New insights into patterns of integration in the femur and pelvis among catarrhines.

OBJECTIVES: Integration reflects the level of coordinated variation of the phenotype. The integration of postcranial elements can be studied from a functional perspective, especially with regards to locomotion. This study investigates the link between locomotion, femoral structural properties, and femur-pelvis complex morphology. MATERIALS AND METHODS: We measured (1) morphological integration between femoral and pelvic morphologies using geometric morphometrics, and (2) covariation between femoral/pelvic morphologies and femoral diaphyseal cross-sectional properties, which we defined as morpho-structural integration. Morphological and morpho-structural integration patterns were measured among humans (n = 19), chimpanzees and bonobos (n = 16), and baboons (n = 14), whose locomotion are distinct. RESULTS: Baboons show the highest magnitude of morphological integration and the lowest of morpho-structural integration. Chimpanzees and bonobos show intermediate magnitude of morphological and morpho-structural integration. Yet, body size seems to have a considerable influence on both integration patterns, limiting the interpretations. Finally, humans present the lowest morphological integration and the highest morpho-structural integration between femoral morphology and structural properties but not between pelvic morphology and femur. DISCUSSION: Morphological and morpho-structural integration depict distinct strategies among the samples. A strong morphological integration among baboon's femur-pelvis module might highlight evidence for long-term adaptation to quadrupedalism. In humans, it is likely that distinct selective pressures associated with the respective function of the pelvis and the femur tend to decrease morphological integration. Conversely, high mechanical loading on the hindlimbs during bipedal locomotion might result in specific combination of structural and morphological features within the femur.

Predicting primate tongue morphology based on geometrical skull matching. A first step towards an application on fossil hominins.

As part of a long-term research project aiming at generating a biomechanical model of a fossil human tongue from a carefully designed 3D Finite Element mesh of a living human tongue, we present a computer-based method that optimally registers 3D CT images of the head and neck of the living human into similar images of another primate. We quantitatively evaluate the method on a baboon. The method generates a geometric deformation field which is used to build up a 3D Finite Element mesh of the baboon tongue. In order to assess the method's ability to generate a realistic tongue from bony structure information alone, as would be the case for fossil humans, its performance is evaluated and compared under two conditions in which different anatomical information is available: (1) combined information from soft-tissue and bony structures; (2) information from bony structures alone. An Uncertainty Quantification method is used to evaluate the sensitivity of the transformation to two crucial parameters, namely the resolution of the transformation grid and the weight of a smoothness constraint applied to the transformation, and to determine the best possible meshes. In both conditions the baboon tongue morphology is realistically predicted, evidencing that bony structures alone provide enough relevant information to generate soft tissue.

Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis.

APJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ. Apelin-F13A-NODAGA (AP747) was synthesized and radiolabeled with gallium-68 ([68Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [67Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [68Ga]Ga-AP747 for APJ was evaluated in vitro by autoradiography and in vivo by small animal PET/CT in both colon adenocarcinoma mouse model and Matrigel plug mouse model. Dynamic of [68Ga]Ga-AP747 PET/CT biodistributions was realized on healthy mice and pigs for two hours, and quantification of signal in organs showed a suitable pharmacokinetic profile for PET imaging, largely excreted by urinary route. Matrigel mice and hindlimb ischemic mice were submitted to a 21-day longitudinal follow-up with [68Ga]Ga-AP747 and [68Ga]Ga-RGD2 small animal PET/CT. [68Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [68Ga]Ga-RGD2. Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [68Ga]Ga-AP747 PET signal was more than twice higher than that of [68Ga]Ga-RGD2 on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [68Ga]Ga-AP747 PET signal on day 7 and late hindlimb perfusion on day 21. We developed a new PET radiotracer that specifically binds to APJ, [68Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [68Ga]Ga-RGD2.

FairEmbo Concept for Postpartum Hemorrhage: Evaluation of the Efficacy of Suture Fragment Compared with Gelatin Sponge Torpedo Embolization in a Post-Gravid Swine Model.

