Spatially coordinated dynamic gene transcription in living pituitary tissue

PubMed Central

Featherstone, Karen; Hey, Kirsty; Momiji, Hiroshi; McNamara, Anne V; Patist, Amanda L; Woodburn, Joanna; Spiller, David G; Christian, Helen C; McNeilly, Alan S; Mullins, John J; Finkenstädt, Bärbel F; Rand, David A; White, Michael RH; Davis, Julian RE

2016-01-01

Transcription at individual genes in single cells is often pulsatile and stochastic. A key question emerges regarding how this behaviour contributes to tissue phenotype, but it has been a challenge to quantitatively analyse this in living cells over time, as opposed to studying snap-shots of gene expression state. We have used imaging of reporter gene expression to track transcription in living pituitary tissue. We integrated live-cell imaging data with statistical modelling for quantitative real-time estimation of the timing of switching between transcriptional states across a whole tissue. Multiple levels of transcription rate were identified, indicating that gene expression is not a simple binary ‘on-off’ process. Immature tissue displayed shorter durations of high-expressing states than the adult. In adult pituitary tissue, direct cell contacts involving gap junctions allowed local spatial coordination of prolactin gene expression. Our findings identify how heterogeneous transcriptional dynamics of single cells may contribute to overall tissue behaviour. DOI: http://dx.doi.org/10.7554/eLife.08494.001 PMID:26828110

Non-invasive assessment of pulsatile intracranial pressure with phase-contrast magnetic resonance imaging

PubMed Central

Lindstrøm, Erika Kristina; Vatnehol, Svein Are Sirirud; Mardal, Kent-André; Emblem, Kyrre Eeg; Eide, Per Kristian

2017-01-01

Invasive monitoring of pulsatile intracranial pressure can accurately predict shunt response in patients with idiopathic normal pressure hydrocephalus, but may potentially cause complications such as bleeding and infection. We tested how a proposed surrogate parameter for pulsatile intracranial pressure, the phase-contrast magnetic resonance imaging derived pulse pressure gradient, compared with its invasive counterpart. In 22 patients with suspected idiopathic normal pressure hydrocephalus, preceding invasive intracranial pressure monitoring, and any surgical shunt procedure, we calculated the pulse pressure gradient from phase-contrast magnetic resonance imaging derived cerebrospinal fluid flow velocities obtained at the upper cervical spinal canal using a simplified Navier-Stokes equation. Repeated measurements of the pulse pressure gradient were also undertaken in four healthy controls. Of 17 shunted patients, 16 responded, indicating high proportion of “true” normal pressure hydrocephalus in the patient cohort. However, there was no correlation between the magnetic resonance imaging derived pulse pressure gradient and pulsatile intracranial pressure (R = -.18, P = .43). Pulse pressure gradients were also similar in patients and healthy controls (P = .26), and did not differ between individuals with pulsatile intracranial pressure above or below established thresholds for shunt treatment (P = .97). Assessment of pulse pressure gradient at level C2 was therefore not found feasible to replace invasive monitoring of pulsatile intracranial pressure in selection of patients with idiopathic normal pressure hydrocephalus for surgical shunting. Unlike invasive, overnight monitoring, the pulse pressure gradient from magnetic resonance imaging comprises short-term pressure fluctuations only. Moreover, complexity of cervical cerebrospinal fluid flow and -pulsatility at the upper cervical spinal canal may render the pulse pressure gradient a poor surrogate marker for intracranial pressure pulsations. PMID:29190788

Non-invasive assessment of pulsatile intracranial pressure with phase-contrast magnetic resonance imaging.

PubMed

Ringstad, Geir; Lindstrøm, Erika Kristina; Vatnehol, Svein Are Sirirud; Mardal, Kent-André; Emblem, Kyrre Eeg; Eide, Per Kristian

2017-01-01

Invasive monitoring of pulsatile intracranial pressure can accurately predict shunt response in patients with idiopathic normal pressure hydrocephalus, but may potentially cause complications such as bleeding and infection. We tested how a proposed surrogate parameter for pulsatile intracranial pressure, the phase-contrast magnetic resonance imaging derived pulse pressure gradient, compared with its invasive counterpart. In 22 patients with suspected idiopathic normal pressure hydrocephalus, preceding invasive intracranial pressure monitoring, and any surgical shunt procedure, we calculated the pulse pressure gradient from phase-contrast magnetic resonance imaging derived cerebrospinal fluid flow velocities obtained at the upper cervical spinal canal using a simplified Navier-Stokes equation. Repeated measurements of the pulse pressure gradient were also undertaken in four healthy controls. Of 17 shunted patients, 16 responded, indicating high proportion of "true" normal pressure hydrocephalus in the patient cohort. However, there was no correlation between the magnetic resonance imaging derived pulse pressure gradient and pulsatile intracranial pressure (R = -.18, P = .43). Pulse pressure gradients were also similar in patients and healthy controls (P = .26), and did not differ between individuals with pulsatile intracranial pressure above or below established thresholds for shunt treatment (P = .97). Assessment of pulse pressure gradient at level C2 was therefore not found feasible to replace invasive monitoring of pulsatile intracranial pressure in selection of patients with idiopathic normal pressure hydrocephalus for surgical shunting. Unlike invasive, overnight monitoring, the pulse pressure gradient from magnetic resonance imaging comprises short-term pressure fluctuations only. Moreover, complexity of cervical cerebrospinal fluid flow and -pulsatility at the upper cervical spinal canal may render the pulse pressure gradient a poor surrogate marker for intracranial pressure pulsations.

Pulsatile perfusion bioreactor for cardiac tissue engineering.

PubMed

Brown, Melissa A; Iyer, Rohin K; Radisic, Milica

2008-01-01

Cardiovascular disease is the number one cause of mortality in North America. Cardiac tissue engineering aims to engineer a contractile patch of physiological thickness to use in surgical repair of diseased heart tissue. We previously reported that perfusion of engineered cardiac constructs resulted in improved tissue assembly. Because heart tissues respond to mechanical stimuli in vitro and experience rhythmic mechanical forces during contraction in vivo, we hypothesized that provision of pulsatile interstitial medium flow to an engineered cardiac patch would result in enhanced tissue assembly by way of mechanical conditioning and improved mass transport. Thus, we constructed a novel perfusion bioreactor capable of providing pulsatile fluid flow at physiologically relevant shear stresses and flow rates. Pulsatile perfusion (PP) was achieved by incorporation of a normally closed solenoid pinch valve into the perfusion loop and was carried out at a frequency of 1 Hz and a flow rate of 1.50 mL/min (PP) or 0.32 mL/min (PP-LF). Nonpulsatile flow at 1.50 mL/min (NP) or 0.32 mL/min (NP-LF) served as controls. Static controls were cultivated in well plates. The main experimental groups were seeded with cells enriched for cardiomyocytes by one preplating step (64% cardiac Troponin I+, 34% prolyl-4-hydroxylase+), whereas pure cardiac fibroblasts and cells enriched for cardiomyocytes by two preplating steps (81% cardiac Troponin I+, 16% prolyl-4-hydroxylase+) served as controls. Cultivation under pulsatile flow had beneficial effects on contractile properties. Specifically, the excitation threshold was significantly lower in the PP condition (pulsatile perfusion at 1.50 mL/min) than in the Static control, and the contraction amplitude was the highest; whereas high maximum capture rate was observed for the PP-LF conditions (pulsatile perfusion at 0.32 mL/min). The enhanced hypertrophy index observed for the PP-LF group was consistent with the highest cellular length and diameter in this group. Within the same cultivation groups (Static, NP-LF, PP-LF, PP, and NP) there were no significant differences in the diameter between fibroblasts and cardiomyocytes, although cardiomyocytes were significantly more elongated than fibroblasts under PP-LF conditions. Cultivation of control cell populations resulted in noncontractile constructs when cardiac fibroblasts were used (as expected) and no overall improvement in functional properties when two steps of preplating were used to enrich for cardiomyocytes in comparison with only one step of preplating.

Dynamic culturing of cartilage tissue: the significance of hydrostatic pressure.

PubMed

Correia, Cristina; Pereira, Ana L; Duarte, Ana R C; Frias, Ana M; Pedro, Adriano J; Oliveira, João T; Sousa, Rui A; Reis, Rui L

2012-10-01

Human articular cartilage functions under a wide range of mechanical loads in synovial joints, where hydrostatic pressure (HP) is the prevalent actuating force. We hypothesized that the formation of engineered cartilage can be augmented by applying such physiologic stimuli to chondrogenic cells or stem cells, cultured in hydrogels, using custom-designed HP bioreactors. To test this hypothesis, we investigated the effects of distinct HP regimens on cartilage formation in vitro by either human nasal chondrocytes (HNCs) or human adipose stem cells (hASCs) encapsulated in gellan gum (GG) hydrogels. To this end, we varied the frequency of low HP, by applying pulsatile hydrostatic pressure or a steady hydrostatic pressure load to HNC-GG constructs over a period of 3 weeks, and evaluated their effects on cartilage tissue-engineering outcomes. HNCs (10×10(6) cells/mL) were encapsulated in GG hydrogels (1.5%) and cultured in a chondrogenic medium under three regimens for 3 weeks: (1) 0.4 MPa Pulsatile HP; (2) 0.4 MPa Steady HP; and (3) Static. Subsequently, we applied the pulsatile regimen to hASC-GG constructs and varied the amplitude of loading, by generating both low (0.4 MPa) and physiologic (5 MPa) HP levels. hASCs (10×10(6) cells/mL) were encapsulated in GG hydrogels (1.5%) and cultured in a chondrogenic medium under three regimens for 4 weeks: (1) 0.4 MPa Pulsatile HP; (2) 5 MPa Pulsatile HP; and (3) Static. In the HNC study, the best tissue development was achieved by the pulsatile HP regimen, whereas in the hASC study, greater chondrogenic differentiation and matrix deposition were obtained for physiologic loading, as evidenced by gene expression of aggrecan, collagen type II, and sox-9; metachromatic staining of cartilage extracellular matrix; and immunolocalization of collagens. We thus propose that both HNCs and hASCs detect and respond to physical forces, thus resembling joint loading, by enhancing cartilage tissue development in a frequency- and amplitude-dependant manner.

Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study.

PubMed

Mitchell, Gary F; van Buchem, Mark A; Sigurdsson, Sigurdur; Gotal, John D; Jonsdottir, Maria K; Kjartansson, Ólafur; Garcia, Melissa; Aspelund, Thor; Harris, Tamara B; Gudnason, Vilmundur; Launer, Lenore J

2011-11-01

Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 ± 0.037 SD/SD, P<0.001), grey matter (-0.079 ± 0.038 SD/SD, P = 0.038) and white matter (-0.128 ± 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse wave velocity (-0.095 ± 0.043 SD/SD, P = 0.028) and carotid pulse pressure (-0.114 ± 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (-0.165 ± 0.039 SD/SD, P<0.001), slower processing speed (-0.118 ± 0.033 SD/SD, P<0.001) and worse performance on tests assessing executive function (-0.155 ± 0.041 SD/SD, P<0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains.

Volumetric velocimetry downstream of a percutaneous heart valve

NASA Astrophysics Data System (ADS)

Raghav, Vrishank; Clifford, Christopher; Midha, Prem; Okafor, Ikechukwu; Thurow, Brian; Yoganathan, Ajit; Auburn University Collaboration; Georgia Institute of Technology Collaboration

2017-11-01

Transcatheter aortic valve replacement has emerged as a safe and effective treatment for severe, symptomatic aortic stenosis in intermediate or greater surgical risk patients. However, despite excellent short-term outcomes, improved imaging and awareness has led to the identification of leaflet thrombosis on the aortic side of the prosthesis. Upon implantation, the transcatheter heart valve (THV) becomes enclosed in the native aortic valve leaflet tissue dividing the native sinus into two regions - a smaller anatomical sinus and a neo-sinus. To understand the causes for thrombosis, plenoptic Particle Image Velocimetry (PIV) is used to investigate the pulsatile three-dimensional flow in the sinus and neo-sinus region of the THV. Experiments are conducted on both a real and a transparent THV model in a pulsatile flow loop capable of replicating physiological hemodynamics. Comparisons with planar PIV results demonstrate the feasibility of using Plenoptic PIV to study heart valve fluid dynamics. Large three-dimensional regions of low velocity magnitude and low viscous shear stress were observed near the heart valve which could increase particle residence time potentially leading to formation of clots the THV leaflet.

Integration of actomyosin contractility with cell-cell adhesion during dorsal closure.

PubMed

Duque, Julia; Gorfinkiel, Nicole

2016-12-15

In this work, we combine genetic perturbation, time-lapse imaging and quantitative image analysis to investigate how pulsatile actomyosin contractility drives cell oscillations, apical cell contraction and tissue closure during morphogenesis of the amnioserosa, the main force-generating tissue during the dorsal closure in Drosophila We show that Myosin activity determines the oscillatory and contractile behaviour of amnioserosa cells. Reducing Myosin activity prevents cell shape oscillations and reduces cell contractility. By contrast, increasing Myosin activity increases the amplitude of cell shape oscillations and the time cells spend in the contracted phase relative to the expanded phase during an oscillatory cycle, promoting cell contractility and tissue closure. Furthermore, we show that in AS cells, Rok controls Myosin foci formation and Mbs regulates not only Myosin phosphorylation but also adhesion dynamics through control of Moesin phosphorylation, showing that Mbs coordinates actomyosin contractility with cell-cell adhesion during amnioserosa morphogenesis. © 2016. Published by The Company of Biologists Ltd.

Effects of pacing magnitudes and forms on bistability width in a modeled ventricular tissue

NASA Astrophysics Data System (ADS)

Huang, Xiaodong; Liu, Xuemei; Zheng, Lixian; Mi, Yuanyuan; Qian, Yu

2013-07-01

Bistability in periodically paced cardiac tissue is relevant to cardiac arrhythmias and its control. In the present paper, one-dimensional tissue of the phase I Luo-Rudy model is numerically investigated. The effects of various parameters of pacing signals on bistability width are studied. The following conclusions are obtained: (i) Pacing can be classified into two types: pulsatile and sinusoidal types. Pulsatile pacing reduces bistability width as its magnitude is increased. Sinusoidal pacing increases the width as its amplitude is increased. (ii) In a pacing period the hyperpolarizing part plays a more important role than the depolarizing part. Variations of the hyperpolarizing ratio in a period evidently change the width of bistability and its variation tendency. (iii) A dynamical mechanism is proposed to qualitatively explain the phenomena, which reveals the reason for the different effects of pulsatile and sinusoidal pacing on bistability. The methods for changing bistability width by external pacing may help control arrhythmias in cardiology.

Dynamic Culturing of Cartilage Tissue: The Significance of Hydrostatic Pressure

PubMed Central

Pereira, Ana L.; Duarte, Ana R.C.; Frias, Ana M.; Pedro, Adriano J.; Oliveira, João T.; Sousa, Rui A.; Reis, Rui L.

2012-01-01

Human articular cartilage functions under a wide range of mechanical loads in synovial joints, where hydrostatic pressure (HP) is the prevalent actuating force. We hypothesized that the formation of engineered cartilage can be augmented by applying such physiologic stimuli to chondrogenic cells or stem cells, cultured in hydrogels, using custom-designed HP bioreactors. To test this hypothesis, we investigated the effects of distinct HP regimens on cartilage formation in vitro by either human nasal chondrocytes (HNCs) or human adipose stem cells (hASCs) encapsulated in gellan gum (GG) hydrogels. To this end, we varied the frequency of low HP, by applying pulsatile hydrostatic pressure or a steady hydrostatic pressure load to HNC-GG constructs over a period of 3 weeks, and evaluated their effects on cartilage tissue-engineering outcomes. HNCs (10×106 cells/mL) were encapsulated in GG hydrogels (1.5%) and cultured in a chondrogenic medium under three regimens for 3 weeks: (1) 0.4 MPa Pulsatile HP; (2) 0.4 MPa Steady HP; and (3) Static. Subsequently, we applied the pulsatile regimen to hASC-GG constructs and varied the amplitude of loading, by generating both low (0.4 MPa) and physiologic (5 MPa) HP levels. hASCs (10×106 cells/mL) were encapsulated in GG hydrogels (1.5%) and cultured in a chondrogenic medium under three regimens for 4 weeks: (1) 0.4 MPa Pulsatile HP; (2) 5 MPa Pulsatile HP; and (3) Static. In the HNC study, the best tissue development was achieved by the pulsatile HP regimen, whereas in the hASC study, greater chondrogenic differentiation and matrix deposition were obtained for physiologic loading, as evidenced by gene expression of aggrecan, collagen type II, and sox-9; metachromatic staining of cartilage extracellular matrix; and immunolocalization of collagens. We thus propose that both HNCs and hASCs detect and respond to physical forces, thus resembling joint loading, by enhancing cartilage tissue development in a frequency- and amplitude-dependant manner. PMID:22559784

Assessing photoplethysmographic imaging performance beyond facial perfusion analysis

NASA Astrophysics Data System (ADS)

Amelard, Robert; Hughson, Richard L.; Greaves, Danielle K.; Clausi, David A.; Wong, Alexander

2017-02-01

Photoplethysmographic imaging (PPGI) systems are relatively new non-contact biophotonic diffuse reflectance systems able to assess arterial pulsations through transient changes in light-tissue interaction. Many PPGI studies have focused on extracting heart rate from the face or hand. Though PPGI systems can be used for widefield imaging of any anatomical area, whole-body investigations are lacking. Here, using a novel PPGI system, coded hemodynamic imaging (CHI), we explored and analyzed the pulsatility at major arterial locations across the whole body, including the neck (carotid artery), arm/wrist (brachial, radial and ulnar arteries), and leg/feet (popliteal and tibial arteries). CHI was positioned 1.5 m from the participant, and diffuse reactance from a broadband tungsten-halogen illumination was filtered using 850{1000 nm bandpass filter for deep tissue penetration. Images were acquired over a highly varying 24-participant sample (11/13 female/male, age 28.7+/-12.4 years, BMI 25.5+/-5.2 kg/m2), and a preliminary case study was performed. B-mode ultrasound images were acquired to validate observations through planar arterial characteristics.

Modern Diagnostic Techniques for the Assessment of Ocular Blood Flow in Myopia: Current State of Knowledge.

PubMed

Grudzińska, Ewa; Modrzejewska, Monika

2018-01-01

Myopia is the most common refractive error and the subject of interest of various studies assessing ocular blood flow. Increasing refractive error and axial elongation of the eye result in the stretching and thinning of the scleral, choroid, and retinal tissues and the decrease in retinal vessel diameter, disturbing ocular blood flow. Local and systemic factors known to change ocular blood flow include glaucoma, medications and fluctuations in intraocular pressure, and metabolic parameters. Techniques and tools assessing ocular blood flow include, among others, laser Doppler flowmetry (LDF), retinal function imager (RFI), laser speckle contrast imaging (LSCI), magnetic resonance imaging (MRI), optical coherence tomography angiography (OCTA), pulsatile ocular blood flowmeter (POBF), fundus pulsation amplitude (FPA), colour Doppler imaging (CDI), and Doppler optical coherence tomography (DOCT). Many researchers consistently reported lower blood flow parameters in myopic eyes regardless of the used diagnostic method. It is unclear whether this is a primary change that causes secondary thinning of ocular tissues or quite the opposite; that is, the mechanical stretching of the eye wall reduces its thickness and causes a secondary lower demand of tissues for oxygen. This paper presents a review of studies assessing ocular blood flow in myopes.

Elimination of motion, pulsatile flow and cross-talk artifacts using blade sequences in lumbar spine MR imaging.

PubMed

Lavdas, Eleftherios; Mavroidis, Panayiotis; Kostopoulos, Spiros; Glotsos, Dimitrios; Roka, Violeta; Koutsiaris, Aristotle G; Batsikas, Georgios; Sakkas, Georgios K; Tsagkalis, Antonios; Notaras, Ioannis; Stathakis, Sotirios; Papanikolaou, Nikos; Vassiou, Katerina

2013-07-01

The purpose of this study is to evaluate the ability of T2 turbo spin echo (TSE) axial and sagittal BLADE sequences in reducing or even eliminating motion, pulsatile flow and cross-talk artifacts in lumbar spine MRI examinations. Forty four patients, who had routinely undergone a lumbar spine examination, participated in the study. The following pairs of sequences with and without BLADE were compared: a) T2 TSE Sagittal (SAG) in thirty two cases, and b) T2 TSE Axial (AX) also in thirty two cases. Both quantitative and qualitative analyses were performed based on measurements in different normal anatomical structures and examination of seven characteristics, respectively. The qualitative analysis was performed by experienced radiologists. Also, the presence of image motion, pulsatile flow and cross-talk artifacts was evaluated. Based on the results of the qualitative analysis for the different sequences and anatomical structures, the BLADE sequences were found to be significantly superior to the conventional ones in all the cases. The BLADE sequences eliminated the motion artifacts in all the cases. In our results, it was found that in the examined sequences (sagittal and axial) the differences between the BLADE and conventional sequences regarding the elimination of motion, pulsatile flow and cross-talk artifacts were statistically significant. In all the comparisons, the T2 TSE BLADE sequences were significantly superior to the corresponding conventional sequences regarding the classification of their image quality. In conclusion, this technique appears to be capable of potentially eliminating motion, pulsatile flow and cross-talk artifacts in lumbar spine MR images and producing high quality images in collaborative and non-collaborative patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Electrical stimulation systems for cardiac tissue engineering

PubMed Central

Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana

2009-01-01

We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures. PMID:19180087

Bioreactor-induced mesenchymal progenitor cell differentiation and elastic fiber assembly in engineered vascular tissues.

PubMed

Lin, Shigang; Mequanint, Kibret

2017-09-01

In vitro maturation of engineered vascular tissues (EVT) requires the appropriate incorporation of smooth muscle cells (SMC) and extracellular matrix (ECM) components similar to native arteries. To this end, the aim of the current study was to fabricate 4mm inner diameter vascular tissues using mesenchymal progenitor cells seeded into tubular scaffolds. A dual-pump bioreactor operating either in perfusion or pulsatile perfusion mode was used to generate physiological-like stimuli to promote progenitor cell differentiation, extracellular elastin production, and tissue maturation. Our data demonstrated that pulsatile forces and perfusion of 3D tubular constructs from both the lumenal and ablumenal sides with culture media significantly improved tissue assembly, effectively inducing mesenchymal progenitor cell differentiation to SMCs with contemporaneous elastin production. With bioreactor cultivation, progenitor cells differentiated toward smooth muscle lineage characterized by the expression of smooth muscle (SM)-specific markers smooth muscle alpha actin (SM-α-actin) and smooth muscle myosin heavy chain (SM-MHC). More importantly, pulsatile perfusion bioreactor cultivation enhanced the synthesis of tropoelastin and its extracellular cross-linking into elastic fiber compared with static culture controls. Taken together, the current study demonstrated progenitor cell differentiation and vascular tissue assembly, and provides insights into elastin synthesis and assembly to fibers. Incorporation of elastin into engineered vascular tissues represents a critical design goal for both mechanical and biological functions. In the present study, we seeded porous tubular scaffolds with multipotent mesenchymal progenitor cells and cultured in dual-pump pulsatile perfusion bioreactor. Physiological-like stimuli generated by bioreactor not only induced mesenchymal progenitor cell differentiation to vascular smooth muscle lineage but also actively promoted elastin synthesis and fiber assembly. Gene expression and protein synthesis analyses coupled with histological and immunofluorescence staining revealed that elastin-containing vascular tissues were fabricated. More importantly, co-localization and co-immunoprecipitation experiments demonstrated that elastin and fibrillin-1 were abundant throughout the cross-section of the tissue constructs suggesting a process of elastin protein crosslinking. This study paves a way forward to engineer elastin-containing functional vascular substitutes from multipotent progenitor cells in a bioreactor. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Ultrasonic Apparatus and Technique to Measure Changes in Intracranial Pressure

NASA Technical Reports Server (NTRS)

Yost, William T. (Inventor); Cantrell, John H. (Inventor)

2002-01-01

Changes in intracranial pressure can be measured dynamically and non-invasively by monitoring one or more cerebrospinal fluid pulsatile components. Pulsatile components such as systolic and diastolic blood pressures are partially transferred to the cerebrospinal fluid by way of blood vessels contained in the surrounding brain tissue and membrane. As intracranial pressure varies these cerebrospinal fluid pulsatile components also vary. Thus, intracranial pressure can be dynamically measured. Furthermore, use of acoustics allows the measurement to be completely non-invasive. In the preferred embodiment, phase comparison of a reflected acoustic signal to a reference signal using a constant frequency pulsed phase-locked-loop ultrasonic device allows the pulsatile components to be monitored. Calibrating the device by inducing a known change in intracranial pressure allows conversion to changes in intracranial pressure.

Spatial probabilistic pulsatility model for enhancing photoplethysmographic imaging systems

NASA Astrophysics Data System (ADS)

Amelard, Robert; Clausi, David A.; Wong, Alexander

2016-11-01

Photoplethysmographic imaging (PPGI) is a widefield noncontact biophotonic technology able to remotely monitor cardiovascular function over anatomical areas. Although spatial context can provide insight into physiologically relevant sampling locations, existing PPGI systems rely on coarse spatial averaging with no anatomical priors for assessing arterial pulsatility. Here, we developed a continuous probabilistic pulsatility model for importance-weighted blood pulse waveform extraction. Using a data-driven approach, the model was constructed using a 23 participant sample with a large demographic variability (11/12 female/male, age 11 to 60 years, BMI 16.4 to 35.1 kg·m-2). Using time-synchronized ground-truth blood pulse waveforms, spatial correlation priors were computed and projected into a coaligned importance-weighted Cartesian space. A modified Parzen-Rosenblatt kernel density estimation method was used to compute the continuous resolution-agnostic probabilistic pulsatility model. The model identified locations that consistently exhibited pulsatility across the sample. Blood pulse waveform signals extracted with the model exhibited significantly stronger temporal correlation (W=35,p<0.01) and spectral SNR (W=31,p<0.01) compared to uniform spatial averaging. Heart rate estimation was in strong agreement with true heart rate [r2=0.9619, error (μ,σ)=(0.52,1.69) bpm].

Human endothelial cell responses to cardiovascular inspired pulsatile shear stress

NASA Astrophysics Data System (ADS)

Watson, Matthew; Baugh, Lauren; Black, Lauren, III; Kemmerling, Erica

2016-11-01

It is well established that hemodynamic shear stress regulates blood vessel structure and the development of vascular pathology. This process can be studied via in vitro models of endothelial cell responses to pulsatile shear stress. In this study, a macro-scale cone and plate viscometer was designed to mimic various shear stress waveforms found in the body and apply these stresses to human endothelial cells. The device was actuated by a PID-controlled DC gear-motor. Cells were exposed to 24 hours of pulsatile shear and then imaged and stained to track their morphology and secretions. These measurements were compared with control groups of cells exposed to constant shear and no shear. The results showed that flow pulsatility influenced levels of secreted proteins such as VE-cadherin and neuroregulin IHC. Cell morphology was also influenced by flow pulsatility; in general cells exposed to pulsatile shear stress developed a higher aspect ratio than cells exposed to no flow but a lower aspect ratio than cells exposed to steady flow.

In vitro fabrication of a tissue engineered human cardiovascular patch for future use in cardiovascular surgery.

PubMed

Yang, Chao; Sodian, Ralf; Fu, Ping; Lüders, Cora; Lemke, Thees; Du, Jing; Hübler, Michael; Weng, Yuguo; Meyer, Rudolf; Hetzer, Roland

2006-01-01

One approach to tissue engineering has been the development of in vitro conditions for the fabrication of functional cardiovascular structures intended for implantation. In this experiment, we developed a pulsatile flow system that provides biochemical and biomechanical signals in order to regulate autologous, human patch-tissue development in vitro. We constructed a biodegradable patch scaffold from porous poly-4-hydroxy-butyrate (P4HB; pore size 80 to 150 microm). The scaffold was seeded with pediatric aortic cells. The cell-seeded patch constructs were placed in a self-developed bioreactor for 7 days to observe potential tissue formation under dynamic cell culture conditions. As a control, cell-seeded scaffolds were not conditioned in the bioreactor system. After maturation in vitro, the analysis of the tissue engineered constructs included biochemical, biomechanical, morphologic, and immunohistochemical examination. Macroscopically, all tissue engineered constructs were covered by cells. After conditioning in the bioreactor, the cells were mostly viable, had grown into the pores, and had formed tissue on the patch construct. Electron microscopy showed confluent smooth surfaces. Additionally, we demonstrated the capacity to generate collagen and elastin under in vitro pulsatile flow conditions in biochemical examination. Biomechanical testing showed mechanical properties of the tissue engineered human patch tissue without any statistical differences in strength or resistance to stretch between the static controls and the conditioned patches. Immunohistochemical examination stained positive for alpha smooth muscle actin, collagen type I, and fibronectin. There was minor tissue formation in the nonconditioned control samples. Porous P4HB may be used to fabricate a biodegradable patch scaffold. Human vascular cells attached themselves to the polymeric scaffold, and extracellular matrix formation was induced under controlled biomechanical and biodynamic stimuli in a self-developed pulsatile bioreactor system.

Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

PubMed

Eoh, Joon H; Shen, Nian; Burke, Jacqueline A; Hinderer, Svenja; Xia, Zhiyong; Schenke-Layland, Katja; Gerecht, Sharon

2017-04-01

Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications. Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have become of interest due to their ability to supplement tissue engineered scaffolds. Their ability to differentiate into cells of vascular lineages with defined phenotypes serves as a potential solution to a major cause of graft failure in which phenotypic shifts in smooth muscle cells lead to over proliferation and occlusion of the graft. Herein, we have differentiated human induced-pluripotent stem cells in a pulsatile flow bioreactor, resulting in vascular smooth muscle tissue with robust elastic fibers and enhanced functionality. This study highlights an effective approach to engineering elastic functional vascular smooth muscle tissue for tissue engineering and regenerative medicine applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Correlation mapping for visualizing propagation of pulsatile CSF motion in intracranial space based on magnetic resonance phase contrast velocity images: preliminary results.

PubMed

Yatsushiro, Satoshi; Hirayama, Akihiro; Matsumae, Mitsunori; Kajiwara, Nao; Abdullah, Afnizanfaizal; Kuroda, Kagayaki

2014-01-01

Correlation time mapping based on magnetic resonance (MR) velocimetry has been applied to pulsatile cerebrospinal fluid (CSF) motion to visualize the pressure transmission between CSF at different locations and/or between CSF and arterial blood flow. Healthy volunteer experiments demonstrated that the technique exhibited transmitting pulsatile CSF motion from CSF space in the vicinity of blood vessels with short delay and relatively high correlation coefficients. Patient and healthy volunteer experiments indicated that the properties of CSF motion were different from the healthy volunteers. Resultant images in healthy volunteers implied that there were slight individual difference in the CSF driving source locations. Clinical interpretation for these preliminary results is required to apply the present technique for classifying status of hydrocephalus.

3D-Printed Tissue-Mimicking Phantoms for Medical Imaging and Computational Validation Applications

PubMed Central

Shahmirzadi, Danial; Li, Ronny X.; Doyle, Barry J.; Konofagou, Elisa E.; McGloughlin, Tim M.

2014-01-01

Abstract Abdominal aortic aneurysm (AAA) is a permanent, irreversible dilation of the distal region of the aorta. Recent efforts have focused on improved AAA screening and biomechanics-based failure prediction. Idealized and patient-specific AAA phantoms are often employed to validate numerical models and imaging modalities. To produce such phantoms, the investment casting process is frequently used, reconstructing the 3D vessel geometry from computed tomography patient scans. In this study the alternative use of 3D printing to produce phantoms is investigated. The mechanical properties of flexible 3D-printed materials are benchmarked against proven elastomers. We demonstrate the utility of this process with particular application to the emerging imaging modality of ultrasound-based pulse wave imaging, a noninvasive diagnostic methodology being developed to obtain regional vascular wall stiffness properties, differentiating normal and pathologic tissue in vivo. Phantom wall displacements under pulsatile loading conditions were observed, showing good correlation to fluid–structure interaction simulations and regions of peak wall stress predicted by finite element analysis. 3D-printed phantoms show a strong potential to improve medical imaging and computational analysis, potentially helping bridge the gap between experimental and clinical diagnostic tools. PMID:28804733

The Characteristics of Turbulence in Curved Pipes under Highly Pulsatile Flow Conditions

NASA Astrophysics Data System (ADS)

Kalpakli, A.; Örlü, R.; Tillmark, N.; Alfredsson, P. Henrik

High speed stereoscopic particle image velocimetry has been employed to provide unique data from a steady and highly pulsatile turbulent flow at the exit of a 90 degree pipe bend. Both the unsteady behaviour of the Dean cells under steady conditions, the so called "swirl switching" phenomenon, as well as the secondary flow under pulsations have been reconstructed through proper orthogonal decomposition. The present data set constitutes - to the authors' knowledge - the first detailed investigation of a turbulent, pulsatile flow through a pipe bend.

Pulsatility flow around a single cylinder - an experimental model of flow inside an artificial lung

NASA Astrophysics Data System (ADS)

Lin, Yu-Chun; Bull, Joseph L.

2004-11-01

Pulsatile flow past a single cylinder is experimentally investigated using particle image velocimetry. This study aims to elucidate the effects of pulstility on the velocity field, which influences the convection-dominated transport within the fluid. The artificial lung device can be connected in parallel or series with the native lungs and may potentially be used as a bridge to transplant or for pulmonary replacement. The artificial lung consists of hollow microfibers through which gas flows and blood flows around. Blood flow through the device is pulsatile because it is driven entirely by the right heart. Steady flow over bluff bodies has been investigated in many contexts, such as heat exchangers. However, few studies have been investigated the effect of pulsatility. The effects of frequency, amplitude of pulsatility, and average flow rate on the formation of vortices after a cylinder are examined. Vortices near the cylinder are found to develop at lower Reynolds number in pulsatile flow than in steady flow. This work is supported by NIH grant R01 HL69420-01.

Transition in Pulsatile Pipe Flow

NASA Astrophysics Data System (ADS)

Vlachos, Pavlos; Brindise, Melissa

2016-11-01

Transition has been observed to occur in the aorta, and stenotic vessels, where pulsatile flow exists. However, few studies have investigated the characteristics and effects of transition in oscillating or pulsatile flow and none have utilized a physiological waveform. In this work, we explore transition in pipe flow using three pulsatile waveforms which all maintain the same mean and maximum flow rates and range to zero flow, as is physiologically typical. Velocity fields were obtained using planar particle image velocimetry for each pulsatile waveform at six mean Reynolds numbers ranging between 500 and 4000. Turbulent statistics including turbulent kinetic energy (TKE) and Reynolds stresses were computed. Quadrant analysis was used to identify characteristics of the production and dissipation of turbulence. Coherent structures were identified using the λci method. We developed a wavelet-Hilbert time-frequency analysis method to identify high frequency structures and compared these to the coherent structures. The results of this study demonstrate that the different pulsatile waveforms induce different levels of TKE and high frequency structures, suggesting that the rates of acceleration and deceleration influence the onset and development of transition.

Vascular loop in the cerebellopontine angle causing pulsatile tinnitus and headache: a case report

PubMed Central

Ramly, NA; Roslenda, AR; Suraya, A; Asma, A

2014-01-01

Tinnitus is a common disorder, it can be classified as pulsatile and non-pulsatile or objective and subjective. Pulsatile tinnitus is less common than non-pulsatile and can be due to vascular tumour such as glomus or vascular abnormality. We presented an interesting case of a 30 year-old Malay lady with a two-year history of pulsatile tinnitus which was worsening in three months duration. It was associated with intermittent headache. Clinical examination and tuning fork test were unremarkable. Apart from mild hearing loss at high frequency on the left ear, the pure tone audiogram (PTA) was otherwise normal. In view of the patient’s young age with no risk factor for high frequency loss, a magnetic resonance imaging (MRI) was performed to look for any abnormality in the cerebellopontine angle. It revealed a single vessel looping around the left vestibulocochlear and facial nerves at the cisternal portion, likely a branch of the anteroinferior cerebellar artery (AICA). Literature review on the pathophysiology and treatment option in this condition is discussed. PMID:26417253

Fractality of pulsatile flow in speckle images

NASA Astrophysics Data System (ADS)

Nemati, M.; Kenjeres, S.; Urbach, H. P.; Bhattacharya, N.

2016-05-01

The scattering of coherent light from a system with underlying flow can be used to yield essential information about dynamics of the process. In the case of pulsatile flow, there is a rapid change in the properties of the speckle images. This can be studied using the standard laser speckle contrast and also the fractality of images. In this paper, we report the results of experiments performed to study pulsatile flow with speckle images, under different experimental configurations to verify the robustness of the techniques for applications. In order to study flow under various levels of complexity, the measurements were done for three in-vitro phantoms and two in-vivo situations. The pumping mechanisms were varied ranging from mechanical pumps to the human heart for the in vivo case. The speckle images were analyzed using the techniques of fractal dimension and speckle contrast analysis. The results of these techniques for the various experimental scenarios were compared. The fractal dimension is a more sensitive measure to capture the complexity of the signal though it was observed that it is also extremely sensitive to the properties of the scattering medium and cannot recover the signal for thicker diffusers in comparison to speckle contrast.

Tissue-engineered vascular grafts composed of marine collagen and PLGA fibers using pulsatile perfusion bioreactors.

PubMed

Jeong, Sung In; Kim, So Yeon; Cho, Seong Kwan; Chong, Moo Sang; Kim, Kyung Soo; Kim, Hyuck; Lee, Sang Bong; Lee, Young Moo

2007-02-01

Novel tubular scaffolds of marine source collagen and PLGA fibers were fabricated by freeze drying and electrospinning processes for vascular grafts. The hybrid scaffolds, composed of a porous collagen matrix and a fibrous PLGA layer, had an average pore size of 150+/-50 microm. The electrospun fibrous PLGA layer on the surface of a porous tubular collagen scaffold improved the mechanical strength of the collagen scaffolds in both the dry and wet states. Smooth muscle cells (SMCs)- and endothelial cells (ECs)-cultured collagen/PLGA scaffolds exhibited mechanical properties similar to collagen/PLGA scaffolds unseeded with cells, even after culturing for 23 days. The effect of a mechanical stimulation on the proliferation and phenotype of SMCs and ECs, cultured on collagen/PLGA scaffolds, was evaluated. The pulsatile perfusion system enhanced the SMCs and ECs proliferation. In addition, a significant cell alignment in a direction radial to the distending direction was observed in tissues exposed to radial distention, which is similar to the phenomenon of native vessel tissues in vivo. On the other hand, cells in tissues engineered in the static condition were randomly aligned. Immunochemical analyses showed that the expressions of SM alpha-actin, SM myosin heavy chain, EC von Willebrand factor, and EC nitric oxide were upregulated in tissues engineered under a mechano-active condition, compared to vessel tissues engineered in the static condition. These results indicated that the co-culturing of SMCs and ECs, using collagen/PLGA hybrid scaffolds under a pulsatile perfusion system, leads to the enhancement of vascular EC development, as well as the retention of the differentiated cell phenotype.

Quantitative photoacoustic assessment of red blood cell aggregation under pulsatile blood flow: experimental and theoretical approaches

NASA Astrophysics Data System (ADS)

Bok, Tae-Hoon; Hysi, Eno; Kolios, Michael C.

2017-03-01

In the present paper, the optical wavelength dependence on the photoacoustic (PA) assessment of the pulsatile blood flow was investigated by means of the experimental and theoretical approaches analyzing PA radiofrequency spectral parameters such as the spectral slope (SS) and mid-band fit (MBF). For the experimental approach, the pulsatile flow of human whole blood at 60 bpm was imaged using the VevoLAZR system (40-MHz-linear-array probe, 700-900 nm illuminations). For the theoretical approach, a Monte Carlo simulation for the light transmit into a layered tissue phantom and a Green's function based method for the PA wave generation was implemented for illumination wavelengths of 700, 750, 800, 850 and 900 nm. The SS and MBF for the experimental results were compared to theoretical ones as a function of the illumination wavelength. The MBF increased with the optical wavelength in both theory and experiments. This was expected because the MBF is representative of the PA magnitude, and the PA signal from red blood cell (RBC) is dependent on the molar extinction coefficient of oxyhemoglobin. On the other hand, the SS decreased with the wavelength, even though the RBC size (absorber size which is related to the SS) cannot depend on the illumination wavelength. This conflicting result can be interpreted by means of the changes of the fluence pattern for different illumination wavelengths. The SS decrease with the increasing illumination wavelength should be further investigated.

Fast diffuse correlation spectroscopy (DCS) for non-invasive measurement of intracranial pressure (ICP) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Farzam, Parisa; Sutin, Jason; Wu, Kuan-Cheng; Zimmermann, Bernhard B.; Tamborini, Davide; Dubb, Jay; Boas, David A.; Franceschini, Maria Angela

2017-02-01

Intracranial pressure (ICP) monitoring has a key role in the management of neurosurgical and neurological injuries. Currently, the standard clinical monitoring of ICP requires an invasive transducer into the parenchymal tissue or the brain ventricle, with possibility of complications such as hemorrhage and infection. A non-invasive method for measuring ICP, would be highly preferable, as it would allow clinicians to promptly monitor ICP during transport and allow for monitoring in a larger number of patients. We have introduced diffuse correlation spectroscopy (DCS) as a non-invasive ICP monitor by fast measurement of pulsatile cerebral blood flow (CBF). The method is similar to Transcranial Doppler ultrasound (TCD), which derives ICP from the amplitude of the pulsatile cerebral blood flow velocity, with respect to the amplitude of the pulsatile arterial blood pressure. We believe DCS measurement is superior indicator of ICP than TCD estimation because DCS directly measures blood flow, not blood flow velocity, and the small cortical vessels measured by DCS are more susceptible to transmural pressure changes than the large vessels. For fast DCS measurements to recover pulsatile CBF we have developed a custom high-power long-coherent laser and a strategy for delivering it to the tissue within ANSI standards. We have also developed a custom FPGA-based correlator board, which facilitates DCS data acquisitions at 50-100 Hz. We have tested the feasibility of measuring pulsatile CBF and deriving ICP in two challenging scenarios: humans and rats. SNR is low in human adults due to large optode distances. It is similarly low in rats because the fast heart rate in this setting requires a high repetition rate.

A High Performance Pulsatile Pump for Aortic Flow Experiments in 3-Dimensional Models.

PubMed

Chaudhury, Rafeed A; Atlasman, Victor; Pathangey, Girish; Pracht, Nicholas; Adrian, Ronald J; Frakes, David H

2016-06-01

Aortic pathologies such as coarctation, dissection, and aneurysm represent a particularly emergent class of cardiovascular diseases. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these pathologies, as well as for planning their surgical repair. In vitro experiments are required to validate the simulations against real world data, and the experiments require a pulsatile flow pump system that can provide physiologic flow conditions characteristic of the aorta. We designed a newly capable piston-based pulsatile flow pump system that can generate high volume flow rates (850 mL/s), replicate physiologic waveforms, and pump high viscosity fluids against large impedances. The system is also compatible with a broad range of fluid types, and is operable in magnetic resonance imaging environments. Performance of the system was validated using image processing-based analysis of piston motion as well as particle image velocimetry. The new system represents a more capable pumping solution for aortic flow experiments than other available designs, and can be manufactured at a relatively low cost.

Tracking brain motion during the cardiac cycle using spiral cine-DENSE MRI

PubMed Central

Zhong, Xiaodong; Meyer, Craig H.; Schlesinger, David J.; Sheehan, Jason P.; Epstein, Frederick H.; Larner, James M.; Benedict, Stanley H.; Read, Paul W.; Sheng, Ke; Cai, Jing

2009-01-01

Cardiac-synchronized brain motion is well documented, but the accurate measurement of such motion on the pixel-by-pixel basis has been hampered by the lack of proper imaging technique. In this article, the authors present the implementation of an autotracking spiral cine displacement-encoded stimulation echo (DENSE) magnetic resonance imaging (MRI) technique for the measurement of pulsatile brain motion during the cardiac cycle. Displacement-encoded dynamic MR images of three healthy volunteers were acquired throughout the cardiac cycle using the spiral cine-DENSE pulse sequence gated to the R wave of an electrocardiogram. Pixelwise Lagrangian displacement maps were computed, and 2D displacement as a function of time was determined for selected regions of interests. Different intracranial structures exhibited characteristic motion amplitude, direction, and pattern throughout the cardiac cycle. Time-resolved displacement curves revealed the pathway of pulsatile motion from brain stem to peripheral brain lobes. These preliminary results demonstrated that the spiral cine-DENSE MRI technique can be used to measure cardiac-synchronized pulsatile brain motion on the pixel-by-pixel basis with high temporal∕spatial resolution and sensitivity. PMID:19746774

Force Trends and Pulsatility for Catheter Contact Identification in Intracardiac Electrograms during Arrhythmia Ablation.

