A simple CT scan protocol for planning of total hip arthroplasty in patients with femoral neck fractures.

We describe a method for planning total hip arthroplasty (THA) in patients with a displaced femoral neck fracture based on a simple CT scan protocol of the contralateral hip. This protocol was used on 22 consecutive patients during the inclusion period, followed by reconstruction and 2D templating to predict the implant size and positioning. The exact planned size was achieved in 21/22 (95%) cups, 14/22 (64%) femoral stems and 14/22 (64%) femoral heads. There were no intra- or postoperative fractures. After surgery in which this planning method had been applied, the differences in length and lateral offset were less than 5 mm on average relative to the opposite side (mean postoperative leg length difference of -2 mm (-8 to +3 mm) and lateralization of -4 mm (-14 to +3 mm)). While this technique exposes the patient to additional radiation, it does not require any specific devices or surgical approach and could be used in most hospitals. LEVEL OF EVIDENCE: IV.

Mode of Antibacterial Action of Tomatidine C3-Diastereoisomers.

Tomatidine (TO) is a natural narrow-spectrum antibiotic acting on the Staphylococcus aureus small colony variant (SCV) with a minimal inhibitory concentration (MIC) of 0.06 µg/mL while it shows no activity against prototypical strains (MIC > 128 µg/mL). To expand the spectrum of activity of TO, the 3ß-hydroxyl group was substituted with an ethane-1,2-diamine, resulting in two diastereoisomers, TM-02 (C3-ß) and TM-03 (C3-α). These molecules are equally potent against prototypical S. aureus and E. coli strains (MIC 8 and 32 µg/mL, respectively), whereas TM-02 is more potent against SCV (MIC 0.5 µg/mL) and hyperpermeable E. coli strains (MIC 1 µg/mL). The differences in their modes of action were investigated. We used membrane vesicles to confirm the inhibition of the bacterial ATP synthase, the documented target of TO, and measured effects on bacterial cell membranes. Both molecules inhibited E. coli ATP synthase, with Ki values of 1.1 µM and 3.5 µM for TM-02 and TM-03, respectively, and the bactericidal effect of TM-02 was linked to ATP synthase inhibition. Furthermore, TM-02 had no major effect on the membrane fluidity and gradually reduced membrane potential. In contrast, TM-03 caused structural damages to membranes and completely disrupted the membrane potential (>90%). We were successful in broadening the spectrum of activity of TO. C3-ß-diastereoisomers may have more specific antibacterial action than C3-α.

Surface modification effect on contrast agent efficiency for X-ray based spectral photon-counting scanner/luminescence imaging: from fundamental study to in vivo proof of concept.

X-Ray imaging techniques are among the most widely used modalities in medical imaging and their constant evolution has led to the emergence of new technologies. The new generation of computed tomography (CT) systems - spectral photonic counting CT (SPCCT) and X-ray luminescence optical imaging - are examples of such powerful techniques. With these new technologies the rising demand for new contrast agents has led to extensive research in the field of nanoparticles and the possibility to merge the modalities appears to be highly attractive. In this work, we propose the design of lanthanide-based nanocrystals as a multimodal contrast agent with the two aforementioned technologies, allowing SPCCT and optical imaging at the same time. We present a systematic study on the effect of the Tb3+ doping level and surface modification on the generation of contrast with SPCCT and the luminescence properties of GdF3:Tb3+ nanocrystals (NCs), comparing different surface grafting with organic ligands and coatings with silica to make these NCs bio-compatible. A comparison of the luminescence properties of these NCs with UV revealed that the best results were obtained for the Gd0.9Tb0.1F3 composition. This property was confirmed under X-ray excitation in microCT and with SPCCT. Moreover, we could demonstrate that the intensity of the luminescence and the excited state lifetime are strongly affected by the surface modification. Furthermore, whatever the chemical nature of the ligand, the contrast with SPCCT did not change. Finally, the successful proof of concept of multimodal imaging was performed in vivo with nude mice in the SPCCT taking advantage of the so-called color K-edge imaging method.

The PREMISE database of 20 Macaca fascicularis PET/MRI brain images available for research.

Non-human primate studies are unique in translational research, especially in neurosciences where neuroimaging approaches are the preferred methods used for cross-species comparative neurosciences. In this regard, neuroimaging database development and sharing are encouraged to increase the number of subjects available to the community, while limiting the number of animals used in research. Here we present a simultaneous positron emission tomography (PET)/magnetic resonance (MR) dataset of 20 Macaca fascicularis images structured according to the Brain Imaging Data Structure standards. This database contains multiple MR imaging sequences (anatomical, diffusion and perfusion imaging notably), as well as PET perfusion and inflammation imaging using respectively [15O]H2O and [11C]PK11195 radiotracers. We describe the pipeline method to assemble baseline data from various cohorts and qualitatively assess all the data using signal-to-noise and contrast-to-noise ratios as well as the median of intensity and the pseudo-noise-equivalent-count rate (dynamic and at maximum) for PET data. Our study provides a detailed example for quality control integration in preclinical and translational PET/MR studies with the aim of increasing reproducibility. The PREMISE database is stored and available through the PRIME-DE consortium repository.

Objects drawn from haptic perception and vision-based spatial abilities.

Haptic perception is used in the anatomy laboratory with the handling of three-dimensional (3D) prosections, dissections, and synthetic models of anatomical structures. Vision-based spatial ability has been found to correlate with performance on tests of 3D anatomy knowledge in previous studies. The objective was to explore whether haptic-based spatial ability was correlated with vision-based spatial ability. Vision-based spatial ability was measured in a study group of 49 medical graduates with three separate tests: a redrawn Vandenberg and Kuse Mental Rotations Tests in two (MRT A) and three (MRT C) dimensions and a Surface Development Test (SDT). Haptic-based spatial ability was measured using 18 different objects constructed from 10 cubes glued together. Participants were asked to draw these objects from blind haptic perception, and drawings were scored by two independent judges. The maximum score was 24 for each of MRT A and MRT C, 60 for SDT, and 18 for the drawings. The drawing score based on haptic perception [median = 17 (lower quartile = 16, upper quartile = 18)] correlated with MRT A [14 (9, 17)], MRT C [9 (7, 12)] and SDT [44 (36, 52)] scores with a Spearman's rank correlation coefficient of 0.395 (p = 0.0049), 0.507 (p = 0.0002) and 0.606 (p < 0.0001), respectively. Spatial abilities assessed by vision-based tests were correlated with a drawing score based on haptic perception of objects. Future research should investigate the contribution of haptic-based and vision-based spatial abilities on learning 3D anatomy from physical models.

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.

Spatio-Temporal Characterization of Brain Inflammation in a Non-human Primate Stroke Model Mimicking Endovascular Thrombectomy.

Reperfusion therapies in acute ischemic stroke have demonstrated their efficacy in promoting clinical recovery. However, ischemia/reperfusion injury and related inflammation remain a major challenge in patient clinical management. We evaluated the spatio-temporal evolution of inflammation using sequential clinical [11C]PK11195 PET-MRI in a non-human primate (NHP) stroke model mimicking endovascular thrombectomy (EVT) with a neuroprotective cyclosporine A (CsA) treatment. The NHP underwent a 110-min transient endovascular middle cerebral artery occlusion. We acquired [11C]PK11195 dynamic PET-MR imaging at baseline, 7 and 30 days after intervention. Individual voxel-wise analysis was performed thanks to a baseline scan database. We quantified [11C]PK11195 in anatomical regions and in lesioned areas defined on per-occlusion MR diffusion-weighted imaging and perfusion [15O2]H2OPET imaging. [11C]PK11195 parametric maps showed a clear uptake overlapping the lesion core at D7, which further increased at D30. Voxel-wise analysis identified individuals with significant inflammation at D30, with voxels located within the most severe diffusion reduction area during occlusion, mainly in the putamen. The quantitative analysis revealed that thalamic inflammation lasted until D30 and was significantly reduced in the CsA-treated group compared to the placebo. In conclusion, we showed that chronic inflammation matched ADC decrease at occlusion time, a region exposed to an initial burst of damage-associated molecular patterns, in an NHP stroke model mimicking EVT. We described secondary thalamic inflammation and the protective effect of CsA in this region. We propose that major ADC drop in the putamen during occlusion may identify individuals who could benefit from early personalized treatment targeting inflammation.

