Model Selection in Magnetic Resonance Imaging Measurements of Vascular Permeability: Gadomer in a 9L Model of Rat Cerebral Tumor

Abstract

Vasculature in and around the cerebral tumor exhibits a wide range of permeabilities, from normal capillaries with essentially no blood-brain barrier (BBB) leakage to a tumor vasculature that freely passes even such large molecules as albumin. In measuring BBB permeability by magnetic resonance imaging (MRI), various contrast agents, sampling intervals, and contrast distribution models can be selected, each with its effect on the measurement's outcome. Using Gadomer, a large paramagnetic contrast agent, and MRI measures of T 1 over a 25-min period, BBB permeability was estimated in 15 Fischer rats with day-16 9L cerebral gliomas. Three vascular models were developed: (1) impermeable (normal BBB); (2) moderate influx (leakage without efflux); and (3) fast leakage with bidirectional exchange. For data analysis, these form nested models. Sizable inhomogeneity in v D , K i , and k b appeared within each tumor. We conclude that employing nested models enables accurate assessment of transfer constants among areas where BBB permeability, contrast agent distribution volumes, and signal-to-noise vary.

Quantitative measurement of blood‐brain barrier permeability in human using dynamic contrast‐enhanced MRI with fast T1 mapping

“…4 by C pa (t), K 1 can be determined by linear regression, with C tiss (t)/C pa (t) as the dependent variable and as the independent variable. For convenience (size and location), C pa (t) was determined from the time course of the signal change in a pixel containing the sagittal sinus in this study, assumed to be proportional to the arterial concentration of the contrast agent concentration C pa (t) [17]. This voxel was chosen to have minimum noise and a maximum dynamic range, and was Taheri et al Page 6 corrected by the factor (1-hematocrit).…”

“…Slower rates of BBB leakage appear to be important in chronic diseases, such as Alzheimer's disease (20) and Binswanger's disease (21), as shown in qualitative studies of changes in T 1 -weighted image intensities that were monitored for longer periods after contrast agent injection. Quantitative T 1 measurements in animal models show slow rates of BBB leakage (see Ewing et al, 2006 and references therein).…”

“…Furthermore, relative to simple measurements of pixel intensity changes in T 1 -weighted images, quantitative T 1 sampling a high density of time points during the measurement, we reduced noise in the pharmacokinetic curves. Finally, following the approach taken by Ewing et al in studies on an animal model of stroke (13,17) and Larsson et al in human studies (14,15), we used the Patlak model of intercompartment exchange and a graphical approach (27) to calculate the rate of transfer of Gd-DTPA from the blood to extravascular brain using the measured T 1 changes. To our knowledge, this is the first demonstration of this approach to measure BBB influx rate constant in human subjects.…”

A Direct Method for Measuring Mouse Capillary Cortical Blood Volume Using Multiphoton Laser Scanning Microscopy

“…Consequently, studies of the microvasculature and so tumoral blood volume assessments are crucial to understand the tumor growth process and therapy follow-up. Imaging techniques such as magnetic resonance imaging, positron emission tomography and computed tomography can provide useful information on hemodynamic parameters and vascular permeability (Sanden et al, 2000;Eastwood and Provenzale, 2003;Wintermark et al, 2005;Huppert et al, 2006;Ewing et al, 2006). However, they suffer from relatively poor spatial and/or temporal resolution.…”

Enhanced therapeutic agent delivery through magnetic resonance imaging–monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status

“…Moreover, BBB disruption in these tumors is highly heterogeneous, and the tumor core is often the most permeable compared with the impermeable proliferating brain tumor peripheral region. 15,20,42,43 Permeability does not necessarily correlate with tumor histology, size, or anatomical location, and glioblastoma cells have been found at great distances from the enhancing regions of the tumors.…”