Second Harmonic Generation: New Microscope Visualize Live Muscle Units in Action
The basic process of force-generation in muscle has been known for decades, but until now no one has ever seen it work at a microscopic level in a living human. The new microscope could provide unique insights into treating muscular degenerative diseases.
Millions of people each year are diagnosed with diseases that result in the loss of neuromuscular function. One of the complications in treating these people has been an inability to track the progression of disease and provide the best possible therapeutics.
Now, a team of Stanford researchers has developed a microscope that can visualize and measure the force-generating contractions of these patients' individual motor units. This action has been studied for nearly 100 years, but this is the first time it has ever been observed in the muscles of a living human.
The new microscope uses second harmonic generation
The new microscope consists of several small components that all fit neatly on a bedside pushcart. An ultrafast laser light source beams infrared light in 100-femtosecond pulses along an optical fiber from the cart to a handheld unit, which contains the miniaturized optics. This unit connects to an optical needle that is inserted into the patient's muscle. The light travels through the needle and sweeps over the sarcomere.
Through a process called second harmonic generation, the muscle fiber's striated structure converts the infrared light into a green light, which is returned up the needle, through the handset and to a detector and computer on the cart that interprets variations in the green return signal. These green images are pieced together to form an image of a sarcomere activation, and can provide precise measurement of the duration of a muscle twitch.
Gabriel N. Sanchez, Supriyo Sinha, Holly Liske, Xuefeng Chen, Viet Nguyen, Scott L. Delp, Mark J. Schnitzer: In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units, Neuron, Vol 88, Iss 6, p1109–1120 (16 December 2015) http://dx.doi.org/10.1016/j.neuron.2015.11.022