Cerebral volume is unaffected after pre-eclampsia.

OBJECTIVES: Pre-eclampsia has been associated with cardiovascular, cerebrovascular and/or psychological complaints. Signs of altered brain morphology and more white-matter hyperintensities (WMHs) during and shortly after pre-eclampsia have been observed in some, but not all, studies. We compared volumes of cerebral structures and the number of WMHs between formerly pre-eclamptic women and those with normotensive gestational history and assessed the effect of age on brain volumes. METHODS: Structural 7-Tesla magnetic resonance imaging of the brain was performed in 59 formerly pre-eclamptic women (aged 37 ± 6 years, 0.5-16 years postpartum) and 20 women with a history of normotensive pregnancy (aged 39 ± 5 years, 1-18 years postpartum). Fazekas scores were obtained to assess WMH load. Volumes of the whole brain, gray and white matter, brain lobes, and ventricular and pericortical cerebrospinal fluid (CSF) spaces were calculated after semiautomatic segmentation. Group differences were analyzed using ANCOVA and Bayes factors. Results were adjusted for age, educational attainment, presence of current hypertension and total intracranial volume. The effect of age on cerebral volumes was analyzed using linear regression analysis. RESULTS: No changes in global and local brain volumes were observed between formerly pre-eclamptic and control women. Also, no difference in WMH load was observed. Independent of pre-eclamptic history, gray-matter volume significantly decreased with age, while ventricular and pericortical CSF space volumes significantly increased with age. CONCLUSIONS: Volumetric changes of the cerebrum are age-related but are independent of pre-eclamptic history in the first two decades after childbirth. No evidence of greater WMH load after pre-eclampsia was found. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Functional connectivity of limbic system and prefrontal cortex years after pre-eclampsia: 7-Tesla functional magnetic resonance imaging study.

OBJECTIVE: Pre-eclampsia is a vascular complication of pregnancy, associated with a long-term risk of cerebrovascular and mental disorders. We explored whether formerly pre-eclamptic women exhibit differences in functional brain organization, especially in regions that may explain the commonly reported emotional symptoms and cognitive complaints even years after the pregnancy. METHODS: Formerly pre-eclamptic women and control women with a history of normotensive pregnancy underwent structural and functional 7-Tesla magnetic resonance imaging scans. Using graph theoretical analysis, the efficiency and clustering coefficient of the functional brain network were investigated. The study included local analysis focusing on particular brain structures, such as the limbic system and the prefrontal cortex, and global analysis of the whole cerebrum. Univariable and multivariable linear regression was used to investigate the relationship between brain network-related graph measures and the group (formerly pre-eclamptic or control). RESULTS: A total of 17 control parous women and 55 women with a history of pre-eclampsia were recruited. The time intervals between the index pregnancy and recruitment were 8.0 and 5.6 years for the two groups, respectively. Compared with control women, formerly pre-eclamptic women had higher local efficiency in the prefrontal cortex (P = 0.048) and anterior cingulate cortex (P = 0.03) but lower local efficiency and local clustering coefficient in the amygdala (P = 0.004 and P = 0.02, respectively) and parahippocampal cortex (P = 0.007 and P = 0.008, respectively). No differences were found in the global functional brain organization. CONCLUSIONS: Compared to controls with a history of normotensive pregnancy, formerly pre-eclamptic women displayed a different local functional brain organization. These differences in functional connectivity, especially in the limbic regions and the prefrontal cortex, are in line with the psychological and cognitive complaints reported commonly by women with a history of pre-eclampsia. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Blood-brain barrier leakage years after pre-eclampsia: dynamic contrast-enhanced 7-Tesla MRI study.

