Coronary CT Angiography with Photon-counting CT: First-In-Human Results.

Background Spatial resolution, soft-tissue contrast, and dose-efficient capabilities of photon-counting CT (PCCT) potentially allow a better quality and diagnostic confidence of coronary CT angiography (CCTA) in comparison to conventional CT. Purpose To compare the quality of CCTA scans obtained with a clinical prototype PCCT system and an energy-integrating detector (EID) dual-layer CT (DLCT) system. Materials and Methods In this prospective board-approved study with informed consent, participants with coronary artery disease underwent retrospective electrocardiographically gated CCTA with both systems after injection of 65-75 mL of 400 mg/mL iodinated contrast agent at 5 mL/sec. A prior phantom task-based quality assessment of the detectability index of coronary lesions was performed. Ultra-high-resolution parameters were used for PCCT (1024 matrix, 0.25-mm section thickness) and EID DLCT (512 matrix, 0.67-mm section thickness). Three cardiac radiologists independently performed a blinded analysis using a five-point quality score (1 = insufficient, 5 = excellent) for overall image quality, diagnostic confidence, and diagnostic quality of calcifications, stents, and noncalcified plaques. A logistic regression model, adjusted for radiologists, was used to evaluate the proportion of improvement in scores with the best method. Results Fourteen consecutive participants (12 men; mean age, 61 years ± 17) were enrolled. Scores of overall quality and diagnostic confidence were higher with PCCT images with a median of 5 (interquartile range [IQR], 2) and 5 (IQR, 1) versus 4 (IQR, 1) and 4 (IQR, 3) with EID DLCT images, using a mean tube current of 255 mAs ± 0 versus 349 mAs ± 111 for EID DLCT images (P < .01). Proportions of improvement with PCCT images for quality of calcification, stent, and noncalcified plaque were 100%, 92% (95% CI: 71, 98), and 45% (95% CI: 28, 63), respectively. In the phantom study, detectability indexes were 2.3-fold higher for lumen and 2.9-fold higher for noncalcified plaques with PCCT images. Conclusion Coronary CT angiography with a photon-counting CT system demonstrated in humans an improved image quality and diagnostic confidence compared with an energy-integrating dual-layer CT. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Sandfort and Bluemke in this issue.

Comparison of image quality between spectral photon-counting CT and dual-layer CT for the evaluation of lung nodules: a phantom study.

OBJECTIVES: To evaluate the image quality (IQ) of a spectral photon-counting CT (SPCCT) using filtered back projection (FBP) and hybrid iterative reconstruction (IR) algorithms (iDose4), in comparison with a dual-layer CT (DLCT) system, and to choose the best image quality according to the IR level for SPCCT. METHODS: Two phantoms were scanned using a standard lung protocol (120 kVp, 40 mAs) with SPCCT and DLCT systems. Raw data were reconstructed using FBP and 9 iDose4 levels (i1/i2/i3/i4/i5/i6/i7/i9/i11) for SPCCT and 7 for DLCT (i1/i2/i3/i4/i5/i6/i7). Noise power spectrum and task-based transfer function (TTF) were computed. Detectability index (d') was computed for detection of 4 mm ground-glass nodule (GGN) and solid nodule. Two chest radiologists performed an IQ evaluation (noise/nodule sharpness/nodule conspicuity/overall IQ) in consensus, and chose the best image for SPCCT. RESULTS: Noise magnitude was -47% ± 2% lower on average with SPCCT than with DLCT for iDose4 range from i1 to i6. Average NPS spatial frequencies increased for SPCCT in comparison with DLCT. TTF also increased, except for the air insert with FBP, and i1/i2/i3. Higher detectability was found for SPCCT for both GGN and solid nodules. IQ for both types of nodule was rated consistently higher with SPCCT than with DLCT for the same iDose4 level. For SPCCT and both nodules, the scores for noise and conspicuity improved with increasing iDose4 level. iDose4 level 6 provided the best subjective IQ for both types of nodule. CONCLUSIONS: Higher IQ for GGN and solid nodules was demonstrated with SPCCT compared with DLCT with better detectability using iDose4. KEY POINTS: Using spectral photon-counting CT compared with dual-layer CT, noise magnitude was reduced with improvements in spatial resolution and detectability of ground-glass nodules and solid lung nodules. As the iDose4 level increased, noise magnitude was reduced and detectability of ground-glass and solid lung nodules was better for both CT systems. For spectral photon-counting CT imaging, two chest radiologists determined iDose4 level 6 as the best image quality for detecting ground-glass nodules and solid lung nodules.

Virtual versus true non-contrast dual-energy CT imaging for the diagnosis of aortic intramural hematoma.

