Radiomics workflow definition & challenges - German priority program 2177 consensus statement on clinically applied radiomics.

OBJECTIVES: Achieving a consensus on a definition for different aspects of radiomics workflows to support their translation into clinical usage. Furthermore, to assess the perspective of experts on important challenges for a successful clinical workflow implementation. MATERIALS AND METHODS: The consensus was achieved by a multi-stage process. Stage 1 comprised a definition screening, a retrospective analysis with semantic mapping of terms found in 22 workflow definitions, and the compilation of an initial baseline definition. Stages 2 and 3 consisted of a Delphi process with over 45 experts hailing from sites participating in the German Research Foundation (DFG) Priority Program 2177. Stage 2 aimed to achieve a broad consensus for a definition proposal, while stage 3 identified the importance of translational challenges. RESULTS: Workflow definitions from 22 publications (published 2012-2020) were analyzed. Sixty-nine definition terms were extracted, mapped, and semantic ambiguities (e.g., homonymous and synonymous terms) were identified and resolved. The consensus definition was developed via a Delphi process. The final definition comprising seven phases and 37 aspects reached a high overall consensus (> 89% of experts "agree" or "strongly agree"). Two aspects reached no strong consensus. In addition, the Delphi process identified and characterized from the participating experts' perspective the ten most important challenges in radiomics workflows. CONCLUSION: To overcome semantic inconsistencies between existing definitions and offer a well-defined, broad, referenceable terminology, a consensus workflow definition for radiomics-based setups and a terms mapping to existing literature was compiled. Moreover, the most relevant challenges towards clinical application were characterized. CRITICAL RELEVANCE STATEMENT: Lack of standardization represents one major obstacle to successful clinical translation of radiomics. Here, we report a consensus workflow definition on different aspects of radiomics studies and highlight important challenges to advance the clinical adoption of radiomics. KEY POINTS: Published radiomics workflow terminologies are inconsistent, hindering standardization and translation. A consensus radiomics workflow definition proposal with high agreement was developed. Publicly available result resources for further exploitation by the scientific community.

Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells.

The pathophysiology of many neuropsychiatric disorders is still poorly understood. Identification of biomarkers for these diseases could benefit patients due to better classification and stratification. Exosomes excreted into the circulatory system can cross the blood-brain barrier and carry a cell type-specific set of molecules. Thus, exosomes are a source of potential biomarkers for many diseases, including neuropsychiatric disorders. Here, we investigated exosomal proteins produced from human-induced pluripotent stem cells (iPSCs) and iPSC-derived neural stem cells, neural progenitors, neurons, astrocytes, microglia-like cells, and brain capillary endothelial cells. Of the 31 exosome surface markers analyzed, a subset of biomarkers were significantly enriched in astrocytes (CD29, CD44, and CD49e), microglia-like cells (CD44), and neural stem cells (SSEA4). To identify molecular fingerprints associated with disease, circulating exosomes derived from healthy control (HC) individuals were compared against schizophrenia (SCZ) patients and late-onset Alzheimer's disease (LOAD) patients. A significant epitope pattern was identified for LOAD (CD1c and CD2) but not for SCZ compared to HC. Thus, analysis of cell type- and disease-specific exosome signatures of iPSC-derived cell cultures may provide a valuable model system to explore proteomic biomarkers for the identification of novel disease profiles.

Association Between Body Composition and Survival in Patients With Gastroesophageal Adenocarcinoma: An Automated Deep Learning Approach.

PURPOSE: Body composition (BC) may play a role in outcome prognostication in patients with gastroesophageal adenocarcinoma (GEAC). Artificial intelligence provides new possibilities to opportunistically quantify BC from computed tomography (CT) scans. We developed a deep learning (DL) model for fully automatic BC quantification on routine staging CTs and determined its prognostic role in a clinical cohort of patients with GEAC. MATERIALS AND METHODS: We developed and tested a DL model to quantify BC measures defined as subcutaneous and visceral adipose tissue (VAT) and skeletal muscle on routine CT and investigated their prognostic value in a cohort of patients with GEAC using baseline, 3-6-month, and 6-12-month postoperative CTs. Primary outcome was all-cause mortality, and secondary outcome was disease-free survival (DFS). Cox regression assessed the association between (1) BC at baseline and mortality and (2) the decrease in BC between baseline and follow-up scans and mortality/DFS. RESULTS: Model performance was high with Dice coefficients ≥0.94 ± 0.06. Among 299 patients with GEAC (age 63.0 ± 10.7 years; 19.4% female), 140 deaths (47%) occurred over a median follow-up of 31.3 months. At baseline, no BC measure was associated with DFS. Only a substantial decrease in VAT >70% after a 6- to 12-month follow-up was associated with mortality (hazard ratio [HR], 1.99 [95% CI, 1.18 to 3.34]; P = .009) and DFS (HR, 1.73 [95% CI, 1.01 to 2.95]; P = .045) independent of age, sex, BMI, Union for International Cancer Control stage, histologic grading, resection status, neoadjuvant therapy, and time between surgery and follow-up CT. CONCLUSION: DL enables opportunistic estimation of BC from routine staging CT to quantify prognostic information. In patients with GEAC, only a substantial decrease of VAT 6-12 months postsurgery was an independent predictor for DFS beyond traditional risk factors, which may help to identify individuals at high risk who go otherwise unnoticed.

