiles of MK and MKA in the whole-tumor were associated with firm consistency compared with pooled soft and variable consistency (n = 7 vs 9; U test, p = 0.02 for MKA 10 and p = 0.04 for MK10) and lower 10th percentile of MD with variable against soft and firm (n = 5 vs 11; U test, p = 0.02). Higher standard deviation of MKI in the rim was associated with lower grade (n = 22 vs 8; U test, p = 0.04) and in the MKI maps we observed elevated rim-like structure that could be associated with grade. Higher median MKA and lower median MKI distinguished psammomatous type from other pooled meningioma types (n = 5 vs 25; U test; p = 0.03 for MKA 50 and p = 0.03 and p = 0.04 for MKI 50). Conclusion Parameters from tensor-valued dMRI can facilitate prediction of consistency, grade and type.

To investigate core resting state networks in SLE patients with and without neuropsychiatric symptoms by examining functional connectivity changes correlating with results of cognitive testing. Structural MRI and resting state-fMRI (rs-fMRI) were performed in 61 female SLE patients (mean age: 36.8 years, range 18.2-52.0 years) and 20 healthy controls (HC) (mean age 36.2 years, range 23.3-52.2 years) in conjunction with clinical examination and cognitive testing. Alterations in core resting state networks, not found in our healthy controls sample, correlated with cognitive performance gauged by neuropsychological tests in non-neuropsychiatric SLE (nNP) as well as in neuropsychiatric SLE patients (NP). The observed pattern of increased functional connectivity in core resting state networks correlated with reduced cognitive performance on all cognitive domains tested and with a heavy focus on DM, CE, and DM-CE in the NP subgroup. Furthermore, we found that the observed alterations in memory and psychomotor speed correlated with disease duration. In SLE patients both with and without clinically overt neuropsychiatric manifestations, we found changes in the functional connectivity of core resting state networks essential to cognitive functions. These findings may represent a rewiring of functional architecture in response to neuronal damage and could indicate suboptimal compensatory mechanisms at play.

Imaging is an indispensable tool for brain tumour diagnosis, surgical planning, and follow-up. Definite diagnosis, however, often demands histopathological analysis of microscopic features of tissue samples, which have to be obtained by invasive means. A non-invasive alternative may be to probe corresponding microscopic tissue characteristics by MRI, or so called 'microstructure imaging'. The promise of microstructure imaging is one of 'virtual biopsy' with the goal to offset the need for invasive procedures in favour of imaging that can guide pre-surgical planning and can be repeated longitudinally to monitor and predict treatment response. The exploration of such methods is motivated by the striking link between parameters from MRI and tumour histology, for example the correlation between the apparent diffusion coefficient and cellularity. Recent microstructure imaging techniques probe even more subtle and specific features, providing parameters associated to cell shape, size, permeability, and volume distributions. However, the range of scenarios in which these techniques provide reliable imaging biomarkers that can be used to test medical hypotheses or support clinical decisions is yet unknown. Accurate microstructure imaging may moreover require acquisitions that go beyond conventional data acquisition strategies. This review covers a wide range of candidate microstructure imaging methods based on diffusion MRI and relaxometry, and explores advantages, challenges, and potential pitfalls in brain tumour microstructure imaging.

Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17–56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35–1168) mm3 vs. 879 (775–1086) mm3; P

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

Background and aims Chronic pain including temporomandibular disorder (TMD) pain involves a complex interplay between peripheral and central sensitization, endogenous modulatory pathways, cortical processing and integration and numerous psychological, behavioral and social factors. The aim of this study was to compare spectroscopic patterns of N-Acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (MI), glutamate (Glu), and the combination of Glu and glutamine in the posterior insula in patients with chronic generalized or regional chronic TMD pain (gTMD and rTMD, respectively) compared to healthy individuals (HI) in relation to clinical findings of TMD pain. Methods Thirty-six female patients with chronic rTMD or gTMD with at least 3 months duration were included in the study. Ten healthy women were included as controls. All participants completed a questionnaire that comprised assessment of degrees of depression, anxiety, stress, catastrophizing, pain intensity, disability and locations. A clinical Diagnostic Criteria for Temporomandibular Disorders examination that comprised assessment of pain locations, headache, mouth opening capacity, pain on mandibular movement, pain on palpation and temporomandibular joint noises was performed. Pressure-pain threshold (PPT) over the masseter muscle and temporal summation to pressure stimuli were assessed with an algometer. Within a week all participants underwent non-contrast enhanced MRI on a 3T MR scanner assessing T1-w and T2-w fluid attenuation inversion recovery. A single-voxel 1H-MRS examination using point-resolved spectroscopy was performed. The metabolite concentrations of NAA, tCr, Cho, MI, Glu and Glx were analyzed with the LC model. Metabolite levels were calculated as absolute concentrations, normalized to the water signal. Metabolite concentrations were used for statistical analysis from the LC model if the Cramér–Rao bounds were less than 20%. In addition, the ratios NAA/tCr, Cho/tCr, Glu/tCr and MI/tCr were calculated. Results The results showed significantly higher tCr levels within the posterior insula in patients with rTMD or gTMD pain than in HI (p=0.029). Cho was negatively correlated to maximum mouth opening capacity with or without pain (rs=−0.42, n=28, p=0.031 and rs=−0.48, n=28, p=0.034, respectively) as well as pressure-pain threshold on the hand (rs=−0.41, n=28, p=0.031). Glu was positively correlated to temporal summation to painful mechanical stimuli (rs=0.42, n=26, p=0.034). Conclusions The present study found that increased concentrations of Cho and Glu in the posterior insular cortex is related to clinical characteristics of chronic TMD pain, including generalized pain. These findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. Implications The findings in this study have indirect implications for the diagnosis and management of TMD patients. That said, the findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. It is also a further step towards understanding and accepting chronic pain as a disorder in itself.

