Temperature is so crucial to life that our bodies keep it under extremely tight control; if it strays outside a very narrow range, a warm-blooded animal cannot survive. Fevers and inflammations turn up the heat as they fight infections, but only briefly – it's a weapon to handle with respect. For all its importance, this dimension of life remains largely unexplored because of an obstacle: scientists have lacked a method to alter and control temperature within living tissues.
Soon that may change thanks to an advanced ERC grant just awarded to the physicist Thoralf Niendorf, who works at the high end of magnetic resonance imaging (MRI) technology. "Every time a doctor takes an image using MRI, there's an inevitable generation of heat," Niendorf says. "A lack of understanding about its effects has led to strict regulations governing the amount that can reach patient tissues. We're hoping to take this side effect and turn it into a tool for research, diagnosis, and hopefully even therapies.”
Do healthy and diseased tissues have specific temperature profiles?
That will require an instrument which can focus exact amounts of energy on precise, microscopic targets inside animal and human bodies. Niendorf's group has found a way to make it: start with a new ultrahigh-field MRI instrument, then add a custom-designed array of radiofrequency transmitters to shape and focus its powerful electromagnetic field. They have already worked out the theory and tested designs; now, with the new grant, they can build the machine.
At that point they will enter uncharted scientific territory. The first projects will involve thermal phenotyping studies – a term coined by the group – carried out in collaboration with other scientific groups. The goal is to determine whether various tissues have unique thermal properties that can be detected by MRI and might have diagnostic value. The next step will be to observe how tissues respond to highly focused increases in temperature. Disease-related processes may be susceptible in ways that could lead to new, MRI-based therapies. A unique feature of this strategy would be the ability to deliver a treatment and monitor its effects simultaneously, using the same instrument.
Temperature-responsive particles will deliver drugs
Another part of the project will involve an ongoing collaboration with scientific groups in Sydney, Australia and in Berlin who are building temperature-responsive polymers and nano-carriers to deliver drugs or other molecules. Introduced into the body, they remain inactive until heated. They can be loaded with several substances, each released at a specific temperature when the polymers are heated through radiofrequency energy. This would provide a new tool for research that would allow scientists to manipulate tissues over time, in a step-wise manner, from within the body. And the same strategy could be used to deliver successive blows to a disease, targeting different weaknesses.
"Planning this project has already drawn together a group of people with diverse expertise," Niendorf says. "We're excited about opening this dimension of life to new kinds of interdisciplinary exploration. We can't predict exactly what we'll find. But the strict control that animals exercise over temperature hints at vitally important functions across the body that we would like to understand."