Introduction: Coronary atherosclerosis can form large lipid-rich plaques inside the arteries, which are prone to rupture. Rupture can lead to thrombus formation and subsequent obstruction of the blood flow, which is the most common cause of acute coronary events like myocardial infarction. Current imaging modalities lack the ability to image important factors in the diagnosis of these vulnerable plaques or have a limited image quality. A novel imaging modality, intravascular ultrasound (IVUS) combined with intravascular photoacoustics (IVPA), is a good candidate for accurate lipid imaging in atherosclerotic coronary arteries. IVPA enables specific lipid imaging alongside the artery morphology image provided by IVUS. Kaminari Medical is developing the first rotating IVUS and IVPA catheter for this purpose. Objective: The objective of this research project is to develop an image reconstruction method with improved lateral resolution (LR) and Signal-to-Noise Ratio (SNR) compared to the conventional image reconstruction method. Methods and Materials: A literature review was executed to find the state-of-the-art image reconstruction method for IVUS and IVPA. A virtual source synthetic aperture (VSSA) beamforming method with Coherence Factor Weighting (CFW) was selected and implemented to achieve the desired image quality improvement. The principle of the VSSA is that the signals captured at adjacent transducer positions are delayed and summed to use all available image information. The delays are calculated with respect to the virtual sources, which are placed at the natural focus of the beams under the assumption that this yields the best alignment after delaying the signals. A pixel-based implementation of VSSA with CFW was developed on IVUS data which directly reconstructs the image pixel values. Subsequently, the algorithm is optimized to achieve the best image quality for IVUS and IVPA data acquired by the Kaminari Medical catheter. Results: The implementation of the algorithm based on the literature did not show the image quality as expected, most likely due to the invalid assumption that the virtual source should lie at the natural focus of the ultrasound beam. Therefore, the virtual source depth and the opening angle of the beam are optimized to find the parameter combination that achieves the best image quality. For both IVUS and IVPA, narrow beam shapes and a virtual source behind the transducer, thus using diverging beam shapes, should be used to obtain the best LR and SNR. The optimized VSSA leads to an increased SNR by 20.3% and 77.7% for IVUS and IVPA, respectively. The LR is increased by 7% for IVPA but shows a LR reduction for the IVUS data. Conclusion: The optimized VSSA meets the objective of improving the LR and SNR to a large extent. However, it is recommended to focus future work on developing a substitutional weighting method for the CFW to also improve the LR for the IVUS data

Introduction – Cardiovascular diseases are the leading cause of death in the world with one in three succumbing to the disease. The most common cardiovascular disease is coronary artery disease, caused by atherosclerosis resulting in a build-up of plaque within the arteries. This plaque can progress into a vulnerable plaque, which has been linked to an increase in major adverse cardiac events. Identification of a vulnerable plaque can lead to more precise treatment, better patient outcomes, and fewer reinterventions. A technique currently in development is intravascular photoacoustic catheter imaging combined with intravascular ultrasound, which can detect both the composition and the structure of a plaque. Current pullback devices – a device for driving the catheter – don’t exist for a clinical setting for this application and are used for research purposes only. This project is a design study looking into the different aspects that go into the development of such a product with the aim of usability, divided into two goals: Exploring the catheter connection to the pullback device that is suitable for users of the product, and the redesign of the pullback device. Methods and Materials – The first part concerns the design of the catheter connection to the pullback device for users of the product. The users are interventional cardiologists and anyone who interacts with the device in a clinical setting. Catheter connector designs are prototyped and central to a short user experience study. The design space for current catheter connector devices is explored and four connectors are designed. A user experience study is made with the aim of obtaining feedback on different design aspects and what this user group prefers in catheter connector devices. The second part concerns the redesign of the system. A system design is proposed within the set requirements. Results – Catheter connector designs are designed and 3D printed, assembled and placed in mock-up pullback devices as prototypes. These have been shown to users of the product during a user experience study. This study has shown that users (n=5) have clear preference for some design aspects, such as a twisting connection, relatively small connection devices, automatic signal connection parts, among others. A redesign of the system is performed within the set requirements, where design aspects and their consequences are considered. This is done through an iterative design process to enquire feedback from technicians, until a satisfactory system is proposed. This includes the signal transfer to the catheter and back, the rotation of the catheter, the pullback of the catheter, and its housing. Discussion – Catheter connection design aspects have been explored after which a system redesign is proposed. This redesign lacks the connection between the signal connectors of the catheter and the pullback device. This connection is highly dependent on the disconnection method, which is non-trivial and infeasible to explore in this user experience study. The catheter connector could encompass a project in itself. The system redesign originally was aimed at the manufacture of the device, but was deemed infeasible for this project. Instead the project was aimed to be a design study of the development of such a device. As it stand, the current device is larger than preferred by users, which could be scaled down in collaboration with parts manufacturers. This can also downscale the motor for rotation, which is implemented to work at the devices maximum expected power requirements. Conclusion – This thesis focused on the design study of a pullback device for intravascular photoacoustic and ultrasound catheter imaging for users of such a device. Catheter connection design aspects have been explored after which a system redesign is proposed considering the many different aspects that go into such a design. All designs have been handed over to Kaminari Medical

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.