Absolute quantification of cerebral blood flow: correlation between dynamic susceptibility contrast MRI and model-free arterial spin labeling

Purpose

To compare absolute cerebral blood flow (CBF) estimates obtained by model-free arterial spin labeling (ASL) and dynamic susceptibility contrast MRI (DSC-MRI), corrected for partial volume effects (PVEs).

Methods

CBF was measured using DSC-MRI and model-free ASL (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) at 3 T in 15 subjects with brain tumor, and the two modalities were compared with regard to CBF estimates in normal gray matter (GM) and DSC-to-ASL CBF ratios in selected tumor regions. The DSC-MRI CBF maps were calculated using a global arterial input function (AIF) from the sylvian-fissure region, but, in order to minimize PVEs, the AIF time integral was rescaled by a venous output function time integral obtained from the sagittal sinus.

Results

In GM, the average DSC-MRI CBF estimate was 150±45 ml/(min 100 g) (mean±SD) while the corresponding ASL CBF was 44±10 ml/(min 100 g). The linear correlation between GM CBF estimates obtained by DSC-MRI and ASL was r=.89, and observed DSC-to-ASL CBF ratios differed by less than 3% between GM and tumor regions.

Conclusions

A satisfactory positive linear correlation between the CBF estimates obtained by model-free ASL and DSC-MRI was observed, and DSC-to-ASL CBF ratios showed no obvious tissue dependence.     

Magnetic resonance of brain tumors: considerations of imaging contrast on the basis of relaxation measurements

Proton spin-lattice and spin-spin relaxation times have been measured in surgically-removed normal CNS tissues and a variety of tumors of the brain. All measurements were made at 20 MHz and 37 degrees C. Between grey and white matter from autopsy human or canine specimens significant differences in T1 or T2 were observed, with greater differences seen in T1. Such discrimination was reduced in samples obtained from live brain-tumor patients due to lengthening in T1 and T2 of white matter near tumorous lesions. Edematous white matter showed T1 and T2 values higher than those of autopsy disease-free white matter. Compared to normal CNS tissues, most brain tumors examined in this study demonstrated elevated T1 and T2 values. Exceptions, however, did exist. No definitive correlation was indicated on a T1 or T2 basis which allowed a distinction to be made between benign and malignant states. Furthermore, considerable variation in relaxation times occurred from tumor to tumor of the same type, suggesting that within a tumor type there are important differences in physiology, biology, and/or pathologic state. Such variation caused partial overlap in relaxation times among certain tumor types and hence may limit the capability of magnetic resonance imaging (MR) alone for the diagnosis of specific disease. Nonetheless, this study predicts that on the basis of T1 or T2 differences most brain tumors are readily detectable by MR via saturation recovery or inversion recovery with appropriate selections of pulse-spacing parameters. In general, tumors can be discriminated against white matter better than grey matter and contrast between glioma and grey matter is usually superior to that between meningioma and grey matter. This work did not consider tissue-associated proton density which should be addressed together with T1 and T2 for a complete treatment of MR contrast.     

Magnetic field dependence of spin-lattice relaxation enhancement using piperidinyl nitroxyl spin-labels

We examined the magnetic resonance properties of 12 paramagnetic piperidinyl nitroxyls in water and plasma solutions. Paramagnetic contributions to proton relaxation times were measured using 10.7 and 100 MHz spectrometers. Proton relaxation enhancement from nitroxyls increased with ascending molecular weight, in plasma solutions versus equimolar aqueous solutions, and with measurements at 10.7 MHz compared to 100 MHz. Relaxation rates were observed to approximately double at 10.7 MHz compared to 100 MHz and from water to plasma solutions. The data indicate that proton spin-lattice relaxation enhancement is magnetic field-dependent, and increases using nitroxyls of large molecular weight and with chemical substitutents that increase the microviscosity of solvent water molecules. The development of nitroxyls for diagnostic MRI will be aided by understanding these in vitro physical characteristics and trends.     

