Reproducibility and rEliability of Perfusion angiography and prEdiction of wound heAling in criTical limb ischemia.

Critical limb ischemia (CLI) is a serious condition caused by end stage
peripheral artery disease (PAD) in which the viability of the lower extremity
is at risk. The aim of CLI treatment is optimization of inflow to the diseased
part of the lower extremity. This can be achieved by open bypass surgery or in
an endovascular fashion. Unfortunately, the success of endovascular
revascularization is largely unpredictable as demonstrated by a high rate of
failed or delayed wound healing and repeat interventions. Non-invasive
measurements such as toe pressures, TcpO2 or near-infrared spectroscopy (NIRS)
can be helpful but do not correlate well with wound healing and are generally
not available intra-procedurally. Currently, the operators rely largely on
their own experience and *eyeball* the results of their revascularization
efforts by looking at the flow through the arteries below the knee (BTK), the
pedal arteries, and wound blush using iodinated contrast injected into the
arteries and imaged using X-ray.

Philips has developed a tool in order to provide quantitative interpretations
of the images, and thereby assist in the objective intra-procedural evaluation
of revascularization. The tool, referred to as *2D Perfusion* (2DP) is
commercially available, and functions by extracting flow information from the
X-ray images. A protocol for the use of 2DP in CLI patients has been developed
and early results suggest that the extent of increased blood flow to the foot
can be determined. However, these results should be interpreted with some
thought because data on reproducibility and reliability in CLI are missing. If
reproducibility and reliability of PA are good this technique may provide per
procedural information about the target vessels that need to be re-vascularized
to obtain good inflow to the ischemic part of the foot and may determine a
metric above which clinical outcomes are typically favorable.

The objective of this study is twofold. First objective is to determine the
reproducibility and inter-rater reliability of Perfusion Angiography. The
second is to investigate the predictive value of Perfusion Angiography for
wound healing in Critical Limb Ischemia.

This is a single centre pilot study with a prospective observational character
carried out in the St. Antonius Hospital. Operators will be blinded for the
perfusion results during the procedure to prevent treatment bias.

There will be no direct benefit for subjects participating in this study. The
risk associated with participation are related to the use of extra contrast
material and radiation dose.

Risks associated with additional contrast medium.
Subjects with CLI are generally at a higher risk of developing contrast-induced
acute kidney injury (CI-AKI). To minimize this risk subjects with an eGFR <30
will be excluded from this study and the amount of contrast will be limited to
a maximum of 40 mg Iodine or 150 mL of Visipaque 320 (GE Healthcare Inc.).
Furthermore, the protocol used in this study to prevent CI-AKI is in line with
the local hospital doQu guidelines. A recent study showed no difference between
intravenous or intra-arterial contrast administration with respect to the
occurrence of CI-AKI.

Risks associated with additional radiation dose.
To check if the use of extra radiation dose is justifiable the guidelines of
the Netherlands Commission on Radiation Dosimetry May 2016 were used.
The maximum extra radiation dose in this study is 5.6 Gycm2. To calculate the
effective dose as a rule of thumb, this number of corresponds to an extra
radiation dose of 0.23*5.6 = 1.3 mSv.
Taken into account that subjects in this study are generally older than 50
years of age the additional effective dose can be divided by 5-10. This means
that these subjects in this study are in ICRD risk category IIA. Subjects
younger than 50 years of age will be in category IIB.