Thoracoscopic Laser Speckle Contrast Imaging for the Demarcation of Lung Segments

INTRODUCTION AND RATIONALE 1.1 General introduction Despite recent major improvements in diagnosis, staging and treatment, lung cancer remains to be the leading cause of cancer-related deaths worldwide. Since the demonstration of superiority over sublobar lung resection, the current standard-of-care for small lung cancer is a lobectomy. In a lobectomy, one of the three (right lung) or two (left lung) lobes is excised. Albeit effective with respect to the radical excision of the tumour, the substantial loss in lung tissue may be clinically relevant, especially in combination with frequently co-existing lung diseases. This is made possible due to high resolution medical imaging (computed tomography) that enables surgeons to precisely locate small tumors. This paved the way for segmentectomy. Thoracoscopic segmentectomy is a combination of adequate oncological resection with lung-tissue-sparing properties and is being increasingly used because of its several advantages compared with lobar resections. Local recurrences after surgical resection are correlated to the length of the safety margins. These margins are defined by guidelines (2 cm for tumours >2 cm or a margin that is at least as large as the tumour diameter for smaller lesions). By defining the segment that has to be excised pre-operatively, the key to successful pulmonary segmentectomy is to subsequently intraoperatively recognize the intersegmental planes correctly. Although the intersegmental plane is regulated by intersegmental veins, it would be impossible to detect and follow these veins in the distal lung parenchyma, therefore, it is mandatory to identify the intersegmental plane before dividing the lung parenchyma.

1.2 Intersegmental plane detection methods The conventional and most common way to intraoperatively identify the intersegmental plane uses a conventional ventilation method (inflation/deflation technique). The targeted segment may be isolated from the rest of the lobe by selectively inflating the residual segments leaving the target segment atelectatic or, on the contrary, may be selectively inflated leaving the rest of the lobe atelectatic. A limitation of this method is the limited space to manoeuvre during video-assisted surgery.

More recently, optical imaging-based image guided surgery approaches are being developed to intraoperatively identify the intersegmental planes. With the increasing availability of endoscopic fluorescence imaging systems comes the popularity of fluorescence imaging throughout all surgical fields. This led to the development of methylene blue for intersegmental plane identification. However, the most common approach is the use of indocyanine green (ICG) fluorescence imaging. ICG-fluorescence imaging is based on the excitation of ICG, which is an exogenous contrast agent that is intravenously injected. The ICG binds to blood proteins that starts to circulate and gets excreted via the liver.

The ICG enables the surgeon to clearly identify the intersegmental planes after ligation of the main feeding artery. This method shows great potential but comes with limitations. The major limitation is the use of an exogenous contrast agent. After injection, the ICG only has very limited "imaging time window" (minutes) in which the images can be used to determine the intersegmental planes. In practice, this means that the surgeon quickly marks the intersegmental plane using an energy device. In an ideal situation the surgeon has as long as required for this action. Furthermore, the use of dye limits repeatability of measurements due to rest ICG, the extra operating room time required for the injection, wash-in and wash-out of the dye as well as change of camera settings.

1.3 Laser speckle contrast imaging for intersegmental plane detection ICG fluorescence imaging is a perfusion imaging technique that can help identify the intersegmental plane based on a perfusion difference that is created by ligation of the main feeding artery of the segment of interest. After ligation, ICG is infused. The distribution of ICG is visualized on the monitor, using a near-infrared camerasystem. The isolated segment will not exhibit any fluorescent signal and will therewith be identifiable using ICG. Laser speckle contrast imaging (LSCI) is a perfusion imaging technique that seems to have similar use cases as ICG with the added advantage of not using exogenous contrast. LSCI. The first biomedical application of LSCI was reported in the 1981 by Fercher and Briers. The proposed technique from Fercher and Briers was non-real-time and had its practical limitations due to the use of non-digital systems which impeded the clinical use. The first real speed increase to quasi real-time image acquisition and processing happened in the nineties with the introduction of digital photography. Generally, the components required are a low-powered laser diode, a diffuser, a digital camera and processing software.