Downfield-NOE-suppressed amide-CEST-MRI at 7 Tesla provides a unique contrast in human glioblastoma

Purpose The chemical exchange saturation transfer (CEST) effect observed in brain tissue in vivo at the frequency offset 3.5 ppm downfield of water was assigned to amide protons of the protein backbone. Obeying a base-catalyzed exchange process such an amide-CEST effect would correlate with intracellular pH and protein concentration, correlations that are highly interesting for cancer diagnosis. However, recent experiments suggested that, besides the known aliphatic relayed-nuclear Overhauser effect (rNOE) upfield of water, an additional downfield rNOE is apparent in vivo resonating as well around +3.5 ppm. In this study, we present further evidence for the underlying downfield-rNOE signal, and we propose a first method that suppresses the downfield-rNOE contribution to the amide-CEST contrast. Thus, an isolated amide-CEST effect depending mainly on amide proton concentration and pH is generated. Methods The isolation of the exchange mediated amide proton effect was investigated in protein model-solutions and tissue lysates and successfully applied to in vivo CEST images of 11 glioblastoma patients. Results Comparison with gadolinium contrast enhancing longitudinal relaxation time–weighted images revealed that the downfield-rNOE-suppressed amide-CEST contrast forms a unique contrast that delineates tumor regions and show remarkable overlap with the gadolinium contrast enhancement. Conclusion Thus, suppression of the downfield rNOE contribution might be the important step to yield the amide proton CEST contrast originally aimed at

Leptospira and Inflammation

Leptospirosis is an important zoonosis and has a worldwide impact on public health. This paper will discuss both the role of immunogenic and pathogenic molecules during leptospirosis infection and possible new targets for immunotherapy against leptospira components. Leptospira, possess a wide variety of mechanisms that allow them to evade the host immune system and cause infection. Many molecules contribute to the ability of Leptospira to adhere, invade, and colonize. The recent sequencing of the Leptospira genome has increased our knowledge about this pathogen. Although the virulence factors, molecular targets, mechanisms of inflammation, and signaling pathways triggered by leptospiral antigens have been studied, some questions are still unanswered. Toll-like receptors (TLRs) are the primary sensors of invading pathogens. TLRs recognize conserved microbial pattern molecules and activate signaling pathways that are pivotal to innate and adaptive immune responses. Recently, a new molecular target has emerged—the Na/K-ATPase—which may contribute to inflammatory and metabolic alteration in this syndrome. Na/K-ATPase is a target for specific fatty acids of host origin and for bacterial components such as the glycolipoprotein fraction (GLP) that may lead to inflammasome activation. We propose that in addition to TLRs, Na/K-ATPase may play a role in the innate response to leptospirosis infection