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Dynamic Contrast-Enhanced MRI of Malignant Pleural Mesothelioma^*

A Feasibility Study of Noninvasive Assessment, Therapeutic Follow-up, and Possible Predictor of Improved Outcome

^* From the German Cancer Research Center (Drs. Giesel, Tengg-Kobligk, Weber, Zechmann, and Kauczor), Department of Radiology, Heidelberg, Germany; Thoraxklinik (Dr. Bischoff), Heidelberg; and Department of Radiology (Dr. Knopp), The Ohio State University, Columbus, OH.

Correspondence to: Michael V. Knopp, MD, PhD, Professor of Radiology and Biomedical Informatics, Novartis Chair and Director of Imaging Research, Department of Radiology, The Ohio State University, University Hospitals, 657 Means Hall, 1654 Upham Dr, Columbus, OH 43210-1228; e-mail: Knopp.16{at}osu.edu

Abstract

Study objective: Dynamic contrast-enhanced MRI (DCE-MRI) followed by pharmacokinetic analysis has been successfully used in a variety of solid tumors. The aims of this study were to evaluate the feasibility of DCE-MRI in malignant pleural mesothelioma (MPM), to differentiate benign from pathologic tissue and compare pharmacokinetic with clinical parameters and survival in order to map out its microcirculation; and to compare pharmacokinetic with clinical parameter and survival in order to improve our understanding of the in vivo biology of this malignancy.

Methods: Nineteen patients with a diagnosis of MPM who were scheduled to receive chemotherapy with gemcitabine were enrolled in the study. DCE-MRI was performed before treatment (n = 19) and after the third cycle (n = 12) and sixth cycle (n = 7) of chemotherapy. An established pharmacokinetic two-compartment model was used to analyze DCE-MRI. Tumor regions were characterized by the pharmacokinetic parameters amplitude (Amp), redistribution rate constant (kep), and elimination rate constant (kel). Kinetic parameters of tumor tissue and normal tissue were compared using the Student t test. Patients were classified as clinical responders or nonresponders according to clinical outcome, and these groups were compared with the pharmacokinetic parameters derived from DCE-MRI.

Results: Normal and tumor tissue could be distinguished by the pharmacokinetic parameters Amp and kel (p 0.001). Clinical responders had a median kep value within the tumor of 2.6 min, while nonresponders showed a higher value (3.6 min), which coincided with longer survival (780 days vs 460 days).

Conclusions: DCE-MRI can be used in patients with MPM to assess tumor microvascular properties and to demonstrate tumor heterogeneity for therapy monitoring. High pretherapeutic values of kep within the tumor correlated with a poor overall response to therapy.

Key Words: angiogenesis • dynamic contrast enhanced MRI • malignant pleural mesothelioma • therapy monitoring