Pilot study of non-invasive tissue perfusion imaging in Peripheral Arterial Disease with MultiSpectral Optoacoustic Tomography

Peripheral arterial disease (PAD) of the limbs is a progressive and common
disease. Symptoms of PAD include pain, and when the disease progresses to
critical limb-threatening ischemia, resting pain and non-healing ulcers. The
symptoms are the result of impaired tissue perfusion. To determine the severity
of PAD, but even more important to localize ischemic regions in the lower
extremity, tissue perfusion imaging may be extremely relevant. Today, the most
common studied modality for non-invasive tissue perfusion measurements is
transcutaneous partial pressure of oxygen (TcPO2). Unfortunately this technique
has some limitations. It is operator dependent, time consuming and not well
suited for everyday clinical use. A potentially more appropriate technique is
Multi-Spectral Optoacoustic Tomography (MSOT). It is a new non-invasive imaging
technique with real-time visualization of the ratio of oxygenated and
deoxygenated haemoglobin, and therefore tissue oxygen saturation. As such,
anatomical and perfusion characteristics of blood vessels can be combined.
Therefore, this imaging modality has the potential to evaluate the effects of
treatments in patients with PAD quantitatively and accurately.

This study aims to investigate the feasibility and clinical performance of
tissue perfusion imaging with MSOT in the lower extremity of healthy
volunteers, claudicants and patients with critical limb-threatening ischemia.
The main objective is to optimize MSOT to quantify tissue saturation by
resolving oxygenated and deoxygenated haemoglobin in these three categories of
subjects. The second objective is to develop a standardized measurement
protocol for the MSOT imaging in the lower extremity to optimize precision and
accuracy of the measurements.Another objective is to determine changes in
tissue saturation after hyperemia test due to cuff occlusion of the upper leg
in healthy volunteers. Other objectives are to evaluate tissue saturation
determined with MSOT in reference to standard diagnostics such as
ankle/brachial index (ABI), toe systolic blood pressure (TBP), Doppler
ultrasound and TcPO2 measurements. The final objective is to visualize the
affected arteries and to determine tissue perfusion values before and after
supervised exercise in claudicants or revascularization procedures in patients
with critical limb-threatening ischemia.

This study is a single center pilot study to investigate the feasibility and
clinical performance of MSOT imaging in 10 healthy volunteers, 10 claudicants
(Rutherford 2-3) and 10 patients with critical limb-threatening ischemia
(Rutherford 4-6). In all participants MSOT imaging will be performed on the
calf muscle and the plantar side of the foot. Additionally a TcPO2 measurement
will be performed on the calf muscle. Healthy volunteers will undergo cuff
occlusion of the upper leg to induce a hyperemia test during MSOT imaging.
Claudicants will be imaged before and after supervised exercise in combinations
with TcPO2 measurements. Patients with critical limb-threatening ischemia will
receive MSOT imaging before and after revascularization procedures in
combination with TcPO2 measurements. The post-procedure measurements will be
performed before discharge from the hospital and after 6 weeks in combination
with the regular appointmet at the outpatient clinic. In all patients, the
anterior tibial artery and dorsal pedal artery will be imaged before and after
treatment next to the calf muscle and the foot. The measurements are additional
to standard diagnostics such as, ABI, TBP, Doppler ultrasound and CTA, for both
patient groups. The study measurements will not influence diagnostics and
treatment of the patients, and all patients will receive diagnostics and
treatment according to standard of care.

The risks associated with participation with this study are low. The MSOT
system is an investigational device that has been developed by iThera Medical
GmbH in collaboration with the UMCG. The device uses a class IV laser, which
has some potential risk of causing damage to the eye when exposed to the laser
light directly. Special safety measurements, like an interlock system, warning
lights, laser safety training and laser safety goggles with corresponding SOPs
are all taken to minimize risks for the patient and caregiver. Healthy
volunteers will only receive MSOT imaging and TcPO2 measurements once. For
claudicants and patients with critical limb-threatening ischemia no additional
hospital visits are required. MSOT imaging will be scheduled together with
regular appointments and will take about 60 minutes. For both of these patient
groups regular outpatients visits, hospital visits, diagnostics and treatment
are according to standard of care, and not affected by the study. Therefore,
the burden of participation is low. The study results will not affect
diagnostics or treatment of the patients. There are no direct benefits for
patients concerning the treatment they are receiving.