PubMed

Rivas-Lalaleo, David; Muñoz-Romero, Sergio; Huerta, Mónica; Erazo-Rodas, Mayra; Sánchez-Muñoz, Juan José; Rojo-Álvarez, José Luis; García-Alberola, Arcadi

2018-05-02

The intracardiac electrical activation maps are commonly used as a guide in the ablation of cardiac arrhythmias. The use of catheters with force sensors has been proposed in order to know if the electrode is in contact with the tissue during the registration of intracardiac electrograms (EGM). Although threshold criteria on force signals are often used to determine the catheter contact, this may be a limited criterion due to the complexity of the heart dynamics and cardiac vorticity. The present paper is devoted to determining the criteria and force signal profiles that guarantee the contact of the electrode with the tissue. In this study, we analyzed 1391 force signals and their associated EGM recorded during 2 and 8 s, respectively, in 17 patients (82 ± 60 points per patient). We aimed to establish a contact pattern by first visually examining and classifying the signals, according to their likely-contact joint profile and following the suggestions from experts in the doubtful cases. First, we used Principal Component Analysis to scrutinize the force signal dynamics by analyzing the main eigen-directions, first globally and then grouped according to the certainty of their tissue-catheter contact. Second, we used two different linear classifiers (Fisher discriminant and support vector machines) to identify the most relevant components of the previous signal models. We obtained three main types of eigenvectors, namely, pulsatile relevant, non-pulsatile relevant, and irrelevant components. The classifiers reached a moderate to sufficient discrimination capacity (areas under the curve between 0.84 and 0.95 depending on the contact certainty and on the classifier), which allowed us to analyze the relevant properties in the force signals. We conclude that the catheter-tissue contact profiles in force recordings are complex and do not depend only on the signal intensity being above a threshold at a single time instant, but also on time pulsatility and trends. These findings pave the way towards a subsystem which can be included in current intracardiac navigation systems assisted by force contact sensors, and it can provide the clinician with an estimate of the reliability on the tissue-catheter contact in the point-by-point EGM acquisition procedure.

Force Trends and Pulsatility for Catheter Contact Identification in Intracardiac Electrograms during Arrhythmia Ablation

PubMed Central

Muñoz-Romero, Sergio; Erazo-Rodas, Mayra; Sánchez-Muñoz, Juan José; García-Alberola, Arcadi

2018-01-01

The intracardiac electrical activation maps are commonly used as a guide in the ablation of cardiac arrhythmias. The use of catheters with force sensors has been proposed in order to know if the electrode is in contact with the tissue during the registration of intracardiac electrograms (EGM). Although threshold criteria on force signals are often used to determine the catheter contact, this may be a limited criterion due to the complexity of the heart dynamics and cardiac vorticity. The present paper is devoted to determining the criteria and force signal profiles that guarantee the contact of the electrode with the tissue. In this study, we analyzed 1391 force signals and their associated EGM recorded during 2 and 8 s, respectively, in 17 patients (82 ± 60 points per patient). We aimed to establish a contact pattern by first visually examining and classifying the signals, according to their likely-contact joint profile and following the suggestions from experts in the doubtful cases. First, we used Principal Component Analysis to scrutinize the force signal dynamics by analyzing the main eigen-directions, first globally and then grouped according to the certainty of their tissue-catheter contact. Second, we used two different linear classifiers (Fisher discriminant and support vector machines) to identify the most relevant components of the previous signal models. We obtained three main types of eigenvectors, namely, pulsatile relevant, non-pulsatile relevant, and irrelevant components. The classifiers reached a moderate to sufficient discrimination capacity (areas under the curve between 0.84 and 0.95 depending on the contact certainty and on the classifier), which allowed us to analyze the relevant properties in the force signals. We conclude that the catheter-tissue contact profiles in force recordings are complex and do not depend only on the signal intensity being above a threshold at a single time instant, but also on time pulsatility and trends. These findings pave the way towards a subsystem which can be included in current intracardiac navigation systems assisted by force contact sensors, and it can provide the clinician with an estimate of the reliability on the tissue-catheter contact in the point-by-point EGM acquisition procedure. PMID:29724033

Application of full field optical studies for pulsatile flow in a carotid artery phantom

PubMed Central

Nemati, M.; Loozen, G. B.; van der Wekken, N.; van de Belt, G.; Urbach, H. P.; Bhattacharya, N.; Kenjeres, S.

2015-01-01

A preliminary comparative measurement between particle imaging velocimetry (PIV) and laser speckle contrast analysis (LASCA) to study pulsatile flow using ventricular assist device in a patient-specific carotid artery phantom is reported. These full-field optical techniques have both been used to study flow and extract complementary parameters. We use the high spatial resolution of PIV to generate a full velocity map of the flow field and the high temporal resolution of LASCA to extract the detailed frequency spectrum of the fluid pulses. Using this combination of techniques a complete study of complex pulsatile flow in an intricate flow network can be studied. PMID:26504652

Obstructive Hydrocephalus Secondary to Enlarged Virchow-Robin Spaces: A Rare Cause of Pulsatile Tinnitus.

PubMed

Donaldson, Christopher; Chatha, Gurkirat; Chandra, Ronil V; Goldschlager, Tony

2017-05-01

Obstructive hydrocephalus secondary to enlarged Virchow-Robin Spaces (VRS) is a rare entity, with only a few cases reported in the literature. Presenting symptoms vary widely from headaches to dizziness. We report a case of a 31-year-old man who presented with pulsatile tinnitus and magnetic resonance imaging showing obstructive hydrocephalus secondary to tumefactive VRS. After a cerebrospinal fluid diversion procedure in the form of an endoscopic third ventriculostomy, he had almost complete resolution of his symptoms. This is the first case of obstructive hydrocephalus secondary to enlarged VRS, presenting with pulsatile tinnitus. Copyright © 2017 Elsevier Inc. All rights reserved.

Fast blood flow monitoring in deep tissues with real-time software correlators

PubMed Central

Wang, Detian; Parthasarathy, Ashwin B.; Baker, Wesley B.; Gannon, Kimberly; Kavuri, Venki; Ko, Tiffany; Schenkel, Steven; Li, Zhe; Li, Zeren; Mullen, Michael T.; Detre, John A.; Yodh, Arjun G.

2016-01-01

We introduce, validate and demonstrate a new software correlator for high-speed measurement of blood flow in deep tissues based on diffuse correlation spectroscopy (DCS). The software correlator scheme employs standard PC-based data acquisition boards to measure temporal intensity autocorrelation functions continuously at 50 – 100 Hz, the fastest blood flow measurements reported with DCS to date. The data streams, obtained in vivo for typical source-detector separations of 2.5 cm, easily resolve pulsatile heart-beat fluctuations in blood flow which were previously considered to be noise. We employ the device to separate tissue blood flow from tissue absorption/scattering dynamics and thereby show that the origin of the pulsatile DCS signal is primarily flow, and we monitor cerebral autoregulation dynamics in healthy volunteers more accurately than with traditional instrumentation as a result of increased data acquisition rates. Finally, we characterize measurement signal-to-noise ratio and identify count rate and averaging parameters needed for optimal performance. PMID:27231588

Investigation of the mechanism of soft tissue conduction explains several perplexing auditory phenomena.

PubMed

Adelman, Cahtia; Chordekar, Shai; Perez, Ronen; Sohmer, Haim

2014-09-01

Soft tissue conduction (STC) is a recently expounded mode of auditory stimulation in which the clinical bone vibrator delivers auditory frequency vibratory stimuli to skin sites on the head, neck, and thorax. Investigation of the mechanism of STC stimulation has served as a platform for the elucidation of the mechanics of cochlear activation, in general, and to a better understanding of several perplexing auditory phenomena. This review demonstrates that it is likely that the cochlear hair cells can be directly activated at low sound intensities by the fluid pressures initiated in the cochlea; that the fetus in utero, completely enveloped in amniotic fluid, hears by STC; that a speaker hears his/her own voice by air conduction and by STC; and that pulsatile tinnitus is likely due to pulsatile turbulent blood flow producing fluid pressures that reach the cochlea through the soft tissues.

An in vitro experimental study of flow past aortic valve under varied pulsatile conditions

NASA Astrophysics Data System (ADS)

Zhang, Ruihang; Zhang, Yan

2017-11-01

Flow past aortic valve represents a complex fluid-structure interaction phenomenon that involves pulsatile, vortical, and turbulent conditions. The flow characteristics immediately downstream of the valve, such as the variation of pulsatile flow velocity, formation of vortices, distribution of shear stresses, are of particular interest to further elucidate the role of hemodynamics in various aortic diseases. However, the fluid dynamics of a realistic aortic valve is not fully understood. Particularly, it is unclear how the flow fields downstream of the aortic valve would change under varied pulsatile inlet boundary conditions. In this study, an in vitro experiment has been conducted to investigate the flow fields downstream of a silicone aortic valve model within a cardiovascular flow simulator. Phased-locked Particle Image Velocimetry measurements were performed to map the velocity fields and Reynolds normal and shear stresses at different phases in a cardiac cycle. Temporal variations of pressure across the valve model were measured using high frequency transducers. Results have been compared for different pulsatile inlet conditions, including varied frequencies (heart rates), magnitudes (stroke volumes), and cardiac contractile functions (shapes of waveforms).

Quantification of wall shear stress in large blood vessels using Lagrangian interpolation functions with cine phase-contrast magnetic resonance imaging.

PubMed

Cheng, Christopher P; Parker, David; Taylor, Charles A

2002-09-01

Arterial wall shear stress is hypothesized to be an important factor in the localization of atherosclerosis. Current methods to compute wall shear stress from magnetic resonance imaging (MRI) data do not account for flow profiles characteristic of pulsatile flow in noncircular vessel lumens. We describe a method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall. Validation was performed with software phantoms and an in vitro flow phantom. At an image resolution corresponding to in vivo imaging data of the human abdominal aorta, time-averaged, spatially averaged wall shear stress for steady and pulsatile flow were determined to be within 16% and 23% of the analytic solution, respectively. These errors were reduced to 5% and 8% with doubling in image resolution. For the pulsatile software phantom, the oscillation in shear stress was predicted to within 5%. The mean absolute error of circumferentially resolved shear stress for the nonaxisymmetric phantom decreased from 28% to 15% with a doubling in image resolution. The irregularly shaped phantom and in vitro investigation demonstrated convergence of the calculated values with increased image resolution. We quantified the shear stress at the supraceliac and infrarenal regions of a human abdominal aorta to be 3.4 and 2.3 dyn/cm2, respectively.

Phase-sensitive optical coherence tomography characterization of pulse-induced trabecular meshwork displacement in ex vivo non-human primate eyes

NASA Astrophysics Data System (ADS)

Li, Peng; Reif, Roberto; Zhi, Zhongwei; An, Lin; Martin, Elizabeth; Shen, Tueng T.; Johnstone, Murray; Wang, Ruikang K.

2013-03-01

Purpose. It is suspected that the abnormalities of aqueous outflow pump composed of trabecular meshwork (TM) and Schlemm's canal (SC) results in the increased outflow resistance and then elevated intraocular pressure (IOP) in initial glaucoma. In order to explore the casual mechanism and the early diagnosis of glaucoma, the dynamic characterizations of aqueous outflow pump were explored. Methods. As a functional extension of optical coherence tomography (OCT), tissue Doppler OCT (tissue-DOCT) method capable of measuring the slow tissue movement was developed. The tissue-DOCT imaging was conducted on the corneo-scleral limbus of 4 monkey eyes. The eye was mounted in an anterior segment holder, together with a perfusion system to control the mean IOP and to induce the cyclic IOP transients with amplitude 3 mm Hg at frequency 1 pulse/second. IOP was monitored on-line by a pressure transducer. Tissue-DOCT data and pressure data were recorded simultaneously. The IOP-transient induced Doppler velocity, displacement and strain rate of TM and the normalized area of SC were quantified at 7 different mean IOPs (5, 8, 10, 20, 30, 40, 50 mm Hg). Results. The outflow system, including TM, SC and CCs, was visualized in the micro-structural imaging. The IOP-transient induced pulsatile TM movement and SC deformation were detected and quantified by tissue-DOCT. The TM movement was depth-dependent and the largest movement was located in the area closest to SC endothelium (SCE). Both the pulsations of TM and SC were found to be synchronous with the IOP pulse wave. At 8 mm Hg IOP, the global TM movement was around 0.65μm during one IOP transient. As IOP elevated, a gradual attenuation of TM movement and SC deformation was observed. Conclusions. The observed pulsation of TM and SC induced by the pulsatile IOP transients was in good agreement with the predicated role of TM and SC acting as a biomechanical pump (pumping aqueous from anterior chamber into SC and from SC into CCs) in the aqueous outflow system. As the IOP elevated, the attenuated pulsation amplitude of the aqueous outflow pump indicated the failure of the mechanical pump and the increase of aqueous outflow resistance. The promising results revealed the potential of using the proposed tissue-DOCT for diagnosis and associated therapeutic guidance of the initial and progressive glaucoma process by monitoring the pulsation of the outflow pump.

Using a laser-Doppler flowmetry to measure pulsatile microcirculation on the kidney in rats

NASA Astrophysics Data System (ADS)

Jan, Ming-Yie; Chao, Pin-Tsun; Hsu, Tse-Lin; Wang, Yuh-Yin L.; Wang, Wei-Kung

2001-10-01

Although Laser Doppler flowmetery (LDF) been extensively used in measurement of microvascular blood flow of different tissues. However, due to some physiological vibrations, fast oscillations of the renal cortical flux (RCF) are hard to be measured. In the study, a commercial 3mW 780nm Laser Doppler flowmetery, with a single fiber and a de-vibration holder, was used to measure the pulsatile RCF in rats. Considering the fast response due to the heart rate of rats, the time constant (TC) was set to 0.05 second and thus the frequency response is up to 20Hz. Furthermore, a calibration standard and a static blood sample were also measured as the references without the pulsatile driving force. In order not to perturb the RCF with tiny momentum, the applying force that the fiber exerted on the renal surface was controlled below 100 dyne. To enhance the signal to noise ratio (SNR), an averaged periodogram was used to estimate the frequency components of the pulsatile microcirculation. It is found that the dominating fast oscillation of RCF is pulsatile and its harmonic components are directly correlated with those of the heartbeat (correlation coefficient =0.999, P<0.001, n=17). The result shows that, in the kidney, the pulsatile RCF is the dominating component of microcirculation oscillation and driven by the fast propagating blood pressure. This technique could be further utilized to analyze the pharmacological effect and hemodynamic parameters on renal function.

[Diagnosis and management of pulsatile tinnitus of venous origin].

PubMed

Zhang, Yibo; Wang, Wuqing; Dai, Chunfu; Chen, Liang

2010-03-01

To discuss the diagnosis and management of pulsatile tinnitus of venous origin. A retrospective study was conducted on 12 patients who were diagnosed with pulsatile tinnitus of venous origin and treated with ligation of internal jugular veins. We reevaluated the evidences of identifying pulsatile tinnitus of venous origin and reviewed the short-term and long-term postoperative effects and complications. We also reviewed associated articles in this report. Seven patients got relief of tinnitus in less than one week after the surgery, while the other 5 patients had no relief. Seven patients were inquired in this study and the other five lost to follow-up. According to the long review (from one to five years postoperatively), two patients who acquired immediate effect got relief of tinnitus, four including complained of no relief and the seventh aggravated into roaring. Three patients who got no immediate relief got no improvement at all. No one in our review complained of any complications. It's assumed that a history of pulsatile tinnitus, alleviation of tinnitus when pressing jugular veins, tinnitus changing with head position or posture and no occupying lesion in temporal CT scan or cranial MRI are inadequate in diagnosing pulsatile tinnitus of venous origin. Vascular imaging is also necessary to exclude other pathological changes like dura arteriovenous fistula, sigmoid diverticulum and so on. CT arteriography and venography are recommended preferentially. Ligation of internal jugular veins is controversial in patients who have no absence of transverse and sigmoid sinus and identified as pulsatile tinnitus of venous origin.

Heart activity monitoring using 3D hologram based on smartphone.

PubMed

Thap, Tharoeun; Heewon Chung; Jinseok Lee

2016-08-01

In this paper, we used smartphone to obtained pulsatile signal from a fingertip by illuminating the skin tissue using flashlight and with an on-board camera to record the change of the light intensity reflected from the tissue. The pulsatile signal is produced by analyzing average green component values of the frames taken by the camera and the heart rate is estimated in real time by detecting the pulse peaks. Based on each instant obtained heartbeat, we design a heart animation that beats according to each interval of the heartbeat. At the same time, we made a simple pyramid shaped hologram from a transparent OHP film to show the heart animation acting above the smartphone screen in three-dimensional view. With this application, users can actually monitor their heart activity in 3D rather than just to see the pulsatile signal graphically. The performances were done in two different conditions: under bright and dark environments. The holograms were made based on three different materials: grey transparent film, clear transparent film, and hard black acrylic board; the grey transparent film provided better performance and we achieved satisfactory results regardless of all environments.

Nonlinear dynamics of shells conveying pulsatile flow with pulse-wave propagation. Theory and numerical results for a single harmonic pulsation

NASA Astrophysics Data System (ADS)

Tubaldi, Eleonora; Amabili, Marco; Païdoussis, Michael P.

2017-05-01

In deformable shells conveying pulsatile flow, oscillatory pressure changes cause local movements of the fluid and deformation of the shell wall, which propagate downstream in the form of a wave. In biomechanics, it is the propagation of the pulse that determines the pressure gradient during the flow at every location of the arterial tree. In this study, a woven Dacron aortic prosthesis is modelled as an orthotropic circular cylindrical shell described by means of the Novozhilov nonlinear shell theory. Flexible boundary conditions are considered to simulate connection with the remaining tissue. Nonlinear vibrations of the shell conveying pulsatile flow and subjected to pulsatile pressure are investigated taking into account the effects of the pulse-wave propagation. For the first time in literature, coupled fluid-structure Lagrange equations of motion for a non-material volume with wave propagation in case of pulsatile flow are developed. The fluid is modeled as a Newtonian inviscid pulsatile flow and it is formulated using a hybrid model based on the linear potential flow theory and considering the unsteady viscous effects obtained from the unsteady time-averaged Navier-Stokes equations. Contributions of pressure and velocity propagation are also considered in the pressure drop along the shell and in the pulsatile frictional traction on the internal wall in the axial direction. A numerical bifurcation analysis employs a refined reduced order model to investigate the dynamic behavior of a pressurized Dacron aortic graft conveying blood flow. A pulsatile time-dependent blood flow model is considered by applying the first harmonic of the physiological waveforms of velocity and pressure during the heart beating period. Geometrically nonlinear vibration response to pulsatile flow and transmural pulsatile pressure, considering the propagation of pressure and velocity changes inside the shell, is here presented via frequency-response curves, time histories, bifurcation diagrams and Poincaré maps. It is shown that traveling waves of pressure and velocity cause a delay in the radial displacement of the shell at different values of the axial coordinate. The effect of different pulse wave velocities is also studied. Comparisons with the corresponding ideal case without wave propagation (i.e. with the same pulsatile velocity and pressure at any point of the shell) are here discussed. Bifurcation diagrams of Poincaré maps obtained from direct time integration have been used to study the system in the spectral neighborhood of the fundamental natural frequency. By increasing the forcing frequency, the response undergoes very complex nonlinear dynamics (chaos, amplitude modulation and period-doubling bifurcation), here deeply investigated.

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

PubMed

Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

2001-12-01

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

High-Speed Real-Time Resting-State fMRI Using Multi-Slab Echo-Volumar Imaging

PubMed Central

Posse, Stefan; Ackley, Elena; Mutihac, Radu; Zhang, Tongsheng; Hummatov, Ruslan; Akhtari, Massoud; Chohan, Muhammad; Fisch, Bruce; Yonas, Howard

2013-01-01

We recently demonstrated that ultra-high-speed real-time fMRI using multi-slab echo-volumar imaging (MEVI) significantly increases sensitivity for mapping task-related activation and resting-state networks (RSNs) compared to echo-planar imaging (Posse et al., 2012). In the present study we characterize the sensitivity of MEVI for mapping RSN connectivity dynamics, comparing independent component analysis (ICA) and a novel seed-based connectivity analysis (SBCA) that combines sliding-window correlation analysis with meta-statistics. This SBCA approach is shown to minimize the effects of confounds, such as movement, and CSF and white matter signal changes, and enables real-time monitoring of RSN dynamics at time scales of tens of seconds. We demonstrate highly sensitive mapping of eloquent cortex in the vicinity of brain tumors and arterio-venous malformations, and detection of abnormal resting-state connectivity in epilepsy. In patients with motor impairment, resting-state fMRI provided focal localization of sensorimotor cortex compared with more diffuse activation in task-based fMRI. The fast acquisition speed of MEVI enabled segregation of cardiac-related signal pulsation using ICA, which revealed distinct regional differences in pulsation amplitude and waveform, elevated signal pulsation in patients with arterio-venous malformations and a trend toward reduced pulsatility in gray matter of patients compared with healthy controls. Mapping cardiac pulsation in cortical gray matter may carry important functional information that distinguishes healthy from diseased tissue vasculature. This novel fMRI methodology is particularly promising for mapping eloquent cortex in patients with neurological disease, having variable degree of cooperation in task-based fMRI. In conclusion, ultra-high-real-time speed fMRI enhances the sensitivity of mapping the dynamics of resting-state connectivity and cerebro-vascular pulsatility for clinical and neuroscience research applications. PMID:23986677

In vitro reconstruction of hybrid vascular tissue. Hierarchic and oriented cell layers.

PubMed

Kanda, K; Matsuda, T; Oka, T

1993-01-01

Hybrid vascular tissue was hierarchically reconstructed in vitro. A hybrid medial layer composed of type I collagen gel, in which SMCs derived from a mongrel dog were embedded, was formed on the inner surface of a compliant porous polyurethane graft (internal diameter = 3 mm). Endothelial cells (ECs) from the same animal were seeded and cultured on the hybrid media to build an intimal layer. Subsequently, hierarchically structured grafts constructed in this manner were subjected to pulsatile flow (flow rate: 8.5 ml/min; frequency: 60 rpm; amplitude: 5% of graft outer diameter) of culture medium (Medium 199 supplemented with 20% fetal calf serum). After stress loading for as long as 10 days, tissues were morphologically investigated with a light microscope and a scanning electron microscope. Inner surfaces of the hybrid tissues were covered with EC monolayers that aligned along the direction of the flow (i.e., longitudinally). However, SMCs beneath the intima aligned in the circumferential direction. These cellular orientations resembled those in native muscular arteries. The pulsatile stress loaded hybrid tissue mimicked native muscular arteries with respect to hierarchic structure and cellular orientation. In vitro mechanical stress loading on a hybrid graft might provide a high degree of integrity in terms of tissue structure that promises high tolerance toward hydrodynamic stress and regulation of vasomotor tone upon implantation.

Suivi in situ de cultures tridimensionnelles en bioreacteur a perfusion grace a la tomographie d'emission par positrons

NASA Astrophysics Data System (ADS)

Chouinard, Julie

The continuous assessment of developing tissue substitutes is crucial to understand their evolution over time. However, this represents quite a challenge when thick samples must be evaluated with standard microscopy techniques. Common characterization methods are time consuming and usually result in the destruction of the culture. Real-time, in situ, non-invasive and non-destructives methods are needed to monitor the growth of large non-transparent constructs in tissue engineering. Medical imaging modalities, which can provide information on the structure and function of internal organs and tissues in living organisms, have the potential of allowing repetitive monitoring of these 3D cultures in vitro. The working hypothesis of this thesis was to establish standard noninvasive and nondestructive real-time bioreactor imaging protocols for in situ monitoring of the viability and metabolism of endothelial cells when grown in perfused 3D fibrin gel scaffolds. To achieve this goal, a culture chamber with hollow fibers was designed and a pulsatile perfusion bioreactor system, able to promote cell survival and proliferation, was constructed and validated. Standard imaging protocols in Positron Emission Tomography (PET) are not adapted to image bioreactor systems. A suitable method had to be devised using the well-known radiotracer 18F-fluorodeoxyglucose ( 18FDG), a marker of glucose metabolism. Optimal uptake conditions were determined using cell monolayers and the best parameters were then applied on perfused 3D cultures to evaluate perfusion, cell viability and emerging cell structures. After only 12 hours of culture, the cell density could be estimated and cell structures were localized within the fibrin gels after 1-2 weeks of culture. PET is a promising tool for tissue engineering with many specific tracers available that might eventually be able to reveal new information on tissue development. Key words: Endothelial cells, Perfusion bioreactor, Positron Emission Tomography (PET), 18F-fluorodeoxyglucose ( 18FDG), Tissue Engineering, 3D cultures, Fibrin.

Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

PubMed

Zheng, Junjie; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Huang, Bingkun; Liu, Zhaoxiang; Cui, Mingxuan; Xiong, Shuyu; Ma, Wanlu; Min, Le; Kaiser, Ursula B; Nie, Min; Wu, Xueyan

2017-07-01

The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Prospective, self-controlled, 3-month clinical trial. University endocrine clinic. Men with hypogonadotropic hypogonadism caused by CCPHD. Pulsatile GnRH was administered subcutaneously for 3 months. Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice. Copyright © 2017 Endocrine Society

Secondary flow structures in a 180∘ elastic curved vessel with torsion under steady and pulsatile inflow conditions

NASA Astrophysics Data System (ADS)

Najjari, Mohammad Reza; Plesniak, Michael W.

2017-11-01

Secondary flow vortical structures were investigated in an elastic 180° curved pipe with and without torsion under steady and pulsatile flow using particle image velocimetry (PIV). The elastic thin-walled curved pipes were constructed using Sylgard 184, and inserted into a bath of refractive index matched fluid to perform PIV. A vortex identification method was employed to identify various vortical structures in the flow. The secondary flow structures in the planar compliant model with dilatation of 0.61%-3.23% under pulsatile flow rate were compared with the rigid vessel model results, and it was found that local vessel compliance has a negligible effect on secondary flow morphology. The secondary flow structures were found to be more sensitive to out of plane curvature (torsion) than to vessel compliance. Torsion distorts the symmetry of secondary flow and results in more complex vortical structures in both steady and pulsatile flows. In high Re number steady flow with torsion, a single dominant vortical structure can be detected at the middle of the 90° cross section. In pulsatile flow with torsion, the split-Dean and Lyne-type vortices with same rotation direction originating from opposite sides of the cross section tend to merge together. supported by GW Center for Biomimetics and Bioinspired Engineering.

Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain.

PubMed

Iliff, Jeffrey J; Wang, Minghuan; Zeppenfeld, Douglas M; Venkataraman, Arun; Plog, Benjamin A; Liao, Yonghong; Deane, Rashid; Nedergaard, Maiken

2013-11-13

CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloid β, in a pathway that we have termed the "glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ~50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ~60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloid β, in the aging brain.

Astrogliosis and impaired aquaporin-4 and dystrophin systems in idiopathic normal pressure hydrocephalus.

PubMed

Eide, P K; Hansson, H-A

2017-06-19

Idiopathic normal pressure hydrocephalus (iNPH) is one subtype of dementia that may improve following drainage of cerebrospinal fluid (CSF). This prospective observational study explored whether expression of the water channel aquaporin-4 (AQP4) and the anchoring molecule dystrophin 71 (Dp71) are altered at astrocytic perivascular endfeet and in adjacent neuropil of iNPH patient. Observations were related to measurements of pulsatile and static intracranial pressure (ICP). The study included iNPH patients undergoing overnight monitoring of the pulsatile/static ICP in whom a biopsy was taken from the frontal cerebral cortex during placement of the ICP sensor. Reference (Ref) biopsies were sampled from 13 patients who underwent brain surgery for epilepsy, tumours or cerebral aneurysms. The brain tissue specimens were examined by light microscopy, immunohistochemistry, densitometry and morphometry. iNPH patients responding to surgery (n = 44) had elevated pulsatile ICP, indicative of impaired intracranial compliance. As compared to the Ref patients, the cortical biopsies of iNPH patients revealed prominent astrogliosis and reduced expression of AQP4 and Dp71 immunoreactivities in the astrocytic perivascular endfeet and in parts of the adjacent neuropil. There was a significant correlation between degree of astrogliosis and reduction of AQP4 and Dp71 at astrocytic perivascular endfeet. Idiopathic normal pressure hydrocephalus patients responding to CSF diversion present with abnormal pulsatile ICP, indicative of impaired intracranial compliance. A main histopathological finding was astrogliosis and reduction of AQP4 and of Dp71 in astrocytic perivascular endfeet. We propose that the altered AQP4 and Dp71 complex contributes to the subischaemia prevalent in the brain tissue of iNPH. © 2017 British Neuropathological Society.

The pulsating brain: A review of experimental and clinical studies of intracranial pulsatility

PubMed Central

2011-01-01

The maintenance of adequate blood flow to the brain is critical for normal brain function; cerebral blood flow, its regulation and the effect of alteration in this flow with disease have been studied extensively and are very well understood. This flow is not steady, however; the systolic increase in blood pressure over the cardiac cycle causes regular variations in blood flow into and throughout the brain that are synchronous with the heart beat. Because the brain is contained within the fixed skull, these pulsations in flow and pressure are in turn transferred into brain tissue and all of the fluids contained therein including cerebrospinal fluid. While intracranial pulsatility has not been a primary focus of the clinical community, considerable data have accrued over the last sixty years and new applications are emerging to this day. Investigators have found it a useful marker in certain diseases, particularly in hydrocephalus and traumatic brain injury where large changes in intracranial pressure and in the biomechanical properties of the brain can lead to significant changes in pressure and flow pulsatility. In this work, we review the history of intracranial pulsatility beginning with its discovery and early characterization, consider the specific technologies such as transcranial Doppler and phase contrast MRI used to assess various aspects of brain pulsations, and examine the experimental and clinical studies which have used pulsatility to better understand brain function in health and with disease. PMID:21349153

The association between the pulse pressure gradient at the cranio-cervical junction derived from phase-contrast magnetic resonance imaging and invasively measured pulsatile intracranial pressure in symptomatic patients with Chiari malformation type 1.

PubMed

Frič, Radek; Lindstrøm, Erika Kristina; Ringstad, Geir Andre; Mardal, Kent-André; Eide, Per Kristian

2016-12-01

In symptomatic Chiari malformation type 1 (CMI), impaired intracranial compliance (ICC) is associated with an increased cranio-spinal pulsatile pressure gradient. Phase-contrast magnetic resonance imaging (MRI) represents a non-invasive modality for the assessment of the pulse pressure gradient at the cranio-cervical junction (CCJ). We wished to explore how the MRI-derived pulse pressure gradient (MRI-dP) compares with invasively measured pulsatile intracranial pressure (ICP) in CMI, and with healthy controls. From phase-contrast MRI of CMI patients and healthy controls, we computed cerebrospinal fluid (CSF) flow velocities and MRI-dP at the CCJ. We assessed bidirectional flow and compared the flow between the anterior and the posterior subarachnoid space at the CCJ. We computed total intracranial volume (ICV), ventricular CSF volume (VV), and posterior cranial fossa volume (PCFV). We analyzed the static and pulsatile ICP scores from overnight monitoring in CMI patients. Five CMI patients and four healthy subjects were included. The CMI group had a significantly larger extent of tonsillar ectopia, smaller PCFV, and a smaller area of CSF in the FM. The pulsatile ICP (mean ICP wave amplitude, MWA) was abnormally increased in 4/5 CMI patients and correlated positively with MRI-dP. However, the MRI-dP as well as the CSF flow velocities did not differ significantly between CMI and healthy subjects. Moreover, bidirectional flow was observed in both CMI as well as healthy subjects, with no significant difference. In symptomatic CMI patients, we found a significant association between the pulse pressure gradient at the CCJ derived from phase-contrast MRI and the pulsatile ICP (MWA) measured invasively. However, the MRI-dP was close to identical in CMI patients and healthy subjects. Moreover, the CSF flow velocities at the CCJ and the occurrence of bidirectional flow were not different in CMI patients and healthy individuals. Further studies are required to determine the diagnostic role of phase-contrast MRI in CMI patients.

Validation of a stereo camera system to quantify brain deformation due to breathing and pulsatility.

PubMed

Faria, Carlos; Sadowsky, Ofri; Bicho, Estela; Ferrigno, Giancarlo; Joskowicz, Leo; Shoham, Moshe; Vivanti, Refael; De Momi, Elena

2014-11-01

A new stereo vision system is presented to quantify brain shift and pulsatility in open-skull neurosurgeries. The system is endowed with hardware and software synchronous image acquisition with timestamp embedding in the captured images, a brain surface oriented feature detection, and a tracking subroutine robust to occlusions and outliers. A validation experiment for the stereo vision system was conducted against a gold-standard optical tracking system, Optotrak CERTUS. A static and dynamic analysis of the stereo camera tracking error was performed tracking a customized object in different positions, orientations, linear, and angular speeds. The system is able to detect an immobile object position and orientation with a maximum error of 0.5 mm and 1.6° in all depth of field, and tracking a moving object until 3 mm/s with a median error of 0.5 mm. Three stereo video acquisitions were recorded from a patient, immediately after the craniotomy. The cortical pulsatile motion was captured and is represented in the time and frequency domain. The amplitude of motion of the cloud of features' center of mass was inferior to 0.8 mm. Three distinct peaks are identified in the fast Fourier transform analysis related to the sympathovagal balance, breathing, and blood pressure with 0.03-0.05, 0.2, and 1 Hz, respectively. The stereo vision system presented is a precise and robust system to measure brain shift and pulsatility with an accuracy superior to other reported systems.

Dense concentric circle scanning protocol for measuring pulsatile retinal blood flow in rats with Doppler optical coherence tomography

NASA Astrophysics Data System (ADS)

Tan, Bingyao; Hosseinaee, Zohreh; Bizheva, Kostadinka

2017-11-01

The variability in the spatial orientation of retinal blood vessels near the optic nerve head (ONH) results in imprecision of the measured Doppler angle and therefore the pulsatile blood flow (BF), when those parameters are evaluated using Doppler OCT imaging protocols based on dual-concentric circular scans. Here, we utilized a dense concentric circle scanning protocol and evaluated its precision for measuring pulsatile retinal BF in rats for different numbers of the circular scans. An spectral domain optical coherence tomography (SD-OCT) system operating in the 1060-nm spectral range with image acquisition rate of 47,000 A-scans/s was used to acquire concentric circular scans centered at the rat's ONH, with diameters ranging from 0.8 to 1.0 mm. A custom, automatic blood vessel segmentation algorithm was used to track the spatial orientation of the retinal blood vessels in three dimensions, evaluate the spatially dependent Doppler angle and calculate more accurately the axial BF for each major retinal blood vessel. Metrics such as retinal BF, pulsatility index, and resistance index were evaluated for each and all of the major retinal blood vessels. The performance of the proposed dense concentric circle scanning protocols was compared with that of the dual-circle scanning protocol. Results showed a 3.8±2.2 deg difference in the Doppler angle calculation between the two approaches, which resulted in ˜7% difference in the calculated retinal BF.

Obesity, growth hormone and exercise.

PubMed

Thomas, Gwendolyn A; Kraemer, William J; Comstock, Brett A; Dunn-Lewis, Courtenay; Maresh, Carl M; Volek, Jeff S

2013-09-01

Growth hormone (GH) is regulated, suppressed and stimulated by numerous physiological stimuli. However, it is believed that obesity disrupts the physiological and pathological factors that regulate, suppress or stimulate GH release. Pulsatile GH has been potently stimulated in healthy subjects by both aerobic and resistance exercise of the right intensity and duration. GH modulates fuel metabolism, reduces total fat mass and abdominal fat mass, and could be a potent stimulus of lipolysis when administered to obese individuals exogenously. Only pulsatile GH has been shown to augment adipose tissue lipolysis and, therefore, increasing pulsatile GH response may be a therapeutic target. This review discusses the factors that cause secretion of GH, how obesity may alter GH secretion and how both aerobic and resistance exercise stimulates GH, as well as how exercise of a specific intensity may be used as a stimulus for GH release in individuals who are obese. Only five prior studies have investigated exercise as a stimulus of endogenous GH in individuals who are obese. Based on prior literature, resistance exercise may provide a therapeutic target for releasing endogenous GH in individuals who are obese if specific exercise programme variables are utilized. Biological activity of GH indicates that this may be an important precursor to beneficial changes in body fat and lean tissue mass in obese individuals. However, additional research is needed including what molecular GH variants are acutely released and involved at target tissues as a result of different exercise stimuli and what specific exercise programme variables may serve to stimulate GH in individuals who are obese.

The Dynamics of Agglomerated Ferrofluid in Steady and Pulsatile Flows

NASA Astrophysics Data System (ADS)

Williams, Alicia; Stewart, Kelley; Vlachos, Pavlos

2007-11-01

Magnetic Drug Targeting (MDT) is a promising technique to deliver medication via functionalized magnetic particles to target sites in the treatment of diseases. In this work, the physics of steady and pulsatile flows laden with superparamagnetic nanoparticles in a square channel under the influence of a magnetic field induced by a 0.6 Tesla permanent magnet is studied. Herein, the dynamics of ferrofluid shedding from an initially accumulated mass in water are examined through shadowgraph imaging using two orthogonal cameras. Fundamental differences in the ferrofluid behavior occur between the steady and pulsatile flow cases, as expected. For steady flows, vortex ring shedding is visualized from the mass, and periodic shedding occurs only for moderate mass sizes where the shear forces in the flow interact with the magnetic forces. At Reynolds numbers below 500 with pulsatile flow, suction and roll up of the ferrofluid is seen during the low and moderate periods of flow, followed by the ejection of ferrofluid during high flow. These shadowgraphs illustrate the beauty and richness of ferrofluid dynamics, an understanding of which is instrumental to furthering MDT as an effective drug delivery device.

Noncontact blood perfusion mapping in clinical applications

NASA Astrophysics Data System (ADS)

Iakovlev, Dmitry; Dwyer, Vincent; Hu, Sijung; Silberschmidt, Vadim

2016-04-01

Non-contact imaging photoplethysmography (iPPG) to detect pulsatile blood microcirculation in tissue has been selected as a successor to low spatial resolution and slow scanning blood perfusion techniques currently employed by clinicians. The proposed iPPG system employs a novel illumination source constructed of multiple high power LEDs with narrow spectral emission, which are temporally modulated and synchronised with a high performance sCMOS sensor. To ensure spectrum stability and prevent thermal wavelength drift due to junction temperature variations, each LED features a custom-designed thermal management system to effectively dissipate generated heat and auto-adjust current flow. The use of a multi-wavelength approach has resulted in simultaneous microvascular perfusion monitoring at various tissue depths, which is an added benefit for specific clinical applications. A synchronous detection algorithm to extract weak photoplethysmographic pulse-waveforms demonstrated robustness and high efficiency when applied to even small regions of 5 mm2. The experimental results showed evidences that the proposed system could achieve noticeable accuracy in blood perfusion monitoring by creating complex amplitude and phase maps for the tissue under examination.

Retinal nerve fiber layer thickness map and blood flow pulsation measured with SDOCT

NASA Astrophysics Data System (ADS)

Mujat, Mircea; Chan, Raymond C.; Cense, Barry; Pierce, Mark; Park, Hyle; Joo, Chulmin; Chen, Teresa C.; de Boer, Johannes F.

2006-02-01

Spectral-Domain Optical Coherence Tomography (SDOCT) allows for in-vivo video-rate investigation of biomedical tissue depth structure intended for non-invasive optical diagnostics. It has been suggested that OCT can be used for di-agnosis of glaucoma by measuring the thickness of the Retinal Nerve Fiber Layer (RNLF). We present an automated method for determining the RNFL thickness from a 3-D dataset based on edge detection using a deformable spline algo-rithm. The RNFL thickness map is combined with an integrated reflectance map and retinal cross-sectional images to provide the ophthalmologist with a familiar image for interpreting the OCT data. The video-rate capabilities of our SDOCT system allow for mapping the true retinal topography since motion artifacts are significantly reduced as com-pared to slower time-domain systems. Combined with Doppler Velocimetry, SDOCT also provides information on retinal blood flow dynamics. We analyzed the pulsatile nature of the bidirectional flow dynamics in an artery-vein pair for a healthy volunteer at different locations and for different blood vessel diameters. The Doppler phase shift is determined as the phase difference at the same point of adjacent depth profiles, and is integrated over the area delimited by two circles corresponding to the blood vessels location. Its temporal evolution clearly shows the blood flow pulsatile nature, the cardiac cycle, in both artery and vein. The artery is identified as having a stronger variation of the integrated phase shift. We observe that artery pulsation is always easily detectable, while vein pulsation seems to depend on the veins diameter.

Fabrication of novel high surface area mushroom gilled fibers and their effects on human adipose derived stem cells under pulsatile fluid flow for tissue engineering applications.

PubMed

Tuin, Stephen A; Pourdeyhimi, Behnam; Loboa, Elizabeth G

2016-05-01

The fabrication and characterization of novel high surface area hollow gilled fiber tissue engineering scaffolds via industrially relevant, scalable, repeatable, high speed, and economical nonwoven carding technology is described. Scaffolds were validated as tissue engineering scaffolds using human adipose derived stem cells (hASC) exposed to pulsatile fluid flow (PFF). The effects of fiber morphology on the proliferation and viability of hASC, as well as effects of varied magnitudes of shear stress applied via PFF on the expression of the early osteogenic gene marker runt related transcription factor 2 (RUNX2) were evaluated. Gilled fiber scaffolds led to a significant increase in proliferation of hASC after seven days in static culture, and exhibited fewer dead cells compared to pure PLA round fiber controls. Further, hASC-seeded scaffolds exposed to 3 and 6dyn/cm(2) resulted in significantly increased mRNA expression of RUNX2 after one hour of PFF in the absence of soluble osteogenic induction factors. This is the first study to describe a method for the fabrication of high surface area gilled fibers and scaffolds. The scalable manufacturing process and potential fabrication across multiple nonwoven and woven platforms makes them promising candidates for a variety of applications that require high surface area fibrous materials. We report here for the first time the successful fabrication of novel high surface area gilled fiber scaffolds for tissue engineering applications. Gilled fibers led to a significant increase in proliferation of human adipose derived stem cells after one week in culture, and a greater number of viable cells compared to round fiber controls. Further, in the absence of osteogenic induction factors, gilled fibers led to significantly increased mRNA expression of an early marker for osteogenesis after exposure to pulsatile fluid flow. This is the first study to describe gilled fiber fabrication and their potential for tissue engineering applications. The repeatable, industrially scalable, and versatile fabrication process makes them promising candidates for a variety of scaffold-based tissue engineering applications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The effect of vessel material properties and pulsatile wall motion on the fixation of a proximal stent of an endovascular graft.

