MR imaging of liver abscesses; application of Gd-DTPA

The potential utility of Gd-DTPA contrast enhancement of MR images in the evaluation of liver abscesses was assessed in rodents. Twelve rats with surgically implanted sterile liver abscesses were imaged at various stages of focal hepatic inflammation, 48 hours, 4 days, 7 days, 14 days and 21 days after lesion induction. Spin echo images, acquired before and repeatedly after intravenous injection of 0.2 mmol/kg Gd-DTPA, demonstrated improvement of the lesion-to-background contrast ranging from 2% to 40% depending on the stage of the disease. The enhancement pattern also varied with abscess evolution. Two, four and seven-day-old abscesses typically showed a ring enhancement, whereas two- and three-week-old abscesses presented largely homogeneously enhancing lesions. In the earlier lesions, contrast enhanced rim surrounding the low intensity center corresponded histologically to the formation of a capsule consisting of fibrous tissue and inflammatory cells. The center was necrotic. Data show that abscesses can be detected on images acquired with long repetition and echo times without injection of Gd-DTPA. The administration of Gd-DTPA, however, improved the lesion-to-background contrast and helped to define the abscess capsule evolution.     

The effects of iron oxides on proton relaxivity

The magnetic properties and relaxivities of superparamagnetic, ferromagnetic and paramagnetic iron oxides are presented and compared. The iron in colloids of ferromagnetic iron oxide has a large spin-spin relaxivity and a small spin-lattice relaxivity. The iron in colloids of paramagnetic iron oxide has a low spin-spin and spin-lattice relaxivity. The iron in colloids of highly dispersed superparamagnetic iron oxides has a large spin-spin relaxivity and a large spin-lattice relaxivity. Superparamagnetic colloids with various particle sizes in solution have been made by varying the number of superparamagnetic iron oxide crystals per particles in solution. Superparamagnetic colloids of larger solution particle size have a lower spin-lattice relaxivity than colloids comprised of smaller solution particle sizes.     

Biodistribution of GdCl3 and Gd-DTPA and their influence on proton magnetic relaxation in rat tissues

The biodistribution and relative molar effectiveness of the ionic (GdCl3) and chelated (Gd-DTPA) forms of gadolinium (Gd) to enhance proton relaxation rates in rat kidney, liver and spleen were evaluated. Rats were given intravenous injections of either GdCl3 (100 mumol/kg) or Gd-DTPA (178 mumol/kg). Gd-DTPA was primarily contained in the vascular compartment and was quickly accumulated in the kidney after injection with a relaxivity of 4.3 sec-1 (mumol/g kidney)-1. It was eliminated quickly from the body with only 2% of the injected dose remaining after 120 min. After GdCl3 injection, Gd was found primarily in liver and spleen. It accumulated continuously reaching 72% of the injected does in these two tissues after 120 min. Despite this continuous increase in tissue Gd concentration, the relaxation rates showed saturation in liver and spleen. The results suggest that after GdCl3 was injected it distributed either in a protein bound form that was effective at causing relaxation or in a colloid form that was not effective. The biodistribution of GdCl3 was such that it was determined by the phagocytic action of the recticuloendothelial system on a colloid. The biodistribution and tissue relaxivity of Gd-DTPA suggest it will be a useful vascular MRI contrast agent. However, the usefulness of GdCl3 as an MRI contrast agent is limited not only by its acute toxicity but also by its saturable effect on tissue relaxation rates. Consequently, GdCl3 has only a modest influence on tissue relaxivity.     

Dynamic contrast-enhanced MRI with Gd-EOB-DTPA for the quantitative assessment of early-stage liver fibrosis induced by carbon tetrachloride in rabbits

