MGMT ProFWise: Unlocking a New Application for Combined Feature Selection and the Rank-Based Weighting Method to Link MGMT Methylation Status to Serum Protein Expression in Patients with Glioblastoma.

Glioblastoma (GBM) is a fatal brain tumor with limited treatment options. O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is the central molecular biomarker linked to both the response to temozolomide, the standard chemotherapy drug employed for GBM, and to patient survival. However, MGMT status is captured on tumor tissue which, given the difficulty in acquisition, limits the use of this molecular feature for treatment monitoring. MGMT protein expression levels may offer additional insights into the mechanistic understanding of MGMT but, currently, they correlate poorly to promoter methylation. The difficulty of acquiring tumor tissue for MGMT testing drives the need for non-invasive methods to predict MGMT status. Feature selection aims to identify the most informative features to build accurate and interpretable prediction models. This study explores the new application of a combined feature selection (i.e., LASSO and mRMR) and the rank-based weighting method (i.e., MGMT ProFWise) to non-invasively link MGMT promoter methylation status and serum protein expression in patients with GBM. Our method provides promising results, reducing dimensionality (by more than 95%) when employed on two large-scale proteomic datasets (7k SomaScan® panel and CPTAC) for all our analyses. The computational results indicate that the proposed approach provides 14 shared serum biomarkers that may be helpful for diagnostic, prognostic, and/or predictive operations for GBM-related processes, given further validation.

Impact of late gadolinium enhancement image acquisition resolution on neural network based automatic scar segmentation.

BACKGROUND: Automatic myocardial scar segmentation from late gadolinium enhancement (LGE) images using neural networks promises an alternative to time-consuming and observer-dependent semi-automatic approaches. However, alterations in data acquisition, reconstruction as well as post-processing may compromise network performance. The objective of the present work was to systematically assess network performance degradation due to a mismatch of point-spread function between training and testing data. METHODS: Thirty-six high-resolution (0.7×0.7×2.0 mm3) LGE k-space datasets were acquired post-mortem in porcine models of myocardial infarction. The in-plane point-spread function and hence in-plane resolution Δx was retrospectively degraded using k-space lowpass filtering, while field-of-view and matrix size were kept constant. Manual segmentation of the left ventricle (LV) and healthy remote myocardium was performed to quantify location and area (% of myocardium) of scar by thresholding (≥ SD5 above remote). Three standard U-Nets were trained on training resolutions Δxtrain = 0.7, 1.2 and 1.7 mm to predict endo- and epicardial borders of LV myocardium and scar. The scar prediction of the three networks for varying test resolutions (Δxtest = 0.7 to 1.7 mm) was compared against the reference SD5 thresholding at 0.7 mm. Finally, a fourth network trained on a combination of resolutions (Δxtrain = 0.7 to 1.7 mm) was tested. RESULTS: The prediction of relative scar areas showed the highest precision when the resolution of the test data was identical to or close to the resolution used during training. The median fractional scar errors and precisions (IQR) from networks trained and tested on the same resolution were 0.0 percentage points (p.p.) (1.24 - 1.45), and - 0.5 - 0.0 p.p. (2.00 - 3.25) for networks trained and tested on the most differing resolutions, respectively. Deploying the network trained on multiple resolutions resulted in reduced resolution dependency with median scar errors and IQRs of 0.0 p.p. (1.24 - 1.69) for all investigated test resolutions. CONCLUSION: A mismatch of the imaging point-spread function between training and test data can lead to degradation of scar segmentation when using current U-Net architectures as demonstrated on LGE porcine myocardial infarction data. Training networks on multi-resolution data can alleviate the resolution dependency.

The impact of femoral head size on the wear evolution at contacting surfaces of total hip prostheses: A finite element analysis.

