Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: A quantitative noninvasive technique

Abstract

A simple, linear kinetic model has been developed for the noninvasive assessment of capillary permeability to macromolecules in the rat by dynamic magnetic resonance imaging using albumin-Gd-DTPA. Data required by the model are signal intensity responses from a target tissue and a venous structure such as inferior vena cava before and after bolus intravenous injection of albumin-Gd-DTPA. Additional requirements include an early temporal resolution of approximately one image/min and a blood sample for hematocrit. The model does not require measurement of albumin-Gd-DTPA concentration in either arterial or venous blood. Pilot experiments suggest that this technique is adequate for estimation of the fractional leak rate of macromolecules from plasma to interstitial water as well as tissue plasma volume, the product of which yields a measure of the permeability surface area product of the tissue if the extraction fraction is modest (< 0.2). The technique may be generally applicable to the study of abnormal capillary permeability in humans as well as animals.

Assessing permeability alterations of the blood–bone marrow barrier due to total body irradiation: in vivo quantification with contrast enhanced magnetic resonance imaging

“…The tissue enhancement following the administration of small molecular, 'extracellular' contrast agents like the standard MR contrast agent gadoterate depends mainly on the arterial blood supply and the size of the extracellular volume whereas tissue enhancement following injection of macromolecular contrast agents is determined by their fractional plasma volume and microvascular permeability. 14,21,22 Small molecular tracers, such as gadoterate, already extravasate across the intact microvessel endothelium into virtually any extracerebral tissue and thus, are not able to determine an increase in microvascular permeability. [23][24][25][26] Macromolecular blood pool contrast agents on the other hand are confined to the vascular space in normal conditions.…”

“…Therefore, an increased permeability of the microvessel endothelium can be diagnosed and graded by an increased extravasation of macromolecular contrast media into the tissue interstitium with consecutive increased enhancement on the MR image. 14,21,22 Using macromolecular MR contrast agents, investigators have repeatedly quantified irradiation-induced capillary hyperpermeabilities in normal and neoplastic tissues. 17,18 Because of its considerably larger molecular weight than gadoterate (approximately 100 times larger), CMD-Gd-DOTA does not easily penetrate normal sinus endothelium, but traverses hyperpermeable sinusoids following irradiation.…”

Contrast-Enhanced MRI-Guided Photodynamic Cancer Therapy with a Pegylated Bifunctional Polymer Conjugate

“…Relative signal intensity (ΔSI) in the ROIs was calculated as the ratio of post-contrast to pre-contrast signal intensities, and plotted against time to generate dynamic uptake curves of contrast agent in tumor periphery over 15 minutes. The DCE-MRI data was also analyzed pixel by pixel using a homemade MATLAB program and 2D axial vascular flow leakage rate or permeability maps were calculated based on a modified two-compartment model (26).…”

Heterogeneity in the angiogenic response of a BT474 human breast cancer to a novel vascular endothelial growth factor‐receptor tyrosine kinase inhibitor: Assessment by voxel analysis of dynamic contrast‐enhanced MRI

“…For small molecular contrast media (SMCM) like gadopentetate, high temporal resolution is required in order to separately extract estimates of these factors from the kinetic data (13,14). With the combined use of macromolecular contrast media (MMCM) and a unidirectional two-compartment kinetic model (15,16), the fractional plasma volume and the PS-limited endothelial transfer constant can be simultaneously determined (17). The microvascular blood flow rates need not be known.…”