PURPOSE: To assess whether virtual non-contrast (VNC) images derived from contrast dual-layer dual-energy computed tomography (DL-DECT) images could replace true non-contrast (TNC) images for aortic intramural hematoma (IMH) diagnosis in acute aortic syndrome (AAS) imaging protocols by performing quantitative as well as qualitative phantom and clinical studies. MATERIALS AND METHODS: Patients with confirmed IMH were included retrospectively in two centers. For in vitro imaging, a custom-made phantom of IMH was placed in a semi-anthropomorphic thorax phantom (QRM GmbH) and imaged on a DL-DECT at 120 kVp under various conditions of patient size, radiation exposure, and reconstruction modes. For in vivo imaging, 21 patients (70 ± 13 years) who underwent AAS imaging protocols at 120 kVp were included. In both studies, contrast-to-noise ratio (CNR) between hematoma and lumen was compared using a paired t test. Diagnostic confidence (1 = non-diagnostic, 4 = exemplary) for VNC and TNC images was rated by two radiologists and compared. Effective radiation doses for each acquisition were calculated. RESULTS: In both the phantom and clinical studies, we observed that the CNRs were similar between the VNC and TNC images. Moreover, both methods allowed differentiating the hyper-attenuation within the hematoma from the blood. Finally, we obtained equivalent high diagnostic confidence with both VNC and TNC images (VNC = 3.2 ± 0.7, TNC = 3.1 ± 0.7; p = 0.3). Finally, by suppressing TNC acquisition and using VNC, the mean effective dose reduction would be 40%. CONCLUSION: DL-DECT offers similar performances with VNC and TNC images for IMH diagnosis without compromise in diagnostic image quality. KEY POINTS: • Dual-layer dual-energy CT enables virtual non-contrast imaging from a contrast-enhanced acquisition. • Virtual non-contrast imaging with dual-layer dual-energy CT reduces the number of acquisitions and radiation exposure in acute aortic syndrome imaging protocol. • Dual-layer dual-energy CT has the potential to become a suitable imaging tool for acute aortic syndrome.

Spectral Photon-counting CT: Initial Experience with Dual-Contrast Agent K-Edge Colonography.

Purpose To investigate the feasibility of using spectral photon-counting computed tomography (CT) to differentiate between gadolinium-based and nonionic iodine-based contrast material in a colon phantom by using the characteristic k edge of gadolinium. Materials and Methods A custom-made colon phantom was filled with nonionic iodine-based contrast material, and a gadolinium-filled capsule representing a contrast material-enhanced polyp was positioned on the colon wall. The colon phantom was scanned with a preclinical spectral photon-counting CT system to obtain spectral and conventional data. By fully using the multibin spectral information, material decomposition was performed to generate iodine and gadolinium maps. Quantitative measurements were performed within the lumen and polyp to quantitatively determine the absolute content of iodine and gadolinium. Results In a conventional CT section, absorption values of both contrast agents were similar at approximately 110 HU. Contrast material maps clearly differentiated the distributions, with gadolinium solely in the polyp and iodine in the lumen of the colon. Quantitative measurements of contrast material concentrations in the colon and polyp matched well with those of actual prepared mixtures. Conclusion Dual-contrast spectral photon-counting CT colonography with iodine-filled lumen and gadolinium-tagged polyps may enable ready differentiation between polyps and tagged fecal material. © RSNA, 2016.

Modulation of synaptic function through the α-neurexin-specific ligand neurexophilin-1.

Neurotransmission at different synapses is highly variable, and cell-adhesion molecules like α-neurexins (α-Nrxn) and their extracellular binding partners determine synapse function. Although α-Nrxn affect transmission at excitatory and inhibitory synapses, the contribution of neurexophilin-1 (Nxph1), an α-Nrxn ligand with restricted expression in subpopulations of inhibitory neurons, is unclear. To reveal its role, we investigated mice that either lack or overexpress Nxph1. We found that genetic deletion of Nxph1 impaired GABAB receptor (GABA(B)R)-dependent short-term depression of inhibitory synapses in the nucleus reticularis thalami, a region where Nxph1 is normally expressed at high levels. To test the conclusion that Nxph1 supports presynaptic GABA(B)R, we expressed Nxph1 ectopically at excitatory terminals in the neocortex, which normally do not contain this molecule but can be modulated by GABA(B)R. We generated Nxph1-GFP transgenic mice under control of the Thy1.2 promoter and observed a reduced short-term facilitation at these excitatory synapses, representing an inverse phenotype to the knockout. Consistently, the diminished facilitation could be reversed by pharmacologically blocking GABA(B)R with CGP-55845. Moreover, a complete rescue was achieved by additional blocking of postsynaptic GABA(A)R with intracellular picrotoxin or gabazine, suggesting that Nxph1 is able to recruit or stabilize both presynaptic GABA(B)R and postsynaptic GABA(A)R. In support, immunoelectron microscopy validated the localization of ectopic Nxph1 at the synaptic cleft of excitatory synapses in transgenic mice and revealed an enrichment of GABA(A)R and GABA(B)R subunits compared with wild-type animals. Thus, our data propose that Nxph1 plays an instructive role in synaptic short-term plasticity and the configuration with GABA receptors.