A reference agent model for DCE MRI can be used to quantify the relative vascular permeability of two MRI contrast agents

Dynamic Contrast Enhancement (DCE) MRI has been used to measure the kinetic transport constant, K^trans, which is used to assess tumor angiogenesis and the effects of anti-angiogenic therapies. Standard DCE MRI methods must measure the pharmacokinetics of a contrast agent in the blood stream, known as the Arterial Input Function (AIF), which is then used as a reference for the pharmacokinetics of the agent in tumor tissue. However, the AIF is difficult to measure in pre-clinical tumor models and in patients. Moreover the AIF is dependent on the Fahraeus effect that causes a highly variable hematocrit (Hct) in tumor microvasculature, leading to erroneous estimates of K^trans. To overcome these problems, we have developed the Reference Agent Model (RAM) for DCE MRI analyses, which determines the relative K^trans of two contrast agents that are simultaneously co-injected and detected in the same tissue during a single DCE-MRI session. The RAM obviates the need to monitor the AIF because one contrast agent effectively serves as an internal reference in the tumor tissue for the other agent, and it also eliminates the systematic errors in the estimated K^trans caused by assuming an erroneous Hct. Simulations demonstrated that the RAM can accurately and precisely estimate the relative K^trans (R^Ktrans) of two agents. To experimentally evaluate the utility of RAM for analyzing DCE MRI results, we optimized a previously reported multiecho ¹⁹F MRI method to detect two perfluorinated contrast agents that were co-injected during a single in vivo study and selectively detected in the same tumor location. The results demonstrated that RAM determined R^Ktrans with excellent accuracy and precision.     

Magnetohydrodynamic thermochemotherapy and MRI of mouse tumors

A dextran-ferrite magnetic fluid was successfully tested as magnetic resonance imaging (MRI) contrast agent. The same magnetic fluid was then combined with Melphalan, a chemotherapeutic drug, and used for magnetohydrodynamic thermochemotherapy of different tumors. The placement of the tumors in an AC magnetic field led to hyperthermia at 46 °C for 30 min. In combination with tumor slime aspiration, a 30% regression of ∼130 mm³ non-metastatic P388 tumors in BDF₁ mice was reached, together with a life span increase of 290%. The same procedure associated with cyclophosphamide treatment of ∼500 mm³ metastases tumor increased the animal's life span by 180%.     

In situ preparation of high relaxivity iron oxide nanoparticles by coating with chitosan: A potential MRI contrast agent useful for cell tracking

Iron oxide nanocrystals are of considerable interest in nanoscience and nanotechnology because of their nanoscale dimensions, nontoxic nature, and superior magnetic properties. Colloidal solutions of magnetic nanoparticles (ferrofluids) with a high magnetite content are highly desirable for most molecular imaging applications. In this paper, we present a method for in situ coating of superparamagnetic iron oxide (SPIO) with chitosan in order to increase the content of magnetite. Iron chloride salts (Fe³⁺ and Fe²⁺) were directly coprecipitated inside a porous matrix of chitosan by Co-60 γ-ray irradiation in an aqueous solution of acetic acid. Following sonication, iron oxide nanoparticles were formed inside the chitosan matrix at a pH value of 9.5 and a temperature of 50 °C. The [Fe³⁺]:[Fe²⁺]:[NH₄OH] molar ratio was 1.6:1:15.8. The final ferrofluid was formed with a pH adjustment to approximately 2.0/3.0, alongside with the addition of mannitol and lactic acid. We subsequently characterized the particle size, the zeta potential, the iron concentration, the magnetic contrast, and the cellular uptake of our ferrofluid. Results showed a z-average diameter of 87.2 nm, a polydispersity index (PDI) of 0.251, a zeta potential of 47.9 mV, and an iron concentration of 10.4 mg Fe/mL. The MRI parameters included an R1 value of 22.0 mM⁻¹ s⁻¹, an R2 value of 202.6 mM⁻¹ s⁻¹, and a R2/R1 ratio of 9.2. An uptake of the ferrofluid by mouse macrophages was observed. Altogether, our data show that Co-60 γ-ray radiation on solid chitosan may improve chitosan coating of iron oxide nanoparticles and tackle its aqueous solubility at pH 7. Additionally, our methodology allowed to obtain a ferrofluid with a higher content of magnetite and a fairly unimodal distribution of monodisperse clusters. Finally, MRI and cell experiments demonstrated the potential usefulness of this product as a potential MRI contrast agent that might be used for cell tracking.     

