Short-term outcome after treatment of talocrural instability in cats using modified type II transarticular external skeletal fixation.

Transarticular external skeletal fixation (TESF) is repeatedly used for temporary stabilisation of tarsal joint in cats. Hence, this study aimed to evaluate the use of temporary modified type II TESF for management of talocrural instability (TCI) in cats without joint arthrodesis and to rate short-term outcomes and complications. Medical records of all cats treated for TCI between January 2012 and December 2021 were reviewed. Information was collected including signalment, degree of lameness, type of TCI, accompanying soft tissue and bone injuries, and post-operative follow-up assessment including time of frame removal, complications, degree of lameness, range of joint motion and ankylosis. Surgical management didn't involve debridement of the articular cartilage. Eighty-five percent of cats had satisfactory joint stability at the time of frame removal. Eighteen cats exhibited minor complications, six cats had major complications, and 8 cats showed persistent lameness. All cats showed reduction of joint motion range by 20°-30° directly after frame removal while returned to normal in 79% of cats 4 weeks later. Variable degrees of joint ankylosis were reported. In conclusion, this study supports the use of temporary modified type II TESF for management of TCI in cats without joint involvement as an excellent alternative to tarsal arthrodesis.

Iatrogenic Air Embolisms During Endovascular Interventions: Impact of Origin and Number of Air Bubbles on Cerebral Infarctions.

PURPOSE: Cerebral infarctions caused by air embolisms (AE) are a feared risk in endovascular procedures; however, the relevance and pathophysiology of these AEs is still largely unclear. The objective of this study was to investigate the impact of the origin (aorta, carotid artery or right atrium) and number of air bubbles on cerebral infarctions in an experimental in vivo model. METHODS: In 20 rats 1200 or 2000 highly calibrated micro air bubbles (MAB) with a size of 85 µm were injected at the aortic valve (group Ao), into the common carotid artery (group CA) or into the right atrium (group RA) using a microcatheter via a transfemoral access, resembling endovascular interventions in humans. Magnetic resonance imaging (MRI) using a 9.4T system was performed 1 h after MAB injection followed by finalization. RESULTS: The number (5.5 vs. 5.5 median) and embolic patterns of infarctions did not significantly differ between groups Ao and CA. The number of infarctions were significantly higher comparing 2000 and 1200 injected MABs (6 vs. 4.5; p < 0.001). The infarctions were significantly larger for group CA (median infarction volume: 0.41 mm3 vs. 0.19 mm3; p < 0.001). In group RA and in the control group no infarctions were detected. Histopathological analyses showed early signs of ischemic stroke. CONCLUSION: Iatrogenic AEs originating at the ascending aorta cause a similar number and pattern of cerebral infarctions compared to those with origin at the carotid artery. These findings underline the relevance and potential risk of AE occurring during endovascular interventions at the aortic valve and ascending aorta.

[Is JAK inhibition an option in the treatment of interstitial lung disease in rheumatoid arthritis?] / Ist JAK-Hemmung eine Option in der Behandlung der interstitiellen Lungenerkrankung bei einer rheumatoiden Arthritis?

A 69-year-old male patient with seropositive erosive rheumatoid arthritis (RA) presented to our clinic due to progressive dyspnea. High-resolution computed tomography (HRCT) and immunological bronchioalveolar lavage revealed ground-glass opacities and a lymphocytic alveolitis caused by interstitial lung disease (ILD) in RA. Considering previous forms of treatment, disease-modifying antirheumatic drug (DMARD) treatment was switched to tofacitinib. Tofacitinib treatment demonstrated a 33% reduction in ground-glass opacities by artificial intelligence-based quantification of pulmonary HRCT over the course of 6 months, which was associated with an improvement in dyspnea symptoms. In conclusion, tofacitinib represents an effective anti-inflammatory therapeutic option in the treatment of RA-ILD.

Iatrogenic air embolism: influence of air bubble size on cerebral infarctions in an experimental in vivo and numerical simulation model.

