Muscle [15O]H2O PET

Radiowater bolus-injection, or [15O]CO2 inhalation studies can be analyzed with kinetic model fitting or autoradiographic (ARG) method. Both methods are based on the same model for [15O]H2O, and both can be applied to dynamic PET scan data, but static PET image data can only be analyzed with the ARG method.

Steady-state [15O]H2O or [15O]CO2 studies of skeletal muscle (Ruotsalainen et al., 1997) are not commonly performed on humans due to relatively high radiation dose and duration of the scan, but they are applicable for in animal studies (Carter et al., 1997).

Arterial blood data, collected using on-line sampling system, must be calibrated and corrected for physical decay, dispersion and time delay. Time delay may not be the same in different legs or muscle regions, and therefore it should be corrected for each region separately; when computing parametric images this is not possible for statistical reasons (Burchert et al., 1997).

Simulated and measured muscle TACs
One-tissue compartmental model can be used to simulate realistic muscle PET time-radioactivity concentration curves even in spreadsheet. Download the spreadsheet in Google Docs, Excel (.xlsx), or OpenDocument (.ods) format.

Exercise studies, when one leg is at rest, can also be analyzed semi-quantitatively by calculating exercise-to-resting muscle ROI ratios (Ament et al., 1998); radioactivity concentration has roughly linear relationship with muscle perfusion (Burchert et al., 1997).

Parametric perfusion images

ARG method

ARG method can be used to calculate the perfusion in skeletal muscle (Ruotsalainen et al., 1997). Method can produce parametric blood flow images in good quality, and results are reliable, because partition volume of water in skeletal muscle is relatively constant and arterial volume fraction is usually low and relatively stable.

Example perfusion image from femoral region calculated using ARG method
Perfusion can be measured in exercising femoral muscle, with the other leg in rest. Note that the look-up table for the ARG method must cover both low and high perfusion ranges, and, for more precise results, rest and exercise leg may need to be analyzed using different integration time.

In ARG method, a fixed partition coefficient (p) and arterial blood volume (VA) must be used. For skeletal muscle usual assumptions are p=0.99 and VA=0.

Kinetic method

If dynamic PET data is collected, then basis function (Boellaard et al., 2005) and multilinear approach (linearization described by van den Hoff et al., 1993, and applied to skeletal muscle by Burchert et al., 1997) for kinetic model are viable alternatives to the ARG method, and may provide better quantification especially if there are large perfusion differences in the regions of interest, or arterial volume fraction is not small or can vary greatly, or if also other tissues (with different or unknown partition coefficient of water) than skeletal muscle are to be analyzed from the same PET image. In practice, partition coefficient may be impossible to measure accurately in resting muscle where perfusion is low (Burchert et al., 1997).

Example perfusion image from femoral region calculated using NNLS method Example p image from femoral region calculated using NNLS method Example Va image from femoral region calculated using NNLS method
Parametric perfusion, K1/k2, and Va maps from the same study computed using multilinear method.
Example perfusion image from femoral region calculated using BFM method Example p image from femoral region calculated using BFM method Example Va image from femoral region calculated using BFM method
Parametric perfusion, K1/k2, and Va maps from the same study computed using BFM method.

Fischman et al (2002) validated kinetic analysis of [15O]H2O PET in dog hindlimb muscles against microsphere method in a wide perfusion range.

Clinical results

Peripheral vascular disease (PVD) has been studied with radiowater PET, but no significant differences have been found between patients and healthy subjects (Depairon et al., 1991; Burchert et al., 1997). Exercise-induced perfusion increase was significantly lower in ischemic than in normal legs, which can help to identify severely ischemic leg regions and to decide the level of amputation (Scremin et al, 2010).


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Updated at: 2019-02-19
Created at: 2016-11-10
Written by: Vesa Oikonen