Search results for: perfusion systems

Authors: Vineeth Siripuram, Abhineet Nigam

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A bioreactor is an engineered system that supports a biologically active environment. Along the years, the advancements in bioreactors have been widely accepted all over the world for varied applications ranging from sewage treatment to tissue cloning. Driven by tissue and organ shortage, tissue engineering has emerged as an alternative to transplantation for the reconstruction of lost or damaged organs. In this study, Computational fluid dynamics (CFD) has been used to model porous medium flow in scaffolds (taken from the literature) with different flow patterns. A detailed analysis of different scaffold geometries and their influence on cell deposition in the perfusion system is been carried out using Computational fluid dynamics (CFD). Considering the fact that, the scaffold should mimic the organs or tissues structures in a three-dimensional manner, certain assumptions were made accordingly. The research on scaffolds has been extensively carried out in different bioreactors. However, there has been less focus on the morphology of the scaffolds and the flow patterns in which the perfusion system is laid upon. The objective of this paper is to employ a computational approach using CFD simulation to determine the optimal morphology and the anisotropic measurements of the various samples of scaffolds. Using predictive computational modelling approach, variables which exert dominant effects on the cell deposition within the scaffold were prioritised and corresponding changes in morphology of scaffold and flow patterns in the perfusion systems are made. A Eulerian approach was carried on in multiple CFD simulations, and it is observed that the morphological and topological changes in the scaffold perfusion system are of great importance in the commercial applications of scaffolds.

Keywords: cell seeding, CFD, flow patterns, modelling, perfusion systems, scaffold

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Authors: Mohammad Emran, Colton Wayne, Shannon M Koehler, P. Stephen Almond, Haroon Patel

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Purpose: Assessment of anastomotic perfusion in Hirschsprung disease using Indocyanine Green (ICG)-near-infrared (NIR) fluorescence angiography. Introduction: Anastomotic stricture and leak are well-known complications of Hirschsprung pull-through procedures. Complications are due to tension, infection, and/or poor perfusion. While a surgeon can visually determine and control the amount of tension and contamination, assessment of perfusion is subject to surgeon determination. Intraoperative use of ICG-NIR enhances this decision-making process by illustrating perfusion intensity and adequacy in the pulled-through bowel segment. This technique, proven to reduce anastomotic stricture and leak in adults, has not been studied in children to our knowledge. ICG, an FDA approved, nontoxic, non-immunogenic, intravascular (IV) dye, has been used in adults and children for over 60 years, with few side effects. ICG-NIR was used in this report to demonstrate the adequacy of perfusion during transanal pullthrough for Hirschsprung’s disease. Method: 8 patients with Hirschsprung disease were evaluated with ICG-NIR technology. Levels of affected area ranged from sigmoid to total colonic Hirschsprung disease. After leveling, but prior to anastomosis, ICG was administered at 1.25 mg (< 2 mg/kg) and perfusion visualized using an NIR camera, before and during anastomosis. Video and photo imaging was performed and perfusion of the bowel was compared to surrounding tissues. This showed the degree of perfusion and demarcation of perfused and non-perfused bowel. The anastomosis was completed uneventfully and the patients all did well. Results: There were no complications of stricture or leak. 5 of 8 patients (62.5%) had modification of the plan based on ICG-NIR imaging. Conclusion: Technologies that enhance surgeons’ ability to visualize bowel perfusion prior to anastomosis in Hirschsprung’s patients may help reduce post-operative complications. Further studies are needed to assess the potential benefits.

Keywords: colonic anastomosis, fluorescence angiography, Hirschsprung disease, pediatric surgery, SPY

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Authors: Devam Sheth

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Nuclear imaging with stress myocardial perfusion (stress test) is the preferred first line investigation for noninvasive evaluation of ischaemic heart condition. The sensitivity of this test is close to 90 % making it a very reliable test. However, rarely it gives a false negative result which can be explained by the phenomenon termed as “balanced ischaemia”. We present the case of a 78 year Caucasian female without any significant past cardiac history, who presents with chest pain and shortness of breath since one day. The initial ECG and cardiac enzymes were non-impressive. Few hours later, she had some substernal chest pain along with some ST segment depression in the lateral leads. Stress test comes back negative for any significant perfusion defects. However, given her typical symptoms, she underwent a cardiac catheterization which revealed significant triple vessel disease mandating her to get a bypass surgery. This unusual phenomenon of false nuclear stress test in the setting of positive ECG changes can be explained only by balanced ischemia wherein due to global myocardial ischemia, the stress test fails to reveal relative perfusion defects in the affected segments.

Keywords: balanced, false positive, ischemia, myocardial perfusion imaging

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Authors: Jitendra Pratap, Daphne Prybyszcuk, Luke Elliott, Arnold Ng

