Compartmental pharmacokinetics of nefopam during mild hypothermia

Background Nefopam is a non-opioid, non-steroidal, centrally acting analgesic which has an opioid-sparing effect. It also reduces the threshold (triggering core temperature) for shivering without causing sedation or respiratory depression. The drug is therefore useful as both an analgesic and to facilitate induction of therapeutic hypothermia. However, compartmental pharmacokinetics during hypothermia are lacking for nefopam. Methods We conducted a prospective, randomized, blinded study in eight volunteers. On two different occasions, one of two nefopam concentrations was administered and more than 30 arterial blood samples were gathered during 12 h. Plasma concentrations were determined using gas chromatography/mass spectrometry to investigate the pharmacokinetics of nefopam with non-linear mixed-effect modelling. Results A two-compartment mammillary model with moderate inter-individual variability and inter-occasional variability independent of covariates was found to best describe the data [mean (se): V1=24.13 (2.8) litre; V2=183.34 (13.5) litre; Clel=0.54 (0.07) litre min−1; Cldist=2.84 (0.42) litre min−1]. Conclusions The compartmental data set describing a two-compartment model was determined and could be implemented to drive automated pumps. Thus, work load could be distributed to a pump establishing and maintaining any desired plasma concentration deemed necessary for a treatment with therapeutical hypothermi

Laminar analysis of the cortical T1/T2-weighted ratio at 7T

Objective: In this observational study, we explored cortical structure as function of cortical depth through a laminar analysis of the T1/T2-weighted (T1w/T2w) ratio, which has been related to dendrite density in ex vivo brain tissue specimens of patients with MS. Methods: In 39 patients (22 relapsing-remitting, 13 female, age 41.1 ± 10.6 years; 17 progressive, 11 female, age 54.1 ± 9.9 years) and 21 healthy controls (8 female, , age 41.6 ± 10.6 years), we performed a voxel-wise analysis of T1w/T2w ratio maps from high-resolution 7T images from the subpial surface to the gray matter/white matter boundary. Six layers were sampled to ensure accuracy based on mean cortical thickness and image resolution. Results: At the voxel-wise comparison (p < 0.05, family wise error rate corrected), the whole MS group showed lower T1w/T2w ratio values than controls, both when considering the entire cortex and each individual layer, with peaks occurring in the fusiform, temporo-occipital, and superior and middle frontal cortex. In relapsing-remitting patients, differences in the T1w/T2w ratio were only identified in the subpial layer, with the peak occurring in the fusiform cortex, whereas results obtained in progressive patients mirrored the widespread damage found in the whole group. Conclusions: Laminar analysis of T1w/T2w ratio mapping confirms the presence of cortical damage in MS and shows a variable expression of intracortical damage according to the disease phenotype. Although in the relapsing-remitting stage, only the subpial layer appears susceptible to damage, in progressive patients, widespread cortical abnormalities can be observed, not only, as described before, with regard to myelin/iron concentration but, possibly, to other microstructural features

Ondansetron does not reduce the shivering threshold in healthy volunteers

Background. Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control, and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (triggering core temperatures) in humans. Methods. Control (placebo) and ondansetron infusions at the target plasma concentration of 250 ng ml−1 were studied in healthy volunteers on two different days. Each day, skin and core temperatures were increased to provoke sweating; then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction and shivering thresholds after compensating for changes in mean-skin temperature. Data were analysed using t-tests and presented as means (sds); P<0.05 was taken as significant. Results. Ondensetron plasma concentrations were 278 (57), 234 (55) and 243 (58) ng ml−1 at the sweating, vasoconstriction and shivering thresholds, respectively; these corresponded to ≈50 mg of ondansetron which is approximately 10 times the dose used for postoperative nausea and vomiting. Ondansetron did not change the sweating (control 37.4 (0.4)°C, ondansetron 37.6 (0.3)°C, P=0.16), vasoconstriction (37.0 (0.5)°C vs 37.1 (0.3)°C; P=0.70), or shivering threshold (36.3 (0.5)°C vs 36.3 (0.6)°C; P=0.76). No sedation was observed on either study day. Conclusions. Ondansetron appears to have little potential for facilitating induction of therapeutic hypothermi

Combining navigator and optical prospective motion correction for high-quality 500 μm resolution quantitative multi-parameter mapping at 7T

Purpose: High-resolution quantitative multi-parameter mapping shows promise for non-invasively characterizing human brain microstructure but is limited by physiological artifacts. We implemented corrections for rigid head movement and respiration-related B0-fluctuations and evaluated them in healthy volunteers and dementia patients. Methods: Camera-based optical prospective motion correction (PMC) and FID navigator correction were implemented in a gradient and RF-spoiled multi-echo 3D gradient echo sequence for mapping proton density (PD), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*). We studied their effectiveness separately and in concert in young volunteers and then evaluated the navigator correction (NAVcor) with PMC in a group of elderly volunteers and dementia patients. We used spatial homogeneity within white matter (WM) and gray matter (GM) and scan-rescan measures as quality metrics. Results: NAVcor and PMC reduced artifacts and improved the homogeneity and reproducibility of parameter maps. In elderly participants, NAVcor improved scan-rescan reproducibility of parameter maps (coefficient of variation decreased by 14.7% and 11.9% within WM and GM respectively). Spurious inhomogeneities within WM were reduced more in the elderly than in the young cohort (by 9% vs. 2%). PMC increased regional GM/WM contrast and was especially important in the elderly cohort, which moved twice as much as the young cohort. We did not find a significant interaction between the two corrections. Conclusion: Navigator correction and PMC significantly improved the quality of PD, R1, and R2* maps, particularly in less compliant elderly volunteers and dementia patients. <br

