Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate.
As alterations in tissue pH underlie many pathological processes, the capability to image tissue pH in the clinic could offer new ways of detecting disease and response to treatment. Dynamic nuclear polarization is an emerging technique for substantially increasing the sensitivity of magnetic resonance imaging experiments. Here we show that tissue pH can be imaged in vivo from the ratio of the signal intensities of hyperpolarized bicarbonate (H(13)CO(3)(-)) and (13)CO(2) following intravenous injection of hyperpolarized H(13)CO(3)(-). The technique was demonstrated in a mouse tumour model, which showed that the average tumour interstitial pH was significantly lower than the surrounding tissue. Given that bicarbonate is an endogenous molecule that can be infused in relatively high concentrations into patients, we propose that this technique could be used clinically to image pathological processes that are associated with alterations in tissue pH, such as cancer, ischaemia and inflammation.
Gallagher
Ferdia A
FA
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Kettunen
Mikko I
MI
Day
Sam E
SE
Hu
De-En
DE
Ardenkjaer-Larsen
Jan Henrik
JH
Zandt
René in 't
Ri
Jensen
Pernille R
PR
Karlsson
Magnus
M
Golman
Klaes
K
Lerche
Mathilde H
MH
Brindle
Kevin M
KM
D000136:Acid-Base Equilibrium; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D002256:Carbonic Anhydrases / Q000378:metabolism; D002384:Catalysis; D006863:Hydrogen-Ion Concentration; D008223:Lymphoma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009368:Neoplasm Transplantation; D019047:Phantoms, Imaging
D001639:Bicarbonates; D002247:Carbon Isotopes; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases