Quantitative MRI for brain lesion diagnosis in dogs and cats: A comprehensive overview.

MRI is widely used for the detection and characterization of brain lesions. There is a growing interest in the potential benefits of quantitative MRI (qMRI) in veterinary brain lesion diagnosis. Yet, the use of data processing tools in the veterinary field is not as democratized as for the diagnosis of human brain pathologies. Several reviews have addressed the characterization of brain lesions in cats and dogs. None of them is specifically focused on quantitative MRI data processing techniques for the diagnosis of brain lesions in the veterinary field. This paper aims to provide an overview of the evolution of qMRI on cats and dogs both in the clinical and preclinical fields. We analyze the achievements in the field as well as the remaining challenges in the diffusion of data processing tools for veterinary brain lesions characterization.

Can magnetisation transfer magnetic resonance imaging help for the follow-up of synthetic hernia composite meshes fate? A pilot study.

PURPOSE: This study aims at evaluating the non-invasive Magnetic Resonance Imaging (MRI) technic to visualize a synthetic composite hernia mesh using a rodent model and to document the integration of this device over 4 months. METHODS: Uncoated polyethylene terephthalate mesh and synthetic composite mesh-faced on the visceral side with a chemically engineered layer of copolymer of glycolide, caprolactone, trimethylene carbonate, and lactide to minimize tissue attachment-were placed intraperitoneally in rats, facing the caecum previously scraped to promote petechial bleeding and subsequent adhesions. Meshes fate follow-up was performed 4, 10, and 16-weeks post-implantation using a rodent dedicated high field MRI. Magnetization transfer (MT) images were acquired, associated with pneumoperitonealMRI performed after intraperitoneal injection of 8 mL gas to induce mechanical stress on the abdominal wall. RESULTS: Uncoated meshes were clearly visible using both T2-weighted and MT imaging during the whole study while composite meshes conspicuity was not so evident on T2-weighted MRI and could be improved using MT imaging. Adhesions and collagen infiltration were massive for the uncoated meshes as expected. On the contrary, composite meshes showed very limited adhesion, and, if any, occurring at the edge of the mesh, starting at the fixation points. CONCLUSIONS: Magnetization transfer imaging allows to detect mesh integration and, associated with pneumoperitoneum, was able to probe the effective minimizing effect of the synthetic polymeric barrier on visceral attachments. However, magnetization transfer imaging could not unambiguously allow the visualization of the mesh through the polymeric barrier.

Tissue oxygenation mapping by combined chemical shift and T1 magnetic resonance imaging.

PURPOSE: To propose a method for determining tissue oxygenation via the measurement of fat T1 . The method is based on a 2D fat/water chemical shift-encoded and T1 -weighted acquisition. THEORY AND METHODS: A 2D data set was acquired with a fast spin echo sequence with several echo asymmetries and repetition times, wherein one dimension is related to the fat/water phase modulation and the other to the T1 saturation recovery. A joint magnitude-based process of phase modulation and T1 evolution allowed for the collection of the fat fraction and T1 maps with resolved fat or water dominance ambiguity while avoiding the phased error problem. RESULTS: In vitro imaging allowed for the attribution of fat content for different water/oil emulsions that demonstrated longitudinal relaxation rate (R1 ) sensitivity to the oxygenated emulsion environment. The fat R1 values were subsequently compared to reference values, which were measured using low receiver bandwidth acquisition to enhance water and fat signal separations. In vivo feasibility of tissue oxygenation assessment was demonstrated by investigating interscapular brown adipose tissue modifications during an air/carbogen challenge in rats. CONCLUSION: The proposed method offers a precise and robust estimate of tissue oxygenation illustrated by the method's ability to detect-brown adipose tissue oxygenation modifications. Magn Reson Med 79:1981-1991, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Imaging visceral adhesion to polymeric mesh using pneumoperitoneal-MRI in an experimental rat model.