BACKGROUND: Postpartum hemorrhage is the leading cause of maternal mortality in emerging countries. This study aims to evaluate the effectiveness and safety of uterine artery embolization (UAE) using suture fragment (FairEmbo concept) in a swine model. METHODS: Seven female swine uteri were embolized. The left uterine artery was embolized with 1 cm fragments of absorbable suture (Optime® 0), and with gelatin sponge torpedoes for the contralateral side for comparison. The embolization effectiveness and the time for arterial recanalization with digital subtraction angiography (DSA) controls at D0, D7, and M1, were evaluated. Follow-up protocol also included clinical monitoring and macroscopical analyses at M1. A Mann-Whitney test (significance at P 0.05) was used for statistics. RESULTS: A technical success was obtained for the seven arteries on each side, with no off-target embolization. The procedure time (10 min versus 3.7 min) and number of fragments (13.8 versus 5.7) required for complete occlusion were significantly greater in the FairEmbo group. All arteries were repermeabilized at M1. No necrosis was macroscopically visible at harvest at M1. CONCLUSION: This experimental study suggests that UAE with SBM FairEmbo method is feasible, safe, and effective in comparison with gelatin sponge procedure.

Evaluation of Multiple Embolic Agents for Embolization of the Superior Rectal Artery in an Animal Model.

OBJECTIVE: To prospectively compare the safety of transcatheter embolization of superior rectal arteries in healthy pigs with multiple agents such as coils, spheres and liquids. MATERIALS AND METHODS: Nine adult domestic pigs (three males, mean weight: 60 kg [50-70]) were randomly assigned to the embolization group: copolymer of ethylene vinyl alcohol (EVOH)-Onyx® (group 1, n = 3), microspheres 500 µ (group 2, n = 3), 2-mm micro-coils (group 3, n = 3). After a selective angiogram has been acquired, the embolic agent was infused at the distal part of rectal arteries. An angio-CT was performed before and after each embolization. After one week, angiography was repeated prior to euthanasia. At necropsy, the anorectal juncture was removed for histopathologic examination. RESULTS: At necropsy, 100% of animals embolized with Onyx developed a significant necrosis zone of the distal part of the rectum. Histological examination revealed a mural infarction. For the micro-coil and microsphere groups, gross examination of the intestines did not reveal any evidence of ischaemia. The coils were found in the distal arterial vasculature of the meso-rectum, allowing a downstream revascularization by collaterals. The microspheres and onyx in the rectal wall, more distally. CONCLUSION: Microspheres appear to induce fewer histologic complications than the liquid embolic agent and provide a more distal occlusion than micro-coils. These results suggest that, for superior rectal artery embolization, a super-selective embolization using spheres in human clinical conditions should be more effective and as safe as coil embolization. EVOH might be an unsafe embolization agent for haemorrhoids.

Comparison of a New 68Ga-Radiolabelled PET Imaging Agent sCD146 and RGD Peptide for In Vivo Evaluation of Angiogenesis in Mouse Model of Myocardial Infarction.

Ischemic vascular diseases are associated with elevated tissue expression of angiomotin (AMOT), a promising molecular target for PET imaging. On that basis, we developed an AMOT-targeting radiotracer, 68Ga-sCD146 and performed the first in vivo evaluation on a myocardial infarction mice model and then, compared AMOT expression and αvß3-integrin expression with 68Ga-sCD146 and 68Ga-RGD2 imaging. After myocardial infarction (MI) induced by permanent ligation of the left anterior descending coronary artery, myocardial perfusion was evaluated by Doppler ultrasound and by 18F-FDG PET imaging. 68Ga-sCD146 and 68Ga-RGD2 PET imaging were performed. In myocardial infarction model, heart-to-muscle ratio of 68Ga-sCD146 imaging showed a significantly higher radiotracer uptake in the infarcted area of MI animals than in sham (* p = 0.04). Interestingly, we also observed significant correlations between 68Ga-sCD146 imaging and delayed residual perfusion assessed by 18F-FDG (* p = 0.04), with lowest tissue fibrosis assessed by histological staining (* p = 0.04) and with functional recovery assessed by ultrasound imaging (** p = 0.01). 68Ga-sCD146 demonstrated an increase in AMOT expression after MI. Altogether, significant correlations of early post-ischemic 68Ga-sCD146 uptake with late heart perfusion, lower tissue fibrosis and better functional recovery, make 68Ga-sCD146 a promising radiotracer for tissue angiogenesis assessment after MI.