基于合金介电常数的可控特性增强光子自旋霍尔效应

基于平面角谱理论,系统研究了BK7玻璃-合金薄膜-空气结构中合金介电常数的变化对反射光自旋霍尔效应的调控规律.数值仿真结果表明,该结构发生表面等离激元共振的共振角主要受合金介电常数实部的影响,随介电常数实部的增加而增大,而虚部对共振角变化的影响相对较小.不同介电常数合金在其共振角处得到的较大光子自旋霍尔效应横移呈集中的带状分布,选取介电常数-2.8+1.6i的Ag-Ni合金时,光子自旋霍尔效应横移能达到1.2×10~5 nm.研究还发现将入射角固定为44.1°时,光子自旋霍尔效应横移随合金介电常数的变化呈轴对称分布,并以最大值为中心呈球面状辐射,离中心点越远光子自旋霍尔效应横移越小.选取介电常数-10.6+1.2i的Ag-Au合金时,光子自旋霍尔效应横移最大能达到8000 nm,相比于以往纯金属纳米结构BK7玻璃-金-空气中得到的最大光子自旋霍尔效应横移3000 nm有了较大的提高.该研究不仅能够有效增强光子自旋霍尔效应,还能为设计等离激元共振传感器等纳米光子器件提供理论依据.     

Hyperpolarization of 13C through order transfer from parahydrogen: a new contrast agent for MRI

The order within proton pairs in organic molecules, resulting from hydrogenation with parahydrogen, can be transferred in great part to nearby carbon 13 spins through adequate field manipulations. The molecules with hyperpolarized 13C thus obtained can be used as new contrast agents of high efficiency in MRI. After a brief presentation of the hydrogenation process and apparatus, in relatively low magnetic field, we describe the procedure of order transfer to the 13C spins through a sudden drop from the initial field to zero field followed by an adiabatic remagnetization. The expected final polarizations in the absence of relaxation are given for several compounds. Finally, we show an example of MR images observed in vivo on animals as an illustration of the contrast capacity of this new method.     

Gd complexes of diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide as a new liver-specific MRI contrast agent

This study was to describe the synthesis of complexes of gadolinium diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide Gd-DTPA-CSn (n = 6, 8, 11) as a new class of contrast agent as well as its magnetic property in a pilot magnetic resonance imaging. The efficacy of the contrast agent was assessed by measuring the longitudinal relaxivity (r₁), FLASH imaging in phantoms in vitro and signal intensity in vivo of the rat abdominal axial imaging. The r₁ of Gd-DTPA-CS₁₁ was up to 11.65 mM^− 1·s^− 1, which was 3 times higher than that of the analogous MRI contrast agent Gd-DTPA in commercial use. In vivo MR images of rat obtained with Gd-DTPA-CS₁₁ showed strong signal enhancement in liver and the vessels of the liver parenchyma during the extended period of time. The present study suggests that the new synthesized gadolinium complexes can be used as a new class of practical liver-specific MRI contrast agent because of its superior performance compared with Gd-DTPA.     

Effect of ovariectomy on contrast agent diffusion into lumbar intervertebral disc: a dynamic contrast-enhanced MRI study in female rats

Purpose

The purpose was to study the effect of estrogen deficiency on contrast agent diffusion into intervertebral disc in a rat model.

Materials and Methods

Seven-month-old female Sprague–Dawley rats were used. Fourteen rats had ovariectomy, and nine rats had sham surgery. Magnetic resonance imaging (MRI) of sagittal midsection of lumbar spine was performed with a 1.5-T magnet. Dynamic MRI was performed after a bolus injection of Gd-DOTA (0.3 mmol/kg) through tail vein. Eight hundred images were acquired at 0.6 s per acquisition. Regions of interests were drawn over three discs per rat. Maximum enhancement (E_max) and enhancement slope (E_slope) were evaluated. MRI was carried out at baseline and 8 weeks postsurgery.

