Tissue differentiation during surgery

Brain tumors have devastating effects on a patient’s health and live. In order to treat the patient, the tumor has to be removed during surgery as thoroughly as possible while trying to preserve the surrounding brain tissue.

This is a difficult balancing act:

  • If not enough tissue is removed, a part of the tumor remains and it can grow back.
  • If too much tissue or the wrong tissue is removed, damage to the patient’s brain can leave the patient impaired.
Visualization of fluorescence-stained structures using BLUE 4001 during glioma surgery
Visualization of fluorescence-stained structures using BLUE 4001 during glioma surgery
Unfortunately, even with the best surgical microscopes the most tumors cannot be distinguished from the surrounding healthy tissue during surgery. Hence, it remains a big challenge to resolve the boundary between healthy tissue and the tumor. Thus, a technology which would enable neuro surgeons to differentiate tumor from non-tumor tissue during surgery is needed. This would allow the surgeon to remove the tumor much more safely and reliably while preserving the healthy brain tissue, thereby greatly reducing the risk for the patient.
To date, mainly four techniques are used to differentiate tumor tissue from healthy tissue:
  • Magnetic Resonance Imaging (MRI)
  • Intraoperative Fluorescence Imaging
  • Intraoperative Pathology
  • Medical Ultrasound

However, each of these techniques has significant limitations. Hence, a new technique is needed which overcomes the limitations of the established techniques. The following four criteria determine the value of such a new technology for practical applications:

  • visualization in real time (no averaging over longer periods required)
  • visualization in widefield
  • contrast agents are not required
  • visualization in 3D

A technology which fulfills all the criteria listed above would be ideal. However, it is already enough if a new technology is better than the established techniques.

  Magnetic Resonance Imaging (MRI) Intraoperative Flourescence Imaging Intraoperative Pathology Medical Ultrasound


  • Very reliable method
  • 3D visualization of the tumor also below the surface
  • Is directly integrated in one of the main working tools of the surgeon.
  • Provides direct 2D visualization of the tumor.
  • Reliable detection of tumor tissue by looking at the cellular structure under an optical microscope.
  • Standard clinical ultrasound can provide 3D visualization several tenth of cms into tissue


  • MRI is mainly used to produce preoperative data. This information becomes unreliable during surgery as brain matter shifts (as the skull is opened and tissue is removed).
  • Reliable intraoperative data is not readily available. There are only very few hospitals with intraoperative MRI machines as these systems are very expensive and using intraoperative MRI interrupts the workflow during surgery (metallic instruments need to be removed, patient has the be brought to MRI machine, …)
  • Does not work for many tumors. For many cancers types there is no suitable fluorescence signal available.
  • It does not provide visualization below the surface which is optically not accessable.
  • Interrupts the workflow and costs a lot of time. Tissue has to be brought to the lab of the pathologist, where it is analyzed.
  • It does not provide an image but just information about the point where sample is collected.
  • Very limited resolution. In practice it is difficult to detect tumors smaller than 3 mms.
  • Requires physical contact, as acoustic impedance needs to be matched. If for example the soundwaves have to travel through air to reach the tissue, large parts of the soundwave are reflected at the boundary between tissue and air. The ultrasound device needs to be brought into contact with tissue or vacancies have to be filled with water. Hence, it often interrupts the workflow during surgery.



BLUE 400 von ZEISS


Medical ultrasound

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