BACKGROUND: Intraperitoneal mesh implantation is often associated with formation of adhesion to the mesh. This experimental study examines the potential of minimally invasive pneumoperitoneal-MRI to assess these adhesions in a preclinical context. METHODS: Uncoated polyethylene terephthalate meshes were placed intraperitoneally in rats, in regard to the caecum previously scraped to promote petechial bleeding and subsequent adhesions. Examinations were performed 2-weeks post mesh implantation using a rodent dedicated high field MRI. Respiratory-triggered T2-weighted images were acquired prior to and after intraperitoneal injection of ~8-10 mL gas to induce a mechanical stress on the abdominal wall. RESULTS: Adhesions are occasionally seen in sham-operated rats as opposed to rats receiving polyethylene terephthalate meshes. On high-resolution images, meshes can be detected due to their characteristic net shape. However, evidence of adherence is only found if intraperitoneal gas injection is performed, when a ~1-cm elevation of the abdominal wall is observed. When adherence occurs between the mesh and the caecum, the latter remains in contact with the wall. Looser adherences between visceral tissue and meshes are also observed. CONCLUSIONS: T2-weighted pneumoperitoneal-MRI is a powerful tool for assessing adherence after intraperitoneal mesh implantation. According to the mini-invasive procedure adopted here, this approach may allow a temporal follow-up of adherence fate.

Early postsurgical visualization of composite mesh used in ventral hernia repair by amide proton transfer MRI.

PURPOSE: The feasibility of noninvasive visualization of composite meshes used in ventral hernia repair by amide-proton transfer magnetic resonance imaging (APT-MRI) was explored. METHODS: Magnetization transfer asymmetry ratio images of composite meshes were obtained in vitro and in vivo from fast-spin echo acquisitions with frequency saturation offsets of ±3.5 ppm with respect to water frequency and no saturation. Three rats were assessed with APT-MRI each week for 1 month after the intraperitoneal implantation of two meshes, one on each side of the incision. One mesh was coated with collagen and the other was not. RESULTS: In vitro, meshes were delineated with APT-MRI as a thin continuous linear hypersignal located on one side of the mesh. Unlike collagen-free meshes, collagen-coated meshes were easily identified in vivo with APT-MRI during the first 3 weeks postimplantation. The composite meshes magnetization transfer asymmetry ratio (8.7 ± 2.8%) were significantly different from the muscle magnetization transfer asymmetry ratio value (-0.9 ± 1.6%). After a month, the mesh value dropped down to 1.1 ± 3.9%. Muscle and mesh magnetization transfer asymmetry ratio values were not significantly different and mesh conspicuity was no longer possible. CONCLUSION: The results suggest that APT-MRI is a promising technique for noninvasive, early postsurgical visualization of composite meshes used in ventral hernia repair.

Diversely substituted poly(N-vinyl amide) derivatives towards non-toxic, stealth and pH-responsive lipid nanocapsules.

Surface modification of lipid nanocapsules (LNC) is necessary to impart stealth properties to these drug carriers and enhance their accumulation into the tumor microenvironment. While pegylation is commonly used to prolong the circulation time of LNC, the increased presence of anti-PEG antibodies in the human population and the internalization issues associated to the PEG shell are strong incentives to search alternatives. This work describes the development of amphiphilic poly(N-vinyl amide)-based (co)polymers, including pH-responsive ones, and their use as LNC modifiers towards improved drug delivery systems. RAFT polymerization gave access to a series of LNC modifiers composed of poly(N-methyl-N-vinyl acetamide), poly(N-vinyl pyrrolidone) or pH-responsive vinylimidazole-based sequence bearing a variety of lipophilic end-groups, namely octadecyl, dioctadecyl or phospholipid groups, for anchoring to the LNC. Decoration of the LNC with these families of poly(N-vinyl amide) derivatives was achieved via both post-insertion and per-formulation methods. This offered valuable and non-toxic LNC protection from opsonization by complement activation, emphasized the benefit of dioctadecyl in the per-formulation approach and highlighted the great potential of poly(N-methyl-N-vinyl acetamide) as PEG alternative. Moreover, incorporation of imidazole moieties in the shell of the carrier imparted pH-responsiveness to the LNC likely to increase the cellular uptake in the acidic tumor microenvironment, opening up new possibilities in the field of active targeting.

Experimental models of disseminated scedosporiosis with cerebral involvement.

