Elsevier

Magnetic Resonance Imaging

Volume 18, Issue 10, December 2000, Pages 1201-1214
Magnetic Resonance Imaging

Pharmacokinetic analysis of glioma compartments with dynamic Gd-DTPA-enhanced magnetic resonance imaging

https://doi.org/10.1016/S0730-725X(00)00223-XGet rights and content

Abstract

Dynamic contrast-enhanced magnetic resonance imaging (MRI) is widely used for measuring perfusion and blood volume, especially cerebral blood volume (CBV). In case of blood-brain barrier (BBB) disruption, the conventional techniques only partially determine the pharmacokinetic parameters of contrast medium (CM) exchange between different compartments. Here a modified pharmacokinetic model is applied, which is based on the bidirectional CM exchange between blood and two interstitial compartments in terms of the fractional volumes of the compartments and the vessel permeabilities between them. The evaluation technique using this model allows one to quantify the fractional volumes of the different compartments (blood, cells, slowly and fast enhancing interstitium) as well as the vessel permeabilities and cerebral blood flow (CBF) with a single T1-weighted dynamic MRI measurement. The method has been successfully applied in 25 glioma patients for generating maps of all of these parameters. The fractional volume maps allow for the differentiation of glioma vascularization types. The maps show a good correlation with the histological grading of these tumors. Furthermore, regions with enhanced interstitial volumes are found in high-grade gliomas. Differences in permeability maps of Gd-DTPA apart from BBB disruption do not exist between different tissue types. CBF measured in high-grade glioma is less pronounced than it would be expected from their blood volume. Therefore pharmacokinetic imaging provides an additional tool for glioma characterization.

Introduction

Magnetic resonance imaging (MRI) today is not only a method for visualizing tissue contrasts but provides functional information as well. Application of the paramagnetic contrast medium (CM) Gd-DTPA has considerably improved the sensitivity and specificity of MRI. Nevertheless, contrast-enhanced MRI alone provides only a static impression of signal enhancement and does not make use of the kinetic properties of MR signal variation, whereas dynamic measurement of signal-time curves is a useful technique for obtaining functional information on blood volume and blood flow [1], interstitial [2], [3], [4], [5], [6] and cell volume [7], [8], vascular permeability [2], [3], [4], [5], [6], [9], [10] and blood-brain barrier (BBB) integrity. These parameters determine the signal-time curves after intravenous administration of a short CM (Gd-DTPA) bolus and offer the possibility to separate gliomas [11], [12], [13] and other tumors [[5], [6],74] by dynamic MRI (dMRI).

The aim of our investigation was to develop a comprehensive technique for measurement and evaluation which allows a pixelwise calculation of a full set of these parameters generated by one dynamic MR examination [7]. The measuring technique should offer an adequate time and signal-to-noise resolution of these kinetics to yield a description of the measured signal-time curves in terms of the above pharmacokinetic parameters. The pharmacokinetic model used is adapted to the signal time curves measured.

The method is described here in detail and has been applied to 25 glioma patients. The outcome of different gliomas in these maps is described. A correlation for blood volume maps with WHO grading is performed.

Section snippets

Pharmacokinetic modeling

For evaluation of the dynamic MR images, a slightly modified pharmacokinetic model is used. In the absence of any transcapillary fluid flow, the transport of Gd-DTPA is governed by diffusion [15]. Significant active transport between the compartments is excluded in our model. The compound is not taken up by cells. Thus there is only a bidirectional exchange of the contrast agent between vascular blood plasma (concentration Cp(t)) and interstitial (alternative extravascular extracellular or

Blood volume maps and correlation with WHO grading

The percentage blood volume maps, Vb/Vt, of the four exemplary patients are shown in Fig. 5. The tumors on these maps cover a wide range of fractional vascular volumes (Fig. 6). The fractional blood volume differs not only from patient to patient but also by a factor of more than 2 between hot spots and poorly vascularized tumor regions (patients 7 and 24 in Fig. 5, Fig. 6). Recurrent tumors (patient 17) seem to be vascularized more homogeneously than the original ones (patient 24). Because

Discussion

Two different techniques are typically used for evaluation of dynamic MRI. The first has been developed for patients with an intact BBB and does not consider any outflow of the CM Gd-DTPA into the interstitial compartment [27], [39]. Furthermore, only the bolus is used for qualitative measurement of blood volume distribution. Signal contributions from CM enhancement in the interstitial volume or in the blood after bolus administration increase uncertainties [34], [40].

T2- and T2∗-weighted

Acknowledgements

The research was supported by grants from the German Research Foundation (DFG). The authors thank Dr. Budschig from the Department of Neurosurgery at Gertraudenkrankenhaus, Berlin, and Dr. R. Wurm from the Department of Radiation Therapy at Charité, Berlin, for their support.

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