What have we learned from 20 years of using highly crosslinked PE in total hip arthroplasty?

Slightly more than 20 years after its first clinical use, highly cross-linked polyethylene (HXLPE) has been widely adopted. Despite initial concerns about oxidation and lack of fatigue resistance, first generation HXLPE, with 15 years of follow-up and widespread use, continues to provide excellent results, even in a young, active population. Remelted HXLPE might have a lower wear rate than annealed HXLPE and will no doubt have a better resistance to oxidation. Second generation materials, consisting of polyethylene (PE) that is sequentially irradiated then annealed and PE that is infused with antioxidants, also have provided encouraging short- and medium-term results. Data from national joint registers confirm data from clinical trials. Even in more challenging cases (dual mobility, hip resurfacing, revision surgery and thin liners), HXLPE has generated promising results. However, failures (rim fractures) have been documented, including for all the latest HXLPE generations. Consequently, certain precautions must be taken during its use and close patient monitoring is necessary.

Do our hands see what our eyes see? Investigating spatial and haptic abilities.

Spatial abilities (SAs) are cognitive resources used to mentally manipulate representations of objects to solve problems. Haptic abilities (HAs) represent tactile interactions with real-world objects transforming somatic information into mental representations. Both are proposed to be factors in anatomy education, yet relationships between SAs and HAs remain unknown. The objective of the current study was to explore SA-HA interactions. A haptic ability test (HAT) was developed based on the mental rotations test (MRT) with three-dimensional (3D) objects. The HAT was undertaken in three sensory conditions: (1) sighted, (2) sighted with haptics, and (3) haptics. Participants (n = 22; 13 females, 9 males) completed the MRT and were categorized into high spatial abilities (HSAs) (n = 12, mean± standard deviation: 13.7 ± 3.0) and low spatial abilities (LSAs) (n = 10, 5.6 ± 2.0) based on score distributions about the overall mean. Each SA group's HAT scores were compared across the three sensory conditions. Spearman's correlation coefficients between MRT and HAT scores indicated a statistically significant correlation in sighted condition (r = 0.553, p = 0.015) but were not significant in the sighted with haptics (r = 0.0.078, p = 0.212) and haptics (r = 0.043, p = 0.279) conditions. These data suggest HAs appear unrelated to SAs. With haptic exploration, LSA HAT scores were compensated; comparing HSA with LSA: sighted with haptics [median (lower and upper quartiles): 12 (12,13) vs. 12 (11,13), p = 0.254], and haptics [12 (11,13) vs. 12 (10,12), p = 0.381] conditions. Migrations to online anatomy teaching may unwittingly remove important sensory modalities from the learner. Understanding learner behaviors and performance when haptic inputs are removed from the learning environment represents valuable insight informing future anatomy curriculum and resource development.

A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs.

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.

PET-MRI nanoparticles imaging of blood-brain barrier damage and modulation after stroke reperfusion.

In an acute ischaemic stroke, understanding the dynamics of blood-brain barrier injury is of particular importance for the prevention of symptomatic haemorrhagic transformation. However, the available techniques assessing blood-brain barrier permeability are not quantitative and are little used in the context of acute reperfusion therapy. Nanoparticles cross the healthy or impaired blood-brain barrier through combined passive and active processes. Imaging and quantifying their transfer rate could better characterize blood-brain barrier damage and refine the delivery of neuroprotective agents. We previously developed an original endovascular stroke model of acute ischaemic stroke treated by mechanical thrombectomy followed by positron emission tomography-magnetic resonance imaging. Cerebral capillary permeability was quantified for two molecule sizes: small clinical gadolinium Gd-DOTA (<1 nm) and AGuIX® nanoparticles (∼5 nm) used for brain theranostics. On dynamic contrast-enhanced magnetic resonance imaging, the baseline transfer constant K trans was 0.94 [0.48, 1.72] and 0.16 [0.08, 0.33] ×10-3 min-1, respectively, in the normal brain parenchyma, consistent with their respective sizes, and 1.90 [1.23, 3.95] and 2.86 [1.39, 4.52] ×10-3 min-1 in choroid plexus, confirming higher permeability than brain parenchyma. At early reperfusion, K trans for both Gd-DOTA and AGuIX® nanoparticles was significantly higher within the ischaemic area compared to the contralateral hemisphere; 2.23 [1.17, 4.13] and 0.82 [0.46, 1.87] ×10-3 min-1 for Gd-DOTA and AGuIX® nanoparticles, respectively. With AGuIX® nanoparticles, K trans also increased within the ischaemic growth areas, suggesting added value for AGuIX®. Finally, K trans was significantly lower in both the lesion and the choroid plexus in a drug-treated group (ciclosporin A, n = 7) compared to placebo (n = 5). K trans quantification with AGuIX® nanoparticles can monitor early blood-brain barrier damage and treatment effect in ischaemic stroke after reperfusion.

