July 8, 2009

Tissue at risk

On the future of therapy in acute stroke: Ideas are discussed how to miniaturize parts of a neuro intensive care unit and bring it in the brain: a lab-in-the-brain.

Today I presented a poster on the Berlin Brain Computer Interfaces (BBCI) Workshop 2009–Advances in Neurotechnology. Following my open science policy we published it the same day on Nature Precedings, a free online service that enables researchers in the life sciences to openly share preliminary findings. The title is "ECoG-based short-range recurrent stimulation techniques to stabilize tissue at risk of progressive damage: Theory based on clinical observations".

The aim of therapy in acute stroke

The research focus in acute stroke therapy is on the tissue at risk (TAR), that is, the zone in the brain surrounding a small infarct core, which develops during stroke usually within minutes (red in the illustration above). The tissue in the surrounding region (yellow) is at risk of infarction. In the chronic outcome it could be lost. The aim of stroke therapy is salvage of this tissue.

Whether in stroke outcome the lost tissue eventually includes much of the surrounding TAR zone or is mainly limited to the initial infarct core critically depends on certain partly unknown events that happen during a therapeutic time window of about two weeks. In this period waves of mass neural depolarization have been recored using Electrocorticography (ECoG) by an international group of clinical and basic scientists (called COSBID). ECoG is like EEG (Electroencephalography) but the electrodes, in this case an electrode stripe, are placed directly on the exposed surface of the brain. This COSBID group is now testing the hypothesis that such waves worsen stroke outcome.

lab-in-a-brain = brain-computer-interface + lab-on-a-chip

At the Institute of Theoretical Physics of the Institute of Technology in Berlin, we have investigated with computer models how to prevent such waves using time-delayed and nonlocal feedback techniques. This is a control method known as chaos control. However, we are using it not to control chaotic behavior but to abort waves such as those recorded by the ECoG electrodes.

As I cooperate with several COSBID members on seizure activity and migraines, it was a natural idea to suggest that our clinical and theoretical efforts should also be combined in the research field of stroke. Currently this project is in the stage of development and the device used in the neuro intensive care unit is running in an open loop condition, that is, there is no feedback in place. We plan to test this in a closed loop condition with an integrated lab-on-a-chip device together with Thomas Franke from Augsburg and Harvard University, an international expert in microfluidics and in lab-on-a-chip applications that enable miniaturized drug administrations on demand.

Above you see the front cover of a recent review by Thomas Franke and Achim Wixforth "Microfluidics for Miniaturized Laboratories on a Chip (ChemPhysChem 9, 2140)". Such minaturized devices allow for precise and local release of effective drugs on demand. Tiny volumes of picoliters (1/1000 nanoliter) can be controlled electronically to a designated position and delivered to the affected region in the tissue.

Bring the nurse in the brain and let chaos control tell her what to do

The task of this lab-in-a-brain is rather simple though not easy to accomplish: administering medication to the right place at the right time when certain events happen. Today the physician or nurse is interacting with the patient when the ECoG data indicates a stress situation. We just need to miniaturize the nurse and bring her into in the brain. Chaos control tells her what optimal time-delays for medication release are and what the optimal spacing between the release side and wave detection side is.

These studies were published in the journal Chaos (Volume 18, 026110. 2008 and Volume 19, 015110, 2009) and we are honored that both our papers were selected by the American Institute of Physics (AIP) and the American Physical Society (APS) for free online-publication in the Virtual Journal of Biological Physics Research to allow quick access in cutting-edge research fields.

Stroke-free cyborgs

How far in the future are you looking with this Blog post? Well there are cyborgs among us, like Prof. Kevin Warwick which probably would say it will happen yesterday.

Whether near or far future, the open exchange of such ideas is important and it is much supported by the Berlin Bernstein Focus Neurotechnology (BFNT), which has organized the workshop mentioned in the outset of this post. In another BFNT in Freiburg–Tübingen similar ideas are followed. There the aim is to investigate new migraine treatments by interacting with early precursors of migraine. The group around Holger Kaube, Cornelius Weiller, and Gerald Urban suggest a project: Real time metabolite sensing for feedback control of behavior in neurological disorders in which "[the] long term goal of the project is the development of implantable encapsulated microsensors in migraine patients, which will enable them to monitor and control local cortical metabolic activity within a physiological range to avoid breakdown of energy homeostasis with dysfunction and possibly brain tissue damage."

Are we on the avenue to become migraine and stroke-free Cyborgs one day? In any case, neurotechnology is amazingly fast moving forwards. Let me repeat a old Yiddish saying that Niels Birbaumer, one of the pioneers in this field, recalled today at the end of his talk:

"Fun lojter hofenung wer ich noch meschuge"
(I have so much hope that it drives me batty)

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