Detection of zonal renal ischemia with contrast‐enhanced MR imaging with a macromolecular blood pool contrast agent

Vexler, Vladimir; Berthezène, Yves; Clémеnt, Olivier; Mühler, Andreas; Rosenau, Werner; Moseley, Michael E.; Brasch, Robert C.

doi:10.1002/jmri.1880020311

Cited by 26 publications

(7 citation statements)

References 19 publications

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“…Albumin-(DTPA)35 was also used for the detection of focal changes in renal perfusion in a myoglobinuric acute renal failure model in the rat. Contrast-enhanced MR imaging data in this model correlated well with pathological data and microsphere perfusion results [25]. The effects of varying the molecular weight of (Gd-DTPA)-polylysine on blood pharmacokinetics and dynamic tissue MR imaging signal enhancement characteristics were studied by Vexler et al [26] in normal rats.…”

Section: Publicationssupporting

confidence: 61%

Dendrimers in Diagnostics

Krause¹,

Hackmann-Schlichter²,

Maier³

et al. 2000

Dendrimers II

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Dendrimers are currently under investigation as potential polymeric carriers of contrast agents for magnetic resonance imaging (MRI), scintigraphy and X-ray techniques, i.e. computed tomography (CT). The objective for synthesizing large molecular weight contrast agents is to modify the pharmacokinetic behavior of presently available small-sized compounds from a broad extracellular to an intravascular distribution. Major target indications include angiography, tissue perfusion determination and tumor detection and differentiation. In principle, imaging moieties, e.g. metal chelates for MRI and scintigraphy and triiodobenzene derivatives for CT, are coupled to a dendrimeric carrier characterized by a defined molecular weight. The structures and sizes of these carriers are presently optimized. So far, however, no compound has reached the status of clinical application. Possible hurdles to overcome are synthetic problems such as drug uniformity, reproducible production of pure compounds and analytical issues, e.g. demonstrating purity . In principle, proof of concept for dendrimeric contrast agents as intravascular and tumor-targeting substances seems to have been established. However, a lot of effort is still necessary before a dendrimeric contrast agent will finally be available for wide-spread use in patients.

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Section: Publicationssupporting

confidence: 61%

Dendrimers in Diagnostics

Krause¹,

Hackmann-Schlichter²,

Maier³

et al. 2000

Dendrimers II

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“…Prototype blood-pool agents for MR imaging such as Gd-DTPA-labeled albumin and polylysine have been shown in animal models to have considerable clinical potential. Applications include the detection of tissue ischemia (23), capillary plasma volume changes (24,25), and changes in capillary integrity in tumors, chemotoxicity, and inflammation (26)(27)(28)(29). The clinical realization of the potential diagnostic benefits offered by macromolecular MR imaging enhancement currently awaits the availability of formulations with suitable safety, enhancement, and pharmacokinetic characteristics.…”

Section: Discussionmentioning

confidence: 99%

Effect of varying the molecular weight of the MR contrast agent Gd‐DTPA‐polylysine on blood pharmacokinetics and enhancement patterns

Vexler¹,

Clémеnt²,

Schmitt‐Willich³

et al. 1994

Magnetic Resonance Imaging

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102

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The effects of varying the molecular weight of gadolinium-DTPA (diethylenetriaminepentaacetic acid)-polylysine, a macromolecular magnetic resonance (MR) imaging contrast agent, on blood pharmacokinetics and dynamic tissue MR imaging signal enhancement characteristics were studied in normal rats. Blood elimination half-life, total blood clearance, volume of the central compartment (Vcc) and the steady-state distribution volume (Vssd) were calculated for four Gd-DTPA-polylysine polymers with average molecular weights of 36, 43.9, 139, and 480 kd and compared with corresponding values for Gd-DTPA (0.57 kd) and Gd-DTPA-albumin (92 kd). Blood elimination half-life increased seven-fold with an increase in molecular weight from 36 to 480 kd. The Vcc values for all polylysine polymers did not differ significantly from the Vcc value for Gd-DTPA-albumin but were significantly smaller than the Vcc value for Gd-DTPA. The Vssd value for Gd-DTPA did not differ significantly from the Vssd value for the 36- and 43.9-kd polymers but was significantly larger than the Vssd values for the 139- and 480-kd polymers and for Gd-DTPA-albumin. On T1-weighted coronal spin-echo MR images, dynamic signal enhancement profiles in liver and kidney for the 36-, 43.9-, and 480-kd Gd-DTPA-polylysine chelates corresponded to the blood pharmacokinetic data. Increasing molecular weight of Gd-DTPA-polylysine formulations substantially slows blood clearance and produces a prolonged, almost constant tissue signal enhancement for the 60-minute observation period.

