Real-time Quantitative Optical Perfusion Imaging in Surgery: A Prospective, Observational, In-vivo, Human, Single-Center Study.

Surgeons are nowadays unable to visualize and quantitatively evaluate
microvascularisation in real-time during surgery. Complications due to vascular
compromise are a major problem, especially in reconstructive surgery. Poor
blood perfusion leads to ischemia and even tissue necrosis because of the lack
of nutrients.

In patients with esophageal cancer who receive an esophagectomy can undergo a
reconstruction forming a 'tube' of gastric tissue. Ischemia of this
'gastric-tube' occurs in 5-20% of patients, which results in anastomotic
leakage and stenosis, with high morbidity and even mortality. Patients need a
re-operation or intensive care unit stay and this is correlated with high costs
in healtcare.

In patients with considerable defects due to trauma or disease, e.g. radical
cancer surgery, free flap reconstruction leads to enhanced tissue function and
shape repair. Sufficient perfusion of tissue is essential in free-flap transfer
success. Despite research, 5% of free flap reconstructions lead to necrosis and
tissue loss with a high morbidity and high costs for healthcare.

However, if perfusion and ischemia could be monitored during surgery, then
surgeons could change their reconstructive design and the anesthesiologists
could improve perfusion with fluids, inotropes or vasopressors, if necessary.

In recent decades, innovative optical techniques have been developed that use
the interaction of (harmless) light with tissue. Previous research suggest a
powerful role for these techniques in medical diagnostics. Optical Coherence
tomography (OCT), Indocyanine Green (ICG) fluorescence, Sidestream Darkfield
Microscopy sDF) and Laser Speckle Imaging (LSI) could all be valuable in
imaging perfusion during surgery.

Primary objective
- To assess the reliability and explore the validity of Fluorescence Imaging,
Laser Speckle Contrast Imaging, Optical Coherence Tomography and Sidestream
Dark Field as a perfusion imaging modality, during free flap reconstruction and
gastric tube reconstruction.
To assess the reliability of the techniques we will focus on the interobserver
agreement. We will score the images on the following 5 specific hemodynamic
parameters (following the criteria of perfusion interpretation stated by de
Backer et al.1): total vessel density, proportion of perfused vessels, vessel
diameter, RBC concentration, and blood flow velocity.To explore the validity of
the techniques we will compare the differences in images of good versus sparse
blood flow in terms of the above defined 5 quantitative parameters.

Secondary objectives
- To technical compare the four imaging modalities in terms of resolution,
imaging depth and field of view.

This is a single-center, prospective, observational, in-vivo phase II pilot
study of 40 evaluable adult patients receiving reconstructive surgery in terms
of free flap surgery (n=20) and gastric-tube surgery (n=20). Total study
duration is 2 years. During reconstructive surgery, images of tissue perfusion
will be made with the four optical techniques at different time periods.

All techniques use harmless light to image perfusion during surgery. Patients
are already planned for this type of surgery, so this extra procedure of
imaging carries no additional risk to the patient. In each patient all the
techniques will image before and after reconstruction of tissue (free flap
surgery) or before and after ephedrine (in gastric tube surgery). The only risk
will be the additional time of imaging during surgery, which added about 10-20
minutes to the overall surgical procedure. Furthermore, we will use indocyanine
green for Fluorescence Imaging and ephedrine as perfusion improving agent,
which are both FDA approved. Only patients with contraindications could be at
risk, so these patients will be excluded from our study (see exclusion
criteria).
We therefore classify the proposed research as a study with negligible risk
according to the NFU- (Nederlandse Federatie van Universitaire Medische Centra)
criteria for human research.