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Introduction: Coronary CT angiography is a non-invasive imaging technique for the assessment of coronary artery disease and has high sensitivity and negative predictive value. However, the correlation between the degree of CT coronary stenosis and the significance of hemodynamic obstruction is poor. The assessment of myocardial perfusion has mostly been undertaken by Nuclear Medicine (SPECT), but it is now possible to perform stress myocardial CT perfusion (CTP) scans quickly and effectively using CT scanners with high temporal resolution. Myocardial CTP is in many ways similar to neuro perfusion imaging technique, where radiopaque iodinated contrast is injected intravenously, transits the pulmonary and cardiac structures, and then perfuses through the coronary arteries into the myocardium. On the Siemens Force CT scanner, a myocardial perfusion scan is performed using a dynamic axial acquisition, where the scanner shuffles in and out every 1-3 seconds (heart rate dependent) to be able to cover the heart in the z plane. This is usually performed over 38 seconds. Report: A CT myocardial perfusion scan can be utilised to complement the findings of a CT Coronary Angiogram. Implementing a CT Myocardial Perfusion study as part of a routine CT Coronary Angiogram procedure provides a ‘One Stop Shop’ for diagnosis of coronary artery disease. This case study demonstrates that although the CT Coronary Angiogram was within normal limits, the perfusion scan provided additional, clinically significant information in regards to the haemodynamics within the myocardium of a patient with Hypertrophic Obstructive Cardio Myopathy (HOCM). This negated the need for further diagnostics studies such as cardiac ECHO or Nuclear Medicine Stress tests. Conclusion: CT coronary angiography with adenosine stress myocardial CTP was utilised in this case to specifically exclude coronary artery disease in conjunction with accessing perfusion within the hypertrophic myocardium. Adenosine stress myocardial CTP demonstrated the reduced myocardial blood flow within the hypertrophic myocardium, but the coronary arteries did not show any obstructive disease. A CT coronary angiogram scan protocol that incorporates myocardial perfusion can provide diagnostic information on the haemodynamic significance of any coronary artery stenosis and has the potential to be a “One Stop Shop” for cardiac imaging.

Keywords: CT, cardiac, myocardium, perfusion

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Authors: Ahmadreza Bagheri, Seyyed S. Eftekhari, Shervin Rashidinia

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Background: Various stress tests have been proposed yet to assess patients with suspected coronary artery disease. However, their diagnostic properties in terms of sensitivity, specificity, and accuracy are variable and their applicability remained somewhat vague. The aim of this study is to validate per-vessel diagnostic properties of 3 types of stress myocardial perfusion scintigraphy in gated SPECT (Single-Photon Emission Computed Tomography) using either exercise or pharmacological stress testing with dipyridamole or dobutamine. Materials and Methods: Hospital records of 314 patients who referred to Imam Khomeini hospital of Tehran between September 2015 and January 2017 were completely reviewed in this study. All patients underwent coronary angiography within 3 months after stress myocardial perfusion scan. Eventually, the results were analyzed in per-vessel basis to find the proper modality for each involved vessel or scanned site. Results: The mean age of patients was 62.15 ± 4.94 years (30-85) and 35.03% were women. The overall sensitivity, specificity, and accuracy were calculated as 56.59%, 54.24%, and 55.09%, respectively. These values were 56.43% and 53.25%, 54.46% and 47.36%, 56.75% and 54.83% for dipyridamole and exercise, respectively. Ischemia of the anterior wall through exercise stress testing has the highest diagnostic accuracy in detecting LAD (Left Anterior Descending artery) involvement. Inferior wall hypokinesia and anterolateral wall ischemia during exercise stress testing have the highest diagnostic accuracy in detecting RCA (Right Coronary Artery) and LCX artery (Left Circumflex Artery) stenosis, respectively. Conclusion: Stress myocardial perfusion scan should be carried out on the basis of the findings of the preliminary investigations on suspicion of a specific coronary artery or involved myocardial wall.

Keywords: dipyridamole, dobutamine, single-photon emission computed tomography, stress myocardial perfusion scintigraphy

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Authors: Mohammad Java Esmaeily

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Background: We evaluate the effects of tissue and organ perfusion during and after coronary artery bypass graft surgery with either colloid (Voluven) or crystalloid (Lactated ringers) as a prime solution. Materials and Methods: In this prospective randomized-controlled trial study, 70 patients undergoing on-pump coronary artery bypass graft surgery were randomly assigned to receive either colloid (Voluven) or crystalloid (Lactated ringer's) as a prime solution for initiation of cardiopulmonary bypass machine procedure. Tissue and organ perfusion markers, including lactate, troponin I, liver and renal function tests and electrolytes, were measured sequentially before induction (T1) to the second days after surgery (T5). Results: With the exception of chloride and potassium levels, no significant differences were detected in other measurements, and laboratory results were identical entirely in the two groups. Conclusion: Voluven® (hydroxyethyl starch, HES 130/0.4) has a not significant difference in comparison with crystalloid (Lactated ringer's) as priming solution on the basis of organ and tissue perfusion tests assessment.

Keywords: prime, colloid, crystalloid, lactate, troponin, hydroxyethyl starch

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Authors: Elena Petersen, Inna Kornienko, Svetlana Guryeva, Sergey Simakov

