MRI of blood volume with superparamagnetic iron in choroidal melanoma treated with thermotherapy

Functional magnetic resonance imaging (MRI) with a new intravascular contrast agent, monocrystalline iron oxide nanoparticles (MION), was applied to assess the effect of transpupillary thermotherapy in a rabbit model of choroidal melanoma. 3D-spoiled gradient recalled sequences were used for quantitative assessment of blood volume. The MRI-parameters were 5/22/35 degrees (time of repetition (TR)/echo delay (TE)/flip angle (FA)) for T(1)- and 50/61/10 degrees for T(2)-weighted sequences. Images were collected before and at different times after MION injection. In all untreated tissues studied, MION reduced the T(2)-weighted signal intensity within 0.5 h and at 24 h (all p <== 0.012), whereas no significant changes were detected in treated tumors. T(1)-weighted images also revealed differences of MION-related signal changes between treated tumors and other tissues, yet at lower sensitivity and specificity than T(2). The change of T(2)-weighted MRI signal caused by intravascular MION allows early distinction of laser-treated experimental melanomas from untreated tissues. Further study is necessary to determine whether MRI can localize areas of tumor regrowth within tumors treated incompletely.     

Quantitative mapping of transverse relaxivity (1/T(2)) in hepatic iron overload: a single spin-echo imaging methodology

Recent research into the non-invasive assessment of hepatic iron concentrations using magnetic resonance imaging has shown that the proton transverse relaxivity (1/T(2)) varies linearly with liver iron concentration. However, the development of an image-based system for the assessment of hepatic iron distribution has been confounded by the presence of motion induced artifacts in the T(2)-weighted images. We report on the development of a single spin-echo imaging methodology that enables the generation of transverse relaxivity maps over the liver. A simple smoothing technique is used to accommodate the image intensity perturbations caused by abdominal motion. The relaxivity maps are consistent with the variation of iron concentration throughout the liver. A Parzen density estimate and histogram of the relaxivity distribution are generated to assist in the visual assessment of the degree and variability of T(2) shortening with liver iron loading. It was found that one or two Gaussian functions could be used to characterize the relaxivity distributions with a small number of parameters. We propose that this methodology may be used in the clinical setting to monitor hepatic iron concentrations in the advent of an accurate transverse relaxivity calibration curve.     

Modification of nitroxyl contrast agents with multiple spins and their proton T(1) relaxivity

The purpose of this study is to test the performance of multispin nitroxyl contrast agents in improving the sensitivity of MR detection for nitroxyl contrast agents. The relation between T(1) relaxivity and the number of paramagnetic centers in a molecule was investigated. Compound 1 is a single molecule of methoxycarbonyl-PROXYL (MC-PROXYL). Two and three MC-PROXYL molecules were chemically coupled to obtain Compounds 2 and 3, which have two and three nitroxyl spins in the molecule, respectively. A good linear relation, the slope of which increased depending on the number of nitroxyl spins in the molecule, was obtained between T(1)-weighted (fast low-angle shot) MR image contrast enhancement at 7 T and the concentration of nitroxyl contrast agents. T(1)-weighted MR image contrast enhancement and T(1) relaxivity levels of nitroxyl contrast agents were increased depending on the number of nitroxyl spins in the molecule. Multicoupling nitroxyl molecules can enhance the T(1)-weighted contrast effect while maintaining the quantitative behavior of the molecule for up to three spins.     

Structure activity relationship of magnetic particles as MR contrast agents

Structure activity relationship (SAR) of superparamagnetic MR contrast agents is discussed based on physicochemical properties and relaxivity data of 16 different particles. All the magnetic particles reduce both relaxation times, T1 and T2. The effect on T2 is stronger than the effect on T1. The relaxation efficacy varies over a wide range. Minor modifications in the preparation of the magnetic particles result in products with different susceptibility properties. The T2 relaxivity is dependent upon the magnetic susceptibility as well as particle size. Small particles reduce the relaxation times to a larger extent than the larger particles. No significant difference in relaxivity is observed between compact and porous particles. Magnetic particles coated with nonmagnet polymer are effective relaxation agents, while nonmagnetic monodisperse particles show no effect on the relaxivity.     