PurposeTo explore quantitative parameters obtained by dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with Gd-EOB-DTPA in discriminating early-stage liver fibrosis (LF) in a rabbit model.Materials and methodsLF was established in 60 rabbits by the injection of 50% CCl₄ oil solution, whereas 30 rabbits served as the control group. All rabbits underwent pathological examination to determine the LF stage using the METAVIR classification system. DCE MRI was performed, and quantitative parameters, including K^trans, K_ep, V_e, V_p and Re were measured and evaluated among the different LF stages using spearman correlation coefficients and receiver operating characteristic curve.ResultsIn all, 24, 25, and 22 rabbits had stage F0, stage F1, and stage F2 LF, respectively. K^trans (r = 0.803) increased, and K_ep (r = −0.495) and Re (r = −0.701) decreased with LF stage progression (P < 0.001), while no significant correlation was found for V_e or V_p. K^trans and Re were significantly different between all LF stage pairs compared (F0 vs. F1, F0 vs. F2, F1 vs. F2, F0 vs. F1-F2, P < 0.05). With the exception of F0 vs. F1, K_ep differed significantly between stages (P < 0.05). The AUC of K^trans was higher than that of other quantitative parameters, with an AUC of 0.92, 0.99, 0.94 and 0.92 for staging F0 vs. F1, F0 vs. F2, F1 vs. F2, and F0 vs. F1-F2, respectively.ConclusionAmong quantitative parameters of Gd-EOB-DTPA DCE MRI, K^trans was the best predictor for quantitatively differentiating early-stage LF.     

Compatibility of Gd-DTPA perfusion and histologic studies of the brain

Histology, including immunohistochemistry, and magnetic resonance imaging microscopy (microMRI) are complementary techniques for the analysis of brain structure. Therefore, microMRI analysis, often of formalin-fixed tissue, precedes histologic evaluation of the same experimental animal in many studies. However, the application of gadopentetate dimeglumine (Gd-DTPA), while of value for MRI studies, has an unknown effect on subsequent histology. We demonstrate here that for the mouse brain, histology with Nissl staining and immunostaining for microtubule-associated protein 2, using standard techniques for tissue preparation, are unaffected by prior perfusion of the tissue with Gd-DTPA. This conclusion was based on qualitative morphologic comparisons of stained sections, as well as quantification of mean immunofluorescence pixel intensities from Gd-treated (mean+/-S.D.=131.2+/-28.4; n=3) as compared to nontreated specimens (116.2+/-34.7; n=3, P=.7). Therefore, Gd-DTPA may be applied as a microMRI contrast agent in formalin-fixed brain tissue prior to histologic studies.     

NMR relaxivity of coated and non-coated size-sorted maghemite nanoparticles

ABSTRACT

The effect of polymer coating on MNR relaxometry of maghemite nanoparticles has been studied. The samples were carefully sorted by size in order to reach narrow size distribution (<0.2) with size ranging from 4.5 to 12.5?nm. Relaxation dispersion profile as well as studies at a fixed Larmor frequency, were recorded for numerous either uncoated or polymer coated samples. The NMR relaxivities r₁ and r₂ increase with nanoparticle diameter. We have analysed the role of polydispersity for nanoparticles with the same mean size on the dispersion curves. We have compared the role of coating on nanoparticles NMR relaxivity between bare and poly(sodium acrylate-co-maleate) coated nanoparticles. We have investigated the influence of nanoparticle size on the T₁ and T₂ activation energy Ea. While Ea decreases with nanoparticle diameter when determined from T₁, it increases from T₂ determination. The influence is more important for small particles (<9?nm) than for big particles (>9?nm). Moreover, the PAAMA coating changes the energy Ea obtained from T₂: Ea becomes independent of the nanoparticle diameter. These results highlight the need of a complete characterisation of the role of the coating on the relaxation of magnetic particles.     

Gadolinium-labeled liposomes containing amphiphilic Gd-DTPA derivatives of varying chain length: targeted MRI contrast enhancement agents for the liver

Paramagnetic liposomal contrast agents were synthesized and utilized for selective augmentation of T1 MR imaging of the livers of normal Balb/c mice. Amphiphilic gadolinium complexes, which mimic phospholipids, were incorporated into the lamella of small unilamellar liposomes (SUV) such that they become an integral part of its surface. The amphiphilic complexing agents consisted of DTPA reagents in which a pair of alkyl chains of varying lengths are attached via amide linkages. The in vivo lifetimes of the amphiphilic agents were found to be dependent on the chain length of the alkyl groups.     