Odontoid Fracture with Accompanying Severe Atlantoaxial Instability in Elderly Patients-Analysis of Treatment, Adverse Events, and Outcome.

(1) Background: In elderly patients with type II odontoid fractures, accompanying severe atlantoaxial instability (AAI) is discussed as a marker possibly warranting more aggressive surgical therapy. This study aimed to characterize adverse events as well as the radiological and functional outcomes of surgical vs. conservative therapy in patients with odontoid fracture and AAI. (2) Methods: Patients aged 65 years and older with type II odontoid fracture and AAI treated were included. AAI was assumed if the mean subluxation across both atlantoaxial facet joints in the sagittal plane was greater than 50%. Data on demographics, comorbidities, treatment, adverse events, radiological, and functional outcomes were analyzed. (3) Results: Thirty-nine patients were included. Hospitalization time was significantly shorter in conservatively treated patients compared to patients with ventral or dorsal surgery. Adverse events occurred in 11 patients (28.2%), affecting 10 surgically treated patients (35.7%), and 1 conservatively treated patient (9.1%). Moreover, 25 patients were followed-up (64.1%). One secondary dislocation occurred in the conservative group (11.1%) and three in the surgical group (18.8%). (4) Conclusions: Despite the potential for instability in this injury, conservative treatment does not seem to lead to unfavorable short-term results, less adverse events, and a shorter hospital stay and should thus be considered and discussed with patients as a treatment option, even in the presence of severe AAI.

Comparison of T-POD and SAM Pelvic Sling II and the influence of attachment level in the initial management of unstable pelvic type C injuries - a cadaveric study.

BACKGROUND: Type C pelvic fractures (AO/OTA) are severe injuries that frequently lead to bleeding and hemodynamic instability. Pelvic binders play a crucial role in their initial management. Placement at the correct level in the prehospital setting is challenging. The aim of this study was to compare two pelvic binders regarding their effectiveness in reducing intrapelvic volume and increasing intrapelvic pressure in patients with type C pelvic fractures (AO/OTA) when applied at three different levels. METHODS: Rotationally and vertically unstable pelvic injuries (AO/OTA classification 61-C1.1) were produced in five fresh-frozen human cadaveric specimens. Intrapelvic volume, vesical pressure and compression pressure within the pubic symphysis and the sacroiliac joint were measured when applying a SAM Pelvic Sling II and a T-POD at the level of the greater trochanter as well as levels higher and lower than recommended. RESULTS: Comparison of the two pelvic binders positioned at the recommended level (greater trochanter) showed no significant difference in volume reduction (13.85 ± 31.37 cm3, p = 0.442), however, increase in vesical pressure was significantly higher when using the T-POD (5.80 ± 3.27 cmH2O, p = 0.017). When positioned at the level of the iliac crest, vesical pressure increase and intrapelvic volume reduction were significantly greater with the T-POD (14.00 ± 8.57 cmH2O, p = 0.022 and 10.45 ± 5.45 cm3, p = 0.031 respectively). Application of the SAM Pelvic Sling II below the greater trochanter led to a significantly greater decrease in volume (-32.26 ± 7.52 cm3, p = 0.003) than the T-POD. Comparison of the recommended attachment level with incorrect positioning led to no significant differences for the T-POD, while the SAM Pelvic Sling II achieved a significantly lower volume reduction when placed at the iliac crest (40.15 ± 14.57 cm3, p = 0.012) and a significantly lower increase in vesical pressure when applied below the greater trochanter (3.40 ± 1.52 cmH2O, p = 0.007). CONCLUSION: Direct comparison of the two pelvic binders showed that the T-POD achieved significantly greater results when applied at the recommended level and was less susceptible to incorrect positioning. These outcomes support the preferred use of the T-POD for prehospital emergency pelvic stabilisation.