Short-term depression of gap junctional coupling in reticular thalamic neurons of absence epileptic rats.

KEY POINTS: Gap junctional electrical coupling between neurons of the reticular thalamic nucleus (RTN) is critical for hypersynchrony in the thalamo-cortical network. This study investigates the role of electrical coupling in pathological rhythmogenesis in RTN neurons in a rat model of absence epilepsy. Rhythmic activation resulted in a Ca(2+) -dependent short-term depression (STD) of electrical coupling between pairs of RTN neurons in epileptic rats, but not in RTN of a non-epileptic control strain. Pharmacological blockade of gap junctions in RTN in vivo induced a depression of seizure activity. The STD of electrical coupling represents a mechanism of Ca(2+) homeostasis in RTN aimed to counteract excessive synchronization. ABSTRACT: Neurons in the reticular thalamic nucleus (RTN) are coupled by electrical synapses, which play a major role in regulating synchronous activity. This study investigates electrical coupling in RTN neurons from a rat model of childhood absence epilepsy, genetic absence epilepsy rats from Strasbourg (GAERS), compared with a non-epileptic control (NEC) strain, to assess the impact on pathophysiological rhythmogenesis. Whole-cell recordings were obtained from pairs of RTN neurons of GAERS and NEC in vitro. Coupling was determined by injection of hyperpolarizing current steps in one cell and monitoring evoked voltage responses in both activated and coupled cell. The coupling coefficient (cc) was compared under resting condition, during pharmacological interventions and repeated activation using a series of current injections. The effect of gap junctional coupling on seizure expression was investigated by application of gap junctional blockers into RTN of GAERS in vivo. At resting conditions, cc did not differ between GAERS and NEC. During repeated activation, cc declined in GAERS but not in NEC. This depression in cc was restored within 25 s and was prevented by intracellular presence of BAPTA in the activated but not in the coupled cell. Local application of gap junctional blockers into RTN of GAERS in vivo resulted in a decrease of spike wave discharge (SWD) activity. Repeated activation results in a short-term depression (STD) of gap junctional coupling in RTN neurons of GAERS, depending on intracellular Ca(2+) mechanisms in the activated cell. As blockage of gap junctions in vivo results in a decrease of SWD activity, the STD observed in GAERS is considered a compensatory mechanism, aimed to dampen SWD activity.

FGF signalling inhibits neural induction in human embryonic stem cells.

Human embryonic stem cells (hESCs) can exit the self-renewal programme, through the action of signalling molecules, at any given time and differentiate along the three germ layer lineages. We have systematically investigated the specific roles of three signalling pathways, TGFß/SMAD2, BMP/SMAD1, and FGF/ERK, in promoting the transition of hESCs into the neuroectoderm lineage. In this context, inhibition of SMAD2 and ERK signalling served to cooperatively promote exit from hESC self-renewal through the rapid downregulation of NANOG and OCT4. In contrast, inhibition of SMAD1 signalling acted to maintain SOX2 expression and prevent non-neural differentiation via HAND1. Inhibition of FGF/ERK upregulated OTX2 that subsequently induced the neuroectodermal fate determinant PAX6, revealing a novel role for FGF2 in indirectly repressing PAX6 in hESCs. Combined inhibition of the three pathways hence resulted in highly efficient neuroectoderm formation within 4 days, and subsequently, FGF/ERK inhibition promoted rapid differentiation into peripheral neurons. Our study assigns a novel, biphasic role to FGF/ERK signalling in the neural induction of hESCs, which may also have utility for applications requiring the rapid and efficient generation of peripheral neurons.

Feasibility of three-dimensional virtual surgical planning in living liver donors.

