Simultaneous PET and NMR—initial results from isolated, perfused rat hearts
British Journal of Radiology
Using the system described by Paul Marsden et al  , it is possible to acquire simultaneous PET scans and NMR spectra from isolated, perfused rat hearts. The results from three separate series of experiments will be described: firstly, pilot experiments, or feasibility studies, using 11 mM glucose as the sole substrate; secondly, experiments with 10 mM lactate as a co-substrate; and thirdly, experiments on regional ischaemia and reperfusion. The standard, isolated perfused rat heart, first
... cribed by Langendorff in 1895, is a globally perfused preparation in which the aorta is cannulated and a buffer reservoir above the heart provides a pressure head of about 90 mmHg that forces the perfusion fluid through the coronary arteries. If one puts a perfused heart inside an NMR magnet one can acquire a 31 P NMR spectrum, as shown in Figure 1 . There are three important types of information one can obtain from such spectra. Firstly, one can identify the peaks from their position (or frequency, given in magnetic-field-independent units of ppm); in a heart one can identify inorganic phosphate (P i ), phosphocreatine (PCr) and the three peaks of adenosine triphosphate (ATP) (a-, b-and c-phosphates). Secondly, one can quantify the metabolites from the areas under each of the peaks; to quantify ATP, one must use the b-peak because there are other peaks (e.g. adenosine diphosphate (ADP), nicotinamide adenine dinucleotide (reduced form) (NADH)) that have almost identical positions to the c-and a-phosphates. Thirdly, one can determine the intracellular pH of the rat heart, from the position of the P i peak relative to that of PCr. The mini-PET system that we use  , which fits inside the top of the magnet, is shown in Figure 2 , together with the position of the NMR probe and perfused heart, which fit into the bottom of the magnet. An expanded version of the heart, the NMR probe and the PET scanner is shown on the right-hand side of the figure and one can see that the NMR coil completely surrounds the heart; thus the NMR signals observed originate from the whole heart. The PET scanner fits over the top of the NMR probe such that a single, midventricular PET scan is obtained. For the pilot studies , hearts were perfused (100 cm H 2 O pressure) with buffer containing 11 mM glucose for 30 min and the system was then switched to a recirculating one (volume 500 ml) containing trace amounts (50 MBq) of 18 FDG (FDG, fluorodeoxyglucose) in addition to 11 mM glucose; perfusion was continued for a further 2.5 h. PET scans and NMR spectra were taken at 85, 115 and 145 min and the workload was then increased by 20% and a fourth NMR spectrum and PET scan were acquired. The results obtained are shown in Figure 3 . In the first three NMR spectra, peaks from P i , PCr and ATP are visible in the ratios expected for a perfused heart; these metabolites are constant from one spectrum to the next and remain so, even when the workload is increased (fourth spectrum). Thus, the heart can maintain its energy status when the workload is increased, by increasing its energy supply. This was borne out by the quantification of the PET scans that showed that the rate of fluorodeoxyglucose 6-phosphate (FDG6P) accumulation increased when the workload was increased (data not shown). Figure 1. 31 P NMR spectrum of an isolated, perfused rat heart. Peaks are as labelled.