In vivo online magnetic resonance quantification of absolute metabolite concentrations in microdialysate.
In order to study metabolic processes in animal models of diseases and in patients, microdialysis probes have evolved as powerful tools that are minimally invasive. However, analyses of microdialysate, performed remotely, do not provide real-time monitoring of microdialysate composition. Microdialysate solutions can theoretically be analyzed online inside a preclicinal or clinical MRI scanner using MRS techniques. Due to low NMR sensitivity, acquisitions of real-time NMR spectra on very small solution volumes (μL) with low metabolite concentrations (mM range) represent a major issue. To address this challenge we introduce the approach of combining a microdialysis probe with a custom-built magnetic resonance microprobe that allows for online metabolic analysis (1H and13C) with high sensitivity under continuous flow conditions. This system is mounted inside an MRI scanner and allows performing simultaneously MRI experiments and rapid MRS metabolic analysis of the microdialysate. The feasibility of this approach is demonstrated by analyzing extracellular brain cancer cells (glioma) in vitro and brain metabolites in an animal model in vivo. We expect that our approach is readily translatable into clinical settings and can be used for a better and precise understanding of diseases linked to metabolic dysfunction.
ISM, UMR 5255, Université Bordeaux, 33076, Bordeaux, France.
Stefan
S
Glöggler
ISM, UMR 5255, Université Bordeaux, 33076, Bordeaux, France.
Silvia
S
Rizzitelli
ISM, UMR 5255, Université Bordeaux, 33076, Bordeaux, France.
Noël
N
Pinaud
RMSB, UMR 5536, Université Bordeaux, 33076, Bordeaux, France.
Gérard
G
Raffard
ISM, UMR 5255, Université Bordeaux, 33076, Bordeaux, France.
Vanessa
V
Zhendre
RMSB, UMR 5536, Université Bordeaux, 33076, Bordeaux, France.
Véronique
V
Bouchaud
RMSB, UMR 5536, Université Bordeaux, 33076, Bordeaux, France.
Stéphane
S
Sanchez
CEA I2BM NeuroSpin, 91191, Gif-sur-Yvette, France.
Guillaume
G
Radecki
CEA I2BM NeuroSpin, 91191, Gif-sur-Yvette, France.
Luisa
L
Ciobanu
NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay, 91191, Gif-sur-Yvette, France.
Alan
A
Wong
ISM, UMR 5255, Université Bordeaux, 33076, Bordeaux, France.
Yannick
Y
Crémillieux
D000818:Animals; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D004867:Equipment Design; D005260:Female; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D009862:Online Systems; D051381:Rats; D017208:Rats, Wistar