PURPOSE: The aim of the study was to determine the accuracy, reproducibility, and improvement in the clinical workflow of a semiautomatic computed tomography (CT) virtual surgical planning program in estimating graft volume using actual graft weight as a standard of reference in living liver donors. MATERIALS AND METHODS: This retrospective study was approved by our Institutional Review Board and the requirement for informed consent was waived. A total of 105 liver donor candidates who underwent preoperative liver CT were reviewed. Volumes of the whole liver (V T), four hepatic segments, and predicted volumes of the hepatic graft (V pred) were obtained using a semiautomatic analysis program by radiologists and a conventional manual volumetry program by surgeons. Intraobserver and interobserver agreements of V T and V pred were assessed using intraclass correlation coefficients (ICCs). V pred was also compared to the actual graft weight (W act) and analysis times were recorded. In addition, potential vascular complications were assessed using the surgical planning function of the software. RESULTS: The mean processing time of hepatic volumetry, segmentation, and surgical planning using software was significantly shorter than that using manual volumetry (175.9 ± 46.6 vs. 916.6 ± 52.8 s, P < 0.001). V T and V pred obtained using the semiautomatic analysis program showed significant intra and interobserver agreements (ICC = 0.98-0.99), and V pred showed strong correlation with W act (r = 0.83-0.86, P < 0.0001). Furthermore, image review using the liver analysis program detected 80% (4/5) vascular complications. CONCLUSION: Liver volumetry and estimation of graft volume using liver analysis software provided good accuracy and excellent reproducibility in a short time than manual volumetry method and was useful for identifying vascular complications.

Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2.

OBJECTIVE: The outbreak of hemolytic-uremic syndrome and diarrhea caused by Shiga toxin-producing Escherichia coli O104:H4 in Germany during May to July 2011 involved severe and characteristic neurologic manifestations with a strong female preponderance. Owing to these observations, we designed a series of experimental studies to evaluate the underlying mechanism of action of this clinical picture. METHODS: A magnetic resonance imaging and electroencephalographic study of patients was performed to evaluate the clinical picture in detail. Thereafter, combinations of different experimental settings, including electrophysiological and histological analyses, as well as calcium imaging in brain slices of rats, were conducted. RESULTS: We report on 7 female patients with neurologic symptoms and signs including bilateral thalamic lesions and encephalopathic changes indicative of a predominant involvement of the thalamus. Experimental studies in rats revealed an enhanced expression of the Shiga toxin receptor globotriaosylceramide on thalamic neurons in female rats as compared to other brain regions in the same rats and to male animals. Incubation of brain slices with Shiga toxin 2 evoked a strong membrane depolarization and intracellular calcium accumulation in neurons, associated with neuronal apoptosis, predominantly in the thalamic area. INTERPRETATION: These findings suggest that the direct cytotoxic effect of Shiga toxin 2 in the thalamus might contribute to the pathophysiology of neuronal complications in hemolytic-uremic syndrome.

Ca(2+)-dependent large conductance K(+) currents in thalamocortical relay neurons of different rat strains.

Mutations in genes coding for Ca(2+) channels were found in patients with childhood absence epilepsy (CAE) indicating a contribution of Ca(2+)-dependent mechanisms to the generation of spike-wave discharges (SWD) in humans. Since the involvement of Ca(2+) signals remains unclear, the aim of the present study was to elucidate the function of a Ca(2+)-dependent K(+) channel (BKCa) under physiological conditions and in the pathophysiological state of CAE. The activation of BKCa channels is dependent on both voltage and intracellular Ca(2+) concentrations. Moreover, these channels exhibit an outstandingly high level of regulatory heterogeneity that builds the basis for the influence of BKCa channels on different aspects of neuronal activity. Here, we analyse the contribution of BKCa channels to firing of thalamocortical relay neurons, and we test the hypothesis that BKCa channel activity affects the phenotype of a genetic rat model of CAE. We found that the activation of the ß2-adrenergic receptor/protein kinase A pathway resulted in BKCa channel inhibition. Furthermore, BKCa channels affect the number of action potentials fired in a burst and produced spike frequency adaptation during tonic activity. The latter result was confirmed by a computer modelling approach. We demonstrate that the ß2-adrenergic inhibition of BKCa channels prevents spike frequency adaptation and, thus, might significantly support the tonic firing mode of thalamocortical relay neurons. In addition, we show that BKCa channel functioning differs in epileptic WAG/Rij and thereby likely contributes to highly synchronised, epileptic network activity.

Behavioural and histopathological assessment of the effects of periodic fasting on pentylenetetrazol-induced seizures in rats.

