A study of non-invasive Patlak quantification for whole-body dynamic FDG-PET studies of mice

Physiological changes in dynamic PET images can be quantitatively estimated by kinetic modeling technique. The process of PET quantification usually requires an input function in the form of a plasma-time activity curve (PTAC), which is generally obtained by invasive arterial blood sampling. However, invasive arterial blood sampling poses many challenges especially for small animal studies, due to the subjects' limited blood volume and small blood vessels. A simple non-invasive quantification method based on Patlak graphical analysis (PGA) has been recently proposed to use a reference region to derive the relative influx rate for a target region without invasive blood sampling, and evaluated by using the simulation data of human brain FDG-PET studies. In this study, the non-invasive Patlak (nPGA) method was extended to whole-body dynamic small animal FDG-PET studies. The performance of nPGA was systematically investigated by using experimental mouse studies and computer simulations. The mouse studies showed high linearity of relative influx rates between the nPGA and PGA for most pairs of reference and target regions, when an appropriate underlying kinetic model was used. The simulation results demonstrated that the accuracy of the nPGA method was comparable to that of the PGA method, with a higher reliability for most pairs of reference and target regions. The results proved that the nPGA method could provide a non-invasive and indirect way for quantifying the FDG kinetics of tumor in small animal studies.     

Non-invasive methods for the determination of body and carcass composition in livestock: dual-energy X-ray absorptiometry,computed tomography,magnetic resonance imaging and ultrasound: invited review

The ability to accurately measure body or carcass composition is important for performance testing, grading and finally selection or payment of meat-producing animals. Advances especially in non-invasive techniques are mainly based on the development of electronic and computer-driven methods in order to provide objective phenotypic data. The preference for a specific technique depends on the target animal species or carcass, combined with technical and practical aspects such as accuracy, reliability, cost, portability, speed, ease of use, safety and for in vivo measurements the need for fixation or sedation. The techniques rely on specific device-driven signals, which interact with tissues in the body or carcass at the atomic or molecular level, resulting in secondary or attenuated signals detected by the instruments and analyzed quantitatively. The electromagnetic signal produced by the instrument may originate from mechanical energy such as sound waves (ultrasound – US), ‘photon’ radiation (X-ray-computed tomography – CT, dual-energy X-ray absorptiometry – DXA) or radio frequency waves (magnetic resonance imaging – MRI). The signals detected by the corresponding instruments are processed to measure, for example, tissue depths, areas, volumes or distributions of fat, muscle (water, protein) and partly bone or bone mineral. Among the above techniques, CT is the most accurate one followed by MRI and DXA, whereas US can be used for all sizes of farm animal species even under field conditions. CT, MRI and US can provide volume data, whereas only DXA delivers immediate whole-body composition results without (2D) image manipulation. A combination of simple US and more expensive CT, MRI or DXA might be applied for farm animal selection programs in a stepwise approach.     

Validity and reliability of dual-energy X-ray absorptiometry for the assessment of abdominal adiposity.

A number of methods exist for the estimation of abdominal obesity, ranging from waist-to-hip ratio to computed tomography (CT). Although dual-energy X-ray absorptiometry (DXA) was originally used to measure bone density and total body composition, recent improvements in software allow it to determine abdominal fat mass. Sixty-five men and women aged 18-72 yr participated in a series of studies to examine the validity and reliability of the DXA to accurately measure abdominal fat. Total body fat and abdominal regional fat were measured by DXA using a Lunar DPX-IQ. Multislice CT scans were performed between L1 and L4 vertebral bodies (region of interest) using a Picker PQ5000 CT scanner, and volumetric analyses were carried out on a Voxel Q workstation. Both abdominal total tissue mass (P = 0.02) and abdominal fat mass (P < 0.0001) in the L1-L4 region of interest were significantly lower as measured by DXA compared with multislice CT. However, Bland-Altman analysis demonstrated good concordance between DXA and CT for abdominal total tissue mass (i.e., limits of agreement = -1.56-2.54 kg) and fat mass (i.e., limits of agreement = -0.40-1.94 kg). DXA also showed excellent reliability among three different operators to determine total, fat, and lean body mass in the L1-L4 region of interest (intraclass correlations, R = 0.94, 0.97, and 0.89, respectively). In conclusion, the DXA L1-L4 region of interest compared with CT proved to be both reliable and accurate method to determine abdominal obesity.     