PubMed

Corbett, T J; Molony, D S; Callanan, A; McGloughlin, T M

2011-01-01

Migration is a serious failure mechanism associated with endovascular abdominal aortic aneurysm (AAA) repair (EVAR). The effect of vessel material properties and pulsatile wall motion on stent fixation has not been previously investigated. A proximal stent from a commercially available stent graft was implanted into the proximal neck of silicone rubber abdominal aortic aneurysm models of varying proximal neck stiffness (β=25.39 and 20.44). The stent was then dislodged by placing distal force on the stent struts. The peak force to completely dislodge the stent was measured using a loadcell. Dislodgment was performed at ambient pressure with no flow (NF) and during pulsatile flow (PF) at pressures of 120/80 mmHg and 140/100 mmHg to determine if pulsatile wall motions affected the dislodgement force. An imaging analysis was performed at ambient pressure and at pressures of 120 mmHg and 140 mmHg to investigate diameter changes on the model due to the radial force of the stent and internal pressurisation. Stent displacement forces were ~50% higher in the stiffer model (7.16-8.4 N) than in the more compliant model (3.67-4.21 N). The mean displacement force was significantly reduced by 10.95-12.83% from the case of NF to the case of PF at 120/80 mmHg. A further increase in pressure to 140/120 mmHg had no significant effect on the displacement force. The imaging analysis showed that the diameter in the region of the stent was 0.37 mm greater in the less stiff model at all the pressures which could reduce the fixation of the stent. The results suggest that the fixation of passively fixated aortic stents could be comprised in more compliant walls and that pulsatile motions of the wall can reduce the maximum stent fixation. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

Non-contact hemodynamic imaging reveals the jugular venous pulse waveform

NASA Astrophysics Data System (ADS)

Amelard, Robert; Hughson, Richard L.; Greaves, Danielle K.; Pfisterer, Kaylen J.; Leung, Jason; Clausi, David A.; Wong, Alexander

2017-01-01

Cardiovascular monitoring is important to prevent diseases from progressing. The jugular venous pulse (JVP) waveform offers important clinical information about cardiac health, but is not routinely examined due to its invasive catheterisation procedure. Here, we demonstrate for the first time that the JVP can be consistently observed in a non-contact manner using a photoplethysmographic imaging system. The observed jugular waveform was strongly negatively correlated to the arterial waveform (r = -0.73 ± 0.17), consistent with ultrasound findings. Pulsatile venous flow was observed over a spatially cohesive region of the neck. Critical inflection points (c, x, v, y waves) of the JVP were observed across all participants. The anatomical locations of the strongest pulsatile venous flow were consistent with major venous pathways identified through ultrasound.

Non-contact hemodynamic imaging reveals the jugular venous pulse waveform

PubMed Central

Amelard, Robert; Hughson, Richard L.; Greaves, Danielle K.; Pfisterer, Kaylen J.; Leung, Jason; Clausi, David A.; Wong, Alexander

2017-01-01

Cardiovascular monitoring is important to prevent diseases from progressing. The jugular venous pulse (JVP) waveform offers important clinical information about cardiac health, but is not routinely examined due to its invasive catheterisation procedure. Here, we demonstrate for the first time that the JVP can be consistently observed in a non-contact manner using a photoplethysmographic imaging system. The observed jugular waveform was strongly negatively correlated to the arterial waveform (r = −0.73 ± 0.17), consistent with ultrasound findings. Pulsatile venous flow was observed over a spatially cohesive region of the neck. Critical inflection points (c, x, v, y waves) of the JVP were observed across all participants. The anatomical locations of the strongest pulsatile venous flow were consistent with major venous pathways identified through ultrasound. PMID:28065933

The effect of the pulsatile electromagnetic field in children suffering from bronchial asthma.

PubMed

Sadlonova, J; Korpas, J; Salat, D; Miko, L; Kudlicka, J

2003-01-01

From the bibliography it is well known that pulsatile electromagnetic field has an anti-inflammatory and analgesic effect. It causes vasodilatation, myorelaxation, hyper-production of connective tissue and activation of the cell membrane. Therefore our aim was to study the possible therapeutic effect of pulsatile electromagnetic field in asthmatic children. Forty-two children participating in this study were divided in two groups. The 1st group consisting of 21 children (11 females, 10 males, aged 11.8 +/- 0.4 yr) was treated by pulsatile electromagnetic field and pharmacologically. The 2nd group served as control, consisting also of 21 children (11 females, 10 males, aged 11.7 +/- 0.3 yr) and was treated only pharmacologically. Therapeutic effect of the pulsatile electromagnetic field was assessed on the basis of pulmonary tests performed by means of a Spirometer 100 Handi (Germany). The indexes FVC, IVC, ERV, IRV, FEV1, FEV1/FVC%, MEF75,50,25, PEF, PIF and the changes of the flow-volume loop were also registered. The pulsatile electromagnetic field was applied by means of the device MTU 500H, Therapy System (Brno, Czech Republic) for 5 days, two times daily for 30 minutes (magnetic induction: 3 mT, frequency: 4 Hz as recommended by the manufacturer). The results in children of the 1st group showed an improvement of FVC of about 70 ml, IVC of about 110 ml, FEV1 of about 80 ml, MEF75 of about 30 ml, PEF of about 480 ml, PIF of about 550 ml. The increases of ERV, IRV and FEV1/FVC and decreases of MEF25,50 were statistically insignificant. The results in the 2nd group were less clear. The flow-volume loop showed a mild improvement in 14 children. This improvement in the 2nd group was less significant. The clinical status of children and their mood became better. We believe that the pulsatile electro-magnetotherapy in children suffering from asthma is effective. On the basis of our results we can recommend it as a complementary therapy.

Pulsatile turbulent flow through pipe bends at high Dean and Womersley numbers

NASA Astrophysics Data System (ADS)

Kalpakli, Athanasia; Örlü, Ramis; Tillmark, Nils; Alfredsson, P. Henrik

2011-12-01

Turbulent pulsatile flows through pipe bends are prevalent in internal combustion engine components which consist of bent pipe sections and branching conduits. Nonetheless, most of the studies related to pulsatile flows in pipe bends focus on incompressible, low Womersley and low Dean number flows, primarily because they aim in modeling blood flow, while internal combustion engine related flows have mainly been addressed in terms of integral quantities and consist of single point measurements. The present study aims at bridging the gap between these two fields by means of time-resolved stereoscopic particle image velocimetry measurements in a pipe bend with conditions that are close to those encountered in exhaust manifolds. The time/phase-resolved three-dimensional cross-sectional flow-field 3 pipe diameters downstream the pipe bend is captured and the interplay between different secondary motions throughout a pulse cycle is discussed.

White matter hyperintensities in migraine: Clinical significance and central pulsatile hemodynamic correlates.

PubMed

Cheng, Chun-Yu; Cheng, Hao-Min; Chen, Shih-Pin; Chung, Chih-Ping; Lin, Yung-Yang; Hu, Han-Hwa; Chen, Chen-Huan; Wang, Shuu-Jiun

2018-06-01

Background The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities in migraine patients has not been clarified. Methods Sixty patients with migraine (20-50 years old; women, 68%) without overt vascular risk factors and 30 demographically-matched healthy controls were recruited prospectively. Cerebral white matter hyperintensities volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure, carotid-femoral pulse wave velocity, and carotid augmentation index were measured by applanation tonometry. Carotid pulsatility index was derived from Doppler ultrasound carotid artery flow analysis. Results Compared to the controls, the migraine patients had higher white matter hyperintensities frequency (odds ratio, 2.75; p = 0.04) and greater mean white matter hyperintensities volume (0.174 vs. 0.049, cm 3 , p = 0.04). Multivariable regression analysis showed that white matter hyperintensities volume in migraine patients was positively associated with central systolic blood pressure ( p = 0.04) and carotid-femoral pulse wave velocity ( p < 0.001), but negatively associated with carotid pulsatility index ( p = 0.04) after controlling for potential confounding factors. The interaction effects observed indicated that the influence of carotid-femoral pulse wave velocity ( p = 0.004) and central systolic blood pressure ( p = 0.03) on white matter hyperintensities formation was greater for the lower-carotid pulsatility index subgroup of migraine patients. White matter hyperintensities volume in migraine patients increased with decreasing carotid pulsatility index and with increasing central systolic blood pressure or carotid-femoral pulse wave velocity. Conclusions White matter hyperintensities are more common in patients with migraine than in healthy controls. Increased aortic stiffness or central systolic blood pressure in the presence of low intracranial artery resistance may predispose patients with migraine to white matter hyperintensities formation.

Secondary flow vortical structures in a 180∘ elastic curved vessel with torsion under steady and pulsatile inflow conditions

NASA Astrophysics Data System (ADS)

Najjari, Mohammad Reza; Plesniak, Michael W.

2018-01-01

Secondary flow structures in a 180∘ curved pipe model of an artery are studied using particle image velocimetry. Both steady and pulsatile inflow conditions are investigated. In planar curved pipes with steady flow, multiple (two, four, six) vortices are detected. For pulsatile flow, various pairs of vortices, i.e., Dean, deformed-Dean, Lyne-type, and split-Dean, are present in the cross section of the pipe at 90∘ into the bend. The effects of nonplanar curvature (torsion) and vessel dilatation on these vortical structures are studied. Torsion distorts the symmetric secondary flows (which exist in planar curvatures) and can result in formation of more complex vortical structures. For example, the split-Dean and Lyne-type vortices with same rotation direction originating from opposite sides of the cross section tend to merge together in pulsatile flow. The vortical structures in elastic vessels with dilatation (0.61%-3.23%) are also investigated and the results are compared with rigid model results. It was found that the secondary flow structures in rigid and elastic models are similar, and hence the local compliance of the vessel does not affect the morphology of secondary flow structures.

Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells

PubMed Central

Baird, Michelle A.; Billington, Neil; Wang, Aibing; Adelstein, Robert S.; Sellers, James R.; Fischer, Robert S.; Waterman, Clare M.

2017-01-01

The role of nonmuscle myosin 2 (NM2) pulsatile dynamics in generating contractile forces required for developmental morphogenesis has been characterized, but whether these pulsatile contractions are an intrinsic property of all actomyosin networks is not known. Here we used live-cell fluorescence imaging to show that transient, local assembly of NM2A “pulses” occurs in the cortical cytoskeleton of single adherent cells of mesenchymal, epithelial, and sarcoma origin, independent of developmental signaling cues and cell–cell or cell–ECM interactions. We show that pulses in the cortical cytoskeleton require Rho-associated kinase– or myosin light chain kinase (MLCK) activity, increases in cytosolic calcium, and NM2 ATPase activity. Surprisingly, we find that cortical cytoskeleton pulses specifically require the head domain of NM2A, as they do not occur with either NM2B or a 2B-head-2A-tail chimera. Our results thus suggest that pulsatile contractions in the cortical cytoskeleton are an intrinsic property of the NM2A motor that may mediate its role in homeostatic maintenance of tension in the cortical cytoskeleton of adherent cells. PMID:27881665

Pulsatile pipe flow transition: Flow waveform effects

NASA Astrophysics Data System (ADS)

Brindise, Melissa C.; Vlachos, Pavlos P.

2018-01-01

Although transition is known to exist in various hemodynamic environments, the mechanisms that govern this flow regime and their subsequent effects on biological parameters are not well understood. Previous studies have investigated transition in pulsatile pipe flow using non-physiological sinusoidal waveforms at various Womersley numbers but have produced conflicting results, and multiple input waveform shapes have yet to be explored. In this work, we investigate the effect of the input pulsatile waveform shape on the mechanisms that drive the onset and development of transition using particle image velocimetry, three pulsatile waveforms, and six mean Reynolds numbers. The turbulent kinetic energy budget including dissipation rate, production, and pressure diffusion was computed. The results show that the waveform with a longer deceleration phase duration induced the earliest onset of transition, while the waveform with a longer acceleration period delayed the onset of transition. In accord with the findings of prior studies, for all test cases, turbulence was observed to be produced at the wall and either dissipated or redistributed into the core flow by pressure waves, depending on the mean Reynolds number. Turbulent production increased with increasing temporal velocity gradients until an asymptotic limit was reached. The turbulence dissipation rate was shown to be independent of mean Reynolds number, but a relationship between the temporal gradients of the input velocity waveform and the rate of turbulence dissipation was found. In general, these results demonstrated that the shape of the input pulsatile waveform directly affected the onset and development of transition.

Human Thiel-Embalmed Cadaveric Aortic Model with Perfusion for Endovascular Intervention Training and Medical Device Evaluation.

PubMed

McLeod, Helen; Cox, Ben F; Robertson, James; Duncan, Robyn; Matthew, Shona; Bhat, Raj; Barclay, Avril; Anwar, J; Wilkinson, Tracey; Melzer, Andreas; Houston, J Graeme

2017-09-01

The purpose of this investigation was to evaluate human Thiel-embalmed cadavers with the addition of extracorporeal driven ante-grade pulsatile flow in the aorta as a model for simulation training in interventional techniques and endovascular device testing. Three human cadavers embalmed according to the method of Thiel were selected. Extracorporeal pulsatile ante-grade flow of 2.5 L per min was delivered directly into the aorta of the cadavers via a surgically placed connection. During perfusion, aortic pressure and temperature were recorded and optimized for physiologically similar parameters. Pre- and post-procedure CT imaging was conducted to plan and follow up thoracic and abdominal endovascular aortic repair as it would be in a clinical scenario. Thoracic endovascular aortic repair (TEVAR) and endovascular abdominal repair (EVAR) procedures were conducted in simulation of a clinical case, under fluoroscopic guidance with a multidisciplinary team present. The Thiel cadaveric aortic perfusion model provided pulsatile ante-grade flow, with pressure and temperature, sufficient to conduct a realistic simulation of TEVAR and EVAR procedures. Fluoroscopic imaging provided guidance during the intervention. Pre- and post-procedure CT imaging facilitated planning and follow-up evaluation of the procedure. The human Thiel-embalmed cadavers with the addition of extracorporeal flow within the aorta offer an anatomically appropriate, physiologically similar robust model to simulate aortic endovascular procedures, with potential applications in interventional radiology training and medical device testing as a pre-clinical model.

MR angiography of the renal artery: comparison of breath-hold two-dimensional phase-contrast cine technique with the phased-array coil and breath-hold two-dimensional time-of-flight technique with the body coil.

PubMed

Masui, T; Takehara, Y; Igarashi, T; Ichijo, K; Takahashi, M; Kaneko, M; Nozaki, A

1997-07-01

Breath-hold 2D phase-contrast (PC) cine MR angiography with a phased-array coil and 2D time-of-flight (TOF) MR angiography were performed in the renal arteries and their findings were compared. Breath-hold 2D thin slice PC and TOF MR angiography were performed in 10 normal volunteers for renal arteries. A PC technique with k-space segmentation was utilized with the phased-array coil. A PC technique provided visualization of the renal artery more distally than a TOF technique (4.8 +/- 0.5 cm vs. 3.7 +/- 0.8 cm). With cardiac triggering, distal renal arteries were well demonstrated in PC MR angiography. On PC images, up- or downward movements of the mid to distal renal arteries with aortic pulsatility were recognized. The quality of the images was better with the PC than with the TOF technique (3.4 vs. 2.7). The mid to distal portions of the renal arteries translationally move with aortic pulsatility. To consistently visualize and evaluate them on MR angiography, cardiac triggering might be required to reduce the effects of pulsatile motions of the renal artery in the use of a phased-array coil.

Vortex propagation around a wall-mounted obstacle in pulsatile flow

NASA Astrophysics Data System (ADS)

Carr, Ian A.; Plesniak, Michael W.

2015-11-01

Wall-mounted obstacles are prevalent in nature and engineering applications. Physiological flows observed in human vocal fold pathologies, such as polyps, can be modeled by flow over a wall-mounted protuberance. Despite their prevalence, studies of wall-mounted obstacles have been restricted to steady (constant velocity) freestream flow. In biological and geophysical applications, pulsatile flow is much more common, yet effects of pulsatility on the wake of a wall-mounted obstacle remain to be extensively studied. This study aims to characterize the complex physics produced in this unsteady, separated flow. Experiments were performed in a low-speed wind tunnel with a set of rotating vanes, which produce the pulsatile inflow waveform. Instantaneous and phase-averaged particle image velocimetry (PIV) results acquired around a hemispherical obstacle are presented and compared. A mechanism based on self-induced vortex propagation, analogous to that in vortex rings, is proposed to explain the observed dynamics of coherent structures. Predictions of the propagation velocity based on analytical expressions for vortex rings in a viscous fluid are compared to the experimentally measured propagation velocity. Effects of the unsteady boundary layer on the observed physics are explored. This material is based in part upon work supported by the National Science Foundation under Grant Number CBET-1236351, and GW Center for Biomimetics and Bioinspired Engineering (COBRE).

Secondary flow in a curved artery model with Newtonian and non-Newtonian blood-analog fluids

NASA Astrophysics Data System (ADS)

Najjari, Mohammad Reza; Plesniak, Michael W.

2016-11-01

Steady and pulsatile flows of Newtonian and non-Newtonian fluids through a 180°-curved pipe were investigated using particle image velocimetry (PIV). The experiment was inspired by physiological pulsatile flow through large curved arteries, with a carotid artery flow rate imposed. Sodium iodide (NaI) and sodium thiocyanate (NaSCN) were added to the working fluids to match the refractive index (RI) of the test section to eliminate optical distortion. Rheological measurements revealed that adding NaI or NaSCN changes the viscoelastic properties of non-Newtonian solutions and reduces their shear-thinning property. Measured centerline velocity profiles in the upstream straight pipe agreed well with an analytical solution. In the pulsatile case, secondary flow structures, i.e. deformed-Dean, Dean, Wall and Lyne vortices, were observed in various cross sections along the curved pipe. Vortical structures at each cross section were detected using the d2 vortex identification method. Circulation analysis was performed on each vortex separately during the systolic deceleration phase, and showed that vortices split and rejoin. Secondary flow structures in steady flows were found to be morphologically similar to those in pulsatile flows for sufficiently high Dean number. supported by the George Washington University Center for Biomimetics and Bioinspired Engineering.

Contrast-enhanced color Doppler ultrasonography increases diagnostic accuracy for soft tissue tumors.

PubMed

Oebisu, Naoto; Hoshi, Manabu; Ieguchi, Makoto; Takada, Jun; Iwai, Tadashi; Ohsawa, Masahiko; Nakamura, Hiroaki

2014-10-01

Resolution of ultrasonography (US) has undergone marked development. Additionally, a new-generation contrast medium (Sonazoid) used for US is newly available. Contrast-enhanced US has been widely used for evaluating several types of cancer. In the present study, we evaluated the ability of color Doppler US (CDUS) and Sonazoid to differentiate between benign and malignant soft tissue tumors. A total of 180 patients (87 male, 93 female) were enrolled in the present study. The patient ages ranged from 1 to 91 years (mean 58.1±20.0 years). The maximum size, depth, tumor margins, shape, echogenicity and textural pattern were measured on gray-scale images. CDUS was used to evaluate the intratumoral blood flow with and without Sonazoid. Peak systolic flow velocity (Vp), mean flow velocity (Vm), resistivity index (RI) and pulsatility index (PI) of each detected intratumoral artery were automatically calculated with power Doppler US (PDUS). The present study included 118 benign and 62 malignant tumors. Statistical significances were found in size, depth, tumor margin and textural pattern but not in shape or echogenicity on gray-scale images. Before Sonazoid injection, CDUS findings showed 55% sensitivity, 77% specificity and 69% accuracy, whereas contrast-enhanced CDUS showed 87% sensitivity, 68% specificity and 74% accuracy. There were no statistically significant differences between malignant and benign tumors regarding the mean Vp, Vm, RI and PI values determined on PDUS. In conclusion, contrast-enhanced CDUS proved to be a reliable diagnostic tool for detecting malignant potential in soft tissue tumors.

Dying art of a history and physical: pulsatile tinnitus

PubMed Central

Fekete, Zoltan

2017-01-01

Modern medicine often leaves the history and physical by the wayside. Physicians instead skip directly to diagnostic modalities like MRI and angiography. In this case report, we discuss a patient who presented with migraine symptoms. Auscultation revealed signs of pulsatile tinnitus. Further imaging concluded that it was secondary to a type I dural arteriovenous fistula. Thanks to a proper and thorough history and physical, the patient was streamlined into an accurate and efficient work-up leading to symptomatic relief and quality of life improvement. Imaging is a powerful adjunctive technique in modern medicine, but physicians must not rely on machines to diagnose their patients. If this trend continues, it will have a tremendous negative impact on the cost and calibre of healthcare. Our hope is that this case will spread awareness in the medical community, urging physicians to use the lost art of a history and physical. PMID:29183894

Elimination of motion and pulsation artifacts using BLADE sequences in knee MR imaging.

PubMed

Lavdas, Eleftherios; Mavroidis, Panayiotis; Hatzigeorgiou, Vasiliki; Roka, Violeta; Arikidis, Nikos; Oikonomou, Georgia; Andrianopoulos, Konstantinos; Notaras, Ioannis

2012-10-01

The purpose of this study is to evaluate the ability of proton density (PD)-BLADE sequences in reducing or even eliminating motion and pulsatile flow artifacts in knee magnetic resonance imaging examinations. Eighty consecutive patients, who had been routinely scanned for knee examination, participated in the study. The following pairs of sequences with and without BLADE were compared: (a) PD turbo spin echo (TSE) sagittal (SAG) fat saturation (FS) in 35 patients, (b) PD TSE coronal (COR) FS in 19 patients, (c) T2 TSE axial in 13 patients and (d) PD TSE SAG in 13 patients. Both qualitative and quantitative analyses were performed based on the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and relative contrast (ReCon) measures of normal anatomic structures. The qualitative analysis was performed by experienced radiologists. Also, the presence of image motion and pulsation artifacts was evaluated. Based on the results of the SNR, CRN and ReCon for the different sequences and anatomical structures, the BLADE sequences were significantly superior in 19 cases, whereas the corresponding conventional sequences were significantly superior in only 6 cases. BLADE sequences eliminated motion artifacts in all the cases. However, motion artifacts were shown in (a) six PD TSE SAG FS, (b) three PD TSE COR FS, (c) three PD TSE SAG and (d) two T2 TSE axial conventional sequences. In our results, it was found that, in PD FS sequences (sagittal and coronal), the differences between the BLADE and conventional sequences regarding the elimination of motion and pulsatile flow artifacts were statistically significant. In all the comparisons, the PD FS BLADE sequences (coronal and sagittal) were significantly superior to the corresponding conventional sequences regarding the classification of their image quality. In conclusion, this technique appears to be capable to potentially eliminate motion and pulsatile flow artifacts in MR images. Copyright © 2012 Elsevier Inc. All rights reserved.

Non-invasive measurement of choroidal volume change and ocular rigidity through automated segmentation of high-speed OCT imaging

PubMed Central

Beaton, L.; Mazzaferri, J.; Lalonde, F.; Hidalgo-Aguirre, M.; Descovich, D.; Lesk, M. R.; Costantino, S.

2015-01-01

We have developed a novel optical approach to determine pulsatile ocular volume changes using automated segmentation of the choroid, which, together with Dynamic Contour Tonometry (DCT) measurements of intraocular pressure (IOP), allows estimation of the ocular rigidity (OR) coefficient. Spectral Domain Optical Coherence Tomography (OCT) videos were acquired with Enhanced Depth Imaging (EDI) at 7Hz during ~50 seconds at the fundus. A novel segmentation algorithm based on graph search with an edge-probability weighting scheme was developed to measure choroidal thickness (CT) at each frame. Global ocular volume fluctuations were derived from frame-to-frame CT variations using an approximate eye model. Immediately after imaging, IOP and ocular pulse amplitude (OPA) were measured using DCT. OR was calculated from these peak pressure and volume changes. Our automated segmentation algorithm provides the first non-invasive method for determining ocular volume change due to pulsatile choroidal filling, and the estimation of the OR constant. Future applications of this method offer an important avenue to understanding the biomechanical basis of ocular pathophysiology. PMID:26137373

Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites

PubMed Central

Yu, Deng-Guang; Wang, Ke; Liu, Ping; Chen, Xiaohong

2018-01-01

Background Colon-specific pulsatile drug release, as a combined drug controlled-release model, is a useful drug delivery manner for a series of diseases. New nanomedicines and related preparation methods are highly desired. Methods With diclofenac sodium (DS) as a model drug, a new type of structural nanocomposite (SC), in which composite polyvinylpyrrolidone (PVP)–DS core was coated by shellac, was fabricated via modified coaxial electrospinning. For comparison, traditional PVP–DS monolithic hydrophilic nanocomposites (HCs) were generated using a traditional blending process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), water contact angle (WCA), and in vitro dissolution and ex vivo permeation tests were conducted to characterize the composites. Results SEM images demonstrated that both composites were linear nanofibers with smooth surface morphology and cross sections. TEM disclosed that the SCs had a thin shellac sheath layer of approximately 12 nm. XRD and ATR-FTIR results demonstrated that the crystalline DS was converted into amorphous composites with PVP because of favorable secondary interactions. WCA and in vitro dissolution tests demonstrated that the sheath shellac layers in SC could resist acid conditions and provide typical colon-specific pulsatile release, rather than a pulsatile release of HC under acid conditions. Ex vivo permeation results demonstrated that the SCs were able to furnish a tenfold drug permeation rate than the DS particles on the colon membrane. Conclusion A new SC with a shellac coating on hydrophilic amorphous nanocomposites could furnish a colon-specific pulsatile drug release profile. The modified coaxial process can be exploited as a useful tool to create nanocoatings. PMID:29713169

Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites.

PubMed

Yang, Yao-Yao; Liu, Zhe-Peng; Yu, Deng-Guang; Wang, Ke; Liu, Ping; Chen, Xiaohong

2018-01-01

Colon-specific pulsatile drug release, as a combined drug controlled-release model, is a useful drug delivery manner for a series of diseases. New nanomedicines and related preparation methods are highly desired. With diclofenac sodium (DS) as a model drug, a new type of structural nanocomposite (SC), in which composite polyvinylpyrrolidone (PVP)-DS core was coated by shellac, was fabricated via modified coaxial electrospinning. For comparison, traditional PVP-DS monolithic hydrophilic nanocomposites (HCs) were generated using a traditional blending process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), water contact angle (WCA), and in vitro dissolution and ex vivo permeation tests were conducted to characterize the composites. SEM images demonstrated that both composites were linear nanofibers with smooth surface morphology and cross sections. TEM disclosed that the SCs had a thin shellac sheath layer of approximately 12 nm. XRD and ATR-FTIR results demonstrated that the crystalline DS was converted into amorphous composites with PVP because of favorable secondary interactions. WCA and in vitro dissolution tests demonstrated that the sheath shellac layers in SC could resist acid conditions and provide typical colon-specific pulsatile release, rather than a pulsatile release of HC under acid conditions. Ex vivo permeation results demonstrated that the SCs were able to furnish a tenfold drug permeation rate than the DS particles on the colon membrane. A new SC with a shellac coating on hydrophilic amorphous nanocomposites could furnish a colon-specific pulsatile drug release profile. The modified coaxial process can be exploited as a useful tool to create nanocoatings.

Experimental study of the intraventricular filling vortex in diastolic dysfunction

NASA Astrophysics Data System (ADS)

Santhanakrishnan, Arvind; Samaee, Milad; Nelsen, Nicholas

2016-11-01

Heart failure with normal ejection fraction (HFNEF) is a clinical syndrome that is prevalent in over half of heart failure patients. HFNEF patients typically show diastolic dysfunction, caused by a decrease in relaxation capability of the left ventricular (LV) muscle tissue and/or an increase in LV chamber stiffness. Numerous studies using non-invasive medical imaging have shown that an intraventricular filling vortex is formed in the LV during diastole. We conducted 2D particle image velocimetry and hemodynamics measurements on a left heart simulator to investigate diastolic flow under increasing LV wall stiffness, LV wall thickness and heart rate (HR) conditions. Flexible-walled, optically clear LV physical models cast from silicone were fitted within a fluid-filled acrylic chamber. Pulsatile flow within the LV model was generated using a piston pump and 2-component Windkessel elements were used to tune the least stiff (baseline) LV model to physiological conditions. The results show that peak circulation of the intraventricular filling vortex is diminished in conditions of diastolic dysfunction as compared to the baseline case. Increasing HR exacerbated the circulation of the filling vortex across all cases.

Pulsatile Flow Across a Cylinder--An Investigation of Flow in a Total Artificial Lung

NASA Astrophysics Data System (ADS)

Lin, Yu-Chun

2005-11-01

The effect of pulsatility on flow across a single cylinder has been examined experimentally using particle image velocimetry. This work is motivated by the ongoing development of a total artificial lung (TAL), a device which would serve as a bridge to lung transplant. The prototype TAL consists of hollow microfibers through which oxygen-rich gas flows and blood flows around. Flow through the device is provided entirely by right heart and, therefore, is puslatile. The Peclet number of the flow is large and consequently the development of secondary flow affects the resulting gas exchange. The effects of frequency and average flow rate of pulsatile flow around a cylinder were investigated experimentally in a water tunnel and some of the results were compared with preliminary numerical results. Vortices developed behind the cylinder at lower Reynolds numbers in pulsatile flow than steady flow. The results indicate that there are critical values of the Reynolds number between 3 to 5 and Stokes numbers of 0.22, below which vortices were not observed. The findings suggest that higher Stokes and Reynolds numbers within the device could enhance vortex formation. However, this enhanced gas exchange could be at the expense of higher device resistance and increased likelihood of blood trauma. Intelligent TAL design will require consideration of these effects. This work is supported by NIH grant HL69420.

Quantification of residual limb skeletal muscle perfusion with contrast-enhanced ultrasound during application of a focal junctional tourniquet

PubMed Central

Davidson, Brian P.; Belcik, J. Todd; Mott, Brian H.; Landry, Gregory; Lindner, Jonathan R.

2015-01-01

Objective Focal junctional tourniquets (JTs) have been developed to control hemorrhage from proximal limb injuries. These devices may permit greater collateral perfusion than circumferential tourniquets. We hypothesized that JTs eliminate large-vessel pulse pressure yet allow a small amount of residual limb perfusion that could be useful for maintaining tissue viability. Methods Ten healthy control subjects were studied. Transthoracic echocardiography, Doppler ultrasound of the femoral artery (FA) and posterior tibial artery, and contrast-enhanced ultrasound (CEU) perfusion imaging of the anterior thigh extensor and calf plantar flexor muscles were performed at baseline and during application of a JT over the common FA. Intramuscular arterial pulsatility index was also measured from CEU intensity variation during the cardiac cycle. Results FA flow was eliminated by JTs in all subjects; posterior tibial flow was eliminated in all but one. Perfusion measured in the thigh and calf muscles was similar at baseline (0.33 ± 0.29 vs 0.29 ± 0.22 mL/min/g). Application of the JT resulted in a reduction of perfusion (P < .05) that was similar for the thigh and calf (0.08 ± 0.07 and 0.10 ± 0.03 mL/min/g). On CEU, microvascular flux rate was reduced by ≈55%, and functional microvascular blood volume was reduced by ≈35%. Arterial pulsatility index was reduced by ≈90% in the calf. JT inflation did not alter left ventricle dimensions, fractional shortening, cardiac output, or arterial elastance as a measure of total systolic load. Conclusions Application of a JT eliminates conduit arterial pulse and markedly reduces intramuscular pulse pressure, but thigh and calf skeletal muscle perfusion is maintained at 25% to 35% of basal levels. These data suggest that JTs that are used to control limb hemorrhage allow residual tissue perfusion even when pulse pressure is absent. PMID:25065582

Mechanisms of Mechano-Transduction within Osteoblasts

DTIC Science & Technology

1999-09-01

inositol trisphosphate levels (Reich and Frangos , 1993) with increasing shear stress. In a study concerning the effect of fluid shear...stress on cultured rat calvaria 34 osteoblasts, Hillsley and Frangos (1997) reported no change in collagen or osteopontin expression...Hillsley MV and Frangos JA (1997). Alkaline phosphatase in osteoblasts is down-regulated by pulsatile fluid flow. Calcif Tissue Int 60

Transesophageal Doppler measurement of renal arterial blood flow velocities and indices in children.

PubMed

Zabala, Luis; Ullah, Sana; Pierce, Carol D'Ann; Gautam, Nischal K; Schmitz, Michael L; Sachdeva, Ritu; Craychee, Judith A; Harrison, Dale; Killebrew, Pamela; Bornemeier, Renee A; Prodhan, Parthak

2012-06-01

Doppler-derived renal blood flow indices have been used to assess renal pathologies. However, transesophageal ultrasonography (TEE) has not been previously used to assess these renal variables in pediatric patients. In this study, we (a) assessed whether TEE allows adequate visualization of the renal parenchyma and renal artery, and (b) evaluated the concordance of TEE Doppler-derived renal blood flow measurements/indices compared with a standard transabdominal renal ultrasound (TAU) in children. This prospective cohort study enrolled 28 healthy children between the ages of 1 and 17 years without known renal dysfunction who were undergoing atrial septal defect device closure in the cardiac catheterization laboratory. TEE was used to obtain Doppler renal artery blood velocities (peak systolic velocity, end-diastolic velocity, mean diastolic velocity, resistive index, and pulsatility index), and these values were compared with measurements obtained by TAU. Concordance correlation coefficient (CCC) was used to determine clinically significant agreement between the 2 methods. The Bland-Altman plots were used to determine whether these 2 methods agree sufficiently to be used interchangeably. Statistical significance was accepted at P ≤ 0.05. Obtaining 2-dimensional images of kidney parenchyma and Doppler-derived measurements using TEE in children is feasible. There was statistically significant agreement between the 2 methods for all measurements. The CCC between the 2 imaging techniques was 0.91 for the pulsatility index and 0.66 for the resistive index. These coefficients were sensitive to outliers. When the highest and lowest data points were removed from the analysis, the CCC between the 2 imaging techniques was 0.62 for the pulsatility index and 0.50 for the resistive index. The 95% confidence interval (CI) for pulsatility index was 0.35 to 0.98 and for resistive index was 0.21 to 0.89. The Bland-Altman plots indicate good agreement between the 2 methods; for the pulsatility index, the limits of agreement were -0.80 to 0.53. The correlation of the size of the measurement and the mean difference in methods (-0.14; 95% CI = -0.28, 0.01) was not statistically significant (r = 0.31, P = 0.17). For the resistive index, the limits of agreement were -0.22 to 0.12. The correlation of the size of the measurement and the mean difference in methods (-0.05; 95% CI = -0.09, -0.01) was not statistically significant (r = 0.10, P = 0.65). This study confirms the feasibility of obtaining 2-dimensional images of kidney parenchyma and Doppler-derived measurements using TEE in children. Angle-independent TEE Doppler-derived indices show significant concordance with those derived by TAU. Further studies are required to assess whether this correlation holds true in the presence of renal pathology. This technique has the potential to help modulate intraoperative interventions based on their impact on renal variables and may prove helpful in the perioperative period for children at risk of acute kidney injury.

High-order numerical simulations of pulsatile flow in a curved artery model

NASA Astrophysics Data System (ADS)

Cox, Christopher; Liang, Chunlei; Plesniak, Michael W.

2016-11-01

Cardiovascular flows are pulsatile, incompressible and occur in complex geometries with compliant walls. Together, these factors can produce an environment that can affect the progression of cardiovascular disease by altering wall shear stresses. Unstructured high-order CFD methods are well suited for capturing unsteady vortex-dominated viscous flows, and these methods provide high accuracy for similar cost as low-order methods. We use an in-house three-dimensional flux reconstruction Navier-Stokes solver to simulate secondary flows and vortical structures within a rigid 180-degree curved artery model under pulsatile flow of a Newtonian blood-analog fluid. Our simulations use a physiological flowrate waveform taken from the carotid artery. We are particularly interested in the dynamics during the deceleration phase of the waveform, where we observe the deformed-Dean, Dean, Lyne and Wall vortices. Our numerical results reveal the complex nature of these vortices both in space and time and their effect on overall wall shear stress. Numerical results agree with and complement experimental results obtained in our laboratory using particle image velocimetry. Supported by the GW Center for Biomimetics and Bioinspired Engineering.

Intracranial aneurysmal pulsatility as a new individual criterion for rupture risk evaluation: biomechanical and numeric approach (IRRAs Project).

PubMed

Sanchez, M; Ecker, O; Ambard, D; Jourdan, F; Nicoud, F; Mendez, S; Lejeune, J-P; Thines, L; Dufour, H; Brunel, H; Machi, P; Lobotesis, K; Bonafe, A; Costalat, V

2014-09-01

The present study follows an experimental work based on the characterization of the biomechanical behavior of the aneurysmal wall and a numerical study where a significant difference in term of volume variation between ruptured and unruptured aneurysm was observed in a specific case. Our study was designed to highlight by means of numeric simulations the correlation between aneurysm sac pulsatility and the risk of rupture through the mechanical properties of the wall. In accordance with previous work suggesting a correlation between the risk of rupture and the material properties of cerebral aneurysms, 12 fluid-structure interaction computations were performed on 12 "patient-specific" cases, corresponding to typical shapes and locations of cerebral aneurysms. The variations of the aneurysmal volume during the cardiac cycle (ΔV) are compared by using wall material characteristics of either degraded or nondegraded tissues. Aneurysms were located on 6 different arteries: middle cerebral artery (4), anterior cerebral artery (3), internal carotid artery (1), vertebral artery (1), ophthalmic artery (1), and basilar artery (1). Aneurysms presented different shapes (uniform or multilobulated) and diastolic volumes (from 18 to 392 mm3). The pulsatility (ΔV/V) was significantly larger for a soft aneurysmal material (average of 26%) than for a stiff material (average of 4%). The difference between ΔV, for each condition, was statistically significant: P=.005. The difference in aneurysmal pulsatility as highlighted in this work might be a relevant patient-specific predictor of aneurysm risk of rupture. © 2014 by American Journal of Neuroradiology.

Automatic segmentation and co-registration of gated CT angiography datasets: measuring abdominal aortic pulsatility

NASA Astrophysics Data System (ADS)

Wentz, Robert; Manduca, Armando; Fletcher, J. G.; Siddiki, Hassan; Shields, Raymond C.; Vrtiska, Terri; Spencer, Garrett; Primak, Andrew N.; Zhang, Jie; Nielson, Theresa; McCollough, Cynthia; Yu, Lifeng

2007-03-01

Purpose: To develop robust, novel segmentation and co-registration software to analyze temporally overlapping CT angiography datasets, with an aim to permit automated measurement of regional aortic pulsatility in patients with abdominal aortic aneurysms. Methods: We perform retrospective gated CT angiography in patients with abdominal aortic aneurysms. Multiple, temporally overlapping, time-resolved CT angiography datasets are reconstructed over the cardiac cycle, with aortic segmentation performed using a priori anatomic assumptions for the aorta and heart. Visual quality assessment is performed following automatic segmentation with manual editing. Following subsequent centerline generation, centerlines are cross-registered across phases, with internal validation of co-registration performed by examining registration at the regions of greatest diameter change (i.e. when the second derivative is maximal). Results: We have performed gated CT angiography in 60 patients. Automatic seed placement is successful in 79% of datasets, requiring either no editing (70%) or minimal editing (less than 1 minute; 12%). Causes of error include segmentation into adjacent, high-attenuating, nonvascular tissues; small segmentation errors associated with calcified plaque; and segmentation of non-renal, small paralumbar arteries. Internal validation of cross-registration demonstrates appropriate registration in our patient population. In general, we observed that aortic pulsatility can vary along the course of the abdominal aorta. Pulsation can also vary within an aneurysm as well as between aneurysms, but the clinical significance of these findings remain unknown. Conclusions: Visualization of large vessel pulsatility is possible using ECG-gated CT angiography, partial scan reconstruction, automatic segmentation, centerline generation, and coregistration of temporally resolved datasets.

Dying art of a history and physical: pulsatile tinnitus.

PubMed

Lee, Jonathan; Fekete, Zoltan

2017-11-27

Modern medicine often leaves the history and physical by the wayside. Physicians instead skip directly to diagnostic modalities like MRI and angiography. In this case report, we discuss a patient who presented with migraine symptoms. Auscultation revealed signs of pulsatile tinnitus. Further imaging concluded that it was secondary to a type I dural arteriovenous fistula. Thanks to a proper and thorough history and physical, the patient was streamlined into an accurate and efficient work-up leading to symptomatic relief and quality of life improvement. Imaging is a powerful adjunctive technique in modern medicine, but physicians must not rely on machines to diagnose their patients. If this trend continues, it will have a tremendous negative impact on the cost and calibre of healthcare. Our hope is that this case will spread awareness in the medical community, urging physicians to use the lost art of a history and physical. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Dynamical modes of two almost identical chemical oscillators connected via both pulsatile and diffusive coupling.

PubMed

Safonov, Dmitry A; Vanag, Vladimir K

2018-05-03

The dynamical regimes of two almost identical Belousov-Zhabotinsky oscillators with both pulsatile (with time delay) and diffusive coupling have been studied theoretically with the aid of ordinary differential equations for four combinations of these types of coupling: inhibitory diffusive and inhibitory pulsatile (IDIP); excitatory diffusive and inhibitory pulsatile; inhibitory diffusive and excitatory pulsatile; and finally, excitatory diffusive and excitatory pulsatile (EDEP). The combination of two types of coupling creates a condition for new feedback, which promotes new dynamical modes for the IDIP and EDEP coupling.

Non-mydriatic video ophthalmoscope to measure fast temporal changes of the human retina

NASA Astrophysics Data System (ADS)

Tornow, Ralf P.; Kolář, Radim; Odstrčilík, Jan

2015-07-01

The analysis of fast temporal changes of the human retina can be used to get insight to normal physiological behavior and to detect pathological deviations. This can be important for the early detection of glaucoma and other eye diseases. We developed a small, lightweight, USB powered video ophthalmoscope that allows taking video sequences of the human retina with at least 25 frames per second without dilating the pupil. Short sequences (about 10 s) of the optic nerve head (20° x 15°) are recorded from subjects and registered offline using two-stage process (phase correlation and Lucas-Kanade approach) to compensate for eye movements. From registered video sequences, different parameters can be calculated. Two applications are described here: measurement of (i) cardiac cycle induced pulsatile reflection changes and (ii) eye movements and fixation pattern. Cardiac cycle induced pulsatile reflection changes are caused by changing blood volume in the retina. Waveform and pulse parameters like amplitude and rise time can be measured in any selected areas within the retinal image. Fixation pattern ΔY(ΔX) can be assessed from eye movements during video acquisition. The eye movements ΔX[t], ΔY[t] are derived from image registration results with high temporal (40 ms) and spatial (1,86 arcmin) resolution. Parameters of pulsatile reflection changes and fixation pattern can be affected in beginning glaucoma and the method described here may support early detection of glaucoma and other eye disease.

[Development of elastameric sealant designed for arterial field].

PubMed

Matsuda, Takehisa; Nakajima, Nobuyuki

2013-04-01

The development of a reliable surgical sealant specific for arterial tissues has been long awaited. In this article, first the "ideal" adhesion mechanism formulated from biomechanical concept is proposed for ensured hemostasis in dissected arteries with pulsatile flow. An urethane prepolymer prepared along the design criteria is viscous liquid. Due to its high water absorbility and high reactivity with water, the sealant applied to vascular tissues becomes an elastomer within several minutes. When the sealant was applied to dissected canine abdominal arteries with 3 stay sutures, followed by declamping 5 minutes, neither bleeding nor detrimental effect on tissue morphogenesis was observed. This sealant is being ready to the market.

Comparative Study of Continuous and Pulsatile Left Ventricular Assist Devices on Hemodynamics of a Pediatric End-to-Side Anastomotic Graft

PubMed Central

Yang, Ning; Deutsch, Steven; Paterson, Eric G.; Manning, Keefe B.

2013-01-01

Although there are many studies that focus on understanding the consequence of pumping mode (continuous vs. pulsatile) associated with ventricular assist devices (VADs) on pediatric vascular pulsatility, the impact on local hemodynamics has been largely ignored. Hence, we compare not only the hemodynamic parameters indicative of pulsatility but also the local flow fields in the aorta and the great vessels originating from the aortic arch. A physiologic graft anastomotic model is constructed based on a pediatric, patient specific, aorta with a graft attached on the ascending aorta. The flow is simulated using a previously validated second-order accurate Navier–Stokes flow solver based upon a finite volume approach. The major findings are: (1) pulsatile support provides a greater degree of vascular pulsatility when compared to continuous support, which, however, is still 20% less than pulsatility in the healthy aorta; (2) pulsatile support increases the flow in the great vessels, while continuous support decreases it; (3) complete VAD support results in turbulence in the aorta, with maximum principal Reynolds stresses for pulsatile support and continuous support of 7081 and 249 dyn/cm2, respectively; (4) complete pulsatile support results in a significant increase in predicted hemolysis in the aorta; and (5) pulsatile support causes both higher time-averaged wall shear stresses (WSS) and oscillatory shear indices (OSI) in the aorta than does continuous support. These findings will help to identify the risk of graft failure for pediatric patients with pulsatile and continuous VADs. PMID:24348881

Simulation of blood flow using extended Boltzmann kinetic approach

NASA Astrophysics Data System (ADS)

Chen, Caixia; Chen, Hudong; Freed, David; Shock, Richard; Staroselsky, Ilya; Zhang, Raoyang; Ümit Coşkun, A.; Stone, Peter H.; Feldman, Charles L.

2006-03-01

Lattice Boltzmann (LB) simulations are conducted to obtain the detailed hydrodynamics in a variety of blood vessel setups, including a prototype stented channel and four human coronary artery geometries based on the images obtained from real patients. For a model of stented flow involving an S-shape stent, a pulsatile flow rate is applied as the inlet boundary condition, and the time- and space-dependent flow field is computed. The LB simulation is found to reproduce the analytical solutions for the velocity profiles and wall shear stress distributions for the pulsatile channel flow. For the coronary arteries, the distributions of wall shear stress, which is important for clinical diagnostic purposes, are in good agreement with the conventional CFD predictions.

Multispectral imaging of organ viability during uterine transplantation surgery

NASA Astrophysics Data System (ADS)

Clancy, Neil T.; Saso, Srdjan; Stoyanov, Danail; Sauvage, Vincent; Corless, David J.; Boyd, Michael; Noakes, David E.; Thum, Meen-Yau; Ghaem-Maghami, Sadaf; Smith, J. R.; Elson, Daniel S.

2014-02-01

Uterine transplantation surgery has been proposed as a treatment for permanent absolute uterine factor infertility (AUFI) in the case of loss of the uterus. Due to the complexity of the vasculature correct reanastomosis of the blood supply during transplantation surgery is a crucial step to ensure reperfusion and viability of the organ. While techniques such as fluorescent dye imaging have been proposed to visualise perfusion there is no gold standard for intraoperative visualisation of tissue oxygenation. In this paper results from a liquid crystal tuneable filter (LCTF)-based multispectral imaging (MSI) laparoscope are described. The system was used to monitor uterine oxygen saturation (SaO2) before and after transplantation. Results from surgeries on two animal models (rabbits and sheep) are presented. A feature-based registration algorithm was used to correct for misalignment induced by breathing or peristalsis in the tissues of interest prior to analysis. An absorption spectrum was calculated at each spatial pixel location using reflectance data from a reference standard, and the relative contributions from oxy- and deoxyhaemoglobin were calculated using a least squares regression algorithm with non-negativity constraints. Results acquired during animal surgeries show that cornual oxygenation changes are consistent with those observed in point measurements taken using a pulse oximeter, showing reduced SaO2 following reanastomosis. Values obtained using the MSI laparoscope were lower than those taken with the pulse oximeter, which may be due to the latter's use of the pulsatile arterial blood signal. Future work incorporating immunological test results will help to correlate SaO2 levels with surgical outcomes.

On the stability of lung parenchymal lesions with applications to early pneumothorax diagnosis.

PubMed

Bhandarkar, Archis R; Banerjee, Rohan; Seshaiyer, Padmanabhan

2013-01-01

Spontaneous pneumothorax, a prevalent medical challenge in most trauma cases, is a form of sudden lung collapse closely associated with risk factors such as lung cancer and emphysema. Our work seeks to explore and quantify the currently unknown pathological factors underlying lesion rupture in pneumothorax through biomechanical modeling. We hypothesized that lesion instability is closely associated with elastodynamic strain of the pleural membrane from pulsatile air flow and collagen-elastin dynamics. Based on the principles of continuum mechanics and fluid-structure interaction, our proposed model coupled isotropic tissue deformation with pressure from pulsatile air motion and the pleural fluid. Next, we derived mathematical instability criteria for our ordinary differential equation system and then translated these mathematical instabilities to physically relevant structural instabilities via the incorporation of a finite energy limiter. The introduction of novel biomechanical descriptions for collagen-elastin dynamics allowed us to demonstrate that changes in the protein structure can lead to a transition from stable to unstable domains in the material parameter space for a general lesion. This result allowed us to create a novel streamlined algorithm for detecting material instabilities in transient lung CT scan data via analyzing deformations in a local tissue boundary.

Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells.

PubMed

Baird, Michelle A; Billington, Neil; Wang, Aibing; Adelstein, Robert S; Sellers, James R; Fischer, Robert S; Waterman, Clare M

2017-01-15

The role of nonmuscle myosin 2 (NM2) pulsatile dynamics in generating contractile forces required for developmental morphogenesis has been characterized, but whether these pulsatile contractions are an intrinsic property of all actomyosin networks is not known. Here we used live-cell fluorescence imaging to show that transient, local assembly of NM2A "pulses" occurs in the cortical cytoskeleton of single adherent cells of mesenchymal, epithelial, and sarcoma origin, independent of developmental signaling cues and cell-cell or cell-ECM interactions. We show that pulses in the cortical cytoskeleton require Rho-associated kinase- or myosin light chain kinase (MLCK) activity, increases in cytosolic calcium, and NM2 ATPase activity. Surprisingly, we find that cortical cytoskeleton pulses specifically require the head domain of NM2A, as they do not occur with either NM2B or a 2B-head-2A-tail chimera. Our results thus suggest that pulsatile contractions in the cortical cytoskeleton are an intrinsic property of the NM2A motor that may mediate its role in homeostatic maintenance of tension in the cortical cytoskeleton of adherent cells. © 2017 Baird et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Numerical simulation of particle transport and deposition in the pulmonary vasculature.

PubMed

Sohrabi, Salman; Zheng, Junda; Finol, Ender A; Liu, Yaling

2014-12-01

To quantify the transport and adhesion of drug particles in a complex vascular environment, computational fluid particle dynamics (CFPD) simulations of blood flow and drug particulate were conducted in three different geometries representing the human lung vasculature for steady and pulsatile flow conditions. A fully developed flow profile was assumed as the inlet velocity, and a lumped mathematical model was used for the calculation of the outlet pressure boundary condition. A receptor-ligand model was used to simulate the particle binding probability. The results indicate that bigger particles have lower deposition fraction due to less chance of successful binding. Realistic unsteady flow significantly accelerates the binding activity over a wide range of particle sizes and also improves the particle deposition fraction in bifurcation regions when comparing with steady flow condition. Furthermore, surface imperfections and geometrical complexity coupled with the pulsatility effect can enhance fluid mixing and accordingly particle binding efficiency. The particle binding density at bifurcation regions increases with generation order and drug carriers are washed away faster in steady flow. Thus, when studying drug delivery mechanism in vitro and in vivo, it is important to take into account blood flow pulsatility in realistic geometry. Moreover, tissues close to bifurcations are more susceptible to deterioration due to higher uptake.

Optimization of Electrical Stimulation Parameters for Cardiac Tissue Engineering

PubMed Central

Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

2010-01-01

In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile cardiac tissue constrcuts. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation, to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, and were thus used in tissue engineering studies. Cardiac tissues stimulated at 3V/cm amplitude and 3Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43, and the best developed contractile behavior. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering. PMID:21604379

Systems analysis of thrombus formation

PubMed Central

Diamond, Scott L.

2016-01-01

The systems analysis of thrombosis seeks to quantitatively predict blood function in a given vascular wall and hemodynamic context. Relevant to both venous and arterial thrombosis, a Blood Systems Biology approach should provide metrics for rate and molecular mechanisms of clot growth, thrombotic risk, pharmacological response, and utility of new therapeutic targets. As a rapidly created multicellular aggregate with a polymerized fibrin matrix, blood clots result from hundreds of unique reactions within and around platelets propagating in space and time under hemodynamic conditions. Coronary artery thrombosis is dominated by atherosclerotic plaque rupture, complex pulsatile flows through stenotic regions producing high wall shear stresses, and plaque-derived tissue factor driving thrombin production. In contrast, venous thrombosis is dominated by stasis or depressed flows, endothelial inflammation, white blood cell-derived tissue factor, and ample red blood cell incorporation. By imaging vessels, patient-specific assessment using computational fluid dynamics provides an estimate of local hemodynamics and fractional flow reserve. High dimensional ex vivo phenotyping of platelet and coagulation can now power multiscale computer simulations at the subcellular to cellular to whole vessel scale of heart attacks or strokes. Additionally, an integrated systems biology approach can rank safety and efficacy metrics of various pharmacological interventions or clinical trial designs. PMID:27126646

Dynamic three-dimensional phase-contrast technique in MRI: application to complex flow analysis around the artificial heart valve

NASA Astrophysics Data System (ADS)

Kim, Soo Jeong; Lee, Dong Hyuk; Song, Inchang; Kim, Nam Gook; Park, Jae-Hyeung; Kim, JongHyo; Han, Man Chung; Min, Byong Goo

1998-07-01

Phase-contrast (PC) method of magnetic resonance imaging (MRI) has bee used for quantitative measurements of flow velocity and volume flow rate. It is a noninvasive technique which provides an accurate two-dimensional velocity image. Moreover, Phase Contrast Cine magnetic resonance imaging combines the flow dependent contrast of PC-MRI with the ability of cardiac cine imaging to produce images throughout the cardiac cycle. However, the accuracy of the data acquired from the single through-plane velocity encoding can be reduced by the effect of flow direction, because in many practical cases flow directions are not uniform throughout the whole region of interest. In this study, we present dynamic three-dimensional velocity vector mapping method using PC-MRI which can visualize the complex flow pattern through 3D volume rendered images displayed dynamically. The direction of velocity mapping can be selected along any three orthogonal axes. By vector summation, the three maps can be combined to form a velocity vector map that determines the velocity regardless of the flow direction. At the same time, Cine method is used to observe the dynamic change of flow. We performed a phantom study to evaluate the accuracy of the suggested PC-MRI in continuous and pulsatile flow measurement. Pulsatile flow wave form is generated by the ventricular assistant device (VAD), HEMO-PULSA (Biomedlab, Seoul, Korea). We varied flow velocity, pulsatile flow wave form, and pulsing rate. The PC-MRI-derived velocities were compared with Doppler-derived results. The velocities of the two measurements showed a significant linear correlation. Dynamic three-dimensional velocity vector mapping was carried out for two cases. First, we applied to the flow analysis around the artificial heart valve in a flat phantom. We could observe the flow pattern around the valve through the 3-dimensional cine image. Next, it is applied to the complex flow inside the polymer sac that is used as ventricle in totally implantable artificial heart (TAH). As a result we could observe the flow pattern around the valves of the sac, though complex flow can not be detected correctly in the conventional phase contrast method. In addition, we could calculate the cardiac output from TAH sac by quantitative measurement of the volume of flow across the outlet valve.

21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow... device is placed in a cardiopulmonary bypass circuit downstream from the oxygenator. (b) Classification...

21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow... device is placed in a cardiopulmonary bypass circuit downstream from the oxygenator. (b) Classification...

Pulsatile extracorporeal circulation during on-pump cardiac surgery enhances aortic wall shear stress.

PubMed

Assmann, Alexander; Benim, Ali Cemal; Gül, Fethi; Lux, Philipp; Akhyari, Payam; Boeken, Udo; Joos, Franz; Feindt, Peter; Lichtenberg, Artur

2012-01-03

Controversy on superiority of pulsatile versus non-pulsatile extracorporeal circulation in cardiac surgery still continues. Stroke as one of the major adverse events during cardiopulmonary bypass is, in the majority of cases, caused by mobilization of aortic arteriosclerotic plaques that is inducible by pathologically elevated wall shear stress values. The present study employs computational fluid dynamics to evaluate the aortic blood flow and wall shear stress profiles under the influence of antegrade or retrograde perfusion with pulsatile versus non-pulsatile extracorporeal circulation. While, compared to physiological flow, a non-pulsatile perfusion resulted in generally decreased blood velocities and only moderately increased shear forces (48 Pa versus 20 Pa antegradely and 127 Pa versus 30 Pa retrogradely), a pulsatile perfusion extensively enhanced the occurrence of turbulences, maximum blood flow speed and maximum wall shear stress (1020 Pa versus 20 Pa antegradely and 1178 Pa versus 30 Pa retrogradely). Under these circumstances arteriosclerotic embolism has to be considered. Further simulations and experimental work are necessary to elucidate the impact of our findings on the scientific discourse of pulsatile versus non-pulsatile extracorporeal circulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Power Doppler of the urethra in continent or incontinent, pre- and postmenopausal women.

PubMed

Jármy-Di Bella, Z I; Girão, M J; Sartori, M F; Di Bella Júnior, V; Lederman, H M; Baracat, E C; Lima, G R

2000-06-01

Urethral pressure should exceed bladder pressure, both at rest and on stress, for urinary continence to occur. A decrease in urethral pressure is a major factor explaining the pathogenesis of urinary incontinence. A number of elements, such as smooth and striated periurethral muscles, and connective, vascular and elastic tissues, contribute to urethral pressure. The periurethral vessels are influenced by hormonal changes during the menstrual cycle, during pregnancy and postmenopause. We studied the periurethral vessels in 97 women, 57 of whom were incontinent and 40 continent, using power color Doppler velocimetry. The number of periurethral vessels, systolic peak, minimum diastolic values, pulsatility and resistance indexes, as well as systolic-diastolic ratio, were assessed. Statistically significant differences were found between incontinent women in the premenopausal period and those in the postmenopausal period, regarding the number of periurethral vessels, systolic peak, minimum diastolic values, pulsatility and resistance indexes.

User-guided automated segmentation of time-series ultrasound images for measuring vasoreactivity of the brachial artery induced by flow mediation

NASA Astrophysics Data System (ADS)

Sehgal, Chandra M.; Kao, Yen H.; Cary, Ted W.; Arger, Peter H.; Mohler, Emile R.

2005-04-01

Endothelial dysfunction in response to vasoactive stimuli is closely associated with diseases such as atherosclerosis, hypertension and congestive heart failure. The current method of using ultrasound to image the brachial artery along the longitudinal axis is insensitive for measuring the small vasodilatation that occurs in response to flow mediation. The goal of this study is to overcome this limitation by using cross-sectional imaging of the brachial artery in conjunction with the User-Guided Automated Boundary Detection (UGABD) algorithm for extracting arterial boundaries. High-resolution ultrasound imaging was performed on rigid plastic tubing, on elastic rubber tubing phantoms with steady and pulsatile flow, and on the brachial artery of a healthy volunteer undergoing reactive hyperemia. The area of cross section of time-series images was analyzed by UGABD by propagating the boundary from one frame to the next. The UGABD results were compared by linear correlation with those obtained by manual tracing. UGABD measured the cross-sectional area of the phantom tubing to within 5% of the true area. The algorithm correctly detected pulsatile vasomotion in phantoms and in the brachial artery. A comparison of area measurements made using UGABD with those made by manual tracings yielded a correlation of 0.9 and 0.8 for phantoms and arteries, respectively. The peak vasodilatation due to reactive hyperemia was two orders of magnitude greater in pixel count than that measured by longitudinal imaging. Cross-sectional imaging is more sensitive than longitudinal imaging for measuring flow-mediated dilatation of brachial artery, and thus may be more suitable for evaluating endothelial dysfunction.

Continuous and Pulsatile Pediatric Ventricular Assist Device Hemodynamics with a Viscoelastic Blood Model

PubMed Central

Good, Bryan C.; Deutsch, Steven; Manning, Keefe B.

2015-01-01

Purpose To investigate the effects of pulsatile and continuous pediatric ventricular assist (PVAD) flow and pediatric blood viscoelasticity on hemodynamics in a pediatric aortic graft model. Methods Hemodynamic parameters of pulsatility, along with velocity and wall shear stress (WSS), are analyzed and compared between Newtonian and viscoelastic blood models at a range of physiological pediatric hematocrits using computational fluid dynamics. Results Both pulsatile and continuous PVAD flow lead to a decrease in pulsatility (surplus hemodynamic energy (SHE), ergs/cm3) compared to healthy aortic flow but with continuous PVAD pulsatility up to 2.4 times lower than pulsatile PVAD pulsatility at each aortic outlet. Significant differences are also seen between the two flow modes in velocity and WSS. The higher velocity jet during systole with pulsatile flow leads to higher WSSs at the anastomotic toe and at the aortic branch bifurcations. The lower velocity but continuous flow jet leads to a much different flow field and higher WSSs into diastole. Under a range of physiological pediatric hematocrit (20-60%), both velocity and WSS can vary significantly with the higher hematocrit blood model generally leading to higher peak WSSs but also lower WSSs in regions of flow separation. Conclusions The large decrease in pulsatility seen from continuous PVAD flow could lead to complications in pediatric vascular development while the high WSSs during peak systole from pulsatile PVAD flow could lead to blood damage. Both flow modes lead to similar regions prone to intimal hyperplasia (IH) resulting from low time-averaged WSS (TAWSS) and high oscillatory shear index (OSI). PMID:26643646

Optics based signal processing methods for intraoperative blood vessel detection and quantification in real time (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chaturvedi, Amal; Shukair, Shetha A.; Le Rolland, Paul; Vijayvergia, Mayank; Subramanian, Hariharan; Gunn, Jonathan W.

2016-03-01

Minimally invasive operations require surgeons to make difficult cuts to blood vessels and other tissues with impaired tactile and visual feedback. This leads to inadvertent cuts to blood vessels hidden beneath tissue, causing serious health risks to patients and a non-reimbursable financial burden to hospitals. Intraoperative imaging technologies have been developed, but these expensive systems can be cumbersome and provide only a high-level view of blood vessel networks. In this research, we propose a lean reflectance-based system, comprised of a dual wavelength LED, photodiode, and novel signal processing algorithms for rapid vessel characterization. Since this system takes advantage of the inherent pulsatile light absorption characteristics of blood vessels, no contrast agent is required for its ability to detect the presence of a blood vessel buried deep inside any tissue type (up to a cm) in real time. Once a vessel is detected, the system is able to estimate the distance of the vessel from the probe and the diameter size of the vessel (with a resolution of ~2mm), as well as delineate the type of tissue surrounding the vessel. The system is low-cost, functions in real-time, and could be mounted on already existing surgical tools, such as Kittner dissectors or laparoscopic suction irrigation cannulae. Having been successfully validated ex vivo, this technology will next be tested in a live porcine study and eventually in clinical trials.

Effect of centrifugal forces on formation of secondary flow structures in a 180-degree curved artery model under pulsatile inflow conditions

NASA Astrophysics Data System (ADS)

Callahan, Shannon; Sajjad, Roshan; Bulusu, Kartik V.; Plesniak, Michael W.

2013-11-01

An experimental investigation of secondary flow structures within a 180-degree bent tube model of a curved artery was performed using phase-averaged, two-component, two-dimensional, particle image velocimetry (2C-2D PIV) under pulsatile inflow conditions. Pulsatile waveforms ranging from simple sinusoidal to physiological inflows were supplied. We developed a novel continuous wavelet transform algorithm (PIVlet 1.2) and applied it to vorticity fields for coherent secondary flow structure detection. Regime maps of secondary flow structures revealed new, deceleration-phase-dependent flow morphologies. The temporal instances where streamwise centrifugal forces dominated were associated with large-scale coherent structures, such as deformed Dean-, Lyne- and Wall-type (D-L-W) vortical structures. Magnitudes of streamwise and cross-stream centrifugal forces tend to balance during deceleration phases. Deceleration events were also associated with spatial reorganization and asymmetry in large-scale D-L-W secondary flow structures. Hence, the interaction between streamwise and cross-stream centrifugal forces that affects secondary flow morphologies is explained using a ``residual force'' parameter i.e., the difference in magnitudes of these forces. Supported by the NSF Grant No. CBET- 0828903 and GW Center for Biomimetics and Bioinspired Engineering.

Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect.

PubMed

Schnerr, Roald S; Jansen, Jacobus F A; Uludag, Kamil; Hofman, Paul A M; Wildberger, Joachim E; van Oostenbrugge, Robert J; Backes, Walter H

2017-01-01

Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.

An experimental investigation of velocity fields in divergent glottal models of the human vocal tract

NASA Astrophysics Data System (ADS)

Erath, Byron D.; Plesniak, Michael W.

2005-09-01

In speech, sound production arises from fluid-structure interactions within the larynx as well as viscous flow phenomena that is most likely to occur during the divergent orientation of the vocal folds. Of particular interest are the flow mechanisms that influence the location of flow separation points on the vocal folds walls. Physiologically scaled pulsatile flow fields in 7.5 times real size static divergent glottal models were investigated. Three divergence angles were investigated using phase-averaged particle image velocimetry (PIV). The pulsatile glottal jet exhibited a bi-modal stability toward both glottal walls, although there was a significant amount of variance in the angle the jet deflected from the midline. The attachment of the Coanda effect to the glottal model walls occurred when the pulsatile velocity was a maximum, and the acceleration of the waveform was zero. The location of the separation and reattachment points of the flow from the glottal models was a function of the velocity waveform and divergence angle. Acoustic analogies show that a dipole sound source contribution arising from the fluid interaction (Coanda jet) with the vocal fold walls is expected. [Work funded by NIH Grant RO1 DC03577.

Surgical treatment for the aberrant internal carotid artery in the middle ear with pulsatile tinnitus.

PubMed

Honkura, Yohei; Hidaka, Hiroshi; Ohta, Jun; Gorai, Shigeki; Katori, Yukio; Kobayashi, Toshimitsu

2014-04-01

Many previous reports have indicated that pulsatile tinnitus caused by an aberrant internal carotid artery (ICA) should not be treated surgically because of the risk of infection or aneurysm formation. We herein describe a case of aberrant ICA treated by middle ear surgery for which we introduced a novel approach. An 84-year-old man was presented with a one-year history of tinnitus in his right ear. Otoscopic examination demonstrated a whitish mass in the antero-inferior quadrant of the tympanic membrane associated with rhythmic pulsation. Images obtained by CT, MRI and MRA revealed protrusion of the ICA into the tympanic cavity, making contact with the tympanic membrane. Surgery to separate the tympanic membrane from the ICA was performed in order to relieve the pulsatile tinnitus. After the operation, the patient's aural activity was preserved and the tinnitus did not recur within a follow-up period of one year. In the present case, delicate middle ear surgery was effective for relief of the tinnitus. When treating patients with aberrant IAC showing features similar to the present case, the surgical approach we have described is worth attempting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Imaging prevalence of sigmoid sinus dehiscence among patients with and without pulsatile tinnitus.

PubMed

Schoeff, Stephen; Nicholas, Brian; Mukherjee, Sugoto; Kesser, Bradley W

2014-05-01

Define the radiographic prevalence of sigmoid sinus diverticulum or dehiscence (SSDD) in patients with and without pulsatile tinnitus (PT). Case series with chart review. Tertiary care university medical center. Patients imaged between January 1, 2003, and December 31, 2012. Two groups were evaluated for SSDD. The first ("PT") included patients whose radiology report indicated a clinical history of PT (n = 37 symptomatic ears in 30 patients). The second ("non-PT") included all patients undergoing temporal bone high resolution CT (HRCT) between November 2011 and November 2012 (n = 308 ears in 164 patients) for reasons other than pulsatile tinnitus. Primary outcome measure was the radiographic presence of SSDD. Covariates including age, gender, body mass index (BMI), and audiometric data were analyzed by independent t tests and Fisher's exact test. Within the PT group, SSDD was identified in 24% of ears (9/37) and 23% of patients (7/30); all SSDD patients were female (P = .024). Patients with SSDD were significantly younger (P = .037). SSDD more frequently caused objective tinnitus (P = .016). There was no difference in average BMI between those with and those without SSDD. In the non-PT group, SSDD was identified in 2 (both female) of 164 patients (1.2%; 0.6% of ears). The difference in SSDD prevalence between groups was significant (P < .0001). The prevalence of SSDD in patients with PT was 23%. Among patients with PT, those with SSDD were younger, exclusively female, and presented with objective tinnitus. The prevalence of SSDD among asymptomatic patients in 1 year was 1.2%.

Fluid-structure interaction for nonlinear response of shells conveying pulsatile flow

NASA Astrophysics Data System (ADS)

Tubaldi, Eleonora; Amabili, Marco; Païdoussis, Michael P.

2016-06-01

Circular cylindrical shells with flexible boundary conditions conveying pulsatile flow and subjected to pulsatile pressure are investigated. The equations of motion are obtained based on the nonlinear Novozhilov shell theory via Lagrangian approach. The flow is set in motion by a pulsatile pressure gradient. The fluid is modeled as a Newtonian pulsatile flow and it is formulated using a hybrid model that contains the unsteady effects obtained from the linear potential flow theory and the pulsatile viscous effects obtained from the unsteady time-averaged Navier-Stokes equations. A numerical bifurcation analysis employs a refined reduced order model to investigate the dynamic behavior. The case of shells containing quiescent fluid subjected to the action of a pulsatile transmural pressure is also addressed. Geometrically nonlinear vibration response to pulsatile flow and transmural pressure are here presented via frequency-response curves and time histories. The vibrations involving both a driven mode and a companion mode, which appear due to the axial symmetry, are also investigated. This theoretical framework represents a pioneering study that could be of great interest for biomedical applications. In particular, in the future, a more refined model of the one here presented will possibly be applied to reproduce the dynamic behavior of vascular prostheses used for repairing and replacing damaged and diseased thoracic aorta in cases of aneurysm, dissection or coarctation. For this purpose, a pulsatile time-dependent blood flow model is here considered by applying physiological waveforms of velocity and pressure during the heart beating period. This study provides, for the first time in literature, a fully coupled fluid-structure interaction model with deep insights in the nonlinear vibrations of circular cylindrical shells subjected to pulsatile pressure and pulsatile flow.

Passive optical coherence elastography using a time-reversal approach (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nguyen, Thu-Mai; Zorgani, Ali; Fink, Mathias; Catheline, Stefan; Boccara, A. Claude

2017-02-01

Background and motivation - Conventional Optical Coherence Elastography (OCE) methods consist in launching controlled shear waves in tissues, and measuring their propagation speed using an ultrafast imaging system. However, the use of external shear sources limits transfer to clinical practice, especially for ophthalmic applications. Here, we propose a totally passive OCE method for ocular tissues based on time-reversal of the natural vibrations. Methods - Experiments were first conducted on a tissue-mimicking phantom containing a stiff inclusion. Pulsatile motions were reproduced by stimulating the phantom surface with two piezoelectric actuators excited asynchronously at low frequencies (50-500 Hz). The resulting random displacements were tracked at 190 frames/sec using spectral-domain optical coherence tomography (SD-OCT), with a 10x5µm² resolution over a 3x2mm² field-of-view (lateral x depth). The shear wavefield was numerically refocused (i.e. time-reversed) at each pixel using noise-correlation algorithms. The focal spot size yields the shear wavelength. Results were validated by comparison with shear wave speed measurements obtained from conventional active OCE. In vivo tests were then conducted on anesthetized rats. Results - The stiff inclusion of the phantom was delineated on the wavelength map with a wavelength ratio between the inclusion and the background (1.6) consistent with the speed ratio (1.7). This validates the wavelength measurements. In vivo, natural shear waves were detected in the eye and wavelength maps of the anterior segment showed a clear elastic contrast between the cornea, the sclera and the iris. Conclusion - We validated the time-reversal approach for passive elastography using SD-OCT imaging at low frame-rate. This method could accelerate the clinical transfer of ocular elastography.

Intraoperative laser speckle contrast imaging with retrospective motion correction for quantitative assessment of cerebral blood flow

PubMed Central

Richards, Lisa M.; Towle, Erica L.; Fox, Douglas J.; Dunn, Andrew K.

2014-01-01

Abstract. Although multiple intraoperative cerebral blood flow (CBF) monitoring techniques are currently available, a quantitative method that allows for continuous monitoring and that can be easily integrated into the surgical workflow is still needed. Laser speckle contrast imaging (LSCI) is an optical imaging technique with a high spatiotemporal resolution that has been recently demonstrated as feasible and effective for intraoperative monitoring of CBF during neurosurgical procedures. This study demonstrates the impact of retrospective motion correction on the quantitative analysis of intraoperatively acquired LSCI images. LSCI images were acquired through a surgical microscope during brain tumor resection procedures from 10 patients under baseline conditions and after a cortical stimulation in three of those patients. The patient’s electrocardiogram (ECG) was recorded during acquisition for postprocess correction of pulsatile artifacts. Automatic image registration was retrospectively performed to correct for tissue motion artifacts, and the performance of rigid and nonrigid transformations was compared. In baseline cases, the original images had 25%±27% noise across 16 regions of interest (ROIs). ECG filtering moderately reduced the noise to 20%±21%, while image registration resulted in a further noise reduction of 15%±4%. Combined ECG filtering and image registration significantly reduced the noise to 6.2%±2.6% (p<0.05). Using the combined motion correction, accuracy and sensitivity to small changes in CBF were improved in cortical stimulation cases. There was also excellent agreement between rigid and nonrigid registration methods (15/16 ROIs with <3% difference). Results from this study demonstrate the importance of motion correction for improved visualization of CBF changes in clinical LSCI images. PMID:26157974

Pulsatile tinnitus as the presenting symptom in a patient with posterior reversible encephalopathy syndrome.

PubMed

Mohammed, Hassan; Briggs, Mayen; Phillips, John

2016-09-01

We present a case of posterior reversible encephalopathy syndrome (PRES) presenting with pulsatile tinnitus. We highlight the significance of a detailed neurological and cardiovascular assessment including the measurement of blood pressure in patients presenting with pulsatile tinnitus. Case presentation and literature review. One patient with undiagnosed PRES, who presented to our ear, nose and throat surgery department with pulsatile tinnitus is discussed. Symptoms, signs, investigations and treatments are presented. A literature review is also included. Pulsatile tinnitus can be the presenting symptom of neurovascular disorders, some of which might have serious sequelae if not treated promptly. Detailed neurological and cardiovascular history is recommended in addition to radiological investigations in patients presenting with pulsatile tinnitus.

Abnormal regional activity and functional connectivity in resting-state brain networks associated with etiology confirmed unilateral pulsatile tinnitus in the early stage of disease.

PubMed

Lv, Han; Zhao, Pengfei; Liu, Zhaohui; Li, Rui; Zhang, Ling; Wang, Peng; Yan, Fei; Liu, Liheng; Wang, Guopeng; Zeng, Rong; Li, Ting; Dong, Cheng; Gong, Shusheng; Wang, Zhenchang

2017-03-01

Abnormal neural activities can be revealed by resting-state functional magnetic resonance imaging (rs-fMRI) using analyses of the regional activity and functional connectivity (FC) of the networks in the brain. This study was designed to demonstrate the functional network alterations in the patients with pulsatile tinnitus (PT). In this study, we recruited 45 patients with unilateral PT in the early stage of disease (less than 48 months of disease duration) and 45 normal controls. We used regional homogeneity (ReHo) and seed-based FC computational methods to reveal resting-state brain activity features associated with pulsatile tinnitus. Compared with healthy controls, PT patients showed regional abnormalities mainly in the left middle occipital gyrus (MOG), posterior cingulate gyrus (PCC), precuneus and right anterior insula (AI). When these regions were defined as seeds, we demonstrated widespread modification of interaction between the auditory and non-auditory networks. The auditory network was positively connected with the cognitive control network (CCN), which may associate with tinnitus related distress. Both altered regional activity and changed FC were found in the visual network. The modification of interactions of higher order networks were mainly found in the DMN, CCN and limbic networks. Functional connectivity between the left MOG and left parahippocampal gyrus could also be an index to reflect the disease duration. This study helped us gain a better understanding of the characteristics of neural network modifications in patients with pulsatile tinnitus. Copyright © 2017 Elsevier B.V. All rights reserved.

Pulsatile release of biomolecules from polydimethylsiloxane (PDMS) chips with hydrolytically degradable seals.

PubMed

Intra, Janjira; Glasgow, Justin M; Mai, Hoang Q; Salem, Aliasger K

2008-05-08

We demonstrate, for the first time, a robust novel polydimethylsiloxane (PDMS) chip that can provide controlled pulsatile release of DNA based molecules, proteins and oligonucleotides without external stimuli or triggers. The PDMS chip with arrays of wells was constructed by replica molding. Poly(lactic acid-co-glycolic acid) (PLGA) polymer films of varying composition and thickness were used as seals to the wells. The composition, molecular weight and thickness of the PLGA films were all parameters used to control the degradation rate of the seals and therefore the release profiles. Degradation of the films followed the PLGA composition order of 50:50 PLGA>75:25 PLGA>85:15 PLGA at all time-points beyond week 1. Scanning electron microscopy images showed that films were initially smooth, became porous and ruptured as the osmotic pressure pushed the degrading PLGA film outwards. Pulsatile release of DNA was controlled by the composition and thickness of the PLGA used to seal the well. Transfection experiments in a model Human Embryonic Kidney 293 (HEK293) cell line showed that plasmid DNA loaded in the wells was functional after pulsatile release in comparison to control plasmid DNA at all time-points. Thicker films degraded faster than thinner films and could be used to fine-tune the release of DNA over day length periods. Finally the PDMS chip was shown to provide repeated sequential release of CpG oligonucleotides and a model antigen, Ovalbumin (OVA), indicating significant potential for this device for vaccinations or applications that require defined complex release patterns of a variety of chemicals, drugs and biomolecules.

Clinical spectrum of patients with erosion of the inner ear by jugular bulb abnormalities.

PubMed

Friedmann, David R; Le, B Thuy; Pramanik, Bidyut K; Lalwani, Anil K

2010-02-01

Anatomic variants of the jugular bulb (JB) are common; however, abnormalities such as large high riding JB and JB diverticulum (JBD) are uncommon. Rarely, the abnormal JB may erode into the inner ear. The goal of our study is to report a large series of patients with symptomatic JB erosion into the inner ear. Retrospective review in an academic medical center. Eleven patients with JB abnormality eroding into the inner ear were identified on computed tomography (CT) scan of the temporal bone. Age at presentation was from 5 years to 82 years with six males and five females. The large JB or JBD eroded into the vestibular aqueduct (n = 9) or the posterior semicircular canal (n = 4). The official radiology report usually identified the JB abnormality; however, erosion into these structures by the JB was not mentioned in all but one case. All patients were symptomatic with five having conductive hearing loss (CHL) and three complaining of pulsatile tinnitus. Those with pulsatile tinnitus and four of five with CHL had erosion into the vestibular aqueduct. Vestibular evoked myogenic potential (VEMP) findings in three of six patients were consistent with dehiscence of the inner ear. High riding large JB or JBD can erode into the inner ear and may be associated with CHL and/or pulsatile tinnitus. CT scan is diagnostic and should be examined specifically for these lesions. As patients with pulsatile tinnitus may initially undergo a magnetic resonance imaging scan, identification of JB abnormality should prompt CT scan or VEMP testing to evaluate for inner ear erosion.

Choroidal microcirculation in patients with rotary cardiac assist device.

PubMed

Polska, Elzbieta; Schima, Heinrich; Wieselthaler, Georg; Schmetterer, Leopold

2007-06-01

In recent years, fully implanted rotary blood pumps have been used for long-term cardiac assist in patients with end-stage heart failure. With these pumps, the pulsatility of arterial blood flow and arterial pressure pulse is considerably reduced. Effects on end-organ perfusion, particularly microcirculation, have been assessed. The ocular choroid offers a unique opportunity to study the pulsatile component of blood flow by measurement of fundus pulsation amplitude (FPA) as well as the microcirculation by laser Doppler flowmetry. Both techniques were applied in three male patients with rotary pumps (MicroMed DeBakey VAD), in whom pump velocity was adjusted to four levels of flow between individual minimal need and maximal support. In addition, blood flow velocities in the ophthalmic artery (peak, end-diastolic and mean flow velocity--PSV, EDV and MFV, respectively) were measured using color Doppler imaging. Systolic blood pressure increased by 6 to 22 mm Hg with increasing support. At maximal support FPA was reduced by -60% to -52% as compared with minimal pump support. Blood flow in the choroidal microvasculature, however, did not show relevant changes. A reduction in PSV (-31%, range -47% to -21%) and a pronounced rise in EDV (+93%, range +28% to +147%) was observed, whereas MFV was independent of pump flow. Our data indicate that mean choroidal blood flow is maintained when pump support is varied within therapeutic values, whereas the ratio of pulsatile to non-pulsatile choroidal flow changes. This study shows that, in patients with ventricular assist devices, a normal perfusion rate in the ocular microcirculation is maintained over a wide range of support conditions.

Increasing awareness with recognition of pulsatile tinnitus for nurse practitioners in the primary care setting: A case study.

PubMed

Vecchiarelli, Kelly; Amar, Arun Paul; Emanuele, Donna

2017-09-01

Pulsatile tinnitus is a whooshing sound heard synchronous with the heartbeat. It is an uncommon symptom affecting fewer than 10% of patients with tinnitus. It often goes unrecognized in the primary care setting. Failure to recognize this symptom can result in a missed or delayed diagnosis of a potentially life-threatening condition known as a dural arteriovenous fistula. The purpose of this case study is to provide a structured approach to the identification of pulsatile tinnitus and provide management recommendations. A case study and review of pertinent literature. Pulsatile tinnitus usually has a vascular treatable cause. A comprehensive history and physical examination will alert the nurse practitioner (NP) when pulsatile tinnitus is present. Auscultation in specific areas of the head can detect audible or objective pulsatile tinnitus. Pulsatile tinnitus that is audible to the examiner is an urgent medical condition requiring immediate consultation and referral. Knowledge of pulsatile tinnitus and awareness of this often treatable condition directs the NP to perform a detailed assessment when patients present with tinnitus, directs appropriate referral for care and treatment, and can reduce the risk of delayed or missed diagnosis. ©2017 American Association of Nurse Practitioners.

Method and Apparatus for Non-Invasive Measurement of Changes in Intracranial Pressure

NASA Technical Reports Server (NTRS)

Yost, William T. (Inventor); Cantrell, John H., Jr. (Inventor)

2004-01-01

A method and apparatus for measuring intracranial pressure. In one embodiment, the method comprises the steps of generating an information signal that comprises components (e.g., pulsatile changes and slow changes) that are related to intracranial pressure and blood pressure, generating a reference signal comprising pulsatile components that are solely related to blood pressure, processing the information and reference signals to determine the pulsatile components of the information signal that have generally the same phase as the pulsatile components of the reference signal, and removing from the information signal the pulsatile components determined to have generally the same phase as the pulsatile components of the reference signal so as to provide a data signal having components wherein substantially all of the components are related to intracranial pressure.

Temporally resolved electrocardiogram-triggered diffusion-weighted imaging of the human kidney: correlation between intravoxel incoherent motion parameters and renal blood flow at different time points of the cardiac cycle.

PubMed

Wittsack, Hans-Jörg; Lanzman, Rotem S; Quentin, Michael; Kuhlemann, Julia; Klasen, Janina; Pentang, Gael; Riegger, Caroline; Antoch, Gerald; Blondin, Dirk

2012-04-01

To evaluate the influence of pulsatile blood flow on apparent diffusion coefficients (ADC) and the fraction of pseudodiffusion (F(P)) in the human kidney. The kidneys of 6 healthy volunteers were examined by a 3-T magnetic resonance scanner. Electrocardiogram (ECG)-gated and respiratory-triggered diffusion-weighted imaging (DWI) and phase-contrast flow measurements were performed. Flow imaging of renal arteries was carried out to quantify the dependence of renal blood flow on the cardiac cycle. ECG-triggered DWI was acquired in the coronal plane with 16 b values in the range of 0 s/mm(2) and 750 s/mm(2) at the time of minimum (MIN) (20 milliseconds after R wave) and maximum renal blood flow (MAX) (197 ± 24 milliseconds after R wave). The diffusion coefficients were calculated using the monoexponential approach as well as the biexponential intravoxel incoherent motion model and correlated to phase-contrast flow measurements. Flow imaging showed pulsatile renal blood flow depending on the cardiac cycle. The mean flow velocity at MIN was 45 cm/s as compared with 61 cm/s at MAX. F(p) at MIN (0.29) was significantly lower than at MAX (0.40) (P = 0.001). Similarly, ADC(mono), derived from the monoexponential model, also showed a significant difference (P < 0.001) between MIN (ADC(mono) = 2.14 ± 0.08 × 10(-3) mm(2)/s) and MAX (ADC(mono) = 2.37 ± 0.04 × 10(-3) mm(2)/s). The correlation between renal blood flow and F(p) (r = 0.85) as well as ADC(mono) (r = 0.67) was statistically significant. Temporally resolved ECG-gated DWI enables for the determination of the diffusion coefficients at different time points of the cardiac cycle. ADC(mono) and FP vary significantly among acquisitions at minimum (diastole) and maximum (systole) renal blood flow. Temporally resolved ECG-gated DWI might therefore serve as a novel technique for the assessment of pulsatility in the human kidney.

Optimal endothelialisation of a new compliant poly(carbonate-urea)urethane vascular graft with effect of physiological shear stress.

PubMed

Salacinski, H J; Tai, N R; Punshon, G; Giudiceandrea, A; Hamilton, G; Seifalian, A M

2000-10-01

to define the optimal seeding conditions of a new stress free poly(carbonate-urea)urethane (CPU) graft with compliance similar to that of human artery with honeycomb structure engineered during the manufacturing process to enhance adhesion and growth of endothelial cells. (111)Indium-oxine radiolabeled human umbilical vein endothelial cells (HUVEC) were seeded onto CPU grafts at (a) concentrations from 2-24x10(5)cells/cm(2)and (b) incubated for 0.5, 1, 2, 4 and 6 h. Following incubation, graft segments were subjected to three washing/gamma counting procedures and scanning electron microscopy (SEM). Cell viability was measured using a modified Alamar blue(TM)assay. To test physiological retention a pulsatile flow phantom was used to subject optimally seeded (16x10(5), 4 h) CPU grafts to arterial shear stress for 6 h with real time acquisition of scintigraphic images of seeded grafts using a nuclear medicine gamma camera system. the seeding efficiency of 54+/-13% post three washes was achieved using 16x10(5)cells/cm(2). Similarly in SEM micrographs a seeding density of 16x10(5)cells/cm(2)resulted in a confluent monolayer. Seeded CPU segments incubated for 4 h exhibited significantly higher resistance to wash-off than segments incubated for 30 min (p <0.05). Exposure of seeded grafts to pulsatile shear stress resulted in some cell loss with 67+/-3% of cells adherent following 6 h of perfusion with ongoing metabolic activity. Thus, optimal conditions were 16x10(5)cells/cm(2)at 4 h. the optimal seeding conditions have been defined for "tissue-engineered" vascular graft which allow complete endothelialisation and high cell-to-substrate strength that resists hydrodynamic stress. Copyright 2000 Harcourt Publishers Ltd.

Sigmoid Sinus Diverticulum, Dehiscence, and Venous Sinus Stenosis: Potential Causes of Pulsatile Tinnitus in Patients with Idiopathic Intracranial Hypertension?

PubMed

Lansley, J A; Tucker, W; Eriksen, M R; Riordan-Eva, P; Connor, S E J

2017-09-01

Pulsatile tinnitus is experienced by most patients with idiopathic intracranial hypertension. The pathophysiology remains uncertain; however, transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence have been proposed as potential etiologies. We aimed to determine whether the prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence was increased in patients with idiopathic intracranial hypertension and pulsatile tinnitus relative to those without pulsatile tinnitus and a control group. CT vascular studies of patients with idiopathic intracranial hypertension with pulsatile tinnitus ( n = 42), without pulsatile tinnitus ( n = 37), and controls ( n = 75) were independently reviewed for the presence of severe transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence according to published criteria. The prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence in patients with idiopathic intracranial hypertension with pulsatile tinnitus was compared with that in the nonpulsatile tinnitus idiopathic intracranial hypertension group and the control group. Further comparisons included differing degrees of transverse sinus stenosis (50% and 75%), laterality of transverse sinus stenosis/sigmoid sinus diverticulum/dehiscence, and ipsilateral transverse sinus stenosis combined with sigmoid sinus diverticulum/dehiscence. Severe bilateral transverse sinus stenoses were more frequent in patients with idiopathic intracranial hypertension than in controls ( P < .001), but there was no significant association between transverse sinus stenosis and pulsatile tinnitus within the idiopathic intracranial hypertension group. Sigmoid sinus dehiscence (right- or left-sided) was also more common in patients with idiopathic intracranial hypertension compared with controls ( P = .01), but there was no significant association with pulsatile tinnitus within the idiopathic intracranial hypertension group. While our data corroborate previous studies demonstrating increased prevalence of sigmoid sinus diverticulum/dehiscence and transverse sinus stenosis in idiopathic intracranial hypertension, we did not establish an increased prevalence in patients with idiopathic intracranial hypertension with pulsatile tinnitus compared with those without. It is therefore unlikely that these entities represent a direct structural correlate of pulsatile tinnitus in patients with idiopathic intracranial hypertension. © 2017 by American Journal of Neuroradiology.

Optimum Heart Rate to Minimize Pulsatile External Cardiac Power

NASA Astrophysics Data System (ADS)

Pahlevan, Niema; Gharib, Morteza

2011-11-01

The workload on the left ventricle is composed of steady and pulsatile components. Clinical investigations have confirmed that an abnormal pulsatile load plays an important role in the pathogenesis of left ventricular hypertrophy (LVH) and progression of LVH to congestive heart failure (CHF). The pulsatile load is the result of the complex dynamics of wave propagation and reflection in the compliant arterial vasculature. We hypothesize that aortic waves can be optimized to reduce the left ventricular (LV) pulsatile load. We used an in-vitro experimental approach to investigate our hypothesis. A unique hydraulic model was used for in-vitro experiments. This model has physical and dynamical properties similar to the heart-aorta system. Different compliant models of the artificial aorta were used to test the hypothesis under various aortic rigidities. Our results indicate that: i) there is an optimum heart rate that minimizes LV pulsatile power (this is in agreement with our previous computational study); ii) introducing an extra reflection site at the specific location along the aorta creates constructive wave conditions that reduce the LV pulsatile power.

Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review.

PubMed

Pandit, Vinay; Kumar, Ajay; Ashawat, Mahendra S; Verma, Chander P; Kumar, Pravin

2017-01-01

Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dynamical systems characterization of inertial effects of fluid flow in a curved artery model under pulsatile flow forcing

NASA Astrophysics Data System (ADS)

Leggiero, Michael; Bulusu, Kartik V.; Plesniak, Michael W.

2013-11-01

The main objective of this study was to examine inertial effects in a 180-degree model of curved arteries under pulsatile inflow conditions. Two-component, two-dimensional particle image velocimetery (2C-2D PIV) data were acquired upstream of and at several cross-sectional locations in the curved artery model. A blood-analog fluid comprised of 71% saturated sodium iodide solution, 28% glycerol and 1% distilled water (by volume) was subjected to multi-harmonic pulsatile inflow functions. First, signal time-lag was quantified by cross-correlating the input (voltage-time) supplied to a programmable pump and the output PIV (flow rate-time) measurements. The experiment was then treated as a linear, time-invariant system, and frequency response was estimated for phase shifts across a certain spectrum. Input-output signal dissimilarities were attributable to intrinsic inertial effects of flow. By coupling pressure-time and upstream flow rate-time measurements, the experiment was modeled using system identification methods. Results elucidate the role of inertial effects in fluid flow velocity measurements and the effect of these delays on secondary flow structure detection in a curved artery model. Supported by the NSF Grant No. CBET- 0828903 and GW Center for Biomimetics and Bioinspired Engineering.

Smart Garment Fabrics to Enable Non-Contact Opto-Physiological Monitoring.

PubMed

Iakovlev, Dmitry; Hu, Sijung; Hassan, Harnani; Dwyer, Vincent; Ashayer-Soltani, Roya; Hunt, Chris; Shen, Jinsong

2018-03-29

Imaging photoplethysmography (iPPG) is an emerging technology used to assess microcirculation and cardiovascular signs by collecting backscattered light from illuminated tissue using optical imaging sensors. The aim of this study was to study how effective smart garment fabrics could be capturing physiological signs in a non-contact mode. The present work demonstrates a feasible approach of, instead of using conventional high-power illumination sources, integrating a grid of surface-mounted light emitting diodes (LEDs) into cotton fabric to spotlight the region of interest (ROI). The green and the red LEDs (525 and 660 nm) placed on a small cotton substrate were used to locally illuminate palm skin in a dual-wavelength iPPG setup, where the backscattered light is transmitted to a remote image sensor through the garment fabric. The results show that the illuminations from both wavelength LEDs can be used to extract heart rate (HR) reaching an accuracy of 90% compared to a contact PPG probe. Stretching the fabric over the skin surface alters the morphology of iPPG signals, demonstrating a significantly higher pulsatile amplitude in both channels of green and red illuminations. The skin compression by the fabric could be potentially utilised to enhance the penetration of illumination into cutaneous microvascular beds. The outcome could lead a new avenue of non-contact opto-physiological monitoring and assessment with functional garment fabrics.

Mathematical Modeling of Ischemia-Reperfusion Injury and Postconditioning Therapy.

PubMed

Fong, D; Cummings, L J

2017-11-01

Reperfusion (restoration of blood flow) after a period of ischemia (interruption of blood flow) can paradoxically place tissues at risk of further injury: so-called ischemia-reperfusion injury or IR injury. Recent studies have shown that postconditioning (intermittent periods of further ischemia applied during reperfusion) can reduce IR injury. We develop a mathematical model to describe the reperfusion and postconditioning process following an ischemic insult, treating the blood vessel as a two-dimensional channel, lined with a monolayer of endothelial cells that interact (respiration and mechanotransduction) with the blood flow. We investigate how postconditioning affects the total cell density within the endothelial layer, by varying the frequency of the pulsatile flow and the oxygen concentration at the inflow boundary. We find that, in the scenarios we consider, the pulsatile flow should be of high frequency to minimize cellular damage, while oxygen concentration at the inflow boundary should be held constant, or subject to only low-frequency variations, to maximize cell proliferation.

Brain palpation from physiological vibrations using MRI.

PubMed

Zorgani, Ali; Souchon, Rémi; Dinh, Au-Hoang; Chapelon, Jean-Yves; Ménager, Jean-Michel; Lounis, Samir; Rouvière, Olivier; Catheline, Stefan

2015-10-20

We present a magnetic resonance elastography approach for tissue characterization that is inspired by seismic noise correlation and time reversal. The idea consists of extracting the elasticity from the natural shear waves in living tissues that are caused by cardiac motion, blood pulsatility, and any muscle activity. In contrast to other magnetic resonance elastography techniques, this noise-based approach is, thus, passive and broadband and does not need any synchronization with sources. The experimental demonstration is conducted in a calibrated phantom and in vivo in the brain of two healthy volunteers. Potential applications of this "brain palpation" approach for characterizing brain anomalies and diseases are foreseen.

Enhancement of Arterial Pressure Pulsatility by Controlling Continuous-Flow Left Ventricular Assist Device Flow Rate in Mock Circulatory System.

PubMed

Bozkurt, Selim; van de Vosse, Frans N; Rutten, Marcel C M

Continuous-flow left ventricular assist devices (CF-LVADs) generally operate at a constant speed, which reduces pulsatility in the arteries and may lead to complications such as functional changes in the vascular system, gastrointestinal bleeding, or both. The purpose of this study is to increase the arterial pulse pressure and pulsatility by controlling the CF-LVAD flow rate. A MicroMed DeBakey pump was used as the CF-LVAD. A model simulating the flow rate through the aortic valve was used as a reference model to drive the pump. A mock circulation containing two synchronized servomotor-operated piston pumps acting as left and right ventricles was used as a circulatory system. Proportional-integral control was used as the control method. First, the CF-LVAD was operated at a constant speed. With pulsatile-speed CF-LVAD assistance, the pump was driven such that the same mean pump output was generated. Continuous and pulsatile-speed CF-LVAD assistance provided the same mean arterial pressure and flow rate, while the index of pulsatility increased significantly for both arterial pressure and pump flow rate signals under pulsatile speed pump support. This study shows the possibility of improving the pulsatility of CF-LVAD support by regulating pump speed over a cardiac cycle without reducing the overall level of support.

Assessment of Parylene C Thin Films for Heart Valve Tissue Engineering

PubMed Central

Marei, Isra; Chester, Adrian; Carubelli, Ivan; Prodromakis, Themistoklis; Trantidou, Tatiana

2015-01-01

Background: Scaffolds are a key component of tissue-engineered heart valves (TEHVs). Several approaches had been adopted in the design of scaffolds using both natural and synthetic resources. We have investigated the suitability of parylene C (PC), a vapor deposited polymeric material, for the use as a scaffold in TEHV. Aims: To evaluate the adsorption of extracellular matrix components onto plasma-activated PC and study the biocompatibility of PC by measuring cellular adhesion, viability, apoptosis, and phenotypic expression of valve endothelial and interstitial cells. Finally, the mechanical properties of PC were compared with those of native aortic valve cusp tissue. Methods: PC slides were plasma activated and then coated with gelatin, type I collagen, or fibronectin. Porcine pulmonary valve endothelial and interstitial cells were then grown on plasma oxidized PC with different types of coatings and their adhesion was observed after 20 h of incubation. Cell viability was tested using the MTS assay, and apoptosis was estimated using TUNEL staining. The mechanical properties of PC and valve tissue were measured using a Bose Mechanical Tester. Finally, cell-seeded PC films were exposed to pulsatile pressure and aortic shear stress, respectively, to test their durability in a dynamic environment. Results: Our findings show that collagen and fibronectin could bind to plasma oxidized PC. Both valve endothelial and interstitial cells adhered to protein-coated ECM. PC had a profile of mechanical stiffness and ultimate tensile strength that were comparable with or in excess of those seen in porcine aortic valve cusps. Cells were still attached to PC films after 3 days of exposure to up to 50 mmHg pulsatile pressure or aortic levels of shear stress. Conclusion: PC is a promising candidate for use as a scaffold in tissue engineering heart valves. Additional studies are required to determine both the durability and long-term performance of cell-seeded PC when in a similar hemodynamic environment to that of the aortic valve. PMID:26101808

Current status and approaches to developing press-coated chronodelivery drug systems.

PubMed

Lin, Shan-Yang; Kawashima, Yoshiaki

2012-02-10

The past several decades have seen the development of many controlled-release preparations featuring constant release rates to maintain drug concentrations in the human body, regardless of the patient's physiological condition. However, long-term constant drug concentrations in the blood and tissue can cause problems such as resistance, tolerability, and drug side effects. People vary considerably in their physiological and biochemical conditions during any 24 h period, due to the circadian rhythm, and thus, the constant delivery of a drug into the body seems both unnecessary and undesirable. If the drug release profile mimics a living system's pulsatile hormone secretion, then it may improve drug efficacy, and reduce the toxicity of a specific drug administration schedule. Medication and treatments provided according to the body's circadian rhythms will result in better outcomes. This may be provided by a chronopharmaceutical dosage regimen with pulsatile release that matches the circadian rhythm resulting from a disease state, so optimizing the therapeutic effect while minimizing side effects. The press coating technique is a simple and unique technology used to provide tablets with a programmable lag phase, followed by a fast, or rate-controlled, drug release after administration. The technique offers many advantages, and no special coating solvent or coating equipment is required for manufacturing this type of tablet. The present review article introduces chronopharmaceutical press-coated products from a patient physiological needs perspective. The contents of this article include biological rhythms and pulsatile hormone secretion in humans, the reasons for using pulsatile drug delivery for disease treatment, recent chronopharmaceutical preparations appearing on the market, updated compilation of all research articles and press-coated delivery techniques, factors affecting the performance and drug release characteristics of press-coated delivery systems, and recent challenges for the press coating technique. We also provide a brief overview of press-coating approaches intended for chronotherapy. Copyright © 2011 Elsevier B.V. All rights reserved.

The behaviour of cow blastocyst in vitro: cinematographic and morphometric analysis.

PubMed Central

Massip, A; Mulnard, J; Vanderzwalmen, P; Hanzen, C; Ectors, F

1982-01-01

The behaviour of the cow blastocyst in vitro was studied by time-lapse cinematography and analysed by morphometry. Three types of behaviour were observed: continuous expansion followed by hatching; discontinuous expansion interrupted by few contractions and followed by hatching; discontinuous expansion interrupted by several rapid contractions without hatching. This demonstrated that the pulsatile activity of the blastocyst is not a necessary condition of hatching but also that only a moderate pulsatile activity is compatible with normal hatching. The time of hatching in vitro corresponded approximately with the time of zona loss in vivo (9-10 days). Rupture of the zona occurred at any point of the trophoblast layer. Hatching by herniation through a reduced opening of the zona was occasionally observed. The behavior of the embryos from a particular animal was very similar but differences were noted between embryos from different animals. Images Fig. 3 PMID:7076563

Lifelong Cyclic Mechanical Strain Promotes Large Elastic Artery Stiffening: Increased Pulse Pressure and Old Age-Related Organ Failure.

PubMed

Thorin-Trescases, Nathalie; Thorin, Eric

2016-05-01

The arterial wall is under a huge mechanical constraint imposed by the cardiac cycle that is bound to generate damage with time. Each heartbeat indeed imposes a pulsatile pressure that generates a vascular stretch. Lifetime accumulation of pulsatile stretches will eventually induce fatigue of the elastic large arterial walls, such as aortic and carotid artery walls, promoting their stiffening that will gradually perturb the normal blood flow and local pressure within the organs, and lead to organ failure. The augmented pulse pressure induced by arterial stiffening favours left ventricular hypertrophy because of the repeated extra work against stiff high-pressure arteries, and tissue damage as a result of excessive pulsatile pressure transmitted into the microcirculation, especially in low resistance/high-flow organs such as the brain and kidneys. Vascular aging is therefore characterized by the stiffening of large elastic arteries leading to a gradual increase in pulse pressure with age. In this review we focus on the effect of age-related stiffening of large elastic arteries. We report the clinical evidence linking arterial stiffness and organ failure and discuss the molecular pathways that are activated by the increase of mechanical stress in the wall. We also discuss the possible interventions that could limit arterial stiffening with age, such as regular aerobic exercise training, and some pharmacological approaches. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Demonstration of uneven distribution of intracranial pulsatility in hydrocephalus patients.

PubMed

Eide, Per K

2008-11-01

Data from intracranial pressure (ICP) recordings in patients with hydrocephalus were reviewed to determine whether intracranial pulsatility within the cerebrospinal fluid (CSF) of cerebral ventricles (ICP(LV)) may differ from that within the brain parenchyma (ICP(PAR)), and whether pulsatility may differ between noncommunicating ventricles. The authors retrieved data from recordings previously obtained in 7 patients with hydrocephalus (noncommunicating in 4 and communicating in 3) and shunt failure who received both an external ventricular drainage (EVD) and an ICP sensor as part of surveillance during intensive care. Simultaneous ICP(LV) and ICP(PAR) signals were available in 6 cases, and simultaneous signals from the lateral and fourth ventricles (ICP(LV) and ICP4V, respectively) were recorded in 1 case. The recordings with both signals were parsed into 6-second time windows. Pulsatility was characterized by the wave amplitude and rise time coefficient, and differences in pulsatility between the ICP(LV) and ICP(PAR) signals (6 cases) or ICP(LV) and ICP4V signals (1 case) were determined. There was uneven distribution of intracranial pulsatility in all 7 patients, shown as significantly elevated pulsatility (that is, higher wave amplitudes and rise time coefficients) within the ventricles (ICP(LV)) than within brain parenchyma (ICP(PAR)) in 6 patients, and significantly higher pulsatility in the fourth (ICP4V) than in the lateral (ICP(LV)) ventricles in 1 patient. Differences > or = 1 mm Hg in ICP wave amplitude were found in 0.5-100% (median 9.4%) of observations in the 7 patients (total number of 6-second time windows, 68,242). The present observations demonstrate uneven distribution of intracranial pulsatility in patients with hydrocephalus, higher pulse pressure amplitudes within the ventricular CSF (ICP(LV)) than within the brain parenchyma (ICP(PAR)). This may be one mechanism behind ventricular enlargement in hydrocephalus.

Feasibility of a nickel-metal hydride battery for totally implantable artificial hearts.

PubMed

Okamoto, E; Yoshida, T; Fujiyoshi, M; Shimanaka, M; Takeuchi, A; Mitamura, Y; Mikami, T

1996-01-01

An implantable rechargeable battery is one of the key technologies for totally implantable artificial hearts. The nickel-metal hydride (Ni-MH) battery is promising for its high energy density of 1.5-2.0 times that of a nickel-cadmium battery. In this study, the effects of pulsatile discharge loads on the operating time and cycle life of Ni-MH batteries at 39 degrees C were studied. Two battery cells (TH-3M, 1,200 mAh, phi 14.5 x 49 mm; Toshiba, Tokyo, Japan) in series were charge/discharge cycled at 39 degrees C using a charge current of 1CA (1,200 mA) and then were fully discharged to 1.0 V/cell under either pulsatile discharge loads, which mimicked a systole (1 A for 0.3 sec) and a diastole (0.4 A for 0.3 sec), or a non pulsatile discharge load equivalent to the average of the pulsatile loads (0.7 A). Each cycle life test was interrupted on the 482nd cycle under pulsatile load, and on the 423rd cycle under non pulsatile load, because of malfunction of each battery charger. The tests showed that the pulsatile discharge cells had significantly (p < 0.001) less operating time (74.0 +/- 7.15 min) throughout the test period (up to 482 days) compared to the cells under equivalent non pulsatile discharge loads (93.7 +/- 7.74 min). The pulsatile-discharged Ni-MH cells provide significantly less operating time than the constantly discharged cells; the Ni-MH battery has an operating time of over 78 min and a cycle life of almost 500 cycles at 39 degrees C. In conclusion, the Ni-MH battery is feasible as an implantable back-up battery for a totally implantable artificial heart system.

Three-dimensional constructive interference in steady-state magnetic resonance imaging in syringomyelia: advantages over conventional imaging.

PubMed

Roser, Florian; Ebner, Florian H; Danz, Søren; Riether, Felix; Ritz, Rainer; Dietz, Klaus; Naegele, Thomas; Tatagiba, Marcos S

2008-05-01

Neuroradiology has become indispensable in detecting the pathophysiology in syringomyelia. Constructive interference in steady-state (CISS) magnetic resonance (MR) imaging can provide superior contrast at the sub-arachnoid tissue borders. As this region is critical in preoperative evaluation, the authors hypothesized that CISS imaging would provide superior assessment of syrinx pathology and surgical planning. Based on records collected from a database of 130 patients with syringomyelia treated at the authors' institution, 59 patients were prospectively evaluated with complete neuroradiological examinations. In addition to routine acquisitions with FLAIR, T1- and T2-weighted, and contrast-enhanced MR imaging series, the authors obtained sagittal cardiac-gated sequences to visualize cerebrospinal fluid (CSF) pulsations and axial 3D CISS MR sequences to detect focal arachnoid webs. Statistical qualitative and quantitative evaluations of spinal cord/CSF contrast, spinal cord/CSF delineation, motion artifacts, and artifacts induced by pulsatile CSF flow were performed. The 3D CISS MR sequences demonstrated a contrast-to-noise ratio significantly better than any other routine imaging sequence (p < 0.001). Moreover, 3D CISS imaging can detect more subarachnoid webs and cavitations in the syrinx than T2-weighted MR imaging with less flow-void artifact. The limitation of 3D CISS imaging is a susceptibility to motion artifacts that can cause reduced spatial resolution. Lengthy acquisition times for axial segments can be reduced with multiplanar reconstruction of 3D CISS-generated sagittal images. Constructive interference in steady-state imaging is the MR sequence of choice in the preoperative evaluation of syringomyelia, allowing significantly higher detection rates of focal subarachnoid webs, whereas standard T2-weighted MR imaging shows turbulent CSF flow voids. Constructive interference in steady-state MR imaging enables the neurosurgeon to accurately identify cases requiring decompression for obstructed CSF. Motion artifacts can be eliminated with technical variations.

Lung protection in cardio-pulmonary bypass.

PubMed

Salameh, A; Greimann, W; Vollroth, M; Dhein, S; Bahramsoltani, M; Dahnert, I

2017-02-01

Since the invention of the heart-lung machine paediatric cardiac surgery developed rapidly. For correction of complex cardiac malformations the application of a cardio-pulmonary bypass (CPB) has become indispensable but possible negative effects of this technique should not be neglected. Especially, both bypassed organs i.e. heart and lung are not perfused during the procedure and therefore are threatened by ischemia and reperfusion injury. Additionally, CPB was developed with a non-pulsatile flow but there are clinical observations that pulsatile flow might be superior with improved patient outcomes. Thus, the aim of our study was to evaluate the effect of CPB on lung structure and to assess whether different flow modalities (pulsatile vs. non-pulsatile flow) or application of the antibiotic minocycline might be advantageous. Thirty five piglets of four weeks age were examined and divided into five experimental groups: control (no CPB) without or with minocycline, CPB (non-pulsatile flow) without or with minocycline and CPB with pulsatile flow. CPB was performed for 90 min followed by a 120 min reperfusion and recovery phase. Thereafter, adenosine triphosphate-content of lung biopsies and histology was carried out. We found that CPB was associated with a significant thickening of alveolar wall accompanied by an infiltration of neutrophil leucocytes. Moreover, markers for hypoxia, apoptosis, nitrosative stress, inflammation and DNA damage were significantly elevated after CPB. These cellular damages could be partially inhibited by minocycline or pulsatile flow. Both, minocycline and pulsatile flow attenuate lung damage after CPB.

The Influence of Different Operating Conditions on the Blood Damage of a Pulsatile Ventricular Assist Device.

PubMed

Xu, Zihao; Yang, Ming; Wang, Xianghui; Wang, Zhong

2015-01-01

Because of pulsatile blood flow's benefit for myocardial recovery, perfusion of coronary arteries and end organs, pulsatile ventricular assist devices (VADs) are still widely used as paracorporeal mechanical circulatory support devices in clinical applications, especially in pediatric heart failure patients. However, severe blood damage limits the VAD's service period. Besides optimizing the VAD geometry to reduce blood damage, the blood damage may also be decreased by changing the operating conditions. In this article, a pulsatile VAD was used to investigate the influence of operating conditions on its blood damage, including hemolysis, platelet activation, and platelet deposition. Three motion profiles of pusher plate (sine, cosine, and polynomial), three stroke volumes (ejection fractions) (56 ml [70%], 42 ml [52.5%], and 28 ml [35%]), three pulsatile rates (75, 100, and 150 bpm), and two assist modes (copulsation and counterpulsation) were implemented respectively in VAD fluid-structure interaction simulations to calculate blood damage. The blood damage indices indicate that cosine motion profile, higher ejection fraction, higher pulsatile rate, and counterpulsation can decrease platelet deposition whereas increase hemolysis and platelet activation, and vice versa. The results suggest that different operating conditions have different effects on pulsatile VAD's blood damage and may be beneficial to choose suitable operating condition to reduce blood damage in clinical applications.

Flow characteristics around a deformable stenosis under pulsatile flow condition

NASA Astrophysics Data System (ADS)

Choi, Woorak; Park, Jun Hong; Byeon, Hyeokjun; Lee, Sang Joon

2018-01-01

A specific portion of a vulnerable stenosis is deformed periodically under a pulsatile blood flow condition. Detailed analysis of such deformable stenosis is important because stenotic deformation can increase the likelihood of rupture, which may lead to sudden cardiac death or stroke. Various diagnostic indices have been developed for a nondeformable stenosis by using flow characteristics and resultant pressure drop across the stenosis. However, the effects of the stenotic deformation on the flow characteristics remain poorly understood. In this study, the flows around a deformable stenosis model and two different rigid stenosis models were investigated under a pulsatile flow condition. Particle image velocimetry was employed to measure flow structures around the three stenosis models. The deformable stenosis model was deformed to achieve high geometrical slope and height when the flow rate was increased. The deformation of the stenotic shape enhanced jet deflection toward the opposite vessel wall of the stenosis. The jet deflection in the deformable model increased the rate of jet velocity and turbulent kinetic energy (TKE) production as compared with those in the rigid models. The effect of stenotic deformation on the pulsating waveform related with the pressure drop was analyzed using the TKE production rate. The deformable stenosis model exhibited a phase delay of the peak point in the waveform. These results revealed the potential use of pressure drop waveform as a diagnostic index for deformable stenosis.

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device.

PubMed

Gohean, Jeffrey R; George, Mitchell J; Pate, Thomas D; Kurusz, Mark; Longoria, Raul G; Smalling, Richard W

2013-01-01

The purpose of this investigation is to use a computational model to compare a synchronized valveless pulsatile left ventricular assist device with continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate the support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous pulsatile valveless dual-piston positive displacement pump. These results were compared with measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared with the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device.

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device

PubMed Central

Gohean, Jeffrey R.; George, Mitchell J.; Pate, Thomas D.; Kurusz, Mark; Longoria, Raul G.; Smalling, Richard W.

2012-01-01

The purpose of this investigation is to utilize a computational model to compare a synchronized valveless pulsatile left ventricular assist device to continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous, pulsatile, valveless, dual piston positive displacement pump. These results were compared to measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared to the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device. PMID:23438771

Pulsatile support using a rotary left ventricular assist device with an electrocardiography-synchronized rotational speed control mode for tracking heart rate variability.

PubMed

Arakawa, Mamoru; Nishimura, Takashi; Takewa, Yoshiaki; Umeki, Akihide; Ando, Masahiko; Kishimoto, Yuichiro; Kishimoto, Satoru; Fujii, Yutaka; Date, Kazuma; Kyo, Shunei; Adachi, Hideo; Tatsumi, Eisuke

2016-06-01

We previously developed a novel control system for a continuous-flow left ventricular assist device (LVAD), the EVAHEART, and demonstrated that sufficient pulsatility can be created by increasing its rotational speed in the systolic phase (pulsatile mode) in a normal heart animal model. In the present study, we assessed this system in its reliability and ability to follow heart rate variability. We implanted an EVAHEART via left thoracotomy into five goats for the Study for Fixed Heart Rate with ventricular pacing at 80, 100, 120 and 140 beats/min and six goats for the Study for native heart rhythm. We tested three modes: the circuit clamp, the continuous mode and the pulsatile mode. In the pulsatile mode, rotational speed was increased during the initial 35 % of the RR interval by automatic control based on the electrocardiogram. Pulsatility was evaluated by pulse pressure and dP/dt max of aortic pressure. As a result, comparing the pulsatile mode with the continuous mode, the pulse pressure was 28.5 ± 5.7 vs. 20.3 ± 7.9 mmHg, mean dP/dt max was 775.0 ± 230.5 vs 442.4 ± 184.7 mmHg/s at 80 bpm in the study for fixed heart rate, respectively (P < 0.05). The system successfully determined the heart rate to be 94.6 % in native heart rhythm. Furthermore, pulse pressure was 41.5 ± 7.9 vs. 27.8 ± 5.6 mmHg, mean dP/dt max was 716.2 ± 133.9 vs 405.2 ± 86.0 mmHg/s, respectively (P < 0.01). In conclusion, our newly developed the pulsatile mode for continuous-flow LVADs reliably provided physiological pulsatility with following heart rate variability.

Induction of ovulation in clomiphene-resistant polycystic ovary syndrome with pulsatile GnRH.

PubMed

Tan, S L; Farhi, J; Homburg, R; Jacobs, H S

1996-08-01

To determine the efficacy of pulsatile GnRH alone and in combination with clomiphene citrate or gonadotropins in a stepwise approach for inducing ovulation in women with clomiphene-resistant polycystic ovary syndrome (PCOS). Eighty women with clomiphene-resistant anovulatory infertility and PCOS were given subcutaneous pulsatile GnRH (15 micrograms every 90 minutes) using a portable infusion pump. If no follicular development was seen, clomiphene citrate (100 mg/day for 5 days) was given concurrently with the hormone in the next cycle of treatment. Those who still failed to ovulate regularly were treated with combined pulsatile GnRH with intramuscular gonadotropins (one ampule per day for 5-7 days). RESULTS. Sixty-six of 131 (50%) pulsatile GnRH cycles, 94 of 142 (66%) pulsatile GnRH with clomiphene cycles, and 48 of 69 (70%) pulsatile GnRH with gonadotropin cycles were ovulatory. Monofollicular response (one follicle at least 14 mm on the day of ovulation) occurred in 80.6, 83.9, and 53.6% of cycles, and multifollicular response occurred in 4.8, 3.1, and 21.6% of cycles in the three groups, respectively. Mild ovarian hyperstimulation occurred in one of the 342 cycles. The cumulative conception rate was 30% after three cycles, 60% after six cycles, and 73% after nine cycles. The miscarriage rate was 22% (ten of 45 pregnancies), and 35 women (78%) had live births (33 singletons and two sets of twins). The use of subcutaneous pulsatile GnRH alone and in combination with clomiphene citrate or gonadotropins for induction of ovulation in clomiphene-resistant PCOS in a stepwise approach produces a high cumulative conception rate associated with a low rate of multiple pregnancy and ovarian hyperstimulation syndrome.

Stent-Assisted Coil Embolization of a Transverse-Sigmoid Sinus Diverticulum Presenting with Pulsatile Tinnitus.

PubMed

Li, Baomin; Lv, Xianli; Wu, Zhongxue; Cao, Xiangyu; Wang, Jun; Ge, Aili; Liu, Xinfeng; Li, Sheng

When tinnitus is pulse-synchronous, a vascular etiology is suggested. We present a case of persistent and troublesome pulsatile tinnitus caused by a transverse-sigmoid sinus diverticulum that was endovascularly treated with stent-assisted coiling. A 39-yearold woman presented with a 4-year history of progressive pulsatile tinnitus involving the right ear. Slight pulsatile bruit was heard on the right mastoid bone by auscultation. Cerebral angiography demonstrated a diverticulum of the transverse-sigmoid sinus. The procedure was performed with an 8F guiding catheter (Cordis, USA) catheterized into the right sigmoid sinus. The diverticulum was completely coiled following deployment of a 5.5 mm-50 mm Leo stent. This patient awakened without any neurological deficit and with immediate resolution of her tinnitus. This case report describes a stent-assisted coil embolization of venous sinus diverticulum, which provides immediate resolution of pulsatile tinnitus.

Photoplethysmography Signal Analysis for Optimal Region-of-Interest Determination in Video Imaging on a Built-In Smartphone under Different Conditions.

PubMed

Nam, Yunyoung; Nam, Yun-Cheol

2017-10-19

Smartphones and tablets are widely used in medical fields, which can improve healthcare and reduce healthcare costs. Many medical applications for smartphones and tablets have already been developed and widely used by both health professionals and patients. Specifically, video recordings of fingertips made using a smartphone camera contain a pulsatile component caused by the cardiac pulse equivalent to that present in a photoplethysmographic signal. By performing peak detection on the pulsatile signal, it is possible to estimate a continuous heart rate and a respiratory rate. To estimate the heart rate and respiratory rate accurately, which pixel regions of the color bands give the most optimal signal quality should be investigated. In this paper, we investigate signal quality to determine the best signal quality by the largest amplitude values for three different smartphones under different conditions. We conducted several experiments to obtain reliable PPG signals and compared the PPG signal strength in the three color bands when the flashlight was both on and off. We also evaluated the intensity changes of PPG signals obtained from the smartphones with motion artifacts and fingertip pressure force. Furthermore, we have compared the PSNR of PPG signals of the full-size images with that of the region of interests (ROIs).

Classification of Unsteady Flow Patterns in a Rotodynamic Blood Pump: Introduction of Non-Dimensional Regime Map.

PubMed

Shu, Fangjun; Vandenberghe, Stijn; Brackett, Jaclyn; Antaki, James F

2015-09-01

Rotodynamic blood pumps (also known as rotary or continuous flow blood pumps) are commonly evaluated in vitro under steady flow conditions. However, when these devices are used clinically as ventricular assist devices (VADs), the flow is pulsatile due to the contribution of the native heart. This study investigated the influence of this unsteady flow upon the internal hemodynamics of a centrifugal blood pump. The flow field within the median axial plane of the flow path was visualized with particle image velocimetry (PIV) using a transparent replica of the Levacor VAD. The replica was inserted in a dynamic cardiovascular simulator that synchronized the image acquisition to the cardiac cycle. As compared to steady flow, pulsatile conditions produced periodic, transient recirculation regions within the impeller and separation in the outlet diffuser. Dimensional analysis revealed that the flow characteristics could be uniquely described by the non-dimensional flow coefficient (Φ) and its time derivative ([Formula: see text]), thereby eliminating impeller speed from the experimental matrix. Four regimes within the Φ-[Formula: see text] plane were found to classify the flow patterns, well-attached or disturbed. These results and methods can be generalized to provide insights for both design and operation of rotodynamic blood pumps for safety and efficacy.

Influence of blood flow velocity on arterial distensibility of carotid artery in healthy men.

PubMed

Tomoto, Tsubasa; Maeda, Seiji; Sugawara, Jun

2017-01-01

Decreased distensibility of carotid artery is independently associated with the incidence of cardiovascular and cerebrovascular events. Arterial distensibility is determined by vascular tone. Since shear stress is an important driving force of vasodilatory substances production form endothelial cells, we hypothesized that local basal (i.e., resting) arterial blood flow velocity is associated with regional arterial distensibility. To test this hypothesis, we determined the influence of local blood flow velocity on carotid arterial distensibility in cross-sectional study design. In a total of 73 apparent healthy men (18-64 years), carotid arterial properties, including measures of carotid arterial distensibility and BFV at rest, were evaluated via B-mode and Doppler ultrasound imaging and applanation tonometry system. Carotid arterial peak BFV and the absolute and normalized pulsatile BFV significantly correlated with age (r = -0.453 to -0.600, p < 0.0001), whereas mean and minimum BFV were not influenced by age. Distensibility coefficient of carotid artery correlated with peak BFV (r = 0.305, p < 0.01) and more strongly with pulsatile (i.e., systolic minus end-diastolic) BFV (r = 0.406, p < 0.0001) and the normalized pulsatile BFV by time-averaged velocity (r = 0.591, p < 0.0001). Multi-regression analysis revealed that age (β = -0.57, p < 0.0001) was the primary independent determinant for distensibility coefficient. In addition with this, carotid lumen diameter (β = -0.202, p < 0.01) and the normalized pulsatile BFV (β = 0.237, p < 0.05) were significant independent determinants of distensibility coefficient. Qualitatively similar results (although inverse in direction) were obtained by use of β-stiffness index. These results suggest that greater gradient of blood flow velocity during a cardiac cycle are favorably associated with distensibility of carotid artery.

Surface obstacles in pulsatile flow

NASA Astrophysics Data System (ADS)

Carr, Ian A.; Plesniak, Michael W.

2017-11-01

Flows past obstacles mounted on flat surfaces have been widely studied due to their ubiquity in nature and engineering. For nearly all of these studies, the freestream flow over the obstacle was steady, i.e., constant velocity, unidirectional flow. Unsteady, pulsatile flows occur frequently in biology, geophysics, biomedical engineering, etc. Our study is aimed at extending the comprehensive knowledge base that exists for steady flows to considerably more complex pulsatile flows. Characterizing the vortex and wake dynamics of flows around surface obstacles embedded in pulsatile flows can provide insights into the underlying physics in all wake and junction flows. In this study, we experimentally investigate the wake of two canonical obstacles: a cube and a circular cylinder with an aspect ratio of unity. Our previous studies of a surface-mounted hemisphere in pulsatile flow are used as a baseline for these two new, more complex geometries. Phase-averaged PIV and hot-wire anemometry are used to characterize the dynamics of coherent structures in the wake and at the windward junction of the obstacles. Complex physics occur during the deceleration phase of the pulsatile inflow. We propose a framework for understanding these physics based on self-induced vortex propagation, similar to the phenomena exhibited by vortex rings.

Extremely pulsatile flow around a surface-mounted hemisphere: synergistic experiments and simulations

NASA Astrophysics Data System (ADS)

Carr, Ian A.; Beratlis, Nikolaos; Balaras, Elias; Plesniak, Michael W.

2017-11-01

Extremely pulsatile flow (where the amplitude of oscillation pulsation is of the same order as the mean flow) over a three-dimensional, surface-mounted bluff body gives rise a wealth of fluid dynamics phenomena. In this study, we extend our previous experimental work on extremely pulsatile flow around a surface-mounted hemisphere by performing a complementary direct numerical simulation. Results from the experiment and simulation will be presented and compared. After establishing the agreement between experiment and simulation, we will examine the morphology and dynamics of the vortex structures in the wake of the hemisphere, and the effects of extreme pulsatility. The dynamics of the arch-type recirculation vortex is of primary interest, in particular its upstream propagation due to self-induced velocity in the direction opposite to the freestream during deceleration. In addition to the velocity field, the surface pressure field throughout the pulsatile cycle will be presented. These synergistic experiments and simulations provide a detailed view into the complex flow fields associated with pulsatile flow over a surface-mounted hemisphere. This material is based upon work supported by the National Science Foundation under Grant Number CBET-1236351 and the GW Center for Biomimetics and Bioinspired Engineering.

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

PubMed Central

Satin, Leslie S.; Butler, Peter C.; Ha, Joon; Sherman, Arthur S.

2015-01-01

Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. PMID:25637831

DOE Office of Scientific and Technical Information (OSTI.GOV)

N, Gwilliam M; J, Collins D; O, Leach M

Purpose: To assess the feasibility of accurately quantifying the concentration of MRI contrast agent (CA) in pulsatile flowing blood by measuring its T{sub 1}, as is common for the purposes of obtaining a patientspecific arterial input function (AIF). Dynamic contrast enhanced (DCE) - MRI and pharmacokinetic (PK) modelling is widely used to produce measures of vascular function but accurate measurement of the AIF undermines their accuracy. A proposed solution is to measure the T{sub 1} of blood in a large vessel using the Fram double flip angle method during the passage of a bolus of CA. This work expands onmore » previous work by assessing pulsatile flow and the changes in T{sub 1} seen with a CA bolus. Methods: A phantom was developed which used a physiological pump to pass fluid of a known T{sub 1} (812ms) through the centre of a head coil of a clinical 1.5T MRI scanner. Measurements were made using high temporal resolution sequences suitable for DCE-MRI and were used to validate a virtual phantom that simulated the expected errors due to pulsatile flow and bolus of CA concentration changes typically found in patients. Results: : Measured and virtual results showed similar trends, although there were differences that may be attributed to the virtual phantom not accurately simulating the spin history of the fluid before entering the imaging volume. The relationship between T{sub 1} measurement and flow speed was non-linear. T{sub 1} measurement is compromised by new spins flowing into the imaging volume, not being subject to enough excitations to have reached steady-state. The virtual phantom demonstrated a range of recorded T{sub 1} for various simulated T{sub 1} / flow rates. Conclusion: T{sub 1} measurement of flowing blood using standard DCE-MRI sequences is very challenging. Measurement error is non-linear with relation to instantaneous flow speed. Optimising sequence parameters and lowering baseline T{sub 1} of blood should be considered.« less

Estimation of the physiological mechanical conditioning in vascular tissue engineering by a predictive fluid-structure interaction approach.

PubMed

Tresoldi, Claudia; Bianchi, Elena; Pellegata, Alessandro Filippo; Dubini, Gabriele; Mantero, Sara

2017-08-01

The in vitro replication of physiological mechanical conditioning through bioreactors plays a crucial role in the development of functional Small-Caliber Tissue-Engineered Blood Vessels. An in silico scaffold-specific model under pulsatile perfusion provided by a bioreactor was implemented using a fluid-structure interaction (FSI) approach for viscoelastic tubular scaffolds (e.g. decellularized swine arteries, DSA). Results of working pressures, circumferential deformations, and wall shear stress on DSA fell within the desired physiological range and indicated the ability of this model to correctly predict the mechanical conditioning acting on the cells-scaffold system. Consequently, the FSI model allowed us to a priori define the stimulation pattern, driving in vitro physiological maturation of scaffolds, especially with viscoelastic properties.

Mechanical stress regulates transport in a compliant 3D model of the blood-brain barrier.

PubMed

Partyka, Paul P; Godsey, George A; Galie, John R; Kosciuk, Mary C; Acharya, Nimish K; Nagele, Robert G; Galie, Peter A

2017-01-01

Transport of fluid and solutes is tightly controlled within the brain, where vasculature exhibits a blood-brain barrier and there is no organized lymphatic network facilitating waste transport from the interstitial space. Here, using a compliant, three-dimensional co-culture model of the blood-brain barrier, we show that mechanical stimuli exerted by blood flow mediate both the permeability of the endothelial barrier and waste transport along the basement membrane. Application of both shear stress and cyclic strain facilitates tight junction formation in the endothelial monolayer, with and without the presence of astrocyte endfeet in the surrounding matrix. We use both dextran perfusion and TEER measurements to assess the initiation and maintenance of the endothelial barrier, and microparticle image velocimetry to characterize the fluid dynamics within the in vitro vessels. Application of pulsatile flow to the in vitro vessels induces pulsatile strain to the vascular wall, providing an opportunity to investigate stretch-induced transport along the basement membrane. We find that a pulsatile wave speed of approximately 1 mm/s with Womersley number of 0.004 facilitates retrograde transport of high molecular weight dextran along the basement membrane between the basal endothelium and surrounding astrocytes. Together, these findings indicate that the mechanical stress exerted by blood flow is an important regulator of transport both across and along the walls of cerebral microvasculature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aberrant sylvian vein: A newly described cause of pulsatile tinnitus.

PubMed

Liu, Zhaohui; Yu, Jingge; Zhao, Pengfei; Zhang, Hanjuan; Wang, Qian; Wang, Zhenchang

2017-10-01

We herein report a newly described cause of venous pulsatile tinnitus: protrusion of an aberrant sylvian vein into the tympanum. A 60-year-old woman presented with a 4-month history of objective persistent pulsatile tinnitus in the right ear with no other complaints. The pulsatile tinnitus diminished with rotation of the head to the right side or by compression of the right cervical vascular structures. The frequency and intensity of the tinnitus were 125 Hz and 20 dB HL, respectively. Audiometry and otoscopic examination findings were normal. Radiologic examination showed that the right sylvian vein protruded into the tympanum through the dehiscent anterior cortical plate of the tympanum.

Aortic Wave Dynamics and Its Influence on Left Ventricular Workload

PubMed Central

Pahlevan, Niema M.; Gharib, Morteza

2011-01-01

The pumping mechanism of the heart is pulsatile, so the heart generates pulsatile flow that enters into the compliant aorta in the form of pressure and flow waves. We hypothesized that there exists a specific heart rate at which the external left ventricular (LV) power is minimized. To test this hypothesis, we used a computational model to explore the effects of heart rate (HR) and aortic rigidity on left ventricular (LV) power requirement. While both mean and pulsatile parts of the pressure play an important role in LV power requirement elevation, at higher rigidities the effect of pulsatility becomes more dominant. For any given aortic rigidity, there exists an optimum HR that minimizes the LV power requirement at a given cardiac output. The optimum HR shifts to higher values as the aorta becomes more rigid. To conclude, there is an optimum condition for aortic waves that minimizes the LV pulsatile load and consequently the total LV workload. PMID:21853075

Pulsatile Hyperglycaemia Induces Vascular Oxidative Stress and GLUT 1 Expression More Potently than Sustained Hyperglycaemia in Rats on High Fat Diet

PubMed Central

Rakipovski, Günaj; Lykkesfeldt, Jens; Raun, Kirsten

2016-01-01

Introduction Pulsatile hyperglycaemia resulting in oxidative stress may play an important role in the development of macrovascular complications. We investigated the effects of sustained vs. pulsatile hyperglycaemia in insulin resistant rats on markers of oxidative stress, enzyme expression and glucose metabolism in liver and aorta. We hypothesized that liver’s ability to regulate the glucose homeostasis under varying states of hyperglycaemia may indirectly affect oxidative stress status in aorta despite the amount of glucose challenged with. Methods Animals were infused with sustained high (SHG), low (SLG), pulsatile (PLG) glucose or saline (VEH) for 96 h. Oxidative stress status and key regulators of glucose metabolism in liver and aorta were investigated. Results Similar response in plasma lipid oxidation was observed in PLG as in SHG. Likewise, in aorta, PLG and SHG displayed increased expression of glucose transporter 1 (GLUT1), gp-91PHOX and super oxide dismutase (SOD), while only the PLG group showed increased accumulation of oxidative stress and oxidised low density lipoprotein (oxLDL) in aorta. Conclusion Pulsatile hyperglycaemia induced relatively higher levels of oxidative stress systemically and in aorta in particular than overt sustained hyperglycaemia thus supporting the clinical observations that pulsatile hyperglycaemia is an independent risk factor for diabetes related macrovascular complications. PMID:26790104

Pulsatile Hyperglycaemia Induces Vascular Oxidative Stress and GLUT 1 Expression More Potently than Sustained Hyperglycaemia in Rats on High Fat Diet.