OBJECTIVES: Periodic fasting (PF) was suggested to display antiepileptic and neuroprotective effects, which is in stark contrast to severe fasting or starvation. However, these beneficial effects seem to depend on the type and duration of the used feeding protocol. There are discrepancies concerning both antiepileptic and neuroprotective effects of a PF-diet during repetitive seizures in different epilepsy models. This study was designed to evaluate the effects of different PF protocols on behavioural and histopathological consequences of epilepsy in adult rats. METHODS: Recurrent generalized seizures were caused by repetitive injection of pentylenetetrazol (PTZ) for a period of 4 weeks every other day. While control animals had free access to food and water, animals on a PF-diet were on intermittent fasting for 24 hours every 48 hours for 4 weeks before (T1), after (T2), or both before and after (T3) the injection of PTZ. Behavioural studies were carried out after PTZ injections and histological investigations were performed after the experiments were completed. RESULTS: Seizure assessment showed that the severity of seizures was significantly decreased in groups T1 and T3 when compared with control rats. Dark neuron densities in hippocampal CA1 and CA3 areas were decreased in PF groups, but never in the temporal cortex. The PF-diet also decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling-positive neurons in the hippocampus in both areas and all PF-diet protocols. DISCUSSION: These results support the idea that a PF-diet has anticonvulsive and neuroprotective effects on epileptic rats but underlines that different PF-diet protocols can have varying effects. Anticonvulsive effects were strongest when the PF-diet started before the onset of excitotoxic injuries, the number of dark neurons was decreased and apoptosis was prevented by all PF-diet protocols investigated in this work. Further evaluation of PF-diet protocols for possible clinical anticonvulsant and neuroprotective effects is suggested.

Comparison of volumetric and areal bone mineral density in CT and scout scans using spectral detector technology.

BACKGROUND: To determine whether denoised areal bone mineral density (BMD) measurements from scout scans in spectral detector computed tomography (CT) correlate with volumetric trabecular BMD for opportunistic osteoporosis screening. METHODS: A 64-slice single-source dual-layer spectral CT scanner was used to acquire scout scan data of 228 lumbar vertebral bodies within 57 patients. Scout scans in anterior-posterior (AP) view were performed with a dose of < 0.06 mSv and spectrally decomposed into areal BMD (aBMD) values. A spectral dictionary denoising algorithm was applied to increase the signal-to-noise ratio (SNR). Volumetric trabecular bone mineral density (vBMD) was determined via material decomposition. A 3D convolutional network for image segmentation and labeling was applied for automated vBMD quantification. Projected maps were used to compare the classification accuracy of AP and lateral scout scans. RESULTS: The denoising algorithm led to the minimization of anticorrelated noise in spectral maps and an SNR increase from 5.23 to 13.4 (p < 0.002). Correlation analysis between vBMD and measured AP aBMD, projected AP, and lateral aBMD showed a Pearson correlation coefficient of 0.68, 0.81, and 0.90, respectively. The sensitivity and specificity for the osteoporosis classification task were higher in lateral projection images than in AP crystallizing in an increased area under the curve value of 0.99 versus 0.90. CONCLUSION: Denoised material-specific aBMD maps show a positive correlation to vBMD, enabling spectral scout scans as an opportunistic predictor for osteoporotic patients. This could be applied routinely as a screening tool in patients undergoing a CT examination. RELEVANCE STATEMENT: Scout-based DEXA could be applied routinely as a screening tool in patients undergoing a CT examination. KEY POINTS: • Spectral scout scans can be used as a dual-energy x-ray absorptiometry-like screening tool. • Spectral dictionary denoising on projection images increases the signal-to-noise ratio. • Positive correlation between volumetric and areal bone mineral density is observed. • Lateral projections increase osteoporosis classification accuracy compared to anterior-posterior projections.

Gadolinium K-edge angiography with a spectral photon counting CT in atherosclerotic rabbits.

PURPOSE: The purpose of this study was to investigate the feasibility of gadolinium-K-edge-angiography (angio-Gd-K-edge) with gadolinium-based contrast agents (GBCAs) as obtained with spectral photon counting CT (SPCCT) in atherosclerotic rabbits. MATERIALS AND METHODS: Seven atherosclerotic rabbits underwent angio-SPCCT acquisitions with two GBCAs, with similar intravenous injection protocol. Conventional and angio-Gd-K-edge images were reconstructed with the same parameters. Regions of interest were traced in different locations of the aorta and its branches. Hounsfield unit values, Gd concentrations, signal-to-noise (SNR) and contrast-to-noise (CNR) were calculated and compared. The maximum diameter and the diameter of the aorta in regard to atherosclerotic plaques were measured by two observers. Images were subjectively evaluated regarding vessels' enhancement, artefacts, border sharpness and overall image quality. RESULTS: In the analyzable six rabbits, Gd-K-edge allowed visualization of target vessels and no other structures. HU values and Gd concentrations were greatest in the largest artery (descending aorta, 5.6 ± 0.8 [SD] mm), and lowest in the smallest (renal arteries, 2.1 ± 0.3 mm). While greater for conventional images, CNR and SNR were satisfactory for both images (all P < 0.001). For one observer there were no statistically significant differences in either maximum or plaque-diameters (P = 0.45 and all P > 0.05 in post-hoc analysis, respectively). For the second observer, there were no significant differences for images reconstructed with the same parameters (all P < 0.05). All subjective criteria scored higher for conventional images compared to K-edge (all P < 0.01), with the highest scores for enhancement (4.3-4.4 vs. 3.1-3.4). CONCLUSION: With SPCCT, angio-Gd-K-edge after injection of GBCAs in atherosclerotic rabbits is feasible and allows for angiography-like visualization of small arteries and for the reliable measurement of their diameters.

