High variability exists in 3D leg alignment analysis, but underlying principles that might lead to agreement on a universal framework could be identified: A systematic review.

PURPOSE: To (1) investigate the hypothesis that there is high variability in the reported methods to derive axes and joint orientations from three-dimensional (3D) bone models to (a) perform 3D knee-related leg alignment analysis and (b) define coordinate systems for the femur, tibia and leg and (2) identify underlying principles that might lead to agreement on a universal 3D leg alignment analysis framework. METHODS: A systematic review of the literature between January 2006 and June 2024 was performed. Articles explicitly reporting methods to derive axes and joint orientations from CT-based 3D bone models for alignment parameters and/or coordinate systems of the femur, tibia and leg were included. Study characteristics and reported methods were extracted and presented as a qualitative synthesis. RESULTS: A total of 93 studies were included. There was high variability in the reported methods to derive axes and joint orientations from 3D bone models. Nevertheless, the reported methods could be categorized into four groups, and several underlying principles of the four groups could be identified. Furthermore, the definitions of femoral and tibial coordinate systems were most frequently based on the mechanical axis (femoral, 13/19 [68%]; tibial, 13/26 [50%]) and a central medial-lateral axis (femoral, 16/19 [84%]; tibial, 12/26 [46%]); no leg coordinate system was reported. Interestingly, of the included studies that reported on leg alignment parameters (76/93, 82%), only a minority reported expressing these in a complete coordinate system (25/76, 33%). CONCLUSION: There is high variability in 3D knee-related leg alignment analysis. Therefore, universal 3D reference values for alignment parameters cannot yet be defined, and comparison of alignment parameter values between different studies is impossible. However, several underlying principles to the reported methods were identified, which could serve to reach more agreement on a future universal 3D framework for leg alignment analysis. LEVEL OF EVIDENCE: Level I (1).

Sample preparation for lipid analysis of intra-articular adipose tissue by using matrix-assisted laser desorption/ionization imaging.

Mass spectrometry imaging (MSI) is a powerful technique enabling the visualization of the spatial distribution of different molecules in tissue biopsies with different pathologies. Sample handling and preparing adipose tissue for MSI is challenging and prone to molecular delocalization due to tissue melting. In this work, we developed a method for matrix-assisted laser desorption/ionization (MALDI)-MSI to study lipids in human infrapatellar fat pad (IPFP), a biomarker source in musculoskeletal pathologies, while preserving molecular spatial distribution. Cryosectioning at 15 µm with a temperature below -30 °C, thaw-mounting, and sublimation, was demonstrated to preserve IPFP's heterogeneous appearance and spatial distribution of lipids.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) reveals potential lipid markers between infrapatellar fat pad biopsies of osteoarthritis and cartilage defect patients.

The incidence of osteoarthritis (OA) has been expected to increase due to an aging population, as well as an increased incidence of intra-articular (osteo-) chondral damage. Lipids have already been shown to be involved in the inflammatory process of OA. This study aims at revealing region-specific lipid profiles of the infrapatellar fat pad (IPFP) of OA or cartilage defect patients by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which could be used as biomarkers for early OA detection. A higher presence of phospholipids was found in OA patients compared with cartilage defect patients. In addition, a higher abundance of ether-linked phosphatidylethanolamines (PE O-s) containing arachidonic acid was specifically found in OA patients compared with cartilage defect patients. These lipids were mainly found in the connective tissue of the IPFP. Specific lipid species were associated to OA patients compared with cartilage defect patients. PE O-s have been suggested as possible biomarkers for OA. As these were found more abundantly in the connective tissue, the IPFP's intra-tissue heterogeneity might play an important role in biomarker discovery, implying that the amount of fibrous tissue is associated with OA.

The preferred technique for knee synovium biopsy and synovial fluid arthrocentesis.

