Exchange-dependent relaxation in the rotating frame for slow and intermediate exchange - modeling off-resonant spin-lock and chemical exchange saturation transfer

Chemical exchange observed by NMR saturation transfer (CEST) and spin-lock (SL) experiments provide an MRI contrast by indirect detection of exchanging protons. The determination of the relative concentrations and exchange rates is commonly achieved by numerical integration of the Bloch-McConnell equations. We derive an analytical solution of the Bloch-McConnell equations that describes the magnetization of coupled spin populations under radiofrequency irradiation.As CEST and off-resonant SL are equivalent, their steady-state magnetization and dynamics can be predicted by the same single eigenvalue: the longitudinal relaxation rate in the rotating frame R1rho. For the case of slowly exchanging systems, e.g. amide protons, the saturation of the small proton pool is affected by transverse relaxation (R2b). It turns out, that R2b is also significant for intermediate exchange, such as amine- or hydroxyl-exchange or paramagnetic CEST agents, if pools are only partially saturated. We propose a solution for R1rho that includes R2 of the exchanging pool by extending existing approaches, and verify it by numerical simulations. With the appropriate projection factors, we obtain an analytical solution for CEST and SL for nonzero R2 of the exchanging pool, whilst considering the dilution by direct water saturation across the entire Z-spectra. This allows the optimization of irradiation parameters and the quantification of pH-dependent exchange rates and metabolite concentrations. In addition, we propose evaluation methods that correct for concomitant direct saturation effects. It is shown that existing theoretical treatments for CEST are special cases of this approach

Many faces of DAMPs in cancer therapy

A new concept of immunogenic cell death (ICD) has recently been proposed. The immunogenic characteristics of this cell death mode are mediated mainly by molecules called ‘damage-associated molecular patterns’ (DAMPs), most of which are recognized by pattern recognition receptors. Some DAMPs are actively emitted by cells undergoing ICD (e.g. calreticulin (CRT) and adenosine triphosphate (ATP)), whereas others are emitted passively (e.g. high-mobility group box 1 protein (HMGB1)). Recent studies have demonstrated that these DAMPs play a beneficial role in anti-cancer therapy by interacting with the immune system. The molecular pathways involved in translocation of CRT to the cell surface and secretion of ATP from tumor cells undergoing ICD are being elucidated. However, it has also been shown that the same DAMPs could contribute to progression of cancer and promote resistance to anticancer treatments. In this review, we will critically evaluate the beneficial and detrimental roles of DAMPs in cancer therapy, focusing mainly on CRT, ATP and HMGB1

Entwicklung einer Messtechnik zur nicht-invasiven Bestimmung des Gesamtgehalts an N-Acetyl-L-Aspartat im Gehirn des Menschen in vivo

Lokalisierte 1H-MR-Spektroskopie (MRS) ermöglicht die nicht invasive Messung des Metaboliten N-Acetyl-L-Aspartat (NAA) in vivo im Gehirn des Menschen. Da neuronaler Zellverlust einher geht mit einer Abnahme des NAA-Gehalts, könnte der Verlauf von gehirnschädigenden Erkrankungen mit diesem Parameter verfolgt werden. In dieser Arbeit werden neben einem Vorschlag von O. Gonen et al. eigene Ansätze zur Bestimmung des gesamt-Gehalts an NAA im Gehirn (WBNAA) entwickelt und auf 1,5-T-Ganzkörper-MR-Tomographen implementiert. Die Techniken wurden erfolgreich an Phantomen und Probanden getestet. Im Hinblick auf eine klinische Anwendung wurden zudem verschiedene Methoden der absoluten Quantifizierung entwickelt und experimentell überprüft

Umbrella sampling of proton transfer in a creatine–water system

Proton transfer reactions are among the most common processes in chemistry and biology. Proton transfer between creatine and surrounding solvent water is underlying the chemical exchange saturation transfer used as a contrast in magnetic resonance imaging. The free energy barrier, determined by first- principles umbrella sampling simulations (View the MathML sourceEaDFT 3 kcal/mol) is in the same order of magnitude as the experimentally obtained activation energy. The underlying mechanism is a first proton transfer from the guanidinium group to the water pool, followed by a second transition where a proton is “transferred back” from the nearest water molecule to the deprotonated nitrogen atom of creatine

A common language to assess allergic rhinitis control : results from a survey conducted during EAACI 2013 Congress

Peer reviewedPublisher PD

Joint multi-contrast Variational Network reconstruction (jVN) with application to rapid 2D and 3D imaging

Purpose: To improve the image quality of highly accelerated multi-channel MRI data by learning a joint variational network that reconstructs multiple clinical contrasts jointly. Methods: Data from our multi-contrast acquisition was embedded into the variational network architecture where shared anatomical information is exchanged by mixing the input contrasts. Complementary k-space sampling across imaging contrasts and Bunch-Phase/Wave-Encoding were used for data acquisition to improve the reconstruction at high accelerations. At 3T, our joint variational network approach across T1w, T2w and T2-FLAIR-weighted brain scans was tested for retrospective under-sampling at R=6 (2D) and R=4x4 (3D) acceleration. Prospective acceleration was also performed for 3D data where the combined acquisition time for whole brain coverage at 1 mm isotropic resolution across three contrasts was less than three minutes. Results: Across all test datasets, our joint multi-contrast network better preserved fine anatomical details with reduced image-blurring when compared to the corresponding single-contrast reconstructions. Improvement in image quality was also obtained through complementary k-space sampling and Bunch-Phase/Wave-Encoding where the synergistic combination yielded the overall best performance as evidenced by exemplarily slices and quantitative error metrics. Conclusion: By leveraging shared anatomical structures across the jointly reconstructed scans, our joint multi-contrast approach learnt more efficient regularizers which helped to retain natural image appearance and avoid over-smoothing. When synergistically combined with advanced encoding techniques, the performance was further improved, enabling up to R=16-fold acceleration with good image quality. This should help pave the way to very rapid high-resolution brain exams