Primary central nervous system lymphoma: advances in MRI and PET imaging

Abstract

Contrast enhanced magnetic resonance imaging (CE-MRI) remains the imaging modality of choice for initial workup, staging, and response assessment after therapy in patients with primary central nervous system lymphoma (PCNSL). While CE-MRI is a sensitive test to detect blood brain barrier (BBB) dysfunction, it does not biologically represent the true tumor burden. Current response assessment criteria relies heavily on two dimensional anatomical measurements on post contrast T1-weighted (T1W) images, as well as pre-contrast T2-weighted (T2W) imaging. Additional MRI features, such as diffusion-weighted imaging (DWI) and perfusion weighted imaging, can be routinely obtained at most centers with MRI capabilities. Emerging evidence supports the incorporation of these data to better define tumor physiology and provide additional valuable clinical tools capable of identifying high risk subgroups as well as early predictors of response to therapies. Further, novel advanced molecular and pathophysiologic characterization of PCNSL provides insights into promising targeted therapeutic approaches. However, significant institutional imaging variation and inconsistent clinical trial reporting diminishes the reliability, reproducibility and eventual translation in day to day management of patients with PCNSL. Here we review established neuroimaging concepts and provide an overview of published literature about novel imaging techniques that may improve diagnosis and response assessments. Finally, we highlight the need for standardization of image acquisition, post-processing, and incorporation of novel imaging biomarkers in early phase PCNSL clinical trials.

Keywords: Primary central nervous system lymphoma (PCNSL); diffusion-weighted imaging (DWI); magnetic resonance imaging (MRI); positron emission tomography (PET).

Figure 1

Sixty-six-year-old male patient with primary CNS lymphoma. (A) T2W image shows a relatively T2W hypointense mass (yellow arrowheads) centered along the midline within the corpus callosum, which is distinct from the hyperintensity of the extensive surrounding non-tumoral vasogenic edema (white arrows). The mass demonstrates homogeneous diffuse contrast enhancement on post-contrast T1W imaging (B, yellow arrowheads), which is confirmed on T1W pre-contrast imaging (C). There is an additional remote enhancing lesion (B, red arrows), as these patients can often present with multi-focal disease. On DWI (D,E), the mass shows characteristic restricted diffusion seen as bright signal on diffusion trace imaging (D, yellow arrowhead) and confirmed as hypointensity on maps of ADC (E, yellow arrowheads). This has been attributed to paucity of extracellular fluid relative to highly cellular content of these tumors. Of note, the ADC values of non-tumoral vasogenic edema are seen as hyperintense regions on ADC maps, presumably due to greater proportion of extracellular fluid relative to tissue cellularity (E, white arrows). (F) On DSC-MRI maps of rCBV, the mass demonstrates a relatively homogeneous pattern of moderately elevated (>2.0) rCBV (yellow arrowheads). CNS, central nervous system; T2W, T2-weighted; T1W, T1-weighted; DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient; DSC, dynamic susceptibility contrast; MRI, magnetic resonance imaging; rCBV, relative cerebral blood volume.