CEST MRI to study BrAin MetaBolism and Function: insights from OptO fMRI and MR spectroscopy

• Applicants: Professor Dr. Cornelius Faber; Professorin Dr. Verena Hörr
• Subject Area: Medical Physics, Biomedical Technology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 406818964

• Final Report Year: 2023

Final Report Abstract

The investigation of metabolic processes forms the basis for understanding physiological processes, for example in the brain or in the development of various diseases. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are powerful instruments for the molecule-specific, non-invasive observation of metabolism. Compared to MRS, CEST-MRI offers the advantage of spatially resolved information and higher sensitivity. However, the contributions of individual metabolites are sometimes difficult to separate, which is a limitation of the applicability of CEST-MRI. In this project, we took a multimodal approach to decipher the contributions of individual metabolites to the measured CEST signal. We focused on the metabolites glucose, glutamate, and lactate, which are important for brain metabolism. First, we tested different signal preparation methods, compared CEST with the so-called CESL method and developed a line-scanning CEST method that allows very fast data acquisition. With CESL, the phenomenon of so-called Rabi oscillations occurred, for which we were able to implement various correction methods. With linescanning CEST, we were able to investigate the mutarotation kinetics of different sugars in vitro and detect different metabolites in vivo. To calibrate CEST for use in functional imaging of the brain, we used optogenetic methods. After developing several correction procedures for haemodynamic artefacts, we succeeded for the first time in measuring lactate levels in rat brain using an optical fibre and a genetically expressed sensor. The combination of the different experiments showed that the physiological CEST signal in the brain is dominated by glucose and that the so-called glucoCEST is the most promising approach for alternative metabolitebased functional imaging. Furthermore, we were able to show that CEST is very well suited for investigating glucose metabolism in the heart on the one hand and for characterising tumours and detecting a response to cancer therapies at an early stage on the other.

Publications

• Functional MRI Readouts From BOLD and Diffusion Measurements Differentially Respond to Optogenetic Activation and Tissue Heating. Frontiers in Neuroscience, 13.
  Albers, Franziska; Wachsmuth, Lydia; Schache, Daniel; Lambers, Henriette & Faber, Cornelius
  
• Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex. Journal of Neurochemistry, 150(4), 402-419.
  Just, Nathalie & Faber, Cornelius
  
• A comparison of different CEST quantification techniques in vitro and in vivo. EMIM 2020
  Schache D.; Bardin S.; Lambers H.; Flament J.; Boumezbeur F.; Faber C.; Ciobanu L. & Hoerr V.
  
• A cortical rat hemodynamic response function for improved detection of BOLD activation under common experimental conditions. NeuroImage, 208, 116446.
  Lambers, Henriette; Segeroth, Martin; Albers, Franziska; Wachsmuth, Lydia; van Alst, Timo Mauritz & Faber, Cornelius
  
• nteraction between fitting and analytical approaches to improve quantitative CEST analysis. ESMRMB
  Schache D.; Lambers H.; Bardin S.; Boumezbeur F.; Ciobanu L.; Faber C. & Hoerr V.
  
• Glucose mutarotation kinetics determined by ultrafast CEST Line Scanning. ESMRMB 2021
  Schache D.; Bardin S.; Ciobanu L.; Faber C. & Hoerr V.
  
• A comparison between neuronal network based multi-pool Lorentzian fitting and conventional glucoCEST quantification. SAMS 2022
  Schache D.; Nienkötter A.; Hoffmann E.; Gerwing M.; Jiang X. & Hoerr V.
  
• Fiber-based lactate recordings with fluorescence resonance energy transfer sensors by applying an magnetic resonance-informed correction of hemodynamic artifacts. Neurophotonics, 9(03).
  Lambers, Henriette; Wachsmuth, Lydia; Thomas, Dominik; Boumezbeur, Fawzi; Hoesker, Vanessa; Pradier, Bruno & Faber, Cornelius
  
• Ultrafast CEST line scanning as a method to quantify mutarotation kinetics. Journal of Magnetic Resonance, 342, 107270.
  Schache, Daniel; Bardin, Solène; Ciobanu, Luisa; Faber, Cornelius & Hoerr, Verena
  
• A novel method for multipool Lorentzian line-shape fitting of CEST MRI Z-spectra to improve accuracy in quantification of lactate and glucose contributions. ESMRMB 2023
  Lippe C.; Schache D. & Hoerr V.
  
• Cardiac CEST MRI under the influence of short saturation pulses – an analysis approach. ISMRM 2023
  Schache D.; Peddi A.; Nahardani A.; Faber C. & Hoerr V.
  
• In vivo CEST MRI to assess and identify myocardial infarction by using natural D-glucose as a contrast agent. ISMRM 2023
  Peddi A.; Schache D.; Nahardani A.; Kuhlmann M.; Wildgruber M.; Faber C. & Hoerr V.
  
• Multiparametric chemical exchange saturation transfer MRI detects metabolic changes in breast cancer following immunotherapy. Journal of Translational Medicine, 21(1).
  Hoffmann, Emily; Schache, Daniel; Höltke, Carsten; Soltwisch, Jens; Niland, Stephan; Krähling, Tobias; Bergander, Klaus; Grewer, Martin; Geyer, Christiane; Groeneweg, Linda; Eble, Johannes A.; Vogl, Thomas; Roth, Johannes; Heindel, Walter; Maus, Bastian; Helfen, Anne; Faber, Cornelius; Wildgruber, Moritz; Gerwing, Mirjam & Hoerr, Verena
  
• The impact of vasomotion on analysis of rodent fMRI data. Frontiers in Neuroscience, 17.
  Lambers, Henriette; Wachsmuth, Lydia; Lippe, Chris & Faber, Cornelius