‘Some operations involve advanced mathematics’
Technology and medicine are deeply intertwined, according to professor of Orthopaedics, Rob Nelissen. “If you want to move with the times as a university hospital doctor, you need to work with engineers.”
Nelissen, who has had a dual appointment at both the LUMC and TU Delft since 2006, has been working with TU Delft engineers for decades, referring to them as the “crazy guys from Delft” and “my friends in Delft”.
One of these friends was mechanical engineer Edward Valstar, who died in 2017. For years, Nelissen worked in tandem with Valstar, also a Medical Delta professor. They worked together on the development of minimally invasive surgery as a remedy for loose prosthetics. This is a major problem: 10% of all prosthetics become loose within a decade.
Fifteen years ago, Nelissen’s LUMC group had a plan to tackle this issue using gene therapy. But the wider public had its doubts about gene therapy. “Venture capitalists were reluctant to join us in developing the plan. So, I decided to call on my friends in Delft again, hoping to find another solution by working with them.
We developed a technique using a thin needle to inject a type of cement (Polymethyl methacrylate, PMMA) into the gap between the prosthetic and the bone. After fifteen minutes, the cement hardens and the prosthetic is reattached.”
Creative minds
Having to work across disciplines in order to make progress is something Nelissen takes for granted. “In the last decade, technology and medical sciences have become deeply intertwined. As a discipline, orthopaedics no longer really exists.”
In his view, a university hospital, where numerous complex operations are performed, naturally brings together multiple disciplines. “I work with neurosurgeons, radiologists and engineers. All the different specialisms overlap. If you remove one of them, that whole complex process becomes impossible.”
As a backpacker in his younger years, he loved exploring new cultures. “That’s why I enjoy working with engineers – I’m immersing myself in a different culture. Delft is full of creative minds. By talking to each other, you can come up with some great original concepts for improving patient care.”
‘You shouldn’t be afraid of saying stupid things’
Nelissen says he often steps outside his comfort zone. “Medical Delta has encouraged me to do that. I’m now working with Delft biomechanical engineering professor Amir Zadpoor, who holds a chair in Orthopaedic Implants in Leiden. We’re working on techniques for bone surgery that involve advanced mathematics, things that go beyond the mental capacities of a simple doctor.”
Rob Nelissen:
“We’re using 3D printing techniques to design prosthetics to replace joints that work in the same way.”
Bone tumours
“At LUMC we operate a lot on bone tumours. If you remove a piece of bone, it’s replaced by a prosthetic, ideally something that replicates the rigidity and elasticity of the bone as far as possible. Bone is not equally elastic everywhere. Where it attaches to muscles, it’s more flexible, enabling it to give a little when put under pressure, reducing the chance of muscles tearing. We’re using 3D printing techniques to design prosthetics to replace joints that work in the same way.”
The precision removal of bone also requires advanced technology. “If you need to remove a bone tumour from the chest cavity or spinal column, the cuts of the saw need to be extremely precise to prevent damage to the surrounding tissue.
We start by creating a 3D print of the bone tumour and surrounding bone, using this as a template. We can use that to perform the operation with millimetre precision.” Working at the interface of technology and medicine means that you will inevitably say something stupid occasionally. For example, when brainstorming about bacterial infections, a TU Delft engineer suggested incorporating antibiotics into the prosthetics. A bad idea, because the bacteria will quickly develop resistance through continuous exposure to antibiotics.
“You shouldn’t be afraid of saying stupid things. That doesn’t bother me now, although younger researchers may still be hesitant. But you need to look beyond your own discipline.”
‘Managing expectations is important’
Professor of Biomechanical Engineering Jenny Dankelman has regularly been looking over the shoulders of surgeons since the start of her career. This approach can lead to some startling and occasionally sobering insights.
TU Delft researchers working on medical technology do not always have it easy. There are major differences in culture between medical practitioners and engineers, as Prof. Jenny Dankelman (3mE), who has a dual appointment at TU Delft and LUMC, knows from experience.
She has regularly shadowed surgeons in operating theatres throughout her academic career. This approach can lead to some startling and occasionally sobering insights. “There was one example, near the start of my career. I was observing a doctor who was unsure how to reach the large intestine with his instruments.”
Keyhole surgery was still in its infancy. Surgeons had to become skilled in using long instruments to perform operations via small incisions. “The part of the intestine that the surgeons had to operate on was difficult to reach with the existing tools, so the surgeon asked for help. I saw it as an interesting student project and developed a plan. But it turned out a few months later that the problem had resolved itself thanks to a slightly different way of working.”
Mindset
Dankelman advises young researchers to acquaint themselves with the way doctors work and to acquire a lot of medical knowledge of anatomy and physiology. “Doctors act quickly. Obviously, because when a patient is cut open, they need to be stitched up again fast. This creates a certain mindset. But we’re used to endlessly optimising mathematical formulae. If you have a problem, you just set a doctoral candidate to work on it. This results in a prototype four years later that then requires further optimisation. But a doctor will expect you to come up with a solution within a few months. Managing expectations is important when you’re working at the interface between medicine and technology.”
‘The number of approaches increased when Medical Delta became more well-known’
Dankelman has been professor of Minimally Invasive Surgery and Interventional Techniques since 2021. She achieved acclaim for her research into techniques and equipment for keyhole surgery. In minimally invasive surgery, a surgeon operates via small incisions. Compared to open surgery, this technique results in reduced scarring, less trauma, less blood loss, faster recovery and a lower infection risk.
But her work with medical practitioners dates from before that. “I’ve been involved in medical subjects for a long time, with doctors from the LUMC, the Reinier de Graaf Gasthuis hospital, Erasmus MC and the AMC. In around 2000, our group decided that all post-docs and doctoral candidates should have a clinical supervisor in addition to their TU Delft supervisor. We need to have a good understanding of the people we’re developing medical instruments for.”