Result

All disc enhancements demonstrated an initial fast wash-in phase followed by a second slower wash-in phase. For initial wash-in phase, E¹_max and E¹_slope of all rats remained unchanged at the two time points. For second wash-in phase, E²_max and E²_slope of control rats remained unchanged, while with ovariectomized rats, E²_max showed reduction at 8 weeks (4.5%±5.6%) compared to baseline (10.3%±6.3%, P=.037), and E²_slope was lower at 8 weeks (0.015±0.017) than the baseline (0.029±0.022), although it was not statistically significant (P=.101).

Conclusion

Ovariectomy induced detectable decrease in second wash-in phase of contrast agent into lumbar disc.     

The dependence of relaxation rates and chemical shift on the size of the imaged molecules and the concentration of MRI contrast agents

An intriguing phenomenon on enhancement of the relaxation rates and chemical shift of two typical magnetic resonance imaging (MRI) contrast agents based on gadolinium complex is observed. The relaxation enhancement or chemical shift change depends on the size of the molecule where the imaged nuclear species is located: the small molecules show a perfect linear relationship between the concentration and the relaxation enhancement or chemical shift change while for macromolecules pronounced nonlinearity is observed. The phenomenon is also confirmed with real images of a macromolecular sample. A quantitative theoretical interpretation of the phenomenon is proposed and the significance of this phenomenon to MRI of materials and biological systems is discussed.     

Interaction of a high-order Bessel beam with a submerged spherical ultrasound contrast agent shell - Scattering theory

Background and objective

Acoustic scattering properties of ultrasound contrast agents are useful in extending existing or developing new techniques for biomedical imaging applications. A useful first step in this direction is to investigate the acoustic scattering of a new class of acoustic beams, known as helicoidal high-order Bessel beams, to improve the understanding of their scattering characteristics by an ultrasound contrast agent, which at present is very limited.

Method

The transverse acoustic scattering of a commercially available albuminoidal ultrasound contrast agent shell filled with air or a denser gas such as perfluoropropane and placed in a helicoidal Bessel beam of any order is examined numerically. The shell is assumed to possess an outer radius a = 3.5 microns and a thickness of ∼105 nm. Moduli of the total and resonance transverse acoustic scattering form functions are numerically evaluated in the bandwidth 0 < ka? 3, which corresponds to a frequency bandwidth of 0-205 MHz that covers a wide range of applications for imaging with contrast agents. Particular attention is paid to the shell’s material, the content of its interior hollow region and the fluid surrounding its exterior. The contrast agent shell is assumed to be immersed in an ideal compressible fluid so the viscous corrections are not considered. Analytical equations are derived and numerical calculations of the total and resonance form functions are performed with particular emphasis on the effect of varying the half-cone angle, the order of the helicoidal Bessel beam as well as the fluid that fills the interior hollow space.

Results and conclusion

It is shown that shell wave resonance modes can be excited on an encapsulated micro-bubble. The forward and backscattering vanish for a helicoidal high-order Bessel beam. Additionally, the fluid filling the inner core affects the shell’s response significantly. Moreover, there is no monopole contribution to the axial scattering of a helicoidal Bessel beam of order m ? 1 so that the dynamics of contrast agents would be significantly altered. The main finding of the present theory is the suppression or enhancement for a particular resonance that may be used to advantage in imaging with ultrasound contrast agents for clinical applications.     

Pulmonary MRI contrast using Surface Quadrupolar Relaxation (SQUARE) of hyperpolarized Kr

Hyperpolarized ⁸³Kr has previously been demonstrated to enable MRI contrast that is sensitive to the chemical composition of the surface in a porous model system. Methodological advances have lead to a substantial increase in the ⁸³Kr hyperpolarization and the resulting signal intensity. Using the improved methodology for spin exchange optical pumping of isotopically enriched ⁸³Kr, internal anatomical details of ex vivo rodent lung were resolved with hyperpolarized ⁸³Kr MRI after krypton inhalation. Different ⁸³Kr relaxation times were found between the main bronchi and the parenchymal regions in ex vivo rat lungs. The T₁ weighted hyperpolarized ⁸³Kr MRI provided a first demonstration of surface quadrupolar relaxation (SQUARE) pulmonary MRI contrast.     

