Artificial Intelligence-Based Modeling Can Predict Face Shape Based on Underlying Craniomaxillofacial Bone.

Reconstructing facial deformities is often challenging due to the complex 3-dimensional (3D) anatomy of the craniomaxillofacial skeleton and overlying soft tissue structures. Bilateral injuries cannot benefit from mirroring techniques and as such preinjury information (eg, 2D pictures or 3D imaging) may be utilized to determine or estimate the desired 3D face shape. When patient-specific information is not available, other options such as statistical shape models may be employed; however, these models require registration to a consistent orientation which may be challenging. Artificial intelligence (AI) has been used to identify facial features and generate highly realistic simulated faces. As such, it was hypothesized that AI can be used to predict 3D face shape by learning its relationship with the underlying bone surface anatomy in a subject-specific manner. An automated image processing and AI modeling workflow using a modified 3D UNet was generated to estimate 3D face shape using the underlying bone geometry and additional metadata (eg, body mass index and age) obtained from 5 publicly available computed tomography imaging datasets. Visually, the trained models provided a reasonable prediction of the contour and geometry of the facial tissues. The pipeline achieved a validation dice=0.89 when trained on the combined 5 datasets, with the highest dice=0.925 achieved with the single HNSCC dataset. Estimated predefect facial geometry may ultimately be used to aid preoperative craniomaxillofacial surgical planning, providing geometries for intraoperative templates, guides, navigation, molds, and forming tools. Automated face shape prediction may additionally be useful in forensic studies to aid in the identification of unknown skull remains.

Assessing the Nasal Midline in Rhinoplasty: How Good Are We?

BACKGROUND: The challenge of assessing nasal alignment and asymmetry can contribute to high revision rates in rhinoplasty. Comparing to a validated computer algorithm for nasal alignment, the accuracy with which plastic surgeons can assess deviation of the nasal midline from the facial midline was measured. METHODS: Using 20 faces from the Binghamton University 3-dimensional face database, deviation was evaluated from facial midline of the middorsal line for the upper, middle, and lower thirds of the nose. Surgeons were asked to assess extent of deviation from facial midline for each third of the nose using a linear analog scale. Spearman correlations were performed comparing the surgeons' results to the algorithm measurements. Eleven residents and 9 consultant surgeons were tested. RESULTS: Surgeons' assessment of deviation correlated poorly with the algorithm in the upper third ( r =0.32, P <0.0001) and moderately in the middle third ( r =0.49, P <0.0001) and lower third ( r =0.41, P <0.0001) of the nose. No difference in accuracy was found between trainee and consultant surgeons ( P =0.51), and greater experience (>10 y performing nasal surgery) did not significantly affect performance ( P =0.15). The effect of fatigue on the accuracy of assessment was found to be significant ( P =0.0009). CONCLUSIONS: Surgeons have difficulty in visually assessing the 3-dimensional nasal midline irrespective of experience, and surgeon fatigue was found to be adversely affect the accuracy of assessments.

Accuracy of Orbital Shape Reconstruction-Comparative Analysis of Errors in Implant Shape Versus Implant Positioning: A Cadaveric Study.

INTRODUCTION: Orbital blowout fractures are commonly reconstructed with implants shaped to repair orbital cavity defects, restore ocular position and projection, and correct diplopia. Orbital implant shaping has traditionally been performed manually by surgeons, with more recent use of computer-assisted design (CAD). Accuracy of implant placement is also key to reconstruction. This study compares the placement accuracy of orbital implants, testing the hypothesis that CAD-shaped implants indexed to patient anatomy will better restore orbit geometry compared with manually shaped implants and manually placed implants. METHODS: The placement accuracy of orbital implants was assessed within a cadaveric blowout fracture model (3 skulls, 6 orbits) via 3-dimensional CT analysis. Defects were repaired with 4 different techniques: manually placed-manually shaped composite (titanium-reinforced porous polyethylene), manually placed CAD composite, indexed placed CAD composite, and indexed placed CAD titanium mesh. RESULTS: Implant placement accuracy differed significantly with the implant preparation method ( P =0.01). Indexing significantly improved the placement accuracy ( P =0.002). Indexed placed titanium mesh CAD implants (1.42±0.33 mm) were positioned significantly closer to the intact surface versus manually placed-manually shaped composite implants (2.12±0.39 mm). DISCUSSION: Computer-assisted design implants indexed to patient geometry yielded average errors below the acceptable threshold (2 mm) for enophthalmos and diplopia. This study highlights the importance of adequately indexing CAD-designed implants to patient geometry to ensure accurate orbital reconstructions.

Forehead Flap Templates for Nasal Reconstruction Digitally Developed From 2D and 3D Images.

ABSTRACT: The forehead flap is the gold standard procedure for nasal reconstruction to address a partial or complete rhinectomy. Traditionally, the three-dimensional (3D) nasal defect is manually templated intraoperatively to design the two-dimensional (2D) flap shape on intact morphology. In this clinical study, digital preoperative planning is used to template with computer-assisted design and manufacturing. Preoperative digital templates were implemented for 3 representative patients (1 in Supplementary Digital Content, http://links.lww.com/SCS/D60). This includes designs for a hemi-rhinectomy case from 3D mirroring, a partial total rhinectomy case generated from a 3D scan, and a total rhinectomy case generated from a 3D morphable model based on a prepathology 2D photo. Digital unwrapping flattened the patient's 3D nasal geometry designs to 2D skin flap shapes. Finally, the 2D designs were printed as traceable intraoperative templates at a 1:1 scale. This clinical study demonstrates the application of digital 3D preoperative templating to improve workflow for nasal reconstruction.

Biomechanical Properties of Metastatically Involved Osteolytic Bone.

PURPOSE OF REVIEW: Skeletal metastasis involves the uncoupling of physiologic bone remodeling resulting in abnormal bone turnover and radical changes in bony architecture, density, and quality. Bone strength assessment and fracture risk prediction are critical in clinical treatment decision-making. This review focuses on bone tissue and structural mechanisms altered by osteolytic metastasis and the resulting changes to its material and mechanical behavior. RECENT FINDINGS: Both organic and mineral phases of bone tissue are altered by osteolytic metastatic disease, with diminished bone quality evident at multiple length-scales. The mechanical performance of bone with osteolytic lesions is influenced by a combination of tissue-level and structural changes. This review considers the effects of osteolytic metastasis on bone biomechanics demonstrating its negative impact at tissue and structural levels. Future studies need to assess the cumulative impact of cancer treatments on metastatically involved bone quality, and its utility in directing multimodal treatment planning.

Perceptions of using lithium in fracture management: a survey of orthopaedic surgeons, fracture patients and the general public.

BACKGROUND: Lithium, an established psychiatric medication, has recently been shown to enhance new bone formation in preclinical fracture models. Current research is focused on evaluating the efficacy of low-dose, short-term lithium treatment to improve long bone fracture healing through a Phase II randomized clinical trial (LiFT NCT02999022). In working towards future applications of lithium for fracture management, this study aimed to understand the current perceptions of lithium as a psychiatric drug and the potential barriers to its orthopaedic adoption. METHODS: Three questionnaires, evaluating knowledge about lithium and willingness to embrace its use in fracture healing were disseminated among the general population, fracture patients eligible for the LiFT (Lithium for Fracture Treatment) trial and orthopaedic surgeons across Canada. RESULTS: Of the 768 public respondents, 84% were willing to take a medication that would aid fracture healing but only 62.6% if the medication was lithium. Willingness dropped to 44.6% among the 168 respondents who knew about the psychiatric use of lithium. Lack of sufficient knowledge (n = 50) and concerns about side effects including effects on the brain (n = 74) were the main reasons cited by those who were unwilling to use lithium. Of the 29 fracture patients, only 20 patients had previously heard of lithium. Of these, 40% were willing to take lithium for fracture healing with an additional 10% if the dose was low or if the intake duration was short. Only 50% knew that lithium has side effects. Of the 43 orthopaedic surgeons, 38 surgeons knew about clinical use of lithium. Of these, 68% knew that lithium has side effects and 29% knew that it interacts with other drugs. While most agreed that new strategies are needed to improve fracture management, only 68% were willing to prescribe lithium for fractures with an additional 16% if there is scientific evidence and/or a standard dosing protocol. CONCLUSIONS: This study identified a lack of knowledge about uses and side effects of lithium among all three cohorts. A robust educational framework for orthopaedic surgeons, their patients and the members of their clinical care teams will be essential to widespread repurposing of lithium for fracture care.

