Search results for: ineffective tissue cerebral perfusion
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1991

Search results for: ineffective tissue cerebral perfusion

1841 The Contribution of Lower Visual Channels and Evolutionary Origin of the Tunnel Effect

Authors: Shai Gabay

Abstract:

The tunnel effect describes the phenomenon where a moving object seems to persist even when temporarily hidden from view. Numerous studies indicate that humans, infants, and nonhuman primates possess object persistence, relying on spatiotemporal cues to track objects that are dynamically occluded. While this ability is associated with neural activity in the cerebral neocortex of humans and mammals, the role of subcortical mechanisms remains ambiguous. In our current investigation, we explore the functional contribution of monocular aspects of the visual system, predominantly subcortical, to the representation of occluded objects. This is achieved by manipulating whether the reappearance of an object occurs in the same or different eye from its disappearance. Additionally, we employ Archerfish, renowned for their precision in dislodging insect prey with water jets, as a phylogenetic model to probe the evolutionary origins of the tunnel effect. Our findings reveal the active involvement of subcortical structures in the mental representation of occluded objects, a process evident even in species that do not possess cortical tissue.

Keywords: archerfish, tunnel effect, mental representations, monocular channels, subcortical structures

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1840 An Exploration of the Pancreatic Cancer miRNome during the Progression of the Disease

Authors: Barsha Saha, Shouvik Chakravarty, Sukanta Ray, Kshaunish Das, Nidhan K. Biswas, Srikanta Goswami

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Pancreatic Ductal Adenocarcinoma is a well-recognised cause of cancer death with a five-year survival rate of about 9%, and its incidence in India has been found to be increased manifold in recent years. Due to delayed detection, this highly metastatic disease has a poor prognosis. Several molecular alterations happen during the progression of the disease from pre-cancerous conditions, and many such alterations could be investigated for their biomarker potential. MicroRNAs have been shown to be prognostic for PDAC patients in a variety of studies. We hereby used NGS technologies to evaluate the role of small RNA changes during pancreatic cancer development from chronic pancreatitis. Plasma samples were collected from pancreatic cancer patients (n=16), chronic pancreatitis patients (n=8), and also from normal individuals (n=16). Pancreatic tumour tissue (n=5) and adjacent normal tissue samples (n=5) were also collected. Sequencing of small RNAs was carried out after small RNAs were isolated from plasma samples and tissue samples. We find that certain microRNAs are highly deregulated in pancreatic cancer patients in comparison to normal samples. A combinatorial analysis of plasma and tissue microRNAs and subsequent exploration of their targets and altered molecular pathways could not only identify potential biomarkers for disease diagnosis but also help to understand the underlying mechanism.

Keywords: small RNA sequencing, pancreatic cancer, biomarkers, tissue sample

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1839 Mapping Iron Content in the Brain with Magnetic Resonance Imaging and Machine Learning

Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher

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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.

Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping

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1838 Quantification of Global Cerebrovascular Reactivity in the Principal Feeding Arteries of the Human Brain

Authors: Ravinder Kaur

Abstract:

Introduction Global cerebrovascular reactivity (CVR) mapping is a promising clinical assessment for stress-testing the brain using physiological challenges, such as CO₂, to elicit changes in perfusion. It enables real-time assessment of cerebrovascular integrity and health. Conventional imaging approaches solely use steady-state parameters, like cerebral blood flow (CBF), to evaluate the integrity of the resting parenchyma and can erroneously show a healthy brain at rest, despite the underlying pathogenesis in the presence of cerebrovascular disease. Conversely, coupling CO₂ inhalation with phase-contrast MRI neuroimaging interrogates the capacity of the vasculature to respond to changes under stress. It shows promise in providing prognostic value as a novel health marker to measure neurovascular function in disease and to detect early brain vasculature dysfunction. Objective This exploratory study was established to:(a) quantify the CBF response to CO₂ in hypocapnia and hypercapnia,(b) evaluate disparities in CVR between internal carotid (ICA) and vertebral artery (VA), and (c) assess sex-specific variation in CVR. Methodology Phase-contrast MRI was employed to measure the cerebrovascular reactivity to CO₂ (±10 mmHg). The respiratory interventions were presented using the prospectively end-tidal targeting RespirActTM Gen3 system. Post-processing and statistical analysis were conducted. Results In 9 young, healthy subjects, the CBF increased from hypocapnia to hypercapnia in all vessels (4.21±0.76 to 7.20±1.83 mL/sec in ICA, 1.36±0.55 to 2.33±1.31 mL/sec in VA, p < 0.05). The CVR was quantitatively higher in ICA than VA (slope of linear regression: 0.23 vs. 0.07 mL/sec/mmHg, p < 0.05). No statistically significant effect was observed in CVR between male and female (0.25 vs 0.20 mL/sec/mmHg in ICA, 0.09 vs 0.11 mL/sec/mmHg in VA, p > 0.05). Conclusions The principal finding in this investigation validated the modulation of CBF by CO₂. Moreover, it has indicated that regional heterogeneity in hemodynamic response exists in the brain. This study provides scope to standardize the quantification of CVR prior to its clinical translation.

Keywords: cerebrovascular disease, neuroimaging, phase contrast MRI, cerebrovascular reactivity, carbon dioxide

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1837 Gellan Gum/Gamma-Polyglutamic Acid and Glycerol Composited Membrane for Guiding Bone Regeneration

Authors: Chi-Chang Lin, Jiun-Yan Chiu

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Periodontal disease, oral cancer relating trauma is the prominent factor devastating bone tissue that is crucial to reestablishing in clinical. As we know, common symptom, osteoporosis, and infection limiting the ability of the bone tissue to recover cause difficulty before implantation therapy. Regeneration of bone tissue is the fundamental therapy before surgical processes. To promote the growth of bone tissue, many commercial products still have sophisticated problems that need to overcome. Regrettably, there is no available material which is apparently preferable for releasing and controlling of loading dosage, or mitigating inflammation. In our study, a hydrogel-based composite membrane has been prepared by using Gellan gum (GG), gamma-polyglutamic acid (γ-PGA) and glycerol with simple sol-gel method. GG is a natural material that is massively adopted in cartilage. Unfortunately, the strength of pure GG film is a manifest weakness especially under simulating body fluidic conditions. We utilize another biocompatible material, γ-PGA as cross-linker which can form tri-dimension structure that enhancing the strength. Our result indicated the strength of pure GG membrane can be obviously improved by cross-linked with γ-PGA (0.5, 0.6, 0.7, 0.8, 0.9, 1.0 w/v%). Besides, blending with glycerol (0, 1.0, 2.0, 3.0 w/v%) can significantly improve membrane toughness that corresponds to practical use. The innovative composited hydrogel made of GG, γ-PGA, and glycerol is attested with neat results including elongation and biocompatibility that take the advantage of extension covering major trauma. Recommendations are made for treatment to build up the foundation of bone tissue that would help patients to escape from the suffering and shorten the amount of time in recovery.

