In epilepsy patients who have electrodes implanted in their brains as part of their pre-surgical assessment, simultaneous intracranial EEG and fMRI (icEEG-fMRI) may provide important localising ...information and improve understanding of the underlying neuropathology. However, patient safety during icEEG-fMRI has not been addressed.
Here the potential health hazards associated with icEEG-fMRI were evaluated theoretically and the main risks identified as: mechanical forces on electrodes from transient magnetic effects, tissue heating due to interaction with the pulsed RF fields and tissue stimulation due to interactions with the switched magnetic gradient fields. These potential hazards were examined experimentally in vitro on a Siemens 3 T Trio, 1.5 T Avanto and a GE 3 T Signa Excite scanner using a Brain Products MR compatible EEG system.
No electrode flexion was observed. Temperature measurements demonstrated that heating well above guideline limits can occur. However heating could be kept within safe limits (<1.0 °C) by using a head transmit RF coil, ensuring EEG cable placement to exit the RF coil along its central z-axis, using specific EEG cable lengths and limiting MRI sequence specific absorption rates (SARs). We found that the risk of tissue damage due to RF-induced heating is low provided implant and scanner specific SAR limits are observed with a safety margin used to account for uncertainties (e.g. in scanner-reported SAR). The observed scanner gradient switching induced current (0.08 mA) and charge density (0.2 μC/cm2) were well within safety limits (0.5 mA and 30 μC/cm2, respectively). Site-specific testing and a conservative approach to safety are required to avoid the risk of adverse events.
Unit root tests results suggest that inflation in Argentina for the period 1810–2005 is a stationary series when account is taken of structural breaks that coincide with bouts of hyperinflation. A ...GARCH (1,1) model of annual inflation suggests a positive short-run relation between the mean and variance of inflation, supporting Friedman's hypothesis that high inflation is associated with more variable inflation.
Subthalamic nucleus deep brain stimulation is an effective treatment for advanced Parkinson's disease; however, its therapeutic mechanism is unclear. Previous modelling of functional MRI data has ...suggested that deep brain stimulation has modulatory effects on a number of basal ganglia pathways. This work uses an enhanced data collection protocol to collect rare functional MRI data in patients with subthalamic nucleus deep brain stimulation. Eleven patients with Parkinson's disease and subthalamic nucleus deep brain stimulation underwent functional MRI at rest and during a movement task; once with active deep brain stimulation, and once with deep brain stimulation switched off. Dynamic causal modelling and Bayesian model selection were first used to compare a series of plausible biophysical models of the cortico-basal ganglia circuit that could explain the functional MRI activity at rest in an attempt to reproduce and extend the findings from our previous work. General linear modelling of the movement task functional MRI data revealed deep brain stimulation-associated signal increases in the primary motor and cerebellar cortices. Given the significance of the cerebellum in voluntary movement, we then built a more complete model of the motor system by including cerebellar-basal ganglia interactions, and compared the modulatory effects deep brain stimulation had on different circuit components during the movement task and again using the resting state data. Consistent with previous results from our independent cohort, model comparison found that the rest data were best explained by deep brain stimulation-induced increased (effective) connectivity of the cortico-striatal, thalamo-cortical and direct pathway and reduced coupling of subthalamic nucleus afferent and efferent connections. No changes in cerebellar connectivity were identified at rest. In contrast, during the movement task, there was functional recruitment of subcortical-cerebellar pathways, which were additionally modulated by deep brain stimulation, as well as modulation of local (intrinsic) cortical and cerebellar circuits. This work provides in vivo evidence for the modulatory effects of subthalamic nucleus deep brain stimulation on effective connectivity within the cortico-basal ganglia loops at rest, as well as further modulations in the cortico-cerebellar motor system during voluntary movement. We propose that deep brain stimulation has both behaviour-independent effects on basal ganglia connectivity, as well as behaviour-dependent modulatory effects.
Warfare in Atlantic Africa, 1500-1800 investigates the impact of warfare on the history of Africa in the period of the slave trade and the founding of empires. It includes the discussion of: : * the ...relationship between war and the slave trade * the role of Europeans in promoting African wars and supplying African armies * the influence of climatic and ecological factors on warfare patterns and dynamics * the impact of social organization and military technology, including the gunpowder revolution * case studies of warfare in Sierra Leone, the Gold Coast, Benin and West Central Africa
John K. Thornton is Professor of History at Millersville University, Pennsylvania. He is the author of Africa and Africans in the Making of the Atlantic World, 1400-1800 (Cambridge, 1998).
OBJECTIVETo translate the quantitative MRC Centre MRI protocol in Charcot-Marie-Tooth disease type 1A (CMT1A) to a second site; validate its responsiveness in an independent cohort; and test the ...benefit of participant stratification to increase outcome measure responsiveness.
METHODSThree healthy volunteers were scanned for intersite standardization. For the longitudinal patient study, 11 patients with CMT1A were recruited with 10 patients rescanned at a 12-month interval. Three-point Dixon MRI of leg muscles was performed to generate fat fraction (FF) maps, transferred to a central site for quality control and analysis. Clinical data collected included CMT Neuropathy Score.
RESULTSTest-retest reliability of FF within individual healthy calf muscles at the remote site was excellentintraclass correlation coefficient 0.79, limits of agreement −0.67 to +0.85 %FF. In patients, mean calf muscle FF was 21.0% and correlated strongly with disease severity and age. Calf muscle FF significantly increased over 12 months (+1.8 ± 1.7 %FF, p = 0.009). Patients with baseline FF >10% showed a 12-month FF increase of 2.9% ± 1.3% (standardized response mean = 2.19).
CONCLUSIONSWe have validated calf muscle FF as an outcome measure in an independent cohort of patients with CMT1A. Responsiveness is significantly improved by enrolling a stratified patient cohort with baseline calf FF >10%.
The Thirty Years' War, while still regarded as primarily a European war, also has, as some historians recognize, an Atlantic dimension. That Atlantic dimension in turn is widely recognized as ...centering on the Dutch Republic's seizure of Bahia and then Pernambuco in Brazil, and on the other side of the Atlantic, the island colony of São Tomé, the Portuguese fort at Elmina, and the biggest African prize, the colony of Angola, a project that Dutch historians have labeled the "Groot Dessyn" (Great Design). What is more generally overlooked is that on the African side, the Kingdom of Kongo, hostile and independent northern neighbor of Portuguese Angola, played a crucial role in shaping the Dutch strategies on the African side of the Atlantic. It was Kongo's initiative, as I will demonstrate, that caused the Dutch to conceive of having an African colony at all, and it was Kongo diplomacy that led the Dutch to attack Angola, first in 1624 and then, successfully in 1641. Recognizing this African initiative helps us to understand the multilateral and even multicontinental nature of the Thirty Years' War.
BackgroundLower limb muscle magnetic resonance imaging (MRI) obtained fat fraction (FF) can detect disease progression in patients with Charcot-Marie-Tooth disease 1A (CMT1A). However, analysis is ...time-consuming and requires manual segmentation of lower limb muscles. We aimed to assess the responsiveness, efficiency and accuracy of acquiring FF MRI using an artificial intelligence-enabled automated segmentation technique.MethodsWe recruited 20 CMT1A patients and 7 controls for assessment at baseline and 12 months. The three-point-Dixon fat water separation technique was used to determine thigh-level and calf-level muscle FF at a single slice using regions of interest defined using Musclesense, a trained artificial neural network for lower limb muscle image segmentation. A quality control (QC) check and correction of the automated segmentations was undertaken by a trained observer.ResultsThe QC check took on average 30 seconds per slice to complete. Using QC checked segmentations, the mean calf-level FF increased significantly in CMT1A patients from baseline over an average follow-up of 12.5 months (1.15%±1.77%, paired t-test p=0.016). Standardised response mean (SRM) in patients was 0.65. Without QC checks, the mean FF change between baseline and follow-up, at 1.15%±1.68% (paired t-test p=0.01), was almost identical to that seen in the corrected data, with a similar overall SRM at 0.69.ConclusionsUsing automated image segmentation for the first time in a longitudinal study in CMT, we have demonstrated that calf FF has similar responsiveness to previously published data, is efficient with minimal time needed for QC checks and is accurate with minimal corrections needed.
Background: Individuals who are weight-reduced or leptin deficient have a lower energy expenditure coupled with higher hunger and disinhibition and/or delayed satiation compared with ...never-weight-reduced control subjects. Because exogenous leptin inhibits feeding in congenitally leptin-deficient humans, reduced leptin signaling may reduce the expression of feeding inhibition in humans.
Objective: The objective was to test the hypothesis that reduced leptin signaling may reduce the expression of feeding inhibition (ie, blunt satiation) in humans by examining the effects of leptin repletion on feeding behavior after weight loss.
Design: Ten obese humans (4 men, 6 women) were studied as inpatients while they received a weight-maintaining liquid-formula diet. Satiation was studied by measuring intake and ratings of appetite-related dispositions 3 h after ingestion of 300 kcal of the liquid-formula diet. The subjects were studied at each of 3 time periods: 1) while they maintained their usual weight (Wtinitial) and then after weight reduction and stabilization at 10% below initial weight and while they received 5 wk of either 2) twice-daily injections of placebo (Wt-10%placebo) or 3) “replacement doses” of leptin (Wt-10%leptin) in a single-blind crossover design with a 2-wk washout period between treatments. Energy expenditure was also measured at each study period.