Total Hip Arthroplasty has been a revolutionary technique in restoring mobility to patients with damaged hip joints. The introduction of modular components of the hip prosthesis allowed for bespoke solutions based on the requirements of the patient. The femoral stem is designed with a conical trunnion to allow for assembly of different femoral head sizes based on surgical requirements. The femoral head diameters for a metal-on-polyethylene hip prosthesis have typically ranged between 22 mm and 36 mm and are typically manufactured using Cobalt-Chromium alloy. A smaller femoral head diameter is associated with lower wear of the polyethylene, however, there is a higher risk of dislocation. In this study, a finite element model of a standard commercial hip arthroplasty prosthesis was modelled with femoral head diameters ranging from 22 mm to 36 mm to investigate the wear evolution and material loss at both contacting surfaces (acetabular cup and femoral stem trunnion). The finite element model, coupled with a validated in-house wear algorithm modelled a human walking for 10 million steps. The results have shown that as the femoral head size increased, the amount of wear on all contacting surfaces increased. As the femoral head diameter increased from 22 mm to 36 mm, the highly cross-linked polyethylene (XLPE) volumetric wear increased by 61% from 98.6 mm3 to 159.5 mm3 while the femoral head taper surface volumetric wear increased by 21% from 4.18 mm3 to 4.95 mm3. This study has provided an insight into the amount of increased wear as the femoral head size increased which can highlight the life span of these prostheses in the human body.

Trivial aortic valve regurgitation in children and adolescents with structurally normal hearts: physiologic or pathologic?

BACKGROUND: Trivial regurgitation from a normal aortic valve is rarely seen in healthy children and adolescents. The aim of this study was to evaluate timing of presentation, associated conditions, and medium-term prognosis of this incidental finding. METHODS: Paediatric patients observed to have trivial aortic valve regurgitation with otherwise normal echocardiograms were retrospectively analysed. Clinical and echocardiographic parameters were measured and categorised on presentation and follow-up. RESULTS: Sixty patients (39 males) were identified over a 13-year period. Age at presentation was 14.8 years (IQR 12.9-16.0), height z-score was + 0.71 (95% CI + 0.48- + 0.94), and body mass index z-score was + 0.66 (95% CI + 0.40- + 0.92). Median aortic regurgitation vena contracta diameter was 1.0 mm (IQR 0.8-1.3). Aortic valve strands were visualised in 28% and physiologic mitral regurgitation in 32%. Aortic annulus, sinotubular junction, and mid-ascending aorta diameters were normal, and mean aortic sinus diameter was only slightly increased (z-score + 0.23, 95% CI + 0.02- + 0.44). Follow-up data were obtained in 36 patients from 1 to 6.7 years later (median 2.1). Aortic regurgitation was no longer detectable in 28%, and none exhibited worsening. Mitral regurgitation prevalence was lower in those with aortic regurgitation resolution versus persistence (10% versus 50%, p = 0.03). CONCLUSIONS: Trivial aortic regurgitation in paediatric patients with normal hearts is more common in adolescents and is associated with an increased prevalence of aortic valve strands and physiologic mitral regurgitation. These findings do not worsen during growth and may resolve consistent with being physiologic rather than pathologic.

Impingement-related osteolysis in Motec total wrist arthroplasty: an explant analysis and review of the literature.

We present five cases of osteolysis in the Motec total wrist prosthesis, three around the radial implant, one around the metacarpal implant and one around both. Three of these were progressive and required revision, and biomechanical explant analyses of these revised prostheses were performed. Ex vivo testing of the contact points of the Motec implants was also performed at maximum extension. Here, impingement occurs between the metacarpal screw and the dorsal rim of the cup (non-articulating surfaces) with the short-necked prosthesis, leading to metacarpal screw damage, titanium debris formation and osteolysis. An analysis of three previously published cases suggests that this may have been the likely mode of failure in those cases. This complication is preventable by avoiding use of the short-neck prosthesis.Level of evidence: IV.

Long-term results and explant analysis of the ReMotion total wrist arthroplasty.

The ReMotion wrist replacement has good short- to medium-term survival with an acceptable complication profile as we previously reported in a cohort of patients with rheumatoid arthritis. We now report the long-term results of the same cohort and details of explant analysis of revisions undertaken for aseptic loosening. A total of 16 wrists were reviewed. Seven prostheses remain in situ with no obvious signs of wear or radiological loosening at a mean follow-up of 15.5 years. Three wrists had been revised: one for infection and two for aseptic loosening. Five patients (six wrists) died 2-9 years after operation from unrelated causes. Explant analysis demonstrated relatively minor wear compared with the published results of the Universal-2 prosthesis. We hypothesize that this may be explained by differences in polyethylene sterilization and prosthetic design. The ReMotion wrist replacement has favourable long-term results in patients with rheumatoid arthritis with a 16-year survival rate of 78%-86%.Level of evidence: IV.