Scedosporium apiospermum is a soil fungus which can cause severe and often fatal cerebral infections in both immunocompetent patients in the event of near drowning and immunosuppressed patients such as lung transplant recipients. Because of the low susceptibility of this fungus to antifungal drugs, and the low permeability of the blood-brain barrier (BBB), therapeutic drug monitoring is necessary to reach an effective tissue concentration with limited side effects. Indeed, diffusion of the drug in the brain is dependent on several parameters, such as the integrity of the BBB and the activity of efflux pumps. To evaluate drug diffusion, two experimental models were developed in immunocompetent and immunosuppressed rats. Inocula were administered via the penile vein and a clinical scale (0-9) was established, based on weight and clinical and neurologic signs evaluated by the tail suspension test. Cerebral involvement was confirmed by magnetic resonance imaging and histologic examination of brain sections after hematoxylin-eosin-safran or silver staining. Voriconazole or posaconazole was given to the rats at doses ranging from 10 to 75 mg/kg/day via i.v. or oral routes, respectively. Whatever the immune status, the effective doses (defined by a doubling of the survival time and the absence of neurologic sequelae) were 30 mg/kg/day for voriconazole and 50 mg/kg/day for posaconazole. Overall, the results demonstrated that these models may constitute valuable tools for the performance of pharmacokinetic and pharmacodynamic studies for pharmacokinetic-pharmacodynamic modeling.

MRI-visible poly(ε-caprolactone) with controlled contrast agent ratios for enhanced visualization in temporary imaging applications.

Hydrophobic macromolecular contrast agents (MMCAs) are highly desirable to provide safe and efficient magnetic resonance (MR) visibility to implantable medical devices. In this study, we report on the synthesis and evaluation of novel biodegradable poly(ε-caprolactone)-based MMCAs. Poly(α-propargyl-ε-caprolactone-co-ε-caprolactone)s containing 2, 5, and 10 mol % of propargyl groups have been prepared by ring-opening copolymerization of ε-caprolactone and the corresponding propargylated lactone. In parallel, a diazido derivative of the clinically used diethylenetriaminepentaacetic acid (DTPA)/Gd(3+) complex has been synthesized. Finally, MRI-visible poly(ε-caprolactone)s (PCLs) were obtained by the efficient click ligation of these compounds via a Cu(I)-catalyzed [3 + 2] cycloaddition. ICP-MS analyses confirmed the efficient coupling of the complex on the PCL backbone with the MRI-visible PCLs containing 1.0, 2.6, and 3.6 wt % of Gd(3+). The influence of the Gd(3+) grafting density on the T1 relaxation times and on the MRI visibility of the novel biodegradable MMCAs was evaluated. Finally, their stability and cytocompatibility were assessed with regard to their potential as innovative MRI-visible biomaterials for biomedical applications.

Evidence of residual micellar structures in a lipid nanocapsule dispersion. A multi-technique approach.

Nanoemulsions are metastable emulsions in the nanometric range which can be obtained using low-energy processes. A decade ago, it was demonstrated that a non-negligible amount of residual surfactant micelles may coexist with the oil nanodroplets in a model oil/surfactant system. Those micelles were called "wasted" micelles as they did not participate in the formation of the nanodroplets. Little attention has been focused on the potential presence or effect of such secondary structures in nanoemulsions used as drug delivery systems. Here, we present an extensive characterization of lipid nanocapsules, a nanoemulsion obtained from a medium-chain triglyceride mixed with a pegylated surfactant by a process comprising a temperature-dependent phase inversion followed by a cold-water quench. Lipid nanocapsules demonstrate a very good shelf stability. First, for clarity and academic purposes, we briefly present the pros and the cons of the various diffusion-based characterization techniques used i.e., multi-angle and single-angle dynamic light scattering, nanoparticle tracking analysis, fluorescence recovery after photobleaching, and diffusometry nuclear magnetic resonance. Then, combining all these techniques, we show that up to 40 wt% of the surfactant is not involved in the lipid nanocapsule construction but forms residual micellar structures. Those micelles also contain a small quantity of medium-chain triglyceride (2 wt% of the initial amount) and encapsulate around 40 wt% of a fluorescent dye originally dispersed in the oily phase.

Organic nanoparticle tracking during pharmacokinetic studies.

To understand how nanoparticles (NPs) interact with biological barriers and to ensure they maintain their integrity over time, it is crucial to study their in vivo pharmacokinetic (PK) profiles. Many methods of tracking have been used to describe the in vivo fate of NPs and to evaluate their PKs and structural integrity. However, they do not deliver the same level of information and this may cause misinterpretations. Here, the authors review and discuss the different methods for in vivo tracking of organic NPs. Among them, Förster resonance energy transfer (FRET) presents great potential to track NPs' integrity. However, FRET still requires validated methods to extract and quantify NPs in biological fluids and tissues.