Current issues and perspectives in small rodent magnetic resonance imaging using clinical MRI scanners

Small rodents such as mice and rats are frequently used in animal experiments for several reasons. In the past, animal experiments were frequently associated with invasive methods and groups of animals had to be killed to perform longitudinal studies. Today's modern imaging techniques such as magnetic resonance imaging (MRI) allow non-invasive longitudinal monitoring of multiple parameters. Although only a few institutions have access to dedicated small animal MR scanners, most institutions carrying out animal experiments have access to clinical MR scanners. Technological advances and the increasing field strength of clinical scanners make MRI a broadly available and viable technique in preclinical in vivo research. This review provides an overview of current concepts, limitations, and recent studies dealing with small animal imaging using clinical MR scanners.     

Abdominal fat analyzed by DEXA scan reflects visceral body fat and improves the phenotype description and the assessment of metabolic risk in mice

Clinical studies have demonstrated a strong relationship between visceral fat content and metabolic diseases, such as type 2 diabetes and liver steatosis. Obese mouse models are an excellent tool to study metabolic diseases; however, there are limited methods for the noninvasive measurement of fat distribution in mice. Although micromagnetic resonance imaging and microcomputed tomography are the "gold standards" in the measurement of fat distribution, more economical and accessible methods are required. Dual energy X-ray absorptiometry (DEXA) is an effective method in characterizing fat content; however, it cannot discriminate between visceral and subcutaneous fat depots. We demonstrate that an evaluation of abdominal fat content measured by DEXA through the selection of one localized abdominal area strongly correlates with visceral fat content in C57BL/6J mice. We found that DEXA is able to measure fat pad volume ex vivo with high accuracy; however, the measurement of visceral fat in vivo shows an overestimation caused by subcutaneous tissue interference. The overestimation is almost constant for a wide range of values, and thus it is possible to correct the data for a more accurate estimation of visceral fat content. We demonstrate the utility of this technique in characterizing phenotypes of several obese mouse models (ob/ob, db/db, MC4R-KO, and DIO) and evaluating the effect of treatments on visceral fat content in longitudinal studies. Additionally, we also establish abdominal obesity as a potential biomarker for metabolic abnormalities (liver fat accumulation, insulin resistance/diabetes) in mice, similar to that described in humans.     

Selective adipose tissue ablation by localized,sustained drug delivery

The reduction of adipose depots is widely considered to be the optimal approach to limit pathologies associated with obesity. While many current antiobesity strategies are centered on regulating satiety, these approaches typically attempt an overall weight loss and are unable to target distinct adipose depots specifically associated with disease risk. The authors report a novel therapeutic modality utilizing localized and sustained delivery of drugs to provide for the selective ablation of adipose tissue. Using the epididymal fat pad of Sprague-Dawley rats as a model, they injected into the tissue poly(lactide-co-glycolide) microspheres encapsulating tumor necrosis factor-alpha, a well-known regulator of adipose tissue mass. The utility of this approach was investigated in vivo by measuring the fat pad mass relative to the contralateral control within the same animal (n = 4 at each time point) and in vitro by measuring apoptosis in adipose organ cultures. The authors demonstrated control over the localization of tumor necrosis factor-alpha by performing blood analysis. This is the first report of localized drug delivery for adipose tissue ablation, and these results indicate the potential utility of the general tissue ablation approach for treatment of numerous pathologies.     

