Chitosan-based systems for molecular imaging Agrawal, Prashant; Strijkers, Gustav J.; Nicolay, Klaas
Advanced drug delivery reviews,
01/2010, Letnik:
62, Številka:
1
Journal Article
Recenzirano
Molecular imaging enables the non-invasive assessment of biological and biochemical processes in living subjects. Such technologies therefore have the potential to enhance our understanding of ...disease and drug activity during preclinical and clinical drug development. Molecular imaging allows a repetitive and non-invasive study of the same living subject using identical or alternative biological imaging assays at different time points, thus harnessing the statistical power of longitudinal studies, and reducing the number of animals required and cost. Chitosan is a hydrophilic and non-antigenic biopolymer and has a low toxicity toward mammalian cells. Hence, it has great potential as a biomaterial because of its excellent biocompatibility. Conjugated to additional materials, chitosan composites result in a new class of biomaterials that possess mechanical, physicochemical and functional properties, which have potential for use in advanced biomedical imaging applications. The present review will discuss the strengths, limitations and challenges of molecular imaging as well as applications of chitosan nanoparticles in the field of molecular imaging.
Low-back pain (LBP) has been correlated to the presence of intervertebral disc (IVD) degeneration on T2-weighted (T2w) MRI. It remains challenging, however, to accurately stage degenerative disc ...disease (DDD) based on T2w MRI and measurements of IVD height, particularly for early DDD. Several quantitative MRI techniques have been introduced to detect changes in matrix composition signifying early DDD. In this study, we correlated quantitative T2, T1rho and Apparent Diffusion Coefficient (ADC) values to disc mechanical behavior and gold standard early DDD markers in a graded degenerated lumbar IVD caprine model, to assess their potential for early DDD detection.
Lumbar caprine IVDs were injected with either 0.25 U/ml or 0.5 U/ml Chondroïtinase ABC (Cabc) to trigger early DDD-like degeneration. Injection with phosphate-buffered saline (PBS) served as control. IVDs were cultured in a bioreactor for 20 days under axial physiological loading. High-resolution 9.4 T MR images were obtained prior to intervention and after culture. Quantitative MR results were correlated to recovery behavior, histological degeneration grading, and the content of glycosaminoglycans (GAGs) and water.
Cabc-injected IVDs showed aberrancies in biomechanics and loss of GAGs without changes in water-content. All MR sequences detected changes in matrix composition, with T1rho showing largest changes pre-to-post in the nucleus, and significantly more than T2 and ADC. Histologically, degeneration due to Cabc injection was mild. T1rho nucleus values correlated strongest with altered biomechanics, histological degeneration score, and loss of GAGs.
T2- and T1rho quantitative MR-mapping detected early DDD changes. T1rho nucleus values correlated better than T2 and ADC with biomechanical, histological, and GAG changes. Clinical implementation of quantitative MRI, T1rho particularly, could aid in distinguishing DDD more reliably at an earlier stage in the degenerative process.
Diffusion tensor imaging (DTI) is increasingly applied to study skeletal muscle physiology, anatomy, and pathology. The reason for this growing interest is that DTI offers unique, noninvasive, and ...potentially diagnostically relevant imaging readouts of skeletal muscle structure that are difficult or impossible to obtain otherwise. DTI has been shown to be feasible within most skeletal muscles. DTI parameters are highly sensitive to patient‐specific properties such as age, body mass index (BMI), and gender, but also to more transient factors such as exercise, rest, pressure, temperature, and relative joint position. However, when designing a DTI study one should not only be aware of sensitivity to the above‐mentioned factors but also the fact that the DTI parameters are dependent on several acquisition parameters such as echo time, b‐value, and diffusion mixing time. The purpose of this review is to provide an overview of DTI studies covering the technical, demographic, and clinical aspects of DTI in skeletal muscles. First we will focus on the critical aspects of the acquisition protocol. Second, we will cover the reported normal variance in skeletal muscle diffusion parameters, and finally we provide an overview of clinical studies and reported parameter changes due to several (patho‐)physiological conditions. J. Magn. Reson. Imaging 2016;43:773–788
The purpose of this study was to develop a DTI-based method to quantitatively assess fiber angles and changes therein in leg muscles in order to facilitate longitudinal studies on muscle fiber ...architectural adaptations in healthy subjects.
The upper legs of five volunteers were scanned twice on the same day. The right lower legs of five volunteers were scanned twice with the ankle in three positions, i.e. -15° dorsiflexion, 0° neutral position, and 30° plantarflexion. The MRI protocols consisted of a noise scan, a 3-point mDixon scan and a DTI scan. Fiber-angle color maps were generated for four muscles in the upper legs and two muscles in the lower leg. Voxel-wise fiber angles (θ) were calculated from the angle between the principal eigenvector of the diffusion tensor and a reference line defined between the origo and insertion points of each muscle. Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation (CV%), minimal detectable change (MDC), standard error (SE) and Friedman test were used for assessing the feasibility of this method and in order to have an indication of the repeatability and the sensitivity.
Bland-Altman analysis showed good repeatability (CV%<10 and 0.7≤ICC≤0.9) with exception of the Tibialis Anterior (TA) muscle in dorsiflexion position(CV%: 12.2) and the Semitendinosus (ST) muscle (left leg) (CV%: 11.4). The best repeatability metrics were found for the SOL muscle in neutral position (CV%: 2.6). Changes in average θ in TA and SOL with ankle positions were observed in accordance with expected agonist and antagonist functions of both muscles. For example, for the anterior left compartment the change in fiber angle Δθ with respect to the neutral position Δθ = -1.6° ± 0.8° and 2.2° ± 2.8° (p = 0.008), for dorsiflexion and plantarflexion, respectively.