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In vitro organoid cultivation requires the simultaneous provision of necessary vascularization and nutrients perfusion of cells during organoid development. However, many aspects of this problem are still unsolved. The functionality of vascular network intergrowth is limited during early stages of organoid development since a function of the vascular network initiated on final stages of in vitro organoid cultivation. Therefore, a microchannel network should be created in early stages of organoid cultivation in hydrogel matrix aimed to conduct and maintain minimally required the level of nutrients perfusion for all cells in the expanding organoid. The network configuration should be designed properly in order to exclude hypoxic and necrotic zones in expanding organoid at all stages of its cultivation. In vitro vascularization is currently the main issue within the field of tissue engineering. As perfusion and oxygen transport have direct effects on cell viability and differentiation, researchers are currently limited only to tissues of few millimeters in thickness. These limitations are imposed by mass transfer and are defined by the balance between the metabolic demand of the cellular components in the system and the size of the scaffold. Current approaches include growth factor delivery, channeled scaffolds, perfusion bioreactors, microfluidics, cell co-cultures, cell functionalization, modular assembly, and in vivo systems. These approaches may improve cell viability or generate capillary-like structures within a tissue construct. Thus, there is a fundamental disconnect between defining the metabolic needs of tissue through quantitative measurements of oxygen and nutrient diffusion and the potential ease of integration into host vasculature for future in vivo implantation. A model is proposed for growth prognosis of the organoid perfusion based on joint simulations of general nutrient diffusion, nutrient diffusion to the hydrogel matrix through the contact surfaces and microchannels walls, nutrient consumption by the cells of expanding organoid, including biomatrix contraction during tissue development, which is associated with changed consumption rate of growing organoid cells. The model allows computing effective microchannel network design giving minimally required the level of nutrients concentration in all parts of growing organoid. It can be used for preliminary planning of microchannel network design and simulations of nutrients supply rate depending on the stage of organoid development.

Keywords: 3D model, consumption model, diffusion, spheroid, tissue organoid

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Authors: Sultan Z. Mahmud, Emily C. Graff, Adil Bashir

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Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional adapter protein which is associated with the regulation of apoptotic cell death. Recently it has been discovered that PEA-15 is crucial in normal neurodevelopment of domestic cats, a gyrencephalic animal model, although the exact function of PEA-15 in neurodevelopment is unknown. This study investigates how PEA-15 affects the blood-brain barrier (BBB) permeability in cat brain, which can cause abnormalities in tissue metabolite and energy supplies. Severe polymicrogyria and microcephaly have been observed in cats with a loss of function PEA-15 mutation, affecting the normal neurodevelopment of the cat. This suggests that the vital role of PEA-15 in neurodevelopment is associated with gyrification. Neurodevelopment is a highly energy demanding process. The mammalian brain depends on glucose as its main energy source. PEA-15 plays a very important role in glucose uptake and utilization by interacting with phospholipase D1 (PLD1). Mitochondria also plays a critical role in bioenergetics and essential to supply adequate energy needed for neurodevelopment. Cerebral blood flow regulates adequate metabolite supply and recent findings also showed that blood plasma contains mitochondria as well. So the BBB can play a very important role in regulating metabolite and energy supply in the brain. In this study the blood-brain permeability in cat brain was measured using MRI magnetization transfer (MT) effect on the perfusion signal. Perfusion is the tissue mass normalized supply of blood to the capillary bed. Perfusion also accommodates the supply of oxygen and other metabolites to the tissue. A fraction of the arterial blood can diffuse to the tissue, which depends on the BBB permeability. This fraction is known as water extraction fraction (EF). MT is a process of saturating the macromolecules, which has an effect on the blood that has been diffused into the tissue while having minimal effect on intravascular blood water that has not been exchanged with the tissue. Measurement of perfusion signal with and without MT enables to estimate the microvascular blood flow, EF and permeability surface area product (PS) in the brain. All the experiments were performed with Siemens 7T Magnetom with 32 channel head coil. Three control cats and three PEA-15 mutant cats were used for the study. Average EF in white and gray matter was 0.9±0.1 and 0.86±0.15 respectively, perfusion in white and gray matter was 85±15 mL/100g/min and 97±20 mL/100g/min respectively, PS in white and gray matter was 201±25 mL/100g/min and 225±35 mL/100g/min respectively for control cats. For PEA-15 mutant cats, average EF in white and gray matter was 0.81±0.15 and 0.77±0.2 respectively, perfusion in white and gray matter was 140±25 mL/100g/min and 165±18 mL/100g/min respectively, PS in white and gray matter was 240±30 mL/100g/min and 259±21 mL/100g/min respectively. This results show that BBB is compromised in PEA-15 mutant cat brain, where EF is decreased and perfusion as well as PS are increased in the mutant cats compared to the control cats. This findings might further explain the function of PEA-15 in neurodevelopment.

Keywords: BBB, cat brain, magnetization transfer, PEA-15

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Authors: Pengzhou Lu, Liming Xin, Payam Tavakoli, Zhonghua Lin, Roberto V. P. Ribeiro, Mitesh V. Badiwala

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Ex vivo Heart Perfusion (EVHP) has been developed as an alternative strategy to expand cardiac donation by enabling resuscitation and functional assessment of hearts donated from marginal donors, which were previously not accepted. EVHP parameters, such as perfusion flow (PF) and perfusion pressure (PP) are crucial for optimal organ preservation. However, with the heart’s constant physiological changes during EVHP, such as coronary vascular resistance, manual control of these parameters is rendered imprecise and cumbersome for the operator. Additionally, low control precision and the long adjusting time may lead to irreversible damage to the myocardial tissue. To solve this problem, an automatic heart perfusion system was developed by applying a Human-Machine Interface (HMI) and a Programmable-Logic-Controller (PLC)-based circuit to control PF and PP. The PLC-based control system collects the data of PF and PP through flow probes and pressure transducers. It has two control modes: the RPM-flow mode and the pressure mode. The RPM-flow control mode is an open-loop system. It influences PF through providing and maintaining the desired speed inputted through the HMI to the centrifugal pump with a maximum error of 20 rpm. The pressure control mode is a closed-loop system where the operator selects a target Mean Arterial Pressure (MAP) to control PP. The inputs of the pressure control mode are the target MAP, received through the HMI, and the real MAP, received from the pressure transducer. A PID algorithm is applied to maintain the real MAP at the target value with a maximum error of 1mmHg. The precision and control speed of the RPM-flow control mode were examined by comparing the PLC-based system to an experienced operator (EO) across seven RPM adjustment ranges (500, 1000, 2000 and random RPM changes; 8 trials per range) tested in a random order. System’s PID algorithm performance in pressure control was assessed during 10 EVHP experiments using porcine hearts. Precision was examined through monitoring the steady-state pressure error throughout perfusion period, and stabilizing speed was tested by performing two MAP adjustment changes (4 trials per change) of 15 and 20mmHg. A total of 56 trials were performed to validate the RPM-flow control mode. Overall, the PLC-based system demonstrated the significantly faster speed than the EO in all trials (PLC 1.21±0.03, EO 3.69±0.23 seconds; p < 0.001) and greater precision to reach the desired RPM (PLC 10±0.7, EO 33±2.7 mean RPM error; p < 0.001). Regarding pressure control, the PLC-based system has the median precision of ±1mmHg error and the median stabilizing times in changing 15 and 20mmHg of MAP are 15 and 19.5 seconds respectively. The novel PLC-based control system was 3 times faster with 60% less error than the EO for RPM-flow control. In pressure control mode, it demonstrates a high precision and fast stabilizing speed. In summary, this novel system successfully controlled perfusion flow and pressure with high precision, stability and a fast response time through a user-friendly interface. This design may provide a viable technique for future development of novel heart preservation and assessment strategies during EVHP.

Keywords: automatic control system, biomedical engineering, ex-vivo heart perfusion, human-machine interface, programmable logic controller

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Authors: Melikulov A. A., Toshpulotov Sh. G., Akhmedova M. F., Beshimov A. S., Rakhimov M. K. Zokirov N. K.

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Postinfarction ventricular septal defect (PVSD) is a rare but life-threatening complication of acute myocardial infarction. Currently, an alternative direction of minimally invasive treatment of postinfarction ventricular septal defect (PVSD) is being developed - transcatheter closure of the defect using an occluder, but surgical closure of the defect remains the <> correction of post-infarction VSD. Our article presents a case of successful surgical treatment of a patient with a large post-infarction rupture of the interventricular septum (IVS) and post-infarction LV aneurysm under cardiopulmonary bypass and parallel perfusion.

Keywords: echocardiography, myocardial infarction, ventricular septal defect, parallel perfusion

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Authors: Sarwar Beg, Gajanand Sharma, O. P. Katare, Bhupinder Singh

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The current studies entail development of self-nano emulsifying drug delivery systems (SNEDDS) of rosuvastatin, employing rational QbD-based approach for enhancing its oral bioavailability. SNEDDS were prepared using the blend of lipidic and emulsifying excipients, i.e., Peceol, Tween 80, and Transcutol HP. The prepared formulations evaluated for in vitro drug release, ex vivo permeation, in situ perfusion studies and in vivo pharmacokinetic studies in rats, which demonstrated 3-4 fold improvement in biopharmaceutical performance of the developed formulations. Cytotoxicity studies using MTT assay and histopathological studies in intestinal cells revealed the lack of cytotoxicity and thereby safety and efficacy of the developed formulations.

Keywords: SNEDDS, bioavailability, solubility, Quality by Design (QbD)

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Authors: M. Dimitri, M. Ricci, F. Bigi, M. Romiti, A. Corvi

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Tissue engineering has reached a significant milestone with the integration of 3D printing for the creation of complex bioconstructs equipped with vascular networks, crucial for cell maintenance and growth. This study aims to demonstrate the effectiveness of a portable microperfusion system designed to adapt dynamically to the evolving conditions of cell growth within 3D-printed bioconstructs. The microperfusion system was developed to provide a constant and controlled flow of nutrients and oxygen through the integrated vessels in the bioconstruct, replicating in vivo physiological conditions. Through a series of preliminary experiments, we evaluated the system's ability to maintain a favorable environment for cell proliferation and differentiation. Measurements of cell density and viability were performed to monitor the health and functionality of the tissue over time. Preliminary results indicate that the portable microperfusion system not only supports but optimizes cell growth, effectively adapting to changes in metabolic needs during the bioconstruct maturation process. This research opens perspectives in tissue engineering, demonstrating that a portable microperfusion system can be successfully integrated into 3D-printed bioconstructs, promoting sustainable and uniform cell growth. The implications of this study are far-reaching, with potential applications in regenerative medicine and pharmacological research, providing a platform for the development of functional and complex tissues.

