Superparamagnetic particles as an MRI contrast agent for the gastrointestinal tract

Non-biodegradable superparamagnetic particles containing magnetite were evaluated as a potential contrast agent for the gastrointestinal tract. The particles were administered to pigs perorally either suspended in water or mixed with food. The gastrointestinal tract structures were excellently depicted through a lowered signal intensity of their content in both T1 and T2 weighted images. Relatively large volumes with low particle concentration seemed to give a good contrast agent distribution, especially when the administration was extended over a period of time. Problems with artefacts and blurring in the images caused by a too high local concentration of the contrast agent should also be minimized by using low particle concentrations.     

Gadolinium-DTPA as a contrast agent in MRI: initial clinical experience in 20 patients

Magnetic resonance imaging (MRI) was performed in 20 patients before and after intravenous administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) in a dose of 0.1 mmol/kg. Twelve of the patients had clinical and histologic diagnoses of cerebral tumor, six had hepatic tumors, one had hepatic cysts, and one had transitional cell carcinoma of the bladder. Contrast enhancement was seen with all tumors, but not with the hepatic cysts. The degree of enhancement was greater than that seen with computed tomography (CT) in 13 cases, equal to it in six, and less in one. Contrast enhancement was detectable as long as 18 hr after injection of Gd-DTPA in one case of cerebral tumor. The margin between cerebral tumor and peritumoral edema could be delineated with contrast-enhanced MRI to the degree possible with contrast-enhanced CT. In the liver isointense enhancement was seen with saturation-recovery (SR), inversion-recovery (IR), and spin-echo (SE) sequences although not with all three sequences simultaneously. In general IR sequences were most sensitive for display of the contrast agent, but the enhancement often decreased the difference between abnormal and normal tissue. No short-term side effects were encountered and no significant change was seen in urea, creatinine, electrolytes, liver function tests, blood coagulation, or urine testing after injection of Gd-DTPA. Although much more work will be required to evaluate this contrast agent, these initial experiences are very promising.     

Evaluation of methemoglobin as an autologous intravascular MRI contrast agent

Methemoglobin (MetHb) was evaluated as an intravascular paramagnetic contrast agent. Methemoglobin formation was induced by 4-dimethylaminophenol (4-DMAP), causing a reduction in blood T₂* in vitro. The 4-DMAP generated metHb with a time constant of 62 s. A 4-DMAP bolus did not decrease measurably the signal intensity in the in vivo rabbit kidney in the first pass. At steady state, a MetHb concentration of 24.8 ± 2.3% resulted in a signal decrease of 9.2 ± 2.6% in the kidney. Methemoglobin is an effective vascular T₂* relaxation agent, but the formation of MetHb by 4-DMAP is too slow for first-pass imaging. A more effective conversion agent resulting in a bolus of at least 25% MetHb within 5 s would result in a detectable first-pass signal and a viable contrast technique.     

Evaluation of a new ultrasmall superparamagnetic iron oxide contrast agent Clariscan, (NC100150) for MRI of renal perfusion: experimental study in an animal model

PURPOSE: To determine the diagnostic value of a new ultrasmall superparamagnetic iron oxide Clariscan, (NC100150) for the evaluation of renal perfusion in an animal model using a 3D-FFE-EPI sequence. MATERIALS AND METHODS: Four groups of four rabbits each were imaged after bolus injection of NC100150, using a 1.5 T MR system (Gyroscan ACS-NT). T2*w MR images in the coronal plane were acquired over 60 seconds with an echo-shifted 3D-FFE-EPI sequence (TR/TE/alpha = 18/25 msec/8 degrees ). Data were transferred to a workstation and converted into concentration curves. Based on the fitted concentration time curves, parameter maps were calculated pixelwise: bolus arrival time (T0), time-to-peak (TTP), mean transit time (MTT), and relative bolus volume (rBV). Maximum signal decrease was determined with respect to the baseline value. RESULTS: Mean MTT increased from 4.2 seconds at a dose of 0.25 mg to 5.9 seconds at 1.0 mg (P < .0001). The maximum signal decrease was observed at 0.75 mg, corresponding to 85% of the baseline value. Transit times of the contrast bolus were accurately calculated for the cortex and the outer medulla, but at the level of the inner medulla no arterial flow profile was identified. No significant difference between the cortex and the outer medulla was found for either T0 or rBV, but medullar TTP and MTT were prolonged with regard to cortical TTP and MTT (6.3 seconds vs. 5.7 seconds, P < .001; 5.7 seconds vs. 4.2 seconds, P < .0001). CONCLUSION: The employed intravascular contrast agent is well suited to assess renal perfusion. By the use of a T2*w3D perfusion sequence, cortical and medullar transit times can be quantified and physiologic information on regional perfusion differences can be obtained.     