Keywords: bone tissue, gellan gum, regeneration, toughness

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1836 Mechanical Characterization of Brain Tissue in Compression

Authors: Abbas Shafiee, Mohammad Taghi Ahmadian, Maryam Hoviattalab

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The biomechanical behavior of brain tissue is needed for predicting the traumatic brain injury (TBI). Each year over 1.5 million people sustain a TBI in the USA. The appropriate coefficients for injury prediction can be evaluated using experimental data. In this study, an experimental setup on brain soft tissue was developed to perform unconfined compression tests at quasistatic strain rates ∈0.0004 s-1 and 0.008 s-1 and 0.4 stress relaxation test under unconfined uniaxial compression with ∈ 0.67 s-1 ramp rate. The fitted visco-hyperelastic parameters were utilized by using obtained stress-strain curves. The experimental data was validated using finite element analysis (FEA) and previous findings. Also, influence of friction coefficient on unconfined compression and relaxation test and effect of ramp rate in relaxation test is investigated. Results of the findings are implemented on the analysis of a human brain under high acceleration due to impact.

Keywords: brain soft tissue, visco-hyperelastic, finite element analysis (FEA), friction, quasistatic strain rate

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1835 Estimation of Morbidity Level of Industrial Labour Conditions at Zestafoni Ferroalloy Plant

Authors: M. Turmanauli, T. Todua, O. Gvaberidze, R. Javakhadze, N. Chkhaidze, N. Khatiashvili

Abstract:

Background: Mining process has the significant influence on human health and quality of life. In recent years the events in Georgia were reflected on the industry working process, especially minimal requirements of labor safety, hygiene standards of workplace and the regime of work and rest are not observed. This situation is often caused by the lack of responsibility, awareness, and knowledge both of workers and employers. The control of working conditions and its protection has been worsened in many of industries. Materials and Methods: For evaluation of the current situation the prospective epidemiological study by face to face interview method was conducted at Georgian “Manganese Zestafoni Ferroalloy Plant” in 2011-2013. 65.7% of employees (1428 bulletin) were surveyed and the incidence rates of temporary disability days were studied. Results: The average length of a temporary disability single accident was studied taking into consideration as sex groups as well as the whole cohort. According to the classes of harmfulness the following results were received: Class 2.0-10.3%; 3.1-12.4%; 3.2-35.1%; 3.3-12.1%; 3.4-17.6%; 4.0-12.5%. Among the employees 47.5% and 83.1% were tobacco and alcohol consumers respectively. According to the age groups and years of work on the base of previous experience ≥50 ages and ≥21 years of work data prevalence respectively. The obtained data revealed increased morbidity rate according to age and years of work. It was found that the bone and articulate system and connective tissue diseases, aggravation of chronic respiratory diseases, ischemic heart diseases, hypertension and cerebral blood discirculation were the leading among the other diseases. High prevalence of morbidity observed in the workplace with not satisfactory labor conditions from the hygienic point of view. Conclusion: According to received data the causes of morbidity are the followings: unsafety labor conditions; incomplete of preventive medical examinations (preliminary and periodic); lack of access to appropriate health care services; derangement of gathering, recording, and analysis of morbidity data. This epidemiological study was conducted at the JSC “Manganese Ferro Alloy Plant” according to State program “ Prevention of Occupational Diseases” (Program code is 35 03 02 05).

Keywords: occupational health, mining process, morbidity level, cerebral blood discirculation

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1834 Accumulation of Phlorotannins in Abalone Haliotis discus Hannai after Feeding with Eisenia bicyclis

Authors: Bangoura Issa, Ji-Young Kang, M. T. H. Chowdhury, Ji-Eun Lee, Yong-Ki Hong

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Investigation was carried out for the production of value-added abalone Haliotis discus hannai containing bioactive phlorotannin by feeding phlorotannin-rich seaweed Eisenia bicyclis 2 weeks prior to harvesting. Accumulation of phlorotannins was proceded by feeding with E. bicyclis after 4 days of starvation. HPLC purification afforded two major phlorotannins. Mass spectrometry and 1H-nuclear magnetic resonance analysis clarified their structures to be as 7-phloroeckol and eckol. Throughout the feeding period of 20 days, 7-phloroeckolol was accumulated in the muscle (foot muscle tissue) up to 0.18±0.12 mg g-1 dry weight of tissue after 12 days. Eckol reached 0.21±0.03 mg g-1 dry weight of tissue after 18 days. By feeding Laminaria japonica as reference, abalone showed no detection of phlorotannins in the muscle tissue. Seaweed consumption and growth rate of abalone revealed almost similar when feed with E. bicyclis or L. japonicain 20 days. Phlorotannins reduction to half-maximal accumulation values took 1.0 day and 2.7 days for 7-phloroeckol and eckol respectively, after replacing the feed to L. japonica.

Keywords: abalone, accumulation, eisenia bicyclis, phlorotannins

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1833 Investigation of Astrocyte Physiology on Stiffness-Controlled Cellulose Acetate Nanofiber as a Tissue Scaffold

Authors: Sun Il Yu, Jung Hyun Joo, Hwa Sung Shin

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Astrocytes are known as dominant cells in CNS and play a role as a supporter of CNS activity and regeneration. Recently, three-dimensional culture of astrocytes were actively applied to understand in vivo astrocyte works. Electrospun nanofibers are attractive for 3D cell culture system because they have a high surface to volume ratio and porous structure, and have already been used for 3D astrocyte cultures. In this research, the stiffness of cellulose acetate (CA) nanofiber was controlled by heat treatment. As stiffness increased, astrocyte cell viability and adhesion increased. Reactivity of astrocyte was also upregulated in stiffer CA nanofiber in terms of GFAP, an intermediate filament protein. Finally, we demonstrated that stiffness-controllable CA is attractive for astrocyte tissue engineering.

Keywords: astrocyte, cellulose acetate, nanofiber, tissue scaffold

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1832 Non-Invasive Evaluation of Patients After Percutaneous Coronary Revascularization. The Role of Cardiac Imaging

Authors: Abdou Elhendy

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Numerous study have shown the efficacy of the percutaneous intervention (PCI) and coronary stenting in improving left ventricular function and relieving exertional angina. Furthermore, PCI remains the main line of therapy in acute myocardial infarction. Improvement of procedural techniques and new devices have resulted in an increased number of PCI in those with difficult and extensive lesions, multivessel disease as well as total occlusion. Immediate and late outcome may be compromised by acute thrombosis or the development of fibro-intimal hyperplasia. In addition, progression of coronary artery disease proximal or distal to the stent as well as in non-stented arteries is not uncommon. As a result, complications can occur, such as acute myocardial infarction, worsened heart failure or recurrence of angina. In a stent, restenosis can occur without symptoms or with atypical complaints rendering the clinical diagnosis difficult. Routine invasive angiography is not appropriate as a follow up tool due to associated risk and cost and the limited functional assessment. Exercise and pharmacologic stress testing are increasingly used to evaluate the myocardial function, perfusion and adequacy of revascularization. Information obtained by these techniques provide important clues regarding presence and severity of compromise in myocardial blood flow. Stress echocardiography can be performed in conjunction with exercise or dobutamine infusion. The diagnostic accuracy has been moderate, but the results provide excellent prognostic stratification. Adding myocardial contrast agents can improve imaging quality and allows assessment of both function and perfusion. Stress radionuclide myocardial perfusion imaging is an alternative to evaluate these patients. The extent and severity of wall motion and perfusion abnormalities observed during exercise or pharmacologic stress are predictors of survival and risk of cardiac events. According to current guidelines, stress echocardiography and radionuclide imaging are considered to have appropriate indication among patients after PCI who have cardiac symptoms and those who underwent incomplete revascularization. Stress testing is not recommended in asymptomatic patients, particularly early after revascularization, Coronary CT angiography is increasingly used and provides high sensitive for the diagnosis of coronary artery stenosis. Average sensitivity and specificity for the diagnosis of in stent stenosis in pooled data are 79% and 81%, respectively. Limitations include blooming artifacts and low feasibility in patients with small stents or thick struts. Anatomical and functional cardiac imaging modalities are corner stone for the assessment of patients after PCI and provide salient diagnostic and prognostic information. Current imaging techniques cans serve as gate keeper for coronary angiography, thus limiting the risk of invasive procedures to those who are likely to benefit from subsequent revascularization. The determination of which modality to apply requires careful identification of merits and limitation of each technique as well as the unique characteristic of each individual patient.

Keywords: coronary artery disease, stress testing, cardiac imaging, restenosis

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1831 Negative RT-PCR in a Newborn Infected with Zika Virus: A Case Report

Authors: Vallejo Michael, Acuña Edgar, Roa Juan David, Peñuela Rosa, Parra Alejandra, Casallas Daniela, Rodriguez Sheyla

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Congenital Zika Virus Syndrome is an entity composed by a variety of birth defects presented in newborns that have been exposed to the Zika Virus during pregnancy. The syndrome characteristic features are severe microcephaly, cerebral tissue abnormalities, ophthalmological abnormalities such as uveitis and chorioretinitis, arthrogryposis, clubfoot deformity and muscular tone abnormalities. The confirmatory test is the Reverse transcription polymerase chain reaction (RT-PCR) associated to the physical findings. Here we present the case of a newborn with microcephaly whose mother presented a confirmed Zika Virus infection during the third trimester of pregnancy, despite of the evident findings and the history of Zika infection the RT-PCR in amniotic and cerebrospinal fluid of the newborn was negative. RT-PCR has demonstrated a low sensibility in samples with low viral loads, reason why, we propose a clinical diagnosis in patients with clinical history of Zika Virus infection during pregnancy accompanied by evident clinical manifestations of the child.

Keywords: congenital, Zika virus, microcephaly, reverse transcriptase polymerase chain reaction

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1830 The Relationship between Human Neutrophil Elastase Levels and Acute Respiratory Distress Syndrome in Patients with Thoracic Trauma

Authors: Wahyu Purnama Putra, Artono Isharanto

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Thoracic trauma is trauma that hits the thoracic wall or intrathoracic organs, either due to blunt trauma or sharp trauma. Thoracic trauma often causes impaired ventilation-perfusion due to damage to the lung parenchyma. This results in impaired tissue oxygenation, which is one of the causes of acute respiratory distress syndrome (ARDS). These changes are caused by the release of pro-inflammatory mediators, plasmatic proteins, and proteases into the alveolar space associated with ongoing edema, as well as oxidative products that ultimately result in severe inhibition of the surfactant system. This study aims to predict the incidence of acute respiratory distress syndrome (ARDS) through human neutrophil elastase levels. This study examines the relationship between plasma elastase levels as a predictor of the incidence of ARDS in thoracic trauma patients in Malang. This study is an observational cohort study. Data analysis uses the Pearson correlation test and ROC curve (receiver operating characteristic curve). It can be concluded that there is a significant (p= 0.000, r= -0.988) relationship between elastase levels and BGA-3. If the value of elastase levels is limited to 23.79 ± 3.95, the patient will experience mild ARDS. While if the value of elastase levels is limited to 57.68 ± 18.55, in the future, the patient will experience moderate ARDS. Meanwhile, if the elastase level is between 107.85 ± 5.04, the patient will likely experience severe ARDS. Neutrophil elastase levels correlate with the degree of severity of ARDS incidence.

