Cyber Physical & Medical Systems

As part of the COSY-SMILE 2 project, the Institute for Product Development and Mechanical Engineering Design (PKT) supplied numerous models produced using 3D printers. These models eliminate the need for animal testing, ensure high-quality treatment, and enable improved training for surgeons.

It is a race against time. A stroke manifests itself through sudden paralysis or numbness in the face, arm, or leg, speech disorders, visual disturbances, dizziness, unsteadiness, and severe headaches. In such a situation, it is important to call 911 as quickly as possible, because every minute counts. A blood clot blocks the oxygen supply to the brain. “Time is brain,” say experts—the faster the blockage can be removed through surgery, the better the prognosis!
The Institute for Product Development and Design Technology (PKT) at the Technical University of Hamburg, headed by Prof. Dieter Krause, has made an important contribution to enabling doctors to practice the difficult minimally invasive catheter surgery (thrombectomy) more frequently without animal testing. HANNES is the name of the model that replicates the arterial vessels from the groin or wrist to the brain. The acronym stands for “Hamburg Anatomical Neurointerventional Simulation Model.” The model can also be used to practice treating aneurysms (bulges in blood vessels). It works a bit like the well-known skill game “Dr. Bibber” in real life. In Dr. Bibber, plastic organs must be surgically removed from a toy figure with a steady hand. Hannes can be used to practice inserting a microcatheter with a diameter of less than 1 mm from the groin to the brain without turning wrong or damaging any veins.

The individual parts are produced using 3D printing

What sounds like a game can save lives and maintain quality of life. Strokes are one of the most common causes of death and the leading cause of disability. Around 270,000 strokes occur in Germany every year – and the trend is rising. The project is supported by the Federal Ministry of Education and Research (BMFTR) and, initially, by the Medical Technology Research Center Hamburg (FMTHH), a collaboration between TU Hamburg and UKE (University Medical Center Hamburg-Eppendorf). The medical models are being created and adapted by three medical technology doctoral students, Jonte Schmiech, Eve Sobirey, and Marie Wegner. 
The individual parts of the model are produced at PKT using 3D printing. They are based on anonymized patient data. Different areas of the model can be exchanged and adapted. This allows different anatomical conditions to be simulated. The printing materials are selected and modified based on feedback from experienced neurointerventionists at the UKE partner institution to ensure that working on the model feels as realistic as possible. Work is already underway to produce even finer branches than before, with a diameter of less than two millimeters. The team is also considering how to depict the venous system and integrate other clinical pictures.
 
Another advantage of the project is that Hannes can be used for step-by-step learning. This makes it possible to first follow the path of the catheter through the veins directly, and only later is the model covered and orientation is carried out using X-rays. Trainees can also practice the procedure as often as they like until they have mastered it perfectly. And their training success can be measured objectively.

All without animal testing

Hannes is part of the COSY-SMILE-2 (Completely Synthetic Stroke Model for Interventional Development and Education 2) project. The model has been in use at the UKE since 2014. Previously, doctors learned and practiced the procedure on rabbits and pigs. However, their anatomy differs significantly from that of humans. Secondly, the animals had to be anesthetized and then euthanized (killed) for the exercises. The research here follows the 3R motto for animal testing: “Refine, Reduce, Replace.” In this case, the use of animals can now be completely replaced at the UKE. In addition, original instruments can be used for practice, and simple or difficult clinical pictures can be repeated as often as desired.
 
The PKT is also developing other medical models for use in medical technology. And those involved are not only putting a lot of effort into the material, but also into naming it. BERTA is the name given to the “mouse phantom” used for quality assurance in radiation experiments on small animals: Brave Rodent Phantom. The model allows the use of different dose measurement devices and biological samples and looks deceptively real in CT and micro-CT. This ensures the precise positioning of the animals and the alignment of the radiation. As a result, fewer experiments can be carried out on real animals. An example of the other two Rs: Refine and Reduce.
HUGO, the Hamburg prostate biopsy model, assists in training and quality assurance for fusion biopsy of the prostate in humans. And CHARLIE, a clinical phantom for radiation therapy of the pelvic region, enables significantly more precise irradiation of prostate carcinomas.
The PKT focuses on methods for developing modular product families as well as structural analysis and testing technology. The results are applied in aviation, mechanical and plant engineering, and, of course, in medical technology. The employees and Prof. Krause are proud of their results. "It's easy to forget that Hannes is a medical model – he looks so realistic in practical use. Our models are exemplary for the medicine of the future: it is not only more precise and effective, but also significantly more ethical. Of course, sound basic research is essential – we are particularly interested in findings for development and design in close, interdisciplinary exchange with doctors. This makes it all the more rewarding to always have in mind what all this is ultimately for," says Krause.

Further information:
https://www.tuhh.de/pkt/institut

Cancer cells are hungry. That is why tumors are well supplied with blood, enabling them to grow aggressively. How well a tumor is supplied with blood indicates whether and how well a therapy will work. You can imagine this as a road network in which trucks transport goods to individual locations.

In the body, blood vessels form the roads along which important “deliveries” are made: oxygen, drugs, and nutrients are transported via the blood. But just as road networks vary from place to place, there are winding alleys and one-way streets in different directions. Some roads are congested. Similarly, the microscopic vascular networks inside tumors vary from person to person. However, there is currently no clinically applicable, cost-effective method for analyzing blood flow in a tumor precisely and non-invasively.

A research project at the Hamburg University of Technology (TUHH) in cooperation with three renowned US institutions – Stanford University, the Mayo Clinic, and the University of California, San Diego – aims to change this. Using 4D ultrasound images (spatial and temporal) and mathematical models, the researchers are developing a method based on the liver that enables rapid quantitative analysis of tumor vessels – directly at the patient's bedside.

From image to diagnosis: ultrasound reimagined

The principle is both innovative and pragmatic. A modern 3D ultrasound device is used to create time-resolved images. These dynamic image data record how a contrast agent flows through the tumor area. This allows conclusions to be drawn about the vascular structure and blood flow. Especially in the liver, an organ with particularly complex blood flow, this opens up new possibilities for cancer diagnostics and treatment monitoring. This involves determining whether a particular therapy is actually effective or whether a different approach should be chosen.

“Typical ultrasound images provide visual information. What we need are numbers: flow rates, distribution parameters, concrete statements about the vascular structure,” says Dr. Sebastian Götschel, senior researcher at the Institute of Mathematics at the Hamburg University of Technology. “Extracting this information from noisy, temporally and spatially limited image data is challenging. But that is precisely our goal.”

Mathematical models for medicine

Goetschel is a mathematician with broad application-oriented expertise. Before joining the TU Hamburg, he worked at the Zuse Institute in Berlin, earned his doctorate at the FU Berlin, and worked at the Lawrence Berkeley National Laboratory in California. He is a member of the coordination team of the TUHH initiative Machine Learning in Engineering.

In the current project, he is working on a so-called inverse problem – one of the trickiest classes of mathematical problems. Known effects, such as the brightness of pixels in ultrasound, are used to infer unknown causes, such as blood flow velocity or vascular resistance. This requires models that are not only mathematically solvable but also physiologically meaningful.

“We first worked with a simple diffusion model,” explains Götschel. “It was mathematically very ingenious, but physiologically unconvincing because blood does not simply spread diffusely.” Instead, the current model considers arterial and venous blood separately. This results in two coupled equations – one for inflow and one for outflow – whose solution provides a meaningful indicator of blood flow.

From mice to humans: a long way to go

The method will first be tested on animal models and then validated in preclinical studies. A patient study is scheduled for completion in 2029. The imaging data will be compared with tissue samples (histology) and combined with other methods such as super-resolution ultrasound (SRUS). The aim is to develop an analysis method that is robust, reliable, and fast enough to be integrated directly into everyday clinical practice—without the need for complex large-scale equipment such as MRI or CT scanners. These are expensive, not universally accessible, and CT scans also involve radiation exposure.

“An ultrasound device fits on a trolley. That's a huge advantage, especially where resources are scarce,” says Götschel. The computing times should also remain within reasonable limits: a powerful workstation could deliver meaningful results within about an hour. To achieve this, calculations are performed in parallel across many processor cores.

It is also important that the results remain explainable: “We need models that we understand in order to know that the results are credible.” So while neural networks could be part of the solution in the future, the focus for now is on classic modeling.

A Hamburg contribution to international cutting-edge research

TU Hamburg is involved in the project with a compact team. In addition to Götschel, a postdoctoral researcher specializing in computational engineering and a doctoral student focusing on mathematical modeling, simulation, and optimization are working on the implementation. Together with partners in the US, they form an interdisciplinary bridge between mathematics, medicine, physics, and engineering. The project is funded for five years with a total of around three million US dollars from the US National Institutes of Health (NIH).

For Götschel, the project is the perfect combination of his interests: “I think it's great when I can make a real difference with my work. Mathematics is often very abstract. Sometimes you spend years researching something, and in the end, only a few experts around the world are interested. Here, it's different, and we can see directly what our work is good for.”

New types of antennas are able to establish a connection to a satellite from an airplane and maintain it during the flight. Thanks to their extremely flat design, installation in the outer skin of the aircraft can save a significant amount of fuel compared to conventional solutions.

On closer inspection, airplanes have a hump at the top of the fuselage. The antennas for communication via the satellites in space are concealed under this bulge. This protective cover is called a radome. Using satellites from an airplane is no easy matter, as the plane moves and still has to maintain contact with the satellite. Until now, this has been done with antennas that are tracked mechanically. This is done in the same way as with movable satellite antennas, whose round dishes are installed on millions of houses to receive radio and television stations. The Institute of High-Frequency Technology (IHF) at Hamburg University of Technology is now breaking new ground and conducting research on the BANG (Broadband in Aviation - Next Generation) antenna project, which is being developed with the support of Lufthansa Technik. The supervising professor Arne Jacob explains how it works: "We are building the antennas from many very flat individual antennas. The modular design of the antenna makes it possible to replace individual modules and simplifies maintenance."

