Gabriel N. Sanchez

Sarcomere lengths in human extensor carpi radialis brevis measured by microendoscopy

Second‐harmonic generation microendoscopy is a minimally invasive technique to image sarcomeres and measure their lengths in humans, but motion artifact and low signal have limited the use of this novel technique.

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units

Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscles contractile units. Despite the motor units centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans.

Changes in sarcomere lengths of the human vastus lateralis muscle with knee flexion measured using in vivo microendoscopy.

Sarcomeres are the basic contractile units of muscle, and their lengths influence muscle force-generating capacity. Despite their importance, in vivo sarcomere lengths remain unknown for many human muscles. Second harmonic generation (SHG) microendoscopy is a minimally invasive technique for imaging sarcomeres in vivo and measuring their lengths. In this study, we used SHG microendoscopy to visualize sarcomeres of the human vastus lateralis, a large knee extensor muscle important for mobility, to examine how sarcomere lengths change with knee flexion and thus affect the muscle׳s force-generating capacity. We acquired in vivo sarcomere images of several muscle fibers of the resting vastus lateralis in six healthy individuals. Mean sarcomere lengths increased (p=0.031) from 2.84±0.16μm at 50° of knee flexion to 3.17±0.13μm at 110° of knee flexion. The standard deviation of sarcomere lengths among different fibers within a muscle was 0.21±0.09μm. Our results suggest that the sarcomeres of the resting vastus lateralis at 50° of knee flexion are near optimal length. At a knee flexion angle of 110° the resting sarcomeres of vastus lateralis are longer than optimal length. These results show a smaller sarcomere length change and greater conservation of force-generating capacity with knee flexion than estimated in previous studies.

Imaging Sarcomeres of Extensor Carpi Radialis Brevis in Humans Using Minimally Invasive Microendoscopy

Sarcomeres are the smallest contractile elements of muscle. Muscle generates force when overlapping myosin and actin filaments within the sarcomere interact to generate force. The amount of force these interactions generate depends on sarcomere length. The range of sarcomere lengths over which a muscle normally operates in the body is an important factor in analyzing a muscle’s force generating capacity. Measurement of sarcomere lengths in vivo is limited by their small size (2–4 μm) and the inability to use fluorescent dyes in humans. We recently developed a microendoscopy system to image sarcomeres in humans via Second Harmonic Generation (SHG) [1]. Here we demonstrate the use of this microendoscopy system as a robust, minimally-invasive tool for biomechanical analysis by measuring sarcomere lengths of the forearm muscle extensor carpi radialis brevis (ECRB) in 5 human subjects.Copyright