Objectives At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. Methods Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists’ societies and distributed via social media. Results Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24–72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minority of sites use a reporting template (23%). Conclusion Clinical best practice recommendations for glioma imaging assessment are proposed and the current role of advanced MRI modalities in routine use is addressed. Key Points • We recommend the EORTC-NBTS protocol as the clinical standard glioma protocol. • Perfusion MRI is recommended for diagnosis and follow-up of glioma. • Use of advanced imaging could be promoted with increased education activities. • Most response assessment is currently performed qualitatively. • Reporting templates are not widely used, and could facilitate standardisation. Electronic supplementary material The online version of this article (10.1007/s00330-018-5314-5) contains supplementary material, which is available to authorized users.

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

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

PurposeRadiological assessment of primary brain neoplasms, both high (HGG) and low grade tumors (LGG), based on contrast-enhancement alone can be inaccurate. We evaluated the radiological value of amide proton transfer weighted (APTw) MRI as an imaging complement for pre-surgical radiological diagnosis of brain tumors.MethodsTwenty-six patients were evaluated prospectively; (22 males, 4 females, mean age 55 years, range 26-76 years) underwent MRI at 3T using T1-MPRAGE pre- and post-contrast administration, conventional T2w, FLAIR, and APTw imaging pre-surgically for suspected primary/secondary brain tumor. Assessment of the additional value of APTw imaging compared to conventional MRI for correct pre-surgical brain tumor diagnosis. The initial radiological pre-operative diagnosis was based on the conventional contrast-enhanced MR images. The range, minimum, maximum, and mean APTw signals were evaluated. Conventional normality testing was performed; with boxplots/outliers/skewness/kurtosis and a Shapiro-Wilk's test. Mann-Whitney U for analysis of significance for mean/max/min and range APTw signal. A logistic regression model was constructed for mean, max, range and Receiver Operating Characteristic (ROC) curves calculated for individual and combined APTw signals.ResultsConventional radiological diagnosis prior to surgery/biopsy was HGG (8 patients), LGG (12 patients), and metastasis (6 patients). Using the mean and maximum: APTw signal would have changed the pre-operative evaluation the diagnosis in 8 of 22 patients (two LGGs excluded, two METs excluded). Using a cut off value of >2.0% for mean APTw signal integral, 4 of the 12 radiologically suspected LGG would have been diagnosed as high grade glioma, which was confirmed by histopathological diagnosis. APTw mean of >2.0% and max >2.48% outperformed four separate clinical radiological assessments of tumor type, P-values = .004 and = .002, respectively.ConclusionsUsing APTw-images as part of the daily clinical pre-operative radiological evaluation may improve diagnostic precision in differentiating LGGs from HGGs, with potential improvement of patient management and treatment.

Noninvasive imaging methods are sought to objectively predict early response to therapy for high-grade glioma tumors. Quantitative metrics derived from diffusion-weighted imaging, such as apparent diffusion coefficient (ADC), have previously shown promise when used in combination with voxel-based analysis reflecting regional changes. The functional diffusion mapping (fDM) metric is hypothesized to be associated with volume of tumor exhibiting an increasing ADC owing to effective therapeutic action. In this work, the reference fDM-predicted survival (from previous study) for 3 weeks from treatment initiation (midtreatment) is compared to multiple histogram-based metrics using Kaplan–Meier estimator for 80 glioma patients stratified to responders and nonresponders based on the population median value for the given metric. The ADC histogram metric reflecting reduction in midtreatment volume of solid tumor (ADC &lt, 1.25 × 10−3 mm2/s) by &gt, 8% population-median with respect to pretreatment is found to have the same predictive power as the reference fDM of increasing midtreatment ADC volume above 4%. This study establishes the level of correlation between fDM increase and low-ADC tumor volume shrinkage for prediction of early response to radiation therapy in patients with glioma malignancies.

In diffusion MRI (dMRI), microscopic diffusion anisotropy can be obscured by orientation dispersion. Separation of these properties is of high importance, since it could allow dMRI to non-invasively probe elongated structures such as neurites (axons and dendrites). However, conventional dMRI, based on single diffusion encoding (SDE), entangles microscopic anisotropy and orientation dispersion with intra-voxel variance in isotropic diffusivity. SDE-based methods for estimating microscopic anisotropy, such as the neurite orientation dispersion and density imaging (NODDI) method, must thus rely on model assumptions to disentangle these features. An alternative approach is to directly quantify microscopic anisotropy by the use of variable shape of the b-tensor. Along those lines, we here present the 'constrained diffusional variance decomposition' (CODIVIDE) method, which jointly analyzes data acquired with diffusion encoding applied in a single direction at a time (linear tensor encoding, LTE) and in all directions (spherical tensor encoding, STE). We then contrast the two approaches by comparing neurite density estimated using NODDI with microscopic anisotropy estimated using CODIVIDE. Data were acquired in healthy volunteers and in glioma patients. NODDI and CODIVIDE differed the most in gray matter and in gliomas, where NODDI detected a neurite fraction higher than expected from the level of microscopic diffusion anisotropy found with CODIVIDE. The discrepancies could be explained by the NODDI tortuosity assumption, which enforces a connection between the neurite density and the mean diffusivity of tissue. Our results suggest that this assumption is invalid, which leads to a NODDI neurite density that is inconsistent between LTE and STE data. Using simulations, we demonstrate that the NODDI assumptions result in parameter bias that precludes the use of NODDI to map neurite density. With CODIVIDE, we found high levels of microscopic anisotropy in white matter, intermediate levels in structures such as the thalamus and the putamen, and low levels in the cortex and in gliomas. We conclude that accurate mapping of microscopic anisotropy requires data acquired with variable shape of the b-tensor.

Purpose Systemic lupus erythematosus (SLE) is a predominantly female autoimmune disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25–70% of SLE patients. Using diffusion tensor imaging, various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate if changes can be detected in the individual white matter tracts in SLE patients regardless if neuropsychiatric symptoms are present or not. Materials and Methods Magnetic resonance diffusion tractography in several individual white matter tracts that are involved in language and memory tasks, including tracts to cortical association areas, was applied in 21 patients with NPSLE (mean age: 40.7 ± 12.8 years; range: 22–67 years), 18 patients with non-neurologic systemic lupus erythematosus (non-NPSLE) (mean age: 40.6 ± 12 years; range: 22–67 years), and 20 healthy control (HC) individuals (mean age: 40.64 ± 12.7 years; range: 19–60 years). Additional patients were evaluated; however, because of the inability to complete the scans required, they were excluded from the study. The fractional anisotropy of individual fiber tracts was measured and correlated with cognitive function and lupus disease severity index (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]) to assess predictability and diagnostic value of these measures for NPSLE. Results Analyses of variance of the tractography data from the analysis of 21 tracts revealed decreased fractional anisotropy in uncinate fasciculus in the NPSLE patients when compared to non-NPSLE lupus patients and HC individuals (P = 0.002). Non-NPSLE patients also demonstrated decreased fractional anisotropy when compared to healthy patients (P = 0.03). Decreased fractional anisotropy was also identified in the corpus callosum and corona radiata in NPSLE patients when compared to HC individuals; however, these tracts did not show a significant difference between NPSLE and non-NPSLE patients. Decreased fractional anisotropy in the uncinate fasciculus correlated with low SLEDAI score (R2 = 0.32). Conclusions Diffusion tensor tractography corroborates findings of decreased white matter integrity within the anterior corona radiate as well as the corpus callosum as previously described. Specifically, our study identified changes in the uncinate fasciculus in NPSLE and non-NPSLE patients that correlate with clinical changes (SLEDAI scores) and are independent of conventional T2 lesion burden. (Less)

Pouring out the dirty bathwater without throwing away either the baby or its parents : commentary to Saunders et al.

Background: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Material and methods: Thirty-eight (21 women) ALL survivors, median age 38 (27–46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. Results: ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention (p

Purpose: To evaluate the feasibility of a 3-minute b-tensor encoding protocol for diffusion MRI-based assessment of the microscopic anisotropy and tissue heterogeneity in a wide range of intracranial tumors. Methods: B-tensor encoding was performed in 42 patients with intracranial tumors (gliomas, meningiomas, adenomas, metastases). Microscopic anisotropy and tissue heterogeneity were evaluated by estimating the anisotropic kurtosis ($MK_A$) and isotropic kurtosis ($MK_I$), respectively. An extensive imaging protocol was compared with a faster 3-minute protocol. Results: The fast imaging protocol yielded parameters with characteristics in terms of bias and precision similar to the full protocol. Glioblastomas had lower microscopic anisotropy than meningiomas $(MK_A = 0.29 \pm 0.06$ versus $0.45\pm0.08, p = 0.003)$. Metastases had higher tissue heterogeneity $(MK_I = 0.57\pm0.07)$ than both the glioblastomas $(0.44\pm0.06, p < 0.001)$ and meningiomas $(0.46\pm0.06, p = 0.03)$. Conclusion: Evaluation of the microscopic anisotropy and tissue heterogeneity in intracranial tumor patients is feasible in clinically relevant times frames., Submitted to Magnetic Resonance in Medicine

Although neutrophil extracellular traps (NETs) have been highlighted in several systemic inflammatory diseases, their clinical correlates and potential pathological role remain obscure. Herein, we describe a dramatic onset of systemic lupus erythematosus (SLE) with clear-cut pathogenic implications for neutrophils and NET formation in a young woman with cardiac (Libman-Sacks endocarditis) and central nervous system (psychosis and seizures) involvement. Despite extensive search, circulating antiphospholipid autoantibodies, a hallmark of Libman-Sacks endocarditis, could not be detected. Instead, we observed active NET formation in the tissue of the mitral valve, as well as in the circulation. Levels of NET remnants were significantly higher in serially obtained sera from the patient compared with sex-matched blood donors (p=.0011), and showed a non-significant but substantial correlation with blood neutrophil counts (r=0.65, p=.16). The specific neutrophil elastase activity measured in serum seemed to be modulated by the provided immunosuppressive treatment. In addition, we found anti-Ro60/SSA antibodies in the cerebrospinal fluid of the patient but not NET remnants or increased elastase activity. This case illustrates that different disease mechanisms mediated via autoantibodies can occur simultaneously in SLE. NET formation with release of cytotoxic NET remnants is a candidate player in the pathogenesis of this non-canonical form of Libman-Sacks endocarditis occurring in the absence of traditional antiphospholipid autoantibodies. The case description includes longitudinal results with clinical follow-up data and a discussion of the potential roles of NETs in SLE. Funding Agencies|Swedish Rheumatism Association; Swedish Society of Medicine; King Gustaf Vs 80-year Foundation; King Gustaf V and Queen Victorias Freemasons Foundation; Ingrid Asp Foundation; County Council of Ostergotland; SFFR of Ukraine; German Research Foundation (DFG) [CRC1181, GRK1660]; EU [690836 PANG]; Volkswagen-Stiftung [90361]

Purpose: Liquid biopsy has great potential to improve the management of brain tumor patients at high risk of surgery-associated complications. Here, the aim was to explore plasma extracellular vesicle (plEV) immunoprofiling as a tool for noninvasive diagnosis of glioma. Experimental Design: PlEV isolation and analysis were optimized using advanced mass spectrometry, nanoparticle tracking analysis, and electron microscopy. We then established a new procedure that combines size exclusion chromatography isolation and proximity extension assay–based ultrasensitive immunoprofiling of plEV proteins that was applied on a well-defined glioma study cohort (n = 82). Results: Among potential candidates, we for the first time identify syndecan-1 (SDC1) as a plEV constituent that can discriminate between high-grade glioblastoma multiforme (GBM, WHO grade IV) and low-grade glioma [LGG, WHO grade II; area under the ROC curve (AUC): 0.81; sensitivity: 71%; specificity: 91%]. These findings were independently validated by ELISA. Tumor SDC1 mRNA expression similarly discriminated between GBM and LGG in an independent glioma patient population from The Cancer Genome Atlas cohort (AUC: 0.91; sensitivity: 79%; specificity: 91%). In experimental studies with GBM cells, we show that SDC1 is efficiently sorted to secreted EVs. Importantly, we found strong support of plEVSDC1 originating from GBM tumors, as plEVSDC1 correlated with SDC1 protein expression in matched patient tumors, and plEVSDC1 was decreased postoperatively depending on the extent of surgery. Conclusions: Our studies support the concept of circulating plEVs as a tool for noninvasive diagnosis and monitoring of gliomas and should move this field closer to the goal of improving the management of cancer patients.

To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.

In contrast to women with relatively asymptomatic endometriosis, women with endometriosis-associated chronic pelvic pain (CPP) exhibit nonpelvic hyperalgesia and decreased gray matter volume in key neural pain processing regions. Although these findings suggest central pain amplification in endometriosis-associated CPP, the underlying changes in brain chemistry and function associated with central pain amplification remain unknown. We performed proton spectroscopy and seed-based resting functional connectivity magnetic resonance imaging to determine whether women with endometriosis display differences in insula excitatory neurotransmitter concentrations or intrinsic brain connectivity to other pain-related brain regions. Relative to age-matched pain-free controls, women with endometriosis-associated CPP displayed increased levels of combined glutamine-glutamate (Glx) within the anterior insula and greater anterior insula connectivity to the medial prefrontal cortex (mPFC). Increased connectivity between these regions was positively correlated with anterior insula Glx concentrations (r = .87), as well as clinical anxiety (r = .61, P = .02), depression (r = .60, P = .03), and pain intensity (r = .55, P = .05). There were no significant differences in insula metabolite levels or resting-state connectivity in endometriosis patients without CPP versus controls. We conclude that enhanced anterior insula glutamatergic neurotransmission and connectivity with the mPFC, key regions of the salience and default mode networks, may play a role in the pathophysiology of CPP independent of the presence of endometriosis. Perspective Similar to other chronic pain conditions, endometriosis-associated pelvic pain is associated with altered brain chemistry and function in pain processing regions. These findings support central pain amplification as a mechanism of chronic pelvic pain, and clinicians should consider the use of adjunctive therapies that target central pain dysfunction in these women.