For knee osteoarthritis and related conditions, analysis of biomarkers hold promise to improve early diagnosis and/or offer patient-specific treatment. To compare biomarker analyses, reliable, high-quality biopsies are needed. The aim of this work is to summarize the literature on the current best practices of biopsy of the synovium and synovial fluid arthrocentesis. Therefore, PubMed, Embase and Web of Science were systematically searched for articles that applied, demonstrated, or evaluated synovial biopsies or arthrocentesis. Expert recommendations and applications were summarized, and evidence for superiority of techniques was evaluated. Thirty-one studies were identified for inclusion. For arthrocentesis, the superolateral approach in a supine position, with a 0°-30° knee flexion was generally recommended. 18-gage needles, mechanical compression and ultrasound-guidance were found to give superior results. For blind and image-guided synovial biopsy techniques, superolateral and infrapatellar approaches were recommended. Single-handed tools were preconized, including Parker-Pearson needles and forceps. Sample quantity ranged approximately from 2 to 20. Suggestions were compiled for arthrocentesis regarding approach portal and patient position. Further evidence regarding needle size, ultrasound-guidance and mechanical compression were found. More comparative studies are needed before evidence-based protocols can be developed.

Mass Spectrometry-based Biomarkers for Knee Osteoarthritis: A Systematic Review.

INTRODUCTION: Knee osteoarthritis (OA) is a joint disease, affecting multiple tissues in the joint. Early detection and intervention may delay OA development and avoid total knee arthroplasty. Specific biomarker profiles for early detection and guiding clinical decision-making of OA have not yet been identified. One technique that can contribute to the finding of this 'OA biomarker' is mass spectrometry (MS), which offers the possibility to analyze different molecules in tissues or fluids. Several proteomic, lipidomic, metabolomic and other - omic approaches aim to identify these molecular profiles; however, variation in methods and techniques complicate the finding of promising candidate biomarkers. AREAS COVERED: In this systematic review, we aim to provide an overview of molecules in knee OA patients. Possible biomarkers in several tissue types of OA and non-OA patients, as well as current limitations and possible future suggestions will be discussed. EXPERT OPINION: According to this review, we do not believe one specific biomarker will function as predictive molecule for OA. Likely, a group of molecules will give insight in OA development and possible therapeutic targets. For clinical implementation of MS-analysis in clinical decision-making, standardized procedures, large cohort studies and sharing protocols and data is necessary.

Three-dimensional analysis of shape variations and symmetry of the fibula, tibia, calcaneus and talus.

The bones forming the talocrural joint (TCJ) and subtalar joint (STJ) are often assumed to be bilaterally symmetric. Therefore, the contralateral limb (i.e. the fibula, tibia, calcaneus and talus) is used as a template or an intra-subject control in clinical and research practice. However, the validity of the symmetry assumption is controversial, because insufficient information is available on the shape variations and bilateral (a)symmetry of the fibula, tibia, calcaneus and talus. Using three-dimensional spatially dense sampled representations of bone shapes extracted from bilateral computed tomography scans of 66 individuals (55 male, mean age: 61 ±â€…10 years; 11 female, mean age: 53 ±â€…15 years), we analyzed whether: (i) similar shape patterns exist in the left and right bones of the same type; (ii) gender has an effect on bone shape variations; (iii) intra-subject shape variation is smaller than that of inter-subject for a given shape variance direction. For the first set of analyses, all left and right instances of the same type of bone were considered as two separate groups, and statistically compared with each other on multiple aspects including group location (central tendency), variance-covariance scale (dispersion) and orientation (covariance structure) using distance-based permutational tests. For the second and third sets of analyses, all left and right bones of the same type were pooled into one group, and shape variations in the TCJ and STJ bones were extracted using principal component analysis. The effects of gender on age-adjusted bone shape differences were assessed using an analysis of covariance. Moreover, intra-class correlation was employed to evaluate intra- and inter-subject bone shape variations. For each bone type, both sides had similar shape patterns (Ppermutational -values > 0.05). After Bonferroni adjustment, gender led to shape differences, which were mainly in the lateral and medial condyles of the tibia (P = 0.003), the length and height of the calcaneus (P < 0.001), the posterior and anterior talar articular surfaces of the calcaneus (P = 0.001), and in the posterior aspect of the talus (P = 0.001). Intra-subject shape variations in the tibial tuberosity together with the diameter of the tibia, and the curvature of the fibula shaft and the diameter of the fibula were as high as those of inter-subject. This result suggests that the shape symmetry assumption could be violated for some specific shape variations in the fibula and tibia.

Validation of Simendo Knee Arthroscopy Virtual Reality Simulator.

PURPOSE: To determine the face and construct validity as well as educational value and user-friendliness of the Simendo knee arthroscopy virtual reality simulator. METHODS: Sixty participants were recruited and equally divided into novices (0 arthroscopic procedures), intermediates (1-59 arthroscopic procedures), and experts (60 or more arthroscopic procedures). Participants were excluded if they had previously trained with the studied simulator. Construct validity, that is, the ability to discriminate between different levels of expertise, was examined by a navigation task. All participants were asked to perform 5 navigation trials within 10 minutes. Face validity, educational value, and user-friendliness were examined by questionnaires before and after the navigation trials. Face validity is the subjective impression of how closely the simulation replicates the real environment. RESULTS: The novices were significantly slower than the intermediates in the first (P < .001) and the third (P = .031) trial. The novices were significantly slower than the experts in all trials (P = .016), except for the fifth (P = .054). The experts were significantly faster than the intermediates in every trial except for the fourth (P = .069). Median task time for the fifth trial was 63 seconds (44-80 seconds) for novices, 58 seconds (46-80 seconds) for intermediates, and 41 seconds (33-55 seconds) for experts. Ninety-two percent of all participants agreed that the simulator can be used to train for surgical inspection, and 95% indicated sufficient user-friendliness. CONCLUSIONS: Based on the results, this knee simulator can be applied to train the basic arthroscopic hand-eye coordination skills at the start of resident education programs. Further testing is necessary to determine whether the skills are retained. CLINICAL RELEVANCE: The simulator is partly validated, which contributes to training of basic arthroscopic skills without compromising patient safety.

Three-Dimensional Registration of Freehand-Tracked Ultrasound to CT Images of the Talocrural Joint.

A rigid surface⁻volume registration scheme is presented in this study to register computed tomography (CT) and free-hand tracked ultrasound (US) images of the talocrural joint. Prior to registration, bone surfaces expected to be visible in US are extracted from the CT volume and bone contours in 2D US data are enhanced based on monogenic signal representation of 2D US images. A 3D monogenic signal data is reconstructed from the 2D data using the position of the US probe recorded with an optical tracking system. When registering the surface extracted from the CT scan to the monogenic signal feature volume, six transformation parameters are estimated so as to optimize the sum of monogenic signal features over the transformed surface. The robustness of the registration algorithm was tested on a dataset collected from 12 cadaveric ankles. The proposed method was used in a clinical case study to investigate the potential of US imaging for pre-operative planning of arthroscopic access to talar (osteo)chondral defects (OCDs). The results suggest that registrations with a registration error of 2 mm and less is achievable, and US has the potential to be used in assessment of an OCD' arthroscopic accessibility, given the fact that 51% of the talar surface could be visualized.

Navigation forces during wrist arthroscopy: assessment of expert levels.

PURPOSE: To facilitate effective and efficient training in skills laboratory, objective metrics can be used. Forces exerted on the tissues can be a measure of safe tissue manipulation. To provide feedback during training, expert threshold levels need to be determined. The purpose of this study was to define the magnitude and the direction of navigation forces used during arthroscopic inspection of the wrist. METHODS: We developed a set-up to mount a cadaver wrist to a 3D force platform that allowed measurement of the forces exerted on the wrist. Six experts in wrist arthroscopy performed two tasks: (1) Introduction of the camera and visualization of the hook. (2) Navigation through the wrist with visualization of five anatomic structures. The magnitude (Fabs) and direction of force were recorded, with the direction defined as α being the angle in the vertical plane and ß being the angle in the horizontal plane. The 10th-90th percentile of the data were used to set threshold levels for training. RESULTS: The results show distinct force patterns for each of the anatomic landmarks. Median Fabs of the navigation task is 3.8 N (1.8-7.3), α is 3.60 (-54-44) and ß is 260 (0-72). CONCLUSION: Unique expert data on navigation forces during wrist arthroscopy were determined. The defined maximum allowable navigation force of 7.3 N (90th percentile) can be used in providing feedback on performance during skills training. The clinical value is that this study contributes to objective assessment of skills levels.

A novel ultrasound technique for detection of osteochondral defects in the ankle joint: a parametric and feasibility study.

(Osteo)chondral defects (OCDs) in the ankle are currently diagnosed with modalities that are not convenient to use in long-term follow-ups. Ultrasound (US) imaging, which is a cost-effective and non-invasive alternative, has limited ability to discriminate OCDs. We aim to develop a new diagnostic technique based on US wave propagation through the ankle joint. The presence of OCDs is identified when a US signal deviates from a reference signal associated with the healthy joint. The feasibility of the proposed technique is studied using experimentally-validated 2D finite-difference time-domain models of the ankle joint. The normalized maximum cross correlation of experiments and simulation was 0.97. Effects of variables relevant to the ankle joint, US transducers and OCDs were evaluated. Variations in joint space width and transducer orientation made noticeable alterations to the reference signal: normalized root mean square error ranged from 6.29% to 65.25% and from 19.59% to 8064.2%, respectively. The results suggest that the new technique could be used for detection of OCDs, if the effects of other parameters (i.e., parameters related to the ankle joint and US transducers) can be reduced.

It is safe to use the ulnar length difference to correct the radial length difference in the 3D-planning process of a radius osteotomy in patients with a distal radius malunion.

BACKGROUND: A corrective radius osteotomy is often performed in patients with a symptomatic distal radius malunion. In 3D-planned osteotomies, the unaffected radius is mirrored over the malunited radius after adjusting for left-right length differences using both ulnae. This approach assumes that ulnar length differences in a malunion population are similar to those in a healthy population. This study was conducted to analyze the difference in ulnar length in a distal radius malunion population and to assess the potential influence of age, sex, or malunion side on this difference. METHODS: We evaluated 65 adult patients with distal radius malunion using bilateral forearm CT scans. 3D models of both ulnae were constructed, and length differences were determined along a standardized length axis. The results were compared to two populations without a radius malunion. RESULTS: The average absolute ulnar length difference was 2.57 mm (SD 1.81), which was comparable to the two healthy populations. This difference was not significantly affected by age, sex, or malunion side. CONCLUSION: This study demonstrated that using the ulnar length difference to correct for radial length difference in the current 3D planning process, before using the contralateral radius as a template for a corrective osteotomy in patients with radius malunion, is safe.

Three-Dimensional Hinge Axis Orientation Contributes to Simultaneous Alignment Correction in All Three Anatomical Planes in Opening-Wedge High Tibial Osteotomy.

Purpose: To investigate the simultaneous effect of 3-dimensional (3D) hinge axis (HA) orientation on alignment parameters in all 3 anatomical planes in high tibial osteotomy. Methods: A computed tomography-based 3D model of a human tibia/fibula was used to establish a 3D tibial coordinate system based on the tibial mechanical axis. In here, an HA was positioned and an opening-wedge high tibial osteotomy with a rotation angle of 10° over the HA was simulated. HA rotation in the axial plane ranged from 0° to 90° and HA tilt relative to the axial plane ranged from -20° to +20°. The study quantified the simultaneous effect of HA orientation on change of alignment parameters in all anatomical reference planes. Results: HA rotation within the tibial axial plane between orientations perpendicular to the coronal and sagittal planes primarily affected both coronal and sagittal plane alignment, with an inverse relationship between these planes (range: 0°-9.7°); the effect of HA rotation on the change in axial plane alignment was maximally 0.9°. In contrast, HA tilt relative to the tibial axial plane primarily affected axial alignment (maximum change: 6.9°); the effect on change in both coronal and sagittal plane alignment was maximally 0.6°. Conclusions: HA rotation in the tibial axial plane primarily affects sagittal and coronal plane alignment, and HA tilt relative to the tibial axial plane primarily affects axial plane alignment. Clinical Relevance: Integrating 3D HA orientation in malalignment planning and correction offers the potential to minimize unintended corrections in nontargeted planes in uniplanar correction osteotomies and to facilitate intentional multiplanar correction with a single osteotomy.