Recent update on crosslinked polyethylene in total hip arthroplasty.

More than two decades after their clinical introduction, crosslinked polyethylenes (XLPE) have been widely adopted. Though concerns were initially raised regarding oxidation and brittleness, on a large scale, the first generation of XLPE continues to be highly effective 15 years after the surgery, even in a young and active population. Remelted XLPE might display lower wear rates than annealed XLPE. Second generation XLPEs, not only including sequentially irradiated and annealed but also associated with antioxidants, demonstrate encouraging short- to mid-term results. Registry data support clinical trial reports. Even in less favorable settings (lipped liners, dual mobility cups, revision surgery, hip resurfacing) results are promising. However, failures (fractures) have already been described. Therefore, a high level of surveillance remains crucial.

Bactericidal Activity of the Bacterial ATP Synthase Inhibitor Tomatidine and the Combination of Tomatidine and Aminoglycoside Against Persistent and Virulent Forms of Staphylococcus aureus.

Tomatidine (TO), a steroid alkaloid, exerts a strong bactericidal activity on the infection-persistent phenotype of Staphylococcus aureus, the small-colony variant (SCV), with a minimal inhibitory concentration (MIC) of 0.06 µg/ml. Also, the combination of TO to an aminoglycoside (AMG) shows a strong synergistic effect against prototypical (WT) S. aureus (MIC 0.06 µg/ml), which is otherwise unaffected by TO alone (MIC > 128 µg/ml). We have recently established that the ATP synthase (subunit AtpE) was the molecular target of TO and that TO reduces the production of ATP in S. aureus. The purpose of this study was to understand how TO and the TO-AMG combination exert bactericidal activities against S. aureus SCV and WT strains, respectively. The impact of TO and of the TO-gentamicin (GEN) combination on the membrane potential and generation of reactive oxygen species (ROS) were determined using florescent probes. GEN uptake in WT was assessed in the presence of TO. Virulence of SCV and WT strains as well as of in vitro-selected mutants showing resistance to TO or the TO-GEN combination was evaluated in a murine thigh infection model. TO causes a reduction in membrane potential in both WT and SCV, but significant amounts of ROS are only produced in SCVs. Besides, the presence of TO improves the uptake of GEN by the WT strain and the combination TO-GEN generated 2.5-folds more ROS in WT, compared to that induced by GEN alone. Under anaerobic conditions, WT adopts a fermentative slow-growth phenotype and becomes susceptible to TO even if used alone. In vivo, TO- or TO-GEN-resistant strains were significantly altered in their ability to colonize tissues. These results shed light on the mechanism of action of TO and its synergy with AMGs against S. aureus WT. TO bactericidal activity against SCVs is attributable to both a critical drop in the membrane potential accompanied by a substantial ROS production. In the WT, TO helps GEN uptake and ROS is also important for the synergy. Acquiring resistance to TO significantly impairs virulence. The residual ATP synthase activity of SCVs might represent the Achilles' heel of persistent S. aureus.

Spatial abilities training in the field of technical skills in health care: A systematic review.