Background and purpose. Whereas traditional views of language processing in the brain have assumed that the language function is concentrated to a limited number of cortical areas (Broca’s and Wernicke’s areas), current knowledge points at a much more complex system of language and speech processing involving many brain areas, both cortical and subcortical. The purpose of the current study was to make an unbiased assessment of which cerebral areas are affected in first-ever acute ischemic stroke patients identified as having language and speech impairments according to the National Institute of Health Stroke Scale (NIHSS). Methods. Data from thirty-four patients with language and speech impairments, with a score of 1-3 on item 9 on the NIHSS, following ischemic stroke was collected from the Lund Stroke Register. MRI images acquired up to 20 days after stroke onset were used to create an overlap lesion image using MRIcron software. Results. The classical language areas, Wernicke’s and Broca’s area, were affected in less than one fourth of the patients. The most frequently affected region was a subcortical region - the left caudate nucleus and the adjacent corona radiata. Conclusions. These findings contribute to the growing body of evidence that the basal ganglia have a crucial role in the control over language and speech processing.

Different radiological methods play an important role in the work-up of patients complaining of spine pain. Depending on the symptoms and the suspected underlying etiology different methods are selected. In the following presentation we briefly present the different radiological and magnetic resonance tomography methods that are at hand, give some guidance in which method to use, and present the typical imaging findings in some of the most common conditions that presents with spine pain.

Background The purpose of this study was to investigate whether white matter microstructure is altered in patients suffering from systemic lupus erythematosus (SLE), and if so, whether such alterations differed between patients with and without neuropsychiatric symptoms. Methods Structural MRI and diffusion tensor imaging (DTI) were performed in 64 female SLE patients (mean age 36.9 years, range 18.2–52.2 years) and 21 healthy controls (mean age 36.7 years, range 23.3–51.2 years) in conjunction with clinical examination, laboratory tests, cognitive evaluation, and self-assessment questionnaires. The patients were subgrouped according to the American College of Rheumatology Neuropsychiatric Systemic Lupus Erythematosus case definitions into non-neuropsychiatric SLE (nonNPSLE) and neuropsychiatric SLE (NPSLE). Results Comparisons between the SLE group and healthy controls showed that the mean fractional anisotropy (FA) was significantly reduced in the right rostral cingulum (p = 0.038), the mid-sagittal corpus callosum (CC) (p = 0.050), and the forceps minor of the CC (p = 0.015). The mean diffusivity (MD) was significantly increased in the left hippocampal cingulum (p = 0.017). No significant differences in MD or FA values were identified between NPSLE and nonNPSLE patients. Disease duration among all SLE patients correlated significantly with reduced FA in the CC (p

A systematic review of shaken baby syndrome by the Swedish Agency for Health Technology Assessment and Assessment of Social Services generated numerous reactions from professional organisations, even before the review was published. There was also a lively debate after a paper summarising its findings were published in Acta Paediatrica The various responses are worth debating further, as they raise several important issues with regard to research ethics, having an open debate and publishing scientific findings.The responses to the shaken baby syndrome report indicate that scientific scrutiny risks being lost when researchers and organisations are not open to challenging established ideas.

The scientific evidence regarding retinal haemorrhages. Response to Hellgren et al. and Levin

Purpose: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25–70% of patients. Using diffusion tensor imaging (DTI) various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate, if regional changes in white matter integrity can also be detected in SLE patients without neuropsychiatric symptoms (non-NPSLE patients). Methods: Applying DTI and tract based spatial statistics (TBSS) we investigated 19 NPSLE patients, 19 non-NPSLE and 18 healthy controls. Groups were matched for age and sex. Image pre-processing was performed using FSL, following the TBSS pipeline (eddy current correction, estimation of fractional anisotropy (FA), normalization, skeletonization of the group mean FA image). A general linear model with threshold-free cluster enhancement was used to assess significant differences between the three groups. Results: Statistical analyses revealed several regions of decreased prefrontal white matter integrity (decreased FA) in both groups of SLE patients. The changes found in the non-NPSLE patients (as compared to healthy controls) overlapped with those in the NPSLE patients, but were not as pronounced. Conclusions: Our data suggest that changes in regional white matter integrity, in terms of a decrease in FA, are present not only in NPSLE patients, but also in non-NPSLE patients, though to a lesser degree. We also demonstrate that the way statistical maps are corrected for multiple comparisons has a profound influence on whether alterations in white matter integrity in non-NPSLE patients are deemed significant.

