Use of [15O] H2O PET to determine lower extremity muscle perfusion in patients with peripheral artery disease

Peripheral arterial disease (PAD) of the lower extremity is a progressive and
common disease caused by obstructions of the lower extremity arteries. Symptoms
of PAD include pain during exercise, which can progress into chronic
limb-threatening ischemia (CLTI) with pain at rest, and development of
non-healing ulcers. These clinical complaints are the result of impaired tissue
perfusion. To determine the severity and extent of ischemic tissue, tissue
perfusion measurements are deemed necessary. Most diagnostic techniques to
establish the diagnosis of PAD can only detect stenotic lesions of the major
arteries, and do not measure tissue perfusion. There are some non-invasive
techniques that measure skin perfusion, but are not widely used. Transcutaneous
partial pressure of oxygen (TcPO2) is one of the most often used tissue
perfusion techniques and is correlated with Fontaine classification, but it has
low quality of evidence and several limitations, including long measurement
time (15 minutes) and high inter-rater variability.
The technique measures the perfusion of the skin at a small (1 mm2) location
where the sensor is positioned. Perfusion of the skin is known to vary locally,
which is why TcPO2 measurements may not always reflect the global perfusion of
a limb. Therefore, there is need for a study that relates the local tissue
perfusion by TcPO2 with more global perfusion of the affected limbs in PAD
patients. [15O] H2O positron emission tomography (PET) is a gold standard for
tissue perfusion and it is shown that the [15O] H2O PET is able to measure
muscle perfusion. Currently, it is primarily used to measure myocardial
perfusion in patients with coronary artery disease (CAD).

The primary aim of this study is to correlate regional muscle perfusion
measured with [15O] H2O PET in patients with advanced PAD to local skin
perfusion measured with TcPO2.
Secondary objectives are to compare pre-revascularization perfusion rates with
post-revascularization perfusion rates and to correlate regional muscle
perfusion and local skin perfusion with arterial pressure measurements (ankle
brachial index; ABI and toe systolic blood pressure; TBP) to determine a
possible correlation in measuring lower limb perfusion pre- and
post-revascularization.
Another secondary objective is determining the inter- and intra-observer
variability in measuring local muscle perfusion with [15O] H2O PET.

This is a single centre pilot observational study with a study population of 15
patients with PAD Rutherford 4-6 in one leg and Rutherford 0-3 in the
contralateral leg, who are scheduled for endovascular revascularization. For
this research, patients will undergo a [15O] H2O PET scan and local skin
perfusion measurements pre-intervention and 6 weeks post-intervention. Skin
perfusion will be measured with TcPO2 at 4 locations of the lower legs and
feet.
Standard of care pre-intervention consist of arterial pressure measurements,
treadmill test if possible, duplex ultrasound and a CTa. The patients will be
staged following the Rutherford classification. Part of the standard of care 6
weeks post-intervention are arterial pressure measurements, treadmill test if
possible, TBP, and duplex ultrasound. Patients will be staged again at 6 weeks.
This is an observational study and the patients will receive treatment
according to standard of care. The treatment choices will not be affected by
the diagnostic results of the study.

There is limited risk associated with participation in this study. The [15O]
H2O PET/CT gives a combined dose of 1,04mSV, which is within category IIb
according to the Netherlands Commission on Radiation Dosimetry. It is less
radiation then the annual background radiation per person. Therefore, there is
limited risk in participation in this study. TcPO2 will be measured with the PF
6040 TcPO2 unit which is a CE-approved device and will be used in this study
according to intended use. Other measurements (systemic blood pressure, local
skin temperature, oxygen saturation, ABI and TBP) are routine clinical
measurements, with no additional risks.