Gene delivery to the spinal cord using MRI-guided focused ultrasound.

Non-invasive gene delivery across the blood-spinal cord barrier (BSCB) remains a challenge for treatment of spinal cord injury and disease. Here, we demonstrate the use of magnetic resonance image-guided focused ultrasound (MRIgFUS) to mediate non-surgical gene delivery to the spinal cord using self-complementary adeno-associated virus serotype 9 (scAAV9). scAAV9 encoding green fluorescent protein (GFP) was injected intravenously in rats at three dosages: 4 × 10(8), 2 × 10(9) and 7 × 10(9) vector genomes per gram (VG g(-1)). MRIgFUS allowed for transient, targeted permeabilization of the BSCB through the interaction of focused ultrasound (FUS) with systemically injected Definity lipid-shelled microbubbles. Viral delivery at 2 × 10(9) and 7 × 10(9) VG g(-1) leads to robust GFP expression in FUS-targeted regions of the spinal cord. At a dose of 2 × 10(9) VG g(-1), GFP expression was found in 36% of oligodendrocytes, and in 87% of neurons in FUS-treated areas. FUS applications to the spinal cord could address a long-term goal of gene therapy: delivering vectors from the circulation to diseased areas in a non-invasive manner.

Intraoperative scrub nurse turnover in orthopaedic surgery procedures: An opportunity for improved operating room efficiency.

BACKGROUND: Scrub nurses play a crucial role in facilitating orthopaedic surgeries, and thus intraoperative scrub nurse turnover may disrupt the workflow of the surgical team and prolong duration of surgery (DOS). The purpose of this study was to quantify the impact of intraoperative scrub nurse turnover on operative time of orthopaedic surgeries lasting less than 3h in duration. METHODS: Prospectively collected databases from two institutions were retrospectively queried to identify all orthopaedic procedures of maximum mean duration of 180min from March 4th, 2018 to August 31st, 2022. Cases were divided into two groups, those with scrub nurse turnover and those without. Propensity score matching was conducted to match groups by surgeon, hospital, patient age, gender, and ASA classification. Unpaired t-tests were used to compare mean DOS for each surgical procedure. Average treatment effect on treated (ATET) with 95% confidence intervals (CIs) were calculated. RESULTS: Scrub nurse turnover significantly prolonged DOS for both bone forearm facture open reduction and internal fixation (ORIF) (ATET=21.08, p=0.001), ankle ORIF (ATET=21.26, p<0.001), clavicle ORIF (ATET=16.16, p=0.028), femur intramedullary nail (ATET=11.52, p=0.003), rotator cuff repair (ATET=16.88, p<0.001), partial discectomy (ATET=10.52, p=0.001), total knee arthroplasty (TKA) (ATET=5.69, p<0.001), anterior total hip arthroplasty (THA) (ATET=8.80, p<0.001), lateral THA (ATET=7.02, p<0.001), and uncemented hip hemiarthroplasty (ATET=16.79, p=0.049). CONCLUSION: Intraoperative scrub nurse turnover significantly prolongs surgical times in orthopaedic surgeries lasting up to 3h in duration. This highlights the importance of developing strategies to prevent intraoperative scrub nurse turnover to improve OR efficiency and decrease healthcare costs.

Thickness and design features of clinical cranial implants-what should automated methods strive to replicate?

PURPOSE: New deep learning and statistical shape modelling approaches aim to automate the design process for patient-specific cranial implants, as highlighted by the MICCAI AutoImplant Challenges. To ensure applicability, it is important to determine if the training data used in developing these algorithms represent the geometry of implants designed for clinical use. METHODS: Calavera Surgical Design provided a dataset of 206 post-craniectomy skull geometries and their clinically used implants. The MUG500+ dataset includes 29 post-craniectomy skull geometries and implants designed for automating design. For both implant and skull shapes, the inner and outer cortical surfaces were segmented, and the thickness between them was measured. For the implants, a 'rim' was defined that transitions from the repaired defect to the surrounding skull. For unilateral defect cases, skull implants were mirrored to the contra-lateral side and thickness differences were quantified. RESULTS: The average thickness of the clinically used implants was 6.0 ± 0.5 mm, which approximates the thickness on the contra-lateral side of the skull (relative difference of -0.3 ± 1.4 mm). The average thickness of the MUG500+ implants was 2.9 ± 1.0 mm, significantly thinner than the intact skull thickness (relative difference of 2.9 ± 1.2 mm). Rim transitions in the clinical implants (average width of 8.3 ± 3.4 mm) were used to cap and create a smooth boundary with the skull. CONCLUSIONS: For implant modelers or manufacturers, this shape analysis quantified differences of cranial implants (thickness, rim width, surface area, and volume) to help guide future automated design algorithms. After skull completion, a thicker implant can be more versatile for cases involving muscle hollowing or thin skulls, and wider rims can smooth over the defect margins to provide more stability. For clinicians, the differing measurements and implant designs can help inform the options available for their patient specific treatment.

Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective?

The widespread use of systemic and local therapies aimed at spinal metastatic lesions secondary to breast cancer has increased the incidence of mixed osteolytic/osteoblastic patterns of bony disease. The complex structure of these lesions requires novel therapeutic approaches to both reduce tumor burden and restore structural stability. In photodynamic therapy (PDT), a minimally invasive approach can be used to employ light to activate a photosensitizing agent that preferentially accumulates in tumor tissue, leading to cell toxicity and death. Previous work in an osteolytic rat model (MT-1) demonstrated that PDT effectively ablates tumor and improves vertebral structural properties. The aim of this study was to assess the efficacy of PDT in a rat model of mixed osteolytic/osteoblastic spinal metastases. Mixed spinal metastases were generated through intracardiac injection of Ace-1 canine prostate cancer cells into female athymic rats (day 0). A single PDT treatment was applied to lumbar vertebra L2 of tumor-bearing and healthy control rats (day 14). PDT-treated and untreated control rats were euthanized and excised spines imaged with µCT to assess bone quality (day 21). Spines were mechanically tested or histologically processed to assess mechanical integrity, tumor burden, and remodelling properties. Untreated tumor-bearing vertebrae showed large areas of osteolysis and areas of immature, new bone formation. The overall bone quality resulting from these lesions consisted of decreased structural properties but without a significant reduction in mechanical integrity. PDT was shown to significantly decrease tumor burden and osteoclastic activity, thereby improving vertebral bone structural properties. While non-tumor-bearing vertebrae exhibited significantly more new bone formation following PDT, the already heightened level of new bone formation in the mixed tumor-bearing vertebrae was not further increased. As such, the effect of PDT on mixed metastases may be more influenced by suppression of osteoclastic resorption as opposed to the triggering of new bone formation.

Measuring 3D facial displacement of increasing smile expressions.

BACKGROUND: Following paralysis, facial reanimation surgery can restore movement by nerve and/or muscle transfer within the face. The subtleties of lip and cheek movements during smiling are important aspects in assessing reanimation. This study quantifies average 3D movement vectors of the face during smiling based on the diverse Binghamton University 3D facial expression database to yield normative measures of lip and cheek movement. METHODS: The analysis was conducted on 100 subjects with 3D facial scans in a neutral and 4 increasing smile intensities, as well as associated labeled 3D landmark points. Each subject set of 3D scans was rigidly registered to measure average displacement vectors (distance, azimuth, and elevation) between the neutral and happy expressions. RESULTS: The average lip commissure displacement was found to be 9.2, 11.4, 13.5, and 16.0 mm for increasing smile levels 1-4, respectively. Similarly, the average commissure azimuth angle across all 4 smile levels is ∼44 ± 21 degrees, and the average elevation angle across all 4 smile levels is ∼37 ± 15 degrees. The maximum cheek displacement from the neutral expression was 4.5, 5.7, 6.8, and 7.9 mm for the smile levels 1-4, respectively. The average cheek movement azimuth angle is outward (increasing 1-13 degrees), and the elevation angle is upward (increasing 51-59 degrees) from the face. CONCLUSIONS: These data quantifying 3D lip and cheek smile displacements improve the understanding of facial movement and may be applicable to future assessment/planning of facial reanimation surgeries.

Sensitivity analysis of a validated subject-specific finite element model of the human craniofacial skeleton.

Developing a more complete understanding of the mechanical response of the craniofacial skeleton (CFS) to physiological loads is fundamental to improving treatment for traumatic injuries, reconstruction due to neoplasia, and deformities. Characterization of the biomechanics of the CFS is challenging due to its highly complex structure and heterogeneity, motivating the utilization of experimentally validated computational models. As such, the objective of this study was to develop, experimentally validate, and parametrically analyse a patient-specific finite element (FE) model of the CFS to elucidate a better understanding of the factors that are of intrinsic importance to the skeletal structural behaviour of the human CFS. An FE model of a cadaveric craniofacial skeleton was created from subject-specific computed tomography data. The model was validated based on bone strain measurements taken under simulated physiological-like loading through the masseter and temporalis muscles (which are responsible for the majority of craniofacial physiologic loading due to mastication). The baseline subject-specific model using locally defined cortical bone thicknesses produced the strongest correlation to the experimental data (r2 = 0.73). Large effects on strain patterns arising from small parametric changes in cortical thickness suggest that the very thin bony structures present in the CFS are crucial to characterizing the local load distribution in the CFS accurately.

Evaluating the ability of posterior elements to support new instrumentation for spinal fusion.

