In Situ Mapping of Phase Evolutions in Rapidly Heated Zr-Based Bulk Metallic Glass with Oxygen Impurities.

Metallic glasses exhibit unique mechanical properties. For metallic glass composites (MGC), composed of dispersed nanocrystalline phases in an amorphous matrix, these properties can be enhanced or deteriorated depending on the volume fraction and size distribution of the crystalline phases. Understanding the evolution of crystalline phases during devitrification of bulk metallic glasses upon heating is key to realizing the production of these composites. Here, results are presented from a combination of in situ small- and wide-angle X-ray scattering (SAXS and WAXS) measurements during heating of Zr-based metallic glass samples at rates ranging from 102 to 104 Ks-1 with a time resolution of 4ms. By combining a detailed analysis of scattering experiments with numerical simulations, for the first time, it is shown how the amount of oxygen impurities in the samples influences the early stages of devitrification and changes the dominant nucleation mechanism from homogeneous to heterogeneous. During melting, the oxygen rich phase becomes the dominant crystalline phase whereas the main phases dissolve. The approach used in this study is well suited for investigation of rapid phase evolution during devitrification, which is important for the development of MGC.

Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model.

Alveolar epithelial cells (AEC) have been implicated in pathological remodelling. We examined the capacity of AEC to produce extracellular matrix (ECM) and thereby directly contribute towards remodelling in chronic lung diseases. Cryopreserved type 2 AEC (AEC2) from healthy lungs and chronic obstructive pulmonary disease (COPD) afflicted lungs were cultured in decellularized healthy human lung slices for 13 days. Healthy-derived AEC2 were treated with transforming growth factor ß1 (TGF-ß1) to evaluate the plasticity of their ECM production. Evaluation of phenotypic markers and expression of matrisome genes and proteins were evaluated by RNA-sequencing, mass spectrometry and immunohistochemistry. The AEC2 displayed an AEC marker profile similar to freshly isolated AEC2 throughout the 13-day culture period. COPD-derived AECs proliferated as healthy AECs with few differences in gene and protein expression while retaining increased expression of disease marker HLA-A. The AEC2 expressed basement membrane components and a complex set of interstitial ECM proteins. TGF-ß1 stimuli induced a significant change in interstitial ECM production from AEC2 without loss of specific AEC marker expression. This study reveals a previously unexplored potential of AEC to directly contribute to ECM turnover by producing interstitial ECM proteins, motivating a re-evaluation of the role of AEC2 in pathological lung remodelling.

Virtual Development of Process Parameters for Bulk Metallic Glass Formation in Laser-Based Powder Bed Fusion.

The development of process parameters and scanning strategies for bulk metallic glass formation during additive manufacturing is time-consuming and costly. It typically involves trials with varying settings and destructive testing to evaluate the final phase structure of the experimental samples. In this study, we present an alternative method by modelling to predict the influence of the process parameters on the crystalline phase evolution during laser-based powder bed fusion (PBF-LB). The methodology is demonstrated by performing simulations, varying the following parameters: laser power, hatch spacing and hatch length. The results are compared in terms of crystalline volume fraction, crystal number density and mean crystal radius after scanning five consecutive layers. The result from the simulation shows an identical trend for the predicted crystalline phase fraction compared to the experimental estimates. It is shown that a low laser power, large hatch spacing and long hatch lengths are beneficial for glass formation during PBF-LB. The absolute values show an offset though, over-predicted by the numerical model. The method can indicate favourable parameter settings and be a complementary tool in the development of scanning strategies and processing parameters for additive manufacturing of bulk metallic glass.

No-touch saphenous vein grafts in coronary artery surgery (SWEDEGRAFT): Rationale and design of a multicenter, prospective, registry-based randomized clinical trial.

The SWEDEGRAFT study (ClinicalTrials.gov Identifier: NCT03501303) tests the hypothesis that saphenous vein grafts (SVGs) harvested with the "no-touch" technique improves patency of coronary artery bypass grafts compared with the conventional open skeletonized technique. This article describes the rationale and design of the randomized trial and baseline characteristics of the population enrolled during the first 9 months of enrollment. The SWEDEGRAFT study is a prospective, binational multicenter, open-label, registry-based trial in patients undergoing first isolated nonemergent coronary artery bypass grafting (CABG), randomized 1:1 to no-touch or conventional open skeletonized vein harvesting technique, with a planned enrollment of 900 patients. The primary end point is the proportion of patients with graft failure defined as SVGs occluded or stenosed >50% on coronary computed tomography angiography at 2 years after CABG, earlier clinically driven coronary angiography demonstrating an occluded or stenosed >50% vein graft, or death within 2 years. High-quality health registries and coronary computed tomography angiography are used to assess the primary end point. The secondary end points include wound healing in the vein graft sites and the composite outcome of major adverse cardiac events during the first 2 years based on registry data. Demographics of the first 200 patients enrolled in the trial and other CABG patients operated in Sweden during the same time period are comparable when the exclusion criteria are taken into consideration. RCT# NCT03501303.

