Measurement of auricle parameters for planning and post-operative evaluation presents substantial challenges due to the complex 3D structure of the human auricle. Traditional measurement methods rely ...on manual techniques, resulting in limited precision. This study introduces a novel automated surface-based three-dimensional measurement method for quantifying human auricle parameters. The method was applied to virtual auricles reconstructed from Computed Tomography (CT) scans of a cadaver head and subsequent measurement of important clinically relevant aesthetical auricular parameters (length, width, protrusion, position, auriculocephalic angle, and inclination angle). Reference measurements were done manually (using a caliper and using a 3D landmarking method) and measurement precision was compared to the automated method. The CT scans were performed using both a contemporary high-end and a low-end CT scanner. Scans were conducted at a standard scanning dose, and at half the dose. The automatic method demonstrated significantly higher precision in measuring auricle parameters compared to manual methods. Compared to traditional manual measurements, precision improved for auricle length (9×), width (5×), protrusion (5×), Auriculocephalic Angle (5-54×) and posteroanterior position (23×). Concerning parameters without comparison with a manual method, the precision level of supero-inferior position was 0.489 mm; and the precisions of the inclination angle measurements were 1.365 mm and 0.237 mm for the two automated methods investigated. Improved precision of measuring auricle parameters was associated with using the high-end scanner. A higher dose was only associated with a higher precision for the left auricle length. The findings of this study emphasize the advantage of automated surface-based auricle measurements, showcasing improved precision compared to traditional methods. This novel algorithm has the potential to enhance auricle reconstruction and other applications in plastic surgery, offering a promising avenue for future research and clinical application.
Abstract
An oblique double-cut rotation osteotomy (ODCRO) enables correcting a complex bone deformation by aligning, in 3D, the distal, middle and proximal bone segments with a target bone, without ...intersegmental gaps. We propose virtual preoperative planning of an ODCRO. To minimize a residual translation error, we use an optimization algorithm and optimize towards bone length, alignment in the transverse direction, or a balanced reconstruction. We compare the residual alignment error with an oblique single-cut rotation osteotomy using 15 complex bone deformations. The single-cut approach was not feasible in 5 cases, whereas the ODCRO procedure was feasible in all cases. The residual alignment error was smaller for the ODCRO than for the single-cut approach except for one case. In a subset for length reconstruction, the length error of 7.3–21.3 mm was restored to 0.0 mm in 4 of 5 cases, although at the cost of an increased transverse translation. The proposed method renders planning an ODCRO feasible and helps restoring bone alignment and lengthening better than an oblique single-cut rotation osteotomy. Awareness of the challenges and possibilities in preoperative planning of an ODCRO will be of value for future alignment surgery and for patients.
Movement of skin markers with respect to their underlying bone (i.e. soft tissue artifacts (STAs)) might corrupt the accuracy of marker-based movement analyses. This study aims to quantify STAs in 3D ...for foot markers and their effect on multi-segment foot kinematics as calculated by the Oxford and Rizzoli Foot Models (OFM, RFM). Fifteen subjects with asymptomatic feet were seated on a custom-made loading device on a computed tomography (CT) table, with a combined OFM and RFM marker set on their right foot. One unloaded reference CT-scan with neutral foot position was performed, followed by 9 loaded CT-scans at different foot positions. The 3D-displacement (i.e. STA) of each marker in the underlying bone coordinate system between the reference scan and other scans was calculated. Subsequently, segment orientations and joint angles were calculated from the marker positions according to OFM and RFM definitions with and without STAs. The differences in degrees were defined as the errors caused by the marker displacements. Markers on the lateral malleolus and proximally on the posterior aspect of the calcaneus showed the largest STAs. The hindfoot-shank joint angle was most affected by STAs in the most extreme foot position (40° plantar flexion) in the sagittal plane for RFM (mean: 6.7°, max: 11.8°) and the transverse plane for OFM (mean: 3.9°, max: 6.8°). This study showed that STAs introduce clinically relevant errors in multi-segment foot kinematics. Moreover, it identified marker locations that are most affected by STAs, suggesting that their use within multi-segment foot models should be reconsidered.
