Rapid automatic assessment of microvascular density in sidestream dark field images

The purpose of this study was to develop a rapid and fully automatic method for the assessment of microvascular density and perfusion in sidestream dark field (SDF) images. We modified algorithms previously developed by our group for microvascular density assessment and introduced a new method for microvascular perfusion assessment. To validate the new algorithm for microvascular density assessment, we reanalyzed a selection of SDF video clips (n = 325) from a study in intensive care patients and compared the results to (semi-)manually found microvascular densities. The method for microvascular perfusion assessment (temporal SDF image contrast analysis, tSICA) was tested in several video simulations and in one high quality SDF video clip where the microcirculation was imaged before and during circulatory arrest in a cardiac surgery patient. We found that the new method for microvascular density assessment was very rapid (<30 s/clip) and correlated excellently with (semi-)manually measured microvascular density. The new method for microvascular perfusion assessment (tSICA) was shown to be limited by high cell densities and velocities, which severely impedes the applicability of this method in real SDF images. Hence, here we present a validated method for rapid and fully automatic assessment of microvascular density in SDF images. The new method was shown to be much faster than the conventional (semi-)manual method. Due to current SDF imaging hardware limitations, we were not able to automatically detect microvascular perfusion

Enhancement of red blood cell transfusion compatibility using CRISPR‐mediated erythroblast gene editing

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

Corrective osteotomy in symptomatic clavicular malunion using computer-assisted 3-D planning and patient-specific surgical guides

Surgical correction of a symptomatic clavicular malunion requires simultaneous adjustment of the translation as well as the rotation in multiple planes. We describe a corrective osteotomy for a clavicle malunion using 3-D computer assisted preoperative-planning combined with patient-specific surgical guides, along with the benefits and disadvantages of this approach. This method enabled quantifying the malunion by comparing the malunited bone with the normal contralateral clavicle as a template. The postoperative results were encouraging with symmetrical shoulder anatomy and functional improvement. Therefore, we recommend this technique in patients with a symptomatic clavicle malunion, as it allows successful correction of the deformity

Minimizing the translation error in the application of an oblique single-cut rotation osteotomy: Where to cut?

An oblique single cut rotation osteotomy enables correcting angular bone alignment in the coronal, sagittal and transverse planes, with just a single oblique osteotomy, and by rotating one bone segment in the osteotomy plane. However, translational malalignment is likely to exist if the bone is curved or deformed and the location of the oblique osteotomy is not obvious. In this paper we investigate how translational malalignment depends on the osteotomy location. We further propose and evaluate by simulation in 3-D, a method that minimizes translational malalignment by varying the osteotomy location and by sliding the distal bone segment with respect to the proximal bone segment within the oblique osteotomy plane. The method is finally compared to what three surgeons achieve by manually selecting the osteotomy location in 3-D virtual space without planning in-plane translations. The minimization method optimized for length better than the surgeons did, by 3.2 mm on average, range [0.1, 9.4] mm, in 82% of the cases. A better translation in the axial plane was achieved by 4.1 mm on average, range [0.3, 14.4] mm, in 77% of the cases. The proposed method generally performs better than subjectively choosing an osteotomy position along the bone axis. The proposed method is considered a valuable tool for future alignment planning of an oblique single-cut rotation osteotomy since it helps minimizing translational malalignmen

Positioning evaluation of corrective osteotomy for the malunited radius: 3-D CT versus 2-D radiographs

The authors retrospectively investigated the postoperative position of the distal radius after a corrective osteotomy using 2-dimensional (2-D) and 3-dimensional (3-D) imaging techniques to determine whether malposition correlates with clinical outcome. Twenty-five patients who underwent a corrective osteotomy were available for follow-up. The residual positioning errors of the distal end were determined retrospectively using standard 2-D radiographs and 3-D computed tomography evaluations based on a scan of both forearms, with the contralateral healthy radius serving as reference. For 3-D analysis, use of an anatomical coordinate system for each reference bone allowed the authors to express the residual malalignment parameters in displacements (Δx, Δy, Δz) and rotations (Δφx, Δφy, Δφz) for aligning the affected bone in a standardized way with the corresponding reference bone. The authors investigated possible correlations between malalignment parameters and clinical outcome using patients' questionnaires. Two-dimensional radiographic evaluation showed a radial inclination of 24.9°±6.8°, a palmar tilt of 4.5°±8.6°, and an ulnar variance of 0.8±1.7 mm. With 3-D analysis, residual displacements were 2.6±3 (Δx), 2.4±3 (Δy), and -2.2±4 (Δz) mm. Residual rotations were -6.2°±10° (Δφx), 0.3°±7° (Δφy), and -5.1°±10° (Δφz). The large standard deviation is indicative of persistent malalignment in individual cases. Statistically significant correlations were found between 3-D rotational deficits and clinical outcome but not between 2-D evaluation parameters. Considerable residual malalignments and statistically significant correlations between malalignment parameters and clinical outcome confirm the need for better positioning technique

Computerized fetal cardiotocography analysis in early preterm fetal growth restriction - A quantitative comparison of two applications

We developed an open-source software for the computerized analysis of antenatal fetal cardiotocography (CTG) without limitation of duration of the registration, enabling batch processing and adaptation to any digital storage system. STVcalc was developed based on literature about the FetalCare system (Huntleigh Healthcare Ltd, Cardiff, UK). For comparison with FetalCare, we selected the CTGs of all women who delivered in 2011 a small-for-gestational-age (SGA) fetus between 24 and 31 weeks by cesarean section (CS) for fetal distress, or had fetal death, before labor onset. In 471 CTGs from 39 women, the agreement was 99% for a short-term variation (STV) cut-off of 2.6 ms below 29 weeks and 3.0 ms thereafter, and 95% for 3.5 and 4.0 ms, respectively. In 18 (4%) cases, the proportional difference in STV between FetalCare and STVcalc was more than 10%. As only slight differences were observed between the proposed feature-rich application and the FetalCare system, it can be considered valuable for clinical practice and research purposes

Quantitative three-dimensional assessment of Madelung deformity

In the diagnostic work-up of Madelung deformity conventional radiographic imaging is often used, assessing the three-dimensional deformity in a two-dimensional manner. A three-dimensional approach could expand our understanding of Madelung deformity's complex wrist anatomy, while removing inter- and intra-rater differences. We measured previous two-dimensional-based and newly developed three-dimensional-based parameters in 18 patients with Madelung deformity (28 wrists) and 35 healthy participants (56 wrists). Madelung deformity wrists have increased levels of ulnar tilt, lunate subsidence, lunate fossa angle, and palmar carpal displacement. The lunate fossa is more concave and irregular, and angles between scaphoid, lunate, and triquetral bones are decreased. These findings validate the underlying principles of current two-dimensional criteria and reveal previously unknown anatomical abnormalities by utilizing novel three-dimensional parameters to quantify the radiocarpal joint