Multicentric development and validation of a multi-scale and multi-task deep learning model for comprehensive lower extremity alignment analysis.

Osteoarthritis of the knee, a widespread cause of knee disability, is commonly treated in orthopedics due to its rising prevalence. Lower extremity misalignment, pivotal in knee injury etiology and management, necessitates comprehensive mechanical alignment evaluation via frequently-requested weight-bearing long leg radiographs (LLR). Despite LLR's routine use, current analysis techniques are error-prone and time-consuming. To address this, we conducted a multicentric study to develop and validate a deep learning (DL) model for fully automated leg alignment assessment on anterior-posterior LLR, targeting enhanced reliability and efficiency. The DL model, developed using 594 patients' LLR and a 60%/10%/30% data split for training, validation, and testing, executed alignment analyses via a multi-step process, employing a detection network and nine specialized networks. It was designed to assess all vital anatomical and mechanical parameters for standard clinical leg deformity analysis and preoperative planning. Accuracy, reliability, and assessment duration were compared with three specialized orthopedic surgeons across two distinct institutional datasets (136 and 143 radiographs). The algorithm exhibited equivalent performance to the surgeons in terms of alignment accuracy (DL: 0.21 ± 0.18°to 1.06 ± 1.3°vs. OS: 0.21 ± 0.16°to 1.72 ± 1.96°), interrater reliability (ICC DL: 0.90 ± 0.05 to 1.0 ± 0.0 vs. ICC OS: 0.90 ± 0.03 to 1.0 ± 0.0), and clinically acceptable accuracy (DL: 53.9%-100% vs OS 30.8%-100%). Further, automated analysis significantly reduced analysis time compared to manual annotation (DL: 22 ± 0.6 s vs. OS; 101.7 ± 7 s, p ≤ 0.01). By demonstrating that our algorithm not only matches the precision of expert surgeons but also significantly outpaces them in both speed and consistency of measurements, our research underscores a pivotal advancement in harnessing AI to enhance clinical efficiency and decision-making in orthopaedics.

Secondary Dislocations in Type B and C Injuries of the Subaxial Cervical Spine: Risk Factors and Treatment.

INTRODUCTION: This study analyzed the incidence of secondary dislocations (sDLs) after surgical stabilization of AO Spine type B and C injuries of the subaxial cervical spine (sCS). MATERIALS AND METHODS: Patients treated for injuries of the sCS from 2010 to 2020 were retrospectively analyzed for the incidence of sDL within 60 days after first surgery. A univariate analysis of variables potentially influencing the risk of sDL was performed. Patients with solitary anterior stabilization underwent subgroup analysis. The treatment of sDLs was described. RESULTS: A total of 275 patients were included. sDLs occurred in 4.0% of patients (n = 11) in the total sample, most frequently after solitary anterior stabilization with 8.0% (n = 10, p = 0.010). Only one sDL occurred after combined stabilization and no sDLs after posterior stabilization. In the total sample and the anterior subgroup, variables significantly associated with sDL were older age (p = 0.001) and concomitant unstable facet joint injury (p = 0.020). No neurological deterioration occurred due to sDL and most patients were treated with added posterior stabilization. sDL is frequent after solitary anterior stabilization and rare after posterior or combined stabilization. DISCUSSION: Patients of higher age and with unstable facet joint injuries should be followed up diligently to detect sDLs in time. Neurological deterioration does not regularly occur due to sDL, and most patients can be treated with added posterior stabilization.

Adverse events after surgery for injuries to the subaxial cervical spine: analysis of incidence and risk factors.