A multiple motion sensors index for motor state quantification in Parkinson's disease.

AIM: To construct a Treatment Response Index from Multiple Sensors (TRIMS) for quantification of motor state in patients with Parkinson's disease (PD) during a single levodopa dose. Another aim was to compare TRIMS to sensor indexes derived from individual motor tasks. METHOD: Nineteen PD patients performed three motor tests including leg agility, pronation-supination movement of hands, and walking in a clinic while wearing inertial measurement unit sensors on their wrists and ankles. They performed the tests repeatedly before and after taking 150% of their individual oral levodopa-carbidopa equivalent morning dose.Three neurologists blinded to treatment status, viewed patients' videos and rated their motor symptoms, dyskinesia, overall motor state based on selected items of Unified PD Rating Scale (UPDRS) part III, Dyskinesia scale, and Treatment Response Scale (TRS). To build TRIMS, out of initially 178 extracted features from upper- and lower-limbs data, 39 features were selected by stepwise regression method and were used as input to support vector machines to be mapped to mean reference TRS scores using 10-fold cross-validation method. Test-retest reliability, responsiveness to medication, and correlation to TRS as well as other UPDRS items were evaluated for TRIMS. RESULTS: The correlation of TRIMS with TRS was 0.93. TRIMS had good test-retest reliability (ICC = 0.83). Responsiveness of the TRIMS to medication was good compared to TRS indicating its power in capturing the treatment effects. TRIMS was highly correlated to dyskinesia (R = 0.85), bradykinesia (R = 0.84) and gait (R = 0.79) UPDRS items. Correlation of sensor index from the upper-limb to TRS was 0.89. CONCLUSION: Using the fusion of upper- and lower-limbs sensor data to construct TRIMS provided accurate PD motor states estimation and responsive to treatment. In addition, quantification of upper-limb sensor data during walking test provided strong results.

Utilising an Accelerated Delphi Process to Develop Guidance and Protocols for Telepresence Applications in Remote Robotic Surgery Training.

CONTEXT: The role of robot-assisted surgery continues to expand at a time when trainers and proctors have travel restrictions during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To provide guidance on setting up and running an optimised telementoring service that can be integrated into current validated curricula. We define a standardised approach to training candidates in skill acquisition via telepresence technologies. We aim to describe an approach based on the current evidence and available technologies, and define the key elements within optimised telepresence services, by seeking consensus from an expert committee comprising key opinion leaders in training. EVIDENCE ACQUISITION: This project was carried out in phases: a systematic review of the current literature, a teleconference meeting, and then an initial survey were conducted based on the current evidence and expert opinion, and sent to the committee. Twenty-four experts in training, including clinicians, academics, and industry, contributed to the Delphi process. An accelerated Delphi process underwent three rounds and was completed within 72 h. Additions to the second- and third-round surveys were formulated based on the answers and comments from the previous rounds. Consensus opinion was defined as ≥80% agreement. EVIDENCE SYNTHESIS: There was 100% consensus regarding an urgent need for international agreement on guidance for optimised telepresence. Consensus was reached in multiple areas, including (1) infrastructure and functionality; (2) definitions and terminology; (3) protocols for training, communication, and safety issues; and (4) accountability including ethical and legal issues. The resulting formulated guidance showed good internal consistency among experts, with a Cronbach alpha of 0.90. CONCLUSIONS: Using the Delphi methodology, we achieved international consensus among experts for development and content validation of optimised telepresence services for robotic surgery training. This guidance lays the foundation for launching telepresence services in robotic surgery. This guidance will require further validation. PATIENT SUMMARY: Owing to travel restrictions during the coronavirus disease 2019 (COVID-19) pandemic, development of remote training and support via telemedicine is becoming increasingly important. We report a key opinion leader consensus view on a standardised approach to telepresence.

Evaluation of a sensor algorithm for motor state rating in Parkinson's disease.