Keywords: ARDS, human neutrophil elastase, severity, thoracic trauma

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1829 Optimization of Perfusion Distribution in Custom Vascular Stent-Grafts Through Patient-Specific CFD Models

Authors: Scott M. Black, Craig Maclean, Pauline Hall Barrientos, Konstantinos Ritos, Asimina Kazakidi

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Aortic aneurysms and dissections are leading causes of death in cardiovascular disease. Both inevitably lead to hemodynamic instability without surgical intervention in the form of vascular stent-graft deployment. An accurate description of the aortic geometry and blood flow in patient-specific cases is vital for treatment planning and long-term success of such grafts, as they must generate physiological branch perfusion and in-stent hemodynamics. The aim of this study was to create patient-specific computational fluid dynamics (CFD) models through a multi-modality, multi-dimensional approach with boundary condition optimization to predict branch flow rates and in-stent hemodynamics in custom stent-graft configurations. Three-dimensional (3D) thoracoabdominal aortae were reconstructed from four-dimensional flow-magnetic resonance imaging (4D Flow-MRI) and computed tomography (CT) medical images. The former employed a novel approach to generate and enhance vessel lumen contrast via through-plane velocity at discrete, user defined cardiac time steps post-hoc. To produce patient-specific boundary conditions (BCs), the aortic geometry was reduced to a one-dimensional (1D) model. Thereafter, a zero-dimensional (0D) 3-Element Windkessel model (3EWM) was coupled to each terminal branch to represent the distal vasculature. In this coupled 0D-1D model, the 3EWM parameters were optimized to yield branch flow waveforms which are representative of the 4D Flow-MRI-derived in-vivo data. Thereafter, a 0D-3D CFD model was created, utilizing the optimized 3EWM BCs and a 4D Flow-MRI-obtained inlet velocity profile. A sensitivity analysis on the effects of stent-graft configuration and BC parameters was then undertaken using multiple stent-graft configurations and a range of distal vasculature conditions. 4D Flow-MRI granted unparalleled visualization of blood flow throughout the cardiac cycle in both the pre- and postsurgical states. Segmentation and reconstruction of healthy and stented regions from retrospective 4D Flow-MRI images also generated 3D models with geometries which were successfully validated against their CT-derived counterparts. 0D-1D coupling efficiently captured branch flow and pressure waveforms, while 0D-3D models also enabled 3D flow visualization and quantification of clinically relevant hemodynamic parameters for in-stent thrombosis and graft limb occlusion. It was apparent that changes in 3EWM BC parameters had a pronounced effect on perfusion distribution and near-wall hemodynamics. Results show that the 3EWM parameters could be iteratively changed to simulate a range of graft limb diameters and distal vasculature conditions for a given stent-graft to determine the optimal configuration prior to surgery. To conclude, this study outlined a methodology to aid in the prediction post-surgical branch perfusion and in-stent hemodynamics in patient specific cases for the implementation of custom stent-grafts.

Keywords: 4D flow-MRI, computational fluid dynamics, vascular stent-grafts, windkessel

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1828 Exploring the Issue of Occult Hypoperfusion in the Pre-Hospital Setting

Authors: A. Fordham, A. Hudson

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Background: Studies have suggested 16-25% of normotensive trauma patients with no clinical signs of shock have abnormal lactate and BD readings evidencing shock; a phenomenon known as occult hypoperfusion (OH). In light of the scarce quantity of evidence currently documenting OH, this study aimed to identify the prevalence of OH in the pre-hospital setting and explore ways to improve its identification and management. Methods: A quantitative retrospective data analysis was carried out on 75 sets of patient records for trauma patients treated by Kent Surrey Sussex Air Ambulance Trust between November 2013 and October 2014. The KSS HEMS notes and subsequent ED notes were collected. Trends between patients’ SBP on the scene, whether or not they received PRBCs on the scene as well as lactate and BD readings in the ED were assessed. Patients’ KSS HEMS notes written by the HEMS crew were also reviewed and recorded. Results: -Suspected OH was identified in 7% of the patients who did not receive PRBCs in the pre-hospital phase. -SBP heavily influences the physicians’ decision of whether or not to transfuse PRBCs in the pre-hospital phase. Preliminary conclusions: OH is an under-studied and underestimated phenomenon. We suggest a prospective trial is carried out to evaluate whether detecting trauma patients’ tissue perfusion status in the pre-hospital phase using portable devices capable of measuring serum BD and/or lactate could aid more accurate detection and management of all haemorrhaging trauma patients, including patients with OH.

Keywords: occult hypoperfusion, PRBC transfusion, point of care testing, pre-hospital emergency medicine, trauma

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1827 Dynamic Behavior of Brain Tissue under Transient Loading

Authors: Y. J. Zhou, G. Lu

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In this paper, an analytical study is made for the dynamic behavior of human brain tissue under transient loading. In this analytical model the Mooney-Rivlin constitutive law is coupled with visco-elastic constitutive equations to take into account both the nonlinear and time-dependent mechanical behavior of brain tissue. Five ordinary differential equations representing the relationships of five main parameters (radial stress, circumferential stress, radial strain, circumferential strain, and particle velocity) are obtained by using the characteristic method to transform five partial differential equations (two continuity equations, one motion equation, and two constitutive equations). Analytical expressions of the attenuation properties for spherical wave in brain tissue are analytically derived. Numerical results are obtained based on the five ordinary differential equations. The mechanical responses (particle velocity and stress) of brain are compared at different radii including 5, 6, 10, 15 and 25 mm under four different input conditions. The results illustrate that loading curves types of the particle velocity significantly influences the stress in brain tissue. The understanding of the influence by the input loading cures can be used to reduce the potentially injury to brain under head impact by designing protective structures to control the loading curves types.

Keywords: analytical method, mechanical responses, spherical wave propagation, traumatic brain injury

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1826 Coating of Polyelectrolyte Multilayer Thin Films on Poly(S/EGDMA) HIPE Loaded with Hydroxyapatite as a Scaffold for Tissue Engineering Application

Authors: Kornkanok Noulta, Pornsri Pakeyangkoon, Stephen T. Dubas, Pomthong Malakul, Manit Nithithanakul

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In recent years, interest in the development of material for tissue engineering application has increased considerably. Poly(High Internal Phase Emulsion) (PolyHIPE) foam is a material that is good candidate for used in tissue engineering application due to its 3D structure and highly porous with interconnected pore. The PolyHIPE was prepared from poly (styrene/ethylene glycol dimethacrylate) through high internal phase emulsion polymerization technique and loaded with hydroxyapatite (HA) to improve biocompatibility. To further increase hydrophilicity of the obtained polyHIPE, layer-by-layer polyelectrolyte multilayers (PEM) technique was used. A surface property of polyHIPE was characterized by contact angle measurement. Morphology and pore size was observed by scanning electron microscope (SEM). The cell viability was revealed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay technique.

Keywords: polyelectrolyte multilayer thin film, high internal phase emulsion, polyhipe foam, scaffold, tissue engineering

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1825 The Effect of Physical Guidance on Learning a Tracking Task in Children with Cerebral Palsy

Authors: Elham Azimzadeh, Hamidollah Hassanlouei, Hadi Nobari, Georgian Badicu, Jorge Pérez-Gómez, Luca Paolo Ardigò

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Children with cerebral palsy (CP) have weak physical abilities and their limitations may have an effect on performing everyday motor activities. One of the most important and common debilitating factors in CP is the malfunction in the upper extremities to perform motor skills and there is strong evidence that task-specific training may lead to improve general upper limb function among this population. However, augmented feedback enhances the acquisition and learning of a motor task. Practice conditions may alter the difficulty, e.g., the reduced frequency of PG could be more challenging for this population to learn a motor task. So, the purpose of this study was to investigate the effect of physical guidance (PG) on learning a tracking task in children with cerebral palsy (CP). Twenty-five independently ambulant children with spastic hemiplegic CP aged 7-15 years were assigned randomly to five groups. After the pre-test, experimental groups participated in an intervention for eight sessions, 12 trials during each session. The 0% PG group received no PG; the 25% PG group received PG for three trials; the 50% PG group received PG for six trials; the 75% PG group received PG for nine trials; and the 100% PG group, received PG for all 12 trials. PG consisted of placing the experimenter's hand around the children's hand, guiding them to stay on track and complete the task. Learning was inferred by acquisition and delayed retention tests. The tests involved two blocks of 12 trials of the tracking task without any PG being performed by all participants. They were asked to make the movement as accurate as possible (i.e., fewer errors) and the number of total touches (errors) in 24 trials was calculated as the scores of the tests. The results showed that the higher frequency of PG led to more accurate performance during the practice phase. However, the group that received 75% PG had significantly better performance compared to the other groups in the retention phase. It is concluded that the optimal frequency of PG played a critical role in learning a tracking task in children with CP and likely this population may benefit from an optimal level of PG to get the appropriate amount of information confirming the challenge point framework (CPF), which state that too much or too little information will retard learning a motor skill. Therefore, an optimum level of PG may help these children to identify appropriate patterns of motor skill using extrinsic information they receive through PG and improve learning by activating the intrinsic feedback mechanisms.

Keywords: cerebral palsy, challenge point framework, motor learning, physical guidance, tracking task

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1824 Self-Inflating Soft Tissue Expander Outcome for Alveolar Ridge Augmentation a Randomized Controlled Clinical and Histological Study

Authors: Alaa T. Ali, Nevine H. Kheir El Din, Ehab S. Abdelhamid, Ahmed E. Amr

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Objective: Severe alveolar bone resorption is usually associated with a deficient amount of soft tissues. soft tissue expansion is introduced to provide an adequate amount of soft tissue over the grafted area. This study aimed to assess the efficacy of sub-periosteal self-inflating osmotic tissue expanders used as preparatory surgery before horizontal alveolar ridge augmentation using autogenous onlay block bone graft. Methods: A prospective randomized controlled clinical trial was performed. Sixteen partially edentulous patients demanding horizontal bone augmentation in the anterior maxilla were randomly assigned to horizontal ridge augmentation with autogenous bone block grafts harvested from the mandibular symphysis. For the test group, soft tissue expanders were placed sub-periosteally before horizontal ridge augmentation. Impressions were taken before and after STE, and the cast models were optically scanned and superimposed to be used for volumetric analysis. Horizontal ridge augmentation was carried out after STE completion. For the control group, a periosteal releasing incision was performed during bone augmentation procedures. Implants were placed in both groups at re-entry surgery after six months period. A core biopsy was taken. Histomorphometric assessment for newly formed bone surface area, mature collagen area fraction, the osteoblasts count, and blood vessel count were performed. The change in alveolar ridge width was evaluated through bone caliper and CBCT. Results: Soft tissue expander successfully provides a Surplus amount of soft tissues in 5 out of 8 patients in the test group. Complications during the expansion period were perforation through oral mucosa occurred in two patients. Infection occurred in one patient. The mean soft tissue volume gain was 393.9 ± 322mm. After 6 months. The mean horizontal bone gains for the test and control groups were 3.14 mm and 3.69 mm, respectively. Conclusion: STE with a sub-periosteal approach is an applicable method to achieve an additional soft tissue and to reduce bone block graft exposure and wound dehiscence.

Keywords: soft tissue expander, ridge augmentation, block graft, symphysis bone block

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1823 Simulation of X-Ray Tissue Contrast and Dose Optimisation in Radiological Physics to Improve Medical Imaging Students’ Skills

Authors: Peter J. Riley

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Medical Imaging students must understand the roles of Photo-electric Absorption (PE) and Compton Scatter (CS) interactions in patients to enable optimal X-ray imaging in clinical practice. A simulator has been developed that shows relative interaction probabilities, color bars for patient dose from PE, % penetration to the detector, and obscuring CS as Peak Kilovoltage (kVp) changes. Additionally, an anthropomorphic chest X-ray image shows the relative tissue contrasts and overlying CS-fog at that kVp, which determine the detectability of a lesion in the image. A series of interactive exercises with MCQs evaluate the student's understanding; the simulation has improved student perception of the need to acquire "sufficient" rather than maximal contrast to enable patient dose reduction at higher kVp.

