Relationship between choline and apparent diffusion coefficient in patients with gliomas

GLIOMAS ARE SPATIALLY heterogeneous brain tumors with mixed areas that may include necrosis, solid tumor, edema, and varying levels of infiltration into normal tissue. Noninvasive methods for evaluating this heterogeneity are important in directing patient treatment. Conventional magnetic resonance imaging (MRI) is sensitive to morphologic changes that occur in patients with glioma, but such changes are not specific indicators of disease progression or regression, particularly in patients that have undergone therapy. A number of functional and metabolic imaging methods have been proposed in order to provide a more complete evaluation of pathological heterogeneity. Two such imaging modalities are proton magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI). In vivo proton MRSI has been used in a research and clinical setting to measure metabolite levels in the brain. Previous studies have shown that variations in levels of metabolites such as choline, creatine, N-acetylaspartate, lactate, and lipid are associated with brain pathologies and are able to distinguish tumor from normal brain, edema, and treatment induced necrosis (1). Of relevance to the current study is that the levels of choline-containing compounds in brain tumors have been reported to correlate with cell density (2) and the proliferative index, Ki-67 (3). DWI is based on the randomly distributed displacement (Brownian motion) of water molecules, which is affected by cell structures such as membranes, myelin fiber bundles, organelles, etc. (4). The mean diffusivity, also known as the apparent diffusion coefficient (ADC), depends on the intracellular and extracellular environments, as well as tissue configuration and pathological tissue changes (4). Although some studies have reported a correlation between ADC and cell density in high-grade brain tumors (2,5), it is not clear whether this is applicable for all tumor types and grades. Recent observations have suggested that early changes in ADC are predictive of response to therapy and that this is likely to be an important modality for monitoring treatment effects (6). In developing protocols for following response to therapy, it is important to determine whether ADC and choline are alternate measurements of the same phenomenon or whether they represent independent pieces of information that are complementary in nature. Although some studies have reported an inverse correlation between ADC and choline, these have typically considered a heterogeneous patient population and heterogeneous tumor regions (i.e., edema, necrosis, cystic cavity, and solid tumor) (7). Catalaa et al (8) observed a negative correlation between ADC and choline in mixed anatomical regions for a subpopulation of patients with untreated Grade IV gliomas, but were unable to establish a significant relationship for patients with Grade II and Grade III lesions. The purpose of this study was to examine the relationship between normalized ADC and choline levels in regions of tumor both within an individual patient and between patients with tumors of similar grade. Two distinct populations of patients were considered; one group with newly diagnosed Grade II glioma and the other with newly diagnosed Grade IV glioma. We were particularly interested in seeing whether it was possible to verify the previously reported correlations for tissue that was solely within subregions of T2 hyperintensity, contrast enhancement, and necrosis.