Our method facilitates fast inspection and quantification of muscle fiber angles in the lower and upper leg muscles in rest and detection of changes in lower-leg muscle fiber angles with varying ankle angles.
The ventricular walls of the human heart comprise an outer compact layer and an inner trabecular layer. In the context of an increased pre‐test probability, diagnosis left ventricular noncompaction ...cardiomyopathy is given when the left ventricle is excessively trabeculated in volume (trabecular vol >25% of total LV wall volume) or thickness (trabecular/compact (T/C) >2.3). Here, we investigated whether higher spatial resolution affects the detection of trabeculation and thus the assessment of normal and excessively trabeculated wall morphology. First, we screened left ventricles in 1112 post‐natal autopsy hearts. We identified five excessively trabeculated hearts and this low prevalence of excessive trabeculation is in agreement with pathology reports but contrasts the prevalence of approximately 10% of the population found by in vivo non‐invasive imaging. Using macroscopy, histology and low‐ and high‐resolution MRI, the five excessively trabeculated hearts were compared with six normal hearts and seven abnormally trabeculated and excessive trabeculation‐negative hearts. Some abnormally trabeculated hearts could be considered excessively trabeculated macroscopically because of a trabecular outflow or an excessive number of trabeculations, but they were excessive trabeculation‐negative when assessed with MRI‐based measurements (T/C <2.3 and vol <25%). The number of detected trabeculations and T/C ratio were positively correlated with higher spatial resolution. Using measurements on high resolution MRI and with histological validation, we could not replicate the correlation between trabeculations of the left and right ventricle that has been previously reported. In conclusion, higher spatial resolution may affect the sensitivity of diagnostic measurements and in addition could allow for novel measurements such as counting of trabeculations.
Jensen et al. show that higher spatial resolution may affect the sensitivity of diagnostic measurements of noncompaction and in addition could allow for novel measurements such as counting of trabeculations.
To develop a protocol for diffusion-tensor imaging (DTI) of the complete upper legs and to demonstrate feasibility of detection of subclinical sports-related muscle changes in athletes after ...strenuous exercise, which remain undetected by using conventional T2-weighted magnetic resonance (MR) imaging with fat suppression.
The research was approved by the institutional ethics committee review board, and the volunteers provided written consent before the study. Five male amateur long-distance runners underwent an MR examination (DTI, T1-weighted MR imaging, and T2-weighted MR imaging with fat suppression) of both upper legs 1 week before, 2 days after, and 3 weeks after they participated in a marathon. The tensor eigenvalues (λ1, λ2, and λ3), the mean diffusivity, and the fractional anisotropy (FA) were derived from the DTI data. Data per muscle from the three time-points were compared by using a two-way mixed-design analysis of variance with a Bonferroni posthoc test.
The DTI protocol allowed imaging of both complete upper legs with adequate signal-to-noise ratio and within a 20-minute imaging time. After the marathon, T2-weighted MR imaging revealed grade 1 muscle strains in nine of the 180 investigated muscles. The three eigenvalues, mean diffusivity, and FA were significantly increased (P < .05) in the biceps femoris muscle 2 days after running. Mean diffusivity and eigenvalues λ1 and λ2 were significantly (P < .05) increased in the semitendinosus and gracilis muscles 2 days after the marathon.
A feasible method for DTI measurements of the upper legs was developed that fully included frequently injured muscles, such as hamstrings, in one single imaging session. This study also revealed changes in DTI parameters that over time were not revealed by qualitative T2-weighted MR imaging with fat suppression.
Modern medicine has greatly benefited from recent dramatic improvements in imaging techniques. The observation of physiological events through interactions manipulated at the molecular level offers ...unique insight into the function (and dysfunction) of the living organism. The tremendous advances in the development of nanoparticulate molecular imaging agents over the past decade have made it possible to noninvasively image the specificity, pharmacokinetic profiles, biodistribution, and therapeutic efficacy of many novel compounds. Several types of nanoparticles have demonstrated utility for biomedical purposes, including inorganic nanocrystals, such as iron oxide, gold, and quantum dots. Moreover, natural nanoparticles, such as viruses, lipoproteins, or apoferritin, as well as hybrid nanostructures composed of inorganic and natural nanoparticles, have been applied broadly. However, among the most investigated nanoparticle platforms for biomedical purposes are lipidic aggregates, such as liposomal nanoparticles, micelles, and microemulsions. Their relative ease of preparation and functionalization, as well as the ready synthetic ability to combine multiple amphiphilic moieties, are the most important reasons for their popularity. Lipid-based nanoparticle platforms allow the inclusion of a variety of imaging agents, ranging from fluorescent molecules to chelated metals and nanocrystals. In recent years, we have created a variety of multifunctional lipid-based nanoparticles for molecular imaging; many are capable of being used with more than one imaging technique (that is, with multimodal imaging ability). These nanoparticles differ in size, morphology, and specificity for biological markers. In this Account, we discuss the development and characterization of five different particles: liposomes, micelles, nanocrystal micelles, lipid-coated silica, and nanocrystal high-density lipoprotein (HDL). We also demonstrate their application for multimodal molecular imaging, with the main focus on magnetic resonance imaging (MRI), optical techniques, and transmission electron microscopy (TEM). The functionalization of the nanoparticles and the modulation of their pharmacokinetics are discussed. Their application for molecular imaging of key processes in cancer and cardiovascular disease are shown. Finally, we discuss a recent development in which the endogenous nanoparticle HDL was modified to carry different diagnostically active nanocrystal cores to enable multimodal imaging of macrophages in experimental atherosclerosis. The multimodal characteristics of the different contrast agent platforms have proven to be extremely valuable for validation purposes and for understanding mechanisms of particle−target interaction at different levels, ranging from the entire organism down to cellular organelles.
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