Posterior spinal plating devices have recently made a re-emergence as both stand-alone devices and for use in conjunction with anterior fusion. Yet, the structural integrity of the posterior elements to support loads throughout the spine and the impact of plating on posterior element strength has not been well characterized. This study aims to quantify the mechanical strength of the posterior elements (spinous processes/laminae) throughout the spine and to determine the effect of attaching posterior element plating systems on their ultimate load to failure. Vertebral levels from six cadaveric spines were grouped in pairs to account for varying geometries and sizes of the human posterior elements (a total of 59 levels in 5 groups). One sample from each pair was tested in its native state, and the complementary vertebra was tested via posterior plating. Posterior element plating caused moderate reductions in posterior element failure strength (15-24 percent) throughout the cervical, thoracic, and lumbar spine. Bone mineral density of the posterior elements had the most significant impact on ultimate load to failure (a decrease of 0.1 g/cm3, yields a 189N reduction in). The modest structural impact of posterior element plating motivates continued investigation into potential use of less invasive plating devices for posterior spinal fusion.

Modeling and measuring average nasal asymmetry by dorsum midline and nose tip lateral deviation.

In rhinoplasty and nasal reconstruction, achieving symmetry is critical for optimal patient outcomes and reducing re-operation rates. Assessing nasal asymmetry is challenging, both pre- and intra-operatively, if based on only a surgeons' visual perception to assess and adjust the small distances important to cosmesis (<2-3 mm). To measure nasal symmetry, we first developed an algorithm to analyze lateral nasal deviation on facial three-dimensional (3D) scans captured by external surface scanning. In this, nasal deviation is measured by first registering a 3D facial scan to orthogonal axes in order to remove tilt. The lateral position of the nasal midline is then found across transverse planes along the dorsum and nasal tip regions by probing midpoints 1 and 2 mm back from the local maximum projection. The nasal deviation measurement algorithm was validated on a simulated asymmetrical nose model with known nasal deviation. Simulated deviations were applied to the symmetrical average nose using an exponential twist away from the face, with control of the maximum deviation and degree of curvature. Modeled deviations were evaluated with the algorithm at clinically negligible (0.02-0.06 mm) average differences and for small lateral deviations (1-5 mm). Nasal deviation using the algorithms was then measured for the 100 multi-ethnic subjects in the Binghamton University 3D Facial Expression database. Average values for maximum lateral deviation, deviation across the whole nose, and deviation at the nose tip were measured to provide context to deviation measurements in surgical planning. This research presents a new nasal assessment tool that can be useful in improving symmetry in rhinoplasty and reconstruction.

Effects of bone density alterations on strain patterns in the pelvis: application of a finite element model.

Insufficiency fractures occur when physiological loads are applied to bone deficient in mechanical resistance. A better understanding of pelvic mechanics and the effect of bone density alterations could lead to improved diagnosis and treatment of insufficiency fractures. This study aimed to develop and validate a subject-specific three-dimensional (3D) finite element (FE) model of a pelvis, to analyse pelvic strains as a function of interior and cortical surface bone density, and to compare high strain regions with common insufficiency fracture sites. The FE model yielded strong agreement between experimental and model strains. By means of the response surface method, changes to cortical surface bone density using the FE model were found to have a 60 per cent greater influence compared with changes in interior bone density. A small interaction was also found to exist between surface and interior bone densities (< 3 per cent), and a non-linear effect of surface bone density on strain was observed. Areas with greater increases in average principal strains with reductions in density in the FE model corresponded to areas prone to insufficiency fracture. Owing to the influence of cortical surface bone density on strain, it may be considered a strong global (non-linear) indicator for insufficiency fracture risk.

A biomechanical assessment of the coupling of torsion and tension in the human scapholunate ligament.

The mechanical behaviour of human scapholunate ligaments is not well described in the literature with regard to torsion. In this study, intact scapholunate specimens were mechanically tested in torsion to determine whether a simultaneous tensile load was generated. Human intact scapholunate specimens (n = 19) were harvested. The scaphoid and lunate bones were potted in square chambers using epoxy cement, while the interposing ligament remained exposed. Each specimen was mounted rigidly in a specially designed test jig and remained at a fixed axial length during all tests. Specimens were subjected to a torsional load regime that included cyclic preconditioning, ramp-up, stress relaxation, ramp-down, rest, and torsion to failure. Torque and axial tension were monitored simultaneously. The relationship between torsion and tension was determined. Graphs of torque versus tension were generated, from which outcome measures were extracted. Tests demonstrated a clear relationship between applied torsion and the resulting generation of tension for the ligament during ramp-up (torsion-to-tension ratio, 38.86 +/- 29.00 mm; linearity coefficient R2 = 0.89 +/- 0.15; n = 19), stress relaxation (torsion-to-tension ratio, 23.43 +/- 15.84 mm; R2 = 0.90 +/- 0.09; n = 16), and failure tests (torsion-to-tension ratio, 38.81 +/- 26.39mm; R2 = 0.77 +/- 0.20; n = 16). No statistically significant differences were detected between the torsion-to-tension ratios (p = 0.13) or between the linearity (R2) of the best-fit lines (p > 0.085). A strongly coupled linear relationship between torsion and tension for the scapholunate ligament was exhibited in all test phases. This may suggest interplay between these two parameters in the stabilization of the ligament during normal motion and for injury cascades.