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result(s) for
"Osman Ratib"
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Nicotinic Acetylcholine Receptor Density in the “Higher-Order” Thalamus Projecting to the Prefrontal Cortex in Humans: a PET Study
by
Wissmeyer, Michael
,
Picard, Fabienne
,
Garibotto, Valentina
in
Acetylcholine receptors (nicotinic)
,
Brain
,
Cholinergic transmission
2020
PurposeThe parcellation of the thalamus into different nuclei involved in different corticothalamocortical loops reflects its functional diversity. The connections between the mediodorsal nucleus and the prefrontal cortex play a major role in cognition, particularly in the rapid processing of behaviorally relevant information. The thalamus is the brain region with the highest density in α4β2 nicotinic acetylcholine receptors, the main human nicotinic acetylcholine receptor subtype. The aim of this study was to investigate the possible role of the nicotinic cholinergic system in the thalamo-cortical loops measuring receptor density in different subregions of the thalamus, based on their cortical connectivity.ProceduresWe studied α4β2 nicotinic acetylcholine receptors using positron emission tomography and [18F]Fluoro-A-85380, a radiotracer specific for this receptor subtype, in 36 non-smoking male subjects, including 12 healthy controls and 24 patients with epilepsy. [18F]Fluoro-A-85380 ratio index of binding potential was compared by a repeated measures general linear model, including the thalamic subregions and the brain hemisphere as within-subject factor and clinical groups as between-subject factor.ResultsThe “prefrontal” thalamus, the subregion including the mediodorsal nucleus, had a significantly higher nicotinic acetylcholine receptor density than all other thalamic subregions. These findings were confirmed when analyzing solely the 12 healthy controls.ConclusionsThis particular neurochemical organization of the thalamus supports a major role of the cholinergic system in the loops between the thalamus and the prefrontal cortex. The highest nicotinic acetylcholine receptor density in the « higher-order thalamus » could partly explain the beneficial effect of acute nicotine on attentional and executive functions and possibly the pathophysiology of some neuropsychiatric disorders.
Journal Article
Integrating radiomics into holomics for personalised oncology: from algorithms to bedside
by
Gatta, Roberto
,
Ratib, Osman
,
Leimgruber, Antoine
in
Algorithms
,
Artificial intelligence
,
Big Data
2020
Radiomics, artificial intelligence, and deep learning figure amongst recent buzzwords in current medical imaging research and technological development. Analysis of medical big data in assessment and follow-up of personalised treatments has also become a major research topic in the area of precision medicine. In this review, current research trends in radiomics are analysed, from handcrafted radiomics feature extraction and statistical analysis to deep learning. Radiomics algorithms now include genomics and immunomics data to improve patient stratification and prediction of treatment response. Several applications have already shown conclusive results demonstrating the potential of including other “omics” data to existing imaging features. We also discuss further challenges of data harmonisation and management infrastructure to shed a light on the much-needed integration of radiomics and all other “omics” into clinical workflows. In particular, we point to the emerging paradigm shift in the implementation of big data infrastructures to facilitate databanks growth, data extraction and the development of expert software tools. Secured access, sharing, and integration of all health data, called “holomics”, will accelerate the revolution of personalised medicine and oncology as well as expand the role of imaging specialists.