Proton NMR relaxivity of blood samples in the presence of iron,gadolinium and dysprosium compounds

The longitudinal and transverse relaxation rates of some iron, gadolinium and dysprosium compounds have been measured on ¹H in aqueous solutions and in blood as a function of molar concentrations. The different relaxation characteristics were analyzed and certain explanations concerning the molecular sources of these variations were advanced. The evidenced properties of these compounds are promising for interesting applications in medicine.     

The prospective evaluation of Gd-DTPA in 225 consecutive cranial cases: adverse reactions and diagnostic value

This prospective study evaluates two facets of gadopentetate dimeglumine (Gd-DTPA) enhanced MR imaging in 225 consecutive cranial cases in patients greater than 18 years of age: (i) patient and physician perception of adverse reactions, (ii) diagnostic value of the Gd-DTPA enhanced exam. The 225 cases included 173 head cases, 27 IAC cases, and 25 sella cases. Forty-six percent of the cases were abnormal excluding cases of mild atrophy and ischemic white matter disease judged to be related to aging and not pertinent to the patient's presenting complaint. Concerning adverse reactions, 83% of patients had no complaints. Five percent of the patients had reactions that were judged by the physician to be related to Gd-DTPA. All reactions were minor and required no therapy. In a subset of exams (115) that were blindly and independently interpreted by two board-certified, fellowship-trained radiologists, the Gd-DTPA-enhanced exam resulted in a change in diagnosis in 5%-8% of cases. Additionally, a major benefit of Gd-DTPA administration was the increased diagnostic confidence afforded by the addition of a contrast enhanced exam due to improved lesion characterization and exclusion of additional significant intracranial pathology. In 52%-69% of the abnormal cases, Gd-DTPA provided additional diagnostic information and in 26%-39% the absence of enhancement aided in interpretation. The Gd-DTPA-enhanced exam aids in the diagnosis and characterization of neoplastic disease, acoustic neuroma, subacute infarction, inflammatory disease (meningeal and parenchymal), and certain vascular abnormalities.     

Enhancing the relaxivity of paramagnetic coordination complexes through the optimization of the molecular electrostatic potential

The low relaxivity of paramagnetic coordination complexes limits their use as contrast agents in magnetic resonance imaging (MRI). To address this problem, we study the relationship between the molecular structure of these complexes and their relaxivity. While others have investigated the vibrational modes as molecular determinants of the electronic spin relaxation time, we focus on the analysis of the molecular electrostatic potential (MEP) of the paramagnetic coordination complex. Electrostatic forces dominate the interaction between the coordination complex and water. Hence, in addition to steric forces, the molecular electrostatic potential should be a determinant of the lifetime of the water-metal link (t_m), the internuclear distance between the water hydrogens and the metal (R), and the number of water molecules attached to the metal in the inner and outer spheres of coordination. We compute the molecular electrostatic potential for a series of model metalloporphyrins because their physical and biologic properties are well known, and they are putative magnetic resonance imaging contrast agents with affinity to neoplastic tissue. Replacing the sulfonato groups in MnTPPS4 with carboxylate groups in the ortho position of the phenyl rings attached to the meso carbons results in an electrostatic focusing field that should reduce R and increase t_m. Similar substitutions involving polar groups, including one modeled after a well-known picket-fence porphyrin, are not strong enough to generate a focusing field. Instead, these polar groups should modulate the water-metal interactions through steric interactions. Molecular dynamic simulations show a large outer sphere of coordination around the paramagnet that extends almost three times the distance of the inner sphere of coordination.     

大鼠肾脏糖胺聚糖的种类及二糖组成分析

采用两步酶解和离子交换色谱从Wistar大鼠肾脏中提取糖胺聚糖,以醋酸纤维素薄膜电泳分析糖胺聚糖种类,以弱阴离子交换色谱分离各种糖胺聚糖.纯化后的糖胺聚糖分别经特定糖胺聚糖酶裂解,采用强阴离子交换高效液相色谱(SAX-HPLC)紫外检测分析其二糖组成.结果表明,Wistar大鼠肾脏糖胺聚糖主要由硫酸乙酰肝素和少量硫酸皮肤素组成.硫酸乙酰肝素含有8种二糖,其中含有乙酰基二糖总含量高达77.6%,非硫酸化二糖(Ⅳ-A)含量为59.7%;硫酸皮肤素含有6种二糖,其中单硫酸化二糖总含量为54.8%,非硫酸化二糖含量为32.9%.     

