Metabolic rate of oxygen in the skeletal muscle using [15O]O2-PET
Single inhalation [15O]O2 bolus model for skeletal muscle
See references Oikonen et al. 1998, Oikonen 1999, and Nuutila et al. 2000.
PET study is performed as described in MET5702.
Steps of MRO2 calculation:
1. Pre-processing of arterial blood curve
Arterial blood data from the on-line sampler needs to be processed before it can be used as input function in the calculation of oxygen consumption. Also metabolite correction is necessary in muscle studies. Blood curves are corrected for time delay later by the oxygen model fitting software.
Currently, there is no script for this process. It is strongly suggested that you write the commands in a batch/script file to preprocess all of your studies. Detailed instructions can be found in the previous links. Below are the commands needed to preprocess an imaginary study us5678, when population averages of whole body oxygen metabolism are used for metabolite corrections:
blo2kbq -c=S:\Lab\plasma\bsampler_calibration\pump_cal.dat -d=O -i=O -o=us5678blo.kbq us5678.bld o2metab us5678blo.kbq 1.307e-3 2.034e-3 0 0 dft2svg us5678blo.svg us5678blo_o.kbq us5678blo_w.kbq
After this you have two data files, us5678blo_o.kbq and us5678blo_w.kbq, which contain the arterial concentrations of [15O]O2 and [15O]H2O, respectively. Both are needed in the analysis.
The corrected blood TAC should always be plotted and controlled visually. It often contains close-to-zero values in the end, which should be removed with a text editor, or left out when determining the fit time. Check also that sample times are in seconds, not minutes. In the example above the graph was written in SVG file, but there are also other possibilities.
2. Make regional time-activity curves
3. Get arterial O2 content ([O2]a)
Arterial oxygen concentration ([O2]a) is not measured in measured in PET Center blood laboratory but in the hospital laboratory. It is reported in units mL O2/L blood (around 180-200 mL/L). Convert it to units mL O2/dL blood (1 dL = 100 mL = 0.1 L; about 18-20 mL/dL).
If necessary, the concentrations of O2 can be converted between volume and molar units with the molar volume of an ideal gas, 22.4 mL/mmol. Thus, [O2]a in molar units should be about 0.9 mmol O2/100 mL blood.
4. Compute regional MRO2 and OEF values
Estimate the regional MRO2 and OEF (oxygen extraction fraction or ratio, OER) using fit_mo2, version 3.0.0 or later. This program corrects also the input time delay separately for each region, because there is often marked differences in the tracer appearance times between different muscle regions.
Continuing with the previous example, if the measured arterial oxygen concentration for this subject was 19.8 mL/100 mL:
fit_mo2 -co2a=19.8 -svg=us5678fit.svg us5678blo_o.kbq us5678blo_w.kbq us5678.dft 400 us5678mro2.res
Estimated OEF should be between 0.2 and 0.9. If OEF is too close to 0 or 1, you can try to
- check from regional TACs if there is a probable movement artefact; you may need to draw separate ROIs for different time frame sequences and combine the TACs later, or delete one or two time frames from the regional data
- shorten the estimation time
- re-draw the ROIs to make them either smaller (to reduce heterogeneity and movement artefacts) or larger (to reduce noise).
In the above example, the units of MRO2 is ml O2 / (min * 100 ml tissue). If MRO2 is required per tissue mass instead of volume, it can be divided by tissue density (specific gravity), 1.04 g/mL (Reference Man).