Perfusion monitoring in lower limbs of patients with peripheral arterial occlusive disease with continuous ICG video angiography - A pilot study

Peripheral arterial occlusive disease (PAOD) is a common and disabling disease.
In the Netherlands, the prevalence of chronic PAOD in patients older than 55
years is estimated to be 7% and for patients older than 85 years, 56%. PAOD is
a progressive disease, where the first stage is manifested by intermittent
claudication. The intermittent claudication will result in chronic limb
threatening ischemia (CLTI) in 15% of patients. Within 10 years after
diagnosing PAOD, 2% of patients must undergo major limb amputation. From all
patients diagnosed with critical limb threatening ischemia, 25% will undergo a
primary amputation. Of these patients with below the knee amputation, only
about 60% heals by primary intention and 15% requires a renewed amputation at a
higher level (through-knee or transfemoral). Therefore, patients with PAOD
suffer from decreased mobility, severe pain and lower quality of life compared
to the general population. Patients with PAOD have more comorbidity, and often
suffer from diabetes, cardiac and pulmonary diseases.
Symptoms and complications of PAOD, such as (rest) pain and non-healing ulcers
result from impaired peripheral tissue perfusion. This is mostly caused by
large-vessel atherosclerosis, however microvascular impairment due to
peripheral arterial occlusive disease or diabetes can also attribute to
hypoperfusion. Most current methods for assessing potential vascular compromise
include ankle brachial index, colour doppler ultrasound, toe systolic blood
pressure, treadmill test, CT angiography, and sometimes MRA. These methods
assess the arterial inflow into a limb and can be used to detect an arterial
stenosis, however cannot measure the actual peripheral tissue perfusion. An
accurate method for determining actual tissue perfusion is TcPO2 measurement,
which is considered to be the golden standard. Unfortunately, this method is
time consuming, operator dependent, and not applicable in everyday practice.
Moreover, the quality of evidence is low, and it is often not sensitive enough
to detect changes in perfusion during the operation. Assessment of tissue
perfusion is not only necessary to determine the presence or severity of PAOD
but can also be used to evaluate the efficacy of treatment.

Continuous ICG-VA

ICG-VA is an emerging technique for perfusion assessment and has been used in
esophagectomies, breast reconstruction, resection of colorectal liver
metastases, sentinel lymph node mapping, and real-time intraoperative
assessment of anastomotic perfusion after bowel resection. Furthermore, ICG-VA
has been used for the evaluation and quantification of skin perfusion in
patients with peripheral arterial occlusive disease (PAOD) with promising
results. Drawbacks include limited knowledge on its ability to quantify
perfusion and the limited temporal resolution that does not allow for
continuous, dynamic measurements.
Continuous ICG-VA is a promising technique to measure local skin tissue
perfusion with the potential for high sensitivity and real time measurements,
potentially enabling intraprocedural detection of improvement or failure of
therapy. This technique has not been used to quantify skin perfusion before.
First a study should be undertaken to determine feasibility of skin perfusion
measurements with continuous ICG-VA in lower limb tissue in patients with PAOD
(Rutherford class 4-6) and to develop a standardized measurement protocol.
Furthermore, it is not yet known how the accuracy of these measurements
compares to the gold standard TcPO2, ABI, and toe pressure measurements.
The technique utilizes microscopic doses of ICG, injected at a frequent and
regular time interval, to create regular time-intensity curves with an
increasing arterial phase and decreasing venous phase. When occurring in a
regular and frequent manner, these curves together form an oscillating
fluorescent signal, detectable in all vital tissue.

Conclusion

Continuous ICG-VA of the skin may potentially provide real-time and
intraprocedural measurement of tissue perfusion and enable early and even
intraoperative detection of success or failure of endovascular therapy in
patients with PAOD.

To investigate the feasibility of skin perfusion measurements of lower limb
tissue in 20 PAOD patients with continuous ICG-VA. Feasibility is defined as
the ability to detect hypo perfusion in the diseased leg in comparison with the
patient's contralateral control leg in at least half the patients with
continuous ICG-VA with good signal quality and sufficient sound to noise ratio.
Good signal quality defined as: anatomy of interest identifiable and centred in
the camera's field of view; no interference from natural lights (e.g.
daylight); no rapid movements of camera relative to anatomy of interest; no
change in distance from camera to anatomy of interest. Good SNR defined as:
change in fluorescent (ICG) intensity following each ICG bolus is larger than
5x the noise level at baseline (before any ICG is injected).

The secondary objective(s) are:
- to develop a standardized measurement protocol for continuous ICG-VA
measurements
- to investigate the ability of continuous ICG-VA to detect reperfusion after
endovascular revascularisation by using the Bland-Altman method to analyze the
agreement between the continuous ICG-VA measurements and TcPO2 and ABI tests
before and after the procedure
- to analyze the agreement between continuous ICG-VA measurements and toe
pressure measurements before the procedure using the Bland-Altman method

This study is a single centre pilot study to investigate the feasibility of
skin perfusion measurements of lower limb tissue with continuous ICG-VA in 20
patients with PAOD (Rutherford class 4-6).

The risks and burden associated with participating in this study are low. The
patients will be at the hospital as part of standard management and their stay
and treatment will not be affected by our study. All subjects will undergo
TcPO2, ABI, toe pressure and continuous ICG-VA measurements. The burden
regarding this study protocol will be that subjects will receive multiple
microscopic doses (0.001-0.02 mg ICG/kg) of ICG with a total ICG dose well
below the recommended maximum daily dose (5mg/kg/day). Administration of ICG
requires a venous catheter. As part of standard clinical care there patients
however have a venous catheter and there will be no need for an extra catheter.
ICG is a well-known compound that poses negligible risk to subjects. There are
no direct benefits for the patients by participating with this study.