Evaluation of treatment-associated inflammatory response on diffusion-weighted magnetic resonance imaging and 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography imaging biomarkers.

PURPOSE: Functional imaging biomarkers of cancer treatment response offer the potential for early determination of outcome through the assessment of biochemical, physiologic, and microenvironmental readouts. Cell death may result in an immunologic response, thus complicating the interpretation of biomarker readouts. This study evaluated the temporal effect of treatment-associated inflammatory activity on diffusion magnetic resonance imaging and 2-[(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography imaging (FDG-PET) biomarkers to delineate the effects of the inflammatory response on imaging readouts. EXPERIMENTAL DESIGN: Rats with intracerebral 9L gliosarcomas were separated into four groups consisting of control, an immunosuppressive agent dexamethasone (Dex), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and BCNU+Dex. Animals were imaged using diffusion-weighted magnetic resonance imaging and FDG-PET at 0, 3, and 7 days posttreatment. RESULTS: In the BCNU- and BCNU+Dex-treated animal groups, diffusion values increased progressively over the 7-day study period to approximately 23% over baseline. The FDG percentage change of standard uptake value decreased at day 3 (-30.9%) but increased over baseline levels at day 7 (+20.1%). FDG-PET of BCNU+Dex-treated animals were found to have percentage of standard uptake value reductions of -31.4% and -24.7% at days 3 and 7, respectively, following treatment. Activated macrophages were observed on day 7 in the BCNU treatment group with much fewer found in the BCNU+Dex group. CONCLUSIONS: Results revealed that treatment-associated inflammatory response following tumor therapy resulted in the accentuation of tumor diffusion response along with a corresponding increase in tumor FDG uptake due to the presence of glucose-consuming activated macrophages. The dynamics and magnitude of potential inflammatory response should be considered when interpreting imaging biomarker results.

A methodology for registration of a histological slide and in vivo MRI volume based on optimizing mutual information.

We present a method for registering histology and in vivo imaging that requires minimal microtoming and is automatic following the user's initialization. In this demonstration, we register a single hematoxylin-and-eosin-stained histological slide of a coronal section of a rat brain harboring a 9L gliosarcoma with an in vivo 7T MR image volume of the same brain. Because the spatial resolution of the in vivo MRI is limited, we add the step of obtaining a high spatial resolution, ex vivo MRI in situ for intermediate registration. The approach taken was to maximize mutual information in order to optimize the registration between all pairings of image data whether the sources are MRI, tissue block photograph, or stained sample photograph. The warping interpolant used was thin plate splines with the appropriate basis function for either 2-D or 3-D applications. All registrations were implemented by user initialization of the approximate pose between the two data sets, followed by automatic optimization based on maximizing mutual information. Only the higher quality anatomical images were used in the registration process; however, the spatial transformation was directly applied to a quantitative diffusion image. Quantitative diffusion maps from the registered location appeared highly correlated with the H&E slide. Overall, this approach provides a robust method for coregistration of in vivo images with histological sections and will have broad applications in the field of functional and molecular imaging.