Diffusion-Tensor Imaging Versus Digitization in Reconstructing the Masseter Architecture.

Accurate characterization of the craniomaxillofacial (CMF) skeleton using finite element (FE) modeling requires representation of complex geometries, heterogeneous material distributions, and physiological loading. Musculature in CMF FE models are often modeled with simple link elements that do not account for fiber bundles (FBs) and their differential activation. Magnetic resonance (MR) diffusion-tensor imaging (DTI) enables reconstruction of the three-dimensional (3D) FB arrangement within a muscle. However, 3D quantitative validation of DTI-generated FBs is limited. This study compares 3D FB arrangement in terms of pennation angle (PA) and fiber bundle length (FBL) generated through DTI in a human masseter to manual digitization. CT, MR-proton density, and MR-DTI images were acquired from a single cadaveric specimen. Bone and masseter surfaces were reconstructed from CT and MR-proton density images, respectively. PA and FBL were estimated from FBs reconstructed from MR-DTI images using a streamline tracking (STT) algorithm (n = 193) and FBs identified through manual digitization (n = 181) and compared using the Mann-Whitney test. DTI-derived PAs did not differ from the digitized data (p = 0.411), suggesting that MR-DTI can be used to simulate FB orientation and the directionality of transmitted forces. Conversely, a significant difference was observed in FBL (p < 0.01) which may have resulted due to the tractography stopping criterion leading to early tract termination and greater length variability. Overall, this study demonstrated that DTI can yield muscle FB orientation data suitable to representative directionality of physiologic muscle loading in patient-specific CMF FE modeling.

The impact of thermal cycling on Staphylococcus aureus biofilm growth on stainless steel and titanium orthopaedic plates.

BACKGROUND: Orthopaedic implant infections are difficult to eradicate because bacteria adhering to implant surfaces inhibit the ability of the immune system and antibiotics to combat these infections. Thermal cycling is a temperature modulation process that improves performance and longevity of materials through molecular structural reorientation, thereby increasing surface uniformity. Thermal cycling may change material surface properties that reduce the ability for bacteria to adhere to the surface of orthopaedic implants. This study aims to determine whether thermal cycling of orthopaedic implants can reduce bacterial growth. METHODS: In a randomized, blinded in-vitro study, titanium and stainless steel plates treated with thermal cycling were compared to controls. Twenty-seven treated and twenty-seven untreated plates were covered with 10 ml tryptic soy broth containing ~ 105 colony forming units (CFU)/ml of bioluminescent Staphylococcus aureus (S. aureus)Xen29 and incubated at 37 °C for 14d. Quantity and viability of bacteria were characterized using bioluminescence imaging, live/dead staining and determination of CFUs. RESULTS: Significantly fewer CFUs grow on treated stainless steel plates compared to controls (p = 0.0088). Similar findings were seen in titanium plates (p = 0.0048) following removal of an outlier. No differences were evident in live/dead staining using confocal microscopy, or in metabolic activity determined using bioluminescence imaging (stainless steel plates: p = 0.70; titanium plates: p = 0.26). CONCLUSION: This study shows a reduction in CFUs formation on thermal cycled plates in-vitro. Further in-vivo studies are necessary to investigate the influence of thermal cycling on bacterial adhesion during bone healing. Thermal cycling has demonstrated improved wear and strength, with reductions in fatigue and load to failure. The added ability to reduce bacterial adhesions demonstrates another potential benefit of thermal cycling in orthopaedics, representing an opportunity to reduce complications following fracture fixation or arthroplasty.

