Liposomes and Micelles to Target the Blood Pool for Imaging Purposes

Abstract

The blood pool is among body compartments of a special interest for imaging using magnetic resonance (MR) and computed tomography (CT), since with the help of selective blood-pool contrast agents blood perfusion and various cardiac parameters as well as a status of the blood flow and vascular system in any organ can be evaluated. Blood pool-specific imaging agents can also provide minimally invasive angiography, image guidance of minimally invasive procedures, oncologic imaging of angiogenesis, ascertaining organ blood volume, and identifying hemorrhage. Particulate contrast agents (such as liposomes and micelles) whose distribution is limited to the blood pool, should have a size larger than fenestrated capillaries (> 10 nm), contain the reporter (paramagnetic or radiopaque) moiety structurally incorporated within the particulate, and be able to stay in the blood long enough to obtain clinically useful images. We describe here a new generation of long-circulating Gd-loaded liposomes and iodine-loaded micelles to provide an efficient blood pool MR and CT imaging, respectively. In this study, we developed the optimized protocol to prepare a liposomal MR contrast agent with high relaxivity and narrow size distribution. Liposomes were loaded with Gadolinium (Gd) via so called polychelating amphiphilic polymer (PAP) that represents a low-molecular-weight DTPA-polylysine linked via its N-terminus to a lipid anchor, NGPE-PE. Gd-containing liposomes were additionally modified with PEG to provide the longevity in vivo. We demonstrated also that upon the intravenous administration in rabbits and dogs, a new preparation causes prolonged decrease in the blood Tl value, permits to obtain sharp and clear MR images of the vasculature, and may be considered as a potential contrast agent for MRI of the blood pool. In addition, to prepare micellar contrast agents for CT blood-pool imaging, we synthesized an iodine-containing amphiphilic block-copolymer consisting of methoxypoly(ethyleneglycol) and polyl?,N-(triiodobenzoyl)]-L-lysine. In aqueous solutions, it forms stable micelles with an average diameter of 80 nm and an iodine content of 35–40% wt. Iodine-containing micelles were intravenously injected into rats and rabbits at a dose of 170 mg I/kg and produced significant and sustained enhancement of the blood pool (aorta and heart), liver and spleen for a period of at least 3 hours providing clear and informative CT images.     

Recent progresses in gene delivery-based bone tissue engineering

Gene therapy has converged with bone engineering over the past decade, by which a variety of therapeutic genes have been delivered to stimulate bone repair. These genes can be administered via in vivo or ex vivo approach using either viral or nonviral vectors. This article reviews the fundamental aspects and recent progresses in the gene therapy-based bone engineering, with emphasis on the new genes, viral vectors and gene delivery approaches.     

Multifaceted applications of nanomaterials in cell engineering and therapy

Nanomaterials with superior physiochemical properties have been rapidly developed and integrated in every aspect of cell engineering and therapy for translating their great promise to clinical success. Here we demonstrate the multifaceted roles played by innovatively-designed nanomaterials in addressing key challenges in cell engineering and therapy such as cell isolation from heterogeneous cell population, cell instruction in vitro to enable desired functionalities, and targeted cell delivery to therapeutic sites for prompting tissue repair. The emerging trends in this interdisciplinary and dynamic field are also highlighted, where the nanomaterial-engineered cells constitute the basis for establishing in vitro disease model; and nanomaterial-based in situ cell engineering are accomplished directly within the native tissue in vivo. We will witness the increasing importance of nanomaterials in revolutionizing the concept and toolset of cell engineering and therapy which will enrich our scientific understanding of diseases and ultimately fulfill the therapeutic demand in clinical medicine.     

Intérêt de la scintigraphie pulmonaire de perfusion dans les dilatations des bronches de l’enfant

IntroductionBronchiectasis is a chronic disease of the lungs by repeated respiratory infection. An early and adequate diagnosis and management reduce the morbidity and mortality of this disease. The aim of this study is to emphasize the importance of the combination of Computer Tomography (CT) and lung perfusion scan (SPP) in the diagnosis and therapeutic approach.Materials and methodsForty-three children were referred in the nuclear medicine department with a clinical diagnosis of bronchiectasis; they underwent a CT and a SPP.Results and conclusionBy analyzing the results of the SPP and CT separately, we conclude that there is no significant difference between the two investigations. The combination of the two explorations provides a gain in most surgical therapeutic orientation.     