INTRODUCTION: A treatment response objective index (TRIS) was previously developed based on sensor data from pronation-supination tests. This study aimed to examine the performance of TRIS for medication effects in a new population sample with Parkinson's disease (PD) and its usefulness for constructing individual dose-response models. METHODS: Twenty-five patients with PD performed a series of tasks throughout a levodopa challenge while wearing sensors. TRIS was used to determine motor changes in pronation-supination tests following a single levodopa dose, and was compared to clinical ratings including the Treatment Response Scale (TRS) and six sub-items of the UPDRS part III. RESULTS: As expected, correlations between TRIS and clinical ratings were lower in the new population than in the initial study. TRIS was still significantly correlated to TRS (rs = 0.23, P < 0.001) with a root mean square error (RMSE) of 1.33. For the patients (n = 17) with a good levodopa response and clear motor fluctuations, a stronger correlation was found (rs = 0.38, RMSE = 1.29, P < 0.001). The mean TRIS increased significantly when patients went from the practically defined off to their best on state (P = 0.024). Individual dose-response models could be fitted for more participants when TRIS was used for modelling than when TRS ratings were used. CONCLUSION: The objective sensor index shows promise for constructing individual dose-response models, but further evaluations and retraining of the TRIS algorithm are desirable to improve its performance and to ensure its clinical effectiveness.

Utilising the Delphi Process to Develop a Proficiency-based Progression Train-the-trainer Course for Robotic Surgery Training.

CONTEXT: As the role of robot-assisted surgery continues to expand, development of standardised and validated training programmes is becoming increasingly important. OBJECTIVE: To provide guidance on an optimised "train-the-trainer" (TTT) structured educational programme for surgical trainers, in which delegates learn a standardised approach to training candidates in skill acquisition. We aim to describe a TTT course for robotic surgery based on the current published literature and to define the key elements within a TTT course by seeking consensus from an expert committee formed of key opinion leaders in training. EVIDENCE ACQUISITION: The project was carried out in phases: a systematic review of the current evidence was conducted, a face-to-face meeting was held in Philadelphia, and then an initial survey was created based on the current literature and expert opinion and sent to the committee. Thirty-two experts in training, including clinicians, academics, and industry, contributed to the Delphi process. The Delphi process underwent three rounds of survey in total. Additions to the second- and third-round surveys were formulated based on the answers and comments from the previous rounds. Consensus opinion was defined as ≥80% agreement. EVIDENCE SYNTHESIS: There was 100% consensus that there was a need for a standardized TTT course in robotic surgery. A consensus was reached in multiple areas, including the following: (1) definitions and terminologies, (2) qualifications to attend, (3) course objectives, (4) precourse considerations, (5) requirement of e-learning, (6) theory and course content, and (7) measurement of outcomes and performance level verification. The resulting formulated curriculum showed good internal consistency among experts, with a Cronbach alpha of 0.90. CONCLUSIONS: Using the Delphi methodology, we achieved an international consensus among experts to develop and reach content validation for a standardised TTT curriculum for robotic surgery training. This defined content lays the foundation for developing a proficiency-based progression model for trainers in robotic surgery. This TTT curriculum will require further validation. PATIENT SUMMARY: As the role of robot-assisted surgery continues to expand, development of standardised and validated training programmes is becoming increasingly important. There is currently a lack of high-level evidence on how best to train trainers in robot-assisted surgery. We report a consensus view on a standardised "train-the trainer" curriculum focused on robotic surgery. It was formulated by training experts from the USA and Europe, combining current evidence for training with experts' knowledge of surgical training.

Individualization of levodopa treatment using a microtablet dispenser and ambulatory accelerometry.

AIM: This 4-week open-label observational study describes the effect of introducing a microtablet dose dispenser and adjusting doses based on objective free-living motor symptom monitoring in individuals with Parkinson's disease (PD). METHODS: Twenty-eight outpatients with PD on stable levodopa treatment with dose intervals of ≤4 hour had their daytime doses of levodopa replaced with levodopa/carbidopa microtablets, 5/1.25 mg (LC-5) delivered from a dose dispenser device with programmable reminders. After 2 weeks, doses were adjusted based on ambulatory accelerometry and clinical monitoring. RESULTS: Twenty-four participants completed the study per protocol. The daily levodopa dose was increased by 15% (112 mg, P < 0.001) from period 1 to 2, and the dose interval was reduced by 12% (22 minutes, P = 0.003). The treatment adherence to LC-5 was high in both periods. The MDS-UPDRS parts II and III, disease-specific quality of life (PDQ-8), wearing-off symptoms (WOQ-19), and nonmotor symptoms (NMS Quest) improved after dose titration, but the generic quality-of-life measure EQ-5D-5L did not. Blinded expert evaluation of accelerometry results demonstrated improvement in 60% of subjects and worsening in 25%. CONCLUSIONS: The introduction of a levodopa microtablet dispenser and accelerometry aided dose adjustments improve PD symptoms and quality of life in the short term.