Assessment of absolute blood volume in carcinoma by USPIO contrast-enhanced MRI

OBJECTIVES: The characterization of tumor vasculature is essential in studying tumor physiology. The aim of this study was to develop a new method - based on water proton MR density measurements, in combination with ultrasmall superparamagnetic iron oxide (USPIO) administration - to measure absolute blood volume (BV) in murine colon carcinoma. MATERIALS AND METHODS: MRI experiments were performed at 7 T. CPMG imaging was performed on subcutaneous murine colon carcinoma in six mice before and after administration of an USPIO blood-pool contrast agent. Density maps were obtained from the signal amplitude at TE=0 of the CPMG decay fit. Post-USPIO density maps were subtracted from pre-USPIO density maps to quantitatively yield absolute tumor BV maps. In a separate group of mice (n=6), the relative vascular area (RVA) of tumors was determined by immunohistochemistry. RESULTS: Ultrasmall superparamagnetic iron oxide administration resulted in a small decrease in the water proton MR density. The BV averaged over the six tumors was 4.6+/-1.6%. The value of the RVA measured by immunohistochemical staining was equal to 3.9+/-2.2%. CONCLUSIONS: After administration of an USPIO blood-pool agent (T(2) relaxivity > 100 mM(-1) s(-1)), the blood water protons become MRI invisible, and pixel-by-pixel BV map can be obtained by subtracting the calculated post-USPIO density map from the pre-USPIO density map. The value of absolute BV obtained with this novel MR approach is in good agreement with the value of the relative vascular measured by immunohistochemical staining.     

The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

Simple low molecular weight (MW) chelates of Gd(3+) such as those currently used in clinical MRI are considered too insensitive for most molecular imaging applications. Here, we evaluated the detection limit (DL) of a molecularly targeted low MW Gd(3+)-based T(1) agent in a model where the receptor concentration was precisely known. The data demonstrate that receptors clustered together to form a microdomain of high local concentration can be imaged successfully even when the bulk concentration of the receptor is quite low. A GdDO3A-peptide identified by phage display to target the anti-FLAG antibody was synthesized, purified and characterized. T(1-)weighted MR images were compared with the agent bound to antibody in bulk solution and with the agent bound to the antibody localized on agarose beads. Fluorescence competition binding assays show that the agent has a high binding affinity (K(D)=150 nM) for the antibody, while the fully bound relaxivity of the GdDO3A-peptide/anti-FLAG antibody in solution was a relatively modest 17 mM(-1) s(-1). The agent/antibody complex was MR silent at concentrations below approximately 9 microM but was detectable down to 4 microM bulk concentrations when presented to antibody clustered together on the surface of agarose beads. These results provided an estimate of the DLs for other T(1)-based agents with higher fully bound relaxivities or multimeric structures bound to clustered receptor molecules. The results demonstrate that the sensitivity of molecularly targeted contrast agents depends on the local microdomain concentration of the target protein and the molecular relaxivity of the bound complex. A model is presented, which predicts that for a molecularly targeted agent consisting of a single Gd(3+) complex with bound relaxivity of 100 mM(-1) s(-1) or, more reasonably, four tethered Gd(3+) complexes each having a bound relaxivity of 25 mM(-1) s(-1), the DL of a protein microdomain is approximately 690 nM at 9.4 T. These experimental and extrapolated DLs are both well below current literature estimates and suggests that detection of low MW molecularly targeted T(1) agents is not an unrealistic goal.     

Proton T1 and T2 relaxivities of serum proteins

In the present study, T(1) and T(2) of phantoms containing serum sets with varying amounts of proteins, serum samples with certain amounts of proteins, serum diluted by distilled water, and serum treated with iron were measured. In addition, T(1) and T(2) of phantoms containing normal serum, diluted serum, and albumin-doped serum were also measured. Relaxation rates were plotted versus protein concentrations. The slope of relation was taken as relaxivity. The T(1) relaxivities of proteins were ranged from 0.035 to 0.080 s(-1)(g/dl)(-1), whereas T(2) relaxivities were ranged from 0.24 to 0.68 s(-1)(g/dl)(-1). The T(1) and T(2) relaxivities of transferrin iron were 2.40 and 2.60 mM(-1)s(-1), respectively. The contributions of diamagnetic proteins and transferrin iron to the relaxation rate of serum were also calculated for each of diluted serum, normal and albumin-doped serum. The contributions and the average TP relaxivities(calculated by using individual relaxivities and the ratios of protein fractions in TP) were used for TP calculations. The agreement between the calculated TP and TP by autoanalyzer and also the agreement between average TP relaxivities and the TP relaxivities determined from dilution experiments show that the data of relaxivities are reliable. The results suggest that individual protein relaxivities explain the influence of serum TP composition on T(1) and T(2) relaxation times.     

In vitro labeling and MRI of mesenchymal stem cells from human umbilical cord blood

OBJECTIVE: The aim of this study was to label human umbilical cord blood mesenchymal stem cells (MSCs) with poly-l-lysine (PLL)-conjugated superparamagnetic iron oxide particles and to obtain magnetic resonance (MR) images of the labeled MSCs' suspension at 1.5 T. MATERIAL AND METHODS: PLL was conjugated with iron oxide to form superparamagnetic particles called Fe(2)O(3)-PLL. Human umbilical cord blood MSCs were isolated, purified, expanded and incubated with Fe(2)O(3)-PLL. Prussian blue stain was performed to show intracellular iron; spectrometry was used to quantify iron uptake within cells. Tetrazolium salt (MTT) assay was applied to evaluate toxicity and proliferation of MSCs labeled with various concentrations of Fe(2)O(3)-PLL. The cell apoptosis rate was determined by annexin V/propichium iodide (PI) double staining method. Vials containing cells underwent MR imaging (MRI) with T(1), T(2) and T(2)* weighted MRI. RESULTS: Iron-containing intracytoplasmatic vesicles could be observed clearly with Prussian blue staining in all samples except the unlabeled control. The iron content per cell determined by spectrometry was 64.51+/-10.32 pg. Among MSCs with and without labeling of various concentrations of Fe(2)O(3)-PLL, MTT values of light absorption had no statistically significant difference (Kruskal-Wallis test, chi(2)=10.35, P=.17). A concentration at 20 mug/ml of iron appeared most suitable for incubating cells. Of labeled and unlabeled MSCs, the early [annexin V-fluorescein isothiocyanate (FITC)-positive/PI-negative] and late (annexin V-FITC-positive/PI-positive) apoptotic cells were 10.34+/-0.43%/11.36+/-1.30% and 4.01+/-1.76%/2.98+/-1.37%, respectively, and there were no significant differences between them (P>.05). T(2) weighted image (WI) and T(2)*WI demonstrated significant decrease of signal intensity (SI) in vials containing 1 x 10(6) (1 day), 1x10(6) (8 days) and 5 x 10(5) labeled cells, in comparison with unlabeled cells (P<.05). The percentage change of SI (DeltaSI) was significantly higher in 10(6) labeled cells after 1-day culture than that in the same number of labeled cells after 8-day culture and that in 5 x 10(5) labeled cells, particularly on T(2)*WI (P<.05). Among pulse sequences, T(2)*WI demonstrated the highest DeltaSI (P<.05). CONCLUSION: The human umbilical cord blood MSCs can be labeled with Fe(2)O(3)-PLL without significant change in viability and apoptosis. The suspension of labeled MSCs can be imaged with standard 1.5-T MR equipment.     

Nuclear magnetic resonance study of iron overload in liver tissue

Whole-tissue and homogenized samples of human liver were studied in a NMR spectrometer, T1 and T2 relaxation times were measured as a function of added inorganic or organic iron. When inorganic iron (Fe+3) was added, pronounced T1 and T2 shortening was noted. However, when organic iron, in the form of ferritin, was added, the amount of T1 and T2 relaxation enhancement was much reduced for the same amount of added iron. The in vitro ferritin results model the situation found in clinical studies of hemochromatosis. Only in cases of severe iron overload were significant decreases in relaxation times observed. The T2 relaxation time was the more reliable indicator of excessive levels of iron in the liver. The large range of T1 and T2 values encountered in normal volunteers precludes the use of MR to quantitatively measure iron levels in the liver. The T1 and T2 relaxation times measured at intervals for one individual tend to fluctuate as well, making the use of MR to follow the course of treatment of iron overload disorders unreliable.     

