Image Correlation Between Digitally Reconstructed Radiographs, C-arm Fluoroscopic Radiographs, and X-ray: A Phantom Study.

OBJECTIVE: Digitally reconstructed radiographs (DRRs) are planar two-dimensional (2D) X-rays derived from a three-dimensional (3D) computed tomography (CT) dataset. DRRs allow the simulation of radiographs of all desired views and facilitate preoperative planning. However, orthopedic surgeons rely on C-arm fluoroscopic imaging during surgery to verify fracture reduction and implant placement. Pincushion distortion represents a technical limitation of fluoroscopic imaging, resulting in a greater distance between points at the periphery of the image compared to the center. This project, therefore, aimed to assess the image correlation between digitally reconstructed radiographs (DRRs) and fluoroscopic imaging (C-arm) using conventional radiographs (X-ray) as a control. METHODS: A 3D-printed cubic prototype and an anatomical humerus bone model were used. C-arm fluoroscopic radiographs and conventional X-ray images were taken in an anteroposterior (AP) view at 10-degree steps while rotating the objects from 0 to 90 degrees. CT scans were made and used to compute and export DRRs in AP view at 10-degree rotational steps from 0 to 90 degrees. The surface area (cm2) was measured and compared between the different modalities. For automated image analysis of the anatomical humerus model, matching (%) between modalities was calculated using the structural similarity index (SSIM). RESULTS: The overall regression was statistically significant in all models, with an R2 >0.99 when comparing all three imaging modalities of the prototype. Surface correlation in the anatomical humerus model was R2 0.99 between X-ray and C-arm and R2 0.95 between C-arm and X-ray to DRRs, respectively. The SSIM was highest for comparing DRR and C-arm images (0.84±0.01%). CONCLUSIONS: The study indicates a strong agreement between digitally reconstructed radiographs and X-ray/C-arm images. DRRs, therefore, represent a valuable tool for research and clinical application.

Cell lineage tracing and functional assessment of supraspinatus tendon healing in an acute repair murine model.

Rotator cuff supraspinatus tendon injuries are common with high rates of anatomic failure after surgical repair. The purpose of the study was to define clinically relevant features of a mouse model of supraspinatus tendon injury to determine painful, functional, and structural outcomes; we further investigated two cell populations mediating healing using genetic lineage tracing after full detachment and repair of the supraspinatus tendon in mice. The pain was assessed using the mouse grimace scale and function by gait analysis and tensile testing. Histological and microCT analyses were used to determine enthesis/tendon and bone structure, respectively. Lineage tracing was carried out using inducible Cre lines for ScxCreERT2 (tendon cells) and αSMACreERT2 (myofibroblasts and mesenchymal progenitors). Mice only expressed pain transiently after surgery despite long-term impairment of functional and structural properties. Gait, tensile mechanical properties, and bone properties were significantly reduced after injury and repair. Lineage tracing showed relatively few Scx lin tendon cells while αSMA lin cells contributed strongly to scar formation. Despite surgical reattachment of healthy tendon, lineage tracing revealed poor preservation of supraspinatus tendon after acute injury and loss of tendon structure, suggesting that tendon degeneration is also a key impediment of successful rotator cuff repair. Scar formation after surgery is mediated largely by αSMA lin cells and results in permanently reduced functional and structural properties.

Biologics and stem cell-based therapies for rotator cuff repair.

The rotator cuff is composed of several distinct muscles and tendons that function in concert to coordinate shoulder motion. Injuries to these tendons frequently result in permanent dysfunction and persistent pain. Despite considerable advances in operation techniques, surgical repair alone still does not fully restore rotator cuff function. This review focuses on recent research in the use of biologics and stem cell-based therapies to augment repair, highlighting promising avenues for future work and remaining challenges. While a number of animal models are used for rotator cuff studies, the anatomy of the rotator cuff varies dramatically between species. Since the rodent rotator cuff shares the most anatomical features with the human, this review will focus primarily on rodent models to enable consistent interpretation of outcome measures.

Genetic lineage tracing of targeted cell populations during enthesis healing.

Rotator cuff supraspinatus tendon injuries are clinically challenging due to the high rates of failure after surgical repair. One key limitation to functional healing is the failure to regenerate the enthesis transition between tendon and bone, which heals by disorganized scar formation. Using two models of supraspinatus tendon injury in mouse (partial tear and full detachment/repair), the purpose of the study was to determine functional gait outcomes and identify the origin of the cells that mediate healing. Consistent with previous reports, enthesis injuries did not regenerate; partial tear resulted in a localized scar defect adjacent to intact enthesis, while full detachment with repair resulted in full disruption of enthesis alignment and massive scar formation between tendon and enthesis fibrocartilage. Although gait after partial tear injury was largely normal, gait was permanently impaired after full detachment/repair. Genetic lineage tracing of intrinsic tendon and cartilage/fibrocartilage cells (ScxCreERT2 and Sox9CreERT2 , respectively), myofibroblasts (αSMACreERT2 ), and Wnt-responsive stem cells (Axin2CreERT2 ) failed to identify scar-forming cells in partial tear injury. Unmineralized enthesis fibrocartilage was strongly labeled by Sox9CreERT2 while Axin2CrERT2 labeled a subset of tendon cells away from the skeletal insertion site. In contrast to the partial tear model, Axin2CreERT2 labeling showed considerable contribution of Axin2lin cells to the scar after full detachment/repair. Clinical Significance: Clinically relevant models of rotator cuff tendon injuries in mouse enable the use of genetic tools; lineage tracing suggests that distinct mechanisms of healing are activated with full detachment/repair injuries versus partial tear. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3275-3284, 2018.