Characterization of Obesity Phenotypes in Psammomys Obesus (Israeli Sand Rats)

Psammomys obesus (the Israeli sand rat) has been well studied as an animal model of Type 2 diabetes. However, obesity phenotypes in these animals have not been fully characterized. We analyzed phenotypic data including body weight, percentage body fat, blood glucose and plasma insulin concentration for over 600 animals from the Psammomys obesus colony at Deakin University to investigate the relationships between body fat, body weight and Type 2 diabetes using regression analysis and general linear modelling. The body weight distribution in Psammomys obesus approximates a normal distribution and closely resembles that observed in human populations. Animals above the 75th percentile for body weight had increased body fat content and a greater risk of developing diabetes. Increased visceral fat content .was also associated with elevated blood glucose and plasma insulin concentrations in these animals. A familial effect was also demonstrated in Psammomys obesus, and accounted for 51% of the variation in body weight, and 23–26% of the variation in blood glucose and plasma insulin concentrations in these animals. Psammomys obesus represents an excellent animal model of.obesity and Type 2 diabetes that exhibits a phenotypic pattern closely resembling that observed in human population studies. The obesity described in these animals was familial in nature and was significantly associated with Type 2 diabetes.     

Saturated Fatty Acids Modulate Autophagy’s Proteins in the Hypothalamus

Autophagy is an important process that regulates cellular homeostasis by degrading dysfunctional proteins, organelles and lipids. In this study, the hypothesis that obesity could lead to impairment in hypothalamic autophagy in mice was evaluated by examining the hypothalamic distribution and content of autophagic proteins in animal with obesity induced by 8 or 16 weeks high fat diet to induce obesity and in response to intracerebroventricular injections of palmitic acid. The results showed that chronic exposure to a high fat diet leads to an increased expression of inflammatory markers and downregulation of autophagic proteins. In obese mice, autophagic induction leads to the downregulation of proteins, such as JNK and Bax, which are involved in the stress pathways. In neuron cell- line, palmitate has a direct effect on autophagy even without inflammatory activity. Understanding the cellular and molecular bases of overnutrition is essential for identifying new diagnostic and therapeutic targets for obesity.     

Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins

We determined whether acquired obesity is associated with increases in liver or intra-abdominal fat or impaired insulin sensitivity by studying monozygotic (MZ) twin pairs discordant and concordant for obesity. We studied nineteen 24- to 27-yr-old MZ twin pairs, with intrapair differences in body weight ranging from 0.1 to 24.7 kg [body mass index (BMI) range 20.0-33.9 kg/m2], identified from a population-based FinnTwin16 sample. Fat distribution was determined by magnetic resonance imaging, percent body fat by dual-energy X-ray absorptiometry, liver fat by proton spectroscopy, insulin sensitivity by measuring the fasting insulin concentration, and whole body insulin sensitivity by the euglycemic insulin clamp technique. Intrapair differences in BMI were significantly correlated with those in intra-abdominal fat (r = 0.82, P < 0.001) and liver fat (r = 0.57, P = 0.010). Intrapair differences in fasting insulin correlated with those in subcutaneous abdominal (r = 0.60, P = 0.008), intra-abdominal (r = 0.75, P = 0.0001) and liver (r = 0.49, P = 0.048) fat. Intrapair differences in whole body insulin sensitivity correlated with those in subcutaneous abdominal (r = -0.72, P = 0.001) and intra-abdominal (r = -0.55, P = 0.015) but not liver (r = -0.20, P = 0.20) fat. We conclude that acquired obesity is associated with increases in intra-abdominal and liver fat and insulin resistance, independent of genetic factors.     