OBJECTIVE: To conduct a systematic review of the effect of interventions on spatial abilities in the field of technical skills in health care. METHODS: A literature search was conducted up to November 14, 2017 in Scopus and in several databases on EBSCOhost platform. Citations were obtained, articles related to retained citations were reviewed and a final list of included studies was identified. Methods in the field of technical skills relating an intervention to spatial abilities test scores between intervention groups or obtained before and after the intervention were identified as eligible. The quality of included studies was assessed and data were extracted in a systematic way. RESULTS: A series of 5513 citations was obtained. Ninety-nine articles were retained and fully reviewed, yielding four included studies. No difference in the Hidden Figure Test score after one year was observed after residency training in General Surgery of at least nine months. A first-year dental curriculum was not found to elevate the Novel Object Cross-Sections Test score (P = 0.07). A two-semester learning period of abdominal sonography was found to increase the Revised Minnesota Paper Form Board Test score (P < 0.05). A hands-on radiology course using interactive three-dimensional image post-processing software consisting of seven two-hour long seminars on a weekly basis was found to amplify the Cube Perspective Test score (P < 0.001). CONCLUSION: Spatial abilities tests scores were enhanced by courses in abdominal sonography and hands-on radiology, but were not improved by residency training in General Surgery and first-year dental curriculum.

Pre-operative templating in THA. Part I: a classification of architectural hip deformities.

INTRODUCTION: While numerous classifications of hip arthritis have been proposed, none considered the magnitude and direction of femoral head translation relative to the native acetabulum. A more precise classification of architectural hip deformities is necessary to improve preoperative templating and anticipate surgical challenges of total hip arthroplasty (THA). The purpose of the present study was to introduce a classification system to distinguish different types of architectural hip deformities, based on femoral head translation patterns, and to evaluate its repeatability using plain radiographs (qualitative) and Computed Tomography (CT) measurements (quantitative). MATERIALS AND METHODS: We studied pre-operative frontal and lateral hip radiographs and CT scans of 191 hips (184 patients) that received primary THA. The distance between the femoral head center (FC) and the acetabular center (AC) was measured, as well as femoral offset, acetabular offset, head center height, acetabular floor distance and femoral neck angle. The hips were classified qualitatively using frontal plain radiographs, and then quantitatively using CT scans (with an arbitrary threshold of 3 mm as Centered, Medialized, Lateralized, Proximalized or Proximo-lateralized. The agreement between qualitative and quantitative classification methods was compared for applying the same classification. RESULTS: Qualitative classification identified 120 centered (63%), 8 medialized (4%), 49 lateralized (26%), 3 proximalized (2%), and 11 proximo-lateralized (6%) hips, while quantitative classification identified 116 centered (61%), 8 medialized (4%), 51 lateralized (27%), 5 proximalized (3%), and 11 proximo-lateralized (6%) hips. The agreement between the two methods was excellent (0.94; CI 0.90-0.98). Medialization reached 9.7 mm, while lateralization reached 10.9 mm, and proximalization reached 8.5 mm. Proximalized and proximo-lateralized hips had more valgus necks, while medialized hips had more varus necks (p = 0.003). CONCLUSIONS: The classification system enabled repeatable distinction of 5 types of architectural hip deformities. The excellent agreement between quantitative and qualitative methods suggests that plain radiographs are sufficient to classify architectural hip deformities.

Pharmacological MRI to investigate the functional selectivity of 5-HT1A receptor biased agonists.

The emerging concept of "biased agonism" denotes the phenomenon whereby agonists can preferentially direct receptor signalling to specific intracellular responses among the different transduction pathways, thus potentially avoiding side effects and improving therapeutic effects. The aim of this study was to investigate biased agonism by using pharmacological magnetic resonance imaging (phMRI). The cerebral blood oxygen level dependent (BOLD) signal changes induced by increasing doses of two serotonin 5-HT1A receptor biased agonists, NLX-112 and NLX-101, were mapped in anaesthetized rats. Although both compounds display high affinity, selectivity and agonist efficacy for 5-HT1A receptors, NLX-101 is known to preferentially activate post-synaptic receptors, whereas NLX-112 targets both pre- and post-synaptic receptors. We used several doses of agonists in order to determine if the regional selectivity of NLX-101 was dose-dependent. NLX-112 and NLX-101 induced different positive and negative hemodynamic changes patterns at equal doses. Importantly, NLX-101 had no significant effect in regions expressing pre-synaptic receptors contrary to NLX-112. NLX-112 also produced higher BOLD changes than NLX-101 in the orbital cortex, the somatosensory cortex, and the magnocellular preoptic nuclei. In other regions such as the retrosplenial cortex and the dorsal thalamus, the drugs had similar effects. In terms of functional connectivity, NLX-112 induced more widespread changes than NLX-101. The present phMRI study demonstrates that two closely-related agonists display notable differences in their hemodynamic "fingerprints". These data support the concept of biased agonism at 5-HT1A receptors and raise the prospect of identifying novel therapeutics which exhibit improved targeting of brain regions implicated in neuropsychiatric disorders. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

Spatial Abilities Training in Anatomy Education: A Systematic Review.

