Quantifying Radiation-Therapy Brain Injury With 1H-MRS

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DESCRIPTION (provided by applicant): Brain metastases present in 50-80 percent of small-cell-lung-cancer (SCLC) survivors within two years. To reduce this risk and improve their outcome, prophylactic-cranial-irradiation (PCI) is now offered to certain SCLC patients even in the absence of distinct visible brain pathology. Although neurotoxicity is always a concern in brain radiation-therapy (RT), there is currently no direct method to quantify its damage to the central nervous system (CNS). Such knowledge is critical for (a) risk/benefit assessment; and (b) dose determination. Presently, such damage can only be assessed indirectly, using neurocognitive tests. Unfortunately, the results of such tests are often confounded by other factors such as language barriers, patients' state of mind and/or their level of fatigue, fear and depression. Clearly, an objective, i.e., preferably instrumental, non-invasive and, most importantly, sensitive method to quantify RT neurotoxicity is necessary. We propose to quantify the extent of neurona1 cell loss imparted to the brain by RT through the decline of the amino acid derivative N-acetylaspartate (NAA) using state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Since NAA is believed to be present in neuronal cells only, its amount is proportional to their number and/or integrity. Consequently, we will obtain the amount of whole-brain-NAA (WBNAA) in 40 patients pre, immediately post- (2-3 weeks later) and six months after whole-brain radiation-therapy (WBRT). Since we will evaluate the amount of NAA in the entire brain, its signal-to-noise-ratio (SNR) will be excellent, facilitating short, < 15 min. examinations. It will also not be susceptible to misregistration errors that currently beset serial studies, nor will it be sensitive to the local transient edema common in WBRT. The WBNAA measurements will be augmented by the current tool used to evaluate CNS injury - the mini-mental status examination (MMSE) for correlation and comparison. We will use these observations to test the following three hypotheses, H1- H3: H1: That WBRT induces neuronal injury quantifiable with WBNAA in these patients. H2: That WBNAA is more sensitive than MMSE to detect neuronal injury consequences of WBRT. H3: That this neuronal injury may be transient, in part, and could resolve within several months after WBRT.