Our aim with this study was to develop a user-friendly method for pediatric sonographically guided lumbar punctures so that we can visualize intrathecal anatomy, confirm intrathecal injection at the time of injection, and, most importantly, avoid ionizing radiation to a child's already radiosensitive pelvis. Sonographically guided lumbar puncture was prospectively performed in children aged 7 weeks to 16 years. All attempts (n = 9) were successful. We were able to identify relevant anatomy (including the conus in children 10 years and younger), confirm intrathecal injection, visualize intrathecal hematoma, and avoid radiation. Sonography is a promising modality for image-guided lumbar punctures without radiation in children.

Background: Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment. Methods: To identify the clinical action of pregabalin, a proven analgesic, the authors performed three complementary brain neuroimaging procedures: (proton magnetic resonance spectroscopy, functional magnetic resonance imaging, and functional connectivity magnetic resonance imaging) in 17 chronic pain patients diagnosed with fibromyalgia. Results: The authors found that pregabalin but not placebo reduces combined glutamate + glutamine levels within the posterior insula (pregabalin P = 0.016; placebo P = 0.71). Interestingly, reductions in clinical pain were associated with reductions in brain connectivity of this structure to brain regions within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = −0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0.018) but not placebo (P = 0.182). Perhaps most importantly, baseline values for all three neuroimaging markers predicted subsequent analgesic response to pregabalin but not placebo. Conclusions: The results of this study suggest that pregabalin works in part by reducing insular glutamatergic activity, leading to a reduction of the increased functional connectivity seen between brain regions in chronic pain states. The study also supports a role for human brain imaging in the development, assessment, and personalized use of central-acting analgesics.

The purpose of the study was to develop a method for analysis of diffusion parameters along white matter (WM) tracts, using spatial normalization based on anatomical landmarks, and to introduce the apparent area coefficient (AAC). The method's applicability was tested in the inferior fronto-occipital fasciculus (IFO) in patients with progressive supranuclear palsy (PSP) and healthy controls (HCs).A framework for analysis of diffusion parameters was developed. Spatial normalization of the tracts was performed using anatomical landmarks, to avoid deformations caused by cerebral atrophy. Initially, 38 HCs were used to optimize a threshold for the minimal size of regions that differ between groups. The fractional anisotropy, mean diffusivity, AAC, and the hemispheric asymmetry index (AI), were compared between 11 PSP patients and 15 HCs.The method was feasible for analysis of PSP patients and HCs. The AI showed that the observed hemispheric asymmetry of AAC was significantly larger in PSP patients compared with HCs in small regions of the IFO.The method was successfully employed for analysis of diffusion parameters along the IFO in a patient group. This method can be potentially useful in studies of WM diseases, with or without cerebral atrophy.

Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27–46) years. All were treated with a CRT dose of 24 Gy and 11 years (3–13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p

PURPOSE: To provide estimates of the diffusional kurtosis in the healthy brain in anatomically defined areas and list these along previously reported values in pathologies. MATERIALS AND METHODS: Thirty-six volunteers (mean age = 33.1 years; range, 19-64 years) underwent diffusional kurtosis imaging. Mean kurtosis (MK), radial kurtosis (RK), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA) were determined in 26 anatomical structures. Parameter estimates were assessed regarding age dependence. RESULTS: MK varied from 1.38 in the splenium of the corpus callosum to 0.66 in the caudate head, MD varied from 0.68 to 0.62 μm(2) /ms and FA from 0.87 to 0.29. MK, and FA showed a strong positive correlation, RK and RD a strong negative correlation. Parameter estimates showed age correlation in some regions; also the average MK and RK for all WM and all GM areas, respectively, were negatively correlated with age. CONCLUSION: DKI parameter estimates MK and RK varied depending on the anatomical region and varied with age in pooled WM and GM data. MK estimates in the internal capsule, corpus callosum, and thalamus were consistent with previous studies. The range of values of MK and RK in healthy brain overlapped with that in pathologies. J. Magn. Reson. Imaging 2012. © 2012 Wiley Periodicals, Inc. (Less)

Objective.Neuropsychiatric lupus (NPSLE) is a severe and potentially life-threatening condition, reported to occur in 25%–70% of patients with systemic lupus erythematosus (SLE). Brain imaging, especially magnetic resonance imaging, is frequently used to diagnose or exclude overt cerebral pathologies such as edema, hemorrhage, and central thrombosis. More advanced imaging techniques have been applied to demonstrate subtle changes in regional cerebral blood flow and brain structure. We investigated changes in regional gray-matter (GM) volume in SLE patients without neurological manifestations and NPSLE patients at an acute stage of the disease.Methods.Using high-resolution structural images and voxel-based morphometry (VBM), we investigated regional GM volume in 20 NPSLE patients (within 2 weeks of the acute manifestation), 18 SLE patients without neurologic and/or psychiatric manifestations, and 18 healthy controls.Results.VBM analyses revealed several regions of GM atrophy in various parts of the brain in NPSLE and SLE patients. GM atrophy was seen in both groups in the temporal and parietal lobes and was most pronounced in the posterior thalamus bilaterally. Both groups showed an increase in regional GM volume in the posterior parahippocampal gyrus.Conclusion.Our data suggest that changes in regional brain morphology are present in acute NPSLE, but also in SLE (as compared to controls), which might be indicative of a subclinical neurodegenerative process. Further research is needed to investigate whether specific neuropsychiatric symptoms are related to these changes.

Temporomandibular disorders (TMD) include craniocervical pain conditions with unclear etiologies. Central changes are suspected; however, few neuroimaging studies of TMD exist. Single-voxel proton magnetic resonance spectroscopy (1H-MRS) was used before and after pressure-pain testing to assess glutamate (Glu), glutamine (Gln), N-acetylaspartate (NAA), and choline (Cho) levels in the right and left posterior insulae of 11 individuals with myofascial TMD and 11 matched control individuals. Glu levels were significantly lower in all individuals after pain testing. Among those with TMD, left-insular Gln levels were related to reported pain, left posterior insular NAA and Cho levels were significantly higher at baseline than in control individuals, and NAA levels were significantly correlated with pain-symptom duration, suggesting adaptive changes. The results suggest that significant central cellular and molecular changes can occur in individuals with TMD.

Objective Recent scientific findings have reinvigorated interest in examining the role of gamma-aminobutyric acid (GABA), the major inhibitory central nervous system neurotransmitter, in chronic pain conditions. Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM). The purpose of this study was to test the hypothesis that decreased levels of insular and anterior cingulate GABA would be present in FM patients, and that the concentration of this neurotransmitter would be correlated with pressurepain thresholds. Methods. Sixteen FM patients and 17 age-and sex-matched healthy controls underwent pressure-pain testing and a 3T proton magnetic resonance spectroscopy session in which the right anterior insula, right posterior insula, anterior cingulate, and occipital cortex were examined in subjects at rest. Results. GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls (mean +/- SD 1.17 +/- 0.24 arbitrary institutional units versus 1.42 +/- 0.32 arbitrary institutional units; P = 0.016). There was a trend toward increased GABA levels in the anterior cingulate of FM patients compared with healthy controls (P = 0.06). No significant differences between groups were detected in the posterior insula or occipital cortex (P > 0.05 for all comparisons). Within the right posterior insula, higher levels of GABA were positively correlated with pressurepain thresholds in the FM patients (Spearman's rho = 0.63; P = 0.02). Conclusion. Diminished inhibitory neurotransmission resulting from lower concentrations of GABA within the right anterior insula may play a role in the pathophysiology of FM and other central pain syndromes. (Less)

Many of the comments on our systematic literature review on shaken baby syndrome (1) have focused on our criticism of how child protection teams’ classification of study cases and controls are used as gold standard and the faulty circular reasoning associated with that (2,3). Some commentators have also questioned how reasonable it is to focus on the triad of retinal hemorrhages, This article is protected by copyright. All rights reserved.

BACKGROUND AND PURPOSE: Widespread pain sensitivity in patients with FM suggests a CNS processing problem. The purpose of this study was to assess alterations in perfusion as measured by DSC in a number of brain regions implicated in pain processing between patients with FM and healthy controls. MATERIALS AND METHODS: Twenty-one patients with FM and 27 healthy controls underwent conventional MR imaging and DSC. For DSC, 12 regions of interest were placed in brain regions previously implicated in pain processing. rCBF values were calculated for each region of interest. Subjects answered mood/pain coping questionnaires and underwent clinical/experimental pain assessment. RESULTS: There were significant correlations between the thalamic rCBF values and the pain-control beliefs of FM subjects. The strength of the relationship between clinical pain measures and thalamic rCBF values increased after adjusting for pain-control beliefs. There was a significantly different distribution pattern of rCBF values across various brain regions between the FM group and the healthy controls. There was a lower degree of correlation in the FM group between the thalamic rCBF values and the other brain regions relative to the healthy controls. CONCLUSIONS: Significant correlations were found between thalamic rCBF values and pain belief values. These data suggest that there are baseline alterations of brain perfusion in patients with FM. rCBF values of the thalami exhibited lower correlations with respect to other brain regions thought to be involved in pain processing compared with those in healthy controls.