Comparison of the effect of two different bone-targeted radiofrequency ablation (RFA) systems alone and in combination with percutaneous vertebroplasty (PVP) on the biomechanical stability of the metastatic spine.

INTRODUCTION: Radiofrequency ablation (RFA) and percutaneous vertebroplasty (PVP) are used independently and in combination to treat metastatically involved vertebrae with the aim of relieving pain, reducing tumour burden and providing bony mechanical stabilization. PURPOSE: The aim of this work was to characterize the effect of two bone-targeted RFA devices, alone and in combination with PVP, to improve strength and mechanical stability in vertebrae with osteolytic metastatic disease. METHODS: Simulated spinal metastases (n = 12) were treated with one of two bone-targeted RFA devices (bipolar cooled or bone coil RF electrodes), followed by PVP. Under axial compressive loading, spinal canal narrowing was measured in the intact specimen, after tumour simulation, post-RFA and post-PVP. RESULTS: RFA alone resulted in successful tumour shrinkage and cavitation, but further increased canal narrowing under loading. RFA combined with PVP significantly reduced posterior wall stability in samples where sufficient tumour shrinkage and cavitation were coupled with a pattern of cement deposition which extended to posterior vertebral body. CONCLUSIONS: RFA combined with cement deposition in the posterior vertebral body demonstrates significantly more stable vertebrae under axial loading.

Can fluoroscopy-based computer navigation improve entry point selection for intramedullary nailing of femur fractures?

BACKGROUND: The entry point is crucial to an accurate reduction in femoral nailing. Fluoroscopy-based navigation was developed to aid in reducing femur fractures and selecting entry points. QUESTIONS/PURPOSES: We asked: (1) Can the piriformis fossa (PF) and tip of the greater trochanter (TT) be identified with high reproducibility? (2) What is the range of nonneutral images clinically acceptable for entry point selection? (3) Does navigation improve accuracy and precision of landmarking the TT and PF? And (4) does off-angle fluoroscopy within the acceptable range affect landmark accuracy? METHODS: Three orthopaedic surgeons digitized the PF and TT under direct visualization on 10 cadaveric femurs, quantifying the reproducibility of the targeted PF and TT landmarks. Arcs of acceptable AP and lateral images of each femur were acquired in increments of 5° with a C-arm. An experienced orthopaedic surgeon rejected or accepted images for entry point selection by qualitatively assessing the relative positions and sizes of the greater trochanter, lesser trochanter, and femoral neck. Entry points were identified on each image using fluoroscopy and navigation. Hierarchical linear modeling was used to compare accuracy and precision between navigation and fluoroscopy and the effects of image angle. RESULTS: A 29° average arc of acceptable images was found. Reproducibility of the target landmarks for the PF and TT under direct visualization was excellent. Navigation had similar accuracy to fluoroscopy for PF localization but less for TT. Navigation increased precision compared to fluoroscopy for both PF and TT. Image angle affected accuracy of the PF and TT under fluoroscopy and navigation. CONCLUSIONS: Nonorthogonal images reduce accuracy of PF and TT identification with both navigation and fluoroscopy. Navigation increased precision but decreased accuracy and cannot overcome inaccuracies induced by nonorthogonal images.

Vertebral compression fracture after stereotactic body radiotherapy for spinal metastases.

The use of stereotactic body radiotherapy for metastatic spinal tumours is increasing. Serious adverse events for this treatment include vertebral compression fracture (VCF) and radiation myelopathy. Although VCF is a fairly low-risk adverse event (approximately 5% risk) after conventional radiotherapy, crude risk estimates for VCF after spinal SBRT range from 11% to 39%. In this Review, we summarise the evidence and predictive factors for VCF induced by spinal SBRT, review the pathophysiology of VCF in the metastatic spine, and discuss strategies used to prevent and manage this potentially disabling complication.

Modeling stability post zygomatic fracture reconstruction.

Zygomaticomaxillary complex (ZMC) fracture repair is one of the most common surgical procedures performed in craniomaxillofacial trauma management. Miniplates and screws are used to stabilize the fractured bone using small local incisions, however, these procedures are not infrequently associated with hardware-related post-operative complications. The amount of fixation hardware utilized varies depending on the fracture pattern and surgical judgment, with three-point fixation being the conventionally accepted treatment. However, limited experimental testing and clinical studies have suggested that ZMC stabilization may be achieved with less than three-point fixation. In this study, we utilized a previously developed finite element modeling approach that allows for detailed bone and muscle representation to study the mechanical behavior of the fractured craniomaxillofacial skeleton (CMFS) under one, two, or three-point fixation of the ZMC. Results suggest that using a miniplate along the infraorbital rim in three-point fixation increases the amount of strain and load transfer to this region, rather than offloading the bone. Two-point (zygomaticomaxillary and zygomaticofrontal) fixation yielded strain patterns most similar to the intact CMFS. One-point (zygomaticofrontal) fixation resulted in higher tensile and compressive strains in the zygomaticofrontal region and the zygomatic arch, along with a higher tensile strain on the zygomatic body. These modeling results provide biomechanical evidence for the concept of over-engineering in the stabilization of facial fractures. Furthermore, they support previous suggestions that less than three-point fixation of ZMC fractures may be adequate to achieve uneventful healing.

Treatment affects load to failure and microdamage accumulation in healthy and osteolytic rat vertebrae.

Bone turnover and microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This exploratory study aimed to establish an initial understanding of microdamage accumulation and load to failure in healthy and osteolytic rat vertebrae following focal and systemic cancer treatment (docetaxel (DTX), stereotactic body radiotherapy (SBRT), or zoledronic acid (ZA)). Osteolytic spine metastases were developed in 6-week-old athymic female rats via intracardiac injection of HeLa human cervical cancer cells (day 0). Additional rats served as healthy controls. Rats were either untreated, received SBRT to the T10-L6 vertebrae on day 14 (15 Gy, two fractions), DTX on day 7 or 14, or ZA on day 7. Rats were euthanized on day 21. Tumor burden was assessed with bioluminescence images acquired on day 14 and 21, histology of the excised T11 and L5 vertebrae, and ex-vivo µCT images of the T13-L4. Microstructural parameters (bone volume/total volume, trabecular number, spacing, thickness, and bone mineral density) were measured from L2 vertebrae. Load to failure was measured with axial compressive loading of the L1-L3 motion segments. Microdamage accumulation was labeled in T13 vertebrae with BaSO4 staining and was visualized with high resolution µCT imaging. Microdamage volume fraction was defined as the ratio of BaSO4 to bone volume. DTX administered on day 7 reduced tumor growth significantly (p < 0.05). Microdamage accumulation was found to be increased by the presence of metastases but was reduced by all treatments with ZA showing the largest improvement in HeLa cell injected rats. Load to failure was decreased in untreated and SBRT HeLa cell injected rats compared to healthy controls (p < 0.01). There was a moderate negative correlation between load to failure and microdamage volume fraction in vertebrae from rats injected with HeLa cells (R = -0.35, p = 0.031). Strong correlations were also found between microstructural parameters and load to failure and microdamage accumulation. Several factors, including the presence of osteolytic lesions and use of cancer therapies, influence microdamage accumulation and load to failure in rat vertebrae. Understanding the impact of these treatments on fracture risk of metastatic vertebrae is important to improve management of patients with spinal metastases.