PURPOSE: To determine the incidence of severe surgical adverse events (sSAE) after surgery of patients with subaxial cervical spine injury (sCS-Fx) and to identify patient, treatment, and injury-related risk factors. METHODS: Retrospective analysis of clinical and radiological data of sCS-Fx patients treated surgically between 2010 and 2020 at a single national trauma center. Baseline characteristics of demographic data, preexisting conditions, treatment, and injury morphology were extracted. Incidences of sSAEs within 60 days after surgery were analyzed. Univariate analysis and binary logistic regression for the occurrence of one or more sSAEs were performed to identify risk factors. P-values < .05 were considered statistically significant. RESULTS: Two hundred and ninety-two patients were included. At least one sSAE occurred in 49 patients (16.8%). Most frequent were sSAEs of the surgical site (wound healing disorder, infection, etc.) affecting 29 patients (9.9%). Independent potential risk factors in logistic regression were higher age (OR 1.02 [1.003-1.04], p = .022), the presence of one or more modifiers in the AO Spine Subaxial Injury Classification (OR 2.02 [1.03-3.96], p = .041), and potentially unstable or unstable facet injury (OR 2.49 [1.24-4.99], p = .010). Other suspected risk factors were not statistically significant, among these Injury Severity Score, the need for surgery for concomitant injuries, the primary injury type according to AO Spine, and preexisting medical conditions. CONCLUSION: sSAE rates after treatment of sCS-Fx are high. The identified risk factors are not perioperatively modifiable, but their knowledge should guide intra and postoperative care and surgical technique.

MR imaging after patellar MACI and MPFL reconstruction: a comparison of isolated versus combined procedures.

OBJECTIVE: To qualitatively and quantitatively evaluate the 2.5-year MRI outcome after Matrix-associated autologous chondrocyte implantation (MACI) at the patella, reconstruction of the medial patellofemoral ligament (MPFL), and combined procedures. METHODS: In 66 consecutive patients (age 22.8 ± 6.4years) with MACI at the patella (n = 16), MPFL reconstruction (MPFL; n = 31), or combined procedures (n = 19) 3T MRI was performed 2.5 years after surgery. For morphological MRI evaluation WORMS and MOCART scores were obtained. In addition quantitative cartilage T2 and T1rho relaxation times were acquired. Several clinical scores were obtained. Statistical analyses included descriptive statistics, Mann-Whitney-U-tests and Pearson correlations. RESULTS: WORMS scores at follow-up (FU) were significantly worse after combined procedures (8.7 ± 4.9) than after isolated MACI (4.3 ± 3.6, P = 0.005) and after isolated MPFL reconstruction (5.3 ± 5.7, P = 0.004). Bone marrow edema at the patella in the combined group was the only (non-significantly) worsening WORMS parameter from pre- to postoperatively. MOCART scores were significantly worse in the combined group than in the isolated MACI group (57 ± 3 vs 88 ± 9, P < 0.001). Perfect defect filling was achieved in 26% and 69% of cases in the combined and MACI group, respectively (P = 0.031). Global and patellar T2 values were higher in the combined group (Global T2: 34.0 ± 2.8ms) and MACI group (35.5 ± 3.1ms) as compared to the MPFL group (31.1 ± 3.2ms, P < 0.05). T2 values correlated significantly with clinical scores (P < 0.005). Clinical Cincinnati scores were significantly worse in the combined group (P < 0.05). CONCLUSION: After combined surgery with patellar MACI and MPFL reconstruction inferior MRI outcomes were observed than after isolated procedures. Therefore, patients with need for combined surgery may be at particular risk for osteoarthritis.

Paediatric spine injuries in the thoracic and lumbar spine-results of the German multicentre CHILDSPINE study.

BACKGROUND: Paediatric thoracolumbar spine injuries are rare, and meaningful epidemiological data are lacking. OBJECTIVES: The aim of this study was to provide epidemiological data for paediatric patients with thoracolumbar spinal trauma in Germany with a view to enhancing future decision-making in relation to the diagnostics and treatment of these patients. MATERIALS AND METHODS: A retrospective multicentre study includes patients up to 16 years of age who were suffering from thoracolumbar spine injuries who had been treated in six German spine centres between 01/2010 and 12/2016. The clinical database was analysed for patient-specific data, trauma mechanisms, level of injury, and any accompanying injuries. Diagnostic imaging and subsequent treatment were investigated. Patients were divided into three age groups for further evaluation: age group I (0-6 years), age group II (7-9 years) and age group III (10-16 years). RESULTS: A total of 153 children with 345 thoracolumbar spine injuries met the inclusion criteria. The mean age at the time of hospitalization due to the injury was 12.9 (± 3.1) years. Boys were likelier to be affected (1:1.3). In all age groups, falls and traffic accidents were the most common causes of thoracolumbar spine injuries. A total of 95 patients (62.1%) were treated conservatively, while 58 (37.9%) of the children underwent surgical treatment. Minimally invasive procedures were the most chosen procedures. Older children and adolescents were likelier to suffer from higher-grade injuries according to the AOSpine classification. The thoracolumbar junction (T11 to L2) was the most affected level along the thoracolumbar spine (n = 90). Neurological deficits were rarely seen in all age groups. Besides extremity injuries (n = 52, 30.2%), head injuries represented the most common accompanying injuries (n = 53, 30.8%). Regarding spinal injuries, most of the patients showed no evidence of complications during their hospital stay (96.7%). CONCLUSIONS: The thoracolumbar junction was more frequently affected in older children and adolescents. The majority of thoracolumbar spinal column injuries were treated conservatively. Nevertheless, 37.9% of hospitalized children had to be treated surgically, and there was an acceptable complication rate for the surgeries that were performed.