Purpose To assess whether a new method of quantifying therapy-associated hemodynamic alterations may help to distinguish pseudoprogression from true progression in patients with high-grade glioma. Patients and Methods Patients with high-grade glioma received concurrent chemoradiotherapy. Relative cerebral blood volume (rCBV) and blood flow (rCBF) maps were acquired before chemoradiotherapy and at week 3 during treatment on a prospective institutional review board–approved study. Pseudoprogression was defined as imaging changes 1 to 3 months after chemoradiotherapy that mimic tumor progression but stabilized or improved without change in treatment or for which resection revealed radiation effects only. Clinical and conventional magnetic resonance (MR) parameters, including average percent change of rCBV and CBF, were evaluated as potential predictors of pseudoprogression. Parametric response map (PRM), an innovative, voxel-by-voxel method of image analysis, was also performed. Results Median radiation dose was 72 Gy (range, 60 to 78 Gy). Of 27 patients, stable disease/partial response was noted in 13 patients and apparent progression was noted in 14 patients. Adjuvant temozolomide was continued in all patients. Pseudoprogression occurred in six patients. Based on PRM analysis, a significantly reduced blood volume (PRMrCBV) at week 3 was noted in patients with progressive disease as compared with those with pseudoprogression (P < .01). In contrast, change in average percent rCBV or rCBF, MR tumor volume changes, age, extent of resection, and Radiation Therapy Oncology Group recursive partitioning analysis classification did not distinguish progression from pseudoprogression. Conclusion PRMrCBV at week 3 during chemoradiotherapy is a potential early imaging biomarker of response that may be helpful in distinguishing pseudoprogression from true progression in patients with high-grade glioma.

Purpose: To compare apparent diffusion coefficients (ADCs) with distributed diffusion coefficients (DDCs) in high-grade gliomas. Materials and Methods: Twenty patients with high-grade gliomas prospectively underwent diffusion-weighted MRI. Traditional ADC maps were created using b-values of 0 and 1000 s/mm2. In addition, DDC maps were created by applying the stretched-exponential model using b-values of 0, 1000, 2000, and 4000 s/mm2. Whole-tumor ADCs and DDCs (in 10−3 mm2/s) were measured and analyzed with a paired t-test, Pearson's correlation coefficient, and the Bland-Altman method. Results: Tumor ADCs (1.14 ± 0.26) were significantly lower (P = 0.0001) than DDCs (1.64 ± 0.71). Tumor ADCs and DDCs were strongly correlated (R = 0.9716; P < 0.0001), but mean bias ± limits of agreement between tumor ADCs and DDCs was −0.50 ± 0.90. There was a clear trend toward greater discordance between ADC and DDC at high ADC values. Conclusion: Under the assumption that the stretched-exponential model provides a more accurate estimate of the average diffusion rate than the mono-exponential model, our results suggest that for a little diffusion attenuation the mono-exponential fit works rather well for quantifying diffusion in high-grade gliomas, whereas it works less well for a greater degree of diffusion attenuation. J. Magn. Reson. Imaging 2010;31:531–537. © 2010 Wiley-Liss, Inc.

Posterior corrective surgery using “all pedicle screw construct” carries risk of neurovascular complications. The study aims were to assess the screw placement in patients with adolescent idiopathic scoliosis using CT with low-radiation dose, and to evaluate the clinical outcome in patients with misplaced pedicle screws. CTs of 49 consecutive patients (873 screws, 79% thoracic) were retrospectively evaluated by two independent radiologists. A new grading system was developed to distinguish between lateral, medial and anterior cortical perforations, endplate perforation and foraminal perforation. The grading system is based on whether the cortical violation is partial or total rather than on mm-basis. The overall rate of screw misplacement was 17% (n = 149): 8% were laterally placed and 6.1% were medially placed. The rates of anterior cortical, endplate and foraminal perforation were 1.5, 0.9, and 0.5%, respectively. Lateral cortical perforation was more frequent in the thoracic spine (P = 0.005), whereas other types of misplacement including medial cortical perforation were more frequent on the left and the concave side of scoliotic curves (P = 0.002 and 0.003). No neurovascular complications were reported. The association between the occurrence of screw misplacement and the Cobb angle was statistically significant (P = 0.037). Misplacements exceeding half screw diameter should be classified as unacceptable. Low-dose CT implies exposing these young individuals to a significantly lower radiation dose than do other protocols used in daily clinical practice. We recommend using low-dose CT and the grading system proposed here in the postoperative assessment of screw placement.

Radiation therapy is a major treatment modality for malignant and benign brain tumors. Concerns of radiation effects on the brain tissue and neurocognitive function and quality of life increase as survival of patients treated for brain tumors improves. In this article, the clinical and neurobehavioral symptoms and signs of radiation-induced brain injury, possible histopathology, and the potential of functional, metabolic, and molecular imaging as a biomarker for assessment and prediction of neurotoxicity after brain irradiation and imaging findings in radiation necrosis are discussed.