Percutaneous lung and liver CT-guided ablation on swine model using microwave ablation to determine ablation size for clinical practice.

PURPOSE: Microwave ablation (MWA) provides an effective treatment of lung and liver tumors but suffers from a lack of reproducibility of ablation size among currently available technologies. In-vitro evaluations are far removed from clinical practices because of uninfused tissue. This study is in-vivo preclinical testing of a new MWA system on swine lungs and liver. MATERIALS AND METHODS: All ablations were performed under CT guidance and multiple algorithms were tested with a power of 50, 75, and 100 W for durations of 3, 5, 8, 10, and 15 min. A 3 D-evaluation of the ablation zone was carried out using enhanced-CT. The sphericity index, coefficients of variation, and energy efficiency (which corresponds to the volume yield according to the power supplied) were calculated. RESULTS: Fifty liver and 48 lung ablations were performed in 17 swine. The sphericity index varies from 0.50 to 0.80 for liver ablations and from 0.40 to 0.69 for lung ablations. The coefficient of variation was below 15% for 4/5 and 4/8 protocols for lung and liver ablations, respectively. The energy efficiency seems to decrease with the duration of the ablation from 0.60 × 10-3 cm3/J (75 W, 3 min) to 0.26 × 10-3 cm3/J (100 W, 15 min) in the liver and from 0.57 × 10-3 cm3/J (50 W, 10 min) to 0.42 × 10-3 cm3/J (100 W, 12 min) in the lungs. CONCLUSION: A shorter treatment time provides the best energy efficiency, and the best reproducibility is obtained for a 10 min treatment duration. The system tested provides an interesting reproducibility in both lung and liver measurements. Our results may help interventional radiologists in the optimal selection of treatment parameters.

Description of morphological evolution of lung tumors treated by percutaneous radiofrequency ablation: long term follow-up of 100 lesions with chest CT.

PURPOSE: Radiofrequency ablation (RFA) is a safe and effective minimally invasive treatment for pulmonary tumors. Patterns on chest computed tomography (CT) after RFA are classified into five types; however, the follow-up has not been fully described. The objectives of this study were to describe (1) the CT pattern 3 years after RFA and (2) its evolution over 7 years. MATERIALS AND METHODS: Lesions treated with RFA between 2009 and 2017 and with ≥3 years of follow-up CT data were included. Lesions with local recurrences were excluded from the study. The morphology of the ablation zone was classified as nodular, fibrotic, atelectatic, cavitary, and disappeared. Other initial anatomical parameters were recorded. Kruskal-Wallis or Chi-square tests were used to compare the groups. RESULTS: One hundred lung RFA scars were included, and a retrospective longitudinal study was performed. Three years after RFA, nodular, fibrotic, atelectatic, and cavitary scars, and disappearance were observed in 49%, 36%, 5%, 3%, and 6% of the scars, respectively. Evolution over 7 years showed that the fibrosis, atelectasis, and disappearance remained stable over time, whereas 28% of nodular scars evolved into fibrotic scars. Additionally, 45% of cavitary scars evolved into nodular scars. Pleural contact was associated with disappearance, and the use of a 20-mm needle was associated with atelectasis. CONCLUSION: Follow-up after RFA showed that fibrosis, disappearance, and atelectasis remained stable over time. Nodular scars could evolve into fibrotic scars, and cavitary scars could evolve into nodular scars.

Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study.