No effect of hole geometry in microfracture for talar osteochondral defects.

BACKGROUND: Débridement and bone marrow stimulation is an effective treatment option for patients with talar osteochondral defects. However, whether surgical factors affect the success of microfracture treatment of talar osteochondral defects is not well characterized. QUESTIONS/PURPOSES: We hypothesized (1) holes that reach deeper into the bone marrow-filled trabecular bone allow for more hyaline-like repair; and (2) a larger number of holes with a smaller diameter result in more solid integration of the repair tissue, less need for new bone formation, and higher fill of the defect. METHODS: Talar osteochondral defects that were 6 mm in diameter were drilled bilaterally in 16 goats (32 samples). In eight goats, one defect was treated by drilling six 0.45-mm diameter holes in the defect 2 mm deep; in the remaining eight goats, six 0.45-mm diameter holes were punctured to a depth of 4 mm. All contralateral defects were treated with three 1.1-mm diameter holes 3 mm deep, mimicking the clinical situation, as internal controls. After 24 weeks, histologic analyses were performed using Masson-Goldner/Safranin-O sections scored using a modified O'Driscoll histologic score (scale, 0-22) and analyzed for osteoid deposition. Before histology, repair tissue quality and defect fill were assessed by calculating the mean attenuation repair/healthy cartilage ratio on Equilibrium Partitioning of an Ionic Contrast agent (EPIC) micro-CT (µCT) scans. Differences were analyzed by paired comparison and Mann-Whitney U tests. RESULTS: Significant differences were not present between the 2-mm and 4-mm deep hole groups for the median O'Driscoll score (p = 0.31) and the median of the µCT attenuation repair/healthy cartilage ratios (p = 0.61), nor between the 0.45-mm diameter and the 1.1-mm diameter holes in defect fill (p = 0.33), osteoid (p = 0.89), or structural integrity (p = 0.80). CONCLUSIONS: The results indicate that the geometry of microfracture holes does not influence cartilage healing in the caprine talus. CLINICAL RELEVANCE: Bone marrow stimulation technique does not appear to be improved by changing the depth or diameter of the holes.

Medical device regulation: requirements for occupational therapists in The Netherlands who prescribe and manufacture custom-made devices.

PURPOSE: To interpret the Medical Device Regulation for occupational therapists in the Netherlands involved in prescribing and manufacturing custom-made assistive devices and to develop a roadmap for implementation. MATERIALS AND METHODS: Four online iterative co-design workshops were organized under supervision of a senior quality manager to assist in the interpretation of the MDR framework with a focus on custom-made assistive devices; and to assist the implementation by generating guidelines and forms. The workshops for seven participating occupational therapists had an interactive character with Q&A, small and homework assignments, and oral evaluations. Next to occupational therapists, participants with different backgrounds joined such as 3D printing experts, engineers, managers, and researchers. RESULTS: The participants experienced the interpretation of the MDR as informative, but also as complex . Complying with the MDR requires considerable documentation activities that are currently not part of care professionals tasks. This initially raised concerns regarding implementation in daily practice. To facilitate the MDR implementation, forms were created and evaluated for a selected design case together with the participants for future reference. Additionally, instructions were given which forms should be filled out only once per organization, which forms could be reused for similar types of custom-made devices, and which forms should be filled out for each individual custom-made device. CONCLUSIONS: This study provides practical guidelines and forms to support occupational therapists in the Netherlands to prescribe and manufacture custom-made medical devices complying with the MDR. It is recommended to involve engineers and/or quality managers in this process.IMPLICATIONS FOR REHABILITATIONOccupational therapists are considered legal manufacturer when they prescribe and manufacture custom-made medical devices for their clients. As such they are legally obliged to meet the Medical Device Regulation (MDR).When designing and manufacturing "in-house" custom-made medical devices, care organizations need to follow and document activities to demonstrate compliance with the MDR. This study offers practical guidelines and forms to facilitate this.

A comparison of 3-D CT and 2-D plain radiograph measurements of the wrist in extra-articular malunited fractures of the distal radius.

Two-dimensional (2-D) plain radiographs may be insufficient for the evaluation of distal radial malunion, as it is a three-dimensional (3-D) deformity. This study introduced a 3-D measuring method that outputs radial inclination, ulnar variance, palmar tilt and axial rotation. To this end, a standardized and clearly defined coordinate system was constructed that allowed 3-D measurements closely resembling the conventional 2-D method in 35 patients. Mean differences between 3-D and 2-D measurements in affected wrists were 1.8° for radial inclination, 0.8 mm for ulnar variance and 3.7° for palmar tilt. In addition, inter- and intra-observer reproducibility of all 3-D and 2-D measurements were good or excellent (intraclass correlation coefficient >0.75), with 3-D reproducibility always better than 2-D. Axial rotation was present in all patients with a mean of 7.9° (SD 6.9). Although the differences between 2-D and 3-D measurements were small, 3-D evaluation enables the assessment of axial rotation and brings us closer to a routine 3-D evaluation of malunion.Level of evidence: III.

Near-Infrared Spectral Similarity between Ex Vivo Porcine and In Vivo Human Tissue.

BACKGROUND: In vivo diffuse reflectance spectroscopy provides additional contrast in discriminating nerves embedded in adipose tissue during surgery. However, large datasets are required to achieve clinically acceptable classification levels. This study assesses the spectral similarity between ex vivo porcine and in vivo human spectral data of nerve and adipose tissue, as porcine tissue could contribute to generate large datasets. METHODS: Porcine diffuse reflectance spectra were measured at 124 nerve and 151 adipose locations. A previously recorded dataset of 32 in vivo human nerve and 23 adipose tissue locations was used for comparison. In total, 36 features were extracted from the raw porcine to generate binary logistic regression models for all combinations of two, three, four and five features. Feature selection was performed by assessing similar means between normalized features of nerve and of adipose tissue (Kruskal-Wallis test, p < 0.05) and for models performing best on the porcine cross validation set. The human test set was used to assess classification performance. RESULTS: The binary logistic regression models with selected features showed an accuracy of 60% on the test set. CONCLUSIONS: Spectral similarity between ex vivo porcine and in vivo human adipose and nerve tissue was present, but further research is required.

Computed tomography of the ankle in full plantar flexion: a reliable method for preoperative planning of arthroscopic access to osteochondral defects of the talus.

PURPOSE: The purpose of this study was to determine whether preoperative computed tomography (CT) of the ankle joint in full plantar flexion is a reliable and accurate tool to determine the anterior arthroscopic accessibility of talar osteochondral defects (OCDs). METHODS: Twenty consecutive patients were prospectively studied. All patients had an OCD of the talar dome and had a preoperative CT scan of the affected ankle in maximum plantar flexion. Accessibility of the OCD was defined by the distance between the anterior border of the OCD and the anterior distal tibial rim. This distance was measured on sagittal CT reconstructions by 2 investigators. The reference standard was the distance between the same landmarks measured during anterior ankle arthroscopy by an orthopaedic surgeon blinded to the CT scans. Intraobserver and interobserver reliability of CT, as well as the correlation and agreement between CT and arthroscopy, were calculated. RESULTS: The measured distance between the anterior border of the OCD and the anterior distal tibial rim ranged from -3.1 to 9.1 mm on CT and from -3.0 to 8.5 mm on arthroscopy. The intraobserver and interobserver reliability of the measurements made on CT scans (intraclass correlation coefficients >0.99, P < .001), as well as the correlation between CT and arthroscopy, were excellent (r = 0.98, P < .001). CONCLUSIONS: Measurements on CT scans of the ankle in full plantar flexion are a reliable and accurate preoperative method to determine the in situ arthroscopic location of talar OCDs.

Is technique performance a prognostic factor in bone marrow stimulation of the talus?