Combining navigator and optical prospective motion correction for high-quality 500 μm resolution quantitative multi-parameter mapping at 7T

PURPOSE: High-resolution quantitative multi-parameter mapping shows promise for non-invasively characterizing human brain microstructure but is limited by physiological artifacts. We implemented corrections for rigid head movement and respiration-related B0-fluctuations and evaluated them in healthy volunteers and dementia patients. METHODS: Camera-based optical prospective motion correction (PMC) and FID navigator correction were implemented in a gradient and RF-spoiled multi-echo 3D gradient echo sequence for mapping proton density (PD), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*). We studied their effectiveness separately and in concert in young volunteers and then evaluated the navigator correction (NAVcor) with PMC in a group of elderly volunteers and dementia patients. We used spatial homogeneity within white matter (WM) and gray matter (GM) and scan-rescan measures as quality metrics. RESULTS: NAVcor and PMC reduced artifacts and improved the homogeneity and reproducibility of parameter maps. In elderly participants, NAVcor improved scan-rescan reproducibility of parameter maps (coefficient of variation decreased by 14.7% and 11.9% within WM and GM respectively). Spurious inhomogeneities within WM were reduced more in the elderly than in the young cohort (by 9% vs. 2%). PMC increased regional GM/WM contrast and was especially important in the elderly cohort, which moved twice as much as the young cohort. We did not find a significant interaction between the two corrections. CONCLUSION: Navigator correction and PMC significantly improved the quality of PD, R1, and R2* maps, particularly in less compliant elderly volunteers and dementia patients

Modulation der Signalübertragung des Thromboxan A 2 -Rezeptors durch Anästhetika

Thromboxan A2 ist ein wichtiger Mediator (Thrombozytenaktivierung, Vasokonstriktion) der während chirurgischer Behandlung vermehrt freigesetzt wird. Es wird deshalb für eine Reihe von Komplikationen wie Myokardinfarkt und Lungenembolie verantwortlich gemacht. Diese Ereignisse geschehen selten intraoperativ sondern meist postoperativ. Nach Regionalanästhesien sind solche Komplikationen signifikant seltener. Deshalb untersucht diese Arbeit die Wirkung volatiler Anästhetika (Halothan, Isofluran, Sevofluran) und von Lokalanästhetika (Bupivacain, Ropivacain und Lidocain) auf den TXA2-Rezeptor und dessen intrazellulären Signalübertragungsweg. Verwendet wurde dazu das Xenopus-laevis-Modell, mit dem isolierte G-Protein gekoppelte Rezeptoren untersucht werden können. Die verwendeten Anästhetika, außer Sevofluran, suppremieren die Funktion des Rezeptors dosisabhängig und reversibel. Ihre Wirkung entfalten sie am Rezeptor, bzw. G-Protein und beeinflussen die intrazelluläre Signalkaskade nicht

Evaluation of deep decoder for image reconstruction of multi-parametric mapping acquisitions

Image reconstruction is the first post-processing step in magnetic resonance (MR) imaging and determines the base quality for further processing. Modern techniques driven by sparsity constraints lead to better image quality and more options to accelerate the acquisition compared to methods strictly based on analytical models of the imaging process. Deep Decoder (DD) [1], a promising approach of this kind, tunes a convolutional neural network (CNN) as an adaptive function transforming a fixed noise vector to the image of interest. The CNN represents an implicit prior on the structure of clean images leading the network to create essentially a denoised or artifact reduced version of the target image. DD has been successfully applied to MR data with Poisson-sampling [2]. Looking for improved image reconstruction of our own multi-parametric mapping (MPM) MR data [3] acquired in sub-sampled cartesian grid pattern, we want to evaluate the applicability of DD. Following [2] the original DD was modified to process axial slices of MPM data of a human head. The subsampled k-space was zero filled, Fourier transformed, sliced in readout direction and zero padded to 256x256 voxels before processing. Final magnitude images were generated by root-sum-of-squares combination across channels. For comparison different number of filters per layer (128 to 512) and iterations (10k to 100k) were tested. Qualitative inspection showed that models using less than 384 filters reconstructed only very blurry images. Output quality generally increased with number of iterations. All reconstructed images retained a significant amount of SENSE ghosting, specifically for high contrast regions like the skull, rendering the results unusable. Since the DD relies on the affinity of CNNs for structures over random noise, this is not surprising and difficult to counteract. With the cartesian sampling pattern given, DD can in consequence only be used to target data without structured artifacts. In conclusion the DD as used in [2] is not directly applicable to data sampled in cartesian fashion. Future research could instead try to include DD for optimized sensitivity estimation in mSENSE or recovering k-space directly in GRAPPA like methods. [1] R. Heckel and P. Hand, arXiv:1810.03982, Feb. 2019. [2] S. Arora, V. Roeloffs, and M. Lustig, in ISMRM 2020. [3] N. Weiskopf et al., Front Neurosci, vol. 7, p. 95, Jun. 2013