Succinate influences angiogenesis and neovascularization via a hormonelike effect on G-protein-coupled receptor 91 (GPR91). This effect has been demonstrated in the pathophysiology of diabetic retinopathy and rheumatoid arthritis. To evaluate whether succinate can play a role in acute peripheral ischemia, a preclinical study was conducted with ischemic mice treated with succinate or PBS and evaluated by imaging. Acute ischemia was followed by an increased in GPR91 expression in the ischemic muscle. As assessed with LASER-Doppler, succinate treatment resulted in an earlier and more intense reperfusion of the ischemic hindlimb compared to the control group (* p = 0.0189). A microPET study using a radiolabeled integrin ligand ([68Ga]Ga-RGD2) showed an earlier angiogenic activation in the succinate arm compared to control mice (* p = 0.020) with a prolonged effect. Additionally, clinical recovery following ischemia was better in the succinate group. In conclusion, succinate injection promotes earlier angiogenesis after ischemia, resulting in a more effective revascularization and subsequently a better functional recovery.

FairEmbo Concept for Arterial Embolizations: In Vivo Feasibility and Safety Study with Suture-Based Microparticles Compared with Microspheres.

PURPOSE: Microspheres are effective embolic agents, especially for the management of bleeding and oncologic lesions. The first FairEmbo study reported the effectiveness of embolization using suture fragments. The effectiveness and safety of arterial embolization with suture-based microparticles (SBM) were assessed in a swine model. MATERIALS AND METHODS: In this ethical-approved animal study, a polar artery in each kidney was embolized in four swine: one side with hand-cut non-absorbable SBM (Flexocrin 2®) and the contralateral side with Embozene® 900 for comparison. Swine were followed for 3 months (M3) to evaluate the effectiveness and the safety of SBM. Follow-up protocol included clinical monitoring, computed tomography (CT) control and digital subtraction angiography (DSA), followed by histological analyses. The SBM confection parameters were evaluated by automatic microscopic sizer. RStudio software and Mann-Whitney test (significance at P < 0.05) were used for statistics. RESULTS: The average size of SBM was 1002 µm (SD = 258). All targets were effectively embolized by SBM with an angiogram defect estimated at 45.6% (95% CI [35.9-55.2]), compared to 40.5% (95% CI [30.6-55.5]) for Embozene® group (P = 0.342). The average duration of SBM embolization procedure was significantly increased compared to Embozene® embolization (1202 s versus 222 s, P = 0.029). There were no statistical differences in M3 DSA and CT for SBM and Embozene®, with persistence of partial arterial occlusion and atrophic embolized area. No postoperative complications were observed on clinical and CT controls. CONCLUSION: This experimental study suggests that embolization with SBM is feasible, safe and effective in short- and medium-term follow-up as compared to microspheres.

Renal SPECT/CT with 99mTc-dimercaptosuccinic acid is a non-invasive predictive marker for the development of interstitial fibrosis in a rat model of renal insufficiency.

BACKGROUND: Chronic kidney disease (CKD) increases cardiovascular risk and mortality. Renal fibrosis plays a major role in the progression of CKD but, to date, histology remains the gold standard to assess fibrosis. Non-invasive techniques are needed to assess renal parenchymal impairment and to perform the longitudinal evaluation of renal structure. Thus we evaluated renal isotopic imaging by single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) to monitor renal impairment during renal insufficiency in rats. METHODS: Renal insufficiency was induced by an adenine-rich diet (ARD) at 0.25 and 0.5% for 28 days. Renal dysfunction was evaluated by assaying biochemical markers and renal histology. Renal parenchymal impairment was assessed by SPECT/CT isotopic imaging with 99mTc-DMSA on Days 0, 7, 14, 21, 28, 35 and 49. RESULTS: Compared with controls, ARD rats developed renal dysfunction characterized by increased serum creatinine and blood urea nitrogen, fibrosis and tubulointerstitial damage in the kidneys, with a dose-dependent effect of the adenine concentration. 99mTc-DMSA SPECT-CT imaging showed a significant decrease in renal uptake over time in 0.25 and 0.5% ARD rats compared with control rats (P = 0.011 and P = 0.0004, respectively). 99mTc-DMSA uptake on Day 28 was significantly inversely correlated with Sirius red staining evaluated on Day 49 (r = 0.89, P < 0.0001, R2 = 0.67). CONCLUSIONS: 99mTc-DMSA renal scintigraphy allows a longitudinal follow-up of risk of renal fibrosis in rats. We found that the reduction of renal parenchyma in ARD rats is inversely proportional to newly formed fibrous tissue in the kidney. Our results suggest that 99mTc-DMSA renal scintigraphy may be a useful non-invasive prognostic marker of the development of renal fibrosis in animals and should be tested in humans.

Combination of Alcohol and EVOH as a New Embolic Agent: Midterm Tissue and Inflammatory Effects in a Swine Model.

OBJECTIVE: To evaluate the vascular occlusion and midterm tissue toxicity properties of a combination of ethylene-vinyl alcohol (EVOH) (Squid 18®) (75%) and alcohol (25%)-Alco-Squid 18-in a swine model. MATERIALS AND METHODS: Alco-Squid 18 (75% Squid 18® mixed with 25% alcohol) (AS18) was compared to embolization with 96% alcohol alone and to embolization with Squid 18® (S18®) alone. An arteriovenous malformation (AVM) model was created in group 1 (n = 2). Each AVM model was then embolized with AS18 or S18® alone with evaluation of a ratio between the volume of embolic agent divided by the volume of the AVM (evaluated by CT). For group 2 (n = 5), each agent was tested on three different kidneys (upper pole kidney artery). Pre- and postinterventional CTs, angiographies, blood alcohol content dosages, and histological studies (3 months postintervention) were performed. RESULTS: AS18 has better distal distribution than S18® alone, both in the kidneys (mean capsule-S18® distance: 3.9 mm (±0.23) and mean capsule-AS18 distance: 2.3 mm (±0.11) (p=0.029) and in the AVM model. Histological exploration found a higher rate of tubular necrosis with AS18 compared with S18® alone and alcohol alone (3.78 ± 0.44 compared to 2.33 ± 1.22 (p = 0.012) and 1.22 ± 0.67 (p < 0 .0001)). The blood alcohol content was negligible in all cases. CONCLUSION: AS18 can suggest a better distal sclerotic and embolic character as compared with S18® alone without systemic toxicity.

Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal Dysfunction.

BACKGROUND: Uremic toxicity may play a role in the elevated risk of developing cognitive impairment found among patients with CKD. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AhR), which is widely expressed in the central nervous system and which we previously identified as the receptor of indoxyl sulfate in endothelial cells. METHODS: To characterize involvement of uremic toxins in cerebral and neurobehavioral abnormalities in three rat models of CKD, we induced CKD in rats by an adenine-rich diet or by 5/6 nephrectomy; we also used AhR-/- knockout mice overloaded with indoxyl sulfate in drinking water. We assessed neurologic deficits by neurobehavioral tests and blood-brain barrier disruption by SPECT/CT imaging after injection of 99mTc-DTPA, an imaging marker of blood-brain barrier permeability. RESULTS: In CKD rats, we found cognitive impairment in the novel object recognition test, the object location task, and social memory tests and an increase of blood-brain barrier permeability associated with renal dysfunction. We found a significant correlation between 99mTc-DTPA content in brain and both the discrimination index in the novel object recognition test and indoxyl sulfate concentrations in serum. When we added indoxyl sulfate to the drinking water of rats fed an adenine-rich diet, we found an increase in indoxyl sulfate concentrations in serum associated with a stronger impairment in cognition and a higher permeability of the blood-brain barrier. In addition, non-CKD AhR-/- knockout mice were protected against indoxyl sulfate-induced blood-brain barrier disruption and cognitive impairment. CONCLUSIONS: AhR activation by indoxyl sulfate, a uremic toxin, leads to blood-brain barrier disruption associated with cognitive impairment in animal models of CKD.

Feasibility and Efficiency of Sutureless End Enterostomy by Means of a 3D-Printed Device in a Porcine Model.