中国西南纵向岭谷区外来入侵植物对生物多样性的影响

论述中国西南纵向岭谷区外来入侵植物对生物多样性的影响。中国西南纵向岭谷区是我国生物多样性保护的关键地区。目前,该区域已成为外来植物入侵的重灾区,外来入侵植物种类多达70余种,其中,紫茎泽兰Ageratina adenophora（Eupatoriumadenophorum）、飞机草Chromolaena odorata（Eupatorium odoratum）和肿柄菊Tithonia diversifolia等在该区域危害严重,该区域的生态系统的结构与功能遭受破坏,本地物种面临灭绝,农、林、牧生产乃至区域的生态安全受到威胁。该区域的外来入侵植物的危害居全国之冠。研究该区域的外来入侵植物,揭示其危害规律,遏制其危害速度,最终清除该区域的外来入侵植物,恢复该区域的生态平衡,具有十分重要的现实意义和科学价值。文中详细论述了外来入侵植物对植物物种多样性、植物群落多样性、生态系统多样性、农牧业及林业的影响,最后指出消除和控制外来入侵植物的途径。     

The adipose organ at a glance

The main parenchymal cells of the adipose organ are adipocytes. White adipocytes store energy, whereas brown adipocytes dissipate energy for thermogenesis. These two cell types with opposing functions can both originate from endothelial cells, and co-exist in the multiple fat depots of the adipose organ – a feature that I propose is crucial for this organ’s plasticity. This poster review provides an overview of the adipose organ, describing its anatomy, cytology, physiological function and histopathology in obesity. It also highlights the remarkable plasticity of the adipose organ, explaining theories of adipocyte transdifferentiation during chronic cold exposure, physical exercise or lactation, as well as in obesity. White-to-brown adipocyte transdifferentiation is of particular medical relevance, because animal data indicate that higher amounts of brown adipose tissue are positively associated with resistance to obesity and its co-morbidities, and that ‘browning’ of the adipose organ curbs these disorders.     

Magnetic resonance imaging using a clinical whole body system: an introduction to a useful technique in small animal experiments.

A clinical whole body magnetic resonance imaging (MRI) system with high resolution coils was used to obtain non-invasive images of the living rat. The results demonstrate the feasibility of the set-up and the advantages of this new imaging technique: detailed information, no extra costs, longitudinal studies without killing animals and simple anaesthesia. It is concluded that in small animal experimentation, this use of high resolution coils in whole body magnetic resonance systems may be particularly helpful in establishing effects of experimental procedures. Whenever non-invasive visualization is required, especially in longitudinal animal studies, e.g. biomaterial research or tumour investigation, this use of MRI will offer challenging possibilities.     

Increased abdominal-to-peripheral fat distribution contributes to altered autonomic-circulatory control with human aging

Autonomic nervous system (ANS) control of the circulation is altered with aging in adult humans. Similar changes are observed in obesity, particularly abdominal obesity. To determine whether age-associated differences in ANS-circulatory function can be partially explained by increased body fatness, we examined ANS function and three expressions of adiposity (total body fat, abdominal body fat, and abdominal-to-peripheral body fat distribution; dual-energy X-ray absorptiometry) in 43 healthy men: 27 young (25 +/- 1 yr) and 16 older (65 +/- 1). ANS functions assessed included 1) autonomic support of arterial blood pressure (BP; radial artery catheter), i.e., the reduction in BP during versus before acute ganglionic blockade (GB; intravenous trimethaphan); 2) baroreflex buffering, i.e., the increase in systolic BP with continuous incremental and bolus infusions of phenylephrine during versus before GB; 3) cardiovagal baroreflex sensitivity (Oxford technique); and 4) heart rate variability (time- and frequency-domain analyses). Covarying for abdominal-to-peripheral fat distribution reduced or abolished age-related differences in ANS support of BP, cardiovagal baroreflex sensitivity, and heart rate variability but did not affect age-related differences in baroreflex buffering. Covarying for abdominal and total fat had small selective or no effects on age-associated differences in autonomic-circulatory control. Abdominal-to-peripheral fat distribution explains a significant portion of the variance in a number of autonomic-circulatory functions attributable to aging. Therefore, the development of this fat pattern may contribute to several changes in ANS-cardiovascular function observed with aging. These results may help explain how changes in body fat distribution with advancing age are linked to impairments in circulatory control.     