Is three-point fixation needed to mechanically stabilize zygomaticomaxillary complex fractures?

Fixation is critical in zygomaticomaxillary complex (ZMC) fractures to avoid malunion; however, controversy exists as to how much hardware is required to achieve adequate stability. Current fixation regimens may not represent the minimum stabilization needed for uneventful healing. Craniomaxillofacial (CMF) computational models have shown limited load transmission through the infraorbital rim (IOR), and a previous experimental study of ZMC fractures has suggested that IOR plating does not alter CMF bone strain patterns. This study aimed to measure the impact of stabilization on fracture site displacement under muscle loading, testing the hypothesis that three-point fixation is not critical for ZMC fracture stability. Four ZMC complex fractures were simulated on two cadaveric samples and stabilized with three-point plating. Displacements simulating mouth openings of 20 mm and 30 mm were applied to the mandible using a custom apparatus. Fracture gap displacement under load was measured at multiple points along each fracture line, and bone strain was captured using a combination of uniaxial and rosette gauges. Data capture was repeated with the IOR plate removed (two-point fixation) and with the zygomaticomaxillary plate removed (one-point fixation). Fracture displacement under muscle loading was consistent, with gaps of less than 1 mm in 95% of cases (range 0.05-1.44 mm), reflecting clinical stability. Large variabilities were observed in the strain measurements, which may reflect the complexity of CMFS load patterns and the sensitivity of strain values to gauge placement. This study supports the concept of hardware reduction, suggesting that two-point (or even one-point) fixation may provide sufficient stability for a ZMC fracture under applied muscle loading.

Development and validation of a radiofrequency ablation treatment planning system for vertebral metastases.

PURPOSE: Bone-targeted radiofrequency ablation (RFA) is widely used in the treatment of vertebral metastases. While radiation therapy utilizes established treatment planning systems (TPS) based on multimodal imaging to optimize treatment volumes, current RFA of vertebral metastases has been limited to qualitative image-based assessment of tumour location to direct probe selection and access. This study aimed to design, develop and evaluate a computational patient-specific RFA TPS for vertebral metastases. METHODS: A TPS was developed on the open-source 3D slicer platform, including procedural setup, dose calculation (based on finite element modelling), and analysis/visualization modules. Usability testing was carried out by 7 clinicians involved in the treatment of vertebral metastases on retrospective clinical imaging data using a simplified dose calculation engine. In vivo evaluation was performed in a preclinical porcine model (n = 6 vertebrae). RESULTS: Dose analysis was successfully performed, with generation and display of thermal dose volumes, thermal damage, dose volume histograms and isodose contours. Usability testing showed an overall positive response to the TPS as beneficial to safe and effective RFA. The in vivo porcine study showed good agreement between the manually segmented thermally damaged volumes vs. the damage volumes identified from the TPS (Dice Similarity Coefficient = 0.71 ± 0.03, Hausdorff distance = 1.2 ± 0.1 mm). CONCLUSION: A TPS specifically dedicated to RFA in the bony spine could help account for tissue heterogeneities in both thermal and electrical properties. A TPS would enable visualization of damage volumes in 2D and 3D, assisting clinicians in decisions about potential safety and effectiveness prior to performing RFA in the metastatic spine.

Sarcopenia in Men With Bone-Predominant Metastatic Castration-Resistant Prostate Cancer Undergoing Ra-223 Therapy.