Objective. The aim of this study is to present a 3-dimensional (3D)-printed device to simply perform abdominal enterostomy and colostomy. Summary Background Data. Enterostomy and colostomy are frequently performed during abdominal surgery. 3D-printed devices may permit the creation of enterostomy easily. Methods. The device was designed by means of a CAD (computer-aided design) software, Rhinoceros 6 by MC Neel, and manufactured using 3D printers, Factory 2.0 by Omni 3D and Raise 3D N2 Dual Plus by Raise 3D. Colostomy was scheduled on a human cadaver and on 6 Pietrain pigs to test the device and the surgical technique. Results. The test on the cadaver showed that the application of the device was easy. Test on porcine models confirmed that the application of the device was also easy on the living model. The average duration of the surgical procedure was 32 minutes (25-40 minutes). For the female pigs, return to full oral diet and recovery of a normal bowel function was observed at postoperative day 2. The device fell by itself on average on the third day. Until day 10, when euthanasia was practiced, the stoma mucosa had a good coloration indicating a perfect viability of tissues. No complications were observed. Conclusions. This is the first study that describes the use of a 3D-printed device in abdominal surgery. End-type colostomy using a 3D-printed device can be safely and easily performed in an experimental porcine model, without postoperative complications. Further studies are needed to evaluate its utility in the clinical setting.

Determination of optical parameters of the porcine eye and development of a simulated model.

The eye is a very sophisticated system of optical elements for the preeminent sense of vision. In recent years, the number of laser surgery to correct the optical aberration such as myopia or astigmatism has significantly increased. Consequently, improving the knowledge related to the interactions of light with the eye is very important in order to enhance the efficiency of the surgery. For this reason, a complete optical characterization of the porcine eye is presented in this study. Kubelka-Munk and Inverse Adding-Doubling methods were applied to spectroscopy measurement to determine the absorption and scattering coefficients. Furthermore, the refractive index has been measured by ellipsometry. The different parameters were obtained for the cornea, lens, vitreous humor, sclera, iris, choroids and eyelid in the visible and infrared region. Thereafter, the results are implemented in a COMSOL Multiphysics® software to create an eye model. This model gives a better understanding of the propagation of light in the eye by adding optical parts such as the iris, the sclera or the ciliary bodies. Two simulations show the propagation of light from the cornea to the retina but also from the sclera to the retina. This last possibility provides a better understanding of light propagation during eye laser surgery such as, for example, transscleral cyclophotocoagulation. Figure: Eye simulation models allow the development of new laser treatments in a simple and safe way for patients. To this purpose, the creation of an eye simulated model based on optical parameters obtained from experimental data is presented in this study. This model will facilitate the understanding of the light propagation inside the porcine eye.

Early prediction of revascularisation by angiomotin-targeting positron emission tomography.

This study aimed to develop a PET imaging agent of angiomotin (AMOT) expression, a potential biomarker of functional tissue regeneration in post-ischaemic conditions. Methods: Hindlimb ischaemia was induced by ligature and resection of the right femoral artery in mice, and clinical score and limb perfusion were evaluated up to 30 days after surgery. AMOT expression was evaluated by histology and Western blot analysis. NODAGA-conjugates of AMOT ligand, sCD146, were designed, synthesised and radiolabelled with gallium-68. 68Ga-sCD146 microPET/CT imaging was performed from day 1 to day 30 after ischaemia. 68Ga-sCD146 specificity for AMOT was evaluated by autoradiography. Results: Immunohistochemistry showed a significant endothelial overexpression of AMOT from day 5 up to day 10 in the ischaemic hindlimb. 68Ga-sCD146 PET signal intensity correlated significantly with AMOT immunohistochemistry evaluation. 68Ga-sCD146 PET imaging showed a significant uptake in the ischaemic hindlimb from day 2 to day 15, peaking on day 5 (ipsi/contralateral ratio = 2.4 ± 1.3, P = 0.0005) and significantly decreased after pharmacological blocking (62.57 ± 11% decrease in PET signal P = 0.032). Finally, we observed a significant correlation between day 5 68Ga-sCD146 PET signal intensity and clinical recovery (day 28) or hindlimb perfusion recovery (day 30). Conclusions: This work reports for the first time an early and sustained increase in AMOT expression after hindlimb ischaemia in mice. We therefore developed an AMOT-targeting imaging agent, 68Ga-sCD146, and showed its specific uptake up to 21 days after ischaemic hindlimb using microPET imaging. Correlation of early post-ischaemic PET signal with both delayed perfusion recovery and clinical outcome allows us to postulate that 68Ga-sCD146 represents a promising radiotracer for tissue angiogenesis assessment.

