This dissertation addressed two challenges in musculoskeletal biomechanics. The first challenge was to understand the function of total knee prostheses after implantation in patients. Motions of the knee following total knee replacement affect a patient’s ability to perform daily activities, such as walking and rising from a chair, and affect the longevity of the prosthesis. The millimeter-scale translations of the joint are difficult to measure with noninvasive methods such as analysis of skin mounted markers. We addressed this challenge by measuring passive knee kinematics using a surgical navigation system. The specific goal was to isolate the effects of posterior cruciate ligament removal on knee motion after total knee arthroplasty. We measured knee kinematics intraoperatively while the surgeon passively flexed and extended the knee at four surgical time points:​ after initial exposure, after removing the anterior cruciate ligament, after removing the posterior cruciate ligament, and after implanting the prosthesis. We calculated anterior femoral translation and the flexion angle at which femoral rollback began. We found that removing the posterior cruciate ligament introduced abnormal anterior translation, doubling the anterior translation from the initial exposure (from 5.1 ± 4.3 mm to 10.4 ± 5.1 mm) and increasing the flexion angle at which femoral rollback began (from 31.2° ± 9.6° to 49.3° ± 7.3°). Implanting the prosthesis did not restore the motion measured at initial exposure. Relative to the cruciate-deficient case, prosthesis implantation increased the amount of anterior translation (to 16.1 ± 4.4 mm) and did not change the flexion angle at which femoral rollback began. Abnormal anterior translation was observed in low and mid flexion (0°-60°) after removing the posterior cruciate ligament, and normal motion was not restored by the posterior stabilized prosthesis. These findings can be used to interpret further motion analysis during functional tasks and to guide improvements in prosthesis design.

The second challenge was to understand how the motions of sarcomeres, the contractile units of muscle, affect the force-generating capacity of muscles in humans. Sarcomere length over a muscle’s range of motion in the body is an important factor that affects muscle excursions and force-generating capacity. The relationship between sarcomere length and joint angle can be altered in disease, and measurement of this relationship is important for guiding treatments. Second-harmonic generation (SHG) microendoscopy has recently been developed in our laboratories to image sarcomeres and measure their lengths in humans. However, technical challenges such as motion artifacts and low signal have thus far prevented this novel technique from being used to quantify sarcomere lengths in humans. We discovered that an excitation wavelength of 960 nm maximized image signal;​ this enabled an image acquisition rate of 3 frames-per-second, which decreased motion artifact. We then used microendoscopy to directly image sarcomeres in the extensor carpi radialis brevis (ECRB) in seven healthy adults with the wrist in 45° extension and 45° flexion. We determined the average sarcomere lengths and the length variability of in-series sarcomeres from the SHG images. Sarcomere lengths in 45° wrist extension were 2.93 ± 0.29 μm (mean ± standard deviation) and increased to 3.58 ± 0.19 μm in 45° flexion. Within local regions of the fibers the standard deviation of sarcomere lengths in series was 0.20 ± 0.07 μm. These measurements agree with measurements in the same muscle using laser diffraction. The lengths of sarcomeres in series within a small region of an individual fiber can vary substantially. This study demonstrates the suitability of SHG microendoscopy for imaging muscle microstructure and illustrates the potential of this technology to address a new class of questions about muscle architecture and remodeling in humans.

The ability to measure sarcomere operating lengths in humans without surgery enables us to diagnose the involvement of specific muscles in neuromuscular disorders, and to design surgeries that will optimize an individual patient’s outcome. Measurement of sarcomere operating length will also enable a new class of research questions to be addressed about the adaptations of muscles over time in response to surgeries or pharmacologic treatments.