Osteochondrosis in pigs diagnosed with computed tomography: heritabilities and genetic correlations to weight gain in specific age intervals

The aim of this study was to develop a method for scoring osteochondrosis (OC) by using information from computed tomography (CT), as well as to estimate the heritability for OC scored by means of CT (OCwCT) of the medial and lateral condyles at the distal end of the humerus or the femur of the right and left leg and the sum of these scores (OCT). In addition, we were aiming at revealing the genetic relationship between OCwCT traits and growth in different periods (days from birth to 30 kg (D30), days from 30 to 50 kg (D30_50), days from 50 to 70 kg (D50_70), days from 70 to 90 kg (D70_90), days from 90 to 100 kg (D90_100) and days from birth to 100 kg (D100)). The OCwCT was assessed for 1449 boars, and growth data were collected for these 1449 boars and additional 3779 boars tested in the same time period. All boars were tested as part of the Norsvin Landrace boar test and in the same test station. Heritabilities for OCwCT on anatomical locations varied from 0.21 (s.e. = 0.08) on the medial condyle of the right humerus to 0.06 (s.e. = 0.06) on the lateral condyle of the left femur, whereas OCT exhibited the highest heritability (h² = 0.31, s.e. = 0.09). Genetic correlations between OCT and OCwCT for the anatomical locations ranged from 0.94 (s.e. = 0.07) for OCT and OCwCT score for the medial condyle of the humerus right side to 0.26 (s.e. = 0.39) for OCT and the lateral condyle of the femur left side. Genetic correlations between D30 and OCT were medium high and unfavourable (r_g = −0.74). As the boar gain weight, the relationship between growth rate – expressed as number of days spent growing from one interval to the next – and OCT decreased to 0.12 (s.e. = 0.19, i.e. not significantly different from zero) for the trait D90_100 kg. These changes of genetic correlation coefficients coincide with the maturing of the joint cartilage and skeletal structures. In this study, we demonstrate that CT could be used for selection against OC in breeding programmes in pigs and that the genetic correlations between growth periods and OC are decreasing over time.     

Intravascular magnetomotive optical coherence tomography of targeted early‐stage atherosclerotic changes in ex vivo hyperlipidemic rabbit aortas

We report the development of an intravascular magnetomotive optical coherence tomography (IV‐MM‐OCT) system used with targeted protein microspheres to detect early‐stage atherosclerotic fatty streaks/plaques. Magnetic microspheres (MSs) were injected in vivo in rabbits, and after 30 minutes of in vivo circulation, excised ex vivo rabbit aorta samples specimens were then imaged ex vivo with our prototype IV‐MM‐OCT system. The alternating magnetic field gradient was provided by a unique pair of external custom‐built electromagnetic coils that modulated the targeted magnetic MSs. The results showed a statistically significant MM‐OCT signal from the aorta samples specimens injected with targeted MSs.

Representative magnetomotive signal (green) using targeted and non‐targeted magnetomotive microspheres in atherosclerotic diseased rabbit aortas.     

Cuffing‐based photoacoustic flowmetry in humans in the optical diffusive regime

Measuring blood flow speed in the optical diffusive regime in humans has been a long standing challenge for photoacoustic tomography. In this work, we proposed a cuffing‐based method to quantify blood flow speed in humans with a handheld photoacoustic probe. By cuffing and releasing the blood vessel, we can measure the blood flow speed downstream. In phantom experiments, we demonstrated that the minimum and maximum measurable flow speeds were 0.035 mm/s and 42 mm/s, respectively. In human experiments, flow speeds were measured in three different blood vessels: a radial artery in the right forearm, a radial artery in the index finger of the right hand, and a radial vein in the right forearm. Taking advantage of the handheld probe, our method can potentially be used to monitor blood flow speed in the clinic and at the bedside.

     

Volumetric hand‐held optoacoustic angiography as a tool for real‐time screening of dense breast

Existing mammographic screening solutions are generally associated with several major drawbacks, such as exposure to ionizing radiation or insufficient sensitivity in younger populations with radiographically‐dense breast. Even when combined with ultrasound or magnetic resonance imaging, X‐Ray mammography may still attain unspecific or false positive results. Thus, development of new breast imaging tools represents a timely medical challenge. We report on a new approach to high‐resolution functional and anatomical breast angiography using volumetric hand‐held optoacoustic tomography, which employs light intensities safe for human use. Experiments in young healthy volunteers with fibroglandular‐dominated dense breasts revealed the feasibility of rendering three‐dimensional images representing vascular anatomy and functional blood oxygenation parameters at video rate. Sufficient contrast was achieved at depths beyond 2 cm within dense breasts without compromising the real‐time imaging performance. The suggested solution may thus find applicability as a standalone or supplemental screening tool for early detection and follow‐up of carcinomas in radiographically‐dense breasts.

Volumetric handheld optoacoustic tomography scanner uses safe pulses of near‐infrared light to render three‐dimensional images of deep vascular anatomy, blood oxygenation and breast parenchyma at video rate.     

The first endocast of the extinct dodo (Raphus cucullatus) and an anatomical comparison amongst close relatives (Aves,Columbiformes)

The dodo (Raphus cucullatus) became extinct only 100 years after humans first arrived on the Indian Ocean island of Mauritius. Even though it has become an example of oddity, obsolescence, stupidity, and extinction, most aspects of its biology are still unknown. We used high‐resolution X‐ray computed tomography (CT) scanning to examine the endocranial morphology of the dodo and compare this virtual endocast to eight close relatives. Enlarged olfactory bulbs are a shared characteristic of the Raphinae and posteriorly angled semicircular canals are particular to the dodo compared with the other eight species sampled here. A regression of log endocranial volume against log body size shows that the dodo has an endocranial volume on par with other pigeons. Aspects of the dodo's biology are discussed in relation to these endocranial features.