An Overview of CD133 as a Functional Unit of Prognosis and Treatment Resistance in Glioblastoma.

Biomarkers for resistance in Glioblastoma multiforme (GBM) are lacking, and progress in the clinic has been slow to arrive. CD133 (prominin-1) is a membrane-bound glycoprotein on the surface of cancer stem cells (CSCs) that has been associated with poor prognosis, therapy resistance, and tumor recurrence in GBM. Due to its connection to CSCs, to which tumor resistance and recurrence have been partially attributed in GBM, there is a growing field of research revolving around the potential role of CD133 in each of these processes. However, despite encouraging results in vitro and in vivo, the biological interplay of CD133 with these components is still unclear, causing a lack of clinical application. In parallel, omic data from biospecimens that include CD133 are beginning to emerge, increasing the importance of understanding CD133 for the effective use of these highly dimensional data sets. Given the significant mechanistic overlap, prioritization of the most robust findings is necessary to optimize the transition of CD133 to clinical applications using patient-derived biospecimens. As a result, this review aims to compile and analyze the current research regarding CD133 as a functional unit in GBM, exploring its connections to prognosis, the tumor microenvironment, tumor resistance, and tumor recurrence.

Multi-functional bioactive silver- and copper-doped diamond-like carbon coatings for medical implants.

Diamond-like carbon (DLC) coatings doped with bioactive elements of silver (Ag) and copper (Cu) have been receiving increasing attention in the last decade, particularly in the last 5 years, due to their potential to offer a combination of enhanced antimicrobial and mechanical performance. These multi-functional bioactive DLC coatings offer great potential to impart the next generation of load-bearing medical implants with improved wear resistance and strong potency against microbial infections. This review begins with an overview of the status and issues with current total joint implant materials and the state-of-the art in DLC coatings and their application to medical implants. A detailed discussion of recent advances in wear resistant bioactive DLC coatings is then presented with a focus on doping the DLC matrix with controlled quantities of Ag and Cu elements. It is shown that both Ag and Cu doping can impart strong antimicrobial potency against a range of Gram-positive and Gram-negative bacteria, but this is always accompanied so far by a reduction in mechanical performance of the DLC coating matrix. The article concludes with discussion of potential synthesis methods to accurately control bioactive element doping without jeopardising mechanical properties and gives an outlook to the potential long-term impact of developing a superior multifunctional bioactive DLC coating on implant device performance and patient health and wellbeing. STATEMENT OF SIGNIFICANCE: Multi-functional diamond-like carbon (DLC) coatings doped with bioactive elements of silver (Ag) and copper (Cu) offer great potential to impart the next generation of load-bearing medical implants with improved wear resistance and strong potency against microbial infections. This article provides a critical review of the state-of-the-art in Ag and Cu doped DLC coatings, beginning with an overview of the current applications of DLC coatings in implant technology followed by a detailed discussion of Ag/Cu doped DLC coatings with particular focus on the relationship between their mechanical and antimicrobial performance. Finally, it ends with a discussion on the potential long-term impact of developing a truly multifunctional ultra-hard wearing bioactive DLC coating to extend the lifetime of total joint implants.

Metal debris release is commonly seen from explanted total ankle replacements.

This study aimed to characterise the damage mechanisms present on the metal components used in various contemporary total ankle replacements. Twenty-seven explanted total ankle replacements comprising 8 different designs (3 fixed bearing and 5 mobile bearing) were analysed using various explant analysis techniques. Pitting and scratching were the most commonly observed wear features. Microscopic analysis revealed metallic pitting on 52% of tibial components and 95% of talar components. Pitting was identified on more cobalt-chromium than titanium alloy tibial components (63% versus 0%). Non-contact profilometry confirmed the presence of pitting, with significant (p < 0.05) differences in the measured average surface roughness values of pitted and unpitted areas for tibial and talar components. There was macroscopically visible sliding plane scratching, indicating the presence of hard third body particles, on 78% of talar components. Changes to the non-articulating surfaces coatings in terms of coating loss and/or changes in reflectivity was identified visually on 80% of metal components. Scanning electron microscopy with energy dispersive X-ray spectroscopy identified metallic embedded debris in 19% of polyethylene inserts. This explant study demonstrates the release of metal debris from both the metallic tibial and talar component articulating surfaces and non-articulating surface coatings of various contemporary total ankle replacements. Metal particulate debris release from total ankle replacements may be more common than previously recognised. Metal debris should be considered in further study into the aetiology of failed total ankle arthroplasty.

