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S. Azizian Amiri

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Doctoral thesis (2025) - S. Azizian Amiri, J. Dankelman, B.H.W. Hendriks
Breast cancer is the most common cancer in women globally, and breast-conserving surgery (BCS), or lumpectomy, is the primary treatment for early-stage patients. However, achieving clear margins—when the tumor is fully removed—remains a challenge, often requiring re-excision surgeries or additional treatments. Surgeons rely on preoperative images and palpation to estimate the tumor’s borders, but these methods are not always accurate, with incomplete resections occurring in 10% to 50% of cases. In this thesis, we explore the integration of Diffuse Reflectance Spectroscopy (DRS), an optical tissue-sensing technology, into an electrosurgical knife to create a smart electrosurgical knife that addresses this issue. DRS helps to distinguish between cancerous and healthy tissues in real-time by analyzing optical properties, offering a potential solution to ensure clear margins during surgery. Researchers have shown that DRS can differentiate tissues based on their unique optical fingerprints, such as the Fat/Waterratio, which helps determine tumor borders.

We began by identifying the main challenges in combining DRS with an electrosurgical knife. Initial tests on porcine tissue examined the impact of electrosurgery on the optical fibers and their ability to distinguish between tissues (Chapter 2). Microscopic analyses revealed changes in the optical fibers and the formation of debris during electrosurgery, which could interfere with accurate tissue sensing. The chapter concludes with an assessment of the fibers' performance in delivering light and capturing DRS readouts before and after electrosurgery, highlighting the complexities of using this technology in a surgical environment and the need for design modifications to protect the optical fibers from the effects of electrosurgery.

To further investigate design iterations and verify the technology, we describe in Chapter 3 the developed tissue-mimicking phantom materials that replicate the optical properties of human breast tissue. Since breast tissue consists of multiple layers with varying optical characteristics, simulating these complexities was crucial to test the smart electrosurgical knife. These phantom materials mimic both healthy and cancerous tissues, providing a controlled environment to evaluate the knife’s ability to differentiate between tissue types. The results from this chapter helped refine both the design and testing methodology of the knife.

In Chapter 4, we focus on the continued development of the smart electrosurgical knife to ensure it can withstand the demands of prolonged surgery. Several designs were tested on porcine tissue to identify the most effective configuration for integrating DRS. These designs were evaluated for their ability to maintain accurate DRS readings while performing electrosurgery, which involves high temperatures and tissue coagulation. Further experiments using tissue-mimicking materials demonstrated the knife’s ability to identify distinct tissue layers in real-time during electrosurgery.

In Chapter 5, we continued to enhance the design process by incorporating feedback from clinicians. In the first part, the best-performing design from previous experiments was refined based on suggestions from surgeons who tested the device. Various design concepts were produced to optimize the knife's electrosurgical and cutting performance while ensuring the integration of DRS technology. In the second part, the knife's performance was evaluated during a simulated lumpectomy on a tumor-containing phantom. Surgeons performed the surgery four times—twice with a traditional electrosurgical knife relying on preoperative images, and twice with the smart electrosurgical knife providing real-time tissue sensing. The results showed that using the smart knife led to better surgical outcomes, highlighting its potential as an intraoperative tool for margin assessment and its promise for improving the precision and safety of breast cancer surgeries.

In Chapter 6, we focus on simplifying the technology for broader surgical use. We proposed using LEDs and photodetectors instead of wide-band light sources and spectrometers, creating a compact, console-free design. An electronic board was developed to identify optimal wavelengths for breast tissue, and a proof-of-concept showed that this system could distinguish tissue-mimicking materials. We envision a handheld device integrating DRS into the electrosurgical knife, removing the need for bulky equipment and paving the way for a more accessible, user-friendly tool in clinical settings.