Activation of neuropeptide S-expressing neurons in the locus coeruleus by corticotropin-releasing factor.

A recently discovered neurotransmitter system, consisting of neuropeptide S (NPS), NPS receptor, and NPS-expressing neurons in the brain stem, has received considerable interest due to its modulating influence on arousal, anxiety and stress responsiveness. Comparatively little is known about the properties of NPS-expressing neurons. Therefore in the present study, a transgenic mouse line expressing enhanced green fluorescent protein (EGFP) in NPS neurons was used to characterize the cellular and functional properties of NPS-expressing neurons located close to the locus coeruleus. Particular emphasis was on the influence of corticotropin-releasing factor (CRF), given previous evidence of stress-related activation of the NPS system. Upon acute immobilization stress, an increase in c-fos expression was detected immunocytochemically in brain stem NPS-EGFP neurons that also expressed the CRF receptor 1 (CRF1). NPS-EGFP neurons were readily identified in acute slice preparations and responded to CRF application with a membrane depolarization capable of triggering action potentials. CRF-induced responses displayed pharmacological properties indicative of CRF1 that were mediated by both a reduction in membrane potassium conductance and an increase in a non-specific cation conductance different from the hyperpolarization-activated cation conductance Ih, and involved protein kinase A signalling. In conclusion, stress exposure results in activation of brain stem NPS-expressing neurons, involving a CRF1-mediated membrane depolarization via at least two ionic mechanisms. These data provide evidence for a direct interaction between the CRF and the NPS system and thereby extend previous observations of NPS-modulated stress responsiveness towards a mechanistic level.

The sleep relay--the role of the thalamus in central and decentral sleep regulation.

Surprisingly, the concept of sleep, its necessity and function, the mechanisms of action, and its elicitors are far from being completely understood. A key to sleep function is to determine how and when sleep is induced. The aim of this review is to merge the classical concepts of central sleep regulation by the brainstem and hypothalamus with the recent findings on decentral sleep regulation in local neuronal assemblies and sleep regulatory substances that create a scenario in which sleep is both local and use dependent. The interface between these concepts is provided by thalamic cellular and network mechanisms that support rhythmogenesis of sleep-related activity. The brainstem and the hypothalamus centrally set the pace for sleep-related activity throughout the brain. Decentral regulation of the sleep-wake cycle was shown in the cortex, and the homeostat of non-rapid-eye-movement sleep is made up by molecular networks of sleep regulatory substances, allowing individual neurons or small neuronal assemblies to enter sleep-like states. Thalamic neurons provide state-dependent gating of sensory information via their ability to produce different patterns of electrogenic activity during wakefulness and sleep. Many mechanisms of sleep homeostasis or sleep-like states of neuronal assemblies, e.g. by the action of adenosine, can also be found in thalamic neurons, and we summarize cellular and network mechanisms of the thalamus that may elicit non-REM sleep. It is argued that both central and decentral regulators ultimately target the thalamus to induce global sleep-related oscillatory activity. We propose that future studies should integrate ideas of central, decentral, and thalamic sleep generation.

Functional properties and cell type specific distribution of I(h) channels in leech neurons.

The hyperpolarisation-activated cation current (I(h)) has been described in many vertebrate and invertebrate species and cell types. In neurons, I(h) is involved in rhythmogenesis, membrane potential stabilisation and many other functions. In this work, we investigate the distribution and functional properties of I(h) in identified leech neurons of intact segmental ganglia. We found I(h) in the mechanosensory touch (T), pressure (P) and noxious (N) neurons, as well as in Retzius neurons. The current displayed its largest amplitude in P neurons and we investigated its biophysical and pharmacological properties in these cells. I(h) was half-maximally activated at -65 mV and fully activated at -100 mV. The current mutually depended on both Na(+) and K(+) with a permeability ratio p(Na)/p(K) of ∼0.21. The reversal potential was approximately -35 mV. The time course of activation could be approximated by a single time constant of ∼370 ms at -60 mV, but required two time constants at -80 mV of ∼80 and ∼560 ms. The current was half-maximally blocked by 0.3 mmol l(-1) Cs(+) but was insensitive to the bradycardic agent ZD7288. The physiological function of this channel could be a subtle alteration of the firing behaviour of mechanosensory neurons as well as a stabilisation of the resting membrane potential.