Training system
One of her successful inventions was developed together with gynaecologist and Medical Delta professor Frank Willem Jansen. They developed a training system to enable doctors to practice surgery with the help of feedback mechanisms. When conducting a surgical procedure, you can feel what you are doing thanks to a feedback mechanism to your hands and fingers. “That invention was developed further, producing a product that was ultimately marketed.”
Dankelman’s appointment at LUMC dates from 2007. It was converted into a Medical Delta professorship in 2013. How does this kind of dual appointment work in practice? Does it create shorter lines of communication between researchers, more multidisciplinary collaboration and more direct feedback?
“Although the dual appointment is partly symbolic, it can also help with grant applications, because it confirms your close links with medical practitioners. The number of approaches from doctors definitely increased when Medical Delta became more well-known. That’s a great development.
These approaches often happen over drinks at the Medical Delta Cafés, a regular get-together for affiliated members, where they discuss a topical healthcare theme but above all engage in networking and sharing ideas.
“You have to encounter people. Before the lockdowns, I got chatting to a doctor from Erasmus MC about patient safety. Together, we came up with a plan to investigate whether we can develop incubators for transplant surgery in which to store kidneys, livers or lungs.”
Jenny Dankelman:
“We’re using 3D printing techniques to design prosthetics to replace joints that work in the same way.”
‘Every heart
is different’
During open-heart operations at Erasmus MC, advanced electrodes from Delft are being used. How does cardiologist- electrophysiologist Natasja de Groot feel about the working relationship?
It is obvious from the electrodes in the glass case how far technology has developed in the last twenty years. The oldest looks like a shower head with four cables protruding from it leading to computer mouse-sized plugs. They were used by Prof. Natasja de Groot during her PhD research on cardiac arrhythmia in Leiden. The newest electrode is a razor-thin strip with 3 m of multi-layered flat cable attached to it in order to read all 192 channels simultaneously. It was made in Delft by the bio-electronics group of Prof. Wouter Serdijn (Faculty of Electrical Engineering, Mathematics and Computer Science).
While studying medicine, De Groot developed an interest in cardiac arrhythmia – a common but poorly understood disorder.
A heart can beat too fast, too slow or even miss a beat. It can happen to anyone and the chance increases with age.
Unfortunately, treating it by means of ‘ablation’ (which involves damaging heart tissue to halt unwanted conduction) is only moderately effective. Other methods are used that successfully reduce cardiac arrhythmia, but the mechanism is not understood. This is why De Groot set herself the task of “quantifying the electrical properties of the heart.”
A great group of boffins
She embarked on this at the end of last year as a Medical Delta professor with a dual appointment at Erasmus MC and TU Delft. Her research team includes doctors, engineers, a biologist, a vet, a clinical technologist and even an astronomer. “A great group of boffins”, she calls her team. “Everyone has their own passion, but they all enjoy learning from each other.” She describes a cycle in which better instruments lead to better measurements, better analyses and better hypotheses that in turn require better instruments. “We manage to keep each other busy.”
Natasja de Groot:
“Everyone has their own passion, but they all enjoy learning from each other.”
In 2010, she persuaded heart surgeons to hold a special electrode against the heart at eight different pre-defined positions for five seconds during every open-heart operation to record the electric signals. More than a thousand patients have been scanned in this way. Some of them have congenital heart failure or cardiac arrhythmia, others do not. The tens of thousands of signals enabled De Groot to draw the conclusion: “Every heart is electrically unique.”
‘Come on, we’re going to Delft’
Cardiology and telecoms
To gain a better understanding of all the data, she decided she wanted to measure the conduction velocity between measurement points, because differences in this determine how the electric pulse spreads across the heart. It takes the path of least resistance. She contacted her colleague Prof. Ton van der Steen – physicist and ultrasound expert, and one of the original Medical Delta professors. Did he know someone who could perform such calculations? After a couple of phone calls, he jumped up. “Come on”, he said. “We’re going to Delft.”
That’s where she met Prof. Alle-Jan van der Veen. At the department of Microelectronics (Faculty of EEMCS), he had been building expertise on signal processing for communication and astronomy. Although cardiology is very different from telecoms, the underlying mathematical models are similar: a signal runs from A to B. Using the ECG signals, Van der Veen was able to calculate the local conductivity, which partly determines the conduction velocity.
The local conductivity of the heart tissue is displayed on a colour chart. In certain places, a disruption in conduction is displayed as dark blocks. This can indicate scar tissue.
Wouter Serdijn (EEMCS) soon came up with the idea of more sophisticated electrodes. “It’s hardly rocket science”, he now says. “You can often help people from another discipline using existing technology. In that case, it was a contact strip and a multi-layered flex print cable for the 192 signals.” In 2015, the three of them joined cellular biologist Prof. Bianca Brundel from Amsterdam UMC in submitting a research application to CVON (Netherlands Cardiovascular Research Committee, part of the Heart Foundation) for the recording and analysis of bio-electric signals from the heart. For now, this is fundamental research into cardiac activation patterns.
Ultimately, it should result in improved diagnostic measurement instruments to determine how serious cases of cardiac arrhythmia are and hopefully more effective treatments.
The Medical Delta alliance was established in 2006 by three universities (TU Delft, Leiden University and Erasmus University Rotterdam) and two university medical centres (Leiden University Medical Center and Erasmus Medical Center). Medical Delta aims to achieve sustainable care through technological solutions. In the years ahead, almost 300 scientists will be working on this in fifteen different consortia. Businesses, healthcare institutions, the province of Zuid-Holland and major cities are also closely involved. Medical Delta (MD) professors have an impressive record of service at the centres involved. Some 21 professors now even have dual appointments.