Keywords: biofabrication, microfluidic perfusion system, 4D bioprinting

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Authors: Irina Mizeva, Elena Potapova, Viktor Dremin, Mikhail Mezentsev, Valeri Shupletsov

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The local tissue perfusion is regulated by the microvascular tone which is under the control of a number of physiological mechanisms. Laser Doppler flowmetry (LDF) together with wavelet analyses is the most commonly used technique to study the regulatory mechanisms of cutaneous microcirculation. External factors such as temperature, local pressure of the probe on the skin, etc. influence on the blood flow characteristics and are used as physiological tests to evaluate microvascular regulatory mechanisms. Local probe pressure influences on the microcirculation parameters measured by optical methods: diffuse reflectance spectroscopy, fluorescence spectroscopy, and LDF. Therefore, further study of probe pressure effects can be useful to improve the reliability of optical measurement. During pressure tests variation of the mean perfusion measured by means of LDF usually is estimated. An additional information concerning the physiological mechanisms of the vascular tone regulation system in response to local pressure can be obtained using spectral analyses of LDF samples. The aim of the present work was to develop protocol and algorithm of data processing appropriate for study physiological response to the local pressure test. Involving 6 subjects (20±2 years) and providing 5 measurements for every subject we estimated intersubject and-inter group variability of response of both averaged and oscillating parts of the LDF sample on external surface pressure. The final purpose of the work was to find special features which further can be used in wider clinic studies. The cutaneous perfusion measurements were carried out by LAKK-02 (SPE LAZMA Ltd., Russia), the skin loading was provided by the originally designed device which allows one to distribute the pressure around the LDF probe. The probe was installed on the dorsal part of the distal finger of the index figure. We collected measurements continuously for one hour and varied loading from 0 to 180mmHg stepwise with a step duration of 10 minutes. Further, we post-processed the samples using the wavelet transform and traced the energy of oscillations in five frequency bands over time. Weak loading leads to pressure-induced vasodilation, so one should take into account that the perfusion measured under pressure conditions will be overestimated. On the other hand, we revealed a decrease in endothelial associated fluctuations. Further loading (88 mmHg) induces amplification of pulsations in all frequency bands. We assume that such loading leads to a higher number of closed capillaries, higher input of arterioles in the LDF signal and as a consequence more vivid oscillations which mainly are formed in arterioles. External pressure higher than 144 mmHg leads to the decrease of oscillating components, after removing the loading very rapid restore of the tissue perfusion takes place. In this work, we have demonstrated that local skin loading influence on the microcirculation parameters measured by optic technique; this should be taken into account while developing portable electronic devices. The proposed protocol of local loading allows one to evaluate PIV as far as to trace dynamic of blood flow oscillations. This study was supported by the Russian Science Foundation under project N 18-15-00201.

Keywords: blood microcirculation, laser Doppler flowmetry, pressure-induced vasodilation, wavelet analyses blood

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Authors: Rutej R. Mehta, Michael A. Chappell

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Introduction: Arterial spin labelling (ASL) is an increasingly popular perfusion MRI technique, in which arterial blood water is magnetically labelled in the neck before flowing into the brain, providing a non-invasive measure of cerebral blood flow (CBF). The accuracy of ASL CBF measurements, however, is hampered by dispersion effects; the distortion of the ASL labelled bolus during its transit through the vasculature. In spite of this, the current recommended implementation of ASL – the white paper (Alsop et al., MRM, 73.1 (2015): 102-116) – does not account for dispersion, which leads to the introduction of errors in CBF. Given that the transport time from the labelling region to the tissue – the arterial transit time (ATT) – depends on the region of the brain and the condition of the patient, it is likely that these errors will also vary with the ATT. In this study, various dispersion models are assessed in comparison with the white paper (WP) formula for CBF quantification, enabling the errors introduced by the WP to be quantified. Additionally, this study examines the relationship between the errors associated with the WP and the ATT – and how this is influenced by dispersion. Methods: Data were simulated using the standard model for pseudo-continuous ASL, along with various dispersion models, and then quantified using the formula in the WP. The ATT was varied from 0.5s-1.3s, and the errors associated with noise artefacts were computed in order to define the concept of significant error. The instantaneous slope of the error was also computed as an indicator of the sensitivity of the error with fluctuations in ATT. Finally, a regression analysis was performed to obtain the mean error against ATT. Results: An error of 20.9% was found to be comparable to that introduced by typical measurement noise. The WP formula was shown to introduce errors exceeding 20.9% for ATTs beyond 1.25s even when dispersion effects were ignored. Using a Gaussian dispersion model, a mean error of 16% was introduced by using the WP, and a dispersion threshold of σ=0.6 was determined, beyond which the error was found to increase considerably with ATT. The mean error ranged from 44.5% to 73.5% when other physiologically plausible dispersion models were implemented, and the instantaneous slope varied from 35 to 75 as dispersion levels were varied. Conclusion: It has been shown that the WP quantification formula holds only within an ATT window of 0.5 to 1.25s, and that this window gets narrower as dispersion occurs. Provided that the dispersion levels fall below the threshold evaluated in this study, however, the WP can measure CBF with reasonable accuracy if dispersion is correctly modelled by the Gaussian model. However, substantial errors were observed with other common models for dispersion with dispersion levels similar to those that have been observed in literature.

Keywords: arterial spin labelling, dispersion, MRI, perfusion

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Authors: Yu-Chieh Chen, Kuei-Feng Shen, Chia-Ling Chao

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The purpose of this report was to present the nursing experience and case of an unexpected cerebellar hemorrhagic stroke with acute hydrocephalus patient after lumbar spine surgery. The patient had been suffering from an emergent external ventricular drainage and stayed in the Surgical Intensive Care Unit from July 8, 2016, to July 22, 2016. During the period of the case, the data were collected for attendance, evaluation, observation, interview, searching medical record, etc. An integral evaluation of the patient's physiological 'psychological' social and spiritual states was also noted. The author noticed the following major nursing problems including ineffective cerebral perfusion 'physical activity dysfunction' family resource preparation for disability. The author provided nursing care to maintain normal intracranial pressure, along with a well-therapeutic relationship and applied interdisciplinary medical/nursing team to draft an individualized and appropriate nursing plan for them to face the psychosocial impact of the patient disabilities. We also actively participated in the rehabilitation treatments to improve daily activity and confidence. This was deemed necessary to empower them to a more positive attitude in the future.