Results: Both energy expenditure and visual analog scale ratings that reflect satiation were significantly lower at Wt-10%placebo than at Wtinitial and Wt-10%leptin.
Conclusion: The results are consistent with the hypothesis that the absence of leptin signaling after weight loss may blunt the expression of feeding inhibition in humans.
Objectives
Surgical planning of vestibular schwannoma surgery would benefit greatly from a robust method of delineating the facial-vestibulocochlear nerve complex with respect to the tumour. This ...study aimed to optimise a multi-shell readout-segmented diffusion-weighted imaging (rs-DWI) protocol and develop a novel post-processing pipeline to delineate the facial-vestibulocochlear complex within the skull base region, evaluating its accuracy intraoperatively using neuronavigation and tracked electrophysiological recordings.
Methods
In a prospective study of five healthy volunteers and five patients who underwent vestibular schwannoma surgery, rs-DWI was performed and colour tissue maps (CTM) and probabilistic tractography of the cranial nerves were generated. In patients, the average symmetric surface distance (ASSD) and 95% Hausdorff distance (HD-95) were calculated with reference to the neuroradiologist-approved facial nerve segmentation. The accuracy of patient results was assessed intraoperatively using neuronavigation and tracked electrophysiological recordings.
Results
Using CTM alone, the facial-vestibulocochlear complex of healthy volunteer subjects was visualised on 9/10 sides. CTM were generated in all 5 patients with vestibular schwannoma enabling the facial nerve to be accurately identified preoperatively. The mean ASSD between the annotators’ two segmentations was 1.11 mm (SD 0.40) and the mean HD-95 was 4.62 mm (SD 1.78). The median distance from the nerve segmentation to a positive stimulation point was 1.21 mm (IQR 0.81–3.27 mm) and 2.03 mm (IQR 0.99–3.84 mm) for the two annotators, respectively.
Conclusions
rs-DWI may be used to acquire dMRI data of the cranial nerves within the posterior fossa.
Clinical relevance statement
Readout-segmented diffusion-weighted imaging and colour tissue mapping provide 1–2 mm spatially accurate imaging of the facial-vestibulocochlear nerve complex, enabling accurate preoperative localisation of the facial nerve. This study evaluated the technique in 5 healthy volunteers and 5 patients with vestibular schwannoma.
Key Points
•
Readout-segmented diffusion-weighted imaging (rs-DWI) with colour tissue mapping (CTM) visualised the facial-vestibulocochlear nerve complex on 9/10 sides in 5 healthy volunteer subjects.
•
Using rs-DWI and CTM, the facial nerve was visualised in all 5 patients with vestibular schwannoma and within 1.21–2.03 mm of the nerve’s true intraoperative location.
•
Reproducible results were obtained on different scanners.
Objectives
Quantitative magnetic resonance imaging (MRI) can potentially meet the pressing need for objective, sensitive, reproducible outcome measures in neuromuscular disease trials. We tested, in ...healthy volunteers, the consistency, reliability and sensitivity to normal inter-subject variation of MRI methods targeted to lower limb muscle pathology to inform the design of practical but comprehensive MRI outcome measure protocols for use in imminent patient studies.
Methods
Forty-seven healthy volunteers, age 21-81 years, were subject at 3T to three-point Dixon fat-fraction measurement,
T
1
-relaxometry,
T
2
-relaxometry and magnetisation transfer ratio (MTR) imaging at mid-thigh and mid-calf level bilaterally. Fifteen subjects underwent repeat imaging at 2 weeks.
Results
Mean between-muscle fat fraction and T
2
differences were small, but significant (
p
< 0.001). Fat fraction and
T
2
correlated positively, and MTR negatively with subject age in both the thigh and calf, with similar significant correlations with weight at thigh level only (
p
< 0.001 to
p
< 0.05). Scan-rescan and inter-observer intra-class correlation coefficients ranged between 0.62-0.84 and 0.79-0.99 respectively.
Conclusions
Quantitative lower-limb muscle MRI using readily implementable methods was sensitive enough to demonstrate inter-muscle differences (small in health), and correlations with subject age and weight. In combination with high reliability, this strongly supports the suitability of these methods to provide longitudinal outcome measures in neuromuscular disease treatment trials.
Key points
• Quantitative lower limb muscle MRI provides potential outcome measures in neuromuscular diseases
• Bilateral thigh/calf coverage using sequences sensitive to acute and chronic pathology
• Measurements have excellent scan-rescan and interobserver reliability
• Measurements show small but significant inter-subject age and weight dependency
• Readily implementable sequences suitable for further assessment in patient studies