The process of reticulocyte maturation into fully mature erythrocytes that occurs in circulation is known to be characterised by a complex interplay between loss of cell surface area and volume, ...removal of remnant cell organelles and redundant proteins, and highly selective membrane and cytoskeletal remodelling. However, the mechanisms that underlie and drive these maturational processes in vivo are currently poorly understood and, at present, reticulocytes derived through in vitro culture fail to undergo the final transition to erythrocytes. Here, we use high-throughput proteomic methods to highlight differences between erythrocytes, cultured and endogenous reticulocytes. We identify a cytoskeletal protein, non-muscle myosin IIA (NMIIA) as exhibiting differential abundance and phosphorylation status between reticulocytes and erythrocytes and localize it in the proximity of autophagosomal vesicles. An ex vivo circulation system was developed to simulate the mechanical shear component of circulation and demonstrated that mechanical stimulus is necessary, but insufficient for reticulocyte maturation. Using this system in concurrence with NMII inhibition, we demonstrate involvement of NMIIA in reticulocyte remodelling and propose a previously undescribed mechanism of shear stress-responsive vesicle clearance that is crucial for reticulocyte maturation.
Regular blood transfusion is the cornerstone of care for patients with red blood cell (RBC) disorders such as thalassaemia or sickle‐cell disease. With repeated transfusion, alloimmunisation often ...occurs due to incompatibility at the level of minor blood group antigens. We use CRISPR‐mediated genome editing of an immortalised human erythroblast cell line (BEL‐A) to generate multiple enucleation competent cell lines deficient in individual blood groups. Edits are combined to generate a single cell line deficient in multiple antigens responsible for the most common transfusion incompatibilities: ABO (Bombay phenotype), Rh (Rhnull), Kell (K0), Duffy (Fynull), GPB (S−s−U−). These cells can be differentiated to generate deformable reticulocytes, illustrating the capacity for coexistence of multiple rare blood group antigen null phenotypes. This study provides the first proof‐of‐principle demonstration of combinatorial CRISPR‐mediated blood group gene editing to generate customisable or multi‐compatible RBCs for diagnostic reagents or recipients with complicated matching requirements.
Synopsis
CRISPR–Cas9‐mediated genome editing of immortalised erythroblasts is a viable approach to the generation of functional in vitro derived reticulocytes with customised depletion of antigenic blood group proteins that could ultimately facilitate transfusion of patients with unmet clinical needs.
Sustainable immortalised erythroblast lines depleted for individual blood groups can be generated using CRISPR–Cas9 gene editing for serological diagnostics.
Multiple blood group genes can be knocked out to generate multi‐compatible RBCs with future potential to service the unmet clinical transfusion needs of patients with complicated matching requirements.
Five blood group null phenotypes are able to coexist in differentiating erythroblasts for the generation of functional reticulocytes.
CRISPR–Cas9‐mediated genome editing of immortalised erythroblasts is a viable approach to the generation of functional in vitro derived reticulocytes with customised depletion of antigenic blood group proteins that could ultimately facilitate transfusion of patients with unmet clinical needs.
Weight bearing CT (WBCT) of the lower extremity is gaining momentum in evaluation of the foot/ankle and knee. A growing number of international studies use WBCT, which is promising for improving our ...understanding of anatomy and biomechanics during natural loading of the lower extremity. However, we believe there is risk of excessive enthusiasm for WBCT leading to premature application of the technique, before sufficiently robust protocols are in place e.g. standardised limb positioning and imaging planes, choice of anatomical landmarks and image slices used for individual measurements. Lack of standardisation could limit benefits from introducing WBCT in research and clinical practice because useful imaging information could become obscured. Measurements of bones and joints on WBCT are influenced by joint positioning and magnitude of loading, factors that need to be considered within a 3-D coordinate system. A proportion of WBCT studies examine inter- and intraobserver reproducibility for different radiological measurements in the knee or foot with reproducibility generally reported to be high. However, investigations of test–retest reproducibility are still lacking. Thus, the current ability to evaluate, e.g. the effects of surgery or structural disease progression, is questionable. This paper presents an overview of the relevant literature on WBCT in the lower extremity with an emphasis on factors that may affect measurement reproducibility in the foot/ankle and knee. We discuss the caveats of performing WBCT without consensus on imaging procedures and measurements.