Breast MRI using a high-relaxivity contrast agent: an overview

OBJECTIVE: The purpose of this article is to review the use of gadobenate dimeglumine, a high-relaxivity gadolinium-based contrast material, for breast MRI. CONCLUSION: Thanks to its high relaxivity, gadobenate dimeglumine offers valuable advantages in terms of lesion conspicuity, detection rate, and sensitivity for malignant breast lesions. However, a higher enhancement of benign lesions should be taken into account to avoid reduced specificity.     

MRI evaluation of myocardial perfusion without a contrast agent using magnetization transfer

We propose a new magnetic resonance imaging (MRI) technique that is sensitive to myocardial tissue perfusion that obviates the use of an extrinsic contrast agent. Significant advantages of such a technique are that it avoids accumulation of contrast agent when repeated studies are performed on the same subject and that it is completely noninvasive. The method makes use of a combination of magnetization transfer (MT) and T₁^sut (measured spin-lattice reiaxation time in the presence of MT) weighting. in this Communication, we present observations from experiments with an isolated rat heart model that demonstrate increase of MT-weighted signal Intensity and T₁^sut with flow. Also included are data showing that these effects can be made synergistic for enhancing the sensitivity to perfusion. We have observed about a 3% change in MT-weighted intensity end up to 10% change in MTT₁^sut-weighted intensity for a change of 1 ml/min in global flow rate.     

Kinetic characterization of CMD-A2-Gd-DOTA as an intravascular contrast agent for myocardial perfusion measurement with MRI.

Recent developments in magnetic resonance imaging (MRI) using specific contrast media allow the assessment of myocardial perfusion. The purpose of this study was to characterize the intravascular properties of a new macromolecular contrast agent, CMD-A2-Gd-DOTA, to evaluate myocardial perfusion. Two groups of isolated pig hearts perfused at various controlled flows were used. To demonstrate the intravascular properties of CMD-A2-Gd-DOTA, the agent was simultaneously injected with 99mTc-labeled red blood cells in five hearts (group 1). Tracer kinetics of both compounds were assessed by coronary sinus effluent sampling, radioactivity counting and concentration determination in samples for first-pass time curves measurements. Five other hearts (group 2) were studied using a two-slice turboFLASH sequence on a 1.5-T whole-body MRI in order to evaluate first-pass CMD-A2-Gd-DOTA signal intensity (SI) versus time curves. In group 1, for the studied flows ranging from 0.8 to 3.1 ml/min(-1) x g(-1), CMD-A2-Gd-DOTA showed first-pass concentration curves typical of an intravascular contrast agent. In group 2, MRI parameters, i.e., upslope and mean transit time of SI time curves correlated strongly with myocardial perfusion. Within the physiologic range of flows, CMD-A2-Gd-DOTA was able to demonstrate tracer kinetics for in vivo assessment of myocardial perfusion using MRI.     

Iron-EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies

The paramagnetic metal complex iron(III) ethylenebis-(2-hydroxyphenylglycine) [Fe(EHPG)-] is an effective hepatobiliary contrast agent for liver enhancement in magnetic resonance (MR) imaging. The intravenous administration of 0.2 mmol/kg of Fe(EHPG)- to rats yields a 200% increase in the signal intensity of the liver when using a T1-weighted inversion recovery pulse sequence on a 1.4 T imaging system. Biodistribution studies in rats and a rabbit, along with imaging studies in a dog at 0.6 T, confirm that the complex has significant hepatocellular uptake and appears to be excreted unaltered into the bile. Control experiments with a different iron complex, iron(III) diethylenetriaminepentaacetic acid, reveal little hepatic affinity and poor enhancement capability due to its extracellular distribution. This initial evaluation of Fe(EHPG)- demonstrates that paramagnetic metal complexes with hepatobiliary specificity are well suited for enhancement of normal liver parenchyma and may increase the sensitivity of MR in the detection of liver disease.     

First-pass renal perfusion imaging using MS-325, an albumin-targeted MRI contrast agent.