PubMed

Rakipovski, Günaj; Lykkesfeldt, Jens; Raun, Kirsten

2016-01-01

Pulsatile hyperglycaemia resulting in oxidative stress may play an important role in the development of macrovascular complications. We investigated the effects of sustained vs. pulsatile hyperglycaemia in insulin resistant rats on markers of oxidative stress, enzyme expression and glucose metabolism in liver and aorta. We hypothesized that liver's ability to regulate the glucose homeostasis under varying states of hyperglycaemia may indirectly affect oxidative stress status in aorta despite the amount of glucose challenged with. Animals were infused with sustained high (SHG), low (SLG), pulsatile (PLG) glucose or saline (VEH) for 96 h. Oxidative stress status and key regulators of glucose metabolism in liver and aorta were investigated. Similar response in plasma lipid oxidation was observed in PLG as in SHG. Likewise, in aorta, PLG and SHG displayed increased expression of glucose transporter 1 (GLUT1), gp-91PHOX and super oxide dismutase (SOD), while only the PLG group showed increased accumulation of oxidative stress and oxidised low density lipoprotein (oxLDL) in aorta. Pulsatile hyperglycaemia induced relatively higher levels of oxidative stress systemically and in aorta in particular than overt sustained hyperglycaemia thus supporting the clinical observations that pulsatile hyperglycaemia is an independent risk factor for diabetes related macrovascular complications.

Post-stenotic plug-like jet with a vortex ring demonstrated by 4D flow MRI.

PubMed

Kim, Guk Bae; Ha, Hojin; Kweon, Jihoon; Lee, Sang Joon; Kim, Young-Hak; Yang, Dong Hyun; Kim, Namkug

2016-05-01

To investigate the details of the flow structure of a plug-like jet that had a vortex ring in pulsatile stenotic phantoms using 4D flow MRI. Pulsatile Newtonian flows in two stenotic phantoms with 50% and 75% reductions in area were scanned by 4D flow MRI. Blood analog working fluid was circulated via the stenotic phantom using a pulsatile pump at a constant pulsating frequency of 1Hz. The velocity and vorticity fields of the plug-like jet with a vortex ring were quantitatively analyzed in the spatial and temporal domains. Pulsatile stenotic flow showed a plug-like jet at the specific stenotic degree of 50% in our pulsatile waveform design. This plug-like jet was found at the decelerating period in the post-stenotic region of 26.4mm (1.2 D). It revealed a vortex ring structure with vorticity strength in the range of ±100s(-1). We observed a plug-like jet with a vortex ring in pulsatile stenotic flow by in vitro visualization using 4D flow MRI. In this plug-like jet, the local fastest flow region occurred at the post-systole phase in the post-stenotic region, which was distinguishable from a typical stenotic jet flow at systole phase. Copyright © 2015 Elsevier Inc. All rights reserved.

Increasing LH Pulsatility in Women With Hypothalamic Amenorrhoea Using Intravenous Infusion of Kisspeptin-54

PubMed Central

Jayasena, Channa N.; Abbara, Ali; Veldhuis, Johannes D.; Comninos, Alexander N.; Ratnasabapathy, Risheka; De Silva, Akila; Nijher, Gurjinder M. K.; Ganiyu-Dada, Zainab; Mehta, Amrish; Todd, Catriona; Ghatei, Mohammad A.; Bloom, Stephen R.

2014-01-01

Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. Aim: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Methods: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Results: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6 ± 0.4, vehicle; 5.0 ± 0.5, kisspeptin-54, P < .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P < .05 vs vehicle). Conclusions: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA. PMID:24517142

Comparative imaging study in ultrasound, MRI, CT, and DSA using a multimodality renal artery phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Deirdre M.; Fagan, Andrew J.; Moran, Carmel M.

2011-02-15

Purpose: A range of anatomically realistic multimodality renal artery phantoms consisting of vessels with varying degrees of stenosis was developed and evaluated using four imaging techniques currently used to detect renal artery stenosis (RAS). The spatial resolution required to visualize vascular geometry and the velocity detection performance required to adequately characterize blood flow in patients suffering from RAS are currently ill-defined, with the result that no one imaging modality has emerged as a gold standard technique for screening for this disease. Methods: The phantoms, which contained a range of stenosis values (0%, 30%, 50%, 70%, and 85%), were designed formore » use with ultrasound, magnetic resonance imaging, x-ray computed tomography, and x-ray digital subtraction angiography. The construction materials used were optimized with respect to their ultrasonic speed of sound and attenuation coefficient, MR relaxometry (T{sub 1},T{sub 2}) properties, and Hounsfield number/x-ray attenuation coefficient, with a design capable of tolerating high-pressure pulsatile flow. Fiducial targets, incorporated into the phantoms to allow for registration of images among modalities, were chosen to minimize geometric distortions. Results: High quality distortion-free images of the phantoms with good contrast between vessel lumen, fiducial markers, and background tissue to visualize all stenoses were obtained with each modality. Quantitative assessments of the grade of stenosis revealed significant discrepancies between modalities, with each underestimating the stenosis severity for the higher-stenosed phantoms (70% and 85%) by up to 14%, with the greatest discrepancy attributable to DSA. Conclusions: The design and construction of a range of anatomically realistic renal artery phantoms containing varying degrees of stenosis is described. Images obtained using the main four diagnostic techniques used to detect RAS were free from artifacts and exhibited adequate contrast to allow for quantitative measurements of the degree of stenosis in each phantom. Such multimodality phantoms may prove useful in evaluating current and emerging US, MRI, CT, and DSA technology.« less

Flow-gated radial phase-contrast imaging in the presence of weak flow.

PubMed

Peng, Hsu-Hsia; Huang, Teng-Yi; Wang, Fu-Nien; Chung, Hsiao-Wen

2013-01-01

To implement a flow-gating method to acquire phase-contrast (PC) images of carotid arteries without use of an electrocardiography (ECG) signal to synchronize the acquisition of imaging data with pulsatile arterial flow. The flow-gating method was realized through radial scanning and sophisticated post-processing methods including downsampling, complex difference, and correlation analysis to improve the evaluation of flow-gating times in radial phase-contrast scans. Quantitatively comparable results (R = 0.92-0.96, n = 9) of flow-related parameters, including mean velocity, mean flow rate, and flow volume, with conventional ECG-gated imaging demonstrated that the proposed method is highly feasible. The radial flow-gating PC imaging method is applicable in carotid arteries. The proposed flow-gating method can potentially avoid the setting up of ECG-related equipment for brain imaging. This technique has potential use in patients with arrhythmia or weak ECG signals.

A multiple disk centrifugal pump as a blood flow device.

PubMed

Miller, G E; Etter, B D; Dorsi, J M

1990-02-01

A multiple disk, shear force, valveless centrifugal pump was studied to determine its suitability as a blood flow device. A pulsatile version of the Tesla viscous flow turbine was designed by modifying the original steady flow pump concept to produce physiological pressures and flows with the aid of controlling circuitry. Pressures and flows from this pump were compared to a Harvard Apparatus pulsatile piston pump. Both pumps were connected to an artificial circulatory system. Frequency and systolic duration were varied over a range of physiological conditions for both pumps. The results indicated that the Tesla pump, operating in a pulsatile mode, is capable of producing physiologic pressures and flows similar to the Harvard pump and other pulsatile blood pumps.

Arteriovenous malformation of the external ear: a clinical assessment with a scoping review of the literature.

PubMed

Kim, Shin Hye; Han, Seung Hoon; Song, Yoonjae; Park, Chang Sik; Song, Jae-Jin

Auricular Arteriovenous Malformation of the external ear is a rarely encountered disease; in particular, arteriovenous malformation arising from the auricle, with spontaneous bleeding, has seldom been reported. In the current study, we report an unusual case of late-onset auricular arteriovenous malformation originating from the posterior auricular artery that was confirmed by computed tomographic angiography. The case was successfully managed by pre-surgical intravascular embolization followed by total lesion excision. Prompted by this case, we also present a scoping review of the literature. A case of a 60 year-old man with right auricular arteriovenous malformation treated in our tertiary care center, and 52 patients with auricular arteriovenous malformation described in 10 case reports and a retrospective review are presented. Auricular arteriovenous malformation can manifest as swelling of the ear, pulsatile tinnitus, pain, and/or bleeding. On physical examination, a pulsatile swelling and/or a tender mass is evident. When arteriovenous malformation is suspected, the lesions should be visualized using imaging modalities that optimally detect vascular lesions, and managed via embolization, mass excision, or auricular resection. Effectiveness of the various diagnostic methods used and the treatment outcomes were analyzed. Various imaging modalities including Doppler sonography, computed tomographic angiography, magnetic resonance angiography, and/or transfemoral cerebral angiography were used to diagnose 38 cases reported in the literature. In another 15 cases, no imaging was performed; treatment was determined solely by physical examination and auscultation. Of the total of 53 cases, 12 were not treated (their symptoms were merely observed) whereas 20 underwent therapeutic embolization. In total, 32 patients, including 1 patient who was not treated and 10 with persistent or aggravated arteriovenous malformation after previous embolization, underwent mass excision or auricular resection depending on the extent of the lesion. No major postoperative complication was recorded. The postoperative follow-up duration varied from 1 month to 19 years, and only one case of unresectable, residual cervicofacial arteriovenous malformation was recorded. Auricular arteriovenous malformation is a rarely encountered disease, but should be suspected if a patient presents with a swollen ear and pulsatile tinnitus. Appropriate imaging is essential for diagnosis and evaluation of the extent of disease. As embolization affords only relatively poor control, total surgical removal of the vascular mass is recommended. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Particle image velocimetry study of pulsatile flow in bi-leaflet mechanical heart valves with image compensation method.

PubMed

Shi, Yubing; Yeo, Tony Joon Hock; Zhao, Yong; Hwang, Ned H C

2006-12-01

Particle Image Velocimetry (PIV) is an important technique in studying blood flow in heart valves. Previous PIV studies of flow around prosthetic heart valves had different research concentrations, and thus never provided the physical flow field pictures in a complete heart cycle, which compromised their pertinence for a better understanding of the valvular mechanism. In this study, a digital PIV (DPIV) investigation was carried out with improved accuracy, to analyse the pulsatile flow field around the bi-leaflet mechanical heart valve (MHV) in a complete heart cycle. For this purpose a pulsatile flow test rig was constructed to provide the necessary in vitro test environment, and the flow field around a St. Jude size 29 bi-leaflet MHV and a similar MHV model were studied under a simulated physiological pressure waveform with flow rate of 5.2 l/min and pulse rate at 72 beats/min. A phase-locking method was applied to gate the dynamic process of valve leaflet motions. A special image-processing program was applied to eliminate optical distortion caused by the difference in refractive indexes between the blood analogue fluid and the test section. Results clearly showed that, due to the presence of the two leaflets, the valvular flow conduit was partitioned into three flow channels. In the opening process, flow in the two side channels was first to develop under the presence of the forward pressure gradient. The flow in the central channel was developed much later at about the mid-stage of the opening process. Forward flows in all three channels were observed at the late stage of the opening process. At the early closing process, a backward flow developed first in the central channel. Under the influence of the reverse pressure gradient, the flow in the central channel first appeared to be disturbed, which was then transformed into backward flow. The backward flow in the central channel was found to be the main driving factor for the leaflet rotation in the valve closing process. After the valve was fully closed, local flow activities in the proximity of the valve region persisted for a certain time before slowly dying out. In both the valve opening and closing processes, maximum velocity always appeared near the leaflet trailing edges. The flow field features revealed in the present paper improved our understanding of valve motion mechanism under physiological conditions, and this knowledge is very helpful in designing the new generation of MHVs.

Lack of tissue accumulation of grape seed flavanols after daily long-term administration in healthy and cafeteria-diet obese rats.

PubMed

Margalef, Maria; Pons, Zara; Iglesias-Carres, Lisard; Bravo, Francisca Isabel; Muguerza, Begoña; Arola-Arnal, Anna

2015-11-18

After ingestion flavanols are metabolized by phase-II enzymes and the microbiota and are distributed throughout the body depending on several factors. Herein we aim to evaluate whether flavanols are tissue-accumulated after the long-term administration of a grape seed polyphenol extract (GSPE) in rats and to study if compounds present in tissues differ in a cafeteria-diet obesity state. For that, plasma, liver, mesenteric white adipose tissue (MWAT), brain, and aorta flavanol metabolites from standard chow-diet-fed (ST) and cafeteria-diet-fed (CAF) rats were analyzed by high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) 21 h after the last 12-week-daily GSPE (100 mg/kg) dosage. Results showed that long-term GSPE intake did not trigger a flavanol tissue accumulation, indicating a clearance of products at each daily dosage. Therefore, results suggest that polyphenol benefits in a disease state would be due to a daily pulsatile effect. Moreover, obesity induced by diet also influences the metabolism and bioavailability of flavanols in rats.

Long-term subcutaneous pulsatile low dose LH-RH administration for treatment of infertile men with secondary hypogonadotrophic hypogonadism.

PubMed

Skarin, G; Nillius, S J; Wide, L

1984-01-01

Chronic pulsatile subcutaneous low dose LH-RH treatment was given to three infertile men with longstanding (2-4 years) secondary hypothalamic pituitary failure. Before the therapy they had very low serum concentrations of gonadotrophins and testosterone. They were impotent and could not produce any ejaculate for sperm analysis. The pulsatile LH-RH treatment, which was continued up to 250 days, was given by means of a small portable automatically-timed infusion pump. Fifty microliter of the LH-RH solution was infused during one min every 90 min. The LH-RH doses were 1, 5 and 20 micrograms. The serum concentrations of the gonadotrophins and testosterone were normalized in the three patients within 10 days of pulsatile low dose LH-RH therapy. Libido and potency returned. The first ejaculates contained no sperms. With continued LH-RH treatment spermatogenesis was induced and normalized. Two of the men fertilized their wives. The pregnancy tests were positive after 181 and 230 days of treatment, respectively. Two healthy girls have been born. Paternity tests were positive. The third man is still receiving pulsatile LH-RH therapy. He has up till now been treated for four months. Chronic pulsatile s.c. low dose LH-RH administration is a very promising new therapy for those hypogonadal men who previously have required human gonadotrophin treatment to restore fertility.

Pulsatile plasma filtration and cell-free DNA amplification using a water-head-driven point-of-care testing chip.

PubMed

Lee, Yonghun; Kim, Dong-Min; Li, Zhenglin; Kim, Dong-Eun; Kim, Sung-Jin

2018-03-13

We demonstrate a microfiltration chip that separates blood plasma by using water-head-driven pulsatile pressures rather than any external equipment and use it for on-chip amplification of nucleic acids. The chip generates pulsatile pressures to significantly reduce filter clogging without hemolysis, and consists of an oscillator, a plasma-extraction pump, and filter units. The oscillator autonomously converts constant water-head pressure to pulsatile pressure, and the pump uses the pulsatile pressure to extract plasma through the filter. Because the pulsatile pressure can periodically clear blood cells from the filter surface, filter clogging can be effectively reduced. In this way, we achieve plasma extraction with 100% purity and 90% plasma recovery at 15% hematocrit. During a 10 min period, the volume of plasma extracted was 43 μL out of a 243 μL extraction volume at 15% hematocrit. We also studied the influence of the pore size and diameter of the filter, blood loading volume, oscillation period, and hematocrit level on the filtration performance. To demonstrate the utility of our chip for point-of-care testing (POCT) applications, we successfully implemented on-chip amplification of a nucleic acid (miDNA21) in plasma filtered from blood. We expect our chip to be useful not only for POCT applications but also for other bench-top analysis tools using blood plasma.

Prospective, randomized comparison between pulsatile GnRH therapy and combined gonadotropin (FSH+LH) treatment for ovulation induction in women with hypothalamic amenorrhea and underlying polycystic ovary syndrome.

PubMed

Dubourdieu, Sophie; Fréour, Thomas; Dessolle, Lionel; Barrière, Paul

2013-05-01

To compare the efficacy of pulsatile GnRH therapy versus combined gonadotropins for ovulation induction in women with both hypothalamic amenorrhoea and polycystic ovarian syndrome (HA/PCOS) according to their current hypothalamic status. This single-centre, prospective, randomized study was conducted in the Nantes University Hospital, France. Thirty consecutive patients were treated for ovulation induction with either pulsatile GnRH therapy or combined gonadotropins (rFSH+rLH). Frequency of adequate ovarian response (mono- or bi-follicular) and clinical pregnancy rate were then compared between both groups. Ovarian response was similar in both groups with comparable frequency of adequate ovarian response (73% vs 60%), but the clinical pregnancy rate was significantly higher in the pulsatile GnRH therapy group than in the combined gonadotropin group (46% vs 0%). HA/PCOS is a specific subgroup of infertile women. Pulsatile GnRH therapy is an effective and safe method of ovulation induction that can be used successfully in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A computational model-based validation of Guyton's analysis of cardiac output and venous return curves

NASA Technical Reports Server (NTRS)

Mukkamala, R.; Cohen, R. J.; Mark, R. G.

2002-01-01

Guyton developed a popular approach for understanding the factors responsible for cardiac output (CO) regulation in which 1) the heart-lung unit and systemic circulation are independently characterized via CO and venous return (VR) curves, and 2) average CO and right atrial pressure (RAP) of the intact circulation are predicted by graphically intersecting the curves. However, this approach is virtually impossible to verify experimentally. We theoretically evaluated the approach with respect to a nonlinear, computational model of the pulsatile heart and circulation. We developed two sets of open circulation models to generate CO and VR curves, differing by the manner in which average RAP was varied. One set applied constant RAPs, while the other set applied pulsatile RAPs. Accurate prediction of intact, average CO and RAP was achieved only by intersecting the CO and VR curves generated with pulsatile RAPs because of the pulsatility and nonlinearity (e.g., systemic venous collapse) of the intact model. The CO and VR curves generated with pulsatile RAPs were also practically independent. This theoretical study therefore supports the validity of Guyton's graphical analysis.

Scaling the low-shear pulsatile TORVAD for pediatric heart failure

PubMed Central

Gohean, Jeffrey R.; Larson, Erik R.; Hsi, Brian H.; Kurusz, Mark; Smalling, Richard W.; Longoria, Raul G.

2016-01-01

This article provides an overview of the design challenges associated with scaling the low-shear pulsatile TORVAD ventricular assist device (VAD) for treating pediatric heart failure. A cardiovascular system model was used to determine that a 15 ml stroke volume device with a maximum flow rate of 4 L/min can provide full support to pediatric patients with body surface areas between 0.6 to 1.5 m2. Low shear stress in the blood is preserved as the device is scaled down and remains at least two orders of magnitude less than continuous flow VADs. A new magnetic linkage coupling the rotor and piston has been optimized using a finite element model (FEM) resulting in increased heat transfer to the blood while reducing the overall size of TORVAD. Motor FEM has also been used to reduce motor size and improve motor efficiency and heat transfer. FEM analysis predicts no more than 1°C temperature rise on any blood or tissue contacting surface of the device. The iterative computational approach established provides a methodology for developing a TORVAD platform technology with various device sizes for supporting the circulation of infants to adults. PMID:27832001

Scaling the Low-Shear Pulsatile TORVAD for Pediatric Heart Failure.

PubMed

Gohean, Jeffrey R; Larson, Erik R; Hsi, Brian H; Kurusz, Mark; Smalling, Richard W; Longoria, Raul G

This article provides an overview of the design challenges associated with scaling the low-shear pulsatile TORVAD ventricular assist device (VAD) for treating pediatric heart failure. A cardiovascular system model was used to determine that a 15 ml stroke volume device with a maximum flow rate of 4 L/min can provide full support to pediatric patients with body surface areas between 0.6 and 1.5 m. Low-shear stress in the blood is preserved as the device is scaled down and remains at least two orders of magnitude less than continuous flow VADs. A new magnetic linkage coupling the rotor and piston has been optimized using a finite element model (FEM) resulting in increased heat transfer to the blood while reducing the overall size of TORVAD. Motor FEM has also been used to reduce motor size and improve motor efficiency and heat transfer. FEM analysis predicts no more than 1°C temperature rise on any blood or tissue contacting surface of the device. The iterative computational approach established provides a methodology for developing a TORVAD platform technology with various device sizes for supporting the circulation of infants to adults.

Development of a new extracorporeal whole-liver perfusion system.

PubMed

Naruse, Katsutoshi; Sakai, Yasuyuki; Guo, Lei; Natori, Takeshi; Shindoh, Junichi; Karasawa, Yasuaki; Iida, Yuhki; Kojima, Kentaro; Michishita, Kazuya; Makuuchi, Masatoshi

2003-01-01

We have developed a new extracorporeal whole-liver accommodation device in which a whole swine liver is placed in a physiological state by modeling the intraabdominal arrangement in the pig body, with the liver supported by a special inferior vena cava tube. Furthermore, we employed a diaphragm-type artificial heart in our system to produce pulsatile blood flow through the hepatic artery, which is considered to be indispensable to dilate peripheral vessels and supply oxygenated whole blood to the peripheral liver tissue. Beneficial effects were demonstrated in visual findings and bile juice secretion. The color of the liver surface in our system remained bright red, indicating that the liver vessels were well drained and free from congestion, and bile juice secretion was maintained at more than 10 ml/h throughout the perfusion period. Our system exhibited excellent ammonia removal and urea nitrogen synthesis, and serum aspartate aminotransferase levels showed no increase, indicating the absence of hepatocyte destruction. Histological findings showed that the liver could expand appropriately and was free from compression caused by its own weight. In conclusion, our original liver accommodation device enabled appropriate expansion of the whole liver and supplied adequate oxygenated blood to peripheral areas by means of a pulsatile pump.

Rectification of pulsatile stress on soft tissues: a mechanism for normal-pressure hydrocephalus

NASA Astrophysics Data System (ADS)

Jalikop, Shreyas; Hilgenfeldt, Sascha

2011-11-01

Hydrocephalus is a pathological condition of the brain that occurs when cerebrospinal fluid (CSF) accumulates excessively in the brain cavities, resulting in compression of the brain parenchyma. Counter-intuitively, normal-pressure hydrocephalus (NPH) does not show elevated pressure differences across the compressed parenchyma. We investigate the effects of nonlinear tissue mechanics and periodic driving in this system. The latter is due to the cardiac cycle, which provides significant intracranial pressure and volume flow rate fluctuations. Nonlinear rectification of the periodic driving within a model of fluid flow in poroelastic material can lead to compression or expansion of the parenchyma, and this effect does not rely on changes in the mean intracranial pressure. The rectification effects can occur gradually over several days, in agreement with clinical studies of NPH.

Photoplethysmography beyond perfusion and oxygenation monitoring: Pulse wave analysis for hepatic graft monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akl, Tony; Wilson, Mark A.; Ericson, Milton Nance

2014-01-01

Photoplethysmography is a widely used technique in monitoring perfusion and blood oxygen saturation by using the amplitude of the pulsatile signal on one or multiple wavelengths. However, the pulsatile signal carries in its waveform a substantial amount of information about the mechanical properties of the tissue and vasculature under investigation that is still yet to be utilized to its full potential. In this work, we present the feasibility of pulse wave analysis for the application of monitoring hepatic implants and diagnosing graft complications. In particular, we show the possibility of computing the slope of the pulse during the diastole phasemore » to assess the location of vascular complications when they take place. This hypothesis was tested in a series of in vitro experiments using a PDMS based phantom mimicking the optical and mechanical properties of the portal vein. The emptying time of the vessel increased from 305 ms to 515 ms when an occlusion was induced downstream from the phantom. However, in the case of upstream occlusions, the emptying time remained constant. In both cases, a decrease in the amplitude of the pulse was recorded indicating the drop in flow levels. In addition, we show that quantifying the emptying time of the vasculature under investigation can be used to assess its compliance. The emptying time decreased from 305 ms for phantoms with compliance of 15 KPa to 195 ms for phantoms with compliance of 100 KPa. These compliance levels mimic those seen for normal and fibrotic hepatic tissue respectively.« less

Neuroendocrine effects of light

NASA Astrophysics Data System (ADS)

Reiter, Russel J.

1991-09-01

The light/dark cycle to which animals, and possibly humans, are exposed has a major impact on their physiology. The mechanisms whereby specific tissues respond to the light/dark cycle involve the pineal hormone melatonin. The pineal gland, an end organ of the visual system in mammals, produces the hormone melatonin only at night, at which time it is released into the blood. The duration of elevated nightly melatonin provides every tissue with information about the time of day and time of year (in animals that are kept under naturally changing photoperiods). Besides its release in a circadian mode, melatonin is also discharged in a pulsatile manner; the physiological significance, if any, of pulsatile melatonin release remains unknown. The exposure of animals including man to light at night rapidly depresses pineal melatonin synthesis and, therefore, blood melatonin levels drop precipitously. The brightness of light at night required to depress melatonin production is highly species specific. In general, the pineal gland of nocturnally active mammals, which possess rod-dominated retinas, is more sensitive to inhibition by light than is the pineal gland of diurnally active animals (with cone-dominated retinas). Because of the ability of the light/dark cycle to determine melatonin production, the photoperiod is capable of influencing the function of a variety of endocrine and non-endocrine organs. Indeed, melatonin is a ubiquitously acting pineal hormone with its effects on the neuroendocrine system having been most thoroughly investigated. Thus, in nonhuman photoperiodic mammals melatonin regulates seasonal reproduction; in humans also, the indole has been implicated in the control of reproductive physiology.

Videodermoscopy and doppler-ultrasound in spider naevi: towards a new classification?

PubMed

Alegre-Sánchez, A; Bernárdez, C; Fonda-Pascual, P; Moreno-Arrones, O M; López-Gutiérrez, J C; Jaén-Olasolo, P; Boixeda, P

2018-01-01

Spider naevi (SN) are considered a subtype of telangiectasias, currently classified as low-flow vascular malformations. To describe the videodermoscopy and Doppler-ultrasound (US) features of a large group of SN. A retrospective study of cases of SN collected at our Dermatology department during the period between June 2015 and June 2017 was performed. Clinical images, dermoscopic, videodermoscopic and Doppler-US files were reviewed. For each case, the age of the patient, time since onset, size and dermoscopic pattern of the lesions were recorded. The presence of pulsatility was also evaluated visually on the videodermoscopy. Two hundred and thirty-three SN in 189 patients were included. The mean age was 39.5 years (range: 10-76 years). Mean size of the lesions was 4.1 ± 2.0 mm. We described three dermoscopic patterns: network, star and looping. Older age, longer time since onset and larger size were found associated with higher frequency of the looping and star patterns compared to that of network pattern (P < 0.01). Pulsatility during videodermoscopy was found in 88 patients (37%). This pulsatility phenomenon was more commonly associated with the looping pattern (64.7%) than star- (40.3%) or network-like patterns (29.9%) (P < 0.001). In Doppler-US studies, a high-flow with arterial biphasic waveform was found. In the light of the results, we support that SN could be reconsidered in upcoming classifications as lesions closer to the group of high-flow arteriovenous malformations. © 2017 European Academy of Dermatology and Venereology.

Body mapping of human cutaneous microcirculatory perfusion using a real-time laser Doppler imager.

PubMed

Harbi, Pascal; Thacher, Tyler

2013-03-01

There are many pathologies and/or surgical situations where understanding how cutaneous capillary blood flow is behaving would be of clinical benefit. Laser Doppler imaging (LDI) has long been considered an ideal candidate for this yet was never widely adopted. The technology was deemed too slow, needing minutes to record one image. Here, we present the use of a new, real-time LDI, which is sensitive enough to resolve pulsatile blood flow in the microcirculation and can record images and videos instantaneously. We show that when comparing the ratios of absolute perfusion images from different regions of the body, remarkably reproducible data can be obtained when looking at a control population of male volunteers. In the future, we plan to add more control and diseased groups, effectively giving the clinician a non-invasive, safe and easy-to-use diagnostic for assessing the extent of microcirculatory disorders and high-risk surgical situations.

[Parenchymal complications of the transplanted kidney: the role of color-Doppler imaging].

PubMed

Granata, Antonio; Clementi, Silvia; Clementi, Anna; Di Pietro, Fabio; Scarfia, Viviana R; Insalaco, Monica; Aucella, Filippo; Prencipe, Michele; Fiorini, Fulvio; Sicurezza, Elvia

2012-01-01

Kidney transplantation is the treatment of choice for end-stage renal disease, given the better quality of life of transplanted patients when compared to patients on maintenance dialysis. In spite of surgical improvements and new immunosuppressive regimens, part of the transplanted grafts still develop chronic dysfunction. Ultrasonography, both in B-mode and with Doppler ultrasound, is an important diagnostic tool in case of clinical conditions which might impair kidney function. Even though ultrasonography is considered fundamental in the diagnosis of vascular and surgical complications of the transplanted kidney, its role is not fully understood in case of parenchymal complications of the graft. The specificity of Doppler ultrasound is low both in case of acute complications such as acute tubular necrosis, drug toxicity and acute rejection, and in case of chronic conditions such as chronic allograft nephropathy. Single determinations of resistance indices present low diagnostic accuracy, which is higher in case of successive measurements performed during the follow-up of the graft. Modern techniques including tissue pulsatility index, maximal fractional area and contrast-enhanced ultrasound increase the diagnostic power of ultrasonography in case of parenchymal complications of the transplanted kidney.

Preload-Based Starling-Like Control for Rotary Blood Pumps: Numerical Comparison with Pulsatility Control and Constant Speed Operation

PubMed Central

Mansouri, Mahdi; Salamonsen, Robert F.; Lim, Einly; Akmeliawati, Rini; Lovell, Nigel H.

2015-01-01

In this study, we evaluate a preload-based Starling-like controller for implantable rotary blood pumps (IRBPs) using left ventricular end-diastolic pressure (PLVED) as the feedback variable. Simulations are conducted using a validated mathematical model. The controller emulates the response of the natural left ventricle (LV) to changes in PLVED. We report the performance of the preload-based Starling-like controller in comparison with our recently designed pulsatility controller and constant speed operation. In handling the transition from a baseline state to test states, which include vigorous exercise, blood loss and a major reduction in the LV contractility (LVC), the preload controller outperformed pulsatility control and constant speed operation in all three test scenarios. In exercise, preload-control achieved an increase of 54% in mean pump flow (QP-) with minimum loading on the LV, while pulsatility control achieved only a 5% increase in flow and a decrease in mean pump speed. In a hemorrhage scenario, the preload control maintained the greatest safety margin against LV suction. PLVED for the preload controller was 4.9 mmHg, compared with 0.4 mmHg for the pulsatility controller and 0.2 mmHg for the constant speed mode. This was associated with an adequate mean arterial pressure (MAP) of 84 mmHg. In transition to low LVC, QP- for preload control remained constant at 5.22 L/min with a PLVED of 8.0 mmHg. With regards to pulsatility control, QP- fell to the nonviable level of 2.4 L/min with an associated PLVED of 16 mmHg and a MAP of 55 mmHg. Consequently, pulsatility control was deemed inferior to constant speed mode with a PLVED of 11 mmHg and a QP- of 5.13 L/min in low LVC scenario. We conclude that pulsatility control imposes a danger to the patient in the severely reduced LVC scenario, which can be overcome by using a preload-based Starling-like control approach. PMID:25849979

Disinfection of human musculoskeletal allografts in tissue banking: a systematic review.

PubMed

Mohr, J; Germain, M; Winters, M; Fraser, S; Duong, A; Garibaldi, A; Simunovic, N; Alsop, D; Dao, D; Bessemer, R; Ayeni, O R

2016-12-01

Musculoskeletal allografts are typically disinfected using antibiotics, irradiation or chemical methods but protocols vary significantly between tissue banks. It is likely that different disinfection protocols will not have the same level of microorganism kill; they may also have varying effects on the structural integrity of the tissue, which could lead to significant differences in terms of clinical outcome in recipients. Ideally, a disinfection protocol should achieve the greatest bioburden reduction with the lowest possible impact on tissue integrity. A systematic review of three databases found 68 laboratory and clinical studies that analyzed the microbial bioburden or contamination rates of musculoskeletal allografts. The use of peracetic acid-ethanol or ionizing radiation was found to be most effective for disinfection of tissues. The use of irradiation is the most frequently published method for the terminal sterilization of musculoskeletal allografts; it is widely used and its efficacy is well documented in the literature. However, effective disinfection results were still observed using the BioCleanse™ Tissue Sterilization process, pulsatile lavage with antibiotics, ethylene oxide, and chlorhexidine. The variety of effective methods to reduce contamination rate or bioburden, in conjunction with limited high quality evidence provides little support for the recommendation of a single bioburden reduction method.

Color Doppler Sonographic Evaluation of Peak Systolic Velocity and Pulsatility Index in Artery after Pulsed HIFU Exposure

NASA Astrophysics Data System (ADS)

Yang, Feng-Yi; Chiu, Wei-Hsiu; Yeh, Chi-Fang

2011-09-01

The objective of current study was to investigate the functional changes in arteries induced by pulsed-HIFU with or without microbubbles. Sonication was applied at an ultrasound frequency of 1 MHz with a burst length of 50 ms and a repetition frequency of 1 Hz. The duration of the whole sonication was 6s. The abdominal aortas of Sprague-Dawley rats were surgically exposed and sonicated with pulsed HIFU; the pulsed HIFU beam was aimed using color images of the blood flow. There was no obvious normalized peak systolic velocity (PSV) change at various acoustic powers of pulsed-HIFU exposure in the absence of ultrasound contrast agent (UCA). However, the normalized PSV change induced by pulsed-HIFU decreased with the injected dose of UCA at acoustic powers. At this time, the normalized pulsatility index (PI) change in the vessel subjected to pulsed-HIFU increased in proportion to UCA dose. Additional research is needed to investigate the detailed mechanical effects of pulsed-HIFU exposure on blood flow and the structure of vessel walls.

Entrainment and thrust augmentation in pulsatile ejector flows

NASA Technical Reports Server (NTRS)

Sarohia, V.; Bernal, L.; Bui, T.

1981-01-01

This study comprised direct thrust measurements, flow visualization by use of a spark shadowgraph technique, and mean and fluctuating velocity measurements with a pitot tube and linearized constant temperature hot-wire anemometry respectively. A gain in thrust of as much as 10 to 15% was observed for the pulsatile ejector flow as compared to the steady flow configuration. From the velocity profile measurements, it is concluded that this enhanced augmentation for pulsatile flow as compared to a nonpulsatile one was accomplished by a corresponding increased entrainment by the primary jet flow. It is also concluded that the augmentation and total entrainment by a constant area ejector critically depends upon the inlet geometry of the ejector. Experiments were performed to evaluate the influence of primary jet to ejector area ratio, ejector length, and presence of a diffuser on pulsatile ejector performance.

Recent advances in oral pulsatile drug delivery.

PubMed

Kalantzi, Lida E; Karavas, Evangelos; Koutris, Efthimios X; Bikiaris, Dimitrios N

2009-01-01

Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.

Effect of clazosentan, a selective endothelin A receptor antagonist, and tezosentan, a dual endothelin A/B antagonist, on pulsatile shear stress induced constriction of the iliac in the anaesthetized pig.

PubMed

Ruane-O'Hora, Therese; Rae, Mark George; Markos, Farouk

2011-08-01

1. The effects of changes in mean and pulsatile shear stress on the diameter of the iliac of the anaesthetized pig were investigated in the presence of clazosentan and tezosentan. 2. A total of 17 pigs were used. Mean shear stress was increased by infusing acetylcholine downstream (2-20 μg/min) through the deep femoral artery. Pulsatile shear stress was enhanced first by injecting varying volumes (1-10 mL) of calcium gluconate (stock 10 mg/mL) directly into the left ventricle. Second, by electrical stimulation of the left sympathetic nerves to the heart (1-16 Hz, 4 min duration, supramaximal voltage). 3. An increase in mean shear stress induced a vasodilation that was not altered significantly by the selective endothelin A antagonist clazosentan (10 mg/kg i.v.). Similarly, the vasoconstriction induced by an increase in pulsatile shear stress brought about by either calcium gluconate injections or left sympathetic nerve stimulation was unaffected by clazosentan. However, tezosentan (10 mg/kg i.v.), significantly attenuated the vasoconstriction induced by an increase in pulsatile shear stress. 4. In conclusion, an increase in pulsatile shear stress causes vasoconstriction of the pig iliac artery, which is attenuated by dual endothelin receptor antagonism, but not by specific endothelin A blockade. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

Cell sheet-based tissue engineering for fabricating 3-dimensional heart tissues.

PubMed

Shimizu, Tatsuya

2014-01-01

In addition to stem cell biology, tissue engineering is an essential research field for regenerative medicine. In contrast to cell injection, bioengineered tissue transplantation minimizes cell loss and has the potential to repair tissue defects. A popular approach is scaffold-based tissue engineering, which utilizes a biodegradable polymer scaffold for seeding cells; however, new techniques of cell sheet-based tissue engineering have been developed. Cell sheets are harvested from temperature-responsive culture dishes by simply lowering the temperature. Monolayer or stacked cell sheets are transplantable directly onto damaged tissues and cell sheet transplantation has already been clinically applied. Cardiac cell sheet stacking produces pulsatile heart tissue; however, lack of vasculature limits the viable tissue thickness to 3 layers. Multistep transplantation of triple-layer cardiac cell sheets cocultured with endothelial cells has been used to form thick vascularized cardiac tissue in vivo. Furthermore, in vitro functional blood vessel formation within 3-dimensional (3D) tissues has been realized by successfully imitating in vivo conditions. Triple-layer cardiac cell sheets containing endothelial cells were layered on vascular beds and the constructs were media-perfused using novel bioreactor systems. Interestingly, cocultured endothelial cells migrate into the vascular beds and form perfusable blood vessels. An in vitro multistep procedure has also enabled the fabrication of thick, vascularized heart tissues. Cell sheet-based tissue engineering has revealed great potential to fabricate 3D cardiac tissues and should contribute to future treatment of severe heart diseases and human tissue model production.

Optimal wavelength selection for noncontact reflection photoplethysmography

NASA Astrophysics Data System (ADS)

Corral Martinez, Luis F.; Paez, Gonzalo; Strojnik, Marija

2011-08-01

In this work, we obtain backscattered signals from human forehead for wavelengths from 380 to 980 nm. The results reveal bands with strong pulsatile signals that carry useful information. We describe those bands as the most suitable wavelengths in the visible and NIR regions from which heart and respiratory rate parameters can be derived using long distance non-contact reflection photoplethysmography analysis. The latter results show the feasibility of a novel technique for remotely detection of vital signs in humans. This technique, which may include morphological analysis or maps of tissue oxygenation, is a further step to real non-invasive remote monitoring of patients.

A model to simulate the haemodynamic effects of right heart pulsatile flow after modified Fontan procedure.

PubMed

Tamaki, S; Kawazoe, K; Yagihara, T; Abe, T

1992-02-01

The effect of pulsatile pulmonary flow after the modified Fontan procedure was examined in a model that simulated the right heart. An inlet overflow tank (preload), axial pulsatile pump, Wind-Kessel model (afterload), and an outlet overflow tank were connected in series. The standard conditions were flow 2.00 l/min with 12 mm Hg preload pressure, 3.0 Wood units resistance, and an outlet overflow tank pressure at 6 mm Hg. The pump rate was set at 80 beats/min. The simulated pulmonary arterial pressure and pulmonary flow waves produced by this model closely resembled those obtained from patients who had undergone the modified Fontan procedure. All variables except the preload were fixed and changes in pulmonary flow were examined at preload pressures of 8, 12, 15, and 17 mm Hg. As the peak pulmonary arterial pressure increased so did pulmonary flow, until it was greater than during the non-pulsatile state. Because the afterload of this model was fixed, this result suggests that there was a concomitant decrease in resistance. This model indicates that pulsatile pulmonary blood flow is likely to have a beneficial effect on the pulmonary circulation after the modified Fontan procedure.

Pulsatile Flow and Gas Transport of Blood over an Array of Cylinders

NASA Astrophysics Data System (ADS)

Chan, Kit Yan

2005-11-01

In the artificial lung, blood passes through an array of micro-fibers and the gas transfer is strongly dependent on the flow field. The blood flow is unsteady and pulsatile. We have numerically simulated pulsatile flow and gas transfer of blood (modeled as a Casson fluid) over arrays of cylindrical micro-fibers. Oxygen and carbon dioxide are assumed to be in local equilibrium with hemoglobin in blood; and the carbon dioxide facilitated oxygen transport is incorporated into the model by allowing the coupling of carbon dioxide partial pressure and oxygen saturation. The pulsatile flow inputs considered are the sinusoidal and the cardiac waveforms. The squared and staggered arrays of arrangement of the cylinders are considered in this study. Gas transport can be enhanced by: increasing the oscillation frequency; increasing the Reynolds number; increasing the oscillation amplitude; decreasing the void fraction; the use of the cardiac pulsatile input. The overall gas transport is greatly enhanced by the presence of hemoglobin in blood even though the non-Newtonian effect of blood tends to decrease the size and strength of vortices. The pressure drop is also presented as it is an important design parameter confronting the heart.

Polycystic ovarian disease unmasked by pulsatile GnRH therapy in a subgroup of women with hypothalamic amenorrhea.

PubMed

Mattle, Verena; Bilgyicildirim, Aysen; Hadziomerovic, Dijana; Ott, Helmut W; Zervomanolakis, Ioannis; Leyendecker, Gerhard; Wildt, Ludwig

2008-02-01

To present the observation in six out of 120 women treated with pulsatile GnRH for ovulation induction, who developed hyperandrogenemia and polycystic ovaries during treatment. Clinical observation. Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Austria. A total of 120 women initially diagnosed as suffering from primary or secondary hypothalamic amenorrhea were treated for ovulation induction with pulsatile administration of GnRH for up to 140 days. There was no indication of the presence of polycystic ovaries or hyperandrogenemia before therapy. Pulsatile GnRH therapy using the Zyklomat pump. Ovulatory menstrual cycles. Initially, all patients responded to pulsatile GnRH administration with ovulation and corpus luteum formation. During continuation of treatment, 6 patients developed an increase in LH and LH/FSH ratio as well as a progressive rise in serum T levels resulting in hyperandrogenemia. This was accompanied by the development of polycystic ovaries and cessation of follicular maturation. We conclude from these observations that restoration of normal GnRH stimulation of the pituitary gland can result in the development of hyperandrogenemia and polycystic ovaries, suggesting a pituitary or ovarian defect underlying the pathogenesis of this disorder.

Temporal gradients in shear stimulate osteoblastic proliferation via ERK1/2 and retinoblastoma protein

NASA Technical Reports Server (NTRS)

Jiang, Guang-Liang; White, Charles R.; Stevens, Hazel Y.; Frangos, John A.

2002-01-01

Bone cells are subject to interstitial fluid flow (IFF) driven by venous pressure and mechanical loading. Rapid dynamic changes in mechanical loading cause transient gradients in IFF. The effects of pulsatile flow (temporal gradients in fluid shear) on rat UMR106 cells and rat primary osteoblastic cells were studied. Pulsatile flow induced a 95% increase in S-phase UMR106 cells compared with static controls. In contrast, ramped steady flow stimulated only a 3% increase. Similar patterns of S-phase induction were also observed in rat primary osteoblastic cells. Pulsatile flow significantly increased relative UMR106 cell number by 37 and 62% at 1.5 and 24 h, respectively. Pulsatile flow also significantly increased extracellular signal-regulated kinase (ERK1/2) phosphorylation by 418%, whereas ramped steady flow reduced ERK1/2 activation to 17% of control. Correspondingly, retinoblastoma protein was significantly phosphorylated by pulsatile fluid flow. Inhibition of mitogen-activated protein (MAP)/ERK kinase (MEK)1/2 by U0126 (a specific MEK1/2 inhibitor) reduced shear-induced ERK1/2 phosphorylation and cell proliferation. These findings suggest that temporal gradients in fluid shear stress are potent stimuli of bone cell proliferation.

Pulsatile dry cupping in chronic low back pain - a randomized three-armed controlled clinical trial.

