Innovative stroke therapy thanks to Swiss medicine

Rapid and tailored treatments of vascular blockages will be possible thanks to a diagnostic technique created by EMPA, HUG and Clinica Hirslanden

A team from the Swiss Federal Laboratories for Materials Science and Technology, the University Hospital of Geneva and the Hirslanden Clinic is currently developing a diagnostic procedure that can be used to initiate a tailored therapy early (Photo: EMPA)
A team from the Swiss Federal Laboratories for Materials Science and Technology, the University Hospital of Geneva and the Hirslanden Clinic is currently developing a diagnostic procedure that can be used to initiate a tailored therapy early (Photo: EMPA)

A blood clot in the brain that blocks the oxygen supply can cause an acute stroke. In this case, every minute counts.
A team from Swiss Federal Laboratories for Materials Science and Technology, of the University Hospital of Geneva and the Hirslanden Clinic is currently developing a diagnostic procedure that can be used to timely initiate a tailored therapy, as they describe in the current issue of the scientific journal “Scientific Reports”.

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In the center of a blood clot, the scanning electron microscope can clearly visualize red blood cells with a diameter of a few micrometers (Photo: EMPA)
At the center of a blood clot with the scanning electron microscope it is possible to clearly visualize red blood cells with a diameter of a few micrometers
(Photo: EMPA)

Vascular obstruction to be resolved as soon as possible

There are no warning signs: whole areas of the brain can be shut down at any moment.
When a clot blocks a blood vessel, the oxygen supply to the brain is cut off and the affected person suffers an acute stroke.
This life-threatening condition can manifest itself in many different ways: from muscle paralysis to loss of hearing or vision, to loss of consciousness.
But one thing is certain: this is a medical emergency and the time it takes to resolve the vascular obstruction must be as short as possible to save as many nerve cells as possible from dying. This is the only way to prevent permanent neurological damage.
Which treatment is most suitable for this purpose is not always easy to determine with the necessary timeliness.
As already mentioned, on the basis of X-ray analysis and electron microscopy, a team from EMPA, the Hirslanden Clinic and the University Hospital of Geneva is currently developing a method which should allow the optimal therapy to be identified in the shortest time possible.
A first study was published in the scientific journal "Scientific Reports". These data should form the basis for tailor-made treatment in the sense of personalized medicine.

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A cruelly beautiful image of a blood clot about 1,5 millimeters wide in a three-dimensional microcomputed tomography image (Photo: EMPA)
A cruelly beautiful image of a blood clot about 1,5 millimeters wide in a three-dimensional microcomputed tomography image (Photo: EMPA)

Examine each cell individually - every clot is different

The reason for this dilemma is obvious: not all blood clots are the same; depending on the type, different types of cells can aggregate.
Not only that: depending on the predominance of red or white blood cells, or the percentage of fibrin fibers, the thrombus has completely different properties. Also, thrombi differ markedly in shape.
A 15 millimeter long thrombus, which does not completely fill a blood vessel, has different mechanical properties than a few millimeter long clot, which completely blocks a vessel and the blood supply to the underlying brain areas.
The optimal treatment depends on these differences, whether it is a matter of dissolving the clot with drugs, or using a so-called "stent retriever", a sort of small fishing rod with which it is possible to "fish out" the thrombus in the blood vessel and whose material can be selected differently depending on the thrombus.
To make a correct treatment decision, radiology currently relies on conventional computed tomography scans
However, images of the patient's head provide little information about the details of a clot because objects made of similar materials are too difficult to distinguish from one another and to resolve spatially.
Furthermore, in daily clinical practice the image resolution is limited to 200 micrometres.

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In the center of a blood clot, the scanning electron microscope can clearly visualize red blood cells with a diameter of a few micrometers (Photo: EMPA)
At the center of a blood clot with the scanning electron microscope it is possible to clearly visualize red blood cells with a diameter of a few micrometers
(Photo: EMPA)

From the virtual 3D images, properties emerged… unknown

The situation is different with the laboratory methods, which the researchers used for their new study.
The team, including Robert Zboray, Antonia Neels and Somayeh Saghamanesh of EMPA's Center for X-Ray Analytics, examined several blood clots taken from patients during neurosurgical procedures.
For this purpose, several laboratory technologies were combined, resulting in 3D virtual images that revealed detailed and previously unknown properties of blood clots.

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A thrombus can also calcify: under the scanning electron microscope, the blood clot appears homogeneous (grey colored image). Only a special radiographic method in the laboratory, energy dispersive X-ray spectroscopy, shows how severely calcified the thrombus is (purple color image) (Photo: EMPA)
A thrombus can also calcify: under the scanning electron microscope, the blood clot appears homogeneous (grey colored image). Only a special radiographic method in the laboratory, energy dispersive X-ray spectroscopy, shows how severely the thrombus is calcified (purple color image)
(Photo: EMPA)

A 3D micro-tomography to examine individual red blood cells

“We used 3D micro-tomography to examine individual red blood cells down to the micrometre range”, explains Zboray, a researcher at EMPA.
Tomography using phase contrast techniques produces stronger contrast.
Objects that are easy to penetrate, such as muscles, connective tissue or blood clots, can thus be visualized in particularly fine nuances and in their spatial spread.

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A thrombus can also calcify: under the scanning electron microscope, the blood clot appears homogeneous (grey colored image). Only a special radiographic method in the laboratory, energy dispersive X-ray spectroscopy, shows how severely calcified the thrombus is (purple color image) (Photo: EMPA)
A thrombus can also calcify: under the scanning electron microscope, the blood clot appears homogeneous (grey colored image). Only a special radiographic method in the laboratory, energy dispersive X-ray spectroscopy, shows how severely the thrombus is calcified (purple color image)
(Photo: EMPA)

Thrombi "interspersed" also by minerals such as hydroxyapatite

Other technologies, such as scanning electron microscopy and X-ray diffraction and scattering methods, have provided further information down to atomic levels.
Here it was shown for the first time that a thrombus is not only made up of blood cells and fibrin networks, but can also be interspersed with minerals such as hydroxyapatite, as seen from vessel walls in arterial calcification.
However, this detailed information about the peculiarities of a blood clot comes too late, when the thrombus has already been surgically removed.
Furthermore, the newly acquired data cannot be compared with conventional images and with the results obtained in the hospital.
Digitization in medicine, on the other hand, allows data to be modeled in such a way that an algorithm can read the detailed information in the future.

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A thrombus can also calcify: under the scanning electron microscope, the blood clot appears homogeneous (grey colored image). Only a special radiographic method in the laboratory, energy dispersive X-ray spectroscopy, shows how severely calcified the thrombus is (purple color image) (Photo: EMPA)
A thrombus can also calcify: under the scanning electron microscope, the blood clot appears homogeneous (grey colored image). Only a special radiographic method in the laboratory, energy dispersive X-ray spectroscopy, shows how severely the thrombus is calcified (purple color image)
(Photo: EMPA)

A mix of hospital and microscope images filtered by AI

“To do this, we still need to study large numbers of thrombi so that we can use machine learning to identify new features and image patterns related to clot composition, which can then be transferred to conventional hospital images to help distinguish different types of thrombi”, continued Robert Zboray.
Ultimately, the researchers hope that thanks to their findings, conventional hospital images can be interpreted in a very short time, just as if the blood clot were examined in an ultrafast virtual laboratory.
This would pave the way for more accurate and personalized therapy for stroke patients in a timely manner.

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An illustration of blood circulation in the human brain
An illustration of blood circulation in the human brain