BACKGROUND: Cerebral infarctions resulting from iatrogenic air embolism (AE), mainly caused by small air bubbles, are a well-known and often overlooked event in endovascular interventions. Despite their significance, the underlying pathophysiology remains largely unclear. METHODS: In 24 rats, AEs were induced using a microcatheter, positioned in the carotid artery via femoral access. Rats were divided into two study groups, based on the size of the bubbles (85 and 120 µm) and two sub-groups, differing in air volume (0.39 and 0.64 µl). Ultra-high-field magnetic resonance imaging (MRI) was performed 1.5 hours after intervention. MRI findings including the number, single volume and total volume of the infarctions were assessed. A software-based numerical simulation was performed to qualitatively assess the microvascular pathomechanisms. RESULTS: In the study groups 22 of 24 rats (92%) revealed cerebral infarctions. The number of infarctions per rat was higher for the smaller bubbles, for the lower (medians: 5 vs 3; p=0.049) and higher air volume sub-groups (medians: 6 vs 4; p=0.012). Correspondingly, total infarction volume was higher for the smaller bubbles (1.67 vs 0.5 mm³; p=0.042). Simulations confirmed the results of the experiments and suggested that fusion of microbubbles to larger bubbles is the underlying pathomechanism of vascular occlusions. CONCLUSION: In iatrogenic AE, the size of the bubbles can have a major impact on the number and total volume of cerebral infarctions. These findings can help to better understand the pathophysiology of this frequent, often underestimated adverse event in endovascular interventions.

Implementation and evaluation of a complex intervention to improve information availability at the interface between inpatient and outpatient care in older patients with multimorbidity and polypharmacy (HYPERION-TransCare) - study protocol for a pilot and feasibility cluster-randomized controlled trial in general practice in Germany.

BACKGROUND: Despite attempts to improve the cross-sectoral flow of information, difficulties remain in routine healthcare. The resulting negative impact on continuity of care is often associated with poor health outcomes, especially in older patients. Our intervention aims to increase information availability with respect to medications and health conditions at the interface between inpatient and outpatient care and to contribute towards improving the quality of care in older patients. This pilot study focuses on feasibility and implementability. METHODS: The idea of the complex intervention has been developed in a previous study. This intervention will be tested in a prospective, multicenter, cluster-randomized (via web tool), controlled pilot trial with two parallel study arms (intervention and control group). The pilot study will be conducted in 20 general practices in Hesse and Saxony (Germany) and include 200 patients (≥ 65 years of age with multimorbidity and polypharmacy) recruited by the practices. Practice staff and patients will be blinded. We will use qualitative and quantitative methods to assess the feasibility and implementability of the intervention and the study design in a process evaluation covering topics ranging from expectations to experiences. In addition, the feasibility of proposed outcome parameters for the future definitive trial will be explored. The composite endpoint will include health-related patient outcomes (hospitalization, falls, and mortality using, e.g., the FIMA questionnaire), and we will assess information on medications (SIMS questionnaire), symptoms and side effects of the medication (pro-CTCAE questionnaire), and health literacy (HLQ questionnaire). Data will be collected at study begin (baseline) and after 6 months. Furthermore, the study will include surveys and interviews with patients, general practitioners, and healthcare assistants. DISCUSSION: The intervention was developed using a participatory approach involving stakeholders and patients. It aims to empower general practice teams as they provide patient-centered care and play a key role in the coordination and continuity of care. We aim to encourage patients to adopt an active role in their health care. Overall, we want to increase the availability of health-related information for patients and healthcare providers. The results of the pilot study will be used in the design and implementation of the future definitive trial. TRIAL REGISTRATION: The study was registered in DRKS-German Clinical Trials Register: registration number DRKS00027649 (date: 19 January 2022). Date and version identifier 10.07.2023; Version 1.3.

Hepatic passaging of NRAS-mutant melanoma influences adhesive properties and metastatic pattern.