OBJECTIVE: Pre-eclampsia is a hypertensive complication of pregnancy that is associated with an increased risk of long-term cardiovascular and cerebrovascular disorders. Although the underlying mechanism of persistent susceptibility to cerebral complications after pre-eclampsia remains largely unclear, impaired blood-brain barrier (BBB) integrity has been suggested to precede several cerebrovascular diseases. In this study, we aimed to investigate the integrity of the BBB years after pre-eclampsia. METHODS: This was an observational study of premenopausal formerly pre-eclamptic women and controls with a history of normotensive pregnancy who underwent cerebral magnetic resonance imaging (MRI) at ultra-high field (7 Tesla) to assess the integrity of the BBB. Permeability of the BBB was determined by assessing leakage rate and fractional leakage volume of the contrast agent gadobutrol using dynamic contrast-enhanced MRI. BBB leakage measures were determined for the whole brain and lobar white and gray matter. Multivariable analyses were performed, and odds ratios were calculated to compare women with and those without a history of pre-eclampsia, adjusting for potential confounding effects of age, hypertension status at MRI and Fazekas score. RESULTS: Twenty-two formerly pre-eclamptic women (mean age, 37.8 ± 5.4 years) and 13 control women with a history of normotensive pregnancy (mean age, 40.8 ± 5.5 years) were included in the study. The time since the index pregnancy was 6.6 ± 3.2 years in the pre-eclamptic group and 9.0 ± 3.7 years in controls. The leakage rate and fractional leakage volume were significantly higher in formerly pre-eclamptic women than in controls in the global white (P = 0.001) and gray (P = 0.02) matter. Regionally, the frontal (P = 0.04) and parietal (P = 0.009) cortical gray matter, and the frontal (P = 0.001), temporal (P < 0.05) and occipital (P = 0.007) white matter showed higher leakage rates in formerly pre-eclamptic women. The odds of a high leakage rate after pre-eclampsia were generally higher in white-matter regions than in gray-matter regions. CONCLUSION: This observational study demonstrates global impairment of the BBB years after a pre-eclamptic pregnancy, which could be an early marker of long-term cerebrovascular disorders. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study.

PURPOSE: Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). METHODS: We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. RESULTS: All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. CONCLUSION: This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: www.trialregister.nl : NTR7536.

Is CT bulletproof? On the use of CT for characterization of bullets in forensic radiology.

PURPOSE: Forensic investigations could benefit from non-invasive in situ characterization of bullets. Therefore, the use of CT imaging was explored for the analysis of bullet geometry and composition. Bullet visualization with CT is challenging as the metal constituents suffer from excessive X-ray attenuation due to their high atomic number, density, and geometry. METHODS: A metal reference phantom was developed containing small discs of various common metals (aluminum, iron, stainless steel, copper, brass, tungsten, and lead). CT images were acquired with 70-150 kVp and 200-400 mAs and were reconstructed using an extended Hounsfield unit (HU) scale (- 10,240 to + 30,710). For each material, the mean CT number (HU) was measured to construct a metal database. Different bullets (n = 11) were scanned in a soft tissue-mimicking phantom. Bullet size and shape were measured, and composition was evaluated by comparison with the metal database. Also, the effect of bullet orientation within the CT scanner was evaluated. RESULTS: In the reference phantom, metals were classified into three groups according to their atomic number (Z): low (Z ≤ 13; HU < 3000), medium (Z = 25-30; HU = 13,000-20,000), and high (Z ≥ 74; HU > 30,000). External bullet contours could be accurately delineated. Internal interfaces between jacket and core could not be identified. Cross-sectional spatial profile plots of the CT number along bullets' short axis revealed beam hardening and photon starvation effects that depended on bullet size, shape, and orientation within the CT scanner. Therefore, the CT numbers of bullets were unreliable and could not be used for material characterization by comparison with the reference phantom. CONCLUSION: CT-based characterization of bullets was feasible in terms of size and shape but not composition.

Aetiology of cognitive impairment in children with frontal lobe epilepsy.