Pharmacokinetics of gadoversetamide injection, a gadolinium-based contrast agent, in pediatric patients

Objective

The pharmacokinetics of gadoversetamide were examined in pediatric patients scheduled to undergo contrast-enhanced MRI of the central nervous system.

Materials and Methods

One hundred patients received an intravenous injection of gadoversetamide at a dose of 0.1 mmol/kg for a contrast-enhanced MRI procedure. A subpopulation of 30 patients were enrolled to evaluate the pharmacokinetics of gadoversetamide in patients 2–11 and 12–18 years of age. Serial blood and urine samples were collected before and after the administration of gadoversetamide.

Results

The terminal half-life, initial concentration and area under the curve assessments for gadoversetamide showed no significant (P>.05) differences between the age groups or the sexes. Although no sex-related differences occurred in the volume of distribution or clearance, significant (P<.05) age-related differences were found, but once corrected for body mass or surface area the differences were no longer significant.

Conclusions

The pharmacokinetic behavior of gadoversetamide was not significantly altered by differences in age or sex in pediatric patients from 2 to 18 years of age. Although significant differences in volumes of distribution, and clearance occurred between the age groups, these differences appeared to depend on body size rather than on age in pediatric patients between 2 and 18 years of age.     

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.     

Detecting entanglement by the mean value of spin on a quantum computer

We implement a protocol to determine the degree of entanglement between a qubit and the rest of the system on a quantum computer. The protocol is based on results obtained in paper [Frydryszak et al. (2017) [23]]. This protocol is tested on a 5-qubit superconducting quantum processor called ibmq-ourense provided by the IBM company. We determine the values of entanglement of the Schrödinger cat and the Werner states prepared on this device and compare them with the theoretical ones. In addition, a protocol for determining the entanglement of rank-2 mixed states is proposed. We apply this protocol to the mixed state which consists of two Bell states prepared on the ibmq-ourense quantum device.     

Effects of a novel ultrasound contrast agent with long persistence on right ventricular pressure: Comparison with SonoVue

This work investigated the effect of infusion of a self-made ultrasound contrast agent with long persistence (named ZHIFUXIAN) on rat right ventricular pressure and made a preliminary evaluation on the relative safety of the novel microbubbles. Normal saline, SonoVue and ZHIFUXIAN were injected through caudal vein at the total volume of 0.5 ml for each injection. The right ventricular systolic pressure (RVSP) and end-diastolic pressure (RVEDP) were monitored and the changes of the pressure were compared with baseline readings. RVSP increased when saline, SonoVue or ZHIFUXIAN were injected, the greatest change being after SonoVue (about 2 mm Hg), but there was no statistical significance compared with baseline (P > 0.05). There was no significant difference in RVSP between saline, SonoVue and ZHIFUXIAN at any time point. Also, there was no significant difference in RVEDP between groups at each time point and between different time points in each group. The results indicate that the self-made microbubbles effect on right ventricular hemodynamics is equivalent to that of normal saline at the same volume needed for effective enhanced imaging, demonstrating that it does not produce changes in right ventricular blood pressure under the study conditions. Pathological examination also showed it had no obvious influence on lung, liver and kidney.     

Novel mineral contrast agent for magnetic resonance studies of bone implants grown on a chick chorioallantoic membrane