BACKGROUND: Liver metastasis is a poor prognostic factor for treatment of advanced cutaneous melanoma with either immunotherapy or targeted therapies. In this study we focused on NRAS mutated melanoma, a cohort with high unmet clinical need. METHODS: WT31 melanoma was repeatedly passaged over the liver after intravenous injections five times generating the subline WT31_P5IV. The colonization of target organs, morphology, vascularization and the gene expression profiles of metastases were analyzed. RESULTS: After intravenous injection lung metastasis was significantly decreased and a trend towards increased liver metastasis was detected for WT31_P5IV as compared to parental WT31. Besides, the ratio of lung to liver metastases was significantly smaller. Histology of lung metastases revealed reduced proliferation of WT31_P5IV in relation to WT31 while both size and necrotic areas were unaltered. Liver metastases of both sublines showed no differences in vascularization, proliferation or necrosis. To identify tumor-intrinsic factors that altered the metastatic pattern of WT31_P5IV RNA sequencing was performed and revealed a differential regulation of pathways involved in cell adhesion. Ex vivo fluorescence imaging confirmed that initial tumor cell retention in the lungs was significantly reduced in WT31_P5IV in comparison to WT31. CONCLUSION: This study demonstrates that tumor-intrinsic properties influencing the metastatic pattern of NRAS mutated melanoma are strongly affected by hepatic passaging and the hematogenous route tumor cells take. It has implications for the clinical setting as such effects might also occur during metastatic spread or disease progression in melanoma patients.

Added value of chest CT in a machine learning-based prediction model to rule out COVID-19 before inpatient admission: A retrospective university network study.

PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic, hospitals still face the challenge of timely identification of infected individuals before inpatient admission. An artificial intelligence approach based on an established clinical network may improve prospective pandemic preparedness. METHOD: Supervised machine learning was used to construct diagnostic models to predict COVID-19. A pooled database was retrospectively generated from 4437 participant data that were collected between January 2017 and October 2020 at 12 German centers that belong to the radiological cooperative network of the COVID-19 (RACOON) consortium. A total of 692 (15.6 %) participants were COVID-19 positive according to the reference of the reverse transcription-polymerase chain reaction test. The diagnostic models included chest CT features (model R), clinical examination and laboratory test features (model CL), or all three feature categories (model RCL). Performance outcomes included accuracy, sensitivity, specificity, negative and positive predictive value, and area under the receiver operating curve (AUC). RESULTS: Performance of predictive models improved significantly by adding chest CT features to clinical evaluation and laboratory test features. Without (model CL) and with inclusion of chest CT (model RCL), sensitivity was 0.82 and 0.89 (p < 0.0001), specificity was 0.84 and 0.89 (p < 0.0001), negative predictive value was 0.96 and 0.97 (p < 0.0001), AUC was 0.92 and 0.95 (p < 0.0001), and proportion of false negative classifications was 2.6 % and 1.7 % (p < 0.0001), respectively. CONCLUSIONS: Addition of chest CT features to machine learning-based predictive models improves the effectiveness in ruling out COVID-19 before inpatient admission to regular wards.

Lung ultrasound in children and adolescents with long-term effects of COVID-19: Initial results.

Introduction: Chronic health effects following acute COVID-19 are increasingly observed as the pandemic continues and are grouped under long COVID. Although the acute course of the COVID disease is often milder, long COVID also affects children and adolescents. As the symptoms present in Long-COVID often seem to be non-specific and not limited to organ systems, clarification of the causes and the creation of a meaningful, efficient and targeted diagnostic algorithm is urgently needed. Methods: Therefore, in this prospective observational study, we examined 30 children with long COVID using lung ultrasound and compared the results with those of 15 lung-healthy children. Results: In our study, no significant difference was found between the two groups in the morphological criteria of lung ultrasound of the pleura or pleural lung structures. There was no significant correlation between the lung ultrasound findings and clinical Data. Discussion: Our findings are congruent with the current, albeit sparse, data. It is possible that the causes of persistent thoracic symptoms in long COVID might be more likely to be present in functional examinations, but not morphologically imageable. Nonspecific symptoms do not appear to be due to changes in the lung parenchyma. In conclusion, lung ultrasound alone and without baseline in acute disease is not suitable as a standard in the follow-up of long COVID patients. Further investigations on the morphological and functional changes in patient with long COVID is needed.

Perfusion and T2 Relaxation Time as Predictors of Severity and Outcome in Sepsis-Associated Acute Kidney Injury: A Preclinical MRI Study.