OBJECTIVES: Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its aetiology is unknown. MRI scans often reveal no structural brain abnormalities that could explain the cognitive impairment. This does not exclude more subtle morphological abnormalities that can only be detected by automated morphometric techniques. AIMS: With these techniques, we investigate the relationship between cortical brain morphology and cognitive functioning in a cohort of children with FLE and healthy controls. MATERIALS AND METHODS: Thirty-four children aged 8-13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural brain MRI. Patients were grouped as cognitively impaired or unimpaired. Intracranial volume, white matter volume, lobular cortical volume, cortical thickness and volumes of cortex structures were compared between patients and controls, and potential correlations with cognitive status were determined. RESULTS: The group of cognitively impaired children with FLE had significantly smaller left temporal cortex volumes, specifically middle temporal grey matter volume and entorhinal cortex thickness. In addition, cognitively impaired children with FLE had smaller volumes of structures in the left and right frontal cortex, right temporal cortex and the left subcortical area. CONCLUSION: Cognitively impaired children with FLE have smaller volumes of various cortex structures within the frontal lobes and in extra-frontal regions, most notably temporal cortex volumes. These findings might well explain the broad scale of cognitive domains affected in children with FLE complicated by cognitive impairment and highlight that FLE impacts on areas beyond the frontal lobe.

Magnetic resonance imaging-derived arterial peak flow in peripheral arterial disease: towards a standardized measurement.

OBJECTIVE: To determine the best location to measure the arterial peak flow (APF) in patients with peripheral arterial disease in order to facilitate clinical standardization. METHODS: Two hundred and fifty-nine patients with varying degrees of peripheral artery disease (PAD) and 48 patients without PAD were included. All patients underwent magnetic resonance phase-contrast imaging of the common femoral artery (CFA), superficial femoral artery (SFA), and popliteal artery (PA). APF values of patients with PAD were compared with patients with no PAD. The discriminative ability to identify PAD was evaluated by means of receiver-operator characteristic curves and the corresponding areas under the curve (AUC). RESULTS: Mean APF values in patients with PAD were reduced by 42%, 55% and 59% compared with non-PAD patients for the CFA, SFA, and PA, respectively (p < .01). The AUC's were 0.84, 0.92, and 0.93 for the CFA, SFA, and PA, respectively. CONCLUSION: The APF measured at the level of the PA shows the largest differences between patients with PAD and patients with no PAD and the best discriminative ability compared with the APF acquired in the CFA or SFA. The PA seems to be the most suitable level for standardized flow measurements in patients with PAD in order to obtain relevant functional information about the vascular status.

Abdominal aortic aneurysms with high thrombus signal intensity on magnetic resonance imaging are associated with high growth rate.

OBJECTIVES: A layer of intraluminal thrombus is commonly observed in abdominal aortic aneurysms (AAAs). The purpose of this study was to investigate whether AAAs with high thrombus signal intensity (SI) at T1-weighted (T1w) magnetic resonance imaging (MRI) exhibit a faster aneurysm growth rate. METHODS: This was a prospective follow-up study. Patients with a small AAA underwent MRI examinations at 6 month intervals. Aneurysm thrombus and psoas muscle SI at the point of maximal diameter on T1w images were measured and expressed as a ratio (thrombus SI/muscle SI). Based on these measurements, patients were categorized into three groups: AAA with relative thrombus SI above (group A) and below (group B) the mean relative thrombus SI of 1.20. Patients with AAA without thrombus constituted group C. Eight patients were scanned twice within 2 weeks to investigate scan-rescan reproducibility. Aneurysm growth rates were expressed as the change in maximal cross sectional area (cm(2)). RESULTS: A total of 35 patients (m/f: 26/9; age 72 ± 7 years; AAA maximal diameter 4.9 ± 0.5 cm) were included. Mean aneurysm growth rate for patients in group A (n = 11, 1.87 cm(2)/0.5 year) was two-fold higher than group B (n = 17, 0.78 cm(2)/0.5 year, p = .005) and eight-fold higher than group C (n = 7, 0.23 cm(2)/0.5 years, p = .004) at 6 months' follow-up. At 12 months' follow-up, the mean aneurysm growth rate remained significantly higher in group A (n = 7, 3.03 cm(2)/year) than groups B (n = 10, 1.63 cm(2)/year, p = .03) and C (n = 7, 0.73 cm(2)/year, p = .004). The reproducibility for thrombus SI measurements was found to be high with a coefficient of variation of 6.2%. Aneurysm maximal cross-sectional area at baseline was not significantly different for the three groups. CONCLUSIONS: Abdominal aortic aneurysms with high thrombus SI on T1w MR images are associated with higher aneurysm growth rates.

Pediatric frontal lobe epilepsy: white matter abnormalities and cognitive impairment.