PubMed

Teut, M; Ullmann, A; Ortiz, M; Rotter, G; Binting, S; Cree, M; Lotz, F; Roll, S; Brinkhaus, B

2018-04-02

We aimed to investigate the effectiveness of two different forms of dry pulsatile cupping in patients with chronic low back pain (cLBP) compared to medication on demand only in a three-armed randomized trial. 110 cLBP patients were randomized to regular pulsatile cupping with 8 treatments plus paracetamol on demand (n = 37), minimal cupping with 8 treatments plus paracetamol on demand (n = 36) or the control group with paracetamol on demand only (n = 37). Primary outcome was the pain intensity on a visual analogue scale (VAS, 0-100 mm) after 4 weeks, secondary outcome parameter included VAS pain intensity after 12 weeks, back function as measured with the 'Funktionsfragebogen Hannover Rücken' (FFbH-R) and health related quality of life questionnaire Short form 36 (SF-36) after 4 and 12 weeks. The mean baseline-adjusted VAS after 4 weeks was 34.9 mm (95% CI: 28.7; 41.2) for pulsatile cupping, 40.4 (34.2; 46.7) for minimal cupping and 56.1 (49.8; 62.4) for control group, resulting in statistically significant differences between pulsatile cupping vs. control (21.2 (12.2; 30.1); p < 0.001) and minimal cupping vs. control (15.7 (6.9; 24.4); p = 0.001). After 12 weeks, mean adjusted VAS difference between pulsatile cupping vs. control was 15.1 ((3.1; 27.1); p = 0.014), and between minimal cupping vs. control 11.5 ((- 0.44; 23.4); p = 0.059). Differences of VAS between pulsatile cupping and minimal cupping showed no significant differences after 4 or 12 weeks. Pulsatile cupping was also better (- 5.8 (- 11.5;-0.1); p = 0.045) compared to control for back function after 4 weeks, but not after 12 weeks (- 5.4 (- 11.7;0.8); p = 0.088), pulsatile cupping also showed better improvements on SF-36 physical component scale compared to control at 4 and 12 weeks (- 5.6 (- 9.3;-2.0); p = 0.003; - 6.1 (- 9.9;-2.4); p = 0.002). For back function and quality of life minimal cupping group was not statistically different to control after 4 and 12 weeks. Paracetamol intake did not differ between the groups (cupping vs. control (7.3 (- 0.4;15.0); p = 0.063); minimal cupping vs. control (6.3 (- 2.0;14.5); p = 0.133). Both forms of cupping were effective in cLBP without showing significant differences in direct comparison after four weeks, only pulsatile cupping showed effects compared to control after 12 weeks. The study was registered at ClinicalTrials.gov (identifier: NCT02090686 ).

Does Flexible Arterial Tubing Retain More Hemodynamic Energy During Pediatric Pulsatile Extracorporeal Life Support?

PubMed

Wang, Shigang; Kunselman, Allen R; Ündar, Akif

2017-01-01

The objective of this study was to evaluate the hemodynamic performance and energy transmission of flexible arterial tubing as the arterial line in a simulated pediatric pulsatile extracorporeal life support (ECLS) system. The ECLS circuit consisted of a Medos Deltastream DP3 diagonal pump head, Medos Hilite 2400 LT oxygenator, Biomedicus arterial/venous cannula (10 Fr/14 Fr), 3 feet of polyvinyl chloride (PVC) arterial tubing or latex rubber arterial tubing, primed with lactated Ringer's solution and packed red blood cells (hematocrit 40%). Trials were conducted at flow rates of 300 to 1200 mL/min (300 mL/min increments) under nonpulsatile and pulsatile modes at 36°C using either PVC arterial tubing (PVC group) or latex rubber tubing (Latex group). Real-time pressure and flow data were recorded using a custom-based data acquisition system. Mean pressures and energy equivalent pressures (EEP) were the same under nonpulsatile mode between the two groups. Under pulsatile mode, EEPs were significantly great than mean pressure, especially in the Latex group (P < 0.05). There was no difference between the two groups with regards to pressure drops across ECLS circuit, but pulsatile flow created more pressure drops than nonpulsatile flow (P < 0.05). Surplus hemodynamic energy (SHE) levels were always higher in the Latex group than in the PVC group at all sites. Although total hemodynamic energy (THE) losses were higher under pulsatile mode compared to nonpulsatile mode, more THE was delivered to the pseudopatient, particularly in the Latex group (P < 0.05). The results showed that the flexible arterial tubing retained more hemodynamic energy passing through it under pulsatile mode while mean pressures and pressure drops across the ECLS circuit were similar between PVC and latex rubber arterial tubing. Further studies are warranted to verify our findings. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Microstructured Nickel-Titanium Thin Film Leaflets for Hybrid Tissue Engineered Heart Valves Fabricated by Magnetron Sputter Deposition.

PubMed

Loger, K; Engel, A; Haupt, J; Lima de Miranda, R; Lutter, G; Quandt, E

2016-03-01

Heart valves are constantly exposed to high dynamic loading and are prone to degeneration. Therefore, it is a challenge to develop a durable heart valve substitute. A promising approach in heart valve engineering is the development of hybrid scaffolds which are composed of a mechanically strong inorganic mesh enclosed by valvular tissue. In order to engineer an efficient, durable and very thin heart valve for transcatheter implantations, we developed a fabrication process for microstructured heart valve leaflets made from a nickel-titanium (NiTi) thin film shape memory alloy. To examine the capability of microstructured NiTi thin film as a matrix scaffold for tissue engineered hybrid heart valves, leaflets were successfully seeded with smooth muscle cells (SMCs). In vitro pulsatile hydrodynamic testing of the NiTi thin film valve leaflets demonstrated that the SMC layer significantly improved the diastolic sufficiency of the microstructured leaflets, without affecting the systolic efficiency. Compared to an established porcine reference valve model, magnetron sputtered NiTi thin film material demonstrated its suitability for hybrid tissue engineered heart valves.

Adding the 'heart' to hanging drop networks for microphysiological multi-tissue experiments.

PubMed

Rismani Yazdi, Saeed; Shadmani, Amir; Bürgel, Sebastian C; Misun, Patrick M; Hierlemann, Andreas; Frey, Olivier

2015-11-07

Microfluidic hanging-drop networks enable culturing and analysis of 3D microtissue spheroids derived from different cell types under controlled perfusion and investigating inter-tissue communication in multi-tissue formats. In this paper we introduce a compact on-chip pumping approach for flow control in hanging-drop networks. The pump includes one pneumatic chamber located directly above one of the hanging drops and uses the surface tension at the liquid-air-interface for flow actuation. Control of the pneumatic protocol provides a wide range of unidirectional pulsatile and continuous flow profiles. With the proposed concept several independent hanging-drop networks can be operated in parallel with only one single pneumatic actuation line at high fidelity. Closed-loop medium circulation between different organ models for multi-tissue formats and multiple simultaneous assays in parallel are possible. Finally, we implemented a real-time feedback control-loop of the pump actuation based on the beating of a human iPS-derived cardiac microtissue cultured in the same system. This configuration allows for simulating physiological effects on the heart and their impact on flow circulation between the organ models on chip.

Method and apparatus to assess compartment syndrome

NASA Technical Reports Server (NTRS)

Hargens, Alan R. (Inventor); Yost, William T. (Inventor); Ueno, Toshiaki (Inventor)

2008-01-01

A method and apparatus for measuring pressure buildup in a body compartment that encases muscular tissue. The method includes assessing the body compartment configuration and identifying the effect of pulsatile components on at least one compartment dimension. This process is used in preventing tissue necrosis, and in decisions of whether to perform surgery on the body compartment for prevention of Compartment Syndrome. An apparatus is used for measuring excess pressure in the body compartment having components for imparting ultrasonic waves such as a transducer, placing the transducer to impart the ultrasonic waves, capturing the reflected imparted ultrasonic waves, and converting them to electrical signals, a pulsed phase-locked loop device for assessing a body compartment configuration and producing an output signal, and means for mathematically manipulating the output signal to thereby categorize pressure build-up in the body compartment from the mathematical manipulations.

A pulsatile pressure waveform is a sensitive marker for confirming the location of the thoracic epidural space.

PubMed

Lennox, Pamela H; Umedaly, Hamed S; Grant, Raymer P; White, S Adrian; Fitzmaurice, Brett G; Evans, Kenneth G

2006-10-01

The purpose of this study was to assess the validity of using a pulsatile, pressure waveform transduced from the epidural space through an epidural needle or catheter to confirm correct placement for maximal analgesia and to compare 3 different types of catheters' ability to transduce a waveform. A single-center, prospective, randomized trial. A tertiary-referral hospital. Eighty-one patients undergoing posterolateral thoracotomy who required a thoracic epidural catheter for postoperative pain management. Each epidural needle and each epidural catheter was transduced to determine if there was a pulsatile waveform exhibited. Sensitivity of the pulsatile waveform transduced through an epidural needle to identify correct placement of the epidural needle and the sensitivity of each catheter type to identify placement were compared. In 79 of 81 cases (97.5%), the waveform transduced directly through the epidural needle had a pulsatile characteristic as determined by blinded observers. In a total of 53 of 81 epidural catheters (65.4%), the transduced waveform displayed pulsations. Twenty-four of 27 catheters in group S-P/Sims Portex (Smiths Medical MD, Inc, St Paul, MN) (88.9%) transduced a pulsatile tracing from the epidural space, a significantly greater percentage than in the other 2 groups (p = 0.02). The technique of transducing the pressure waveform from the epidural needle inserted in the epidural space is a sensitive and reliable alternative to other techniques for confirmation of correct epidural catheter placement. The technique is simple, sensitive, and inexpensive and uses equipment available in any operating room.

Stability of carotid artery under steady-state and pulsatile blood flow: a fluid-structure interaction study.

PubMed

Saeid Khalafvand, Seyed; Han, Hai-Chao

2015-06-01

It has been shown that arteries may buckle into tortuous shapes under lumen pressure, which in turn could alter blood flow. However, the mechanisms of artery instability under pulsatile flow have not been fully understood. The objective of this study was to simulate the buckling and post-buckling behaviors of the carotid artery under pulsatile flow using a fully coupled fluid-structure interaction (FSI) method. The artery wall was modeled as a nonlinear material with a two-fiber strain-energy function. FSI simulations were performed under steady-state flow and pulsatile flow conditions with a prescribed flow velocity profile at the inlet and different pressures at the outlet to determine the critical buckling pressure. Simulations were performed for normal (160 ml/min) and high (350 ml/min) flow rates and normal (1.5) and reduced (1.3) axial stretch ratios to determine the effects of flow rate and axial tension on stability. The results showed that an artery buckled when the lumen pressure exceeded a critical value. The critical mean buckling pressure at pulsatile flow was 17-23% smaller than at steady-state flow. For both steady-state and pulsatile flow, the high flow rate had very little effect (<5%) on the critical buckling pressure. The fluid and wall stresses were drastically altered at the location with maximum deflection. The maximum lumen shear stress occurred at the inner side of the bend and maximum tensile wall stresses occurred at the outer side. These findings improve our understanding of artery instability in vivo.

Stability of Carotid Artery Under Steady-State and Pulsatile Blood Flow: A Fluid–Structure Interaction Study

PubMed Central

Saeid Khalafvand, Seyed; Han, Hai-Chao

2015-01-01

It has been shown that arteries may buckle into tortuous shapes under lumen pressure, which in turn could alter blood flow. However, the mechanisms of artery instability under pulsatile flow have not been fully understood. The objective of this study was to simulate the buckling and post-buckling behaviors of the carotid artery under pulsatile flow using a fully coupled fluid–structure interaction (FSI) method. The artery wall was modeled as a nonlinear material with a two-fiber strain-energy function. FSI simulations were performed under steady-state flow and pulsatile flow conditions with a prescribed flow velocity profile at the inlet and different pressures at the outlet to determine the critical buckling pressure. Simulations were performed for normal (160 ml/min) and high (350 ml/min) flow rates and normal (1.5) and reduced (1.3) axial stretch ratios to determine the effects of flow rate and axial tension on stability. The results showed that an artery buckled when the lumen pressure exceeded a critical value. The critical mean buckling pressure at pulsatile flow was 17–23% smaller than at steady-state flow. For both steady-state and pulsatile flow, the high flow rate had very little effect (<5%) on the critical buckling pressure. The fluid and wall stresses were drastically altered at the location with maximum deflection. The maximum lumen shear stress occurred at the inner side of the bend and maximum tensile wall stresses occurred at the outer side. These findings improve our understanding of artery instability in vivo. PMID:25761257

Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia.

PubMed

Bachelot, Anne; Chakhtoura, Zeina; Plu-Bureau, Geneviève; Coudert, Mathieu; Coussieu, Christiane; Badachi, Yasmina; Dulon, Jérome; Charbit, Beny; Touraine, Philippe

2012-10-01

Women with classical congenital adrenal hyperplasia (CAH) exhibit reduced fertility due to several factors including anovulation. This has been attributed to a disturbed gonadotropic axis as in polycystic ovary syndrome (PCOS), but there is no precise evaluation. Our aim was to evaluate the gonadotropic axis and LH pulsatility patterns and to determine factor(s) that could account for the potential abnormality of LH pulsatility. Case/control study. Sixteen CAH women (11 with the salt-wasting form and five with the simple virilizing form), aged from 18 to 40 years, and 16 age-matched women, with regular menstrual cycles (28 ± 3 days), were included. LH pulse patterns over 6 h were determined in patients and controls. No differences were observed between patients and controls in terms of mean LH levels, LH pulse amplitude, or LH frequency. In CAH patients, LH pulsatility patterns were heterogeneous, leading us to perform a clustering analysis of LH data, resulting in a two-cluster partition. Patients in cluster 1 had similar LH pulsatility patterns to the controls. Patients in cluster 2 had: lower LH pulse amplitude and frequency and presented menstrual cycle disturbances more frequently; higher 17-OH progesterone, testosterone, progesterone, and androstenedione levels; and lower FSH levels. LH pulsatility may be normal in CAH women well controlled by hormonal treatment. Undertreatment is responsible for hypogonadotropic hypogonadism, with low LH pulse levels and frequency, but not PCOS. Suppression of progesterone and androgen concentrations during the follicular phase of the menstrual cycle should be a major objective in these patients.

Inflammatory Cell Infiltrates in Acute and Chronic Thoracic Aortic Dissection.

PubMed

Wu, Darrell; Choi, Justin C; Sameri, Aryan; Minard, Charles G; Coselli, Joseph S; Shen, Ying H; LeMaire, Scott A

2013-12-01

Thoracic aortic dissection (TAD) is a highly lethal cardiovascular disease. Injury to the intima and media allows pulsatile blood to enter the media, leading to dissection formation. Inflammatory cells then infiltrate the site of aortic injury to clear dead cells and damaged tissue. This excessive inflammation may play a role in aneurysm formation after dissection. Using immunohistochemistry, we compared aortic tissues from patients with acute TAD (n = 11), patients with chronic TAD (n = 35), and donor controls (n = 20) for the presence of CD68+ macrophages, neutrophils, mast cells, and CD3+ T lymphocytes. Tissue samples from patients with acute or chronic TAD generally had significantly more inflammatory cells in both the medial and adventitial layers than did the control samples. In tissues from patients with acute TAD, the adventitia had more of the inflammatory cells studied than did the media. The pattern of increase in inflammatory cells was similar in chronic and acute TAD tissues, except for macrophages, which were seen more frequently in the adventitial layer of acute TAD tissue than in the adventitia of chronic TAD tissue. The inflammatory cell content of both acute and chronic TAD tissue was significantly different from that of control tissue. However, the inflammatory cell profile of aneurysmal chronic TAD was similar to that of acute TAD. This may reflect a sustained injury response that contributes to medial degeneration and aneurysm formation.

Analysis of Computational Fluid Dynamics and Particle Image Velocimetry Models of Distal-End Side-to-Side and End-to-Side Anastomoses for Coronary Artery Bypass Grafting in a Pulsatile Flow.

PubMed

Shintani, Yoshiko; Iino, Kenji; Yamamoto, Yoshitaka; Kato, Hiroki; Takemura, Hirofumi; Kiwata, Takahiro

2017-12-25

Intimal hyperplasia (IH) is a major cause of graft failure. Hemodynamic factors such as stagnation and disturbed blood flow are involved in IH formation. The aim of this study is to perform a comparative analysis of distal-end side-to-side (deSTS) and end-to-side (ETS) anastomoses using computational fluid dynamics (CFD) after validating the results via particle image velocimetry (PIV).Methods and Results:We investigated the characteristics of our target flow fields using CFD under steady and pulsatile flows. CFD via PIV under steady flow in a 10-times-actual-size model was validated. The CFD analysis revealed a recirculation zone in the heel region in the deSTS and ETS anastomoses and at the distal end of the graft, and just distal to the toe of the host artery in the deSTS anastomoses. The recirculation zone sizes changed with the phase shift. We found regions of low wall shear stress and high oscillating shear index in the same areas. The PIV and CFD results were similar. It was demonstrated that the hemodynamic characteristics of CFD and PIV is the difference between the deSTS and ETS anastomoses; that is, the deSTS flow peripheral to the distal end of the graft, at the distal end and just distal to the toe of the host artery is involved in the IH formation.

Influence of cardiac motion on stent lumen visualization in third generation dual-source CT employing a pulsatile heart model.

PubMed

Petri, Nils; Gassenmaier, Tobias; Allmendinger, Thomas; Flohr, Thomas; Voelker, Wolfram; Bley, Thorsten A

2017-02-01

To detect an in-stent restenosis, an invasive coronary angiography is commonly performed. Owing to the risk associated with this procedure, a non-invasive method to detect or exclude an in-stent restenosis is desirable. The purpose of this study was to evaluate the influence of cardiac motion on stent lumen visibility in a third-generation dual-source CT scanner (SOMATOM Force; Siemens Healthcare, Forchheim, Germany), employing a pulsatile heart model (CoroSim ® ; Mecora, Aachen, Germany). 13 coronary stents with a diameter of 3.0 mm were implanted in plastic tubes filled with a contrast medium and then fixed onto the pulsatile phantom heart model. The scans were performed while the heart model mimicked the heartbeat. Coronary stents were scanned in an orientation parallel to the scanner z-axis. The evaluation of the stents was performed by employing a medium sharp convolution kernel optimized for vascular imaging. The mean visible stent lumen was reduced from 65.6 ± 5.7% for the stents at rest to 60.8 ± 4.4% for the stents in motion (p-value: <0.001). While the difference in lumen visibility between stents in motion and at rest was significant, the use of this third-generation dual-source CT scanner enabled a high stent lumen visibility under the influence of cardiac motion. Whether this translates into a clinical setting has to be evaluated in further patient studies. Advances in knowledge: The employed modern CT scanner enables a high stent lumen visibility even under the influence of cardiac motion, which is important to detect or exclude an in-stent restenosis.

Graft flow assessment using a transit time flow meter in fractional flow reserve-guided coronary artery bypass surgery.

PubMed

Honda, Kentaro; Okamura, Yoshitaka; Nishimura, Yoshiharu; Uchita, Shunji; Yuzaki, Mitsuru; Kaneko, Masahiro; Yamamoto, Nobuko; Kubo, Takashi; Akasaka, Takashi

2015-06-01

To evaluate the relationship between preoperative severity of coronary stenosis occurring with fractional flow reserve (FFR), and the intraoperative bypass graft flow pattern. In all, 72 patients were enrolled in this retrospective study. The FFR value of the left anterior descending artery was evaluated, and data on "in situ" bypass grafting from the internal thoracic artery to the left anterior descending artery were assessed. Patients were divided into 3 groups according to preoperative FFR values (Group S: FFR < 0.70; group M: 0.70 ≤ FFR < 0.75; and group N: FFR ≥ 0.75). In groups S, M, and N, respectively, mean graft flow was 24.7 ± 10.6 mL/minute, 19.2 ± 14.0 mL/minute, and 16.0 ± 9.7 mL mL/minute; pulsatility index was 2.35 ± 0.6, 3.02 ± 1.1, and 5.51 ± 8.20; and number of patients with systolic reverse flow was 3 (6.8%), 5 (35.7%), and 4 (28.6%). Significant differences were observed in graft flow (P = .009), pulsatility index (P = .038), and proportion of systolic reverse flow (P = .023) among the 3 groups. In all patients, graft patency was confirmed with intraoperative fluorescence imaging; postoperative graft patency was confirmed with multislice computed tomography or coronary angiography in 69 patients (follow-up interval: 213 days). Early graft failure occurred in 1 patient. As coronary stenosis severity increased, graft flow increased, pulsatility index decreased, and proportion of patients with systolic reverse flow increased. In mild coronary artery stenosis, the chance of flow competition between the native coronary artery and the bypass graft increased. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Changes in the retrobulbar arterial circulation after decrease of the elevated intraocular pressure in men and women with primary open angle glaucoma.

PubMed

Marjanović, Ivan; Martinez, Antonio; Marjanović, Marija; Kontić, Djordje; Hentova-Senćanić, Paraskeva; Marković, Vujica; Bozić, Marija

2013-01-01

An altered perfusion of the optic nerve head has been proposed as a pathogenic factor of glaucoma. The aim of this study was to evaluate the changes of the hemodynamic parameters in the retrobulbar arterial circulation after decrease of the elevated intraocular pressure (IOP) in women and men with primary open angle glaucoma. The study included 60 patients (33 males and 27 females) older than 50 years, with diagnosed and treated primary open angle glaucoma (77 eyes of 39 patients had increased IOP, > 25 mm Hg).They were examined at the Clinic of Eye Diseases (complete ophthalmologic exam) and Clinic of Neurology, Clinical Center of Serbia, Belgrade, from December 2009 to December 2010. Imaging of hemodynamic parameters of three retrobulbar arterial vessels: ophthalmic, central retinal and posterior ciliary arteries with color Doppler was performed. Among women, hemodynamic arterial parameter of the peak-systolic velocity was increased in the central retinal artery and decreased in the ophthalmic artery and posterior ciliary arteries; end-diastolic velocity was increased in all three retrobulbar vascular levels; Pourcelot resistivity index was increased, but pulsatility index was decreased in all three vessels. Among men, peak-systolic velocity, end-diastolic velocity and pulsatility index were decreased in all three vessels; resistivity index was increased in the ophthalmic artery, but decreased in the central retinal artery and posterior ciliary arteries. There was a significant change of the ophthalmic artery pulsatility index in women, and the end-diastolic velocity of the ophthalmic artery in men. There was a difference of the retrobulbar arterial circulation between women and men with primary open angle glaucoma after decrease of the elevated intraocular pressure.The role of vascular factors in the supply of the optic disc neuroretinal rim is important.

Surface obstacles in pulsatile flow

NASA Astrophysics Data System (ADS)

Carr, Ian A.; Plesniak, Michael W.

2016-11-01

Flows past obstacles mounted on flat surfaces have been widely studied due to their ubiquity in nature and engineering. For nearly all of these studies, the freestream flow over the obstacle was steady, i.e. constant velocity unidirectional flow. Unsteady, pulsatile flows occur frequently in biology, geophysics, biomedical engineering, etc. Our study is aimed at extending the comprehensive knowledge base that exists for steady flows to considerably more complex pulsatile flows. Beyond the important practical applications, characterizing the vortex and wake dynamics of flows around surface obstacles embedded in pulsatile flows can provide insights into the underlying physics in all wake and junction flows. In this study, we experimentally investigated the wake of four canonical surface obstacles: hemisphere, cube, and circular cylinders with aspect ratio of 1:1 and 2:1. Phase-averaged PIV and hot-wire anemometry are used to characterize the dynamics of coherent structures in the wake and at the windward junction of the obstacles. Complex physics occur during the deceleration phase of the pulsatile inflow. We propose a framework for understanding these physics based on self-induced vortex propagation, similar to the phenomena exhibited by vortex rings. This material is based in part upon work supported by the National Science Foundation under Grant Number CBET-1236351, and GW Centeor Biomimetics and Bioinspired Engineering (COBRE).

Application of a pressure-relieving air compliance chamber in a single-pulsatile extracorporeal life support system: an experimental study.

PubMed

Kim, Tae Sik; Sun, Kyung; Lee, Kyu Baek; Lee, Hye Won; Baek, Kwang Je; Park, Sung Young; Son, Ho Sung; Kim, Kwang Taik; Kim, Hyoung Mook

2004-12-01

Nonpulsatile blood pumps are mainly used in extracorporeal life support systems. Although pulsating blood flow is known to be physiological, a pulsatile pump is not commonly applied in a circuit with a membrane oxygenator because of damage to the blood cells. The hypothesis that the placement of a pressure-relieving compliance chamber in a circuit might reduce blood cell trauma was tested. An extracorporeal life support circuit was constructed in an acute lung injury model of dogs by oleic acid infusion. The animals were divided into three groups. In group I (n = 6) a nonpulsatile centrifugal pump was used as a control. In group II (n = 4) a single-pulsatile pump was used, and in group III (n = 6) a single-pulsatile pump equipped with a compliance chamber was used. Pump flow was maintained at 1.8-2.0 L/min for 2 h. Hemodynamics and blood gas analyses indicated that the pulsatile groups II and III had better results than the nonpulsatile group I. The plasma-free hemoglobin level, which indicates blood cell trauma, was the lowest in group I and the highest in group II but was significantly decreased in group III. A pressure-relieving compliance chamber could significantly reduce high circuit pressures and blood cell trauma.

Film coatings for oral pulsatile release.

PubMed

Maroni, Alessandra; Zema, Lucia; Loreti, Giulia; Palugan, Luca; Gazzaniga, Andrea

2013-12-05

Pulsatile delivery is generally intended as a release of the active ingredient that is delayed for a programmable period of time to meet particular chronotherapeutic needs and, in the case of oral administration, also target distal intestinal regions, such as the colon. Most oral pulsatile delivery platforms consist in coated formulations wherein the applied polymer serves as the release-controlling agent. When exposed to aqueous media, the coating initially performs as a protective barrier and, subsequently, undergoes a timely failure based on diverse mechanisms depending on its physico-chemical and formulation characteristics. Indeed, it may be ruptured because of the gradual expansion of the core, swell and/or erode due to the glassy-rubbery polymer transition or become permeable thus allowing the drug molecules to diffuse outwards. Otherwise, when the coating is a semipermeable membrane provided with one or more orifices, the drug is released through the latter as a result of an osmotic water influx. The vast majority of pulsatile delivery systems described so far have been prepared by spray-coating, which offers important versatility and feasibility advantages over other techniques such as press- and dip-coating. In the present article, the design, manufacturing and performance of spray-coated pulsatile delivery platforms is thus reviewed. Copyright © 2013 Elsevier B.V. All rights reserved.

Age-specific changes in the regulation of LH-dependent testosterone secretion: assessing responsiveness to varying endogenous gonadotropin output in normal men.

PubMed

Liu, Peter Y; Takahashi, Paul Y; Roebuck, Pamela D; Iranmanesh, Ali; Veldhuis, Johannes D

2005-09-01

Pulsatile and thus total testosterone (Te) secretion declines in older men, albeit for unknown reasons. Analytical models forecast that aging may reduce the capability of endogenous luteinizing hormone (LH) pulses to stimulate Leydig cell steroidogenesis. This notion has been difficult to test experimentally. The present study used graded doses of a selective gonadotropin releasing hormone (GnRH)-receptor antagonist to yield four distinct strata of pulsatile LH release in each of 18 healthy men ages 23-72 yr. Deconvolution analysis was applied to frequently sampled LH and Te concentration time series to quantitate pulsatile Te secretion over a 16-h interval. Log-linear regression was used to relate pulsatile LH secretion to attendant pulsatile Te secretion (LH-Te drive) across the four stepwise interventions in each subject. Linear regression of the 18 individual estimates of LH-Te feedforward dose-response slopes on age disclosed a strongly negative relationship (r = -0.721, P < 0.001). Accordingly, the present data support the thesis that aging in healthy men attenuates amplitude-dependent LH drive of burst-like Te secretion. The experimental strategy of graded suppression of neuroglandular outflow may have utility in estimating dose-response adaptations in other endocrine systems.

Fluid-structure interaction modeling of aneurysmal arteries under steady-state and pulsatile blood flow: a stability analysis.

PubMed

Sharzehee, Mohammadali; Khalafvand, Seyed Saeid; Han, Hai-Chao

2018-02-01

Tortuous aneurysmal arteries are often associated with a higher risk of rupture but the mechanism remains unclear. The goal of this study was to analyze the buckling and post-buckling behaviors of aneurysmal arteries under pulsatile flow. To accomplish this goal, we analyzed the buckling behavior of model carotid and abdominal aorta with aneurysms by utilizing fluid-structure interaction (FSI) method with realistic waveforms boundary conditions. FSI simulations were done under steady-state and pulsatile flow for normal (1.5) and reduced (1.3) axial stretch ratios to investigate the influence of aneurysm, pulsatile lumen pressure and axial tension on stability. Our results indicated that aneurysmal artery buckled at the critical buckling pressure and its deflection nonlinearly increased with increasing lumen pressure. Buckling elevates the peak stress (up to 118%). The maximum aneurysm wall stress at pulsatile FSI flow was (29%) higher than under static pressure at the peak lumen pressure of 130 mmHg. Buckling results show an increase in lumen shear stress at the inner side of the maximum deflection. Vortex flow was dramatically enlarged with increasing lumen pressure and artery diameter. Aneurysmal arteries are more susceptible than normal arteries to mechanical instability which causes high stresses in the aneurysm wall that could lead to aneurysm rupture.

Disturbance of the reproductive axis induced by negative energy balance.

PubMed

Judd, S J

1998-01-01

Animal reproduction is impaired when intake of energy is so restricted that activities essential to life are threatened; this is seen as a homeostatic adjustment that restricts wasteful energy expenditure. Fasting or exercising to a degree requiring considerable energy expenditure has major effects on the hypothalamus, including activation of corticotrophin-releasing factor (CRF) neurons, suppression of thyrotrophin-releasing hormone synthesis, and increased growth hormone secretion; these are associated with increased concentrations of hypothalamic neuropeptide Y mRNA and are corrected by administration of leptin, an adipose-tissue protein with a tertiary structure similar to the cytokine interleukin-2. This response to fasting results from a disordered pattern of activity in the gonadotrophin-releasing hormone (GnRH) pacemaker, characterized by reduced luteinizing hormone pulsatility, particularly during daytime. Animal studies have suggested that the response depends on an intact afferent vagal system from the stomach and the presence of oestrogen. Noradrenergic neurons forming the A2 group increase the activity of CRF neurons that, in turn, inhibit GnRH pulsatility. Reproductive impairment due to fasting is reversed by leptin, and abnormalities of leptin are described in individuals who fast or who develop exercise-induced amenorrhoea. This paper discusses these changes induced by negative energy balance and speculates on the involvement of leptin as a contributor to these abnormalities.

Modelling carotid artery adaptations to dynamic alterations in pressure and flow over the cardiac cycle

PubMed Central

Cardamone, L.; Valentín, A.; Eberth, J. F.; Humphrey, J. D.

2010-01-01

Motivated by recent clinical and laboratory findings of important effects of pulsatile pressure and flow on arterial adaptations, we employ and extend an established constrained mixture framework of growth (change in mass) and remodelling (change in structure) to include such dynamical effects. New descriptors of cell and tissue behavior (constitutive relations) are postulated and refined based on new experimental data from a transverse aortic arch banding model in the mouse that increases pulsatile pressure and flow in one carotid artery. In particular, it is shown that there was a need to refine constitutive relations for the active stress generated by smooth muscle, to include both stress- and stress rate-mediated control of the turnover of cells and matrix and to account for a cyclic stress-mediated loss of elastic fibre integrity and decrease in collagen stiffness in order to capture the reported evolution, over 8 weeks, of luminal radius, wall thickness, axial force and in vivo axial stretch of the hypertensive mouse carotid artery. We submit, therefore, that complex aspects of adaptation by elastic arteries can be predicted by constrained mixture models wherein individual constituents are produced or removed at individual rates and to individual extents depending on changes in both stress and stress rate from normal values. PMID:20484365

Electrophysiology of Hypothalamic Magnocellular Neurons In vitro: A Rhythmic Drive in Organotypic Cultures and Acute Slices.

PubMed

Israel, Jean-Marc; Oliet, Stéphane H; Ciofi, Philippe

2016-01-01

Hypothalamic neurohormones are released in a pulsatile manner. The mechanisms of this pulsatility remain poorly understood and several hypotheses are available, depending upon the neuroendocrine system considered. Among these systems, hypothalamo-neurohypophyseal magnocellular neurons have been early-considered models, as they typically display an electrical activity consisting of bursts of action potentials that is optimal for the release of boluses of the neurohormones oxytocin and vasopressin. The cellular mechanisms underlying this bursting behavior have been studied in vitro, using either acute slices of the adult hypothalamus, or organotypic cultures of neonatal hypothalamic tissue. We have recently proposed, from experiments in organotypic cultures, that specific central pattern generator networks, upstream of magnocellular neurons, determine their bursting activity. Here, we have tested whether a similar hypothesis can be derived from in vitro experiments in acute slices of the adult hypothalamus. To this aim we have screened our electrophysiological recordings of the magnocellular neurons, previously obtained from acute slices, with an analysis of autocorrelation of action potentials to detect a rhythmic drive as we recently did for organotypic cultures. This confirmed that the bursting behavior of magnocellular neurons is governed by central pattern generator networks whose rhythmic drive, and thus probably integrity, is however less satisfactorily preserved in the acute slices from adult brains.

Blood Flow Modulation of Vascular Dynamics

PubMed Central

Lee, Juhyun; Sevag Packard, René R.; Hsiai, Tzung K.

2015-01-01

Purpose of review Blood flow is intimately linked with cardiovascular development, repair, and dysfunction. The current review will build on the fluid mechanical principle underlying hemodynamic shear forces, mechanotransduction, and metabolic effects. Recent findings Pulsatile flow produces both time- (∂τ /∂t)and spatial-varying shear stress (∂τ /∂x) to modulate vascular oxidative stress and inflammatory response with pathophysiological significance to atherosclerosis. The characteristics of hemodynamic shear forces; namely, steady laminar (∂τ /∂t= 0), pulsatile (PSS: unidirectional forward flow), and oscillatory shear stress (OSS: bidirectional with a near net 0 forward flow) modulate mechano-signal transduction to influence metabolic effects on vascular endothelial function. Atheroprotective PSS promotes anti-oxidant, anti-inflammatory, and anti-thrombotic responses, whereas atherogenic OSS induces NADPH oxidase–JNK signaling to increase mitochondrial superoxide production, protein degradation of manganese superoxide dismutase (MnSOD), and post-translational protein modifications of LDL particles in the disturbed flow-exposed regions of vasculature. In the era of tissue regeneration, shear stress has been implicated in re-activation of developmental genes; namely, Wnt and Notch signaling, for vascular development and repair. Summary Blood flow imparts a dynamic continuum from vascular development to repair. Augmentation of PSS confers atheroprotection and re-activation of developmental signaling pathways for regeneration. PMID:26218416

The Decline in Pulsatile GnRH Release, as Reflected by Circulating LH Concentrations, During the Infant-Juvenile Transition in the Agonadal Male Rhesus Monkey (Macaca mulatta) Is Associated With a Reduction in Kisspeptin Content of KNDy Neurons of the Arcuate Nucleus in the Hypothalamus

PubMed Central

Ramaswamy, Suresh; Dwarki, Karthik; Ali, Barkat; Gibbs, Robert B.

2013-01-01

Puberty in primates is timed by 2 hypothalamic events: during late infancy a decline in pulsatile GnRH release occurs, leading to a hypogonadotropic state that maintains quiescence of the prepubertal gonad; and in late juvenile development, pulsatile GnRH release is reactivated and puberty initiated, a phase of development that is dependent on kisspeptin signaling. In the present study, we determined whether the arrest of GnRH pulsatility in infancy was associated with a change in kisspeptin expression in the mediobasal hypothalamus (MBH). Kisspeptin was determined using immunohistochemistry in coronal hypothalamic sections from agonadal male rhesus monkeys during early infancy when GnRH release as reflected by circulating LH concentrations was robust and compared with that in juveniles in which GnRH pulsatility was arrested. The distribution of immunopositive kisspeptin neurons in the arcuate nucleus of the MBH of infants was similar to that previously reported for adults. Kisspeptin cell body number was greater in infants compared with juveniles, and at the middle to posterior level of the arcuate nucleus, this developmental difference was statistically significant. Neurokinin B in the MBH exhibited a similar distribution to that of kisspeptin and was colocalized with kisspeptin in approximately 60% of kisspeptin perikarya at both developmental stages. Intensity of GnRH fiber staining in the median eminence was robust at both stages. These findings indicate that the switch that shuts off pulsatile GnRH release during infancy and that guarantees the subsequent quiescence of the prepubertal gonad involves a reduction in a stimulatory kisspeptin tone to the GnRH neuronal network. PMID:23525220

Blood Pressure and Arterial Load After Transcatheter Aortic Valve Replacement for Aortic Stenosis.

PubMed

Lindman, Brian R; Otto, Catherine M; Douglas, Pamela S; Hahn, Rebecca T; Elmariah, Sammy; Weissman, Neil J; Stewart, William J; Ayele, Girma M; Zhang, Feifan; Zajarias, Alan; Maniar, Hersh S; Jilaihawi, Hasan; Blackstone, Eugene; Chinnakondepalli, Khaja M; Tuzcu, E Murat; Leon, Martin B; Pibarot, Philippe

2017-07-01

After aortic valve replacement, left ventricular afterload is often characterized by the residual valve obstruction. Our objective was to determine whether higher systemic arterial afterload-as reflected in blood pressure, pulsatile and resistive load-is associated with adverse clinical outcomes after transcatheter aortic valve replacement (TAVR). Total, pulsatile, and resistive arterial load were measured in 2141 patients with severe aortic stenosis treated with TAVR in the PARTNER I trial (Placement of Aortic Transcatheter Valve) who had systolic blood pressure (SBP) and an echocardiogram obtained 30 days after TAVR. The primary end point was 30-day to 1-year all-cause mortality. Lower SBP at 30 days after TAVR was associated with higher mortality (20.0% for SBP 100-129 mm Hg versus 12.0% for SBP 130-170 mm Hg; P <0.001). This association remained significant after adjustment, was consistent across subgroups, and confirmed in sensitivity analyses. In adjusted models that included SBP, higher total and pulsatile arterial load were associated with increased mortality ( P <0.001 for all), but resistive load was not. Patients with low 30-day SBP and high pulsatile load had a 3-fold higher mortality than those with high 30-day SBP and low pulsatile load (26.1% versus 8.1%; hazard ratio, 3.62; 95% confidence interval, 2.36-5.55). Even after relief of valve obstruction in patients with aortic stenosis, there is an independent association between post-TAVR blood pressure, systemic arterial load, and mortality. Blood pressure goals in patients with a history of aortic stenosis may need to be redefined. Increased pulsatile arterial load, rather than blood pressure, may be a target for adjunctive medical therapy to improve outcomes after TAVR. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. © 2017 American Heart Association, Inc.

The correlation between pulsatile intracranial pressure and indices of intracranial pressure-volume reserve capacity: results from ventricular infusion testing.

PubMed

Eide, Per Kristian

2016-12-01

OBJECTIVE The objective of this study was to examine how pulsatile and static intracranial pressure (ICP) scores correlate with indices of intracranial pressure-volume reserve capacity, i.e., intracranial elastance (ICE) and intracranial compliance (ICC), as determined during ventricular infusion testing. METHODS All patients undergoing ventricular infusion testing and overnight ICP monitoring during the 6-year period from 2007 to 2012 were included in the study. Clinical data were retrieved from a quality registry, and the ventricular infusion pressure data and ICP scores were retrieved from a pressure database. The ICE and ICC (= 1/ICE) were computed during the infusion phase of the infusion test. RESULTS During the period from 2007 to 2012, 82 patients with possible treatment-dependent hydrocephalus underwent ventricular infusion testing within the department of neurosurgery. The infusion tests revealed a highly significant positive correlation between ICE and the pulsatile ICP scores mean wave amplitude (MWA) and rise-time coefficient (RTC), and the static ICP score mean ICP. The ICE was negatively associated with linear measures of ventricular size. The overnight ICP recordings revealed significantly increased MWA (> 4 mm Hg) and RTC (> 20 mm Hg/sec) values in patients with impaired ICC (< 0.5 ml/mm Hg). CONCLUSIONS In this study cohort, there was a significant positive correlation between pulsatile ICP and ICE measured during ventricular infusion testing. In patients with impaired ICC during infusion testing (ICC < 0.5 ml/mm Hg), overnight ICP recordings showed increased pulsatile ICP (MWA > 4 mm Hg, RTC > 20 mm Hg/sec), but not increased mean ICP (< 10-15 mm Hg). The present data support the assumption that pulsatile ICP (MWA and RTC) may serve as substitute markers of pressure-volume reserve capacity, i.e., ICE and ICC.

Does polycystic ovarian morphology influence the response to treatment with pulsatile GnRH in functional hypothalamic amenorrhea?

PubMed

Dumont, Agathe; Dewailly, Didier; Plouvier, Pauline; Catteau-Jonard, Sophie; Robin, Geoffroy

2016-04-29

Pulsatile GnRH therapy is the gold standard treatment for ovulation induction in women having functional hypothalamic amenorrhea (FHA). The use of pulsatile GnRH therapy in FHA patients with polycystic ovarian morphology (PCOM), called "FHA-PCOM", has been little studied in the literature and results remain contradictory. The aim of this study was to compare the outcomes of pulsatile GnRH therapy for ovulation induction between FHA and "FHA-PCOM" patients in order to search for an eventual impact of PCOM. Retrospective study from August 2002 to June 2015, including 27 patients with FHA and 40 "FHA-PCOM" patients (85 and 104 initiated cycles, respectively) treated by pulsatile GnRH therapy for induction ovulation. The two groups were similar except for markers of PCOM (follicle number per ovary, serum Anti-Müllerian Hormone level and ovarian area), which were significantly higher in patients with "FHA-PCOM". There was no significant difference between the groups concerning the ovarian response: with equivalent doses of GnRH, both groups had similar ovulation (80.8 vs 77.7 %, NS) and excessive response rates (12.5 vs 10.6 %, NS). There was no significant difference in on-going pregnancy rates (26.9 vs 20 % per initiated cycle, NS), as well as in miscarriage, multiple pregnancy or biochemical pregnancy rates. Pulsatile GnRH seems to be a successful and safe method for ovulation induction in "FHA-PCOM" patients. If results were confirmed by prospective studies, GnRH therapy could therefore become a first-line treatment for this specific population, just as it is for women with FHA without PCOM.

A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

PubMed

Vemula, Sateesh Kumar

2015-12-01

A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

Uric acid association with pulsatile and steady components of central and peripheral blood pressures.

PubMed

Lepeytre, Fanny; Lavoie, Pierre-Luc; Troyanov, Stéphan; Madore, François; Agharazii, Mohsen; Goupil, Rémi

2018-03-01

Whether the cardiovascular risk attributed to elevated uric acid levels may be explained by changes in central and peripheral pulsatile and/or steady blood pressure (BP) components remains controversial. In a cross-sectional analysis of normotensive and untreated hypertensive participants of the CARTaGENE populational cohort, we examined the relationship between uric acid, and both pulsatile and steady components of peripheral and central BP, using sex-stratified linear regressions. Of the 20 004 participants, 10 161 individuals without antihypertensive or uric acid-lowering drugs had valid pulse wave analysis and serum uric acid levels. In multivariate analysis, pulsatile components of BP were not associated with uric acid levels, whereas steady components [mean BP (MBP), peripheral and central DBP] were all associated with higher levels of uric acid levels in women and men (all P < 0.001). Furthermore, there was a gradual increase of central SBP (cSBP), DBP and MBP from the lowest to the highest quintiles of uric acid levels but not for MBP-adjusted cSBP. Peripheral and cSBP, which are aggregate measures of pulsatile and steady BP, were also associated with uric acid levels in women (β = 0.063 and 0.072, respectively, both P < 0.001) and men (β = 0.043 and 0.051, both P ≤ 0.003). After further adjustments for MBP to account for the concomitant increase in steady component of BP, SBPs were no longer associated with uric acid levels. Serum uric acid levels appear to be associated with both central and peripheral steady but not pulsatile BP, regardless of sex.

Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

PubMed Central

Boutry, Claire; El-Kadi, Samer W.; Suryawan, Agus; Steinhoff-Wagner, Julia; Stoll, Barbara; Orellana, Renán A.; Nguyen, Hanh V.; Kimball, Scot R.; Fiorotto, Marta L.