Keywords: patient dose optimization, radiological physics, simulation, tissue contrast

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1822 Non-Invasive Imaging of Tissue Using Near Infrared Radiations

Authors: Ashwani Kumar Aggarwal

Abstract:

NIR Light is non-ionizing and can pass easily through living tissues such as breast without any harmful effects. Therefore, use of NIR light for imaging the biological tissue and to quantify its optical properties is a good choice over other invasive methods. Optical tomography involves two steps. One is the forward problem and the other is the reconstruction problem. The forward problem consists of finding the measurements of transmitted light through the tissue from source to detector, given the spatial distribution of absorption and scattering properties. The second step is the reconstruction problem. In X-ray tomography, there is standard method for reconstruction called filtered back projection method or the algebraic reconstruction methods. But this method cannot be applied as such, in optical tomography due to highly scattering nature of biological tissue. A hybrid algorithm for reconstruction has been implemented in this work which takes into account the highly scattered path taken by photons while back projecting the forward data obtained during Monte Carlo simulation. The reconstructed image suffers from blurring due to point spread function. This blurred reconstructed image has been enhanced using a digital filter which is optimal in mean square sense.

Keywords: least-squares optimization, filtering, tomography, laser interaction, light scattering

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1821 Durable Phantom Production Identical to Breast Tissue for Use in Breast Cancer Detection Research Studies

Authors: Hayrettin Eroglu, Adem Kara

Abstract:

Recently there has been significant attention given to imaging of the biological tissues via microwave imaging techniques. In this study, a phantom for the test and calibration of Microwave imaging used in detecting unhealthy breast structure or tumors was produced by using sol gel method. The liquid and gel phantoms being used nowadays are not durable due to evaporation and their organic ingredients, hence a new design was proposed. This phantom was fabricated from materials that were widely available (water, salt, gelatin, and glycerol) and was easy to make. This phantom was aimed to be better from the ones already proposed in the literature in terms of its durability and stability. S Parameters of phantom was measured with 1-18 GHz Probe Kit and permittivity was calculated via Debye method in “85070” commercial software. One, three, and five-week measurements were taken for this phantom. Finally, it was verified that measurement results were very close to the real biological tissue measurement results.

Keywords: phantom, breast tissue, cancer, microwave imaging

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1820 Mercury and Selenium Levels in Swordfish (Xiphias gladius) Fished in the Exclusive Economic Zone of the Republic of Seychelles

Authors: Stephanie Hollanda, Nathalie Bodin, Carine Churlaud, Paco Bustamante

Abstract:

Total mercury (Hg), selenium (Se) and Hg-Se ratios were analyzed in the white muscle, liver and gonads of swordfish, in order to compare concentration between the different tissues and sex, and also the effect of size (fork length). The results show significant difference between tissue types, with the liver having the highest concentration of both Hg and Se. Positive significant correlations between moles of Hg and Se were obtained in the liver and white muscle, but no relationship was obtained in the gonads. No difference in the concentration of Hg and Se was obtained between the sexes in the tissue types, except for Hg in the gonads, which were found to be higher in males. Significant negative relationships were obtained when the Hg-Se ratio was plotted against fork length in all three tissue types.

Keywords: bioaccumulation, large pelagic fish, mercury, selenium, western Indian Ocean

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1819 Improved Mechanical Properties and Osteogenesis in Electrospun Poly L-Lactic Ultrafine Nanofiber Scaffolds Incorporated with Graphene Oxide

Authors: Weili Shao, Qian Wang, Jianxin He

Abstract:

Recently, the applications of graphene oxide in fabricating scaffolds for bone tissue engineering have been received extensive concern. In this work, poly l-lactic/graphene oxide composite nanofibers were successfully fabricated by electrospinning. The morphology structure, porosity and mechanical properties of the composite nanofibers were characterized using different techniques. And mouse mesenchymal stem cells were cultured on the composite nanofiber scaffolds to assess their suitability for bone tissue engineering. The results indicated that the composite nanofiber scaffolds had finer fiber diameter and higher porosity as compared with pure poly l-lactic nanofibers. Furthermore, incorporation of graphene oxide into the poly l-lactic nanofibers increased protein adsorptivity, boosted the Young’s modulus and tensile strength by nearly 4.2-fold and 3.5-fold, respectively, and significantly enhanced adhesion, proliferation, and osteogenesis in mouse mesenchymal stem cells. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering.

Keywords: poly l-lactic, graphene oxide, osteogenesis, bone tissue engineering

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1818 Classification System for Soft Tissue Injuries of Face: Bringing Objectiveness to Injury Severity

Authors: Garg Ramneesh, Uppal Sanjeev, Mittal Rajinder, Shah Sheerin, Jain Vikas, Singla Bhupinder

Abstract:

Introduction: Despite advances in trauma care, a classification system for soft tissue injuries of the face still needs to be objectively defined. Aim: To develop a classification system for soft tissue injuries of the face; that is objective, easy to remember, reproducible, universally applicable, aids in surgical management and helps to develop a structured data that can be used for future use. Material and Methods: This classification system includes those patients that need surgical management of facial injuries. Associated underlying bony fractures have been intentionally excluded. Depending upon the severity of soft tissue injury, these can be graded from 0 to IV (O-Abrasions, I-lacerations, II-Avulsion injuries with no skin loss, III-Avulsion injuries with skin loss that would need graft or flap cover, and IV-complex injuries). Anatomically, the face has been divided into three zones (Zone 1/2/3), as per aesthetic subunits. Zone 1e stands for injury of eyebrows; Zones 2 a/b/c stand for nose, upper eyelid and lower eyelid respectively; Zones 3 a/b/c stand for upper lip, lower lip and cheek respectively. Suffices R and L stand for right or left involved side, B for presence of foreign body like glass or pellets, C for extensive contamination and D for depth which can be graded as D 1/2/3 if depth is still fat, muscle or bone respectively. I is for damage to facial nerve or parotid duct. Results and conclusions: This classification system is easy to remember, clinically applicable and would help in standardization of surgical management of soft tissue injuries of face. Certain inherent limitations of this classification system are inability to classify sutured wounds, hematomas and injuries along or against Langer’s lines.