MRXCAT2.0: Synthesis of realistic numerical phantoms by combining left-ventricular shape learning, biophysical simulations and tissue texture generation.

BACKGROUND: Standardised performance assessment of image acquisition, reconstruction and processing methods is limited by the absence of images paired with ground truth reference values. To this end, we propose MRXCAT2.0 to generate synthetic data, covering healthy and pathological function, using a biophysical model. We exemplify the approach by generating cardiovascular magnetic resonance (CMR) images of healthy, infarcted, dilated and hypertrophic left-ventricular (LV) function. METHOD: In MRXCAT2.0, the XCAT torso phantom is coupled with a statistical shape model, describing population (patho)physiological variability, and a biophysical model, providing known and detailed functional ground truth of LV morphology and function. CMR balanced steady-state free precession images are generated using MRXCAT2.0 while realistic image appearance is ensured by assigning texturized tissue properties to the phantom labels. FINDING: Paired CMR image and ground truth data of LV function were generated with a range of LV masses (85-140 g), ejection fractions (34-51%) and peak radial and circumferential strains (0.45 to 0.95 and - 0.18 to - 0.13, respectively). These ranges cover healthy and pathological cases, including infarction, dilated and hypertrophic cardiomyopathy. The generation of the anatomy takes a few seconds and it improves on current state-of-the-art models where the pathological representation is not explicitly addressed. For the full simulation framework, the biophysical models require approximately two hours, while image generation requires a few minutes per slice. CONCLUSION: MRXCAT2.0 offers synthesis of realistic images embedding population-based anatomical and functional variability and associated ground truth parameters to facilitate a standardized assessment of CMR acquisition, reconstruction and processing methods.

In Vivo CaV3 Channel Inhibition Promotes Maturation of Glucose-Dependent Ca2+ Signaling in Human iPSC-Islets.

CaV3 channels are ontogenetically downregulated with the maturation of certain electrically excitable cells, including pancreatic ß cells. Abnormally exaggerated CaV3 channels drive the dedifferentiation of mature ß cells. This led us to question whether excessive CaV3 channels, retained mistakenly in engineered human-induced pluripotent stem cell-derived islet (hiPSC-islet) cells, act as an obstacle to hiPSC-islet maturation. We addressed this question by using the anterior chamber of the eye (ACE) of immunodeficient mice as a site for recapitulation of in vivo hiPSC-islet maturation in combination with intravitreal drug infusion, intravital microimaging, measurements of cytoplasmic-free Ca2+ concentration ([Ca2+]i) and patch clamp analysis. We observed that the ACE is well suited for recapitulation, observation and intervention of hiPSC-islet maturation. Intriguingly, intraocular hiPSC-islet grafts, retrieved intact following intravitreal infusion of the CaV3 channel blocker NNC55-0396, exhibited decreased basal [Ca2+]i levels and increased glucose-stimulated [Ca2+]i responses. Insulin-expressing cells of these islet grafts indeed expressed the NNC55-0396 target CaV3 channels. Intraocular hiPSC-islets underwent satisfactory engraftment, vascularization and light scattering without being influenced by the intravitreally infused NNC55-0396. These data demonstrate that inhibiting CaV3 channels facilitates the maturation of glucose-activated Ca2+ signaling in hiPSC-islets, supporting the notion that excessive CaV3 channels as a developmental error impede the maturation of engineered hiPSC-islet insulin-expressing cells.

AI Cardiac MRI Scar Analysis Aids Prediction of Major Arrhythmic Events in the Multicenter DERIVATE Registry.