RATIONALE AND OBJECTIVES: MR angiography is proving to be a useful clinical study for the diagnosis of vascular disorders of renal arteries. However, its utility in terms of stenosis characterization is still limited. Renal perfusion could provide supplemental information that could allow for a comprehensive evaluation of renal artery stenosis by MR imaging. METHODS: MS-325 is a small-molecule blood pool agent that reversibly binds with serum albumin and hence leads to higher relaxivity and longer residence times in the blood. In this study, the authors evaluated the use of MS-325 to perform first-pass perfusion imaging and contrast-enhanced MR angiography in the characterization of renal artery stenosis in an animal model. RESULTS: Quantitative perfusion estimates were obtained in the renal cortex (258 +/- 19.8 mL/min/100 g) and are comparable to microsphere measurements (198 +/- 12.2 mL/min/100 g), given the practical constraints. Based on these measurements, perfusion showed minimal changes even when the diameter reductions reached 75%. CONCLUSIONS: MS-325 could provide quantitative perfusion estimates that when combined with MR angiography may lead to comprehensive evaluation of renal artery stenosis.     

Influence of contrast agent dispersion on bolus-based MRI myocardial perfusion measurements: A computational fluid dynamics study

Purpose

Bolus-based dynamic contrast agent (CA) perfusion measurements of the heart are subject to systematic errors due to CA bolus dispersion in the coronary arteries. To better understand these effects on quantification of myocardial blood flow and myocardial perfusion reserve (MPR), an in-silico model of the coronary arteries down to the pre-arteriolar vessels has been developed.

Methods

In this work, a computational fluid dynamics analysis is performed to investigate these errors on the basis of realistic 3D models of the left and right porcine coronary artery trees, including vessels at the pre-arteriolar level. Using advanced boundary conditions, simulations of blood flow and CA transport are conducted at rest and under stress. These are evaluated with regard to dispersion (assessed by the width of CA concentration time curves and associated vascular transport functions) and errors of myocardial blood flow and myocardial perfusion reserve quantification.

Results

Contrast agent dispersion increases with traveled distance as well as vessel diameter, and decreases with higher flow velocities. Overall, the average myocardial blood flow errors are −28% ± 16% and −8.5% ± 3.3% at rest and stress, respectively, and the average myocardial perfusion reserve error is 26% ± 22%. The calculated values are different in the left and right coronary tree.

Conclusion

Contrast agent dispersion is dependent on a complex interplay of several different factors characterizing the cardiovascular bed, including vessel size and integrated vascular length. Quantification errors evoked by the observed CA dispersion show nonnegligible distortion in dynamic CA bolus-based perfusion measurements. We expect future improvements of quantitative perfusion measurements to make the systematic errors described here more apparent.

     

3D pulmonary perfusion MRI and MR angiography of pulmonary embolism in pigs after a single injection of a blood pool MR contrast agent

The purpose of this study was to assess the feasibility of contrast-enhanced 3D perfusion MRI and MR angiography (MRA) of pulmonary embolism (PE) in pigs using a single injection of the blood pool contrast Gadomer. PE was induced in five domestic pigs by injection of autologous blood thrombi. Contrast-enhanced first-pass 3D perfusion MRI (TE/TR/FA: 1.0 ms/2.2 ms/40°; voxel size: 1.3×2.5×4.0 mm³; TA: 1.8 s per data set) and high-resolution 3D MRA (TE/TR/FA: 1.4 ms/3.4 ms/40°; voxel size: 0.8×1.0×1.6 mm³) was performed during and after a single injection of 0.1 mmol/kg body weight of Gadomer. Image data were compared to pre-embolism Gd-DTPA-enhanced MRI and post-embolism thin-section multislice CT (n=2). SNR measurements were performed in the pulmonary arteries and lung. One animal died after induction of PE. In all other animals, perfusion MRI and MRA could be acquired after a single injection of Gadomer. At perfusion MRI, PE could be detected by typical wedge-shaped perfusion defects. While the visualization of central PE at MRA correlated well with the CT, peripheral PE were only visualized by CT. Gadomer achieved a higher peak SNR of the lungs compared to Gd-DTPA (21±8 vs. 13±3). Contrast-enhanced 3D perfusion MRI and MRA of PE can be combined using a single injection of the blood pool contrast agent Gadomer.     

