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Laser light for the diagnosis of stroke

Stroke is one of the most common causes of death in the Western world and in Germany the most common cause of moderate to severe disabilities. Besides effective prevention, the rapid and specific diagnosis of impaired blood circulation in the brain is key in the effective treatment of stroke patients. PD Dr. Thomas Gisler from the University of Konstanz has developed CereFLux, a method that allows the flow of blood in the human brain to be measured within seconds and without contrast agents. The method is based on harmless laser light and, in contrast to other methods, is portable and can be used in narrow environments.

Dr. Thomas Gisler from the University of Konstanz is working on the development of CereFLux, a new method that enables cerebral blood flow to be measured. © Dr. Thomas Gisler

CT angiography (CTA), magnetic resonance tomography (MRT) and positron emission tomography (PET) are the preferred methods for measuring blood flow in the brain non-invasively, i.e. without inserting probes into the brain. Although these methods provide high-resolution images of cerebral blood flow, they nevertheless have some drawbacks. Patients who require such examinations will need to see a doctor at a clinic equipped with the necessary instruments. Moreover, such methods only provide snapshots of the rapidly changing cerebral blood flow and CTA and PET require contrast agents (PET requires radioactive contrast agents) to visualise the flow of blood. 

PD Dr. Thomas Gisler from the University of Konstanz has been seeking a less invasive method to counteract this situation. He has spent many years developing a novel optical method called CereFLux. The tool consists of a diode laser, fibre optics, photodetectors as well as an analysis and control unit. Near-infrared laser light is guided with an optical fibre to the scalp from where it spreads through the skull into the brain. Another optical fibre, which is also attached to the scalp, collects scattered light and guides it to the detector. “The scalp and skullcap are permeable to near-infrared light which can thus penetrate several centimetres into the brain. And this is deep enough to record signals from the brain,” Gisler explains. The scattered light changes slightly in colour due to the flow of the red blood cells. This minimal colour change can be measured indirectly. “The colour change allows us to measure the flow of blood in illuminated tissue areas,” Gisler says. 

Research has shown that the signals mainly arise from the blood flow in the tiniest blood vessels (known as microvasculature) in the cortex. This is the part of the vascular system that is involved in gas exchange with tissue and is therefore prone to stroke-related damage. With regard to non-invasive methods for the measurement of cerebral blood flow, CereFLux closes the gap between non-portable CTA, MRT and PET devices and Doppler sonography (ed. note: medical imaging technique in which ultrasound is enhanced by the so-called Doppler effect). The latter is portable, but has the disadvantage that it only allows the flow of blood to be measured in the large blood vessels that are relatively far from the cortex. “However, detection is highly sensitive and the flow of blood can be determined within a few seconds,” Gisler says.

Additional advantages over standard methods

The optical CereFLux method can also be used in environments where strong electromagnetic interferences occur, for example in intensive care wards and in ambulances. CereFLux is suitable for continuous measurements as the blood cells can be used as a blood flow marker. There is therefore no need to apply radioactively labelled markers to the patient under examination. The sensors are only lightly attached to the scalp and there is therefore zero risk of infection.

At present, CereFLux achieves a spatial resolution of one to two centimetres, depending on the depth of the brain region under investigation. This resolution is relatively low compared to MRT and CTA, and is due to the fact that the skull strongly scatters the light. However, further developments can be expected in this area. “Highly promising approaches to improve spatial resolution using special algorithms and by adapting excitation and detection methods with each other,” Gisler says.

The CereFLux sensor consists of an exciting and a detecting optical fibre which are attached non-invasively to the scalp by way of a sensor patch. The near-infrared light penetrates the scalp and skullcap into the cortex. The detector fibres detect the scattered light that has passed through the area marked in dark red, which is then registered by the photodetector and subsequently analysed. © Dr. Thomas Gisler

Focus on new applications

In addition to being used in stroke diagnosis, CereFLux has the potential of being applied to other areas. There are high hopes for use in oncology and in neonatology. For example, the sensor has the potential to be applied to determine the effectiveness of chemo- and radiotherapy where it can be used to register the reduction of blood flow in treated body areas. Premature babies often suffer brain injuries due to circulatory disorders, which can lead to delayed development and increased mortality rates. CereFLux might be used to measure the flow of blood with the goal of monitoring and adjusting medical treatments as well as reducing the risk of tissue damage. Studies are underway to test the application of CereFLux in patients with peripheral arterial disease. Another potential use of CereFLux is the continuous monitoring of the supply of skeletal muscles with blood during and after surgical interventions. 

Despite the potential advantages of CereFLux for a broad range of applications, Dr. Gisler’s team is mainly focussed on its use in emergency and intensive care medicine. The researchers are aiming to develop a sensor the size of a shoebox, thus making it suitable for mobile applications. “This would allow us to carry out precise measurements in areas where little space is available, for example in the field of traumatology in ambulances and intensive care wards,” said Gisler summarising his team’s objectives. 

Market maturity through cooperation with industry

“We have carried out laboratory tests with around 30 healthy volunteers and found that different stimuli, including optical stimuli, movement and memory exercises, led to elevated brain activity,” Gisler says. The researchers will carry out further tests in order to take CereFLux to market maturity. In addition, they are interested in working with industrial partners in order to further develop the sensor into a handy, mobile device. “We are currently looking for cooperation partners in the medical device industry and university hospitals in order to test the technology in clinical studies and make further improvements. Our goal is to develop the sensor into a marketable commodity which will benefit many patients,” said Gisler summarising his plans.

Further information:
Dr. Thomas Gisler
University of Konstanz
Universitätsstraße 10
78457 Konstanz
E-mail: Thomas.gisler(at)uni-konstanz.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/laser-light-for-the-diagnosis-of-stroke