Format

Send to

Choose Destination
J Cereb Blood Flow Metab. 2014 Apr;34(4):690-8. doi: 10.1038/jcbfm.2014.12. Epub 2014 Feb 5.

Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI.

Author information

1
Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada.
2
Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
3
1] Robarts Research Institute, University of Western Ontario, London, Ontario, Canada [2] Department of Physiology and Biophysics, Neuroscience Centre, Federal University of Minas Gerais, Belo Horizonte, Brazil.
4
1] Robarts Research Institute, University of Western Ontario, London, Ontario, Canada [2] Department of Biochemistry, University of Western Ontario, Western University, London, Ontario, Canada.
5
1] Robarts Research Institute, University of Western Ontario, London, Ontario, Canada [2] Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada [3] Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
6
1] Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada [2] Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.

Abstract

Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading to irreversible cellular damage. Chemical exchange saturation transfer (CEST) effects can be used to generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been used to delineate the ischemic penumbra after ischemic stroke. In the current study, a novel MRI ratiometric technique is presented to measure absolute pH using the ratio of CEST-mediated contrast from amine and amide protons: amine/amide concentration-independent detection (AACID). Effects of CEST were observed at 2.75 parts per million (p.p.m.) for amine protons and at 3.50 p.p.m. for amide protons downfield (i.e., higher frequency) from bulk water. Using numerical simulations and in vitro MRI experiments, we showed that pH measured using AACID was independent of tissue relaxation time constants, macromolecular magnetization transfer effects, protein concentration, and temperature within the physiologic range. After in vivo pH calibration using phosphorus ((31)P) magnetic resonance spectroscopy ((31)P-MRS), local acidosis is detected in mouse brain after focal permanent middle cerebral artery occlusion. In summary, our results suggest that AACID represents a noninvasive method to directly measure the spatial distribution of absolute pH in vivo using CEST MRI.

PMID:
24496171
PMCID:
PMC3982091
DOI:
10.1038/jcbfm.2014.12
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center