GABA uptake-dependent Ca(2+) signaling in developing olfactory bulb astrocytes.

We studied GABAergic signaling in astrocytes of olfactory bulb slices using confocal Ca(2+) imaging and two-photon Na(+) imaging. GABA evoked Ca(2+) transients in astrocytes that persisted in the presence of GABA(A) and GABA(B) receptor antagonists, but were suppressed by inhibition of GABA uptake by SNAP 5114. Withdrawal of external Ca(2+) blocked GABA-induced Ca(2+) transients, and depletion of Ca(2+) stores with cyclopiazonic acid reduced Ca(2+) transients by approximately 90%. This indicates that the Ca(2+) transients depend on external Ca(2+), but are mainly mediated by intracellular Ca(2+) release, conforming with Ca(2+)-induced Ca(2+) release. Inhibition of ryanodine receptors did not affect GABA-induced Ca(2+) transients, whereas the InsP(3) receptor blocker 2-APB inhibited the Ca(2+) transients. GABA also induced Na(+) increases in astrocytes, potentially reducing Na(+)/Ca(2+) exchange. To test whether reduction of Na(+)/Ca(2+) exchange induces Ca(2+) signaling, we inhibited Na(+)/Ca(2+) exchange with KB-R7943, which mimicked GABA-induced Ca(2+) transients. Endogenous GABA release from neurons, activated by stimulation of afferent axons or NMDA application, also triggered Ca(2+) transients in astrocytes. The significance of GABAergic Ca(2+) signaling in astrocytes for control of blood flow is demonstrated by SNAP 5114-sensitive constriction of blood vessels accompanying GABA uptake. The results suggest that GABAergic signaling is composed of GABA uptake-mediated Na(+) rises that reduce Na(+)/Ca(2+) exchange, thereby leading to a Ca(2+) increase sufficient to trigger Ca(2+)-induced Ca(2+) release via InsP(3) receptors. Hence, GABA transporters not only remove GABA from the extracellular space, but may also contribute to intracellular signaling and astrocyte function, such as control of blood flow.

First In-Human Results of Computed Tomography Angiography for Coronary Stent Assessment With a Spectral Photon Counting Computed Tomography.

OBJECTIVES: The aim of this study is to compare the image quality of in vivo coronary stents between an energy integrating detectors dual-layer computed tomography (EID-DLCT) and a clinical prototype of spectral photon counting computed tomography (SPCCT). MATERIALS AND METHODS: In January to June 2021, consecutive patients with coronary stents were prospectively enrolled to undergo a coronary computed tomography (CT) with an EID-DLCT (IQon, Philips) and an SPCCT (Philips). The study was approved by the local ethical committee and patients signed an informed consent. A retrospectively electrocardiogram-gated acquisition was performed with optimized matching parameters on the 2 scanners (EID-DLCT: collimation, 64 × 0.625 mm; kVp, 120, automatic exposure control with target current at 255 mAs; rotation time, 0.27 seconds; SPCCT: collimation, 64 × 0.275 mm; kVp, 120; mAs, 255; rotation time, 0.33 seconds). The injection protocol was the same on both scanners: 65 to 75 mL of Iomeron (Bracco) at 5 mL/s. Images were reconstructed with slice thickness of 0.67 mm, 512 matrix, XCB (Xres cardiac standard) and XCD (Xres cardiac detailed) kernel, iDose 3 for EID-DLCT and 0.25-mm slice thickness, 1024 matrix, Detailed 2 and Sharp kernel, and iDose 6 for SPCCT. Two experienced observers measured the proximal and distal external and internal diameters of the stents to quantify blooming artifacts. Regions of interest were drawn in the lumen of the stent and of the upstream coronary artery. The difference (Δ S-C) between the respective attenuation values was calculated as a quantification of stent-induced artifacts on intrastent image quality. For subjective image quality, 3 experienced observers graded with a 4-point scale the image quality of different parameters: coronary wall before the stent, stent lumen, stent structure, calcifications surrounding the stent, and beam-hardening artifacts. RESULTS: Eight patients (age, 68 years [interquartile range, 8]; all men; body mass index, 26.2 kg/m2 [interquartile range, 4.2]) with 16 stents were scanned. Five stents were not evaluable owing to motion artifacts on the SPCCT. Of the remaining, all were drug eluting stents, of which 6 were platinum-chromium, 3 were cobalt-platinum-iridium, and 1 was stainless steel. For 1 stent, no information could be retrieved. Radiation dose was lower with the SPCCT (fixed CT dose index of 25.7 mGy for SPCCT vs median CT dose index of 35.7 [IQ = 13.6] mGy; P = 0.02). For 1 stent, the internal diameter was not assessable on EID-DLCT. External diameters were smaller and internal diameters were larger with SPCCT (all P < 0.05). Consequently, blooming artifacts were reduced on SPCCT (P < 0.05). Whereas Hounsfield unit values within the coronary arteries on the 2 scanners were similar, the Δ S-C was lower for SPCCT-Sharp as compared with EID-DLCT-XCD and SPCCT-Detailed 2 (P < 0.05). The SPCCT received higher subjective scores than EID-DLCT for stent lumen, stent structure, surrounding calcifications and beam-hardening for both Detailed 2 and Sharp (all P ≤ 0.05). The SPCCT-Sharp was judged better for stent structure and beam-hardening assessment as compared with SPCCT-Detailed 2. CONCLUSION: Spectral photon counting CT demonstrated improved objective and subjective image quality as compared with EID-DLCT for the evaluation of coronary stents even with a reduced radiation dose.