Spatial abilities have been correlated to anatomy knowledge assessment and spatial training has been found to improve spatial abilities in previous systematic reviews. The objective of this systematic review was to evaluate spatial abilities training in anatomy education. A literature search was done from inception to 3 August 2017 in Scopus® and several databases on the EBSCOhost platform. Citations were reviewed and those involving anatomy education, an intervention, and a spatial abilities test were retained and the corresponding full-text articles were reviewed for inclusion. Before and after training studies, as well as comparative training programs, relating a spatial training intervention to spatial abilities were eligible. Of the 2,405 citations obtained, 52 articles were identified and reviewed, yielding eight eligible articles. Instruction in anatomy and mental rotations training were found to improve spatial abilities. For the seven studies retained for the meta-analysis that included the effect of interventions on spatial abilities test scores, the pooled treatment effect difference was 0.49 (95% CI [0.17; 0.82]; n = 11) improvement. For the two studies that included the practice effect on spatial abilities test scores in a control group, the pooled treatment effect difference was 0.47 (95% CI [-0.03; 0.97]; n = 2) improvement. In these two studies, the impact of the intervention on spatial abilities test scores was found despite the practice effect. Evidence was found for improvement of spatial abilities in anatomy education using instruction in anatomy and mental rotations training.

Feasibility of improving vascular imaging in the presence of metallic stents using spectral photon counting CT and K-edge imaging.

Correct visualization of the vascular lumen is impaired in standard computed tomography (CT) because of blooming artifacts, increase of apparent size, induced by metallic stents and vascular calcifications. Recently, due to the introduction of photon-counting detectors in the X-ray imaging field, a new prototype spectral photon-counting CT (SPCCT) based on a modified clinical CT system has been tested in a feasibility study for improving vascular lumen delineation and visualization of coronary stent architecture. Coronary stents of different metal composition were deployed inside plastic tubes containing hydroxyapatite spheres to simulate vascular calcifications and in the abdominal aorta of one New Zealand White (NZW) rabbit. Imaging was performed with an SPCCT prototype, a dual-energy CT system, and a conventional 64-channel CT system (B64). We found the apparent widths of the stents significantly smaller on SPCCT than on the other two systems in vitro (p < 0.01), thus closer to the true size. Consequently, the intra-stent lumen was significantly larger on SPCCT (p < 0.01). In conclusion, owing to the increased spatial resolution of SPCCT, improved lumen visualization and delineation of stent metallic mesh is possible compared to dual-energy and conventional CT.

A Conformational Restriction Strategy for the Identification of a Highly Selective Pyrimido-pyrrolo-oxazine mTOR Inhibitor.

The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conformational restriction approach to explore a novel chemical space for the generation of TORKi. Structure-activity relationship (SAR) studies led to the identification of compound 12b with a ∼450-fold selectivity for mTOR over class I PI3K isoforms. Pharmacokinetic studies in male Sprague Dawley rats highlighted a good exposure after oral dosing and a minimum brain penetration. CYP450 reactive phenotyping pointed out the high metabolic stability of 12b. These results identify the tricyclic pyrimido-pyrrolo-oxazine moiety as a novel scaffold for the development of highly selective mTOR inhibitors for cancer treatment.

Evaluation of Myelin Radiotracers in the Lysolecithin Rat Model of Focal Demyelination: Beware of Pitfalls!

The observation that amyloid radiotracers developed for Alzheimer's disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [11C]PIB was used to show that in vivo PET does not provide sufficient sensitivity to reliably track myelin changes and may be sensitive to LPC side effects instead of demyelination as such. Ex vivo autoradiography with a fluorine radiotracer should be preferred, to adequately evaluate and compare radiotracers for the assessment of myelin content.