MRI anatomy of the rat kidney at 1.5 T in different states of hydration

The objective of this study was to determine correlation between structural anatomy and surface coil spin-echo MR imaging of the rat kidney and the effect of hydration state on MR signal intensities of the cortex and medulla. Twelve rats were studied in a pilot study with a 3-inch surface coil in a 1.5 T magnet under five different states of hydration. Serum and urine osmolality measurements were obtained immediately prior to each scan. Signal intensity measurements were made from both T₁- and T₂-weighted images of the cortex and medulla of both kidneys in each state of hydration. Gross and histological anatomy of the rat kidneys was correlated with the MR images. Four distinct layers were detected in vivo on MRI images of the rat kidney; these correlated with the histological layers. T₁-weighted cortico-medullary differentiation was most pronounced at 48 h dehydration; T₂ cortico-medullary differentiation was greatest at 72 h of dehydration. We concluded that different parts of the mammalian nephron can be identified by MR imaging and that cortico-medullary differentiation is affected by the hydration state of the animal.     

The effect of Gd-DTPA on T(1)-weighted choline signal in human brain tumours

The influence of Gd-DTPA on T(1)-weighted (T(1)W) proton MR spectra has been investigated in 19 patients with histologically verified low (n = 13) or high-grade (n = 6) gliomas. Repeat measurements were performed on 9 patients (7 low-grade and 2 high-grade), with 28 examinations performed in total. Comparison of spectra obtained before and after 0.2 mmol/kg Gd-DTPA showed contrast agent induced broadening of the choline signal without significant signal area change. Lack of enhancement of the choline signal with the T(1)-weighted acquisitions implies that the contrast agent and the trimethylamine-containing species do not undergo significant direct interaction. Contrast agent induced changes in the choline signal observed in this and previous studies may, therefore, be attributable to T2*/susceptibility-based effects.     

Magnetic resonance imaging (MRI) and pathophysiology of the rat kidney in streptozotocin-induced diabetes.

Proton magnetic resonance imaging was performed on rats before induction of diabetes with streptozotocin (STZ) and at 2 and 12 days postinduction. Images revealed an increase in maximal longitudinal and axial dimensions of the kidneys at 2 days and a further increase at 12 days. Similarly, an increase in the size of the remaining kidney was seen in a rat which underwent uninephrectomy as a positive control. Two major differences were observed between the kidney undergoing compensatory hypertrophy and those developing diabetic nephropathy: (i) Expansion of the renal vasculature was seen only in images of the diabetic rat; (ii) A loss in conspicuity of the normal corticomedullary junction was seen in the T2-weighted images of the diabetic rat but not in the uninephrectomized rat. Histologic examination revealed that the medulla increased to a size greater than the cortex during diabetic nephropathy whereas the medullary volume was less than that of the cortex during compensatory hypertrophy. In vitro T1 relaxation times in cortex, outer medulla and inner medulla of kidneys from control rats were measured and compared with the same respective regions in diabetic rats. When these values were correlated with tissue water content, a linear increase in relaxation rate versus percent water content from cortex to inner medulla was found in the control kidneys, but this correlation was absent in diabetic nephropathy. These studies demonstrate that MRI is an effective noninvasive tool for studying the course of renal hypertrophy and hydration changes in the development of renal disease in STZ-induced diabetes in the rat.     