BACKGROUND: Preventing sepsis-associated acute kidney injury (S-AKI) can be challenging because it develops rapidly and is often asymptomatic. Probability assessment of disease progression for therapeutic follow-up and outcome are important to intervene and prevent further damage. PURPOSE: To establish a noninvasive multiparametric MRI (mpMRI) tool, including T1 , T2 , and perfusion mapping, for probability assessment of the outcome of S-AKI. STUDY TYPE: Preclinical randomized prospective study. ANIMAL MODEL: One hundred and forty adult female SD rats (65 control and 75 sepsis). FIELD STRENGTH/SEQUENCE: 9.4T; T1 and perfusion map (FAIR-EPI) and T2 map (multiecho RARE). ASSESSMENT: Experiment 1: To identify renal injury in relation to sepsis severity, serum creatinine levels were determined (31 control and 35 sepsis). Experiment 2: Animals underwent mpMRI (T1 , T2 , perfusion) 18 hours postsepsis. A subgroup of animals was immediately sacrificed for histology examination (nine control and seven sepsis). Result of mpMRI in follow-up subgroup (25 control and 33 sepsis) was used to predict survival outcomes at 96 hours. STATISTICAL TESTS: Mann-Whitney U test, Spearman/Pearson correlation (r), P < 0.05 was considered statistically significant. RESULTS: Severely ill septic animals exhibited significantly increased serum creatinine levels compared to controls (70 ± 30 vs. 34 ± 9 µmol/L, P < 0.0001). Cortical perfusion (480 ± 80 vs. 330 ± 140 mL/100 g tissue/min, P < 0.005), and cortical and medullary T2 relaxation time constants were significantly reduced compared to controls (41 ± 4 vs. 37 ± 5 msec in cortex, P < 0.05, 52 ± 7 vs. 45 ± 6 msec in medulla, P < 0.05). The combination of cortical T2 relaxation time constants and perfusion results at 18 hours could predict survival outcomes at 96 hours with high sensitivity (80%) and specificity (73%) (area under curve of ROC = 0.8, Jmax = 0.52). DATA CONCLUSION: This preclinical study suggests combined T2 relaxation time and perfusion mapping as first line diagnostic tool for treatment planning. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Eighteen-Month Changes in Physical Activity, Body Weight, Quadriceps Strength, and Gait Biomechanics during the COVID-19 Pandemic.

PURPOSE: This study assessed the effects of the COVID-19 pandemic restrictions/lockdowns on physical activity levels, body mass, quadriceps strength, and gait biomechanics over 18 months. METHODS: Ten healthy men were assessed at baseline (~14 wk before first lockdown) and 17.9 ± 0.3 months later (<1 wk after second lockdown). At both times, physical activity levels, body mass, and quadriceps strength were acquired using the International Physical Activity Questionnaire, a force plate, and a dynamometer, respectively. Gait data were also acquired using a motion capture system and force plates during self-paced walking, from which spatiotemporal parameters, knee angles, and external moments were computed. Baseline and follow-up measurements were compared using two-tailed paired t -tests ( α = 0.05). RESULTS: At follow-up, participants spent less time doing vigorous physical activity (∆ = -76 ± 157 min·wk -1 , P = 0.048), exhibited a tendency toward increased sedentary time (∆ = +120 ± 162 min·d -1 , P = 0.056), weighed more (∆ = +2.5 ± 2.8 kg, P = 0.021), and showed a trend toward reduced quadriceps strength (∆ = -0.29 ± 0.45 (N·m)·kg -1 , P = 0.071) compared with baseline. At follow-up, participants walked slower (∆ = -0.09 ± 0.07 m·s -1 , P = 0.005), had greater knee flexion angles at heel strike (∆ = +2.2° ± 1.8°, P = 0.004) and during late stance (∆ = +2.2° ± 1.8°, P = 0.004), had reduced knee extension moments (∆ = -0.09 ± 0.09 (N·m)·kg -1 , P = 0.012) and knee internal rotation moments (∆ = -0.02 ± 0.02 (N·m)·kg -1 , P = 0.012) during late stance. CONCLUSIONS: Healthy men exhibited reduced physical activity levels, increased body weight, a tendency toward reduced quadriceps strength, and altered gait biomechanics over the initial 18 months of the COVID-19 pandemic-alterations that could have far-reaching health consequences.

Whole-body diffusion magnetic resonance imaging with simultaneous multi-slice excitation in children and adolescents.

BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) is an increasingly used guideline-based imaging modality for oncological and non-oncological pathologies during childhood and adolescence. While diffusion-weighted imaging (DWI), a part of WB-MRI, enhances image interpretation and improves sensitivity, it also requires the longest acquisition time during a typical WB-MRI scan protocol. Interleaved short tau inversion recovery (STIR) DWI with simultaneous multi-slice (SMS) acquisition is an effective way to speed up examinations. OBJECTIVE: In this study of children and adolescents, we compared the acquisition time, image quality, signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) values of an interleaved STIR SMS-DWI sequence with a standard non-accelerated DWI sequence for WB-MRI. MATERIALS AND METHODS: Twenty children and adolescents (mean age: 13.9 years) who received two WB-MRI scans at a maximum interval of 18 months, consisting of either standard DWI or SMS-DWI MRI, respectively, were included. For quantitative evaluation, the signal-to-noise ratio (SNR) was determined for b800 images and ADC maps of seven anatomical regions. Image quality evaluation was independently performed by two experienced paediatric radiologists using a 5-point Likert scale. The measurement time per slice stack, pause between measurements including shim and total measurement time of DWI for standard DWI and SMS-DWI were extracted directly from the scan data. RESULTS: When including the shim duration, the acquisition time for SMS-DWI was 43% faster than for standard DWI. Qualitatively, the scores of SMS-DWI were higher in six locations in the b800 images and four locations in the ADC maps. There was substantial agreement between both readers, with a Cohen's kappa of 0.75. Quantitatively, the SNR in the b800 images and the ADC maps did not differ significantly from one another. CONCLUSION: Whole body-MRI with SMS-DWI provided equivalent image quality and reduced the acquisition time almost by half compared to the standard WB-DWI protocol.

The Role of Femoral Head Size and Femoral Head Coverage in Dogs with and without Hip Dysplasia.

The subject of hip dysplasia in dogs is still current and preoccupies both animal owners and veterinarians. Major factors affecting the development of the disorder are hip laxity and incongruent joints. Many studies on etiology, pathogenesis, and early diagnosis have been performed to reduce prevalence and select healthy dogs for breeding. The purpose of the present study was to investigate a possible relationship between dysplasia and femoral head area (FHA), femoral coverage by the acetabulum (CFH) and cranio-caudal distance of the dorsal acetabular rim (CrCdAR). Radiographs of a total of 264 skeletally mature dogs with similar physical characteristics (German wirehaired pointers (GWP), German shepherd dogs (GSD) and Labrador retrievers (LAB)) presented for routine hip dysplasia screening were recruited for the study. FHA, CFH and CrCdAR were measured and related to dysplasia status. Evaluations of FHA (p = 0.011), CFH (p < 0.001) and CrCdAR length (p = 0.003) measurements revealed significant interactions between breed, sex and FCI scores, so they had to be assessed separately. The results revealed that FHA tends to decrease as the hip dysplasia score worsens. There was no significant relationship between FHA and dysplasia assessment. FHA is breed-specific and is larger in normal and near-normal male (p = 0.001, p = 0.020) and female (p = 0.001, p = 0.013) GWP compared to GSD, respectively. FHA is greater in normal male GWP (p = 0.011) and GSD (p = 0.040) compared to females. There was a significant and strong positive correlation between FHA and CrCdAR in all breeds and sexes. Additionally, FCI scoring had a medium (GWP, GSD) to strong (LAB) negative correlation with CFH.

Investigation of Experimental Endovascular Air Embolisms Using a New Model for the Generation and Detection of Highly Calibrated Micro Air Bubbles.

BACKGROUND: Air embolism (AE), especially when affecting the brain, is an underrated and potentially life-threatening complication in various endovascular interventions. This study aims to investigate experimental AEs using a new model to generate micro air bubbles (MAB), to assess the impact of a catheter on these MAB, and to demonstrate the applicability of this model in vivo. MATERIALS AND METHODS: Micro air bubbles were created using a system based on microfluidic channels. The MAB were detected and analyzed automatically. Micro air bubbles, with a target size of 85 µm, were generated and injected through a microcatheter. The MAB diameters proximal and distal to the catheter were assessed and compared. In a subsequent in vivo application, 2000 MAB were injected into the aorta (at the aortic valve) and into the common carotid artery (CCA) of a rat, respectively, using a microcatheter, resembling AE occurring during cardiovascular interventions. RESULTS: Micro air bubbles with a highly calibrated size could be successfully generated (median: 85.5 µm, SD 1.9 µm). After passage of the microcatheter, the MAB were similar in diameter (median: 86.6 µm) but at a lower number (60.1% of the injected MAB) and a substantially higher scattering of diameters (SD 29.6 µm). In vivo injection of MAB into the aorta resulted in cerebral microinfarctions in both hemispheres, whereas injection into the CCA caused exclusively ipsilateral microinfarctions. CONCLUSION: Using this new AE model, MAB can be generated precisely and reproducibly, resulting in cerebral microinfarctions. This model is feasible for further studies on the pathophysiology and prevention of AE in cardiovascular procedures.

