Automatic 3D Postoperative Evaluation of Complex Orthopaedic Interventions.

In clinical practice, image-based postoperative evaluation is still performed without state-of-the-art computer methods, as these are not sufficiently automated. In this study we propose a fully automatic 3D postoperative outcome quantification method for the relevant steps of orthopaedic interventions on the example of Periacetabular Osteotomy of Ganz (PAO). A typical orthopaedic intervention involves cutting bone, anatomy manipulation and repositioning as well as implant placement. Our method includes a segmentation based deep learning approach for detection and quantification of the cuts. Furthermore, anatomy repositioning was quantified through a multi-step registration method, which entailed a coarse alignment of the pre- and postoperative CT images followed by a fine fragment alignment of the repositioned anatomy. Implant (i.e., screw) position was identified by 3D Hough transform for line detection combined with fast voxel traversal based on ray tracing. The feasibility of our approach was investigated on 27 interventions and compared against manually performed 3D outcome evaluations. The results show that our method can accurately assess the quality and accuracy of the surgery. Our evaluation of the fragment repositioning showed a cumulative error for the coarse and fine alignment of 2.1 mm. Our evaluation of screw placement accuracy resulted in a distance error of 1.32 mm for screw head location and an angular deviation of 1.1° for screw axis. As a next step we will explore generalisation capabilities by applying the method to different interventions.

The biomechanical fundamentals of crosslink-augmentation in posterior spinal instrumentation.

Posterior screw-rod constructs can be used to stabilize spinal segments; however, the stiffness is not absolute, and some motion can persist. While the effect of crosslink-augmentation has been evaluated in multiple studies, the fundamental explanation of their effectiveness has not been investigated. The aim of this study was to quantify the parameters "screw rotation" and "parallelogram deformation" in posterior instrumentations with and without crosslinks to analyze and explain their fundamental effect. Biomechanical testing of 15 posteriorly instrumented human spinal segments (Th10/11-L4/L5) was conducted in axial rotation, lateral bending, and flexion-extension with ± 7.5 Nm. Screw rotation and parallelogram deformation were compared for both configurations. Parallelogram deformation occurred predominantly during axial rotation (2.6°) and was reduced by 60% (-1.45°, p = 0.02) by the addition of a crosslink. Simultaneously, screw rotation (0.56°) was reduced by 48% (-0.27°, p = 0.02) in this loading condition. During lateral bending, 0.38° of parallelogram deformation and 1.44° of screw rotation was measured and no significant reduction was achieved by crosslink-augmentation (8%, -0.03°, -p = 0.3 and -13%, -0.19°, p = 0.7 respectively). During flexion-extension, parallelogram deformation was 0.4° and screw rotation was 0.39° and crosslink-augmentation had no significant effect on these values (-0.12°, -30%, p = 0.5 and -0°, -0%, p = 0.8 respectively). In axial rotation, crosslink-augmentation can reduce parallelogram deformation and with that, screw rotation. In lateral bending and flexion-extension parallelogram deformation is minimal and crosslink-augmentation has no significant effect. Since the relatively large screw rotation in lateral bending is not caused by parallelogram deformation, crosslink-augmentation is no adequate countermeasure. The fundamental understanding of the biomechanical effect of crosslink-augmentation helps better understand its potential and limitations in increasing construct stiffness.

Comprehensive quantitative characterization of the human term amnion proteome.

The loss of fetal membrane (FM) integrity and function at an early time point during pregnancy can have devastating consequences for the fetus and the newborn. However, biomaterials for preventive sealing and healing of FMs are currently non-existing, which can be partly attributed to the current fragmentary knowledge of FM biology. Despite recent advances in proteomics analysis, a robust and comprehensive description of the amnion proteome is currently lacking. Here, by an optimized protein sample preparation and offline fractionation before liquid chromatography coupled to mass spectrometry (LC-MS) analysis, we present a characterization of the healthy human term amnion proteome, which covers more than 40% of the previously reported transcripts in similar RNA sequencing datasets and, with more than 5000 identifications, greatly outnumbers previous reports. Together, beyond providing a basis for the study of compromised and preterm ruptured FMs, this comprehensive human amnion proteome is a stepping-stone for the development of novel healing-inducing biomaterials. The proteomic dataset has been deposited in the ProteomeXchange Consortium with the identifier PXD019410.

3D printed clamps for fixation of spinal segments in biomechanical testing.