Adverse Events during Inter-Hospital Transports on Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) may be a lifesaving rescue therapy in refractory, severe respiratory, and/or circulatory failure. To provide the best cost efficiency to the population served and patient outcome, ECMO therapy should be provided by specialized high volume ECMO centers. This requires dedicated transport teams to organize and perform these complex transports. Concerning adverse events and complications during these transfers, only a minimal amount of data has been published. METHODS: To shed light on this matter, all medical transport records from transports on ECMO between January 2010 and June 2016 were analyzed. The data was classified in constituent groups and categorized to risk groups. RESULTS: During the study period, 536 transports on ECMO were performed. The transport records could be identified in 514 of these cases (95.9%). In 163 (31.7%) transports 206 adverse events occurred. In 34 transports two or more adverse events passed on the same trip. No deaths occurred during transport. Sixty-five percent (134) of the complications were Patient related; the most prominent was loss of tidal volume with or without fluid flooding of the lung (n = 57, 43%). Lack of control of equipment was the most common Staff related flaw. Causes due to Equipment/technical (n = 30) could be traced to 14.6% of the events. Vehicle/transportation related complications were reported from 26 transfers, a sub-group in which 50% of the reports concerned malfunction of Ambulance utility/electrical, or Wrong ambulance size at hospital or airport. CONCLUSIONS: If transporting on ECMO high-risk or sudden threat-of-life situations are inevitable and have to be dealt with immediately, sometimes within seconds. A well-trained staff and an experienced high-volume organization are recommended. Key words: extra corporeal membrane oxygenation; ECMO, transport; adverse event; complication.

Levodopa/carbidopa microtablets in Parkinson's disease: a study of pharmacokinetics and blinded motor assessment.

BACKGROUND: Motor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments. OBJECTIVES: This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson's disease. METHODS: This was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations. Patients received 150% of their individual levodopa equivalent morning dose in levodopa-carbidopa microtablets. Blood samples were collected at pre-specified time points. Patients were video recorded and motor function was assessed with six UPDRS part III motor items, dyskinesia score, and the treatment response scale (TRS), rated by three blinded movement disorder specialists. RESULTS: AUC0-4/dose and C max/dose for levodopa was found to be higher in Parkinson's disease patients compared with healthy subjects from a previous study, (p = 0.0008 and p = 0.026, respectively). The mean time to maximum improvement in sum of six UPDRS items score was 78 min (±59) (n = 16), and the mean time to TRS score maximum effect was 54 min (±51) (n = 15). Mean time to onset of dyskinesia was 41 min (±38) (n = 13). CONCLUSIONS: In the PD population, following levodopa/carbidopa microtablet administration in fasting state, the Cmax and AUC0-4/dose were found to be higher compared with results from a previous study in young, healthy subjects. A large between subject variability in response and duration of effect was observed, highlighting the importance of a continuous and individual assessment of motor function in order to optimize treatment effect.

Mechanisms underlying skilled anticipation and recognition in a dynamic and temporally constrained domain.

We examined the mechanisms underlying skilled anticipation and recognition in a dynamic, interactive, and temporally constrained domain. Skilled and less-skilled participants viewed dynamic film stimuli, anticipated event outcome, and provided immediate retrospective verbal reports. Previously viewed and novel sequences were then presented in film or point-light display format. Participants made recognition judgements and again gave retrospective verbal reports on their thought processes. Skilled participants demonstrated superior anticipation accuracy and were more sensitive in distinguishing previously seen from novel stimuli than less-skilled participants. Skilled participants utilised more complex memory representations than less-skilled individuals, as indicated by references in their retrospective reports to more evaluation and prediction statements. The representations activated during anticipation were more complex than those for recognition judgements in both groups. Findings are discussed with reference to long-term working memory theory.

Identifying population differences in whole-brain structural networks: a machine learning approach.