Background Scar burden with late gadolinium enhancement (LGE) cardiac MRI (CMR) predicts arrhythmic events in patients with postinfarction in single-center studies. However, LGE analysis requires experienced human observers, is time consuming, and introduces variability. Purpose To test whether postinfarct scar with LGE CMR can be quantified fully automatically by machines and to compare the ability of LGE CMR scar analyzed by humans and machines to predict arrhythmic events. Materials and Methods This study is a retrospective analysis of the multicenter, multivendor CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry. Patients with chronic heart failure, echocardiographic left ventricular ejection fraction (LVEF) of less than 50%, and LGE CMR were recruited (from January 2015 through December 2020). In the current study, only patients with ischemic cardiomyopathy were included. Quantification of total, dense, and nondense scars was carried out by two experienced readers or a Ternaus network, trained and tested with LGE images of 515 and 246 patients, respectively. Univariable and multivariable Cox analyses were used to assess patient and cardiac characteristics associated with a major adverse cardiac event (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare model performances. Results In 761 patients (mean age, 65 years ± 11, 671 men), 83 MACEs occurred. With use of the testing group, univariable Cox-analysis found New York Heart Association class, left ventricle volume and/or function parameters (by echocardiography or CMR), guideline criterion (LVEF of ≤35% and New York Heart Association class II or III), and LGE scar analyzed by humans or the machine-learning algorithm as predictors of MACE. Machine-based dense or total scar conferred incremental value over the guideline criterion for the association with MACE (AUC: 0.68 vs 0.63, P = .02 and AUC: 0.67 vs 0.63, P = .01, respectively). Modeling with competing risks yielded for dense and total scar (AUC: 0.67 vs 0.61, P = .01 and AUC: 0.66 vs 0.61, P = .005, respectively). Conclusion In this analysis of the multicenter CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry, fully automatic machine learning-based late gadolinium enhancement analysis reliably quantifies myocardial scar mass and improves the current prediction model that uses guideline-based risk criteria for implantable cardioverter defibrillator implantation. ClinicalTrials.gov registration no.: NCT03352648 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Long-term outcomes of the Universal 2 total wrist replacement: revision and loosening at 10 years and beyond.

The aim of this study was to ascertain the long-term revision rates of the Universal 2 wrist prosthesis in a previously published cohort of patients with rheumatoid arthritis. The time to, and reasons for revision were determined. Radiographs were analysed to determine whether loosening had occurred in the long-term according to the Wrightington zonal classification of loosening. Seventy-eight wrists from the original cohort of 85 wrists could be identified for analysis. The longest follow-up was 16 years and 29 wrists had follow-up beyond 10 years. Seventeen wrists had been revised or were on the waiting list for revision, an overall revision rate of 22%. The 10-year survivorship was 78%. Long-term revision was commonly for periprosthetic loosening with pain and component subsidence. In those with more than 10-year follow-up, significant lucency was seen in 16 carpal components and 15 radial components. Explant analysis showed significant polyethylene wear and we postulate this is the principal reason for component loosening.Level of evidence: IV.

Presentation and Prognosis of Excessive Asymptomatic Atrial Ectopy in Children and Adolescents With Structurally and Functionally Normal Hearts.

Excessive premature atrial complexes (PACs) in pediatric patients with a structurally normal heart are presumed to be benign and self-resolving, but no studies have confirmed this. Adults with excessive PACs, however, are at increased risk for future sustained atrial arrhythmias and cardiovascular morbidity and mortality. Therefore, we sought to evaluate the clinical course of frequent PACs in asymptomatic children. Patients < 21 years old with numerous asymptomatic PACs (>50/24 hours) were retrospectively selected over a 10-year period. Demographics, clinical characteristics, and results of cardiovascular testing were tabulated. Two groups were defined: those with a significant (>20%) reduction in burden of atrial ectopy versus those with an insignificant (<20%) reduction or increase. Of 6,902 patients, 343 patients (5%) met criteria. Initial median age was 8.3 (interquartile range [IQR] 4.1 to 14) years with comparable male:female ratio. Follow-up Holters were performed on 188 patients (54.8%) at a median interval of 2.2 (IQR 1.3 to 3.6) years. Overall, there was a significant decrease in atrial ectopy burden from 4.2% (IQR 1.9 to 6.5) down to 0.5% (IQR 0.01 to 2.3), with 166 patients (88.3%), demonstrating a decrease of over 20%. Five percent had a small increase, and 6% had an insignificant decrease. None developed cardiac symptoms or sustained supraventricular tachydysrhythmia. Male gender, athletic participation, and discontinuation of stimulant medications were the chief predictors for a reduction of PAC burden on follow-up. Atrial triplets at presentation were associated with a 5.4% increase. In conclusion, this study confirms that excessive asymptomatic childhood PACs with structurally normal hearts are rare and short-term to medium-term prognosis is benign.

How does bicycling affect the longevity of Total Hip Arthroplasty? A finite element wear analysis.