Keywords: family resourace preparation inability, hemorrhagic sroke, ineffective tissue cerebral perfusion, lumbar spine surgery

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Authors: Nicole Selvi Hill, Archchana Radhakrishnan

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Introduction: Traumatic brain injury (TBI) is a leading cause of mortality among trauma patients. In the management of TBI, the main principle is avoiding cerebral ischemia, as this is a strong determiner of neurological outcomes. The use of vasoactive drugs, such as vasopressin, has an important role in maintaining cerebral perfusion pressure to prevent secondary brain injury. Current guidelines do not suggest a preferred vasoactive drug to administer in the management of TBI, and there is a paucity of information on the therapeutic potential of vasopressin following TBI. Vasopressin is also an endogenous anti-diuretic hormone (AVP), and pathways mediated by AVP play a large role in the underlying pathological processes of TBI. This creates an overlap of discussion regarding the therapeutic potential of vasopressin following TBI. Currently, its popularity lies in vasodilatory and cardiogenic shock in the intensive care setting, with increasing support for its use in haemorrhagic and septic shock. Methodology: This is a review article based on a literature review. An electronic search was conducted via PubMed, Cochrane, EMBASE, and Google Scholar. The aim was to identify clinical studies looking at the therapeutic administration of vasopressin in severe traumatic brain injury. The primary aim was to look at the neurological outcome of patients. The secondary aim was to look at surrogate markers of cerebral perfusion measurements, such as cerebral perfusion pressure, cerebral oxygenation, and cerebral blood flow. Results: Eight papers were included in the final number. Three were animal studies; five were human studies, comprised of three case reports, one retrospective review of data, and one randomised control trial. All animal studies demonstrated the benefits of vasopressors in TBI management. One animal study showed the superiority of vasopressin in reducing intracranial pressure and increasing cerebral oxygenation over a catecholaminergic vasopressor, phenylephrine. All three human case reports were supportive of vasopressin as a rescue therapy in catecholaminergic-resistant hypotension. The retrospective review found vasopressin did not increase cerebral oedema in TBI patients compared to catecholaminergic vasopressors; and demonstrated a significant reduction in the requirements of hyperosmolar therapy in patients that received vasopressin. The randomised control trial results showed no significant differences in primary and secondary outcomes between TBI patients receiving vasopressin versus those receiving catecholaminergic vasopressors. Apart from the randomised control trial, the studies included are of low-level evidence. Conclusion: Studies favour vasopressin within certain parameters of cerebral function compared to control groups. However, the neurological outcomes of patient groups are not known, and animal study results are difficult to extrapolate to humans. It cannot be said with certainty whether vasopressin’s benefits stand above usage of other vasoactive drugs due to the weaknesses of the evidence. Further randomised control trials, which are larger, standardised, and rigorous, are required to improve knowledge in this field.

Keywords: catecholamines, cerebral perfusion pressure, traumatic brain injury, vasopressin, vasopressors

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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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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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Authors: Abdalla Mansour, Dan Brown, Adel Helmy, Rikin Trivedi, Mathew Guilfoyle

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Introduction: Diagnosing delayed cerebral ischaemia (DCI) following aneurysmal subarachnoid haemorrhage (SAH) can be challenging, particularly in poor-grade patients. Objectives: This study sought to assess the value of routine CTP in identifying (or excluding) DCI and in guiding management. Methods: Eight-year retrospective neuroimaging study at a large UK neurosurgical centre. Subjects included a random sample of adult patients with confirmed aneurysmal SAH that had a CTP scan during their inpatient stay, over a 8-year period (May 2014 - May 2022). Data collected through electronic patient record and PACS. Variables included age, WFNS scale, aneurysm site, treatment, the timing of CTP, radiologist report, and DCI management. Results: Over eight years, 916 patients were treated for aneurysmal SAH; this study focused on 466 patients that were randomly selected. Of this sample, 181 (38.84%) had one or more CTP scans following brain aneurysm treatment (Total 318). The first CTP scan in each patient was performed at 1-20 days following ictus (median 4 days). There was radiological evidence of DCI in 83, and no reversible ischaemia was found in 80. Findings were equivocal in the remaining 18. Of the 103 patients treated with clipping, 49 had DCI radiological evidence, in comparison to 31 of 69 patients treated with endovascular embolization. The remaining 9 patients are either unsecured aneurysms or non-aneurysmal SAH. Of the patients with radiological evidence of DCI, 65 had a treatment change following the CTP directed at improving cerebral perfusion. In contrast, treatment was not changed for (61) patients without radiological evidence of DCI. Conclusion: CTP is a useful adjunct to clinical assessment in the diagnosis of DCI and is helpful in identifying patients that may benefit from intensive therapy and those in whom it is unlikely to be effective.