Emerging applications for ferumoxytol as a contrast agent in MRI

Ferumoxytol is an ultrasmall superparamagnetic iron oxide (USPIO) agent initially approved by the Food and Drug Administration (FDA) as an iron replacement therapy for patients with anemia due to chronic renal failure. Recently, ferumoxytol has been investigated extensively as an intravenous contrast agent in magnetic resonance imaging (MRI). Since it causes regional T₁ and T₂* shortening in vivo, conventional pulse sequences can be used following ferumoxytol administration to demonstrate signal enhancement or loss. Ferumoxytol can be administered as a rapid bolus and has a long intravascular half‐life on the order of 14–15 hours, making it a potentially useful agent for vascular and perfusion‐weighted MRI. In comparison to other USPIOs, ferumoxytol is less limited by allergic and idiosyncratic reactions. Furthermore, since ferumoxytol is an iron‐based agent with no potential for causing nephrogenic systemic fibrosis, it may be useful as an alternative to gadolinium‐based contrast agents in patients with compromised renal function. Ferumoxytol is ultimately taken up by macrophages/the reticuloendothelial system in the liver, spleen, and lymph nodes, and this uptake mechanism is being explored as a novel imaging technique for vascular lesions, tumors, and lymph nodes. This article reviews the properties of ferumoxytol relevant to MRI as well as many of the uses for the agent currently under investigation. J. Magn. Reson. Imaging 2015;41:884–898 . © 2014 Wiley Periodicals, Inc .     

A phospholipid spin label used as a liposome-associated MRI contrast agent

Given current clinical use of phospholipid bilayer structures (liposomes/vesicles) as nontoxic drug delivery vehicles, we have addressed the possibility of employing the phospholipids themselves as MRI contrast agents. To this end we have synthesized phosphatidylcholine with a nitroxide spin label replacing one methyl residue of the choline headgroup. This material was mixed with natural phosphatidylcholine in mole ratios from 1:50 to 1:1 and used to prepare sonicated unilamellar vesicles in saline. Expected structural features of these vesicles were verified by freeze-fracture electron microscopy. Proton T1 values of saline were readily decreased to less than 0.3 s by such preparations, yielding a net relaxivity of 0.6 M-1 s-1. The approach seems to be a realistic way of firmly associating a contrast agent of minimal toxicity with ordinary liposomes/vesicles in a manner that is not subject to leakage.     

Dextran-magnetite: a contrast agent for sodium-23 MRI

Dextran-magnetite, a superparamagnetic compound, is a powerful relaxation reagent for sodium. Administered intravenously, it is confined mainly to the vasculature and eliminates the signal from plasma sodium, a significant component of the tissue sodium signal. Applications of dextran-magnetite for in vivo sodium imaging of a normal rat and rats with a tumor and experimentally induced peripheral edema are shown. Our results indicate that dextran-magnetite may be useful for improving tumor detection and for imaging of edema. To our knowledge, this is the first report of a contrast agent suitable for sodium magnetic resonance imaging.     

The value of gadoterate meglumine as a gastrointestinal contrast agent in MRI

To evaluate the safety and efficacy of a gadoterate meglumine formulation as an oral contrast agent, MRI (0.5 T) was performed on 29 patients with abdominal disease before and after administration of contrast material. The patients ingested 16 ml/kg of a gadoterate meglumine solution (10 g/l glucose, 2 mmol/l gadoterate meglumine) over 1 h. Fourteen per cent of patients had mild side effects related to the contrast agent. Significant hyperintense contrast enhancement was achieved for the stomach and duodenum allowing better delineation of gastric and duodenal walls, entire pancreas and spleen on T1- and T2-weighted spin echo sequences. In 5 patients more diagnostic information was available from post-contrast images compared with precontrast images. This study shows that gadoterate meglumine is a safe and well-tolerated contrast agent that improves MRI of the proximal gastrointestinal tract and upper abdomen.Presented at the European Congress of Radiology, Vienna, Austria, 15–20 September 1991 Correspondence to: Y. Miaux     

MRI of hepatic adenomatosis: initial observations with gadoxetic acid contrast agent in three patients

OBJECTIVE: The purpose of our study was to describe the MR signal characteristics of histologically proven liver adenomatosis in three patients using gadoxetic acid, a newly developed liver-specific MR contrast agent. CONCLUSION: In all three patients, more than 100 liver adenomas revealed no metabolism of the new liver-specific contrast agent in the delayed phase. Because of absent or strongly reduced intracellular uptake of gadoxetic acid in all adenomas during delayed contrast-enhanced series, differentiation of adenomas from dysplastic or malignant lesions was not possible.