LED-based photoacoustic imaging of the lymphatic vessels

Abstract

Lymphedema is the accumulation of protein-rich fluid in the intersitium (i.e., dermal backflow (DBF)), causing swelling. It is a commonly seen due to iatrogenic damage to the lymphatics after surgical and radiotherapeutic treatment of cancer. An important microsurgical treatment is lymphovenous bypass (LVB) surgery, during which a lymphatic vessel is anastomosed to a vein to bypass the site of lymphatic flow obstruction. Pre-operative imaging of the lymphatic vessels is a prerequisite for planning of LVB surgery. Imaging of these structures is challenging due to the small size of the lymphatic vessels and the lack of inherit contrast of the lymphatic fluid. In this thesis, we investigated the feasibility of lymphatic vessel imaging using light emitting diode (LED) based photoacoustic imaging (PAI) for LVB surgical planning.
Chapter 1 gives an introduction to the physiology of lymphedema and (surgical) treatment options for lymphedema. Current challenges related to lymphatic vessel imaging and pre-operative planning are also discussed.
The systematic review in Chapter 2 gives an overview of the existing imaging modalities used for pre-operative visualization of the lymphatic vessels. Findings of the systematic literature review emphasized the importance of adequate imaging for clinical decision making and showed the heterogeneity of the field. Indocyanine green (ICG) contrast mediated near-infrared fluorescence lymphography (NIRF-L) has become the most popular in recent years and is currently used at the Erasmus Medical Center Rotterdam. NIRF-L facilitates lymphatic vessel depiction and lymphedema severity assessment based on the extent of DBF. However, NIRF-L has a low resolution and cannot visualize lymphatic vessels in the presence of DBF. Photoacoustic imaging (PAI) using LED light pulses is a novel technique that has properties that may overcome some of the disadvantages of NIRF-L.
Chapter 3 introduces the technical principles of PAI, and dual-wavelength PAI of ICG contrast and hemoglobin in blood is discussed. We performed phantom experiments to show the effect of several parameters on the image quality and demonstrate principle of dual-wavelength (820 & 940 nm) PAI of ICG and blood. The experimental results showed that the ratio between the PA signal at 940 nm and 820 nm differentiates blood from ICG. The 940/820 nm ratio might therefore be useful for in-vivo imaging of the lymphatic vessels and veins. With regards to imaging parameters, there is a trade-off between the frame rate and the image quality depending on the application (static or dynamic processes), and absorber characteristics and depth. Finally, the light pulse width must be tuned based on imaging target characteristics, the desired resolution and signal strength, and the fractional bandwidth of the ultrasound probe.
Chapter 4 describes preliminary results of a clinical feasibility study on handheld LED-based PAI of the lymphatic vessels in patients with secondary limb lymphedema. We investigated novel features such as the possibility of visualizing lymphatic vessel contractility and lymphatic vessel depiction behind DBF patterns. To date, three patients with breast-cancer related lymphedema were included in the study. We demonstrated that dual-wavelength, LED-based PAI can visualize lymphatic and blood vessels even in the presence of DBF. These findings suggest that PAI has potential for pre-operative lymphedema assessment, especially in cases with extensive DBF pattern hindering adequate assessment with NIRF-L.
Chapter 5 provides an overall discussion and future challenges are discussed. In this thesis we demonstrated the potential for lymphatic vessel identification using PAI. However, LED-based PAI is still consistently being improved. Our findings need to be confirmed in larger groups of patients and additional clinical studies. Technological advances are needed to improve user experience, image quality and minimize image artefacts.