Keywords: SAH, vasospasm, aneurysm, delayed cerebral ischemia

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

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

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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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Authors: Yasuyuki Takahashi, Hayato Ishimura, Masao Miyagawa, Teruhito Mochizuki

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Quantitative measurement of myocardium perfusion is possible with single photon emission computed tomography (SPECT) using a semiconductor detector. However, accumulation of ^99mTc-tetrofosmin in the liver may make it difficult to assess that accurately in the inferior myocardium. Our idea is to reduce the high accumulation in the liver by using dynamic SPECT imaging and a technique called time subtraction. We evaluated the performance of a new SPECT system with a cadmium-zinc-telluride solid-state semi- conductor detector (Discovery NM 530c; GE Healthcare). Our system acquired list-mode raw data over 10 minutes for a typical patient. From the data, ten SPECT images were reconstructed, one for every minute of acquired data. Reconstruction with the semiconductor detector was based on an implementation of a 3-D iterative Bayesian reconstruction algorithm. We studied 20 patients with coronary artery disease (mean age 75.4 ± 12.1 years; range 42-86; 16 males and 4 females). In each subject, 259 MBq of ^99mTc-tetrofosmin was injected intravenously. We performed both a phantom and a clinical study using dynamic SPECT. An approximation to a liver-only image is obtained by reconstructing an image from the early projections during which time the liver accumulation dominates (0.5~2.5 minutes SPECT image-5~10 minutes SPECT image). The extracted liver-only image is then subtracted from a later SPECT image that shows both the liver and the myocardial uptake (5~10 minutes SPECT image-liver-only image). The time subtraction of liver was possible in both a phantom and the clinical study. The visualization of the inferior myocardium was improved. In past reports, higher accumulation in the myocardium due to the overlap of the liver is un-diagnosable. Using our time subtraction method, the image quality of the ^99mTc-tetorofosmin myocardial SPECT image is considerably improved.

Keywords: 99mTc-tetrofosmin, dynamic SPECT, time subtraction, semiconductor detector

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Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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Authors: W. Baumgartner, M. Welti, N. Hild, S. C. Hess, W. J. Stark, G. Meier Bürgisser, P. Giovanoli, J. Buschmann

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Perfusion bioreactors are used to solve problems in tissue engineering in terms of sufficient nutrient and oxygen supply. Such problems especially occur in critical size grafts because vascularization is often too slow after implantation ending up in necrotic cores. Biominerizable and biocompatible nanocomposite materials are attractive and suitable scaffold materials for bone tissue engineering because they offer mineral components in organic carriers – mimicking natural bone tissue. In addition, human adipose derived stem cells (ASCs) can potentially be used to increase bone healing as they are capable of differentiating towards osteoblasts or endothelial cells among others. In the present study, electrospun nanocomposite disks of poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/a-CaP) were seeded with human ASCs and eight disks were stacked in a bioreactor running with normal culture medium (no differentiation supplements). Under continuous perfusion and uniaxial cyclic compression, load-displacement curves as a function of time were assessed. Stiffness and energy dissipation were recorded. Moreover, stem cell densities in the layers of the piled scaffold were determined as well as their morphologies and differentiation status (endothelial cell differentiation, chondrogenesis and osteogenesis). While the stiffness of the cell free constructs increased over time caused by the transformation of the a-CaP nanoparticles into flake-like apatite, ASC-seeded constructs showed a constant stiffness. Stem cell density gradients were histologically determined with a linear increase in the flow direction from the bottom to the top of the 3.5 mm high pile (r2 > 0.95). Cell morphology was influenced by the flow rate, with stem cells getting more roundish at higher flow rates. Less than 1 % osteogenesis was found upon osteopontin immunostaining at the end of the experiment (9 days), while no endothelial cell differentiation and no chondrogenesis was triggered under these conditions. All ASCs had mainly remained in their original pluripotent status within this time frame. In summary, we have fabricated a critical size bone graft based on a biominerizable bone-biomimetic nanocomposite with preserved stiffness when seeded with human ASCs. The special feature of this bone graft was that ASC densities inside the piled construct varied with a linear gradient, which is a good starting point for tissue engineering interfaces such as bone-cartilage where the bone tissue is cell rich while the cartilage exhibits low cell densities. As such, this tissue-engineered graft may act as a bone-cartilage interface after the corresponding differentiation of the ASCs.

Keywords: bioreactor, bone, cartilage, nanocomposite, stem cell gradient

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: Abdelkhalek Bakkari

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Image segmentation is a critical step in image processing and pattern recognition. In this paper, we proposed a new robust automatic image classification based on a dynamic fuzzy c-means algorithm and mathematical morphology. The proposed segmentation algorithm (DFCM_MM) has been applied to MR perfusion images. The obtained results show the validity and robustness of the proposed approach.

Keywords: segmentation, classification, dynamic, fuzzy c-means, MR image

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Authors: Aniko Babits, Ahmad Daoud

