Pharmacokinetic MRI for assessment of malignant glioma response to stereotactic radiotherapy: Initial results

The purpose of this study was to assess the value of dynamic, contrast‐enhanced MRI in patients with malignant glioma (a) to predict before stereotactic radiotherapy local tumor control, (b) to investigate temporal changes in tumor microcirculation after stereotactic radiotherapy, and (c) to analyze whether malignant glioma response may be predicted earlier by alterations in the tissue pharmacokinetics rather than in terms of tumor volume. Ninety MRI studies were performed of 18 patients with malignant glioma before and 6, 18, 26, 52, and 72 weeks after the end of stereotactic radiotherapy. The signal time courses of the contrast‐enhanced tumors were analyzed using a pharmacokinetic two‐compartment model that calculates for the parameter A, reflecting the degree of MRI signal enhancement [no units] and the exchange rate constant k21 [min−1]. Before radiotherapy, the amplitude A was significantly (P < .05) lower in patients with subsequent local tumor control (n = 8; mean A = .34 ± .15) compared to patients without subsequent local tumor control (n = 10; mean A = .94 ± .71). In the local tumor control group, early after stereotactic radiotherapy (at 6–18 weeks), there was a significant (P < .05) time‐dependent decrease in the parameter k21, whereas there was still no alteration in the tumor volume. A low amplitude A before radiotherapy, combined with an early drop of k21 after stereotactic radiotherapy, reliably characterized the group of patients with subsequent tumor volume decrease. Our preliminary results suggest that two contrast‐enhanced dynamic MR studies, one before and one early after stereotactic radiotherapy, offer important information on local tumor control within the first 6 to 18 weeks after stereotactic radiotherapy. Moreover, this response may be evidenced before tumor volume changes and provides a therapeutic window to broaden treatment options and to improve treatment outcome.

[1]  M. Knopp,et al.  Effect of radiation on blood volume in low-grade astrocytomas and normal brain tissue: quantification with dynamic susceptibility contrast MR imaging. , 1996, AJR. American journal of roentgenology.

[2]  H. Dvorak,et al.  Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. , 1989, Biochimica et biophysica acta.

[3]  W. Reinhold,et al.  Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. , 1993, The Journal of clinical investigation.

[4]  L. H. Gray,et al.  The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. , 1953, The British journal of radiology.

[5]  P. Gowland,et al.  Dynamic studies of gadolinium uptake in brain tumors using inversion‐recovery echo‐planar imaging , 1992, Magnetic resonance in medicine.

[6]  M. Knopp,et al.  Cervical carcinoma: comparison of standard and pharmacokinetic MR imaging. , 1996, Radiology.

[7]  W A Brock,et al.  Predictive Assays of Tumor Radiocurability , 1988, American journal of clinical oncology.

[8]  M. Knopp,et al.  Intracranial meningeomas: time- and dose-dependent effects of irradiation on tumor microcirculation monitored by dynamic MR imaging. , 1997, Magnetic resonance imaging.

[9]  R K Jain,et al.  Barriers to drug delivery in solid tumors. , 1994, Scientific American.

[10]  W T Yuh,et al.  Assessment of tumor microcirculation: A new role of dynamic contrast MR imaging , 1997, Journal of magnetic resonance imaging : JMRI.

[11]  K. Plate,et al.  Vascular endothelial growth factor and glioma angiogenesis: Coordinate induction of VEGF receptors, distribution of VEGF protein and possible In vivo regulatory mechanisms , 1994, International journal of cancer.

[12]  R. Ball,et al.  Basement membrane and extracellular interstitial matrix components in bladder neoplasia—evidence of angiogenesis , 1994, Histopathology.

[13]  U. Klose,et al.  Dynamic contrast enhancement of intracranial tumors with snapshot-FLASH MR imaging. , 1993, AJNR. American journal of neuroradiology.

[14]  P Vaupel,et al.  Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. , 1996, Cancer research.

[15]  C. Koch,et al.  Binding of 3H-misonidazole to solid human tumors as a measure of tumor hypoxia. , 1986, International journal of radiation oncology, biology, physics.

[16]  Terry Jones,et al.  POSITRON EMISSION TOMOGRAPHY FOR IN-VIVO MEASUREMENT OF REGIONAL BLOOD FLOW, OXYGEN UTILISATION, AND BLOOD VOLUME IN PATIENTS WITH BREAST CARCINOMA , 1984, The Lancet.

[17]  W. J. Lorenz,et al.  Pharmacokinetic Mapping of the Breast: A New Method for Dynamic MR Mammography , 1995, Magnetic resonance in medicine.

[18]  P Vaupel,et al.  Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats. , 1987, Cancer research.

[19]  K J Wolf,et al.  Rheumatoid arthritis: evaluation of hypervascular and fibrous pannus with dynamic MR imaging enhanced with Gd-DTPA. , 1990, Radiology.

[20]  L R Schad,et al.  Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. , 1991, Journal of computer assisted tomography.