3D printed clamps provide multiple advantages compared to potting for the fixation of spinal specimens and in a recent study, superior fixation stability was reported. The aim of this study was to evaluate the fixation efficacy of 3D printed vertebra clamps during routine application and to present and evaluate a novel clamp for sacrum fixation. Further, public access to the template files is provided. 98 human single-level cadaveric specimens were biomechanically tested in flexion-extension (FE), lateral bending (LB), axial rotation (AR), anteroposterior shear (AS), lateral shear (LS) and axial compression-decompression (AC). Loading amplitudes were +/-7.5 Nm for FE, LB and AR, +/- 150 N for AS and LS and + 400/-100 N for AC. The novel sacrum clamp was used in 8 specimens. The median relative motion between clamps and specimens was 0.6° in FE, 0.7° in LB, 0.3° in AR, 0.5 mm in AS, 0.5 mm in LS and 0.1 mm in AC. With sacrum clamps, the median relative motion was 0.3° in FE, 0.1° in LB, 0.08° in AR, 0.8 mm in AS, 0.7 mm in LS and 0.2 mm in AC. The vertebra clamps used during routine testing provided better stability compared to the values in the literature in all six loading directions (p < 0.05). The sacrum clamp showed superior anchoring stability in three loading directions compared to the caudal vertebra clamps (p < 0.05), while inferior stability was measured in AS (p < 0.001). We conclude that 3D printed vertebra clamps and 3D printed sacrum clamps represent reliable methods for specimen fixation during routine biomechanical testing.

Is a cross-connector beneficial for single level traditional or cortical bone trajectory pedicle screw instrumentation?

The cortical bone trajectory (CBT) has been introduced with the aim of better screw hold, however, screw-rod constructs with this trajectory might provide less rigidity in lateral bending (LB) and axial rotation (AR) compared to the constructs with the traditional trajectory (TT). Therefore, the addition of a horizontal cross-connector could be beneficial in counteracting this possible inferiority. The aim of this study was to compare the primary rigidity of TT with CBT screw-rod constructs and to quantify the effect of cross-connector-augmentation in both. Spines of four human cadavers (T9 -L5) were cropped into 15 functional spine units (FSU). Eight FSUs were instrumented with TT and seven FSUs with CBT pedicle screws. The segments were tested in six loading directions in three configurations: uninstrumented, instrumented with and without cross-connector. The motion between the cranial and caudal vertebra was recorded. The range of motion (ROM) between the CBT and the TT group did not differ significantly in either configuration. Cross-connector -augmentation did reduce the ROM in AR (16.3%, 0.27°, p = 0.02), LB (2.9%, 0.07°, p = 0.03) and flexion-extension FE (2.3%, 0.04°, p = 0.02) for the TT group and in AR (20.6%, 0.31°, p = 0.01) for the CBT-group. The primary rigidity of TT and CBT single level screw-rod constructs did not show significant difference. The minimal reduction of ROM due to cross-connector-augmentation seems clinically not relevant. Based on the findings of these study there is no increased necessity to use a cross-connector in a CBT-construct.

HoloYolo: A proof-of-concept study for marker-less surgical navigation of spinal rod implants with augmented reality and on-device machine learning.

BACKGROUND: Existing surgical navigation approaches of the rod bending procedure in spinal fusion rely on optical tracking systems that determine the location of placed pedicle screws using a hand-held marker. METHODS: We propose a novel, marker-less surgical navigation proof-of-concept to bending rod implants. Our method combines augmented reality with on-device machine learning to generate and display a virtual template of the optimal rod shape without touching the instrumented anatomy. Performance was evaluated on lumbosacral spine phantoms against a pointer-based navigation benchmark approach and ground truth data obtained from computed tomography. RESULTS: Our method achieved a mean error of 1.83 ± 1.10 mm compared to 1.87 ± 1.31 mm measured in the marker-based approach, while only requiring 21.33 ± 8.80 s as opposed to 36.65 ± 7.49 s attained by the pointer-based method. CONCLUSION: Our results suggests that the combination of augmented reality and machine learning has the potential to replace conventional pointer-based navigation in the future.

Cross-links in posterior pedicle screw-rod instrumentation of the spine: a systematic review on mechanical, biomechanical, numerical and clinical studies.