Ischemic stroke: etiologic work-up with multidetector CT of heart and extra- and intracranial arteries.

PURPOSE: To assess the potential of a single-session multidetector computed tomography (CT) protocol, as compared with established methods, for the etiologic work-up of acute ischemic stroke. MATERIALS AND METHODS: Patients found to have recently experienced an ischemic stroke were recruited for this prospective study after institutional review board approval was obtained. Each patient was scheduled for two evaluation strategies: (a) a standard approach involving transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE), duplex ultrasonography (US) of the neck vessels, and magnetic resonance (MR) angiography of the neck and brain vessels; and (b) a protocol involving single-session multidetector CT of the heart, neck, and brain vessels. The authors sought to determine the major etiologic factors of stroke, including cardiac sources of embolism and atheroma of the aortic arch and the extra- and intracranial vessels, by using both strategies. RESULTS: Multidetector CT, MR imaging, and duplex US were performed in 46 patients, 39 of whom also underwent TEE. The sensitivity and specificity of multidetector CT were 72% (18 of 25 cases) and 95% (20 of 21 cases), respectively, for detection of cardiac sources and 100% (24 of 24 cases) and 91% (20 of 22 cases), respectively, for detection of major arterial atheroma. For the 46 cases of stroke, the final etiologic classifications determined by using the standard combination approach were cardiac sources in 20 (44%) cases, major arterial atheroma in nine (20%), multiple sources in four (9%), and cryptogenic sources in 13 (28%). Multidetector CT facilitated correct etiologic classification for 38 (83%) of the 46 patients. CONCLUSION: Multidetector CT is a promising tool for etiologic assessment of ischemic stroke, although the identification of minor cardiac sources with this examination requires the establishment of robust criteria.

Feasibility of lung imaging with a large field-of-view spectral photon-counting CT system.

PURPOSE: The purpose of this study was to characterize the technical capabilities and feasibility of a large field-of-view clinical spectral photon-counting computed tomography (SPCCT) prototype for high-resolution (HR) lung imaging. MATERIALS AND METHODS: Measurement of modulation transfer function (MTF) and acquisition of a line pairs phantom were performed. An anthropomorphic lung nodule phantom was scanned with standard (120kVp, 62mAs), low (120kVp, 11mAs), and ultra-low (80kVp, 3mAs) radiation doses. A human volunteer underwent standard (120kVp, 63mAs) and low (120kVp, 11mAs) dose scans after approval by the ethics committee. HR images were reconstructed with 1024 matrix, 300mm field of view and 0.25mm slice thickness using a filtered-back projection (FBP) and two levels of iterative reconstruction (iDose 5 and 9). The conspicuity and sharpness of various lung structures (distal airways, vessels, fissures and proximal bronchial wall), image noise, and overall image quality were independently analyzed by three radiologists and compared to a previous HR lung CT examination of the same volunteer performed with a conventional CT equipped with energy integrating detectors (120kVp, 10mAs, FBP). RESULTS: Ten percent MTF was measured at 22.3lp/cm with a cut-off at 31lp/cm. Up to 28lp/cm were depicted. While mixed and solid nodules were easily depicted on standard and low-dose phantom images, higher iDose levels and slice thicknesses (1mm) were needed to visualize ground-glass components on ultra-low-dose images. Standard dose SPCCT images of in vivo lung structures were of greater conspicuity and sharpness, with greater overall image quality, and similar image noise (despite a flux reduction of 23%) to conventional CT images. Low-dose SPCCT images were of greater or similar conspicuity and sharpness, similar overall image quality, and lower but acceptable image noise (despite a flux reduction of 89%). CONCLUSIONS: A large field-of-view SPCCT prototype demonstrates HR technical capabilities and high image quality for high resolution lung CT in human.