Magnetic resonance imaging (MRI) studies of tissue engineered constructs prior to implantation clearly demonstrate the utility of the MRI technique for studying the bone formation process. To test the utility of our MRI protocols for explant studies, we present a novel test platform in which osteoblast-seeded scaffolds were implanted on the chorioallantoic membrane of a chick embryo. Scaffolds from the following experimental groups were examined by high-resolution MRI: (a) cell-seeded implanted scaffolds (CIM), (b) unseeded implanted scaffolds (UCIM), (c) cell-seeded scaffolds in static culture (CIV) and (d) unseeded scaffolds in static culture (UCIV). The reduction in water proton transverse relaxation times and the concomitant increase in water proton magnetization transfer ratios for CIM and CIV scaffolds, compared to UCIV scaffolds, were consistent with the formation of a bone-like tissue within the polymer scaffold, which was confirmed by immunohistochemistry and fluorescence microscopy. However, the presence of angiogenic vessels and fibrotic adhesions around UCIM scaffolds can confound MRI findings of bone deposition. Consequently, to improve the specificity of the MRI technique for detecting mineralized deposits within explanted tissue engineered bone constructs, we introduce a novel contrast agent that uses alendronate to target a Food and Drug Administration-approved MRI contrast agent (Gd-DOTA) to bone mineral. Our contrast agent termed GdALN was used to uniquely identify mineralized deposits in representative samples from our four experimental groups. After GdALN treatment, both CIM and CIV scaffolds, containing mineralized deposits, showed marked signal enhancement on longitudinal relaxation time-weighted (T1W) images compared to UCIV scaffolds. Relative to UCIV scaffolds, some enhancement was observed in T1W images of GdALN-treated UCIM scaffolds, subjacent to the dark adhesions at the scaffold surface, possibly from dystrophic mineral formed in the fibrotic adhesions. Notably, residual dark areas on T1W images of CIM and UCIM scaffolds were attributable to blood inside infiltrating vessels. In summary, we present the efficacy of GdALN for sensitizing the MRI technique to the deposition of mineralized deposits in explanted polymeric scaffolds.     

Evaluation of MRI issues for a new neurological implant,the Sensor Reservoir

Background and Purpose

A new neurological implant, the Sensor-Reservoir, was developed to provide a relative measurement of ICP, which permits a noninvasive technique to detect and localize occlusions in ventricular drainage systems and, thus, to identify mechanical damage to shunt valves. The “reservoir” of this device can be used to administer medication or a contrast agent, to extract cerebral spinal fluid (CSF), and with the possibility of directly measuring ICP. The Sensor-Reservoir was evaluated to identify possible MRI-related issues at 1.5-T/64-MHz and 3-T/128-MHz.

Materials and Methods

Standard testing techniques were utilized to evaluate magnetic field interactions (i.e., translational attraction and torque), MRI-related heating, and artifacts at 3-T for the Sensor-Reservoir. In addition, 12 samples of the Sensor-Reservoir underwent testing to determine if the function of these devices was affected by exposures to various MRI conditions at 1.5-T/64-MHz and 3-T/128-MHz.

Results

Magnetic field interactions for the Sensor-Reservoir were not substantial. The heating results indicated a highest temperature rise of 1.8 °C, which poses no patient risks. Artifacts were relatively small in relation to the size and shape of the Sensor-Reservoir, but may interfere diagnostically if the area of interest is near the device. All devices were unaffected by exposures to MRI conditions at 1.5-T/64-MHz and 3-T/128-MHz.

Conclusion

When specific guidelines are followed, the Sensor-Reservoir is “MR conditional” for patients undergoing MRI examinations at 3-T or less.     

Superparamagnetic iron oxide nanoparticles as a liver MRI contrast agent: Contribution of microencapsulation to improved biodistribution

We have developed a new method of synthetizing superparamagnetic iron oxide nanoparticles, consisting in the modifications of Molday's method, which ensures high relaxivity (2.4 10⁵ s⁻¹·M⁻¹·L), good chemical stability, singular biodistribution and a considerable safety margin. The ED (Efficace Dose) to LD50 ratio is instead of for Gd-DTPA. In order to develop a magnetite-delivery system to the liver we have incorporated the nanoparticles into biodegradable synthetic microcapsules. Encapsulated ⁵⁹Fe oxide nanoparticles are injected into rats; in these conditions the sequestration is 9-fold greater in liver and 6 and 5 times lower in blood and carcase, respectively. This modification of the biodistribution enables the use of magnetite containing microcapsules at only 0.3 mg/kg iron to obtain an improved contrast in liver.