Models of whole-brain connectivity are valuable for understanding neurological function, development and disease. This paper presents a machine learning based approach to classify subjects according to their approximated structural connectivity patterns and to identify features which represent the key differences between groups. Brain networks are extracted from diffusion magnetic resonance images obtained by a clinically viable acquisition protocol. Connections are tracked between 83 regions of interest automatically extracted by label propagation from multiple brain atlases followed by classifier fusion. Tracts between these regions are propagated by probabilistic tracking, and mean anisotropy measurements along these connections provide the feature vectors for combined principal component analysis and maximum uncertainty linear discriminant analysis. The approach is tested on two populations with different age distributions: 20-30 and 60-90 years. We show that subjects can be classified successfully (with 87.46% accuracy) and that the features extracted from the discriminant analysis agree with current consensus on the neurological impact of ageing.

Multivariate statistical analysis of whole brain structural networks obtained using probabilistic tractography.

This paper presents a new framework for the analysis of anatomical connectivity derived from diffusion tensor MRI. The framework has been applied to estimate whole brain structural networks using diffusion data from 174 adult subjects. In the proposed approach, each brain is first segmented into 83 anatomical regions via label propagation of multiple atlases and subsequent decision fusion. For each pair of anatomical regions the probability of connection and its strength is then estimated using a modified version of probabilistic tractography. The resulting brain networks have been classified according to age and gender using non-linear support vector machines with GentleBoost feature extraction. Classification performance was tested using a leave-one-out approach and the mean accuracy obtained was 85.4%.

A pilot study of facial, cranial and brain MRI morphometry in men with schizophrenia: part 2.

This pilot study applies a new 3D morphometric MR method to test the hypothesis that men with schizophrenia (vs. controls) have deviant facial shapes and landmark relations in cranio/facial/brain (CFB) regions. This constitutes Part 2 of paired articles in this issue of Psychiatry Research: Neuroimaging, in which Part 1 presents the new method in detail. MRI coordinates from CFB landmarks of 23 patients and 15 controls were identified and then aligned with the Procrustes model, leaving shape as the only unit-less geometrical information. Men with schizophrenia had significantly longer mid- and lower-facial heights, and greater lower (left) facial depth, with a tendency toward rotation along the facial midline. This supports findings from earlier anthropometric and 3D studies of the "exterior" (face). In contrast, none of the patient-control differences for the new "interior" (cranial-brain) distances reached statistical significance. These results need to be retested on a larger sample of both sexes.

Cognitive function after on or off pump coronary artery bypass grafting.

OBJECTIVE: To investigate cognitive outcome after on and off pump coronary artery bypass grafting. METHODS: Seventy patients between 50 and 80 years with stable angina pectoris, ejection fraction >30%, serum creatinine <150 micromol/l, and lack of tight main stem stenosis were randomized to on or off pump coronary artery bypass grafting. Standardized neuropsychological tests evaluated attention, verbal and visuo-spatial short-term and working memory, verbal learning, delayed recall, visuo-motor speed, and aspects of executive functions. Levels of anxiety and depression were also investigated. Testing was performed before and at 1 week, 1 and 6 months after surgery. RESULTS: There was no difference in cognitive impairment (defined as a 20% reduction in at least 20% of the tests) between groups. The incidence at 1 week post-operatively was 57% in the on pump group and 58% in the off pump group, after 1 month 30% and 12% and after 6 months 19% and 15%, respectively (p for interaction=0.19). There was no difference between groups in anxiety (p=0.18) or depression (p=0.48). CONCLUSIONS: This prospective, randomized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients.

Hemostasis in off-pump compared to on-pump coronary artery bypass grafting: a prospective, randomized study.