INTRODUCTION: Osteosarcopenia is the progressive loss of musculoskeletal structure and functionality, contributing to disability and mortality. Despite complex interactions between bone and muscle, osteosarcopenia prevention and treatment in men with metastatic castration-resistant prostate cancer (mCRPC) focuses predominantly on bone health. It is unknown whether Radium-223 (Ra-223) therapy affects sarcopenia. METHODS: We identified 52 patients with mCRPC who had received Ra-223 and had a baseline plus ≥1 follow-up abdominopelvic CT scan. The total contour area (TCA) and averaged Hounsfield units (HU) of the left and right psoas muscles were obtained at the inferior L3 endplate, and the psoas muscle index (PMI) was calculated therefrom. Intrapatient musculoskeletal changes were analyzed across various time points. RESULTS: TCA and PMI gradually declined over the study period (P = .002, P = .003, respectively), but Ra-223 therapy did not accelerate sarcopenia, nor the decline of HU compared to the pre-Ra-223 period. The median overall survival of patients with baseline sarcopenia was numerically worse (14.93 vs. 23.23 months, HR 0.612, P = .198). CONCLUSIONS: Ra-223 does not accelerate sarcopenia. Thus, worsening muscle parameters in men with mCRPC undergoing Ra-223 therapy are attributable to other factors. Further research is needed to determine whether baseline sarcopenia predicts poor overall survival in such patients.

Towards clinical applicability and computational efficiency in automatic cranial implant design: An overview of the AutoImplant 2021 cranial implant design challenge.

Cranial implants are commonly used for surgical repair of craniectomy-induced skull defects. These implants are usually generated offline and may require days to weeks to be available. An automated implant design process combined with onsite manufacturing facilities can guarantee immediate implant availability and avoid secondary intervention. To address this need, the AutoImplant II challenge was organized in conjunction with MICCAI 2021, catering for the unmet clinical and computational requirements of automatic cranial implant design. The first edition of AutoImplant (AutoImplant I, 2020) demonstrated the general capabilities and effectiveness of data-driven approaches, including deep learning, for a skull shape completion task on synthetic defects. The second AutoImplant challenge (i.e., AutoImplant II, 2021) built upon the first by adding real clinical craniectomy cases as well as additional synthetic imaging data. The AutoImplant II challenge consisted of three tracks. Tracks 1 and 3 used skull images with synthetic defects to evaluate the ability of submitted approaches to generate implants that recreate the original skull shape. Track 3 consisted of the data from the first challenge (i.e., 100 cases for training, and 110 for evaluation), and Track 1 provided 570 training and 100 validation cases aimed at evaluating skull shape completion algorithms at diverse defect patterns. Track 2 also made progress over the first challenge by providing 11 clinically defective skulls and evaluating the submitted implant designs on these clinical cases. The submitted designs were evaluated quantitatively against imaging data from post-craniectomy as well as by an experienced neurosurgeon. Submissions to these challenge tasks made substantial progress in addressing issues such as generalizability, computational efficiency, data augmentation, and implant refinement. This paper serves as a comprehensive summary and comparison of the submissions to the AutoImplant II challenge. Codes and models are available at https://github.com/Jianningli/Autoimplant_II.

Hierarchical model of fibrillar collagen organization for interpreting the second-order susceptibility tensors in biological tissue.

The second-order nonlinear polarization properties of fibrillar collagen in various rat tissues (vertebrae, tibia, tail tendon, dermis, and cornea) are investigated with polarization-dependent second-harmonic generation (P-SHG) microscopy. Three parameters are extracted: the second-order susceptibility ratio, R = [Formula: see text] ; a measure of the fibril distribution asymmetry, |A|; and the weighted-average fibril orientation, <δ>. A hierarchical organizational model of fibrillar collagen is developed to interpret the second-harmonic generation polarization properties. Highlights of the model include: collagen type (e.g., type-I, type-II), fibril internal structure (e.g., straight, constant-tilt), and fibril architecture (e.g., parallel fibers, intertwined, lamellae). Quantifiable differences in internal structure and architecture of the fibrils are observed. Occurrence histograms of R and |A| distinguished parallel from nonparallel fibril distributions. Parallel distributions possessed low parameter values and variability, whereas nonparallel distributions displayed an increase in values and variability. From the P-SHG parameters of vertebrae tissue, a three-dimensional reconstruction of lamellae of intervertebral disk is presented.