Neuronal Stem Cells from Late-Onset Alzheimer Patients Show Altered Regulation of Sirtuin 1 Depending on Apolipoprotein E Indicating Disturbed Stem Cell Plasticity.

Late-onset Alzheimer's disease (AD) is a complex multifactorial disease. The greatest known risk factor for late-onset AD is the E4 allele of the apolipoprotein E (APOE), while increasing age is the greatest known non-genetic risk factor. The cell type-specific functions of neural stem cells (NSCs), in particular their stem cell plasticity, remain poorly explored in the context of AD pathology. Here, we describe a new model that employs late-onset AD patient-derived induced pluripotent stem cells (iPSCs) to generate NSCs and to examine the role played by APOE4 in the expression of aging markers such as sirtuin 1 (SIRT1) in comparison to healthy subjects carrying APOE3. The effect of aging was investigated by using iPSC-derived NSCs from old age subjects as healthy matched controls. Transcript and protein analysis revealed that genes were expressed differently in NSCs from late-onset AD patients, e.g., exhibiting reduced autophagy-related protein 7 (ATG7), phosphatase and tensin homolog (PTEN), and fibroblast growth factor 2 (FGF2). Since SIRT1 expression differed between APOE3 and APOE4 NSCs, the suppression of APOE function in NSCs also repressed the expression of SIRT1. However, the forced expression of APOE3 by plasmids did not recover differently expressed genes. The altered aging markers indicate decreased plasticity of NSCs. Our study provides a suitable in vitro model to investigate changes in human NSCs associated with aging, APOE4, and late-onset AD.

Survival and Clinical Outcomes after Unconstrained Total Knee Arthroplasty for Tibial Plateau Fractures-A Retrospective Study with Minimum 4-Year Follow-Up.

This study investigated survival, complications, revisions, and patient-reported outcomes (PROs) for unconstrained total knee arthroplasty (TKA) in posttraumatic osteoarthritis (PTO) caused by intraarticular tibial plateau fractures with minimum four years follow-up. Forty-nine patients (71.4% male; 58.7 years) were included. Kaplan-Meier analysis was performed with failure defined as TKA removal. Patients without failure underwent pre- and postoperative evaluation (range of motion (ROM), Oxford Knee Score (OKS), Knee Society Score (KSS), anatomical femorotibial angle (aFTA), proximal tibial slope (PTS)) and Short Form-12 (SF-12) Physical (PCS) and Mental Component Summary (MCS) assessment at final follow-up. Fifteen (30.6%) patients had a complication, and eight (16.3%) patients underwent prosthesis removal at median 2.5 years. Cumulative survival rate of TKA was 79.6% at 20 years. A total of 32 patients with a mean follow-up of 11.8 years underwent further analyses. ROM (p = 0.028), aFTA (p = 0.044), pPS (p = 0.009), OKS (p < 0.001) and KSS (p < 0.001) improved significantly. SF-12 PCS was 42.3 and MCS was 54.4 at final follow-up. In general, one third of patients suffer a complication, and one in six patients has their prosthesis removed after TKA for PTO due to tibial plateau fractures. In patients who do not fail, TKA significantly improves clinical and radiographic outcomes at long-term follow-up.

Odontoid fracture in geriatric patients - analysis of complications and outcome following conservative treatment vs. ventral and dorsal surgery.

BACKGROUND: Different treatment options are discussed for geriatric odontoid fracture. The aim of this study was to compare the treatment options for geriatric odontoid fractures. METHODS: Included were patients with the following criteria: age ≥ 65 years, identification of seniors at risk (ISAR score ≥ 2), and odontoid fracture type A/B according to Eysel and Roosen. Three groups were compared: conservative treatment, surgical therapy with ventral screw osteosynthesis or dorsal instrumentation. At a follow-up examination, the range of motion and the trabecular bone fracture healing rate were evaluated. Furthermore, demographic patient data, neurological status, length of stay at the hospital and at the intensive care unit (ICU) as well as the duration of surgery and occurring complications were analyzed. RESULTS: A total of 72 patients were included and 43 patients could be re-examined (range: 2.7 ± 2.1 months). Patients with dorsal instrumentation had a better rotation. Other directions of motion were not significantly different. The trabecular bone fracture healing rate was 78.6%. The patients with dorsal instrumentation were hospitalized significantly longer; however, their duration at the ICU was shortest. There was no significant difference in complications. CONCLUSION: Geriatric patients with odontoid fracture require individual treatment planning. Dorsal instrumentation may offer some advantages.