As the number of young and active individuals undergoing Total Hip Arthroplasty (THA) are increasing yearly, there is a need for hip prostheses to have increased longevity. Current investigations into the longevity of these prostheses only include walking as the patient's activity as there is limited data on the amount and intensity of other activity performed by the patient. To further understand the evolution of wear and increase the longevity of these implants, the impact of different activities on the hip prosthesis needs to be investigated. In this study, a finite element model and wear algorithm was developed to simulate both walking and bicycling over a 5-year period. The XLPE acetabular cup volumetric wear rate was found to be 33 mm3/yr while the femoral head taper wear rates were between 0.01 - 0.39 mm3/yr. The results showed that by adding bicycling of up to 80 km per week with normal walking activity, the XLPE mean volumetric wear rate increased by 67% and the metallic mean volumetric wear rate by 11%. However, the patient may gain further health benefits from this additional activity. Assistive electric bikes may also be used to further reduce the loads on the hip joint, allowing for lower amounts of wear.

Explant analysis of a Discocerv cervical disc: A case study for a ceramic-on-ceramic cervical disc.

Explant analyses are key to better understanding the effectiveness of medical implants in replacing natural joints. For the first time, an explanted Discocerv cervical disc was examined. The implant utilised the articulation of a caudal zirconia cup (inferior component) and a cephalic alumina head (superior component). The articulating surface of the superior alumina head had an average surface roughness of 0.016 ± 0.003 µm (Sa) and the articulating surface of the inferior zirconia cup had an average surface roughness of 0.015 ± 0.002 µm (Sa). Both articulating surfaces had negative skewness, indicating the removal of local peaks. The difference between the average surface roughness of the components was not significant (p-value: 0.741). Dark grey marks were observed on both of the articulating surfaces, which were found to be adhered titanium debris that was generated due to component impingement. This titanium debris may explain the small amount of metallosis that was reported at explantation. Some transfer of zirconium to the alumina articulating surface was also seen.

Erratum: Author Correction: The influence of HLA genotype on the development of metal hypersensitivity following joint replacement.

[This corrects the article DOI: 10.1038/s43856-022-00137-0.].

The influence of HLA genotype on the development of metal hypersensitivity following joint replacement.

Background: Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed-type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established. Methods: At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype, and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time-dependent receiver operator curves. Results: Using next-generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure, and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1% for pre-operative and post-operative models respectively. Conclusions: The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient's genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient-specific responses to different biomaterials.

Rapid inference of personalised left-ventricular meshes by deformation-based differentiable mesh voxelization.

We propose a differentiable volumetric mesh voxelization technique based on deformation of a shape-model, and demonstrate that it can be used to predict left-ventricular anatomies directly from magnetic resonance image slice data. The predicted anatomies are volumetric meshes suitable for direct inclusion in biophysical simulations. The proposed method can leverage existing (pixel-based) segmentation networks, and does not require any ground truth paired image and mesh training data. We demonstrate that this approach produces accurate predictions from few slices, and can combine information from images acquired in different views (e.g. fusing shape information from short axis and long axis slices). We demonstrate that the proposed method is several times faster than a state-of-the-art registration based method. Additionally, we show that our method can correct for slice misalignment, and is robust to incomplete and inaccurate input data. We further demonstrate that by fitting a mesh to every frame of 4D data we can determine ejection fraction, stroke volume and strain.

Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells.

We exploited the anterior chamber of the eye (ACE) of immunodeficient mice as an ectopic site for both transplantation and microimaging of engineered surrogate islets from human induced pluripotent stem cells (hiPSC-SIs). These islets contained a majority of insulin-expressing cells, positive or negative for PDX1 and NKX6.1, and a minority of glucagon- or somatostatin-positive cells. Single, non-aggregated hiPSC-SIs were satisfactorily engrafted onto the iris. They underwent gradual vascularization and progressively increased their light scattering signals, reflecting the abundance of zinc-insulin crystal packaged inside mature insulin secretory granules. Intracameral hiPSC-SIs retrieved from recipients showed enhanced insulin immunofluorescence in correlation with the parallel increase in overall vascularization and light backscattering during the post-transplantation period. This approach enables longitudinal, nondestructive and intravital microimaging of cell fates, engraftment, vascularization and mature insulin secretory granules of single hiPSC-SI grafts, and may offer a feasible and reliable means to screen compounds for promoting in vivo hiPSC-SI maturation.