Journal Article
Local recurrence of squamous cell carcinoma of the head and neck after radio(chemo)therapy: Diagnostic performance of FDG-PET/MRI with diffusion-weighted sequences
by
Combescure, Christophe
,
Becker, Minerva
,
Dulguerov, Nicolas
in
Benign
,
Clustering
,
Complementarity
2018
PurposeTo determine the diagnostic performance of FDG-PET/MRI with diffusion-weighted imaging (FDG-PET/DWIMRI) for detection and local staging of head and neck squamous cell carcinoma (HNSCC) after radio(chemo)therapy.Materials and methodsThis was a prospective study that included 74 consecutive patients with previous radio(chemo)therapy for HNSCC and in whom tumour recurrence or radiation-induced complications were suspected clinically. The patients underwent hybrid PET/MRI examinations with morphological MRI, DWI and FDG-PET. Experienced readers blinded to clinical/histopathological data evaluated images according to established diagnostic criteria taking into account the complementarity of multiparametric information. The standard of reference was histopathology with whole-organ sections and follow-up ≥24 months. Statistical analysis considered data clustering.ResultsThe proof of diagnosis was histology in 46/74 (62.2%) patients and follow-up (mean ± SD = 34 ± 8 months) in 28/74 (37.8%). Thirty-eight patients had 43 HNSCCs and 46 patients (10 with and 36 without tumours) had 62 benign lesions/complications. Sensitivity, specificity, and positive and negative predictive value of PET/DWIMRI were 97.4%, 91.7%, 92.5% and 97.1% per patient, and 93.0%, 93.5%, 90.9%, and 95.1% per lesion, respectively. Agreement between imaging-based and pathological T-stage was excellent (kappa = 0.84, p < 0.001).ConclusionFDG-PET/DWIMRI yields excellent results for detection and T-classification of HNSCC after radio(chemo)therapy.Key points• FDG-PET/DWIMRI yields excellent results for the detection of post-radio(chemo)therapy HNSCC recurrence.• Prospective one-centre study showed excellent agreement between imaging-based and pathological T-stage.• 97.5% of positive concordant MRI, DWI and FDG-PET results correspond to recurrence.• 87% of discordant MRI, DWI and FDG-PET results correspond to benign lesions.• Multiparametric FDG-PET/DWIMRI facilitates planning of salvage surgery in the irradiated neck.
Journal Article
The hospital of the future: rethinking architectural design to enable new patient-centered treatment concepts
2022
PurposeToday’s hospitals are designed as collections of individual departments, with limited communication and collaboration between medical sub-specialties. Patients are constantly being moved between different places, which is detrimental for patient experience, overall efficiency and capacity. Instead, we argue that care should be brought to the patient, not vice versa, and thus propose a novel hospital architecture concept that we refer to as Patient Hub. It envisions a truly patient-centered, department-less facility, in which all critical functions occur in the same building and on the same floor.MethodsTo demonstrate the feasibility and benefits of our concept, we selected an exemplary patient scenario and used 3D software to simulate resulting workflows for both the Patient Hub and a traditional hospital based on a generic hospital template by Kaiser-Permanente.ResultsAccording to our workflow simulations, the Patient Hub model effectively eliminates waiting and transfer times, drastically simplifies wayfinding, reduces overall traveling distances by 54%, reduces elevator runs by 78% and improves access to quality views from 67 to 100% for patient rooms, from 0 to 100% for exam rooms and from 0 to 38% for corridors. In addition, the interaction of related medical fields is improved while maintaining the quality of care and the relationship between patients and caregivers.ConclusionWith the Patient Hub concept, we aim at rethinking traditional hospital layouts. We were able to demonstrate, alas on a proof-of-concept basis, that it is indeed feasible to place the patient at the very center of operations, while increasing overall efficiency and capacity at the same time and maintaining the quality of care.
Journal Article
Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy
by
Wissmeyer, Michael
,
Goldstein, Rachel
,
Picard, Fabienne
in
Abnormalities
,
Acetylcholine receptors (nicotinic)
,
Availability
2019
PurposeMutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [18F]-F-85380-A (F-A-85380), an α4β2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy.MethodsWe included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [18F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis.ResultsIn the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BPRI, corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BPRI increase in the ACC could distinguish IGE patients from controls and from patients with focal epilepsy with good accuracy.ConclusionsWe observed focal changes of density/availability of nicotinic receptors in IGE, namely an increase in the ACC. These data suggest that the modulation of α4β2 nicotinic receptors plays a role not only in ADNFLE, but also in other genetic epileptic syndromes such as IGE and could serve as a biomarker of epilepsy syndromes with a genetic background.