Role of DHEA-S on body fat distribution: gender- and depot-specific stimulation of adipose tissue lipolysis

The objective of this work was to study the possible impact of DHEA-S on body fat distribution and the specific action of the hormone on lipolysis from visceral and subcutaneous human adipose tissue. First, a clinical evaluation was performed in 84 obese patients (29 men, 55 women), measuring serum DHEA-S, computed tomography (CT) anthropometric parameters of abdominal fat distribution. In a second experiment, subcutaneous and visceral adipose tissue samples were obtained from 20 obese patients (10 men, 10 women) and cultured in vitro under stimulation with DHEA-S to further assess a possible effect of this hormone on adipose tissue lipolysis. Serum DHEA-S was inversely and specifically associated with visceral fat area (VA) as assessed by CT in men and with waist-to-hip ratio in women. In vitro, DHEA-S increased lipolysis in women's subcutaneous adipose tissue at 2 h, while in men, the effect was evident in visceral tissue and after 24 h of treatment. In conclusion, DHEA-S contributes to gender-related differences in body fat distribution probably by a differential lipolytic action. We have demonstrated for the first time in vitro that DHEA-S stimulates lipolysis preferably in subcutaneous fat in women and in visceral fat in men.     

Dual Lipolytic Control of Body Fat Storage and Mobilization in Drosophila

Energy homeostasis is a fundamental property of animal life, providing a genetically fixed balance between fat storage and mobilization. The importance of body fat regulation is emphasized by dysfunctions resulting in obesity and lipodystrophy in humans. Packaging of storage fat in intracellular lipid droplets, and the various molecules and mechanisms guiding storage-fat mobilization, are conserved between mammals and insects. We generated a Drosophila mutant lacking the receptor (AKHR) of the adipokinetic hormone signaling pathway, an insect lipolytic pathway related to ß-adrenergic signaling in mammals. Combined genetic, physiological, and biochemical analyses provide in vivo evidence that AKHR is as important for chronic accumulation and acute mobilization of storage fat as is the Brummer lipase, the homolog of mammalian adipose triglyceride lipase (ATGL). Simultaneous loss of Brummer and AKHR causes extreme obesity and blocks acute storage-fat mobilization in flies. Our data demonstrate that storage-fat mobilization in the fly is coordinated by two lipocatabolic systems, which are essential to adjust normal body fat content and ensure lifelong fat-storage homeostasis.     

Dual lipolytic control of body fat storage and mobilization in Drosophila

Energy homeostasis is a fundamental property of animal life, providing a genetically fixed balance between fat storage and mobilization. The importance of body fat regulation is emphasized by dysfunctions resulting in obesity and lipodystrophy in humans. Packaging of storage fat in intracellular lipid droplets, and the various molecules and mechanisms guiding storage-fat mobilization, are conserved between mammals and insects. We generated a Drosophila mutant lacking the receptor (AKHR) of the adipokinetic hormone signaling pathway, an insect lipolytic pathway related to ß-adrenergic signaling in mammals. Combined genetic, physiological, and biochemical analyses provide in vivo evidence that AKHR is as important for chronic accumulation and acute mobilization of storage fat as is the Brummer lipase, the homolog of mammalian adipose triglyceride lipase (ATGL). Simultaneous loss of Brummer and AKHR causes extreme obesity and blocks acute storage-fat mobilization in flies. Our data demonstrate that storage-fat mobilization in the fly is coordinated by two lipocatabolic systems, which are essential to adjust normal body fat content and ensure lifelong fat-storage homeostasis.     