[Long-term examinations of the lumbal disc and facet joint changes in 5 German Shepard dogs]. / Verlaufsuntersuchung der lumbalen Bandscheiben- und Facettengelenkveränderungen bei 5 Deutschen Schäferhunden.

OBJECT AND PURPOSE: The purpose of this first-time long-term observational study was to evaluate the changes of the caudal lumbar spine at the locations L5/6, L6/7, and L7/S1 in 5 German shepherd dogs over a 6-year time period using computed tomography (CT) and magnetic resonance imaging (MRI). The dogs had a mean age of 26 months at the time of the first examination. In addition, it was evaluated whether a breeding examination, with regard to disc degeneration, is justified in young dog. MATERIAL AND METHODS: The locations L7/S1, L6/7, and L5/6 were examined in more detail with regard to their signal intensity changes, the facet joint angle changes in dorsal (dors) and transverse (trans) planes, and disc surface changes in sagittal (sag) and transverse (trans) reconstruction planes with CT and MRT in 2015 and 2021. All data were collected computer-based and analyzed statistically. Subsequently, the results were compared to the measured signal intensity and to the subjective disc degeneration grading according to Seiler used in practice. RESULTS: Over the period of 6 years a significant loss of the measured signal intensity of the intervertebral discs in the transverse plane and an overall facet joint widening in the transverse plane of 0.54° as well as in the dorsal plane of 1.8° was evident. In addition, there was no evidence of a relationship between the size of the facet joint angle and the degree of disc degeneration. Furthermore, regardless of the initial degree of degeneration, the discs showed low signal intensity and higher Seiler grade during follow-up. CONCLUSION AND CLINICAL RELEVANCE: The results of the present study group indicate that an inconspicuous condition of the lumbar intervertebral discs at the time of the initial breeding examination in the young dog does not allow an accurate prediction of the subsequent degree of degeneration and that there are ongoing remodeling processes at the facet joints even in healthy German shepherd dogs.

Utilization of a cloud-based radiology analytics platform to monitor imaging volumes at a large tertiary center.

Rationale and objective: In this study, we evaluate the ability of a novel cloud-based radiology analytics platform to continuously monitor imaging volumes at a large tertiary center following institutional protocol and policy changes. Materials and methods: We evaluated response to environmental factors through the lens of the COVID-19 pandemic. Analysis involved 11 CT/18 MR imaging systems at a large tertiary center. A vendor neutral, cloud-based analytics tool (CBRAP) was used to retrospectively collect information via DICOM headers on imaging exams between Oct. 2019 to Aug. 2021. Exams were stratified by modality (CT or MRI) and organized by body region. Pre-pandemic scan volumes (Oct 2019-Feb. 2010) were compared with volumes during/after two waves of COVID-19 in Illinois (Mar. to May 2020 & Oct. to Dec. 2020) using a t-test or Mann-Whitney U test. Results: The CBRAP was able to analyze 169,530 CT and 110,837 MR images, providing a detailed snapshot of baseline and post-pandemic CT and MR imaging across the radiology enterprise at our tertiary center. The CBRAP allowed for further subdivision in its reporting, showing monthly trends in average scan volumes specifically in the head, abdomen, spine, MSK, thorax, neck, GU system, or breast. Conclusion: The CBRAP retrieved data for 300,000 + imaging exams across multiple modalities at a large tertiary center in a highly populated, urban environment. The ability to analyze large imaging volumes across multiple waves of COVID-19 and evaluate quality-improvement endeavors/imaging protocol changes displays the usefulness of the CBRAP as an advanced imaging analytics tool.