Beyond radiation therapy: photodynamic therapy maintains structural integrity of irradiated healthy and metastatically involved vertebrae in a pre-clinical in vivo model.

Spinal metastasis commonly occurs in advanced breast cancer. Treatment is often multimodal including radiation therapy (RT), bisphosphonates (BPs), and surgery, yet alternative minimally invasive local treatments are needed. Photodynamic therapy (PDT) has been shown to ablate tumor cells and enhance bone formation secondary to metastatic breast cancer, demonstrating potential as a treatment for spinal metastasis. Combined with previous BP treatment, bone formation was further enhanced by PDT. This study aimed to determine the effects of PDT in combination with previous RT on healthy and metastatically involved vertebrae. Forty-six athymic rats underwent RT (4 Gy on day-7), twenty-three of them were inoculated with MT-1 human breast cancer cells on day 0. Thirteen healthy and ten metastatically involved rats underwent PDT treatment on day 14. All rats were sacrificed on day 21. L2 vertebrae were analyzed using µCT imaging, mechanical testing, and histological methods. In healthy vertebrae, while modest increases in trabecular structure were found in RT + PDT compared to RT only, mechanical stability was negatively affected. The 4 Gy RT dose was found to ablate all tumor cells and prevent further vertebral metastasis. As such, in metastatically involved rats, no differences in stereological or mechanical properties were detected. RT + PDT and RT-only treatment resulted in greatly improved vertebral structural and mechanical properties versus untreated or PDT-only treatment in metastatically involved rats, due to early tumor destruction in RT-treated groups. Increased amounts of woven bone and osteoid volume were found in PDT-treated vertebrae. Further investigation is needed to understand if structural improvements seen in RT + PDT treatment can translate into longer-term improvements in strength to support the potential of PDT as a viable adjuvant treatment for spinal metastasis postradiation.

Multimodal µCT/µMR based semiautomated segmentation of rat vertebrae affected by mixed osteolytic/osteoblastic metastases.

PURPOSE: Multimodal microimaging in preclinical models is used to examine the effect of spinal metastases on bony structure; however, the evaluation of tumor burden and its effect on microstructure has thus far been mainly qualitative or semiquantitative. Quantitative analysis of multimodality imaging is a time consuming task, motivating automated methods. As such, this study aimed to develop a low complexity semiautomated multimodal µCT/µMR based approach to segment rat vertebral structure affected by mixed osteolytic/osteoblastic destruction. METHODS: Mixed vertebral metastases were developed via intracardiac injection of Ace-1 canine prostate cancer cells in three 4-week-old rnu/rnu rats. µCT imaging (for high resolution bone visualization), T1-weighted µMR imaging (for bone registration), and T2-weighted µMR imaging (for osteolytic tumor visualization) were conducted on one L1, three L2, and one L3 vertebrae (excised). One sample (L1-L3) was processed for undecalcified histology and stained with Goldner's trichome. The µCT and µMR images were registered using a 3D rigid registration algorithm with a mutual information metric. The vertebral microarchitecture was segmented from the µCT images using atlas-based demons deformable registration, levelset curvature evolution, and intensity-based thresholding techniques. The µCT based segmentation contours of the whole vertebrae were used to mask the T2-weighted µMR images, from which the osteolytic tumor tissue was segmented (intensity-based thresholding). RESULTS: Accurate registration of µCT and µMRI modalities yielded precise segmentation of whole vertebrae, trabecular centrums, individual trabeculae, and osteolytic tumor tissue. While the algorithm identified the osteoblastic tumor attached to the vertebral pereosteal surfaces, it was limited in segmenting osteoblastic tissue located within the trabecular centrums. CONCLUSIONS: This semiautomated segmentation method yielded accurate registration of µCT and µMRI modalities with application to the development of mathematical models analyzing the mechanical stability of metastatically involved vertebrae and in preclinical applications evaluating new and existing treatment effects on tumor burden and skeletal microstructure.