Jeffry S. Mann

Tumor angiography using high-resolution, three-dimensional magnetic resonance imaging: Comparison of gadopentetate dimeglumine and a macromolecular blood-pool contrast agent

RATIONALE AND OBJECTIVES We compared the peritumoral vascular definition in rats using either a paramagnetic extracellular or a macromolecular contrast medium in combination with high-resolution magnetic resonance (MR) imaging. METHODS High-resolution, three-dimensional spoiled gradient-refocused acquisition in a steady state (SPGR) images were acquired from tumor-bearing Fischer-344 rats before, immediately after, and again 40 min after administration of gadopentetate dimeglumine (0.1 mmol Gd/kg; n = 10) and albumin-(Gd-DTPA)30 (0.05 mmol Gd/kg; n = 5). Small peritumoral vessels were analyzed semiquantitatively on maximum intensity projection angiograms using a 4-point scoring system; quantitative analyses included signal-to-background ratios (SBRs) and signal-to-noise ratios. RESULTS Gadopentetate dimeglumine caused a transient and low-scoring (0.2 +/- 0.1, SBR = 1.9 +/- 0.2) vessel definition but strong rim enhancement (score = 1.4 +/- 0.2). Albumin-(Gd-DTPA)30 produced persistent, high-quality angiograms (score = 2.6 +/- 0.2, SBR = 7.4 +/- 0.2) but minimal rim enhancement (score = 0.3 +/- 0.2). CONCLUSION Albumin-(Gd-DTPA)30 combined with high-resolution MR imaging produces time-persistent, detailed angiographic definition of peritumoral vessels. Vascular maps obtained with gadopentetate dimeglumine enhancement are not time persistent or of equal quality.

Comparison of MR Contrast–enhancing Properties of Albumin-(biotin)10-(gadopentetate)25, a Macromolecular MR Blood Pool Contrast Agent, and Its Microscopic Distribution

Macromolecular contrast media (MMCM) specifically designed to enhance the blood pool do not substantially penetrate the endothelial barrier of most normal tissues but will penetrate tumor microvascular endothelium readily. Consequently, steady increase in tissue accumulation and resulting MRI enhancement, relative to the temporal response for blood enhancement, have been used to detect and estimate the tumor microvascular permeability. Quantitative estimates of tissue blood volume and estimates of the permeability may be used to differentiate the biology of tumors. MMCM-enhanced MRI techniques can be used to improve the specificity of tumor diagnosis and lesion differentiation (1,2). Quantitative information about the transendothelial diffusion of blood pool agents comes from both macroscopic and microscopic approaches. The transport can be monitored macroscopically by measuring the MR signal intensities (SI) in blood and tissues after contrast agent administration. Microscopic distribution of a blood pool agent in normal tissue has been studied using electron microscopy (3). We developed an MRI and light microscopically detectable blood pool agent comprised of human serum albumin (HSA) double-labeled with Gd-DTPA groups and biotin to permit correlation of the histologic transcapillary diffusion of MMCM as a function of time in normal and neoplastic tissues to the MR-derived estimates of capillary leakiness.

MRI mapping of microvascular permeability and tissue blood volume

A quick and automated method for quantitative spatial mapping of tissue characteristics derived from contrast enhanced MR imaging by a macromolecular contrast medium (MMCM) was used in normal rats. Specifically, an established two compartment unidirectional flow kinetic model was automatically implemented on a pixel by pixel basis to calculate permeability surface area product (PS) and tissue fractional blood volume (BV) from MRI dynamic intensity data. The utility of PS and BV maps were evaluated in the normal rat abdomen where a range of fractional- BV was found: from 100% in the vena cava to 1% in skeletal muscles, with intermediate values for liver and kidney. Tissue permeability depicted on the PS maps was generally low for normal tissues.