Fast internet while flying

In future, it should be possible to use them to make phone calls and be online during a flight. "This takes place on board via electromagnetic waves, at frequencies of several tens of gigahertz, at which the waves are not visible," says Prof. Jacob. "The task of antennas is to bundle these waves. You can think of it like the beam of a flashlight. And this beam - also known as the antenna lobe - is no longer directed mechanically, but electronically at the satellite." Such antennas (phased arrays) no longer have anything in common with conventional antennas. They consist of many small individual antennas, which in turn are assembled into modules about one centimeter thick. And they also work completely differently: each of these small antennas transmits or receives the same signal, but with a tiny time delay to its neighbors. This time delay is now set so that the waves constructively overlap in the desired direction. Because this is done electronically, the antenna lobe generated in this way can be tracked quickly and flexibly. Continuous transmission and reception is now possible without moving the antenna mechanically.

New technology saves fuel

"We want to carry out the first measurements on our demonstrator at our project partner Lufthansa Technik soon," says Prof. Jacob. The demonstrator is still much smaller than the real antenna that will one day be installed in the aircraft. It initially only consists of a single five by five centimeter module. Overall, however, the entire electronic antenna will be no larger than 0.25 square meters and particularly flat - so that the hump on top of the aircraft's outer skin will no longer be 35 centimeters high, but only a few centimeters. That doesn't sound like much, but it means considerably less air resistance for an aircraft. And therefore significantly lower fuel consumption. With the same aim, the transmitting and receiving antenna are to be integrated into an aperture in order to reduce the footprint and weight. For the demonstrator module, this means that eight of its antenna elements can transmit and receive and eight others only transmit. The modular design also makes the antennas safer to operate. With electronically controlled antennas in the aircraft, the frequent statement: "Unfortunately, I have no reception at the moment" should no longer occur.

More information

More information is avalaible on the website of the Institute of High-Frequency Technology

Contactless detection of epilepsy

Epilepsy is a regulatory disorder of the brain. If it is not treated, it manifests itself in adults, for example, in the form of seizures or even unconsciousness. In newborns and young children, however, epilepsy is often overlooked because they do not exhibit seizures, and can therefore be fatal.

Epilepsy research is usually done only at specialized centers. This involves measuring and analyzing brain waves using an EEG (electroencephalography). This can only take place over short periods of a few hours and severely restricts the subjects during the measurements, as they are wired and not allowed to move. There is also the question of how meaningful the measurements are, since measurements are not taken under real conditions, but only under artificial conditions and over a short period of time.

Detecting danger at an early stage

For this reason, Prof. Alexander Kölpin from the Institute of High Frequency Technology (IHF) at the Technical University of Hamburg is investigating a method as part of the publicly funded BrainEpP project that enables non-contact and continuous monitoring of cardiovascular functions in young adults, infants and even premature babies. The activation of the autonomic nervous system can be inferred from the measured parameters. It is controlled by two systems with opposing effects: the sympathetic and parasympathetic nervous systems. Together they regulate vital bodily functions such as respiration, heartbeat or digestion. The fine structure of extracted cardiac signals provides information about how well this regulation takes place. Not only can epileptic seizures be estimated from this without an EEG, but incipient disturbances should also be detected before a seizure occurs. In case of such an alarm, the seizure could be suppressed with medication and the quality of life of many affected persons could be increased as well as the risk of dying in case of a seizure could be reduced. After all, it is suspected that up to 20 percent of all sudden infant deaths are related to an undiagnosed epileptic condition.

Measuring the smallest vibrations

The monitoring takes place without any contact from a short distance of up to one meter through clothing or bed covers. A so-called high-frequency interferometer is used, which transmits electromagnetic waves at minimum power, which are reflected by the body surface and received by the sensor. From this, the smallest vibrations of the body surface of only a few micrometers deflection can be recorded, as they are caused by heartbeat and breathing. This distance measurement data can be continuously collected and automatically segmented and classified using machine learning. The BrainEpP project searches the measurement data for specific markers, i.e. measurable indicators, of an impending epileptic seizure.

The contactless recording of vital data thus allows continuous monitoring of vulnerable groups of people without restricting their quality of life. Medical changes can thus be detected at an early stage, before health crises arise. This is all the more important in the case of children because epilepsy, a disease that is difficult to recognize, can lead to death if left untreated.

Project partners in the BrainEpP project, which is funded by the German Federal Ministry of Education and Research (BMBF), are the University Hospital Erlangen and the companies Geratherm Respiratory, Silicon Radar, DeMeTec and Voigtmann.