Non-invasive monitoring of neoadjuvant radiation therapy response in soft tissue sarcomas by multiparametric MRI and quantification of circulating tumor DNA-A study protocol.

BACKGROUND: Wide resection remains the cornerstone of localized soft-tissue sarcomas (STS) treatment. Neoadjuvant radiation therapy (NRT) may decrease the risk of local recurrences; however, its effectiveness for different histological STS subtypes has not been systematically investigated. The proposed prospective study evaluates the NRT response in STS using liquid biopsies and the correlation of multiparametric magnetic resonance imaging (mpMRI) with histopathology and immunohistochemistry. METHODS: Patients with localized high-grade STS, who qualify for NRT, are included in this study. LIQUID BIOPSIES: Quantification of circulating tumor DNA (ctDNA) in patient blood samples is performed by targeted next-generation sequencing. Soft-tissue sarcoma subtype-specific panel sequencing in combination with patient-specific exome sequencing allows the detection of individual structural variants and point mutations. Circulating free DNA is isolated from peritherapeutically collected patient plasma samples and ctDNA quantified therein. Identification of breakpoints is carried out using FACTERA. Bioinformatic analysis is performed using samtools, picard, fgbio, and the MIRACUM Pipeline. MPMRI: Combination of conventional MRI sequences with diffusion-weighted imaging, intravoxel-incoherent motion, and dynamic contrast enhancement. Multiparametric MRI is performed before, during, and after NRT. We aim to correlate mpMRI data with the resected specimen's macroscopical, histological, and immunohistochemical findings. RESULTS: Preliminary data support the notion that quantification of ctDNA in combination with tumor mass characterization through co-registration of mpMRI and histopathology can predict NRT response of STS. CLINICAL RELEVANCE: The methods presented in this prospective study are necessary to assess therapy response in heterogeneous tumors and lay the foundation of future patient- and tumor-specific therapy concepts. These methods can be applied to various tumor entities. Thus, the participation and support of a wider group of oncologic surgeons are needed to validate these findings on a larger patient cohort.

Human isogenic cells of the neurovascular unit exert transcriptomic cell type-specific effects on a blood-brain barrier in vitro model of late-onset Alzheimer disease.

BACKGROUND: The function of the blood-brain barrier (BBB) is impaired in late-onset Alzheimer disease (LOAD), but the associated molecular mechanisms, particularly with respect to the high-risk APOE4/4 genotype, are not well understood. For this purpose, we developed a multicellular isogenic model of the neurovascular unit (NVU) based on human induced pluripotent stem cells. METHODS: The human NVU was modeled in vitro using isogenic co-cultures of astrocytes, brain capillary endothelial-like cells (BCECs), microglia-like cells, neural stem cells (NSCs), and pericytes. Physiological and pathophysiological properties were investigated as well as the influence of each single cell type on the characteristics and function of BCECs. The barriers established by BCECs were analyzed for specific gene transcription using high-throughput quantitative PCR. RESULTS: Co-cultures were found to tighten the barrier of BCECs and alter its transcriptomic profile under both healthy and disease conditions. In vitro differentiation of brain cell types that constitute the NVU was not affected by the LOAD background. The supportive effect of NSCs on the barrier established by BCECs was diminished under LOAD conditions. Transcriptomes of LOAD BCECs were modulated by different brain cell types. NSCs were found to have the strongest effect on BCEC gene regulation and maintenance of the BBB. Co-cultures showed cell type-specific functional contributions to BBB integrity under healthy and LOAD conditions. CONCLUSIONS: Cell type-dependent transcriptional effects on LOAD BCECs were identified. Our study suggests that different brain cell types of the NVU have unique roles in maintaining barrier integrity that vary under healthy and LOAD conditions. .

Ankle Sprains in Athletes: Current Epidemiological, Clinical and Imaging Trends.