PURPOSE: Dorsal screw-rod instrumentations are used for a variety of spinal disorders. Cross-links (CL) can be added to such constructs, however, no clear recommendations exist. This study aims to provide an overview of the available evidence on the effectiveness of CL, potentially allowing to formulate recommendations on their use. METHODS: A systematic literature review was performed on PubMed and 37 original articles were included and grouped into mechanical, biomechanical, finite element and clinical studies. The change in range of motion (ROM) was analyzed in mechanical and biomechanical studies, ROM, stiffness and stress distribution were evaluated in finite element studies and clinical outcome parameters were analyzed in clinical studies. RESULTS: A relative consistent reduction in ROM in axial rotation with CL-augmentation was reported, while minor and less consistent effects were observed in flexion-extension and lateral bending. The use of CLs was clinical beneficial in C1/2 fusion, while the limited clinical studies on other anatomic regions show no significant benefit for CL-augmentation. CONCLUSION: While CL provides some additional axial rotation stability in most situations, lateral bending and flexion-extension are less affected. Based on clinical data, CL-augmentation can only be recommended for C1/2 instrumentations, while for other cases, further clinical studies are needed to allow for evidence-based recommendations.

Osteosarcoma-Derived Extracellular Vesicles Induce Lung Fibroblast Reprogramming.

Tumor-secreted extracellular vesicles (EVs) have been identified as mediators of cancer-host intercellular communication and shown to support pre-metastatic niche formation by modulating stromal cells at future metastatic sites. While osteosarcoma, the most common primary malignant bone tumor in children and adolescents, has a high propensity for pulmonary metastases, the interaction of osteosarcoma cells with resident lung cells remains poorly understood. Here, we deliver foundational in vitro evidence that osteosarcoma cell-derived EVs drive myofibroblast/cancer-associated fibroblast differentiation. Human lung fibroblasts displayed increased invasive competence, in addition to increased α-smooth muscle actin expression and fibronectin production upon EV treatment. Furthermore, we demonstrate, through the use of transforming growth factor beta receptor 1 (TGFBR1) inhibitors and CRISPR-Cas9-mediated knockouts, that TGFß1 present in osteosarcoma cell-derived EVs is responsible for lung fibroblast differentiation. Overall, our study highlights osteosarcoma-derived EVs as novel regulators of lung fibroblast activation and provides mechanistic insight into how osteosarcoma cells can modulate distant cells to potentially support metastatic progression.

T1- and T2*-Mapping for Assessment of Tendon Tissue Biophysical Properties: A Phantom MRI Study.

OBJECTIVES: The aim of this study was to quantitatively assess changes in collagen structure using MR T1- and T2*-mapping in a novel controlled ex vivo tendon model setup. MATERIALS AND METHODS: Twenty-four cadaveric bovine flexor tendons underwent MRI at 3 T before and after chemical modifications, representing mechanical degeneration and augmentation. Collagen degradation (COL), augmenting collagen fiber cross-linking (CXL), and a control (phosphate-buffered saline [PBS]) were examined in experimental groups, using histopathology as standard of reference. Variable echo-time and variable-flip angle gradient-echo sequences were used for T2*- and T1-mapping, respectively. Standard T1- and T2-weighted spin-echo sequences were acquired for visual assessment of tendon texture. Tendons were assessed subsequently for their biomechanical properties and compared with quantitative MRI analysis. RESULTS: T1- and T2*-mapping was feasible and repeatable for untreated (mean, 545 milliseconds, 2.0 milliseconds) and treated tendons. Mean T1 and T2* values of COL, CXL, and PBS tendons were 1459, 934, and 1017 milliseconds, and 5.5, 3.6, and 2.5 milliseconds, respectively. T2* values were significantly different between enzymatically degraded tendons, cross-linked tendons, and controls, and were significantly correlated with mechanical tendon properties (r = -0.74, P < 0.01). T1 values and visual assessment could not differentiate CXL from PBS tendons. Photo-spectroscopy showed increased autofluorescence of cross-linked tendons, whereas histopathology verified degenerative lesions of enzymatically degraded tendons. CONCLUSIONS: T2*-mapping has the potential to detect and quantify subtle changes in tendon collagen structure not visible on conventional clinical MRI. Tendon T2* values might serve as a biomarker for biochemical alterations associated with tendon pathology.

Computer assisted reconstruction of complex proximal humerus fractures for preoperative planning.

Operative treatment of displaced fractures of the proximal humerus is among the most difficult problems in orthopedic shoulder surgery. An accurate preoperative assessment of fragment displacement is crucial for a successful joint restoration. We present a computer assisted approach to precisely quantify these displacements. The bone is virtually reconstructed by multi-fragment alignment. In case of largely displaced pieces, a reconstruction template based on the contralateral humerus is incorporated in the algorithm to determine the optimal assembly. Cadaver experiments were carried out to evaluate our approach. All cases could be successfully reconstructed with little user interaction, and only requiring a few minutes of processing time. On average, the reassembled bone geometries resulted in a translational displacement error of 1.3±0.4 mm and a rotational error of 3.4±2.2°, respectively.