Magnetoplex based on MnFe<Subscript>2</Subscript>O<Subscript>4</Subscript> nanocrystals for magnetic labeling and MR imaging of human mesenchymal stem cells

For efficient labeling and tracking via magnetic resonance (MR) imaging of human mesenchymal stem cells (h-MSCs), magnetic labeling agents must be responsive to an external magnetic field. Thus, we developed ultrasensitive magnetoplex as a magnetic labeling agent composed of PEGylated MnFe₂O₄ nanocrystals (PMNCs) and polycationics (poly-l-lysine, PLL) for efficient labeling of the h-MSCs and monitoring of the transplanted h-MSCs for a long term. PMNCs were prepared by nanoemulsion methods composed of MnFe₂O₄ nanocrystals (MNCs) and amphiphilic polymers (mPEG–dodecanoic acid). The prepared PMNCs exhibited excellent biocompatibility and their polycationic complexes (PMNCs/PLL) demonstrated remarkable sensitivity compared with magnetic iron oxide nanoparticles (MION)/PLL or Ferumoxides/PLL. Furthermore, PMNCs demonstrated the potentials for novel diagnostic and therapeutic strategies with potential applications in various biomedical fields.     

用MRI无损检测胆囊中的胆汁成

为了探索用磁共振成象方法无损伤检测胆囊中的胆汁成分的可能性,我们用0.5T的磁共振成象仪,对38例禁食期胆囊疾病患者(12例急性无并发症胆囊炎及胆结石,1例化浓性胆囊炎,2例急性出血性胆囊炎,14例慢性胆囊炎及胆结石,5例胆囊息肉,4例障碍性黄疸进行了轴向腹部胆囊部位T1-加权自旋-回波成象.结果表明:禁食或胆囊疾病患者胆汁中胆固醇(p=0.014),脂肪酸(p=0.001),和铁(p<0.001)的浓度对T₁-加权成象(TR/TE=620/25ms)的肝-胆信号强度比有明显的负影响,同时发现总蛋白质,总胆红素及Na⁺,K⁺,Cl^-,Mg⁺⁺离子的浓度对肝-胆MRI信号强度比无显著影响,由此可见,T₁-加权MRI中的肝-胆信号强度比反映了胆囊中的胆汁成分,其中影响肝-胆信号强度比的最重要因素是胆囊中胆汁所含胆固醇、脂肪酸和铁的浓度.     

MRI with superparamagnetic iron oxide: efficacy in the detection and characterization of focal hepatic lesions

The purpose of this study was to evaluate the potential of superparamagnetic iron oxide particles (SPIO) as tissue specific contrast agent in magnetic resonance (MR) imaging in detection and characterization of focal hepatic lesions. We investigated 45 patients with focal hepatic lesions. T1-weighted SE (TR 650/TE 15 ms) and T2-weighted SE (TR 2015-2030/TE 45 and 90 ms) unenhanced images were obtained. After SPIO application we performed T1-weighted images with and T2-weighted images with and without fat suppression using the same image parameters. Liver signal intensity decreased by 74% (min 47%, max 83%) on T2-weighted images after application of the contrast agent. Benign lesions (FNH, adenoma) showed an average signal drop of 40% (min 20%, max 47%) whereas malignant lesions showed no significant change of signal intensity on post-contrast images. The mean tumor-to-liver contrast-to-noise ratio (C/N) was improved in all post-contrast sequences irrespective of the lesion type. An additional increase of tumor-to-liver contrast by use of fat suppression technique could be established in the slightly T2-weighted sequence (TE 45 ms). In metastases, divided in different size groups, we could determine a significant size relation of tumor-to-liver C/N. After SPIO application the number of detected lesions increased distinctly, especially small foci are more easily demonstrated. SPIO particles are a efficacious contrast agent for MR examinations of the liver. For tumor characterization T1- and T2-weighted pre- and post-contrast images are necessary. The T1-weighted sequences are helpful to differentiate benign lesions such as cysts and hemangiomas from malignant lesions. Detection and differential diagnoses of hepatic lesions are improved by use of the SPIO-particles.     