The zonal architecture of human articular cartilage described by T2 relaxation time in the presence of Gd-DTPA2-

The depth-wise variation of T(2) relaxation time is known to reflect the collagen network architecture in cartilage, while the delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique is sensitive to tissue proteoglycan (PG) concentration. As the cartilage PG content varies along the tissue depth, the depth-dependent accumulation of the contrast agent may affect the inherent T(2) of cartilage in a nonconstant manner. Therefore, T(2) and dGEMRIC are typically measured in separate MRI sessions. In the present in vitro MRI study at 9.4 T, depth-wise T(2) profiles and collagenous zone thicknesses as determined from T(2) maps in the absence and presence of Gd-DTPA(2-) (T(2) and T(2Gd), respectively) were compared in samples of intact human articular cartilage (n=65). These T(2) measures were further correlated with birefringence (BF) of polarized light microscopy (PLM) to quantify the ability of MRI to predict the properties of the collagen fibril network. The reproducibility of the T(2) measurement in the current setup was also studied. Typical tri-laminar collagen network architecture was observed both with and without Gd-DTPA(2-). The inverse of BF (1/BF) correlated significantly with both T(2) and T(2Gd) (r=0.91, slope=0.56 and r=0.90, slope=0.63), respectively. The statistically significant linear correlations between zone thicknesses as determined from T(2) and T(2Gd) were r=0.55 (slope=0.49), r=0.74 (slope=0.71) and r=0.95 (slope=0.94) for superficial, middle and deep tissue zones, respectively. Reproducibility of the T(2) measurement was worst for superficial cartilage. Consistent with PLM, T(2) and T(2Gd) measurements reveal highly similar depth-dependent information on collagen network in intact human cartilage. Thus, dGEMRIC and T(2) measurements in one MRI session are feasible for intact articular cartilage in vitro.     

Usefulness of MR-seminography using Gd-DTPA in intermediate magnetic field MRI equipment

T(2)-weighted fast advanced spin-echo imaging with gadolinium (hereinafter referred to as "MR-seminography") of the genital tract was evaluated for its usefulness in non-invasive investigation into the morphology of these organs. Twenty healthy male volunteers who are confirmed as free of genital tract obstruction were entered into the study. The genital tract was imaged using the 0.5 T MRI system by fast advanced spin echo (FASE) method. Based on quantitative evaluation, visibility evaluation, and the visualization of the genital tract in each subject, the contrast-enhanced images were assessed in comparison with those at pre-injection of the contrast agent by four specialists. Also examined were the morphology of the seminal vesicle according to age group using "Ishigami-Mori's classification," and the age angle of the main ducts. MR-seminography produced high contrast images and revealed a significantly decreased signal in the pelvic organs under investigation. In the analysis of individual subjects, the area from the proximal portion of the vas deferens to the ampulla and the seminal vesicles was on the whole well visualized except for the distal portion of the vas deferens and the ejaculatory duct. With regard to seminal vesicle morphology, type II was predominant. The age angle showed a trend toward widening with age. MR-seminography is non-invasive, useful, and therefore a highly recommended procedure for observation of the morphology in the area from the proximal portion of the vas deferens to the seminal vesicle.     

Paramagnetic liposomes as MRI contrast agents: influence of liposomal physicochemical properties on the in vitro relaxivity

The in vitro contrast efficacy of liposome encapsulated gadolinium-[10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid] (GdHPDO3A) has been assessed by relaxometry. The internal concentrations were 150 and 250 mM Gd. Two types of liposome compositions were investigated: a phospholipid blend consisting of both hydrogenated phosphatidylcholine (HPC) and phosphatidylserine (HPS) with a gel-to-liquid crystalline phase transition temperature (T_m) of 50°C, and a mixture of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) with a T_m of 41°C. The investigated liposome size range was 70–400 nm. The T₁ and T₂ relaxivities (r₁ and r₂) of liposome encapsulated GdHPDO3A were significantly reduced at 37°C and 0.47 T, compared to those of non-liposomal metal chelate, due to an exchange limitation of the dipolar relaxation process. The highest relaxivity values were obtained for the DPPC/DPPG liposomes, and were attributed to a higher liposome water permeability and to a more efficient water exchange across the membrane. A reduction in liposome size increased the r₁, confirming the exchange limited dipolar relaxation. The increased r₁ with increasing temperature demonstrated the prerequisite of rapid water exchange between the interior and exterior of the liposome for efficient dipolar relaxation enhancement. Susceptibility effects were present in the liposome systems as the r₂/r₁ ratio increased with increasing liposome size and internal Gd concentration. In summary, the current work has shown the influence of key physicochemical properties, such as liposome size, membrane composition and permeability, on the in vitro relaxivity of liposome encapsulated GdHPDO3A.