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Histologic confirmation of microvascular hyperpermeability to macromolecular MR contrast medium in reperfused
M Saeed1, C F van Dijke, J S Mann
1Department of Radiology, University of California, San Francisco 94143, USA.
Abstract:
A macromolecular MR contrast medium (MMCM) designed to permit histochemical staining and specific tissue localization, albumin-(biotin)10-(Gd-DTPA)25 (Bio-Alb-Gd), was used in a rat model of reperfused myocardial infarction to confirm the presence and distribution of microvascular hyperpermeability. T1-weighted spin-echo images were acquired before and after administration of Bio-Alb-Gd. An avidin-biotin-complex (ABC) stain, specific for the biotinylated MR contrast medium, was used to define the MMCM distribution and to detect any regional change in microvascular permeability related to infarction. Immediately after Bio-Alb-Gd administration, the infarcted region was enhanced, with greatest signal intensity noted at the rim and less at the center. There was a gradual increase in signal intensity of the initially hypointense central region. The steady increase in signal intensity of the central region suggested convection transport of MMCM through the interstitial space and its influx into cellular compartment after leakage from the vascular compartment. Histologic findings confirmed regional microvascular hyperpermeability corresponding to the site of infarction and a predominant rim distribution of the MMCM. Bio-Alb-Gd was identified at high microscopic power in the intravascular, interstitial, and intracellular spaces at the periphery of reperfused infarcted myocardium. Bio-Alb-Gd can be used as an MR contrast medium in reperfused infarcted myocardium to confirm the existence and to localize altered microvascular permeability to macromolecules. Bio-Alb-Gd contrast technique removes all the ambiguity between the distribution of the MR or other imaging contrast agent and the distribution of the substrate for histochemical staining.
Insights
This study demonstrates that albumin-(biotin)10-(Gd-DTPA)25 (Bio-Alb-Gd), a macromolecular MR contrast medium, effectively confirms and localizes microvascular hyperpermeability in reperfused myocardial infarction models. Histochemical staining further validates its distribution and permeability findings.
Area of Science:
- Biomedical Imaging
- Cardiovascular Research
- Histochemistry
Background:
- Assessing microvascular hyperpermeability in myocardial infarction is crucial for understanding tissue damage and guiding treatment.
- Current methods may lack specificity in differentiating contrast agent distribution from underlying biological processes.
Purpose of the Study:
- To evaluate the utility of a novel biotinylated macromolecular MR contrast medium (Bio-Alb-Gd) for detecting and localizing microvascular hyperpermeability in a rat model of reperfused myocardial infarction.
- To correlate MR imaging findings with histochemical staining to confirm the distribution of the contrast medium and assess microvascular integrity.
Main Methods:
- Administration of Bio-Alb-Gd, a macromolecular MR contrast medium, to rats with reperfused myocardial infarction.
- Acquisition of T1-weighted spin-echo MR images before and after contrast administration.
- Application of avidin-biotin-complex (ABC) staining specific for the biotinylated contrast medium to analyze its distribution via histology.
Main Results:
- MR imaging showed immediate enhancement in the infarcted region, particularly at the rim, with gradual signal increase in the central area over time.
- Histologic analysis confirmed regional microvascular hyperpermeability at the infarction site, with Bio-Alb-Gd predominantly localized at the rim.
- Bio-Alb-Gd was observed in intravascular, interstitial, and intracellular spaces, indicating leakage and transport across the compromised vasculature.
Conclusions:
- Bio-Alb-Gd serves as an effective MR contrast medium for confirming and localizing altered microvascular permeability to macromolecules in reperfused myocardial infarction.
- This technique integrates MR imaging with histochemical specificity, reducing ambiguity in assessing contrast agent distribution and microvascular changes.