Finally, Chapter 7 reviews the key findings from the research and presents concluding remarks. The thesis demonstrates the potential of integrating DRS into surgical tools for real-time tissue identification, offering a valuable solution to the problem of incomplete tumor resection.
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Journal article (2024) - Pierre Ambrosini, Sara AzizianAmiri, Eliane Zeestraten, Tessa van Ginhoven, Ricardo Marroquim, Theo van Walsum
Purpose: For tumor resection, surgeons need to localize the tumor. For this purpose, a magnetic seed can be inserted into the tumor by a radiologist and, during surgery, a magnetic detection probe informs the distance to the seed for localization. In this case, the surgeon still needs to mentally reconstruct the position of the tumor from the probe’s information. The purpose of this study is to develop and assess a method for 3D localization and visualization of the seed, facilitating the localization of the tumor. Methods: We propose a method for 3D localization of the magnetic seed by extending the magnetic detection probe with a tracking-based localization. We attach a position sensor (QR-code or optical marker) to the probe in order to track its 3D pose (respectively, using a head-mounted display with a camera or optical tracker). Following an acquisition protocol, the 3D probe tip and seed position are subsequently obtained by solving a system of equations based on the distances and the 3D probe poses. Results: The method was evaluated with an optical tracking system. An experimental setup using QR-code tracking (resp. using an optical marker) achieves an average of 1.6 mm (resp. 0.8 mm) 3D distance between the localized seed and the ground truth. Using a breast phantom setup, the average 3D distance is 4.7 mm with a QR-code and 2.1 mm with an optical marker. Conclusion: Tracking the magnetic detection probe allows 3D localization of a magnetic seed, which opens doors for augmented reality target visualization during surgery. Such an approach should enhance the perception of the localized region of interest during the intervention, especially for breast tumor resection where magnetic seeds can already be used in the protocol. ...

Investigating a Smart Electrosurgical Knife's Functionality During Electrosurgery

Journal article (2024) - Sara Azizian Amiri, Jenny Dankelman, Benno H.W. Hendriks
Objective: Detecting the cancerous growth margin and achieving a negative margin is one of the challenges that surgeons face during cancer procedures. A smart electrosurgical knife with integrated optical fibers has been designed previously to enable real-time use of diffuse reflectance spectroscopy for intraoperative margin assessment. In this paper, the thermal effect of the electrosurgical knife on tissue sensing is investigated. Methods: Porcine tissues and phantoms were used to investigate the performance of the smart electrosurgical knife after electrosurgery. The fat-to-water content ratio (F/W-ratio) served as the discriminative parameter for distinguishing tissues and tissue mimicking phantoms with varying fat content. The F/W-ratio of tissues and phantoms was measured with the smart electrosurgical knife before and after 14 minutes of electrosurgery. Additionally, a layered porcine tissue and phantom were sliced and measured from top to bottom with the smart electrosurgical knife. Results: Mapping the thermal activity of the electrosurgical knife's electrode during animal tissue electrosurgery revealed temperatures exceeding 400 °C. Electrosurgery for 14 minutes had no impact on the device's accurate detection of the F/W-ratio. The smart electrosurgical knife enables real-time tissue detection and predicts the fat content of the next layer from 4 mm ahead. Conclusion: The design of the smart electrosurgical knife outlined in this paper demonstrates its potential utility for tissue detection during electrosurgery. Significance: In the future, the smart electrosurgical knife could be a valuable intraoperative margin assessment tool, aiding surgeons in detecting tumor borders and achieving negative margins. ...
Emerging intraoperative tumor margin assessment techniques require the development of more complex and reliable organ phantoms to assess the performance of the technique before its translation into the clinic. In this work, electrically conductive tissue-mimicking materials (TMMs) based on fat, water and agar/gelatin were produced with tunable optical properties. The composition of the phantoms allowed for the assessment of tumor margins using diffuse reflectance spectroscopy, as the fat/water ratio served as a discriminating factor between the healthy and malignant tissue. Moreover, the possibility of using polyvinyl alcohol (PVA) or transglutaminase in combination with fat, water and gelatin for developing TMMs was studied. The diffuse spectral response of the developed phantom materials had a good match with the spectral response of porcine muscle and adipose tissue, as well as in vitro human breast tissue. Using the developed recipe, anatomically relevant heterogeneous breast phantoms representing the optical properties of different layers of the human breast were fabricated using 3D-printed molds. These TMMs can be used for further development of phantoms applicable for simulating the realistic breast conserving surgery workflow in order to evaluate the intraoperative optical-based tumor margin assessment techniques during electrosurgery. ...
Distinguishing the diseased breast tissue from the healthy tissue is a sorely challenging task for the surgeons during breast conserving surgery (BCS) as both tissues own relatively similar visual and haptic characteristics. It has been shown that diffused reflectance spectroscopy (DRS) has the potential to be used as a real-time tumor margin detection technique during BCS. In this research, an electrosurgical knife is equipped with fiber-based DRS sensing to provide the surgeon with real-time oncological guidance during BCS. To prevent overheating of the fibers, they were placed inside quartz tubes which were mounted on the electrosurgical knife. The effect of using quartz tubes and debris formation during electrosurgery on the DRS measurements on porcine tissue was investigated. Furthermore to investigate the performance of the new device, a heterogeneous breast phantom representing optical properties and anatomical shape of the real breast was developed. The new device was then used to cut through the phantom’s layers to assess the performance of the new knife while cutting. Finally, a BCS was performed on the phantom using the new knife without receiving visual and haptic feedback from the tissue. The results show that both using the quartz tubes and the formed debris do not have a significant effect on the DRS output. Moreover, the DRS outputs obtained during cutting the layered phantom showed the transition between the layers clearly, demonstrating that the cutting effect on the phantom tissue does not significantly affect the measurements . The X-ray images from the phantom before and after BCS using the new device confirmed the complete resection of the tumors from the breast phantom. The results indicate that the electrosurgical knife equipped with DRS is a promising technique for simultaneously distinguishing and cutting the tissue, and assessing real-time tumor margins during BCS. ...