Morbidity and mortality of hepatic right lobe living donors: systematic review and perspectives.

BACKGROUND AND AIMS: The main restriction in the development of adult-adult Living Donor Liver Transplantation (LDLT) is the risk of morbidity and mortality for donors, which raises ethical questions. The objectives of this study are to review published studies dealing with morbidity and mortality in LDLT and to identify the proposed management and strategies for preventing donor mortality and morbidity in LDLT. METHODS: The Medline database was searched from 2000 to 2017 using the MeSH terms "liver transplantation" and "morbidity" or "mortality" in combination with keywords "living donor liver transplantation". RESULTS: Among the 382 articles obtained, 43 articles were relevant for morbidity, 15 for mortality and 6 for both morbidity and mortality. Twenty-three papers reported donor deaths. The major cause of death was sepsis (30%). Morbidity ranged from 10% to 78.3% depending on the studies. CONCLUSIONS: The living donors' morbidity and mortality is high, currently representing the main restriction in the development of LDLT. Some promising techniques, such as the donor portal vein flow modulation could lead to the further development of LDLT.

Portal vein stenosis preconditioning of living donor liver in swine: early mechanisms of liver regeneration and gain of hepatic functional mass.

To reduce the morbidity and mortality risk for the donor in living donor liver transplantation (LDLT), we previously identified 20% left portal vein (LPV) stenosis as an effective preconditioning method to induce cell proliferation in the contralateral lobe without downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours after preconditioning and investigate the changes in liver volume and function. Fourteen pigs were used this study. Five pigs were used to study the genetic, cellular and molecular mechanisms set up in the early hours following the establishment of our preconditioning. The remaining nine pigs were equally divided into three groups: sham-operated animals, 20% LPV stenosis, and 100% LPV stenosis. Volumetric scanning and 99 mTc-Mebrofenin hepatobiliary scintigraphy were performed before preconditioning and 14 days after to study morphological and functional changes in the liver. We demonstrated that liver regeneration triggered by 20% LPV stenosis in the contralateral lobe involves TNF-α, IL-6, and inducible nitric oxide synthase 2 by means of STAT3 and hepatocyte growth factor. We confirmed that our preconditioning was responsible for an increase in the total liver volume. Finally, we demonstrated that this volumetric gain was associated with an increase in hepatic functional capacity. NEW & NOTEWORTHY We describe a new preconditioning method for major hepatectomy that is applicable to hepatectomy for donation. We identified 20% left portal vein stenosis as effective preconditioning that is capable of inducing cell proliferation in the contralateral lobe without the downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours following preconditioning, and we confirm that 20% left portal vein stenosis is responsible for an increase in the functional capacity and total liver volume in a porcine model.

Erythropoietin Pretreatment of Transplanted Endothelial Colony-Forming Cells Enhances Recovery in a Cerebral Ischemia Model by Increasing Their Homing Ability: A SPECT/CT Study.