Keywords: soft tissue injuries, face, avulsion, classification

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1817 System for Mechanical Stimulation of the Mesenchymal Stem Cells Supporting Differentiation into Osteogenic Cells

Authors: Jana Stepanovska, Roman Matejka, Jozef Rosina, Marta Vandrovcova, Lucie Bacakova

Abstract:

The aim of this study was to develop a system for mechanical and also electrical stimulation controlling in vitro osteogenesis under conditions more similar to the in vivo bone microenvironment than traditional static cultivation, which would achieve good adhesion, growth and other specific behaviors of osteogenic cells in cultures. An engineered culture system for mechanical stimulation of the mesenchymal stem cells on the charged surface was designed. The bioreactor allows efficient mechanical loading inducing an electrical response and perfusion of the culture chamber with seeded cells. The mesenchymal stem cells were seeded to specific charged materials, like polarized hydroxyapatite (Hap) or other materials with piezoelectric and ferroelectric features, to create electrical potentials for stimulating of the cells. The material of the matrix was TiNb alloy designed for these purposes, and it was covered by BaTiO3 film, like a kind of piezoelectric material. The process of mechanical stimulation inducing electrical response is controlled by measuring electrical potential in the chamber. It was performed a series of experiments, where the cells were seeded, perfused and stimulated up to 48 hours under different conditions, especially pressure and perfusion. The analysis of the proteins expression was done, which demonstrated the effective mechanical and electrical stimulation. The experiments demonstrated effective stimulation of the cells in comparison with the static culture. This work was supported by the Ministry of Health, grant No. 15-29153A and the Grant Agency of the Czech Republic grant No. GA15-01558S.

Keywords: charged surface, dynamic cultivation, electrical stimulation, ferroelectric layers, mechanical stimulation, piezoelectric layers

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1816 Long-Term Outcomes of Dysphagia in Children with Severe Cerebral Palsy Using Videofluoroscopic Evaluation

Authors: Eun Jae Ko, In Young Sung, Eui Soo Joeng

Abstract:

Oropharyngeal dysphagia is prevalent in children with cerebral palsy (CP). There are many studies concerning this problem, however, studies examining long term outcomes of dysphagia using videofluoroscopic study (VFSS) are very rare. The Aim of this study is to investigate long-term outcomes of dysphagia in children with severe CP using initial VFSS. It was a retrospective study and chart review was done from January 2000 to December 2013. Thirty one patients under 18 years who have been diagnosed as CP in outpatient clinic of Rehabilitation Medicine, and who did VFSS were included. Long-term outcomes such as feeding method, height percentile, weight percentile, and body mass index (BMI) were tracked up for at least 3 years by medical records. Significant differences between initial and follow-up datas were investigated. The patients consisted of 18 males and 13 females, and the mean age was 31.0±18.0 months old. 64.5% of patients were doing oral diet, and 25.8% of patients were doing non-oral diet. When comparing VFSS findings among oral feeding patients, oral and non-oral feeding patients, and non-oral feeding patients at initial period, dysphagia severity, supraglottic penetration, and subglottic aspiration showed significant differences. Most of the patients who could feed orally at initial period were found to have the same feeding method at follow-up. But among eight patients who required non-oral feeding initially, three patients became possible to feed orally, and one patient was doing oral and non-oral feeding method together at follow-up. Follow up feeding method showed correlation with dysphagia severity by initial VFSS. Weight percentile was decreased in patients with GMFCS level V at follow up, which may represent poor nutritional status due to severe dysphagia compared to other patients. Initial VFSS severity would play a significant role in making an assumption about future diet in children with severe CP. Patients with GMFCS level V seem to have serious dysphagia at follow up and have nutritional deficiency over time, therefore, more careful nutritional support is needed in children with severe CP are suggested.

Keywords: cerebral palsy, child, dysphagia, videofluoroscopic study

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1815 Operating Characteristics of Point-of-Care Ultrasound in Identifying Skin and Soft Tissue Abscesses in the Emergency Department

Authors: Sathyaseelan Subramaniam, Jacqueline Bober, Jennifer Chao, Shahriar Zehtabchi

Abstract:

Background: Emergency physicians frequently evaluate skin and soft tissue infections in order to differentiate abscess from cellulitis. This helps determine which patients will benefit from incision and drainage. Our objective was to determine the operating characteristics of point-of-care ultrasound (POCUS) compared to clinical examination in identifying abscesses in emergency department (ED) patients with features of skin and soft tissue infections. Methods: We performed a comprehensive search in the following databases: Medline, Web of Science, EMBASE, CINAHL and Cochrane Library. Trials were included if they compared the operating characteristics of POCUS with clinical examination in identifying skin and soft tissue abscesses. Trials that included patients with oropharyngeal abscesses or that requiring abscess drainage in the operating room were excluded. The presence of an abscess was determined by pus drainage. No pus seen on incision or resolution of symptoms without pus drainage at follow up, determined the absence of an abscess. Quality of included trials was assessed using GRADE criteria. Operating characteristics of POCUS are reported as sensitivity, specificity, positive likelihood (LR+) and negative likelihood (LR-) ratios and the respective 95% confidence intervals (CI). Summary measures were calculated by generating a hierarchical summary receiver operating characteristic model (HSROC). Results: Out of 3203 references identified, 5 observational studies with 615 patients in aggregate were included (2 adults and 3 pediatrics). We rated the quality of 3 trials as low and 2 as very low. The operating characteristics of POCUS and clinical examination in identifying soft tissue abscesses are presented in the table. The HSROC for POCUS revealed a sensitivity of 96% (95% CI = 89-98%), specificity of 79% (95% CI = 71-86), LR+ of 4.6 (95% CI = 3.2-6.8), and LR- of 0.06 (95% CI = 0.02-0.2). Conclusion: Existing evidence indicates that POCUS is useful in identifying abscesses in ED patients with skin or soft tissue infections.

Keywords: abscess, point-of-care ultrasound, pocus, skin and soft tissue infection

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1814 Ex-vivo Bio-distribution Studies of a Potential Lung Perfusion Agent

Authors: Shabnam Sarwar, Franck Lacoeuille, Nadia Withofs, Roland Hustinx

Abstract:

After the development of a potential surrogate of MAA, and its successful application for the diagnosis of pulmonary embolism in artificially embolized rats’ lungs, this microparticulate system were radiolabelled with gallium-68 to synthesize 68Ga-SBMP with high radiochemical purity >99%. As a prerequisite step of clinical trials, 68Ga- labelled starch based microparticles (SBMP) were analysed for their in-vivo behavior in small animals. The purpose of the presented work includes the ex-vivo biodistribution studies of 68Ga-SBMP in order to assess the activity uptake in target organs with respect to time, excretion pathways of the radiopharmaceutical, %ID/g in major organs, T/NT ratios, in-vivo stability of the radiotracer and subsequently the microparticles in the target organs. Radiolabelling of starch based microparticles was performed by incubating it with 68Ga generator eluate (430±26 MBq) at room temperature and pressure without using any harsh reaction condition. For Ex-vivo biodistribution studies healthy White Wistar rats weighing between 345-460 g were injected intravenously 68Ga-SBMP 20±8 MBq, containing about 2,00,000-6,00,000 SBMP particles in a volume of 700µL. The rats were euthanized at predefined time intervals (5min, 30min, 60min and 120min) and their organ parts were cut, washed, and put in the pre-weighed tubes and measured for radioactivity counts through automatic Gamma counter. The 68Ga-SBMP produced >99% RCP just after 10-20 min incubation through a simple and robust procedure. Biodistribution of 68Ga-SBMP showed that initially just after 5 min post injection major uptake was observed in the lungs following by blood, heart, liver, kidneys, bladder, urine, spleen, stomach, small intestine, colon, skin and skeleton, thymus and at last the smallest activity was found in brain. Radioactivity counts stayed stable in lungs with gradual decrease with the passage of time, and after 2h post injection, almost half of the activity were seen in lungs. This is a sufficient time to perform PET/CT lungs scanning in humans while activity in the liver, spleen, gut and urinary system decreased with time. The results showed that urinary system is the excretion pathways instead of hepatobiliary excretion. There was a high value of T/NT ratios which suggest fine tune images for PET/CT lung perfusion studies henceforth further pre-clinical studies and then clinical trials should be planned in order to utilize this potential lung perfusion agent.

Keywords: starch based microparticles, gallium-68, biodistribution, target organs, excretion pathways

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1813 Probing Mechanical Mechanism of Three-Hinge Formation on a Growing Brain: A Numerical and Experimental Study

Authors: Mir Jalil Razavi, Tianming Liu, Xianqiao Wang

Abstract:

Cortical folding, characterized by convex gyri and concave sulci, has an intrinsic relationship to the brain’s functional organization. Understanding the mechanism of the brain’s convoluted patterns can provide useful clues into normal and pathological brain function. During the development, the cerebral cortex experiences a noticeable expansion in volume and surface area accompanied by tremendous tissue folding which may be attributed to many possible factors. Despite decades of endeavors, the fundamental mechanism and key regulators of this crucial process remain incompletely understood. Therefore, to taking even a small role in unraveling of brain folding mystery, we present a mechanical model to find mechanism of 3-hinges formation in a growing brain that it has not been addressed before. A 3-hinge is defined as a gyral region where three gyral crests (hinge-lines) join. The reasons that how and why brain prefers to develop 3-hinges have not been answered very well. Therefore, we offer a theoretical and computational explanation to mechanism of 3-hinges formation in a growing brain and validate it by experimental observations. In theoretical approach, the dynamic behavior of brain tissue is examined and described with the aid of a large strain and nonlinear constitutive model. Derived constitute model is used in the computational model to define material behavior. Since the theoretical approach cannot predict the evolution of cortical complex convolution after instability, non-linear finite element models are employed to study the 3-hinges formation and secondary morphological folds of the developing brain. Three-dimensional (3D) finite element analyses on a multi-layer soft tissue model which mimics a small piece of the brain are performed to investigate the fundamental mechanism of consistent hinge formation in the cortical folding. Results show that after certain amount growth of cortex, mechanical model starts to be unstable and then by formation of creases enters to a new configuration with lower strain energy. By further growth of the model, formed shallow creases start to form convoluted patterns and then develop 3-hinge patterns. Simulation results related to 3-hinges in models show good agreement with experimental observations from macaque, chimpanzee and human brain images. These results have great potential to reveal fundamental principles of brain architecture and to produce a unified theoretical framework that convincingly explains the intrinsic relationship between cortical folding and 3-hinges formation. This achieved fundamental understanding of the intrinsic relationship between cortical folding and 3-hinges formation would potentially shed new insights into the diagnosis of many brain disorders such as schizophrenia, autism, lissencephaly and polymicrogyria.

Keywords: brain, cortical folding, finite element, three hinge

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1812 Association of Mir-196a Expression in Esophageal Tissue with Barrett´s Esophagus and Esophageal Adenocarcinoma

Authors: Petra Borilova Linhartova, Michaela Ruckova, Sabina Sevcikova, Natalie Mlcuchova, Jan Bohm, Katerina Zukalova, Monika Vlachova, Jiri Dolina, Lumir Kunovsky, Radek Kroupa, Zdenek Pavlovsky, Zdenek Danek, Tereza Deissova, Lydie Izakovicova Holla, Ondrej Slaby, Zdenek Kala

Abstract:

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. Specific microRNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, were repeatedly proved to play key roles in the pathogenesis of these diseases. This pilot study aimed to analyze four selected miRNAs in esophageal tissues from healthy controls (HC) and patients with reflux esophagitis (RE)/BE/EAC, as well as to compare expression at the site of Barrett's mucosa/adenocarcinoma and healthy esophageal tissue outside the area of the main pathology in patients with BE/EAC. In this pilot study, 22 individuals (3 HC, 8 RE, 5 BE, 6 EAC) were included and endoscopically examined. RNA was isolated from the fresh-frozen esophageal tissue (stored in the RNAlater™ Stabilization Solution −70°C) using the AllPrep DNA/RNA/miRNA Universal Kit. Subsequent RT-qPCR analysis was performed using selected TaqMan MicroRNA Assays for miR-21, miR-34a, miR-196a, miR-196b, and endogenous control (RNU44). While the expression of miR-21 in the esophageal tissue with the main pathology was decreased in BE and EAC patients in comparison to the group of HC and RE patients (p=0.01), the expression of miR-196a was increased in the BE and EAC patients (p<0.01). Correlations between those miRNAs expression in tissue and severity of diagnosis were observed (p<0.05). In addition, miR-196a was significantly more expressed at the site with the main pathology than in paired adjacent esophageal tissue in BE and EAC patients (p<0.01). In conclusion, our pilot results showed that miR-196a, which regulates the proliferation, invasion, and migration (and was previously associated with esophageal squamous cell carcinoma and marked as a potential therapeutic target), could be a diagnostic tissue biomarker for BE and EAC as well.

Keywords: microRNA, barrett´s esophagus, esophageal adenocarcinoma, biomarker

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