Journal Article
Higher availability of α4β2 nicotinic receptors (nAChRs) in dorsal ACC is linked to more efficient interference control
by
Wissmeyer, Michael
,
Picard, Fabienne
,
Seimbille, Yann
in
Acetylcholine receptors (nicotinic)
,
Adolescent
,
Adult
2020
Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the human brain and play an important role in the neuromodulation of brain networks implicated in attentional processes. Previous work in humans showed that heteromeric α4β2 nAChRs are abundant in the cingulo-insular network underlying attentional control. It has been proposed that cholinergic neuromodulation by α4β2 nAChRs is involved in attentional control during demanding tasks, when additional resources are needed to minimize interference from task-irrelevant stimuli and focus on task-relevant stimuli. Here we investigate the link between the availability of α4β2 nAChRs in the cingulo-insular network and behavioral measures of interference control using two versions of the Stroop paradigm, a task known to recruit cingulo-insular areas. We used a previously published PET dataset acquired in 24 non-smoking male subjects in the context of a larger study which investigated the brain distribution of nAChRs in two clinical groups using 2-[(18)F]F-A-85380 PET. We found that higher availability of α4β2 nAChRs in the dorsal anterior cingulate cortex (ACC) predicted better interference control independently of group and age. In line with animal models, our results support the view that the availability of α4β2 nAChRs in the dorsal ACC is linked with more efficient attentional control.
•The cingulo-insular network displays high availability of α4β2 nicotinic receptors.•Higher availability of α4β2 nAChRs in the dorsal ACC predicts better interference control.•Availability of α4β2 nAChRs in the insula or in the DLPFC does not predict interference control.
Journal Article
Structural Basis of Bone Fragility in Young Subjects with Inflammatory Bowel Disease: A High-resolution pQCT Study of the SWISS IBD Cohort (SIBDC)
by
Chevalley, Thierry
,
Zawadynski, Sophie
,
Ratib, Osman
in
Absorptiometry, Photon
,
Adolescent
,
Adrenal Cortex Hormones - adverse effects
2017
The onset of inflammatory bowel disease (IBD) during childhood/adolescence compromises peak bone mass acquisition and predisposes to fractures later in life. However, the structural basis for bone fragility in young adults with IBD remains unknown.MethodsOne hundred two young subjects from the Swiss IBD cohort were included. Areal bone mineral density (aBMD) at distal radius, hip, and spine as well as morphometric vertebral fractures were assessed using dual-energy x-ray absorptiometry technique. Volumetric (v)BMD, trabecular, and cortical bone microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computed tomography. Areal, vBMD, and microstructure were compared between patients with IBD and healthy matched controls (n = 389). Multiple regression analysis was used to evaluate variables associated with bone microarchitecture and fractures.ResultsClinical fractures were reported in 37 IBD subjects (mean age 23 yrs), mostly of the forearm; 5 subjects had morphometric vertebral fractures. After adjusting for age, sex, and height, tibia trabecular (Tb)vBMD, thickness, and distribution were significantly associated with fractures, whereas aBMD was not. After adjusting for aBMD, radius Tb distribution and tibia (Tb)vBMD and trabecular thickness still remained associated with fractures. Compared with healthy controls, patients with IBD had significantly lower aBMD at all sites, as well as alteration in (Tb)vBMD and trabecular microstructure at the distal radius and tibia, and these alterations were correlated with disease severity.ConclusionsYoung patients with IBD have low aBMD and altered trabecular bone microarchitecture compared with healthy controls. The latter is independently associated with fractures and may predispose increased susceptibility to fragility fractures throughout life.
Journal Article
Performance Evaluation of the FLEX Triumph X-PET Scanner Using the National Electrical Manufacturers Association NU-4 Standards
2010
The purpose of this work was to evaluate the performance characteristics of the preclinical X-PET subsystem of the FLEX Triumph PET/CT scanner based on the NU 4-2008 standards of the National Electrical Manufacturers Association (NEMA).
The performance parameters evaluated include the spatial resolution, scatter fraction, count losses and random coincidences, sensitivity, and image-quality characteristics. The PET detector array consisted of 11,520 individual bismuth germanate crystals arranged in 48 rings and 180 blocks, with an axial field of view (FOV) of 11.6 cm and a inner ring diameter of 16.5 cm. The spatial resolution was measured with a small (22)Na point source (diameter, 0.25 mm) at different radial offsets from the center. Sensitivity was calculated using the same source by stepping the source axially through the axial FOV of the scanner. Scatter fraction and counting-rate performances were determined using a mouse- and rat-sized phantom with an (18)F line source insert. The NEMA image-quality phantom and rodent imaging were also performed to access the overall imaging capabilities of the scanner.
Tangential spatial resolution in terms of full width at half maximum varied between 2.2 mm at the center of the FOV and 2.3 mm at a radial offset of 2.5 cm. The radial spatial resolution varied between 2.0 at the center and 4.4 mm at a radial offset of 2.3 cm. The peak system absolute sensitivity was 5.9% at the center of the FOV. The absolute system sensitivity was 0.67 counts/s/Bq, and the relative total system sensitivity was 73.9%. The scatter fraction for the mouse-sized phantom was 7.9%, with a peak true counting rate of 168 kilocounts per second (kcps) at 0.3 MBq/mL and a peak noise-equivalent counting rate of 106 kcps at 0.17 MBq/mL. The rat-sized phantom had a scatter fraction of 21%, with a peak true counting rate of 93 kcps at 0.034 MBq/mL and a peak noise-equivalent counting rate of 49 kcps at 0.02 MBq/mL. Recovery coefficients for the image-quality phantom ranged from 0.13 to 0.88.
The performance of the X-PET scanner based on the NEMA NU 4-2008 standards was fully characterized. The overall performance demonstrates that the X-PET system is suitable for preclinical research.
Journal Article
Adapting anatomy teaching to surgical trends: a combination of classical dissection, medical imaging, and 3D-printing technologies
2016
Purpose
Many regions worldwide report difficulties in recruiting applicants to surgery. One strategy proposed to reverse this trend consists of early exposure of medical students to the field. Against this backdrop, the present study presents an innovative approach for anatomy teaching, integrating a surgically relevant trend: 3D printing.
Methods
Whole-body computed tomography (CT) was made of two cadavers. Twelve students performed measurements and 3D reconstructions of selected anatomical structures (Osirix, Mimics). 3D printed (3DP) models were obtained (ZPrinter 310 Plus), and the students completed the analogous measurements on these replicas. Finally, classical anatomical dissection was performed and the same parameters were measured. The differences between the values obtained by the three modalities were submitted to standard statistical analysis (Wilcoxon two-tail paired test).
Results
Qualitative comparison of the digital 3D reconstructions based on the students’ manual CT segmentation and the anatomical reality showed excellent correlation. Quantitatively, the values measured on the CT images and the physical models created by 3D printing differed from those measured on the cadavers by less than 2 mm. Students were highly appreciative of the approach (CT, 3DP, cadaver). Their average satisfaction score was 5.8 on a 1–6 scale.
Conclusions
This study shows that the approach proposed can be achieved. The results obtained also show that CT-based 3D printed models are close to the authentic anatomic reality. The program allows early and interactive exposure of medical students to a surgically relevant trend—in this case 3D printing.
Journal Article
Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis
2017
Extracellular ATP is a central signaling molecule in inflammatory responses. Pannexin1 (Panx1) channels release ATP in a controlled manner and have been implicated in various inflammatory pathologies, but their role in atherogenesis remains elusive. Using atherosclerosis-susceptible mouse models with ubiquitous deletion of Panx1 (
Panx1
−/−
Apoe
−/−
) or with Cre recombinase-mediated deletion of Panx1 in endothelial cells and monocytes (
Tie2-Cre
Tg
Panx1
fl/fl
Apoe
−/−
;
Panx1
del
Apoe
−/−
), we identified a novel role for Panx1 in the lymphatic vasculature. Atherosclerotic lesion development in response to high-cholesterol diet was enhanced in
Panx1
del
Apoe
−/−
mice, pointing to an atheroprotective role for Panx1 in endothelial and/or monocytic cells. Unexpectedly, atherogenesis was not changed in mice with ubiquitous Panx1 deletion, but
Panx1
−/−
Apoe
−/−
mice displayed reduced body weight, serum cholesterol, triglycerides and free fatty acids, suggesting altered lipid metabolism in these Panx1-deficient mice. Mechanistically,
Panx1
−/−
Apoe
−/−
mice showed impairment of lymphatic vessel function with decreased drainage of interstitial fluids and reduced dietary fat absorption. Thus, the detrimental effect of Panx1 deletion in endothelial and/or monocytic cells during atherogenesis is counterbalanced by an opposite effect resulting from impaired lymphatic function in ubiquitous Panx1-deficient mice. Collectively, our findings unveil a pivotal role of Panx1 in linking lymphatic function to lipid metabolism and atherosclerotic plaque development.
Journal Article