Influence of neurovascular anatomy on perforation site in different mouse strains using the filament perforation model for induction of subarachnoid hemorrhage.

BACKGROUND: Filament perforation is a widely-used method to induce subarachnoid hemorrhage (SAH) in mice. Whereas the perforation site has been assumed to be in the branching of middle cerebral artery (MCA) and anterior cerebral artery (ACA), we recently observed more proximal perforations. METHODS: Filament perforation was performed in CD1- (n = 10) and C57Bl/6N-mice (n = 9) ex vivo. The filament was left in place and the perforation site was microscopically assessed. Digital subtraction angiography (DSA) was performed in CD1- (n = 9) and C57Bl/6J-mice (n = 29) and anatomical differences of the internal carotid artery (ICA) were determined. RESULTS: Whereas in C57Bl/6N-mice perforation occurred in the proximal intracranial ICA in 89% (n = 8), in CD1-mice the perforation site was in the proximal ICA in 50% (n = 5), in the branching between MCA and ACA in 40% (n = 4), and in the proximal ACA in 10% (n = 1). DSA revealed a stronger angulation (p<0.001) of the ICA in CD1-mice (163.5±2.81°) compared to C57Bl/6J-mice (124.5±5.49°). Body weight and ICA-angle showed no significant correlation in C57Bl/6J- (r = -0.06, pweight/angle = 0.757) and CD1-mice (r = -0.468, pweight/angle = 0.242). CONCLUSION: Filament perforation in mice occurs not only at the hitherto presumed branching between MCA and ACA, but seems to depend on mouse strain and anatomy as the proximal intracranial ICA may also be perforated frequently.

A novel free-breathing abdominal RAVE T2/T1 hybrid MRI sequence in patients with cystic fibrosis: Preliminary results.

OBJECTIVES: Patients with cystic fibrosis (CF) increasingly require imaging for the diagnosis of abdominal complications. We prospectively evaluated the image quality and signal-to-noise ratio (SNR) of a modern radial volumetric encoding (RAVE) T2/T1 hybrid sequence for abdominal magnetic resonance imaging (MRI). RAVET2/T1 is a three-dimensional radial sequence with fat saturation and blood flow suppression that acquires T2- and T1-weighted contrasts in one scan in an identical slice position during free-breathing. METHODS: Sixteen CF patients underwent axial T2 HASTE (1000 ms/93 ms TR/TE), T1 DIXON (6.8 ms/2.4 ms/4.8 ms TR/TE1/TE2), and RAVE T2/T1 hybrid sequence (1200 ms/1.7 ms/3.3 ms/4.9 ms/102 ms TR/TE1/TE2/TE3/TE4) of the upper abdomen at 1.5 Tesla. The SNR values in six different regions were assessed and compared using the Wilcoxon signed-rank test. The image quality criteria were rated on a 5-point Likert scale. RESULTS: In all regions, the SNR was significantly higher in the T2 weighted aspect of the RAVE T2/T1 hybrid sequence compared to T2 HASTE (p < 0.05) and significantly lower in the T1 weighted in-phase aspect of the RAVE T2/T1 hybrid sequence compared to the T1 DIXON sequence (p < 0.05). Qualitatively the T2 weighted aspect of the RAVE T2/T1 hybrid sequence was rated significantly higher than the T2 HASTE in 6 of 7 categories (p < 0.05) and the T1 weighted in-phase aspect of the RAVE T2/T1 hybrid sequence was rated significantly higher than the T1 DIXON in 2 of 6 categories (p < 0.05). CONCLUSIONS: The abdominal radial RAVE T2/T1 hybrid sequence provided higher image quality and SNR than the T2HASTEsequence. Together with increased robustness against motion artifacts, the RAVE T2/T1 hybrid sequence appears to be a good tool for abdominal imaging in CF patients.

Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy.