BACKGROUND: We hypothesized that off-pump coronary artery bypass grafting has less impact on the hemostatic systems than on-pump surgery. METHODS: Thirty-one patients were randomized to on-pump or off-pump coronary artery bypass grafting. Factors of hemostasis as well as markers of endothelial activation were measured up to 24 hours after the operation: Fibrin D dimer, prothrombin fragment 1+2, alpha2-macroglobulin, protein C1 esterase inhibitor, fibronectin, and von Willebrand factor. Overall hemostasis potential, overall coagulation potential, and overall fibrinolysis potential were determined with a previously developed assay. We also measured platelet count before and after surgery. RESULTS: Fibrin D dimer and prothrombin fragment 1+2 concentrations were lower during surgery in the off-pump group (p < 0.001). Four hours after admission to the intensive care unit, these differences were eliminated. alpha2-macroglobulin, protein C1 esterase inhibitor, fibronectin, and von Willebrand factor concentrations did not differ between groups (p = 0.59, p = 0.28, p = 0.22, and p = 0.69). Protein C1 esterase inhibitor and von Willebrand factor concentrations increased over time (p < 0.001) in both groups. Overall hemostasis potential and overall coagulation potential increased over time (p < 0.001), while overall fibrinolysis potential decreased (p < 0.001) with no difference between groups (p = 0.69, p = 0.91). Platelet count decreased on the first postoperative day (p < 0.001), but increased from the first to the third postoperative day (p = 0.004) in both groups without any inter group difference (p = 0.82). CONCLUSIONS: There was a tendency toward less activation of coagulation and fibrinolysis in low-risk patients during elective off-pump coronary artery bypass surgery when compared with on-pump surgery.

Pulmonary hemodynamics and gas exchange in off pump coronary artery bypass grafting.

OBJECTIVES: To investigate the influence of cardiopulmonary bypass on pulmonary hemodynamics and gas exchange. METHODS: Low risk patients admitted for elective coronary artery bypass grafting were randomized to either on (n=25) or off pump (n=25) surgery. Central hemodynamics, gas exchange, and venous admixture were studied during and up to 20 h after surgery. RESULTS: There was no difference in pulmonary vascular resistance index (P=0.16), right ventricular stroke work index (P>0.2), mean pulmonary artery pressure (P>0.2) or pulmonary capillary wedge pressure (P>0.2) between groups. Soon after surgery there was a tendency towards higher cardiac index (P=0.07) in the off pump group. Arterial oxygen tension (P>0.2), hematocrit (P>0.2), venous admixture (P>0.2), and arterial-venous oxygen content difference (P=0.12) did not differ between groups. CONCLUSIONS: This prospective, randomized study showed no difference in pulmonary hemodynamics, pulmonary gas exchange, and venous admixture, in low risk patients undergoing off pump compared to on pump coronary artery bypass surgery.

In and ex vivo MR evaluation of acute myocardial ischemia in pigs by determining R1 in steady state after the administration of the intravascular contrast agent NC100150 injection.

RATIONALE AND OBJECTIVES: To study the dose response in perfused and nonperfused myocardium by measuring relaxation rate (R1) in a steady-state situation after injection of the intravascular contrast agent NC100150 Injection in pigs and whether the dose response differs in vivo and ex vivo. MATERIALS AND METHODS: The left anterior descending artery was occluded. R1 was measured using a Look-Locker sequence for 2 dose groups (2 mg Fe/kg bw, n = 4, and 5 mg Fe/kg bw, n = 5) and a control group (n = 3). RESULTS: A significant increase in R1 was found in perfused myocardium after contrast agent injection, in contrast to nonperfused myocardium. There was a significantly larger difference in R1 between perfused and nonperfused myocardium in the 5 mg Fe/kg bw dose group compared with the other 2 groups. The difference in R1 between perfused and nonperfused myocardium was significantly higher in vivo than ex vivo. CONCLUSION: A nearly linear R1 dose response was found in perfused myocardium in vivo. The dose response ex vivo was less steep possibly due to larger water exchange limitations.

Functional evaluation of cerebral microembolization in the rat.

This study investigates the effects of cerebral microembolism on motor performance and risk assessment behavior in the rat. Cerebral infarcts were produced in rats by injecting small plastic beads into the left heart ventricle under short-acting anesthesia. The functional outcome was tested 24 h later by subjecting the animals to a series of consecutive behavioral tests. Thereafter, the rats were anesthetized and underwent magnetic resonance imaging. On average about seven infarcts per brain were found. The volume of the individual infarcts was largest in the hippocampus (mean=4.26 mm(3)) and smallest in the white matter (mean=0.83 mm(3)). Embolized animals performed spontaneous and evident locomotion. The activity was, however, significantly decreased compared to rats treated with vehicle. More specific tests for motor ability revealed reduced gait capacity and muscular strength. A significant relationship was found between behaviors reflecting motor ability and the total volume of infarcted tissue in the brain stem, cortex and cerebellum. Also the behavioral profile of risk and benefit assessment was found to be altered by the microembolization. It is concluded that the combination of the microembolization method and behavioral tests provides a valuable tool for further studies of the pathophysiology of, and potential treatment for, cerebral infarction.