Purpose: Ankle injuries are frequent sports injuries. Despite optimizing treatment strategies during recent years, the percentage of chronification following an ankle sprain remains high. The purpose of this review article is, to highlight current epidemiological, clinical and novel advanced cross-sectional imaging trends that may help to evaluate ankle sprain injuries. Methods: Systematic PubMed literature research. Identification and review of studies (i) analyzing and describing ankle sprain and (ii) focusing on advanced cross-sectional imaging techniques at the ankle. Results: The ankle is one of the most frequently injured body parts in sports. During the COVID-19 pandemic, there was a change in sporting behavior and sports injuries. Ankle sprains account for about 16-40% of the sports-related injuries. Novel cross-sectional imaging techniques, including Compressed Sensing MRI, 3D MRI, ankle MRI with traction or plantarflexion-supination, quantitative MRI, CT-like MRI, CT arthrography, weight-bearing cone beam CT, dual-energy CT, photon-counting CT, and projection-based metal artifact reduction CT may be introduced for detection and evaluation of specific pathologies after ankle injury. While simple ankle sprains are generally treated conservatively, unstable syndesmotic injuries may undergo stabilization using suture-button-fixation. Minced cartilage implantation is a novel cartilage repair technique for osteochondral defects at the ankle. Conclusion: Applications and advantages of different cross-sectional imaging techniques at the ankle are highlighted. In a personalized approach, optimal imaging techniques may be chosen that best detect and delineate structural ankle injuries in athletes.

Development and Evaluation of MR-Based Radiogenomic Models to Differentiate Atypical Lipomatous Tumors from Lipomas.

BACKGROUND: The aim of this study was to develop and validate radiogenomic models to predict the MDM2 gene amplification status and differentiate between ALTs and lipomas on preoperative MR images. METHODS: MR images were obtained in 257 patients diagnosed with ALTs (n = 65) or lipomas (n = 192) using histology and the MDM2 gene analysis as a reference standard. The protocols included T2-, T1-, and fat-suppressed contrast-enhanced T1-weighted sequences. Additionally, 50 patients were obtained from a different hospital for external testing. Radiomic features were selected using mRMR. Using repeated nested cross-validation, the machine-learning models were trained on radiomic features and demographic information. For comparison, the external test set was evaluated by three radiology residents and one attending radiologist. RESULTS: A LASSO classifier trained on radiomic features from all sequences performed best, with an AUC of 0.88, 70% sensitivity, 81% specificity, and 76% accuracy. In comparison, the radiology residents achieved 60-70% accuracy, 55-80% sensitivity, and 63-77% specificity, while the attending radiologist achieved 90% accuracy, 96% sensitivity, and 87% specificity. CONCLUSION: A radiogenomic model combining features from multiple MR sequences showed the best performance in predicting the MDM2 gene amplification status. The model showed a higher accuracy compared to the radiology residents, though lower compared to the attending radiologist.

Multiparametric magnetic resonance imaging for radiation therapy response monitoring in soft tissue sarcomas: a histology and MRI co-registration algorithm.

Rationale: To establish a spatially exact co-registration procedure between in vivo multiparametric magnetic resonance imaging (mpMRI) and (immuno)histopathology of soft tissue sarcomas (STS) to identify imaging parameters that reflect radiation therapy response of STS. Methods: The mpMRI-Protocol included diffusion-weighted (DWI), intravoxel-incoherent motion (IVIM), and dynamic contrast-enhancing (DCE) imaging. The resection specimen was embedded in 6.5% agarose after initial fixation in formalin. To ensure identical alignment of histopathological sectioning and in vivo imaging, an ex vivo MRI scan of the specimen was rigidly co-registered with the in vivo mpMRI. The deviating angulation of the specimen to the in vivo location of the tumor was determined. The agarose block was trimmed accordingly. A second ex vivo MRI in a dedicated localizer with a 4 mm grid was performed, which was matched to a custom-built sectioning machine. Microtomy sections were stained with hematoxylin and eosin. Immunohistochemical staining was performed with anti-ALDH1A1 antibodies as a radioresistance and anti-MIB1 antibodies as a proliferation marker. Fusion of the digitized microtomy sections with the in vivo mpMRI was accomplished through nonrigid co-registration to the in vivo mpMRI. Co-registration accuracy was qualitatively assessed by visual assessment and quantitatively evaluated by computing target registration errors (TRE). Results: The study sample comprised nine tumor sections from three STS patients. Visual assessment after nonrigid co-registration showed a strong morphological correlation of the histopathological specimens with ex vivo MRI and in vivo mpMRI after neoadjuvant radiation therapy. Quantitative assessment of the co-registration procedure using TRE analysis of different pairs of pathology and MRI sections revealed highly accurate structural alignment, with a total median TRE of 2.25 mm (histology - ex vivo MRI), 2.22 mm (histology - in vivo mpMRI), and 2.02 mm (ex vivo MRI - in vivo mpMRI). There was no significant difference between TREs of the different pairs of sections or caudal, middle, and cranial tumor parts, respectively. Conclusion: Our initial results show a promising approach to obtaining accurate co-registration between histopathology and in vivo MRI for STS. In a larger cohort of patients, the method established here will enable the prospective identification and validation of in vivo imaging biomarkers for radiation therapy response prediction and monitoring in STS patients via precise molecular and cellular correlation.