Although results of bone marrow stimulation in osteochondral defects of the talus (OCLT) have been satisfactory, the technique performance has not yet been subjected to review as a prognostic factor. The aim of this systematic review is to determine whether variation within technique influences outcome of bone marrow stimulation for OCLT. Electronic databases were searched for articles on OCLT treated with bone marrow stimulation techniques, providing a technique description. Six articles on microfracture were included (198 patients). Lesion size averaged 0.9 cm (2) to 4.5 cm (2), and follow-up varied from 2 to 6 years. Key elements were removal of unstable cartilage, hole depth variation between 2 and 4 mm until bleeding or fat droplets occurred, and a distance between the created holes of 3 to 4 mm. The success rate (excellent/good results by any clinical outcome score) was 81%. There is a vast similarity in the technique with similar outcomes as in previous general reviews; therefore variation in technique as currently described in the literature does not seem to influence the outcome of bone marrow stimulation for OCLT. Whether the instruments used or the hole depth and geometry influence clinical outcome remains to be determined. Microfracture is safe and effective for OCLTs smaller than 15 mm. However, in this review, only 81% of patients obtained satisfactory results. Larger clinical trials are needed with clearly defined patient groups, technique descriptions, and reproducible outcome measures to provide insight in the specific indications and the preferred technique of bone marrow stimulation.

Automated 3D Sampling and Imaging of Uneven Sample Surfaces with LA-REIMS.

The analysis of samples with large height variations remains a challenge for mass spectrometry imaging (MSI), despite many technological advantages. Ambient sampling and ionization MS techniques allow for the molecular analysis of sample surfaces with height variations, but most techniques lack MSI capabilities. We developed a 3D MS scanner for the automated sampling and imaging of a 3D surface with laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS). The sample is moved automatically with a constant distance between the laser probe and sample surface in the 3D MS Scanner. The topography of the surface was scanned with a laser point distance sensor to define the MS measurement points. MS acquisition was performed with LA-REIMS using a surgical CO2 laser coupled to a qTOF instrument. The topographical scan and MS acquisition can be completed within 1 h using the 3D MS scanner for 300 measurement points on uneven samples with a spatial resolution of 2 mm in the top view, corresponding to 22.04 cm2. Comparison between the automated acquisition with the 3D MS scanner and manual acquisition by hand showed that the automation resulted in increased reproducibility between the measurement points. 3D visualizations of molecular distributions related to structural differences were shown for an apple, a marrowbone, and a human femoral head to demonstrate the imaging feasibility of the system. The developed 3D MS scanner allows for the automated sampling of surfaces with uneven topographies with LA-REIMS, which can be used for the 3D visualization of molecular distributions of these surfaces.

Translation of 3D Anatomy to 2D Radiographic Angle Measurements in the Ankle Joint: Validity and Reliability.

Background: The objective consisted of 2 elements, primarily to define 2 bone geometry variations of the ankle that may be of prognostic value on ankle instability and secondly to translate these bone variations from a 3D model to a simple 2D radiographic measurement for clinical use. Methods: The 3D tibial and talar shape differences derived from earlier studies were translated to two 2D radiographic parameters: the medial malleolar height angle (MMHA) and talar convexity angle (TCA) respectively to ensure clinical use. To assess validity, the MMHA and TCA were measured on 3D polygons derived from lower leg computed tomographic (CT) scans and 2D digitally reconstructed radiographs (DRRs) of these polygons. To assess reliability, the MMHA and TCA were measured on standard radiographs by 2 observers calculating the intraclass correlation coefficient (ICC). Results: The 3D angle measurements on the polygons showed substantial to excellent agreement with the 2D measurements on DRR for both the MMHA (ICC 0.84-0.93) and TCA (ICC 0.88-0.96). The interobserver reliability was moderate with an ICC of 0.58 and an ICC of 0.64 for both the MMHA and TCA, respectively. The intraobserver reliability was excellent with an ICC of 0.96 and 0.97 for the MMHA and the TCA, respectively. Conclusion: Two newly defined radiographic parameters (MMHA and TCA) are valid and can be assessed with excellent intraobserver reliability on standard radiographs. The interobserver reliability was moderate and indicates training is required to ensure uniformity in measurement technique. The current method may be used to translate more variations in bone shape prior to implementation in clinical practice. Level of Evidence: Level III, cohort study.