Clinical outcome in cases of pediatric low grade astrocytoma (LGA), the single most common type of solid tumor in children, is unpredictable. Although complete resection is often curative, this is not possible, in many instances, because LGA tends to invade midline brain structures having essential systemic physiological significance. After partial resection, LGA may remain stable, may continue to grown, or may undergo malignant transformation. Even modest postoperative growth can result in severe neurological deficits or death. After partial resection, several adjunctive management options are available for biologically aggressive tumors. Fractionated radiation therapy or chemotherapy may be used, but these options are often deferred as long as possible to avoid therapy-attributable developmental problems. Stereotactic radiation therapy may be used to ablate aggressive tumor foci (""""""""pruning"""""""") as a means of controlling volumetric growth thereby permitting the child to develop to the point where global radiation therapy or chemotherapy can be considered. Conventional diagnostic neuroimaging methods are unable to identify biologically aggressive LGA so that adjunctive therapy may be offered nor are they capable of identifying the location of tumor subvolumes exhibiting aggressive characteristics for """"""""pruning"""""""". We hypothesize that choline signal measures obtained from newly developed proton magnetic resonance spectroscopic imaging (1H-MRSI) technology will overcome these shortcomings. The hypothesis is based on studies which suggest that choline signal levels are related proliferative activity and on our own work which has shown that histopathologically homogeneous LGA cases exhibit heterogeneous patterns of tumoral choline signal. The hypothesis will be tested with clinical/laboratory correlation study and two pilot clinical trials. In the clinical/laboratory correlation study, pre-operative determination of metabolically relevant regions of interest with 1H-MRSI will be followed by intra-surgical excision of samples identified. These will be analyzed immunocytochemically for proliferative and apoptosis characteristics. In the clinical pilot trials, we will seek to establish that post-therapy choline measures are predictive of future growth and that 1H-MRSI may be used in target planning for focal therapies.
| Haney, S M; Thompson, P M; Cloughesy, T F et al. (2001) Mapping therapeutic response in a patient with malignant glioma. J Comput Assist Tomogr 25:529-36 |
| Gupta, R K; Cloughesy, T F; Sinha, U et al. (2000) Relationships between choline magnetic resonance spectroscopy, apparent diffusion coefficient and quantitative histopathology in human glioma. J Neurooncol 50:215-26 |
| Gupta, R K; Sinha, U; Cloughesy, T F et al. (1999) Inverse correlation between choline magnetic resonance spectroscopy signal intensity and the apparent diffusion coefficient in human glioma. Magn Reson Med 41:2-7 |