Endothelial colony-forming cells (ECFCs) are promising candidates for cell therapy of ischemic diseases, as less than 10% of patients with an ischemic stroke are eligible for thrombolysis. We previously reported that erythropoietin priming of ECFCs increased their in vitro and in vivo angiogenic properties in mice with hindlimb ischemia. The present study used SPECT/CT to evaluate whether priming of ECFCs with erythropoietin could enhance their homing to the ischemic site after transient middle cerebral artery occlusion (MCAO) followed by reperfusion in rats and potentiate their protective or regenerative effect on blood-brain barrier (BBB) disruption, cerebral apoptosis, and cerebral blood flow (CBF). METHODS: Rats underwent a 1-h MCAO followed by reperfusion and then 1 d after MCAO received an intravenous injection of either PBS (control, n = 10), PBS-primed ECFCs (ECFCPBS, n = 13), or erythropoietin-primed ECFCs (ECFCEPO, n = 10). ECFC homing and the effect on BBB disruption, cerebral apoptosis, and CBF were evaluated by SPECT/CT up to 14 d after MCAO. The results were expressed as median ± interquartile range for ipsilateral-to-contralateral ratio of the activity in middle cerebral artery-vascularized territories in each hemisphere. Histologic evaluation of neuronal survival and astrocytic proliferation was performed on day 14. RESULTS: Erythropoietin priming increased homing of ECFCs to the ischemic hemisphere (ECFCPBS, 111.0% ± 16.0%; ECFCEPO, 146.5% ± 13.3%). BBB disruption was significantly reduced (control, 387% ± 153%; ECFCPBS, 151% ± 46% [P < 0.05]; ECFCEPO, 112% ± 9% [P < 0.001]) and correlated negatively with ECFC homing (Pearson r = -0.6930, P = 0.0002). Cerebral apoptosis was significantly reduced (control, 161% ± 10%; ECFCPBS, 141% ± 9% [P < 0.05]; ECFCEPO,118% ± 5% [P < 0.001]) and correlated negatively with ECFC homing (r = -0.7251, P < 0.0001). CBF was significantly restored with ECFCs and almost totally so with erythropoietin priming (control, 72% ± 2%; ECFCPBS, 90% ± 4% [P < 0.01]; ECFCEPO, 99% ± 4% [P < 0.001]) and correlated positively with ECFC homing (r = 0.7348, P < 0.0001). Immunoblocking against the CD146 receptor on ECFCs highlighted its notable role in ECFC homing with erythropoietin priming (ECFCEPO, 147% ± 14%, n = 4; ECFCEPO with antibody against CD146, 101% ± 12%, n = 4 [P < 0.05]). CONCLUSION: Priming with erythropoietin before cell transplantation is an efficient strategy to amplify the migratory and engraftment capacities of ECFCs and their beneficial impact on BBB disruption, apoptosis, and CBF.

A nanoengineered embolic agent for precise radiofrequency ablation.

The purpose of the work is to investigate whether the electromagnetic properties of multi-walled carbon nanotubes (MWCNT) in the presence of radiofrequency (RF) energy is (1) safe, and (2) improves the precision of the therapeutic efficiency of the RF-ablation (RFA) procedure. An in vitro phantom was created for evaluating temperature near RF treated nanotubes. For the in vivo study, three baboons and six pigs were submitted for RFA procedure in superior/inferior kidney poles embolized with a non-adherent, lipophilic embolic agent (marsembol) with or without MWCNT. Tissue damage in the surrounding kill zone was assayed through caspase-3 activation. The in vitro results showed marked heat increase only in the region of the nanotubes. In vivo, necrosis/ischemic damage resulted from RFA therapy alone, RFA plus marsembol only. In marsembol + MWCNT condition, dramatic disruption of cell membranes and sub-cellular organelles was found whereas the nuclear membranes and basal cell membranes remained largely intact. The marsembol vaporized under RFA and tissue fluid filled the space. This caused the MWCNT to cluster within the new aqueous environment. RFA plus marsembol + MWCNT created a well-defined demarcation between healthy and apoptotic cells as evidenced by a marked reduction of caspase-3 expression. By contrast, there was a much less defined ablation zone in the absence of MWCNT. In conclusion, the combination of RFA plus marsembol + MWCNT embolization delineated the kill zone in vitro and in vivo. We demonstrate that MWCNTs remain in the ablation region thus minimizing their migration to the systemic circulation.