OBJECTIVES: Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE). Its etiology remains unknown. With diffusion tensor imaging, we have studied cerebral white matter properties and associations with cognitive functioning in children with FLE and healthy controls. METHODS: Thirty children aged 8-13 years with FLE of unknown cause and 39 healthy age-matched controls underwent neuropsychological assessment, structural and diffusion-weighted brain MRI. Patients were grouped as cognitively impaired or unimpaired, and their white matter diffusion properties were compared with the controls. RESULTS: Children with FLE had reduced apparent diffusion coefficients in various posteriorly located tract bundles, a reduced fractional anisotropy (FA) of the white matter tract between the right frontal and right occipital lobe, and smaller volumes of several collections of interlobar bundle tracts, compared with controls. The cognitively impaired patient group demonstrated significant increases in FA of the white matter of both occipital lobes, a reduced FA of white matter tract bundles between the right frontal and both left occipital lobe and subcortical white matter area, and smaller volumes of two collections of tract bundles connecting the frontal lobe with the temporal and parietal lobes, compared with controls. CONCLUSIONS: Children with FLE had white matter abnormalities mainly in posterior brain regions, not confined to the area of the seizure focus. Cognitively impaired children with FLE showed the most pronounced white matter abnormalities. These possibly reflect disturbed maturation and might be part of the etiology of the cognitive impairment.

Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy.

Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.

Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women.

OBJECTIVE: Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD. METHODS: 12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years). RESULTS: In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C. CONCLUSIONS: The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.

First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer: a phase II study including molecular imaging.

BACKGROUND: Both bevacizumab and erlotinib have clinical activity in non-small-cell lung cancer (NSCLC). Preclinical data suggest synergistic activity. PATIENTS AND METHODS: Chemonaive patients with stage IIIb or IV non-squamous NSCLC were treated with bevacizumab 15 mg/kg every 3 weeks and erlotinib 150 mg daily until progression. Primary end point was non-progression rate (NPR) at 6 weeks. Tumor response was measured with computed tomography, 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). KRAS and EGFR mutations were assessed in tumor samples. RESULTS: Forty-seven patients were included. Median follow-up was 15.2 months. NPR at 6 weeks was 75%. Median progression-free survival (PFS) was 3.8 [95% confidence interval (CI) 2.3-5.4] months and median overall survival (OS) was 6.9 (95% CI 5.5-8.4) months. Toxicity was mainly mild. The presence of KRAS (n = 10) or EGFR mutations (n = 5) did not influence outcome. After 3 weeks of treatment, >20% decrease in standard uptake value as measured with positron emission tomography predicted for longer PFS (9.7 versus 2.8 months; P = 0.01) and >40% decrease in K(trans) as assessed by DCE-MRI did not predict for longer PFS. CONCLUSIONS: First-line treatment with bevacizumab and erlotinib in stage IIIb/IV NSCLC resulted in an NPR of 75%. OS was however disappointing. Early response evaluation with FDG-PET is the best predictive test for PFS.

Association of physical activity and sedentary time with structural brain networks-The Maastricht Study.

We assessed whether objectively measured low- and high-intensity physical activity (LPA and HPA) and sedentary time (ST) were associated with white matter connectivity, both throughout the whole brain and in brain regions involved in motor function. In the large population-based Maastricht Study (n = 1715, age 59.6 ± 8.1 (mean ± standard deviation) years, and 48% women), the amounts of LPA, HPA, and ST were objectively measured during 7 days by an activPAL accelerometer. In addition, using 3T structural and diffusion MRI, we calculated whole brain node degree and node degree of the basal ganglia and primary motor cortex. Multivariable linear regression analysis was performed, and we report standardized regression coefficients (stß) adjusted for age, sex, education level, wake time, diabetes status, BMI, office systolic blood pressure, antihypertensive medication, total-cholesterol-to-HDL-cholesterol ratio, lipid-modifying medication, alcohol use, smoking status, and history of cardiovascular disease. Lower HPA was associated with lower whole brain node degree after full adjustment (stß [95%CI] = - 0.062 [- 0.101, - 0.013]; p = 0.014), whereas lower LPA (stß [95%CI] = - 0.013 [- 0.061, 0.034]; p = 0.580) and higher ST (stß [95%CI] = - 0.030 [- 0.081, 0.021]; p = 0.250) was not. In addition, lower HPA was associated with lower node degree of the basal ganglia after full adjustment (stß [95%CI] = - 0.070 [- 0.121, - 0.018]; p = 0.009). Objectively measured lower HPA, but not lower LPA and higher ST, was associated with lower whole brain node degree and node degree in specific brain regions highly specialized in motor function. Further research is needed to establish whether more HPA may preserve structural brain connectivity.