Background: Neuronopathic Gaucher disease (nGD) is a rare neurodegenerative disorder caused by biallelic mutations in GBA and buildup of glycosphingolipids in lysosomes. Neuronal injury and cell death are prominent pathological features; however, the role of GBA in individual cell types and involvement of microglia, blood-derived macrophages, and immune infiltrates in nGD pathophysiology remains enigmatic. Methods: Here, using single-cell resolution of mouse nGD brains, lipidomics, and newly generated biomarkers, we found induction of neuroinflammation pathways involving microglia, NK cells, astrocytes, and neurons. Results: Targeted rescue of Gba in microglia and neurons, respectively, in Gba-deficient, nGD mice reversed the buildup of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph), concomitant with amelioration of neuroinflammation, reduced serum neurofilament light chain (Nf-L), and improved survival. Serum GlcSph concentration was correlated with serum Nf-L and ApoE in nGD mouse models as well as in GD patients. Gba rescue in microglia/macrophage compartment prolonged survival, which was further enhanced upon treatment with brain-permeant inhibitor of glucosylceramide synthase, effects mediated via improved glycosphingolipid homeostasis, and reversal of neuroinflammation involving activation of microglia, brain macrophages, and NK cells. Conclusions: Together, our study delineates individual cellular effects of Gba deficiency in nGD brains, highlighting the central role of neuroinflammation driven by microglia activation. Brain-permeant small-molecule inhibitor of glucosylceramide synthase reduced the accumulation of bioactive glycosphingolipids, concomitant with amelioration of neuroinflammation involving microglia, NK cells, astrocytes, and neurons. Our findings advance nGD disease biology whilst identifying compelling biomarkers of nGD to improve patient management, enrich clinical trials, and illuminate therapeutic targets. Funding: Research grant from Sanofi; other support includes R01NS110354, Yale Liver Center P30DK034989, pilot project grant.

High-resolution CINE imaging of active guided knee motion using continuously acquired golden-angle radial MRI and rotary sensor information.

To explore and extend on dynamic imaging of joint motion, an MRI-safe device guiding knee motion with an attached rotary encoder was used in MRI measurements of multiple knee flexion-extension cycles using radial gradient echo imaging with the golden-angle as azimuthal angle increment. Reproducibility of knee motion was investigated. Real-time and CINE mode anatomical images were reconstructed for different knee flexion angles by synchronizing the encoder information with the MRI data, and performing flexion angle selective gating across multiple motion cycles. When investigating the influence of the rotation angle window width on reconstructed CINE images, it was found that angle windows between 0.5° and 3° exhibited acceptable image sharpness without suffering from significant motion-induced blurring. Furthermore, due to flexible retrospective image reconstruction afforded by the radial golden-angle imaging, the number of motion cycles included in the reconstruction could be retrospectively reduced to investigate the corresponding influence of acquisition time on image quality. Finally, motion reproducibility between motion cycles and accuracy of the flexion angle selective gating were sufficient to acquire whole-knee 3D dynamic imaging with a retrospectively gated 3D cone UTE sequence.

MRI Tracking of Iron Oxide Labelled Canine Mesenchymal Stem Cells in Artificial Stifle Defects.

OBJECTIVES: The aim of this study was to describe ultrasmall superparamagnetic iron oxides labelling of canine adipose-derived mesenchymal stem cells (AdMSCs) and the detection and semiquantitative evaluation of the labelled cells after implantation in artificial canine stifle defects using magnetic resonance imaging. METHODS: Magnetic resonance imaging examinations of 10 paired (n = 20) cadaveric stifle joints were evaluated after creation of chondral defects and embedding of ultrasmall superparamagnetic iron oxides labelled canine mesenchymal stem cells. To prove the feasibility of the labelling for in vivo usage, Prussian blue staining, cell vitality tests and intralesional administration of labelled cells were conducted. Magnetic resonance imaging of ex vivo defects filled with different cell concentrations was obtained to depict the cell content semiquantitatively via signal intensity measurements (region of interest). RESULTS: Prussian blue staining showed that the labelling was effective. According to the vitality tests, it had no significant short-term influence on cell viability and proliferation rate. For the evaluation of the defect T2* sequences were feasible and stifle defects were visible allowing measurements of the signal intensity in all cases. Increasing the cell concentration within the chondral defects resulted in an inversely proportional, significant reduction of signal intensity according to the region of interest. CLINICAL SIGNIFICANCE: Ultrasmall superparamagnetic iron oxides labelling was effective. The detection of the AdMSCs in a complex anatomical structure like the surface of the femoral condyle was possible and the T2* signal intensity of the implant region was significantly correlated with the concentration of the AdMSCs.