The effect of electrosurgery on tissue discrimination using ex vivo animal tissue models

Using an intraoperative margin assessment technique during breast-conserving surgery (BCS) helps surgeons to decrease the risk of positive margin occurrence. Diffuse reflectance spectroscopy (DRS) has the potential to discriminate healthy breast tissue from cancerous tissue. We investigated the performance of an electrosurgical knife integrated with a DRS on porcine muscle and adipose tissue. Characterization of the formed debris on the optical fibers after electrosurgery revealed that the contamination is mostly burned tissue. Even with contaminated optical fibers, both tissues could still be discriminated with DRS based on fat/water ratio. Therefore, an electrosurgical knife integrated with DRS may be a promising technology to provide the surgeon with real-time guidance during BCS. ...
We systematically reviewed the currently available evidence on how the design parameters of surface nanopatterns (e.g. height, diameter, and interspacing) relate to their bactericidal behavior. The systematic search of the literature resulted in 46 studies that satisfied the inclusion criteria of examining the bactericidal behavior of nanopatterns with known design parameters in absence of antibacterial agents. Twelve of the included studies also assessed the cytocompatibility of the nanopatterns. Natural and synthetic nanopatterns with a wide range of design parameters were reported in the included studies to exhibit bactericidal behavior. However, most design parameters were in the following ranges: heights of 100–1000 nm, diameters of 10–300 nm, and interspacings of <500 nm. The most commonly used type of nanopatterns were nanopillars, which could kill bacteria in the following range of design parameters: heights of 100–900 nm, diameters of 20–207 nm, and interspacings of 9–380 nm. The vast majority of the cytocompatibility studies (11 out of 12) showed no adverse effects of bactericidal nanopatterns with the only exception being nanopatterns with extremely high aspect ratios. The paper concludes with a discussion on the evidence available in the literature regarding the killing mechanisms of nanopatterns and the effects of other parameters including surface affinity of bacteria, cell size, and extracellular polymeric substance (EPS) on the killing efficiency. Statement of significance: The use of nanopatterns to kill bacteria without the need for antibiotics represents a rapidly growing area of research. However, the optimum design parameters to maximize the bactericidal behavior of such physical features need to be fully identified. The present manuscript provides a systematic review of the bactericidal nanopatterned surfaces. Identifying the effective range of dimensions in terms of height, diameter, and interspacings, as well as covering their impact on mammalian cells, has enabled a comprehensive discussion including the bactericidal mechanisms and the factors controlling the bactericidal efficiency. Overall, this review helps the readers have a better understanding of the state-of-the-art in the design of bactericidal nanopatterns, serving as a design guideline and contributing to the design of future experimental studies. ...