title: Intracranial meningeomas: time- and dose-dependent effects of irradiation on tumor microcirculation monitored by dynamic MR imaging.
abstract: The purpose of this study was the characterization of the time- and dose-dependent effects of irradiation on tumor microcirculation by means of dynamic MR imaging and correlation of the estimated data with tumor response in patients with meningeomas. Dynamic MR imaging studies were performed in 20 patients with intracranial meningeomas prior to (n = 20) and at 6 (n = 17), 18 (n = 17), and 50 wk (n = 14) after the end of radiotherapy. In seven of these patients, dynamic measurements were also performed during fractionated radiotherapy after approximate 20 Gy and 54 Gy. During and after short-time infusion of gadopentetate dimeglumine, the kinetics of lesion response was resolved using a strongly T1-weighted saturation recovery TurboFLASH (SRTF) sequence. The signal-time courses of the suspected lesions were analyzed using a pharmacokinetic two-compartment model. The calculated parameters amplitude A (reflecting gadopentetate dimeglumine accumulation in the extracellular space) and exchange rate constant k21 (depending on vascular permeability and blood flow) were displayed as color-coded images and analyzed as a function of time of therapy and radiation dose. All meningeomas showed a high exchange rate constant k21 (median, 5.7 min-1; range, 1.9-23.0 min-1) and a high amplitude A (median, 1.5 arbitrary units; range, 1.1-2.7) prior to X-ray treatment. During radiotherapy we found a dose related significant (p < .01) increase of k21 accompanied by an increase of the amplitude A as compared to the pretreatment values. Analysis of tumor volume 6, 18, and 50 wk after X-ray treatment revealed two different groups. In the responder group (n = 13) the median of the tumor volume decreased from 10.0 to 7.5 cm3. For this group, we found a significant drop (p < .01) of the median of the amplitude A and a decrease of the exchange rate constant k21. In the nonresponder group (n = 4) the median of the tumor volume increased after radiation from 3.5 to 4.5 cm3. The pharmacokinetic analysis revealed a decrease of the amplitude A-and an increase of the exchange rate constant k21. The response of meningeomas to radiotherapy is influenced by the effect of X-rays on tumor microcirculation. This effect on tumor microcirculation can be derived by analysis of pharmacokinetic maps obtained from dynamic MR images. Furthermore, these pharmacokinetic maps can possibly be used to differentiate groups of patients who respond or do not respond to radiotherapy and, thus, could benefit from another treatment modality.
authors.affiliation: Department of Radiology, German Cancer Research Center (dkfz), Heidelberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hawighorst
authors.forename: R
authors.initials: R
authors.lastname: Engenhart
authors.forename: M V
authors.initials: MV
authors.lastname: Knopp
authors.forename: G
authors.initials: G
authors.lastname: Brix
authors.forename: M
authors.initials: M
authors.lastname: Grandy
authors.forename: M
authors.initials: M
authors.lastname: Essig
authors.forename: P
authors.initials: P
authors.lastname: Miltner
authors.forename: I
authors.initials: I
authors.lastname: Zuna
authors.forename: M
authors.initials: M
authors.lastname: Fuss
authors.forename: G
authors.initials: G
authors.lastname: van Kaick
mesh_terms: D003287:Contrast Media / Q000493:pharmacokinetics; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics; D019786:Gadolinium DTPA; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008536:Meglumine / Q000493:pharmacokinetics; D008577:Meningeal Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy*; D008579:Meningioma / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy*; D008833:Microcirculation / Q000528:radiation effects; D008875:Middle Aged; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011879:Radiotherapy Dosage; D011882:Radiotherapy, High-Energy; D013997:Time Factors
chemical_list: D003287:Contrast Media; D004338:Drug Combinations; D009942:Organometallic Compounds; D008536:Meglumine; D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA