SENTINEL LYMPH NODE BIOPSY USING MAGNETIC NANOPARTICLES - TOWARDS IMPLEMENTATION IN LAPAROSCOPIC SURGERY
The PhD defence of Lennert Molenaar will take place (partly) online and can be followed by a live stream.
Lennert Molenaar is a PhD student in the research group Magnetic Detection and Imaging. Supervisors are prof.dr. I.A.M.J. Broeders from the Faculty of Electrical Engineering, Mathematics and Computer Science and prof.dr.ir. B. ten Haken from the Faculty of Science & Technology.
The overall aim of this thesis is to explore the usage of magnetic nanoparticles for sentinel lymph node biopsies in the abdomen, and further development of a novel magnetic detection prototype for laparoscopic surgery.
The central medical problem which a sentinel lymph node biopsy (SLNB) tries to solve can be split into two parts. First, when a primary tumour and surrounding lymph nodes (LNs) are surgically treated by radical removal, unneeded tissue damage is caused if all removed LNs did not contain tumour cells. Second, chance of tumour recurrence is high if tumour cells spread to LNs outside the selected LN resection area, leading to a worse patient prognosis. By using a tracer to identify the primary draining lymph nodes (sentinel lymph nodes, SLNs) and removing those regardless of the anatomical area, less tissue damage is expected but with still a high accuracy to detect possible tumour cells.
The used tracer in this thesis consists of superparamagnetic iron oxide nanoparticles. With a magnetic core and polymer coating, the tracer is seen as inert by the human body and is encapsuled by white blood cells in LNs, resulting in an adequate biocompatibility. The main parameter of interest of this tracer is it superparamagnetic (nonlinear) behaviour. Because of this behaviour, it is possible to automatically remove background or linear signals (e.g. surgical steel and the human body) and determine tracer signal with the used differential magnetometry method.
To find this tracer signal, a magnetometer is required. Currently, there is only one commercially available magnetometer, which senses magnetic tracer, surgical steel and even the human body. To compensate, manual balancing of the device between every measurement is necessary, which is time consuming. A novel magnetometer is further developed (described in this thesis), which does not need balancing and can also be used during laparoscopic surgery. However, there are several technical challenges to create such a device, which are described in this thesis.
Since the principle of SLNB is of interest for theoretically all primary cancers, Chapter 2 uses a variation of the principle in a non-invasive method for colon cancer patients. Magnetic tracer is directly injected around the colon tumour after resection (i.e. ex vivo injection). After pathological LN dissection of the resected tissue, fast magnetic measurements were executed (less than a second per measurement) to determine and quantify magnetic tracer. This study showed that the used ex vivo tracer injection method needs to be improved. However, having a fast method to differentiate between LNs and SLNs to selectively perform extensive pathological research on the selected SLNs is an interesting concept to improve patient nodal staging.
In order to select SLNs during surgery, the injected tracer needs to be detected. However, detection can sometimes be difficult. Chapter 3 introduces the concept of using a hybrid tracer (part magnetic and part fluorescent tracer) to improve tracer findability for the surgeon. A scan of the region of interest is made with DiffMag handheld probe to create a roadmap as overlay for the surgical view. The complete concept was tested in a pig and led to successful tracer detection.
Despite SLNB being standard-of-care for breast and melanoma cancer patients and its potential for other tumour types, complete adaptation for prostate cancer patients is still out. Chapter 4 uses a magnetic tracer to identify SLNs for prostate cancer patients. This magnetic tracer was successfully imaged with MRI, found during ex vivo measurements in LNs and LNs were confirmed to contain tracer during pathological research. Furthermore, the commercially available magnetometer was compared with our developed prototype and is proven to work comparable, but does not need manual balancing between measurements.
The concept of this novel magnetometer is further used in a second prototype (the LapDiffMag), which focuses on compatibility during laparoscopic surgery. Since standard magnetometers need a certain probe thickness for the necessary detection depth, open surgery compatibility is only possible. Chapter 5 describes the principle of separating all required magnetic coils into two parts: a thinner detection probe to be used by the surgeon and a large magnetic field excitation coil below the patient. The technical properties were tested and compared with the first prototype. It became clear that an improved excitation coil is needed, since the used coil creates a limited magnetic field for in human use.
With a clear need for an improved excitation coil, development of such a new excitation coil is described in Chapter 6. The design choices are explained, as well as the production process. First test results are shown, and future necessary work is described. The complete LapDiffMag (consisting of the described detection probe, excitation coil and control unit) still needs further development and testing before clinical use. However, a major achievement is the successful development of a novel magnetic detector suitable for laparoscopic surgery, especially given the technical challenge of decreasing probe diameter without losing depth sensitivity.
Finally, Chapter 7 gives an overview of the main thesis findings and a future perspective how to continue this work to enable clinical implementation.