Pharmacological MRI: a nebulous concept?

In their recent TiPS article [1xPharmacological magnetic resonance imaging: a new application for functional MRI. Leslie, R.A. and James, M.F. Trends Pharmacol. Sci. 2000; 21: 314–318Abstract | Full Text | Full Text PDF | PubMed | Scopus (112)See all References[1], Leslie and James define pharmacological magnetic resonance imaging (phMRI) as the use of functional MRI (fMRI) to monitor drug-induced changes in brain activity. We question whether it is reasonable and appropriate to dub such a restricted application of a specific nuclear magnetic resonance (NMR) methodology with the general terms ‘pharmacological’ and ‘MRI’? Are we to dub other MRI applications [2xIn vivo magnetic resonance methods in pharmaceutical research: current status and perspectives. Rudin, M. et al. NMR Biomed. 1999; 12: 69–97Crossref | PubMed | Scopus (92)See all References[2] such as T1-MRI, T2-MRI, perfusion MRI, diffusion-weighted MRI (DWI-MRI), contrast-enhanced MRI (CE-MRI), magnetization transfer MRI (MT-MRI), etc., used to investigate effects of drugs at various sites (e.g. joints, tumours, heart, vessels, lung and kidney), similarly? We think not and suggest that to do so would serve no useful purpose. In addition, the authors’ definition of pharmacology seems to be too restricted. Would they not define as pharmacological the fact that a drug dose-dependently reduces infarct sizes measured by ‘anatomical’ MRI ([3xCalcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion as determined by quantitative magnetic resonance imaging. Sauter, A. and Rudin, M. Stroke. 1986; 17: 1228–1234Crossref | PubMedSee all References[3])?Leslie and James also imply that positron emission tomography (PET) and related technologies are primarily used for ‘localization of ligands in the living body’. However, long before the introduction of fMRI, PET-based methods were used extensively in humans to monitor changes of brain function that are associated with mechanical, sensory, cognitive and, of course, pharmacological stimuli. The value of the review by Leslie and James could have been increased by elaboration of the strengths and weaknesses of fMRI compared with the more established methods that are used to investigate brain function under various physiological and pathological conditions [e.g. PET, single photon emission computed tomography (SPECT), magnetoencephalography (MEG), electroencephalography (EEG), among others].Finally, we do not believe that fMRI, as indeed NMR in general, will inherently lead to new insights and possibly replace the other methods that are in use to address fundamental issues in pharmaceutical research, such as validation of drug targets, defining specific ‘fingerprints’ of drugs, etc., as suggested in Box 2 of the TiPS article. It is our belief that NMR is, and will remain, most successful where its main advantage, namely its non-invasiveness, is relevant. Unfortunately, the list of potential NMR applications is defined not only by the imagination of scientists, as suggested in this article, but also by the limitation in sensitivity of NMR that are dictated by the laws of physics.