The effect and reproducibility of different clinical DTI gradient sets on small world brain connectivity measures.

Advances in computational network analysis have enabled the characterization of topological properties in large scale networks including the human brain. Information on structural networks in the brain can be obtained in-vivo by performing tractography on diffusion tensor imaging (DTI) data. However, little is known about the reproducibility of network properties derived from whole brain tractography data, which has important consequences for minimally detectable abnormalities or changes over time. Moreover, acquisition parameters, such as the number of gradient directions and gradient strength, possibly influence network metrics and the corresponding reproducibility derived from tractography data. The aim of the present study is twofold: (i) to determine the effect of several clinically available DTI sampling schemes, differing in number of gradient directions and gradient amplitude, on small world metrics and (ii) to evaluate the interscan reproducibility of small world metrics. DTI experiments were conducted on six healthy volunteers scanned twice. Probabilistic tractography was performed to reconstruct structural connections between regions defined from an anatomical atlas. The observed reproducibility of the network measures was high, reflected by low values for the coefficient of variation (<3.8%), advocating the use of graph theoretical measurements to study neurological diseases. Small world metrics were dependent on the choice of DTI gradient scheme and showed stronger connectivity with increasing directional resolution. The interscan reproducibility was not dependent on the gradient scheme. These findings should be considered when comparing results across studies using different gradient schemes or designing new studies.

Nocturnal epileptiform EEG discharges, nocturnal epileptic seizures, and language impairments in children: review of the literature.

This review addresses the effect on language function of nocturnal epileptiform EEG discharges and nocturnal epileptic seizures in children. In clinical practice, language impairment is frequently reported in association with nocturnal epileptiform activity. Vice versa, nocturnal epileptiform EEG abnormalities are a common finding in children with specific language impairment. We suggest a spectrum that is characterized by nocturnal epileptiform activity and language impairment ranging from specific language impairment to rolandic epilepsy, nocturnal frontal lobe epilepsy, electrical status epilepticus of sleep, and Landau-Kleffner syndrome. In this spectrum, children with specific language impairment have the best outcome, and children with electrical status epilepticus of sleep or Landau-Kleffner syndrome, the worst. The exact nature of this relationship and the factors causing this spectrum are unknown. We suggest that nocturnal epileptiform EEG discharges and nocturnal epileptic seizures during development will cause or contribute to diseased neuronal networks involving language. The diseased neuronal networks are less efficient compared with normal neuronal networks. This disorganization may cause language impairments.

Optimal Detection of Subtle Gadolinium Leakage in CSF with Heavily T2-Weighted Fluid-Attenuated Inversion Recovery Imaging.

Pericortical enhancement on postcontrast FLAIR images is a marker for subtle leptomeningeal blood-brain barrier leakage. We explored the optimal FLAIR sequence parameters for the detection of low gadolinium concentrations within the CSF. On the basis of phantom experiments and human in vivo data, we showed that detection of subtle pericortical enhancement can be facilitated by using a relatively long TE. Future studies should choose their FLAIR sequence parameters carefully when assessing pericortical enhancement due to subtle blood-brain barrier leakage.

Spinal cord functional MRI at 3 T: gradient echo echo-planar imaging versus turbo spin echo.

The purpose of this study was to evaluate and compare turbo spin echo (TSE) with gradient echo echo-planar imaging (GE-EPI) pulse sequences for functional magnetic resonance imaging (fMRI) of spinal cord activation at 3 T field strength. Healthy volunteers underwent TSE and GE-EPI spinal fMRI. The activation paradigm comprised the temporal alternation of finger motion and rest. Pulse sequences were optimized to obtain sufficient image quality and optimal sensitivity to small T(2) or T(2)* relaxation time changes. Spinal cord activation measured by the two pulse sequences was evaluated with respect to spatial distribution of activation, signal sensitivity, and reproducibility. For the GE-EPI sequence, fMRI activation was maximal in the spinal cord segments at the levels of the fifth cervical down to the first thoracic vertebra. For the TSE sequence, fMRI measurements showed no distinct location with maximal activation. Percentage signal change and number of activated voxels were approximately twice as high for GE-EPI compared to TSE fMRI. Reproducibility of the signal changes was much better for GE-EPI than for TSE imaging. To conclude, multi-subjects averaged GE-EPI is more location specific for blood-oxygen-level-dependent (BOLD) activation, more sensitive, and is suggested to be more reproducible than TSE fMRI.

Cognitive fMRI and soluble telencephalin assessment in patients with localization-related epilepsy.

Objectives - The use of telencephalin as a possible marker for altered cortical function as demonstrated by functional MRI was investigated in a pilot study with 16 patients with localization-related epilepsy and secondarily generalized seizures. Materials and methods - Functional MRI of verbal working memory performance (Sternberg paradigm) and self-regulatory control processes (Stroop paradigm) was used to examine cortical activation in 16 patients with localization-related epilepsy and secondarily generalized seizures. Additionally, blood serum concentrations of soluble telencephalin (marker for neuronal damage) were determined. Results - In three patients (one temporal and two frontal focus), telencephalin was detected. All three patients had lower functional MRI activation in the frontotemporal region (P = 0.04), but not in other regions (P > 0.35) compared with patients without detectable telencephalin. Additionally, an association of levetiracetam and frontotemporal activation was observed. Conclusions - These preliminary data in a heterogeneous group suggest an association between decreased frontotemporal activation on fMRI and both detectable telencephalin serum levels and levetiracetam use. Future longitudinal studies with larger patient groups are required to confirm these observations. It is hypothesized that altered local function of the frontotemporal cortex in localization-related epilepsy might be better predicted by the biochemical marker telencephalin than epilepsy characteristics such as seizure focus.

Abnormal Blood Oxygen Level-Dependent Fluctuations in Focal Cortical Dysplasia and the Perilesional Zone: Initial Findings.

BACKGROUND AND PURPOSE: Focal cortical dysplasia is a common cause of intractable epilepsy for which neurosurgery is an option. Delineations of a focal cortical dysplasia lesion on structural brain images may not necessarily reflect the functional borders of normal tissue. Our objective was to determine whether abnormalities in spontaneous blood oxygen level-dependent fluctuations arise in focal cortical dysplasia lesions and proximal regions. MATERIALS AND METHODS: Fourteen patients with focal cortical dysplasia-related epilepsy and 16 healthy controls underwent structural and resting-state functional MR imaging. Three known blood oxygen level-dependent measures were determined, including the fractional amplitude of low-frequency fluctuations, regional homogeneity, and wavelet entropy. These measures were evaluated in the lesion and perilesional zone and normalized to the contralateral cortex of patients with focal cortical dysplasia and healthy controls. RESULTS: Patients showed significantly decreased fractional amplitude of low-frequency fluctuations and increased wavelet entropy in the focal cortical dysplasia lesion and the perilesional zone (≤2 cm) relative to the contralateral homotopic cortex and the same regions in healthy controls. Regional homogeneity was significantly increased in the focal cortical dysplasia lesion compared with the contralateral homotopic cortex and healthy controls. CONCLUSIONS: Abnormalities in spontaneous blood oxygen level-dependent fluctuations were seen up to 2 cm distant from the radiologically visible boundary. It was demonstrated that functional boundaries go beyond structural boundaries of focal cortical dysplasia lesions. Validation is required to reveal whether this information is valuable for surgical planning and outcome evaluation of focal cortical dysplasia lesions and comparing current results with electrophysiologic analysis.

Interaction between blood-brain barrier and glymphatic system in solute clearance.

Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-ß, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-ß accumulation and Alzheimer's disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer's disease.