Ex vivo assessment of polyol coated-iron oxide nanoparticles for MRI diagnosis applications: toxicological and MRI contrast enhancement effects

Polyol synthesis is a promising method to obtain directly pharmaceutical grade colloidal dispersion of superparamagnetic iron oxide nanoparticles (SPIONs). Here, we study the biocompatibility and performance as T2-MRI contrast agents (CAs) of high quality magnetic colloidal dispersions (average hydrodynamic aggregate diameter of 16-27 nm) consisting of polyol-synthesized SPIONs (5 nm in mean particle size) coated with triethylene glycol (TEG) chains (TEG-SPIONs), which were subsequently functionalized to carboxyl-terminated meso-2-3-dimercaptosuccinic acid (DMSA) coated-iron oxide nanoparticles (DMSA-SPIONs). Standard MTT assays on HeLa, U87MG, and HepG2 cells revealed that colloidal dispersions of TEG-coated iron oxide nanoparticles did not induce any loss of cell viability after 3 days incubation with dose concentrations below 50 μg Fe/ml. However, after these nanoparticles were functionalized with DMSA molecules, an increase on their cytotoxicity was observed, so that particles bearing free terminal carboxyl groups on their surface were not cytotoxic only at low concentrations (<10 μg Fe/ml). Moreover, cell uptake assays on HeLa and U87MG and hemolysis tests have demonstrated that TEG-SPIONs and DMSA-SPIONs were well internalized by the cells and did not induce any adverse effect on the red blood cells at the tested concentrations. Finally, in vitro relaxivity measurements and post mortem MRI studies in mice indicated that both types of coated-iron oxide nanoparticles produced higher negative T2-MRI contrast enhancement than that measured for a similar commercial T2-MRI CAs consisting in dextran-coated ultra-small iron oxide nanoparticles (Ferumoxtran-10). In conclusion, the above attributes make both types of as synthesized coated-iron oxide nanoparticles, but especially DMSA-SPIONs, promising candidates as T2-MRI CAs for nanoparticle-enhanced MRI diagnosis applications.     

Relaxivity of Gd-based contrast agents on X nuclei with long intrinsic relaxation times in aqueous solutions

The relaxivity of commercially available gadolinium (Gd)-based contrast agents was studied for X-nuclei resonances with long intrinsic relaxation times ranging from 6 s to several hundred seconds. Omniscan in pure 13C formic acid had a relaxivity of 2.9 mM(-1) s(-1), whereas its relaxivity on glutamate C1 and C5 in aqueous solution was approximately 0.5 mM(-1) s(-1). Both relaxivities allow the preparation of solutions with a predetermined short T1 and suggest that in vitro substantial sensitivity gains in their measurement can be achieved. 6Li has a long intrinsic relaxation time, on the order of several minutes, which was strongly affected by the contrast agents. Relaxivity ranged from approximately 0.1 mM(-1) s(-1) for Omniscan to 0.3 for Magnevist, whereas the relaxivity of Gd-DOTP was at 11 mM(-1) s(-1), which is two orders of magnitude higher. Overall, these experiments suggest that the presence of 0.1- to 10-microM contrast agents should be detectable, provided sufficient sensitivity is available, such as that afforded by hyperpolarization, recently introduced to in vivo imaging.     

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.     

L-赖氨酸长链烷基酯双DTPA酰胺钆(Ⅲ)配合物的合成、表征与弛豫效能

通过二乙三胺五乙酸单环酸酐(DTPA-MA)分别与L-赖氨酸的十八酯、十六酯、十四酯和十二酯的双酰化反应, 制得四种含有双DTPA螯合单元的新型配体. 它们与GdCl3·6H2O配合得到相应的双核钆(Ⅲ)配合物. 表征了配体和配合物的结构, 测试了配合物的纵向弛豫效能(R1). 结果表明: 这四种新钆配合物的R1都高于Gd-DTPA.     

MR enteroclysis using iron oxide particles (ferristene) as an endoluminal contrast agent: an open phase III trial