For wrist complaints related to motion, a 2-D radiograph or CT scan of the static wrist may not always be considered diagnostic. 3-D motion imaging, i.e., multiple 3DCT scans in time (4DCT), enables ...quantifying carpal motion and comparing motion patterns of the affected wrist with those of the healthy contralateral side. The accuracy and precision of the method, however, is limited by noise and motion artifacts. Although, the technique is considered promising in existing literature, the accuracy and precision of carpal motion analysis has never been investigated systematically. In this paper, we introduce and evaluate a semi-automatic segmentation- and registration-based method for 3-D carpal motion analysis. We investigate the accuracy and precision of the method, and its dependency on motion and scan parameters (angular velocity, dose, gantry revolution angle for image reconstruction, and scanner type) using a wrist phantom. During standstill the positioning error was ≤ 0.23 mm and ≤ 0.78°. A partial gantry revolution for 3-D reconstruction introduced image deformation, contributing to a positioning error of approx. 0.8 mm. This error increased with reduced dose, and with increasing angular velocity of the wrist phantom. In cases where the phantom was rotating about an axis parallel to the rotation axis of the gantry, and in a direction opposite to the gantry, the positioning error increased, probably because of the apparent increase in angular velocity with respect to the gantry. Slow carpal motion 4DCT analysis is feasible using a regular CT scanner. A partial gantry revolution angle for 3-D reconstruction may introduce image deformation, which decreases the accuracy of carpal motion analysis. Knowing the positioning error in 4DCT imaging with the proposed method is considered valuable when investigating wrist injury since it enables discrimination of actual motion from apparent motion caused by methodological error.
Background:
The detection and localization of electrophysiological substrates currently involve invasive cardiac mapping. Electrocardiographic imaging (ECGI) using the equivalent dipole layer (EDL) ...method allows the noninvasive estimation of endocardial and epicardial activation and repolarization times (AT and RT), but the RT validation is limited to
in silico
studies. We aimed to assess the temporal and spatial accuracy of the EDL method in reconstructing the RTs from the surface ECG under physiological circumstances and situations with artificially induced increased repolarization heterogeneity.
Methods:
In four Langendorff-perfused pig hearts, we simultaneously recorded unipolar electrograms from plunge needles and pseudo-ECGs from a volume-conducting container equipped with 61 electrodes. The RTs were computed from the ECGs during atrial and ventricular pacing and compared with those measured from the local unipolar electrograms. Regional RT prolongation (cooling) or shortening (pinacidil) was achieved by selective perfusion of the left anterior descending artery (LAD) region.
Results:
The differences between the computed and measured RTs were 19.0 ± 17.8 and 18.6 ± 13.7 ms for atrial and ventricular paced beats, respectively. The region of artificially delayed or shortened repolarization was correctly identified, with minimum/maximum RT roughly in the center of the region in three hearts. In one heart, the reconstructed region was shifted by ~2.5 cm. The total absolute difference between the measured and calculated RTs for all analyzed patterns in selectively perfused hearts (
n
= 5) was 39.6 ± 27.1 ms.
Conclusion:
The noninvasive ECG repolarization imaging using the EDL method of atrial and ventricular paced beats allows adequate quantitative reconstruction of regions of altered repolarization.
In unstable shoulders, excessive anteroinferior position of the humeral head relative to the glenoid can lead to a dislocation. Measuring humeral head position could therefore be valuable in ...quantifying shoulder laxity. The aim of this study was to measure (1) position of the humeral head relative to the glenoid and (2) joint space thickness during passive motion in unstable shoulders caused by traumatic anterior dislocations and in contralateral uninjured shoulders. A prospective cross-sectional CT-study was performed in patients with unilateral anterior shoulder instability. Patients underwent CT scanning of both injured and uninjured side in supine position (0° abduction and 0° external rotation) and in 60°, 90°, and 120° of abduction with 90° of external rotation without an external load. Subsequently, 3D virtual models were created of the humerus and the scapula to create a glenoid coordinate system to identify poster-anterior, inferior-superior, and lateral-medial position of the humeral head relative to the glenoid. Joint space thickness was defined as the average distance between the subchondral bone surfaces of the humeral head and glenoid. Fifteen consecutive patients were included. In supine position, the humeral head was positioned more anteriorly (p = 0.004), inferiorly (p = 0.019), and laterally (p = 0.021) in the injured compared to the uninjured shoulder. No differences were observed in any of the other positions. A joint-space thickness map, showing the bone-to-bone distances, identified the Hill-Sachs lesion footprint on the glenoid surface in external rotation and abduction, but no differences on average joint space thickness were observed in any position.