Visceral Fat Accumulation as a Risk Factor for Prostate Cancer

Objective: No clear association between obesity or body fat distribution and prostate cancer has been shown. We investigated the relation between visceral fat accumulation as measured by computed tomography (CT) and the occurrence of prostate cancer. Research Methods and Procedures: We compared body fat distribution assessed by a direct method (CT) in 63 prostate cancer cases with 63 age‐matched healthy community controls. A CT scan at the level of the fourth lumbar vertebra was performed in all participants. Results: Patients presented a significantly higher mean total abdominal fat area (509.2 ± 226.1 vs. 334.3 ± 132.9 cm², p < 0.001), mostly because of a higher mean visceral fat area (VF; 324.7 ± 145.6 vs. 177.4 ± 88.4 cm², p < 0.001) and a significantly higher mean ratio between visceral and subcutaneous fat areas (V/S ratio; 1.8 ± 0.4 vs. 1.2 ± 0.4, p < 0.001). A significantly higher risk of prostate cancer was found for participants with higher VF (odds ratio = 4.6; 95% confidence interval = 2.6 to 8.2 per SD increase) and V/S ratio (odds ratio = 6.0; 95% confidence interval = 2.3 to 11.0 per SD increase). Discussion: These results suggest a role for visceral obesity, quantified by CT, as a risk factor for prostate cancer. The action of the adipocytokines secreted by visceral fat cells, steroid hormone disturbances, and increased levels of insulin or other hormones noted in visceral obesity may explain this association.     

Comparison of DXA and CT in the Assessment of Body Composition in Premenopausal Women With Obesity and Anorexia Nervosa

Accurate methods for assessing body composition in subjects with obesity and anorexia nervosa (AN) are important for determination of metabolic and cardiovascular risk factors and to monitor therapeutic interventions. The purpose of our study was to assess the accuracy of dual‐energy X‐ray absorptiometry (DXA) for measuring abdominal and thigh fat, and thigh muscle mass in premenopausal women with obesity, AN, and normal weight compared to computed tomography (CT). In addition, we wanted to assess the impact of hydration on DXA‐derived measures of body composition by using bioelectrical impedance analysis (BIA). We studied a total of 91 premenopausal women (34 obese, 39 with AN, and 18 lean controls). Our results demonstrate strong correlations between DXA‐ and CT‐derived body composition measurements in AN, obese, and lean controls (r = 0.77–0.95, P < 0.0001). After controlling for total body water (TBW), the correlation coefficients were comparable. DXA trunk fat correlated with CT visceral fat (r = 0.51–0.70, P < 0.0001). DXA underestimated trunk and thigh fat and overestimated thigh muscle mass and this error increased with increasing weight. Our study showed that DXA is a useful method for assessing body composition in premenopausal women within the phenotypic spectrum ranging from obesity to AN. However, it is important to recognize that DXA may not accurately assess body composition in markedly obese women. The level of hydration does not significantly affect most DXA body composition measurements, with the exceptions of thigh fat.     

Murine model of allergen induced asthma

Asthma is a major cause of morbidity and mortality, affecting some 300 million people throughout the world (1). More than 8% of the US population has asthma, with the prevalence increasing (2). As with other diseases, animal models of allergic airway disease greatly facilitate understanding of the underlying pathophysiology, help identify potential therapeutic targets, and allow preclinical testing of possible new therapies. Models of allergic airway disease have been developed in several animal species, but murine models are particularly attractive due to the low cost, ready availability, and well-characterized immune systems of these animals (3). Availability of a variety of transgenic strains further increases the attractiveness of these models (4). Here we describe two murine models of allergic airway disease, both employing ovalbumin as the antigen. Following initial sensitization by intraperitoneal injection, one model delivers the antigen challenge by nebulization, the other by intratracheal delivery. These two models offer complementary advantages, with each mimicking the major features of human asthma (5). The major features of acute asthma include an exaggerated airway response to stimuli such as methacholine (airway hyperresponsiveness; AHR) and eosinophil-rich airway inflammation. These are also prominent effects of allergen challenge in our murine models (5,6), and we describe techniques for measuring them and thus evaluating the effects of experimental manipulation. Specifically, we describe both invasive (7) and non-invasive (8) techniques for measuring airway hyperresponsiveness as well as methods for assessing infiltration of inflammatory cells into the airways and the lung. Airway inflammatory cells are collected by bronchoalveolar lavage while lung histopathology is used to assess markers of inflammation throughout the organ. These techniques provide powerful tools for studying asthma in ways that would not be possible in humans.     

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.