Posts Tagged ‘automation’

On the trail of prostate cancer

If the physicians detect malignant tumor tissue in the biopsy, they usually have to remove the prostate. However, besides the aggressive form of prostate cancer, there is also a type that only grows very slowly and may not need to be operated on. It has been difficult to differentiate it from the aggressively growing tumors until now, though. The result: physicians operate on the majority of the 70,000 people in Germany who are diagnosed with prostate cancer every year. "Some of these interventions could potentially be avoided if we were to have a biomarker that reveal- ed what kind of cancer is involved," says Prof. Friedemann Horn, Professor of Molecular Immunology at the University of Leipzig and department head of the Fraunhofer Institute for Cell Therapy and Immunology IZI in Leipzig. The term ‘biomarker’ denotes a measurement value that shows whether a person or an organ is healthy or diseased — these could be metabolic products, specific proteins, or nucleic acids, for instance.

Biomarkers provide insight

Researchers are hoping now to locate biomarkers like this through the RIBOLUTION Project, which is short for "Integrated Platform for Identification and Validation of Innovative RNA-based Biomarkers for Personalized Medicine" ( The project is being supported by the Fraunhofer Future Foundation. The Fraunhofer Institutes for Applied Information Technology FIT, Interfacial Engineering and Biotechnology IGB, Manufacturing Engineering and Automation IPA, Toxicology and Experimental Medicine ITEM, and Cell Therapy and Immunology IZI are participating in addition to several universities. The project involves not nearly just prostate cancer — researchers also hope to improve the diagnoses of other endemic diseases like rheumatism and chronic obstructive lung disease, which is characterized by coughing, production of sputum and difficulty in breathing. The research will concentrate on the search for ribonucleic acids, RNAs for short, that can indicate the biological state of cells and tissues very accurately.

However, how do the scientists know which biomarkers are early indicators of prostate cancer, or which RNA differentiates slow-growing tumors from aggressive ones? To find these kinds of biomarkers, the scientists compare healthy and tumorous tissue. Physicians at the University Hospital Dresden led by Prof. Manfred Wirth have been storing specimens of these in liquid nitrogen for fifteen years and documenting the course of the disease in patients even after they are released. Before the researchers could investigate these samples in detail, however, they had to prepare them: they cleaved every single tissue sample into 150 ultra-thin sections — each only a few thousandths of a millimeter thick — and classified them anew. "In the meantime, we now have more than 100,000 tissue sections that are unambiguously classified. There has never been a biological database of this quality before now," according to Horn.

Researchers have sequenced the complete genome for 64 of these specimens — that is, analyzed and quantified any RNA present in the samples. They have obtained a very large quantity of data for their efforts: 300,000 RNAs have been decoded, with the information adding up to 50 terabytes — that represents about 100,000 CDs. The scientists have compared the data and have already found 4,000 RNAs out of the 300,000 that could turn out to be biomarkers. They will check these again against a larger group of patients and trim the selection down further. "We are excited about the initial results of this validation process," reports Horn. He sees a good chance that several of the biomarkers discovered can improve the diagnoses of prostate cancer.

"Interest from the medical technology industry is gigantic," says Horn. If the results of RIBOLUTION are confirmed, then a corresponding biomarker assay, i.e. a biomarker test kit, could be on the market in few years — and physicians as well as patients could simply and quickly obtain information about the state of prostate cancer. The market is big: over 100,000 assays would be needed just in Germany annually.

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Special camera detects tumors

Tumor removal surgeries pose a great challenge even to skillful and experienced surgeons. For one thing, tumor margins are blending into healthy tissue and are difficult to differentiate. For another, distributed domains of cancer and pre-malignancies are difficult to recognize. Up to now, doctors depend exclusively upon their trained eyes when excising pieces of tumors. In future, a new special camera system can help visualize during operation even the smallest, easy-to-overlook malignant pieces of tumor and thereby support the surgeons during complicated interventions.

The trick: the camera can display fluorescent molecules that "paint" the cancer tissue. These are injected into the patients blood circulation prior to the operation and selectively attach onto the tumor during their trip through the body. If the corresponding area is then illuminated with a specific wavelength, fluorescence is emitted and the malignant tissue glows green, blue, red, or any other color, depending on the injected dye, while the healthy tissue appears the same. In this way, the surgeon can see clasters of tumors cells that cannot be recognized by the naked eye.

New system reveals several dyes simultaneously

Researchers at the Fraunhofer Project Group for Automation in Medicine and Biotechnology (PAMB), which belongs to the Fraunhofer Institute for Manufacturing Engineering and Auto- mation (IPA), have developed a new surgical aid, a multispectral fluorescence camera system. In the future, this special camera will integrate into various medical imaging systems such as, surgical microscopes and endoscopes, etc. The scientists from Mannheim, Germany, will make the debut of a prototype of this high-tech system at the Medica Trade Fair in Düsseldorf in the joint Fraunhofer booth (Halle 10, Booth F05) between 20-23 November. The novel aspect about this camera: it can display several fluorescent dyes and the reflectance image simultaneously in real time — systems available until now have not been able to achieve this. The advantage: arteries and delicate nerves that must not be injured during an intervention can likewise be colored with dye. They too can then be detected with the new camera, since they are set apart from their surroundings.

"The visibility of the dye to the camera depends in large part on the selection of the correct set of fluorescence filters. The filter separates the incident excitation wave- lengths from the fluorescing wavelengths so that the diseased tissue is also set apart from its surroundings, even at very low light intensities," says Nikolas Dimitriadis, a scientist at PAMB. The researchers and their colleague require only one camera and one set of filters for their photographs, which can present up to four dyes at the same time. Software developed in-house analyses and processes the images in seconds and presents it continuously on a monitor during surgery. The information from the fluores- cent image is superposed on the normal color image. "The operator receives significantly more accurate information. Millimeter-sized tumor remnants or metastases that a surgeon would otherwise possibly overlook are recognizable in detail on the monitor. Patients operated under fluorescent light have improved chances of survival," says Dr. Nikolas Dimitriadis, head of the Biomedical Optics Group at PAMB.

In order to be able to employ the multispectral fluorescence camera system as adapt- ably as possible, it can be converted to other combinations of dyes. "One preparation that is already available to make tumors visible is 5-amino levulinic acid (5-ALA). Physicians employ this especially for glioblastomas — one of the most frequent malig- nant brain tumors in adults," explains Dimitriadis. 5-ALA leads to an accumulation of a red dye in the tumor and can likewise be detected with the camera. The multispectral fluorescence imaging system should have passed testing for use with humans as soon as next year. The first clinical tests with patients suffering from glioblastomas are planned for 2014.

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