Generation of a set of induced pluripotent stem cell lines from two Alzheimer disease patients carrying APOE4 (MLUi007-J; MLUi008-A) and healthy old donors carrying APOE3 (MLUi009-A; MLUi010-B) to study APOE in aging and disease.

Late-onset Alzheimer disease (LOAD) is the most frequent neurodegenerative disease, and the APOE ε4 allele is the most prominent risk factor for LOAD. Four human induced pluripotent stem cell (iPSC) lines MLUi007-J, MLUi008-B, MLUi009-A, and MLUi010-B were generated from LOAD patients and healthy matched donors by reprogramming of B-lymphoblastoid cells (B-LCLs) with episomal plasmids. The application of B-LCLs holds a great promise to model LOAD and other diseases because they can easily be generated from primary peripheral blood mononuclear cells (PBMCs) by infection with the Epstein-Barr virus (EBV).

Associations of myosteatosis with disc degeneration: A 3T magnetic resonance imaging study in individuals with impaired glycaemia.

BACKGROUND: Intervertebral disc degeneration (IVDD) may be linked to dysregulations of skeletal muscle glucose metabolism and fatty alterations of muscle composition (Myosteatosis). Our aim was to evaluate the different associations of magnetic resonance imaging (MRI)-based paravertebral myosteatosis with lumbar disc degeneration in individuals with impaired glucose metabolism and normoglycaemic controls. METHODS: In total, 304 individuals (mean age: 56.3 ± 9.1 years, 53.6% male sex, mean body mass index [BMI]: 27.6 ± 4.7 kg/m2 ) from a population-based cohort study who underwent 3-Tesla whole-body chemical-shift-encoded (six echo times) and T2-weighted single-shot-fast-spin-echo MRI were included. Lumbar disc degeneration was assessed at motion segments L1 to L5, categorized according to the Pfirrmann score and defined as Pfirrmann grade > 2 and/or disc bulging/herniation on at least one segment. Fat content of the autochthonous back muscles and the quadratus lumborum muscle was quantified as proton density fat fraction (PDFFmuscle ). Logistic regression models adjusted for age, sex, BMI and regular physical activity were calculated to evaluate the association between PDFFmuscle and outcome IVDD. RESULTS: The overall prevalence of IVDD was 79.6%. There was no significant difference in the prevalence or severity distribution of IVDD between participants with or without impaired glucose metabolism (77.7% vs. 80.7%, P = 0.63 and P = 0.71, respectively). PDFFmuscle was significantly and positively associated with an increased risk for the presence of IVDD in participants with impaired glycaemia when adjusted for age, sex and BMI (PDFFautochthonous back muscles : odds ratio [OR] 2.16, 95% confidence interval [CI] [1.09, 4.3], P = 0.03; PDFFquadratus lumborum : OR 2.01, 95% CI [1.04, 3.85], P = 0.04). After further adjustment for regular physical activity, the results attenuated, albeit approaching statistical significance (PDFFautochthonous back muscles : OR 1.97, 95% CI [0.97, 3.99], P = 0.06; PDFFquadratus lumborum : OR 1.86, 95% CI [0.92, 3.76], P = 0.09). No significant associations were shown in healthy controls (PDFFautochthonous back muscles : OR 0.62, 95% CI [0.34, 1.14], P = 0.13; PDFFquadratus lumborum : OR 1.06, 95% CI [0.6, 1.89], P = 0.83). CONCLUSIONS: Paravertebral myosteatosis is positively associated with intervertebral disc disease in individuals with impaired glucose metabolism, independent of age, sex and BMI. Regular physical activity may confound these associations. Longitudinal studies will help to better understand the pathophysiological role of skeletal muscle in those with concomitant disturbed glucose haemostasis and intervertebral disc disease, as well as possible underlying causal relationships.