To evaluate efficacy and safety of a superparamagnetic iron oxide contrast agent (ferristene) as an endoluminal contrast medium for magnetic resonance (MR) enteroclysis in a phase III trial. Twenty-three patients with history of known or suspected small bowel Crohn's disease underwent MR imaging of the abdomen at 0.5 T unit. The imaging protocol included two phases: the first one without administration of any contrast agent and the second one, where the small bowel was filled by enteroclysis with 800 ml of the luminal iron oxide contrast medium and Gd-DTPA (0.1 mmol/Kg) was administered intravenously. Axial Spin-Echo (SE) T1-weighted (T1w), proton-density and T2w images, sagittal and coronal SE T1w and Short TI Inversion Recovery (STIR) sequences were subsequently obtained. Three investigators blindly evaluated images to determine small bowel distribution of ferristene, presence of artifacts, delineation of bowel lesion/wall and the diagnostic value of ferristene combined with gadolinium. Pre- and postcontrast signal intensity measurements of bowel lesion/wall, bowel lumen and background noise were also calculated. Three patients withdrew before the procedure, therefore 20 patients were effectively included in the study. No significant difference between the three investigators' evaluations of the improvement of the diagnostic information was found (percentage of improvement of 90% with 95% confidence limits of 68% and 99%). A statistically significant difference between the first and third investigators was found for grading of quality of delineation of bowel lesion/wall. Signal intensity measures showed a significant increase of the bowel lesion/wall and background noise/lesion for the SE T1w images. No serious adverse event was reported in our series. MR enteroclysis using ferristene as an endoluminal contrast agent appears to be a safe and efficient procedure for the study of the small bowel.     

Facile Synthesis of Lactobionic Acid‐Targeted Iron Oxide Nanoparticles with Ultrahigh Relaxivity for Targeted MR Imaging of an Orthotopic Model of Human Hepatocellular Carcinoma

Development of multifunctional nanoprobes for tumor diagnosis is extremely important in the field of molecular imaging. In this study, the facile synthesis of lactobionic acid (LA)‐targeted superparamagnetic iron oxide (Fe₃O₄) nanoparticles (NPs) with ultrahigh relaxivity for targeted magnetic resonance (MR) imaging of an orthotopic hepatocellular carcinoma (HCC) is reported. Polyethyleneimine (PEI)‐stabilized Fe₃O₄ NPs prepared via a mild reduction route are sequentially coupled with fluorescein isothiocyanate and polyethylene glycol‐LA (LA‐PEG‐COOH) segment, followed by acetylation of the remaining PEI surface amines. The formed LA‐targeted Fe₃O₄ NPs are thoroughly characterized. It is shown that the developed multifunctional LA‐targeted Fe₃O₄ NPs are colloidally stable and water‐dispersible, display an ultrahigh r ₂ relaxivity (579.89 × 10^?3 m ^?1 s^?1) and excellent hemocompatibility and cytocompatibility in the given concentration range, and can target HepG2 cells overexpressing asialoglycoprotein receptors as confirmed by in vitro cellular uptake assay, flow cytometry, and confocal microscopy. Most strikingly, the developed multifunctional LA‐targeted Fe₃O₄ NPs can be used as a nanoprobe for targeted MR imaging of HepG2 cells in vitro and an orthotopic tumor model of HCC in vivo. With the ultrahigh r ₂ relaxivity and the versatile PEI amine‐mediated conjugation chemistry, a range of different Fe₃O₄ NP‐based nanoprobes may be developed for theranostics of different types of cancer.     

Evaluation of two new gadolinium chelates as contrast agents for MRI

Two new gadolinium chelates were investigated for potential use as tissue-specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N″-bis(3-hydroxy-6-methyl-2-pyridylmethyl)diethylenetriamine-N,N′,N″-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7-13-triaza-4,10-16-trioxacyclooctadecane-N,N′,N″-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T₁-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney.     

Paramagnetic contribution of serum iron to the spin-lattice relaxation rate (1/T 1) determined by MRI

T ₁ maps of phantoms containing the samples of pure serum or Mn(II)-doped serum at pH=2 were imaged by 1.5 T and 1 T MR Imagers. TheT ₁ measurements made for the determination of the paramagnetic increase were carried out before and after adding ascorbic acid. The difference of the 1/T ₁ in samples with and without ascorbic acid was evaluated as the paramagnetic contribution (PMC) of serum iron. As iron content of serum varied from iron deficient to iron overload, the PMC values increased from 0.93 to 0.565 s^?1 at 1.5 T and from 0.103 to 0.609 s^?1 at 1 T. For confirmative purposes, serum iron of each sample was determined from the paramagnetic contribution and also by an autoanalyzer. The contents of serum iron determined from PMC were in good agreement with those by the autoanalyzer and also with the literature. The data suggest that the paramagnetic contribution of serum iron can be measured by MRI.