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“…While BSA-DTPA-Gd and Gd-dextran have been used to examine the vasculature of living organisms (3,(16)(17)(18), the use of gelatin with this contrast perfusion allows for greater image contrast and reproducibility due to the increased retention of the contrast agent. With vascular perfusion of BSA-DTPA-Gd followed by MR microscopic examination, we have been able to resolve and identify blood vessels down to 20 am in diameter in mouse embryos at 9.5 days of gestation.…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance microscopy of mouse embryos.

Smith

Johnson

Groman

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

156

112

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The increased use of the mouse as a model for various aspects of ammalian biology has caused a renewed interest in developing strategies for examining and comparing normal and abnormal mouse embryonic development and anatomy. In this study, we have explored the use of magnetic resonance microscopy as a tool for these purposes. Techniques for the fixation, embedding, perfusion, and image acquisition of mouse embryos are described. The perfusion of bovine serum albumin-diethylenetriaminepentaacetic anhydridegadolinium as a contrast agent enhances images of the developing embryonic vasculature during critical stages of organogenesis and allows for comparisons when embryos have been treated with teratogens such as retinoic acid. The acquired three-dimensional data sets are available for archiving, distributing, and postacqulsition manipulations such as computer segmentation of anatomical structuresThe mouse has become the animal model of choice for studying mammalian embryonic development because of the experimental techniques that have developed around it and because of its long and detailed history as a genetic model. However, technologies for analysis of developmental anatomy and mutant structures have not kept pace with technologies involving the manipulation of the mouse germ line to produce these developmental phenotypes. The storage, interpretation, and dissemination of the large amounts of data on these abnormal phenotypes presents an important challenge. The wide acceptance of the mouse as a preferred animal model is complemented by the extensive collection and documentation of >1000 mutant loci of mice (1). Transgenic technology has become commonplace, allowing the transfer offoreign genes into the mouse germ line and has led to the growth of service laboratories producing many lines of transgenic mice for investigators. Additionally, the germ line of mice can be manipulated by targeting mutations into specific genes in embryonic stem cells, making it possible to study the immediate and ultimate functions of the specific genes (2). A vast body of in situ hybridization information concerning the three-dimensional expression patterns of genes in the mouse embryo is quickly developing as more genes are isolated and examined. Current formats for describing morphological abnormalities of embryonic gene expression are inadequate because they are two dimensional, whereas the information being generated is three and four dimensional. In addition, investigators creating abnormal mice do not always have adequate training to evaluate the morphological changes being studied. For these reasons, there is a growing need for a means by which multidimensional anatomy can be recorded and easily transmitted to many investigators.In this report, we describe how magnetic resonance (MR) microscopy can be used to acquire three-dimensional data sets of embryonic anatomy for study on personal computers, how the embryonic vasculature can be enhanced and examined, and how anatomical structures can be computersegmented from a...

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Detection of zonal renal ischemia with contrast‐enhanced MR imaging with a macromolecular blood pool contrast agent

Cited by 26 publications

References 19 publications

Dendrimers in Diagnostics

Dendrimers in Diagnostics

Effect of varying the molecular weight of the MR contrast agent Gd‐DTPA‐polylysine on blood pharmacokinetics and enhancement patterns

Magnetic resonance microscopy of mouse embryos.

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