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Introduction: The beach chair position (BCP) is a good approach to almost all types of shoulder procedures. However, moving an anaesthetized patient from the supine to sitting position may pose a risk of cerebral hypoperfusion and potential cerebral ischaemia as a result of significant reductions in blood pressure and cardiac output. Hypocapnia in ventilated patients and impaired blood flow to the vertebral artery due to hyperextension, rotation, or tilt of the head may have an impact too. Co-morbidities that may increase the risk of cerebral ischaemia in the BCP include diabetes with autonomic neuropathy, cerebrovascular disease, cardiac disease, severe hypertension, generalized vascular disease, history of fainting, and febrile conditions. Beach chair surgery requires a careful anaesthetic and surgical management to optimize patient safety and minimize the risk of adverse outcomes. Methods: We describe the necessary steps for optimal patient positioning and the aims of intraoperative management, including anaesthetic techniques to ensure patient safety in the BCP. Results: Regardless of the anaesthetic technique, adequate patient positioning is paramount in the BCP. The key steps to BCP are aimed at optimizing surgical success and minimizing the risk of severe neurovascular complications. The primary aim of anaesthetic management is to maintain cardiac output and mean arterial pressure (MAP) to protect cerebral perfusion. Blood pressure management includes treating a fall in MAP of more than 25% from baseline or a MAP less than 70 mmHg. This can be achieved by using intravenous fluids or vasopressors. A number of anaesthetic techniques could also improve cerebral oxygenation, including avoidance of intermittent positive pressure ventilation (IPPV) with general anaesthesia (GA), using regional anaesthesia, maintaining normocapnia and normothermia, and the application of compression stockings. Conclusions: In summary, BCP is a reliable and effective position to perform shoulder procedures. Simple steps to patient positioning and careful anaesthetic management could maximize patient safety and avoid unwanted adverse outcomes in patients undergoing surgery in BCP.

Keywords: beach chair position, cerebral oxygenation, cerebral perfusion, sitting position

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Authors: Natascha C. D'Amico, Enzo Grossi, Giovanni Valbusa, Ala Malasevschi, Gianpiero Cardone, Sergio Papa

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Purpose: To characterize, through a radiomic approach, the nature of areas classified PI-RADS (Prostate Imaging Reporting and Data System) 3/5, recognized in multiparametric prostate magnetic resonance with T2-weighted (T2w), diffusion and perfusion sequences with paramagnetic contrast. Methods and Materials: 24 cases undergoing multiparametric prostate MR and biopsy were admitted to this pilot study. Clinical outcome of the PI-RADS 3/5 was found through biopsy, finding 8 malignant tumours. The analysed images were acquired with a Philips achieva 1.5T machine with a CE- T2-weighted sequence in the axial plane. Semi-automatic tumour segmentation was carried out on MR images using 3DSlicer image analysis software. 45 shape-based, intensity-based and texture-based features were extracted and represented the input for preprocessing. An evolutionary algorithm (a TWIST system based on KNN algorithm) was used to subdivide the dataset into training and testing set and select features yielding the maximal amount of information. After this pre-processing 20 input variables were selected and different machine learning systems were used to develop a predictive model based on a training testing crossover procedure. Results: The best machine learning system (three-layers feed-forward neural network) obtained a global accuracy of 90% ( 80 % sensitivity and 100% specificity ) with a ROC of 0.82. Conclusion: Machine learning systems coupled with radiomics show a promising potential in distinguishing benign from malign tumours in PI-RADS 3/5 areas.

Keywords: machine learning, MR prostate, PI-Rads 3, radiomics

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Authors: Daniel Nieto, Ramiro Couceiro

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Microfluidic chips have demonstrated their significant application potentials in microbiological processing and chemical reactions, with the goal of developing monolithic and compact chip-sized multifunctional systems. Heat generation and thermal control are critical in some of the biochemical processes. The paper presents a laser direct-write technique for rapid prototyping and manufacturing of microheater chips and its applicability for perfusion cell culture outside a cell incubator. The aim of the microheater is to take the role of conventional incubators for cell culture for facilitating microscopic observation or other online monitoring activities during cell culture and provides portability of cell culture operation. Microheaters (5 mm × 5 mm) have been successfully fabricated on soda-lime glass substrates covered with aluminum layer of thickness 120 nm. Experimental results show that the microheaters exhibit good performance in temperature rise and decay characteristics, with localized heating at targeted spatial domains. These microheaters were suitable for a maximum long-term operation temperature of 120ºC and validated for long-time operation at 37ºC. for 24 hours. Results demonstrated that the physiology of the cultured SW480 adenocarcinoma of the colon cell line on the developed microheater chip was consistent with that of an incubator.

Keywords: laser microfabrication, microheater, bioengineering, cell culture

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Authors: O.Ofoegbu, S. Roongnapa, A.N. Eboatu

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Most polluted environments, most challengingly, aerosol types, contain a cocktail of different toxicants. Multi-templating of matrices have been the recent target by researchers in a bid to solving complex mixed-toxicant challenges using single or common remediation systems. This investigation looks at the effect of such multi-templated system vis-a-vis the synthesis by non-covalent interaction, of a molecularly imprinted polymer architecture using nicotine and its structural analogue Phenylalanine amide individually and, in the blend, (50:50), as template materials in a Chitosan-Methacrylic acid functional monomer matrix. The temperature for polymerization is 60OC and time for polymerization, 12hrs (water bath heating), 4mins for (microwave heating). The characteristic thermal properties of the molecularly imprinted materials are investigated using Simultaneous Thermal Analysis (STA) profiling, while the absorption and separation efficiencies based on the relative retention times and peak areas of templates were studied amongst other properties. Transmission Electron Microscopy (TEM) results obtained, show the creation of heterogeneous nanocavities, regardless, the introduction of Caffeine a close structural analogue presented near-zero perfusion. This confirms the selectivity and specificity of the templated polymers despite its dual-templated nature. The STA results presented the materials as having decomposition temperatures above 250OC and a relative loss in mass of less than19% over a period within 50mins of heating. Consequent to this outcome, multi-templated systems can be fabricated to sequester specifically and selectively targeted toxicants in a mixed toxicant populated system effectively.

Keywords: chitosan, dual-templated, methacrylic acid, mixed-toxicants, molecularly-imprinted-polymer

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