2016-01-01

Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have shown previously that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in skeletal muscle compared with continuous feeding alone. To determine the long-term effects of leucine pulses, neonatal piglets (n = 11–12/group) were continuously fed formula via orogastric tube for 21 days, with an additional parenteral infusion of either leucine (CON + LEU; 800 μmol·kg−1·h−1) or alanine (CON + ALA) for 1 h every 4 h. The results show that body and muscle weights and lean gain were ∼25% greater, and fat gain was 48% lower in CON + LEU than CON + ALA; weights of other tissues were unaffected by treatment. Fractional protein synthesis rates in longissimus dorsi, gastrocnemius, and soleus muscles were ∼30% higher in CON + LEU compared with CON + ALA and were associated with decreased Deptor abundance and increased mTORC1, mTORC2, 4E-BP1, and S6K1 phosphorylation, SNAT2 abundance, and association of eIF4E with eIF4G and RagC with mTOR. There were no treatment effects on PKB, eIF2α, eEF2, or PRAS40 phosphorylation, Rheb, SLC38A9, v-ATPase, LAMTOR1, LAMTOR2, RagA, RagC, and LAT1 abundance, the proportion of polysomes to nonpolysomes, or the proportion of mRNAs encoding rpS4 or rpS8 associated with polysomes. Our results demonstrate that pulsatile delivery of a leucine supplement during 21 days of continuous enteral feeding enhances lean growth by stimulating the mTORC1-dependent translation initiation pathway, leading to protein synthesis in skeletal muscle of neonates. PMID:26884386

Tensile Shear Properties of the Friction Stir Lap Welded Joints and Material Flow Mechanism Under Pulsatile Revolutions

NASA Astrophysics Data System (ADS)

Hu, Yanying; Liu, Huijie; Du, Shuaishuai

2018-06-01

The aim of the present article is to offer insight into the effects of pin profiles on interface defects, tensile shear properties, microstructures, and the material flow of friction stir lap welded joints. The results indicate that, compared to the lap joints welded by the single threaded plane pin, the three-plane threaded pin, and the triangle threaded pin, the lap joint obtained by the conventional conical threaded pin is characterized by the minimum interface defect. The alternate threads and planes on the pin provide periodical stress, leading to pulsatile material flow patterns. Under the effect of pulsatile revolutions, an asymmetrical flow field is formed around the tool. The threads on the pin force the surrounding material to flow downward. The planes cannot only promote the horizontal flow of the material by scraping, but also provide extra space for the material vertical flow. A heuristic model is established to describe the material flow mechanism during friction stir lap welding under the effect of pulsatile revolutions.

The effect of acute exercise on pulsatile release of luteinizing hormone in women runners.

PubMed

Cumming, D C; Vickovic, M M; Wall, S R; Fluker, M R; Belcastro, A N

1985-11-01

Endurance exercise has been associated with reproductive dysfunction. We have previously suggested that pulsatile release of luteinizing hormone is impaired at rest in normal menstruating runners compared with sedentary women. To determine whether acute exercise had any effect on pulsatile release of luteinizing hormone we investigated serum luteinizing hormone levels in six normal menstruating runners at rest and after 60 minutes of running exercise. Exercise induced an increment in circulating luteinizing hormone levels greater than the change in hematocrit. The luteinizing hormone pulse frequency, calculated as the number of luteinizing hormone pulses per 6 hours, was reduced after exercise compared with values obtained at rest. There was no significant difference in pulse amplitude or area under the 6-hour curve between resting and postexercise situations. These data suggest that acute exercise has an inhibitory effect on luteinizing hormone pulsatile release at the hypothalamic level in eumenorrheic runners that is in addition to the previously described effect of training.

Low-pressure sequential compression of lower limbs enhances forearm skin blood flow.

PubMed

Amah, Guy; Voicu, Sebastian; Bonnin, Philippe; Kubis, Nathalie

2016-12-01

We investigated whether forearm skin blood flow could be improved when a multilayer pulsatile inflatable suit was applied at a low pressure to the lower limbs and abdomen. We hypothesized that a non-invasive purely mechanical stimulation of the lower limbs could induce remote forearm blood flow modifications. The pulsatile suit induced a sequential compartmentalized low compression (65 mmHg), which was synchronized with each diastole of the cardiac cycle with each phase evolving centripetally (lower limbs to abdomen). Modifications of the forearm skin blood flow were continuously recorded by laser Doppler flowmetry (LDF) at baseline and during the pulsatile suit application. Endothelium-dependent and endothelium-independent vasodilations of the forearm skin microcirculation were measured by LDF in response to a local transdermal iontophoretic application of acetylcholine (ACh-test) and to hyperthermia (hyperT- test). Twenty-four healthy volunteers, 12 men and 12 women (43±14 years) were included in the study. LDF responses increased 1) under pulsatile suit (97±106%, p.

Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets

PubMed Central

Mukhitov, Nikita; Roper, Michael G.; Bertram, Richard

2016-01-01

Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal’s ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion. PMID:27788129

Comparison of 2-dimensional, 3-dimensional, and vascular ultrasonographic parameters for endometrial receptivity between 2 consecutive stimulated in vitro fertilization cycles.

PubMed

Ng, Ernest Hung Yu; Chan, Carina Chi Wai; Tang, Oi Shan; Ho, Pak Chung

2007-07-01

We compared the ultrasonographic parameters for endometrial receptivity between 2 consecutive in vitro fertilization (IVF) cycles in the same patients. Patients who had undergone 2 in vitro fertilization cycles between November 2002 and December 2004 were recruited. A 3-dimensional ultrasonographic examination with power Doppler imaging was performed on the day of oocyte retrieval to determine the endometrial thickness, endometrial pattern, pulsatility and resistive indices of uterine vessels, endometrial volume, vascularization index, flow index, and vascularization flow index of endometrial and subendometrial regions. Of 662 patients, 95 (14.4%) underwent 2 consecutive cycles using the same stimulation regimen during the study period. There were no significant differences in these ultrasonographic parameters between the first and second cycles. The intraclass correlation coefficient (ICC) for endometrial volume was significantly higher than that of other ultrasonographic parameters. The ICC for the endometrial thickness, uterine pulsatility index, and endometrial 3-dimensional power Doppler flow indices were similar. Ultrasonographic parameters for endometrial receptivity were comparable in the 2 consecutive stimulated cycles. The endometrial volume had the highest ICC among these ultrasonographic parameters and was most reproducible between 2 cycles.

[Gigantism with low serum level of growth hormone: a case report].

PubMed

Ran, X; Zhang, L; Xiong, P; Zhao, T; Tong, N; Li, X

2001-12-01

Gigantism with low or normal basal concentrations of growth hormone (GH) is a rare condition, possibly due to abnormal GH secretory patterns, enhanced tissue sensitivity to GH, or the existence of an unidentified growth promoting factor. Here we report an 11 year-old female case of gigantism with a normal pituitary gland. Her height was 181 cm, body weight 77 kg, and bone age 11.1 years. Her basal serum GH levels were lower than 1 ng/ml. The levels of T3, T4, FT3, FT4, TSH, E2, LH, FSH, PRL, PTC and ACTH were normal. Serum GH response to insulin-induced hypoglycemia or arginine stimulation tests was blunted. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-1 and the existence of an unidentified growth promoting factor or biologically active anti-GH receptor antibodies may cause clinical gigantism.

Design of a novel bioreactor and application in vascular tissue engineering

NASA Astrophysics Data System (ADS)

Zhang, Zhi-Xiong; Xi, Ting-Fei; Wang, Ying-Jun; Chen, Xiao-Song; Zhang, Jian; Wang, Chun-Ren; Gu, Yong-Quan; Chen, Liang; Li, Jian-Xin; Chen, Bing

2008-11-01

Endothelial cells (ECs) detachment under high shear stress at the early period of transplantation resulted in thrombosis and occlusion. To solve this problem, we developed a novel bioreactor. The bioreactor mimicked the formation of pulsatile flow in physiological conditions. Human umbilical vein ECs were seeded onto the lumen of living tissue conduits grown within dog peritoneal cavity. The shear stress generated by the bioreactor was increased step by step from 1.5 ± 0.8 dyn/cm 2 to 5.3 ± 2.4 dyn/cm 2, and was applied to ECs after static culture for 2 days. The results showed that completely confluent monolayer ECs were elongated, and were oriented parallel to the flow direction. The bioreactor could provide good environment for formation of endothelium. Stepwise increase shear stress could strengthen cell-cell and cell-extracellular matrix. The flow conditions of the bioreactor play a key role to determine the quality of the ECs lining.

Arachnoid Cyst in the Middle Cranial Fossa Presenting with Pulsatile Exophthalmos: Case Report and Literature Review

PubMed Central

SAITO, Atsushi; KON, Hiroyuki; HARYU, Shinya; MINO, Masaki; SASAKI, Tatsuya; NISHIJIMA, Michiharu

2014-01-01

A 20-year-old woman suffered gradual progression of right pulsatile exophthalmos and slight headache. Computed tomography (CT) demonstrated outward and downward displacement of the right globe and an arachnoid cyst in the right middle cranial fossa associated with thinned and anterior protrusion of a bony orbit. Microscopic cystocisternotomy was performed and the cerebrospinal fluid (CSF) inside of the cyst communicated into the carotid cistern and cistern in the posterior cranial fossa. Pulsatile exophthalmos improved immediately after surgery. Arachnoid cyst in the middle cranial fossa presenting with exophthalmos is rare. Microscopic cystocisternotomy might successfully improve CSF flow and relieve exophthalmos. PMID:24305013

Quantitative flow and velocity measurements of pulsatile blood flow with 4D-DSA

NASA Astrophysics Data System (ADS)

Shaughnessy, Gabe; Hoffman, Carson; Schafer, Sebastian; Mistretta, Charles A.; Strother, Charles M.

2017-03-01

Time resolved 3D angiographic data from 4D DSA provides a unique environment to explore physical properties of blood flow. Utilizing the pulsatility of the contrast waveform, the Fourier components can be used to track the waveform motion through vessels. Areas of strong pulsatility are determined through the FFT power spectrum. Using this method, we find an accuracy from 4D-DSA flow measurements within 7.6% and 6.8% RMSE of ICA PCVIPR and phantom flow probe validation measurements, respectively. The availability of velocity and flow information with fast acquisition could provide a more quantitative approach to treatment planning and evaluation in interventional radiology.

Flow-induced Flutter of Heart Valves: Experiments with Canonical Models

NASA Astrophysics Data System (ADS)

Dou, Zhongwang; Seo, Jung-Hee; Mittal, Rajat

2017-11-01

For the better understanding of hemodynamics associated with valvular function in health and disease, the flow-induced flutter of heart valve leaflets is studied using benchtop experiments with canonical valve models. A simple experimental model with flexible leaflets is constructed and a pulsatile pump drives the flow through the leaflets. We quantify the leaflet dynamics using digital image analysis and also characterize the dynamics of the flow around the leaflets using particle imaging velocimetry. Experiments are conducted over a wide range of flow and leaflet parameters and data curated for use as a benchmark for validation of computational fluid-structure interaction models. The authors would like to acknowledge Supported from NSF Grants IIS-1344772, CBET-1511200 and NSF XSEDE Grant TG-CTS100002.

Early prepubertal ontogeny of pulsatile gonadotropin-releasing hormone (GnRH) secretion: I. Inhibitory autofeedback control through prolyl endopeptidase degradation of GnRH.

PubMed

Yamanaka, C; Lebrethon, M C; Vandersmissen, E; Gerard, A; Purnelle, G; Lemaitre, M; Wilk, S; Bourguignon, J P

1999-10-01

GnRH[1-5], a subproduct resulting from degradation of GnRH by prolyl endopeptidase (PEP) and endopeptidase 24.15 (EP24.15) was known to account for an inhibitory autofeedback of GnRH secretion through an effect at the N-methyl-D-aspartate (NMDA) receptors. This study aimed at determining the possible role of such a mechanism in the early developmental changes in frequency of pulsatile GnRH secretion. Using retrochiasmatic explants from fetal male rats (day 20-21 of gestation), no GnRH pulses could be observed in vitro, whereas pulses occurred at a mean interval of 86 min from the day of birth onwards. This interval decreased steadily until day 25 (39 min), during the period preceding the onset of puberty. Based on GnRH[1-10] or GnRH[1-9] degradation and GnRH[1-5] generation after incubation with hypothalamic extracts, EP24.15 activity did not change with age, whereas PEP activity was maximal at days 5-10 and decreased subsequently until day 50. These changes were consistent with the ontogenetic variations in PEP messenger RNAs (mRNAs) quantitated using RT-PCR. Using fetal explants, the NMDA-evoked release of GnRH was potentiated in a dose-dependent manner by bacitracin, a competitive PEP inhibitor and the desensitization to the NMDA effect was prevented using 2 mM of bacitracin. At day 5, a higher bacitracin concentration of 20 mM was required for a similar effect. Pulsatile GnRH secretion from fetal explants was not caused to occur using bacitracin or Fmoc-Prolyl-Pyrrolidine-2-nitrile (Fmoc-Pro-PyrrCN), a noncompetitive PEP inhibitor. At postnatal days 5 and 15, a significant acceleration of pulsatility was obtained using 1 microM of Fmoc-Pro-PyrrCN or 2 mM of bacitracin. At 25 and 50 days, a lower bacitracin concentration of 20 microM was effective as well in increasing the frequency of GnRH pulsatility. We conclude that the GnRH inhibitory autofeedback resulting from degradation of the peptide is operational in the fetal hypothalamus but does not explain the absence of pulsatile GnRH secretion at that early age. After birth, PEP activity is high and may account for the low frequency of pulsatility. The potency of that effect decreases before the onset of puberty and may contribute to the acceleration of GnRH pulsatility.

Development and optimization of press coated floating pulsatile drug delivery of sumatriptan succinate.

PubMed

Jagdale, Swati C; Pawar, Chandrakala R

2014-01-01

Floating pulsatile is combined approach designed according to circadian rhythm to deliver the drug at right time, in right quantity and at right site as per pathophysiological need of disease with prolong gastric residence and lag phase followed by burst release. As the migraine follows circadian rhythm in which headache is more painful at the awakening time, the dosage form should be given during night time to release drug when pain get worsen. Present work deals with formulation and optimization of floating pulsatile tablet of sumatriptan succinate. Core tablet containing crospovidone as superdisintegrant (10%) showed burst release. Lag time was maintained using swellable polymer as polyoxN12K and xanthum gum. 3(2) experimental design was carried out. Developed formulations were evaluated for physical characteristics, in vitro and in vivo study. Optimized batch F2 with concentration of polyox N12K (73.43%) and xanthum gum (26.56%) of total polymer weight showed floating lag time 15±2 sec, drug content 99.58±0.2 %, hardness 6±0.2 Kg/cm(2) and drug release 99.54±2% with pulsatile manner followed lag period of 7±0.1h. In vivo x-ray study confirms prolong gastric residence of system. Programmable pulsatile release has been achieved by formulation F2 which meet demand of chronotherapeutic objective of migraine.

Synchronous activation of gonadotropin-releasing hormone gene transcription and secretion by pulsatile kisspeptin stimulation

PubMed Central

Choe, Han Kyoung; Kim, Hee-Dae; Park, Sung Ho; Lee, Han-Woong; Park, Jae-Yong; Seong, Jae Young; Lightman, Stafford L.; Son, Gi Hoon; Kim, Kyungjin

2013-01-01

Pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH) is essential for pituitary gonadotrope function. Although the importance of pulsatile GnRH secretion has been recognized for several decades, the mechanisms underlying GnRH pulse generation in hypothalamic neural networks remain elusive. Here, we demonstrate the ultradian rhythm of GnRH gene transcription in single GnRH neurons using cultured hypothalamic slices prepared from transgenic mice expressing a GnRH promoter-driven destabilized luciferase reporter. Although GnRH promoter activity in each GnRH neuron exhibited an ultradian pattern of oscillations with a period of ∼10 h, GnRH neuronal cultures exhibited partially synchronized bursts of GnRH transcriptional activity at ∼2-h intervals. Surprisingly, pulsatile administration of kisspeptin, a potent GnRH secretagogue, evoked dramatic synchronous activation of GnRH gene transcription with robust stimulation of pulsatile GnRH secretion. We also addressed the issue of hierarchical interaction between the circadian and ultradian rhythms by using Bmal1-deficient mice with defective circadian clocks. The circadian molecular oscillator barely affected basal ultradian oscillation of GnRH transcription but was heavily involved in kisspeptin-evoked responses of GnRH neurons. In conclusion, we have clearly shown synchronous bursts of GnRH gene transcription in the hypothalamic GnRH neuronal population in association with episodic neurohormone secretion, thereby providing insight into GnRH pulse generation. PMID:23509283

Time and pH dependent colon specific, pulsatile delivery of theophylline for nocturnal asthma.

PubMed

Mastiholimath, V S; Dandagi, P M; Jain, S Samata; Gadad, A P; Kulkarni, A R

2007-01-02

In this study, investigation of an oral colon specific, pulsatile device to achieve time and/or site specific release of theophylline, based on chronopharmaceutical consideration. The basic design consists of an insoluble hard gelatin capsule body, filled with eudragit microcapsules of theophylline and sealed with a hydrogel plug. The entire device was enteric coated, so that the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. The theophylline microcapsules were prepared in four batches, with Eudragit L-100 and S-100 (1:2) by varying drug to polymer ratio and evaluated for the particle size, drug content and in vitro release profile and from the obtained results; one better formulation was selected for further fabrication of pulsatile capsule. Different hydrogel polymers were used as plugs, to maintain a suitable lag period and it was found that the drug release was controlled by the proportion of polymers used. In vitro release studies of pulsatile device revealed that, increasing the hydrophilic polymer content resulted in delayed release of theophylline from microcapsules. The gamma scintigraphic study pointed out the capability of the system to release drug in lower parts of GIT after a programmed lag time for nocturnal asthma. Programmable pulsatile, colon-specific release has been achieved from a capsule device over a 2-24h period, consistent with the demands of chronotherapeutic drug delivery.

Differential response of endothelial cells to simvastatin when conditioned with steady, non-reversing pulsatile or oscillating shear stress.

PubMed

Rossi, Joanna; Jonak, Paul; Rouleau, Leonie; Danielczak, Lisa; Tardif, Jean-Claude; Leask, Richard L

2011-01-01

Few studies have investigated whether fluid mechanics can impair or enhance endothelial cell response to pharmacological agents such as statin drugs. We evaluated and compared Kruppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) expression in human abdominal aortic endothelial cells (HAAEC) treated with increasing simvastatin concentrations (0.1, 1 or 10 μM) under static culture and shear stress (steady, non-reversing pulsatile, and oscillating). Simvastatin, steady flow, and non-reversing pulsatile flow each separately upregulated KLF2, eNOS, and TM mRNA. At lower simvastatin concentrations (0.1 and 1 μM), the combination of statin and unidirectional steady or pulsatile flow produced an overall additive increase in mRNA levels. At higher simvastatin concentration (10 μM), a synergistic increase in eNOS and TM mRNA expression was observed. In contrast, oscillating flow impaired KLF2 and TM, but not eNOS expression by simvastatin at 1 μM. A higher simvastatin concentration of 10 μM overcame the inhibitory effect of oscillating flow. Our findings suggest that oscillating shear stress renders the endothelial cells less responsive to simvastatin than cells exposed to unidirectional steady or pulsatile flow. Consequently, the pleiotropic effects of statins in vivo may be less effective in endothelial cells exposed to atheroprone hemodynamics.

A Pulsatile Cardiovascular Computer Model for Teaching Heart-Blood Vessel Interaction.

ERIC Educational Resources Information Center

Campbell, Kenneth; And Others

1982-01-01

Describes a model which gives realistic predictions of pulsatile pressure, flow, and volume events in the cardiovascular system. Includes computer oriented laboratory exercises for veterinary and graduate students; equations of the dynamic and algebraic models; and a flow chart for the cardiovascular teaching program. (JN)

Real-time intravascular photoacoustic-ultrasound imaging of lipid-laden plaque at speed of video-rate level

NASA Astrophysics Data System (ADS)

Hui, Jie; Cao, Yingchun; Zhang, Yi; Kole, Ayeeshik; Wang, Pu; Yu, Guangli; Eakins, Gregory; Sturek, Michael; Chen, Weibiao; Cheng, Ji-Xin

2017-03-01

Intravascular photoacoustic-ultrasound (IVPA-US) imaging is an emerging hybrid modality for the detection of lipidladen plaques by providing simultaneous morphological and lipid-specific chemical information of an artery wall. The clinical utility of IVPA-US technology requires real-time imaging and display at speed of video-rate level. Here, we demonstrate a compact and portable IVPA-US system capable of imaging at up to 25 frames per second in real-time display mode. This unprecedented imaging speed was achieved by concurrent innovations in excitation laser source, rotary joint assembly, 1 mm IVPA-US catheter, differentiated A-line strategy, and real-time image processing and display algorithms. By imaging pulsatile motion at different imaging speeds, 16 frames per second was deemed to be adequate to suppress motion artifacts from cardiac pulsation for in vivo applications. Our lateral resolution results further verified the number of A-lines used for a cross-sectional IVPA image reconstruction. The translational capability of this system for the detection of lipid-laden plaques was validated by ex vivo imaging of an atherosclerotic human coronary artery at 16 frames per second, which showed strong correlation to gold-standard histopathology.

Adding the ‘heart’ to hanging drop networks for microphysiological multi-tissue experiments†

PubMed Central

Yazdi, Saeed Rismani; Shadmani, Amir; Bürgel, Sebastian C.; Misun, Patrick M.; Hierlemann, Andreas; Frey, Olivier

2017-01-01

Microfluidic hanging-drop networks enable culturing and analysis of 3D microtissue spheroids derived from different cell types under controlled perfusion and investigating inter-tissue communication in multi-tissue formats. In this paper we introduce a compact on-chip pumping approach for flow control in hanging-drop networks. The pump includes one pneumatic chamber located directly above one of the hanging drops and uses the surface tension at the liquid–air-interface for flow actuation. Control of the pneumatic protocol provides a wide range of unidirectional pulsatile and continuous flow profiles. With the proposed concept several independent hanging-drop networks can be operated in parallel with only one single pneumatic actuation line at high fidelity. Closed-loop medium circulation between different organ models for multi-tissue formats and multiple simultaneous assays in parallel are possible. Finally, we implemented a real-time feedback control-loop of the pump actuation based on the beating of a human iPS-derived cardiac microtissue cultured in the same system. This configuration allows for simulating physiological effects on the heart and their impact on flow circulation between the organ models on chip. PMID:26401602

Extracorporeal bypass model of blood circulation for the study of microvascular hemodynamics.

PubMed

Nam, Kweon-Ho; Yeom, Eunseop; Lee, Sang Joon

2012-05-01

Many studies have been performed to better understand the hemodynamics in microvessels, such as arterioles and venules. However, due to the heterogeneous features of size, shape, blood-flow velocity, and pulsatility of microvessels, conducting a systematic study on these factors has been almost impossible. Although in vitro studies have been performed for this purpose, the usefulness of in vitro data is limited by the fact that the rheological properties of blood are changed as blood is exposed to in vitro environments. The purpose of the present study is to investigate the feasibility of a rat extracorporeal bypass model that combines in vivo and in vitro models. An arteriovenous shunt loop with a sub-bypass loop of fluorinated ethylene propylene (FEP) microtube was constructed between the jugular vein and femoral artery of a rat. Three pinch valves were installed in the main loop. Microscopic images of the blood flow in the FEP tube were sequentially captured with a high-speed camera, and the whole velocity field information was obtained using a micro-particle image velocimetry technique. Experimental results reveal that the velocity fields of the blood flow inside the microtube are well measured because the FEP tube is transparent and has nearly the same refractive index as water. The flow velocity and the pulsatility index of the blood flow in the microtube can be controlled by adjusting the three pinch valves installed upstream, midstream, and downstream of the bypass loop. This hybrid model that combines in vivo and in vitro models can be useful in studying microvascular hemodynamics. Copyright © 2012 Elsevier Inc. All rights reserved.

Recent technologies in pulsatile drug delivery systems

PubMed Central

Jain, Deepika; Raturi, Richa; Jain, Vikas; Bansal, Praveen; Singh, Ranjit

2011-01-01

Pulsatile drug delivery systems (PDDS) have attracted attraction because of their multiple benefits over conventional dosage forms. They deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. These systems are designed according to the circadian rhythm of the body, and the drug is released rapidly and completely as a pulse after a lag time. These products follow the sigmoid release profile characterized by a time period. These systems are beneficial for drugs with chronopharmacological behavior, where nocturnal dosing is required, and for drugs that show the first-pass effect. This review covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Marketed technologies, such as PulsincapTM, Diffucaps®, CODAS®, OROS® and PULSYSTM, follow the above mechanism to render a sigmoidal drug release profile. Diseases wherein PDDS are promising include asthma, peptic ulcers, cardiovascular ailments, arthritis and attention deficit syndrome in children and hypercholesterolemia. Pulsatile drug delivery systems have the potential to bring new developments in the therapy of many diseases. PMID:23507727

Alkaline phosphatase in osteoblasts is down-regulated by pulsatile fluid flow

NASA Technical Reports Server (NTRS)

Hillsley, M. V.; Frangos, J. A.

1997-01-01

It is our hypothesis that interstitial fluid flow plays a role in the bone remodeling response to mechanical loading. The fluid flow-induced expression of three proteins (collagen, osteopontin, and alkaline phosphatase) involved in bone remodeling was investigated. Rat calvarial osteoblasts subjected to pulsatile fluid flow at an average shear stress of 5 dyne/cm2 showed decreased alkaline phosphatase (AP) mRNA expression after only 1 hour of flow. After 3 hours of flow, AP mRNA levels had decreased to 30% of stationary control levels and remained at this level for an additional 5 hours of flow. Steady flow (4 dyne/cm2 fluid shear stress), in contrast, resulted in a delayed and less dramatic decrease in AP mRNA expression to 63% of control levels after 8 hours of flow. The reduced AP mRNA expression under pulsatile flow conditions was followed by reduced AP enzyme activity after 24 hours. No changes in collagen or osteopontin mRNA expression were detected over 8 hours of pulsatile flow. This is the first time fluid flow has been shown to affect gene expression in osteoblasts.

Generating pulsatility by pump speed modulation with continuous-flow total artificial heart in awake calves.

PubMed

Fukamachi, Kiyotaka; Karimov, Jamshid H; Sunagawa, Gengo; Horvath, David J; Byram, Nicole; Kuban, Barry D; Dessoffy, Raymond; Sale, Shiva; Golding, Leonard A R; Moazami, Nader

2017-12-01

The purpose of this study was to evaluate the effects of sinusoidal pump speed modulation of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) on hemodynamics and pump flow in an awake chronic calf model. The sinusoidal pump speed modulations, performed on the day of elective sacrifice, were set at ±15 and ± 25% of mean pump speed at 80 bpm in four awake calves with a CFTAH. The systemic and pulmonary arterial pulse pressures increased to 12.0 and 12.3 mmHg (±15% modulation) and to 15.9 and 15.7 mmHg (±25% modulation), respectively. The pulsatility index and surplus hemodynamic energy significantly increased, respectively, to 1.05 and 1346 ergs/cm at ±15% speed modulation and to 1.51 and 3381 ergs/cm at ±25% speed modulation. This study showed that it is feasible to generate pressure pulsatility with pump speed modulation; the platform is suitable for evaluating the physiologic impact of pulsatility and allows determination of the best speed modulations in terms of magnitude, frequency, and profiles.

Morphine enhances nitric oxide release in the mammalian gastrointestinal tract via the micro(3) opiate receptor subtype: a hormonal role for endogenous morphine.

PubMed

Stefano, G B; Zhu, W; Cadet, P; Bilfinger, T V; Mantione, K

2004-03-01

Studies from our laboratory have revealed a novel micro opiate receptor, micro(3), which is expressed in both human vascular tissues and leukocytes. The micro(3) receptor is selective for opiate alkaloids, insensitive to opioid peptides and is coupled to constitutive nitric oxide (cNO) release. We now identify the micro(3) receptor characteristics in mammalian gut tissues. It appears that the various regions of the mouse gut release low levels of NO (0.02 to 4.6 nM ) in a pulsatile manner. We demonstrate that morphine stimulates cNO release (peak level 17 nM) in the mouse stomach, small intestine and large intestine in a naloxone and L-NAME antagonizable manner. Opioid peptides do not exhibit cNO-stimulating capabilities in these tissues. Taken together, we surmise morphine acts as a hormone to limit gut activity via micro(3) coupled to NO release since micro opiate receptors are found in the gut and endogenous morphine is not but is found in blood.

Kisspeptin and LH pulsatile temporal coupling in PCOS patients.

PubMed

Katulski, Krzysztof; Podfigurna, Agnieszka; Czyzyk, Adam; Meczekalski, Blazej; Genazzani, Alessandro D

2018-05-04

To evaluate the temporal coupling between spontaneous kisspeptin and luteinizing hormone (LH) pulsatile releases in polycystic ovary syndrome (PCOS) patients. We examined 71 patients diagnosed with PCOS. A 2 h pulsatility study was performed to evaluate serum kisspeptin and LH pulse frequency and concentration, sampled every 10 min; baseline follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), cortisol, 17-hydroksy-progesterone (17OHP), testosterone (T), free testosterone index (FTI, and insulin levels were also measured. Detect and Specific Concordance (SC) algorithms were used to evaluate the temporal coupling associations between spontaneous episodic secretion of kisspeptin and LH. All PCOS patients demonstrated LH and kisspeptin pulsatile secretions. When the SC index was calculated across the sample of PCOS patients (n = 71), no temporal coupling was observed between kisspeptin and LH pulses. When PCOS patients were subdivided according to their menstrual cyclicity, oligomenorrheic patients demonstrated elevated kisspeptin pulse frequency. Additionally, the SC index reveled a temporal coupling between kisspeptin and LH secretory peaks only in eumenorrheic patients (n = 30, intermenstrual interval < 45 days). Oligomenorrheic PCOS patients (intermenstrual interval > 45 days) did not demonstrate temporal coupling between kisspeptin and LH secretory peaks. The study of the endogenous kisspeptin and LH pulsatile release revealed the temporal coupling of kisspeptin with LH secretory pulses only in eumenorrheic. This data supports the hypothesis that neuroendocrine impairments in PCOS affect the coupling of kisspeptin with LH pulses and potentially worsen as the disease progresses, becoming unequivocally evident in oligomenorrheic PCOS patients.

The Effect of Pulsatile Versus Nonpulsatile Blood Flow on Viscoelasticity and Red Blood Cell Aggregation in Extracorporeal Circulation

PubMed Central

Ahn, Chi Bum; Kang, Yang Jun; Kim, Myoung Gon; Yang, Sung; Lim, Choon Hak; Son, Ho Sung; Kim, Ji Sung; Lee, So Young; Son, Kuk Hui; Sun, Kyung

2016-01-01

Background Extracorporeal circulation (ECC) can induce alterations in blood viscoelasticity and cause red blood cell (RBC) aggregation. In this study, the authors evaluated the effects of pump flow pulsatility on blood viscoelasticity and RBC aggregation. Methods Mongrel dogs were randomly assigned to two groups: a nonpulsatile pump group (n=6) or a pulsatile pump group (n=6). After ECC was started at a pump flow rate of 80 mL/kg/min, cardiac fibrillation was induced. Blood sampling was performed before and at 1, 2, and 3 hours after ECC commencement. To eliminate bias induced by hematocrit and plasma, all blood samples were adjusted to a hematocrit of 45% using baseline plasma. Blood viscoelasticity, plasma viscosity, hematocrit, arterial blood gas analysis, central venous O2 saturation, and lactate were measured. Results The blood viscosity and aggregation index decreased abruptly 1 hour after ECC and then remained low during ECC in both groups, but blood elasticity did not change during ECC. Blood viscosity, blood elasticity, plasma viscosity, and the aggregation index were not significantly different in the groups at any time. Hematocrit decreased abruptly 1 hour after ECC in both groups due to dilution by the priming solution used. Conclusion After ECC, blood viscoelasticity and RBC aggregation were not different in the pulsatile and nonpulsatile groups in the adult dog model. Furthermore, pulsatile flow did not have a more harmful effect on blood viscoelasticity or RBC aggregation than nonpulsatile flow. PMID:27298790

The Effect of Pulsatile Versus Nonpulsatile Blood Flow on Viscoelasticity and Red Blood Cell Aggregation in Extracorporeal Circulation.

PubMed

Ahn, Chi Bum; Kang, Yang Jun; Kim, Myoung Gon; Yang, Sung; Lim, Choon Hak; Son, Ho Sung; Kim, Ji Sung; Lee, So Young; Son, Kuk Hui; Sun, Kyung

2016-06-01

Extracorporeal circulation (ECC) can induce alterations in blood viscoelasticity and cause red blood cell (RBC) aggregation. In this study, the authors evaluated the effects of pump flow pulsatility on blood viscoelasticity and RBC aggregation. Mongrel dogs were randomly assigned to two groups: a nonpulsatile pump group (n=6) or a pulsatile pump group (n=6). After ECC was started at a pump flow rate of 80 mL/kg/min, cardiac fibrillation was induced. Blood sampling was performed before and at 1, 2, and 3 hours after ECC commencement. To eliminate bias induced by hematocrit and plasma, all blood samples were adjusted to a hematocrit of 45% using baseline plasma. Blood viscoelasticity, plasma viscosity, hematocrit, arterial blood gas analysis, central venous O2 saturation, and lactate were measured. The blood viscosity and aggregation index decreased abruptly 1 hour after ECC and then remained low during ECC in both groups, but blood elasticity did not change during ECC. Blood viscosity, blood elasticity, plasma viscosity, and the aggregation index were not significantly different in the groups at any time. Hematocrit decreased abruptly 1 hour after ECC in both groups due to dilution by the priming solution used. After ECC, blood viscoelasticity and RBC aggregation were not different in the pulsatile and nonpulsatile groups in the adult dog model. Furthermore, pulsatile flow did not have a more harmful effect on blood viscoelasticity or RBC aggregation than nonpulsatile flow.

Microbubble transport through a bifurcating vessel network with pulsatile flow.

PubMed

Valassis, Doug T; Dodde, Robert E; Esphuniyani, Brijesh; Fowlkes, J Brian; Bull, Joseph L

2012-02-01

Motivated by two-phase microfluidics and by the clinical applications of air embolism and a developmental gas embolotherapy technique, experimental and theoretical models of microbubble transport in pulsatile flow are presented. The one-dimensional time-dependent theoretical model is developed from an unsteady Bernoulli equation that has been modified to include viscous and unsteady effects. Results of both experiments and theory show that roll angle (the angle the plane of the bifurcating network makes with the horizontal) is an important contributor to bubble splitting ratio at each bifurcation within the bifurcating network. When compared to corresponding constant flow, pulsatile flow was shown to produce insignificant changes to the overall splitting ratio of the bubble despite the order one Womersley numbers, suggesting that bubble splitting through the vasculature could be modeled adequately with a more modest constant flow model. However, bubble lodging was affected by the flow pulsatility, and the effects of pulsatile flow were evident in the dependence of splitting ratio of bubble length. The ability of bubbles to remain lodged after reaching a steady state in the bifurcations is promising for the effectiveness of gas embolotherapy to occlude blood flow to tumors, and indicates the importance of understanding where lodging will occur in air embolism. The ability to accurately predict the bubble dynamics in unsteady flow within a bifurcating network is demonstrated and suggests the potential for bubbles in microfluidics devices to encode information in both steady and unsteady aspects of their dynamics.

Regulated recovery of pulsatile growth hormone secretion from negative feedback: a preclinical investigation

PubMed Central

Bowers, Cyril Y.

2011-01-01

Although stimulatory (feedforward) and inhibitory (feedback) dynamics jointly control neurohormone secretion, the factors that supervise feedback restraint are poorly understood. To parse the regulation of growth hormone (GH) escape from negative feedback, 25 healthy men and women were studied eight times each during an experimental GH feedback clamp. The clamp comprised combined bolus infusion of GH or saline and continuous stimulation by saline GH-releasing hormone (GHRH), GHRP-2, or both peptides after randomly ordered supplementation with placebo (both sexes) vs. E2 (estrogen; women) and T (testosterone; men). Endpoints were GH pulsatility and entropy (a model-free measure of feedback quenching). Gender determined recovery of pulsatile GH secretion from negative feedback in all four secretagog regimens (0.003 ≤ P ≤ 0.017 for women>men). Peptidyl secretagog controlled the mass, number, and duration of feedback-inhibited GH secretory bursts (each, P < 0.001). E2/T administration potentiated both pulsatile (P = 0.006) and entropic (P < 0.001) modes of GH recovery. IGF-I positively predicted the escape of GH secretory burst number and mode (P = 0.022), whereas body mass index negatively forecast GH secretory burst number and mass (P = 0.005). The composite of gender, body mass index, E2, IGF-I, and peptidyl secretagog strongly regulates the escape of pulsatile and entropic GH secretion from autonegative feedback. The ensemble factors identified in this preclinical investigation enlarge the dynamic model of GH control in humans. PMID:21795635

Altered neuroendocrine regulation of gonadotropin secretion in women distance runners.

PubMed

Veldhuis, J D; Evans, W S; Demers, L M; Thorner, M O; Wakat, D; Rogol, A D

1985-09-01

We tested the hypothesis that the neuroendocrine control of gonadotropin secretion is altered in certain women distance runners with secondary amenorrhea. To this end, we quantitated the frequency and amplitude of spontaneous pulsatile LH secretion during a 24-h interval in nine such women. The ability of the pituitary gland to release LH normally was assessed by administration of graded bolus doses of GnRH during the subsequent 8 h. Compared to normally menstruating women, six of nine amenorrheic distance runners had a distinct reduction in spontaneous LH pulse frequency, with one, three, six, five, four, or two pulses per 24 h (normal, 8-15 pulses/24 h). This reduction in LH pulse frequency occurred without any significant alterations in plasma concentrations of estradiol and free testosterone or 24-h integrated serum concentrations of LH, FSH, or PRL. Moreover, in long-distance runners, the capacity of the pituitary gland to release LH was normal or accentuated in response to exogenous pulses of GnRH. In the six women athletes with diminished spontaneous LH pulsatility, acute ovarian responsiveness also was normal, since serum estradiol concentrations increased normally in response to the GnRH-induced LH pulses. Although long-distance runners had significantly lower estimated percent body fat compared to control women, specific changes in pulsatile gonadotropin release did not correlate with degree of body leanness. In summary, certain long-distance runners with secondary amenorrhea or severe oligomenorrhea have unambiguously decreased spontaneous LH pulse frequency with intact pituitary responsiveness to GnRH. This neuroendocrine disturbance may be relevant to exercise-associated amenorrhea, since pulsatile LH release is a prerequisite for cyclic ovarian function. We speculate that such alterations in pulsatile LH release in exercising women reflect an adaptive response of the hypothalamic pulse generator controlling the intermittent GnRH signal to the pituitary gland. The basis for amenorrhea in the remaining runners who have normal pulsatile properties of LH release is not known.

Resistance Training Augments Cerebral Blood Flow Pulsatility: Cross-Sectional Study.

PubMed

Nakamura, Nobuhiro; Muraoka, Isao

2018-06-11

Increased central arterial stiffness and/or decreased compliance reduces buffer function and increases cerebral blood flow (CBF) pulsatility, which leads to increased cerebral microvascular damage, resulting in the augmentation of the risk of cerebrovascular diseases. Resistance-trained men showed higher central arterial stiffness and lower arterial compliance than age-matched, sedentary men. This study examined the effect of increased central arterial stiffness and/or decreased arterial compliance on CBF pulsatility. The study participants included 31 young healthy men (15 resistance-trained men, aged 21 ± 1 years; and 16 controls, aged 23 ± 1 years). β-Stiffness index and arterial compliance were measured in the right carotid artery as index of central arterial stiffness and compliance, respectively. The pulsatility index (PI) was measured in the middle cerebral artery as index of CBF pulsatility. β-Stiffness index and PI were significantly higher in the resistance-trained group than in the control group (β-stiffness index: 5.3 ± 0.3 vs. 3.5 ± 0.3 a.u., P < 0.05, PI: 0.80 ± 0.02 vs. 0.70 ± 0.02, P < 0.05). The resistance-trained group showed significantly lower arterial compliance than the control group (0.16 ± 0.01 vs. 0.23 ± 0.01 mm2/mm Hg, P < 0.05). Positive and negative correlations were observed between β-stiffness index and PI (r = 0.39, P < 0.05), and between arterial compliance and PI (r = -0.59, P < 0.05), respectively. The resistance-trained group showed higher central arterial stiffness and PI and lower arterial compliance. Central arterial stiffness and arterial compliance were associated with PI. Increased arterial stiffness and decreased arterial compliance with resistance training impair buffer function, resulting in increased CBF pulsatility. Trial Number UMIN000023816 URL: http://www.umin.ac.jp/icdr/index.html Official scientific title of the study: effect of increase arterial stiffness by resistance training on cerebral hemodynamic.

Non-dimensional physics of pulsatile cardiovascular networks and energy efficiency.

PubMed

Yigit, Berk; Pekkan, Kerem

2016-01-01

In Nature, there exist a variety of cardiovascular circulation networks in which the energetic ventricular load has both steady and pulsatile components. Steady load is related to the mean cardiac output (CO) and the haemodynamic resistance of the peripheral vascular system. On the other hand, the pulsatile load is determined by the simultaneous pressure and flow waveforms at the ventricular outlet, which in turn are governed through arterial wave dynamics (transmission) and pulse decay characteristics (windkessel effect). Both the steady and pulsatile contributions of the haemodynamic power load are critical for characterizing/comparing disease states and for predicting the performance of cardiovascular devices. However, haemodynamic performance parameters vary significantly from subject to subject because of body size, heart rate and subject-specific CO. Therefore, a 'normalized' energy dissipation index, as a function of the 'non-dimensional' physical parameters that govern the circulation networks, is needed for comparative/integrative biological studies and clinical decision-making. In this paper, a complete network-independent non-dimensional formulation that incorporates pulsatile flow regimes is developed. Mechanical design variables of cardiovascular flow systems are identified and the Buckingham Pi theorem is formally applied to obtain the corresponding non-dimensional scaling parameter sets. Two scaling approaches are considered to address both the lumped parameter networks and the distributed circulation components. The validity of these non-dimensional number sets is tested extensively through the existing empirical allometric scaling laws of circulation systems. Additional validation studies are performed using a parametric numerical arterial model that represents the transmission and windkessel characteristics, which are adjusted to represent different body sizes and non-dimensional haemodynamic states. Simulations demonstrate that the proposed non-dimensional indices are independent of body size for healthy conditions, but are sensitive to deviations caused by off-design disease states that alter the energetic load. Sensitivity simulations are used to identify the relationship between pulsatile power loss and non-dimensional characteristics, and optimal operational states are computed. © 2016 The Author(s).

POCS-enhanced correction of motion artifacts in parallel MRI.

PubMed

Samsonov, Alexey A; Velikina, Julia; Jung, Youngkyoo; Kholmovski, Eugene G; Johnson, Chris R; Block, Walter F

2010-04-01

A new method for correction of MRI motion artifacts induced by corrupted k-space data, acquired by multiple receiver coils such as phased arrays, is presented. In our approach, a projections onto convex sets (POCS)-based method for reconstruction of sensitivity encoded MRI data (POCSENSE) is employed to identify corrupted k-space samples. After the erroneous data are discarded from the dataset, the artifact-free images are restored from the remaining data using coil sensitivity profiles. The error detection and data restoration are based on informational redundancy of phased-array data and may be applied to full and reduced datasets. An important advantage of the new POCS-based method is that, in addition to multicoil data redundancy, it can use a priori known properties about the imaged object for improved MR image artifact correction. The use of such information was shown to improve significantly k-space error detection and image artifact correction. The method was validated on data corrupted by simulated and real motion such as head motion and pulsatile flow.

Sympathetic Chain Schwannoma Resembling Carotid Body Tumour.

PubMed

Najeeb, Tallat; Khan, Musaddiq

2016-06-01

Schwannomas are rare, benign nerve sheath tumours of parapharyngeal space. Differential diagnosis should include salivary gland tumours, paragangliomas, neurofibromas, and metastatic lymph nodes. The tumours may arise from vagus nerve and cervical sympathetic chain (CSC). Diagnosis is usually made by imaging techniques: contrast CT, magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA). Fine needle aspiration cytology (FNAC) is useful diagnostic procedure but poor results are seen in neurogenic tumours. Rarely, a vascular CSC schwannoma at the level of carotid arteries bifurcation may mimic carotid body tumour (CBT) on imaging techniques, especially if they are vascular, causing splaying of internal and external carotid arteries. Clinically patient was asymptomatic except for a pulsatile swelling in neck for 5 years. The presented case resembled CBTclinically, on ultrasound and on imaging techniques causing splaying of carotid arteries. FNAC was inconclusive and was always hemorrhagic. During operation, it was found to be CSC schwannoma just posterior to carotid body. CSC was sacrificed and patient developed Horner syndrome postoperatively.

Estimating right ventricular stroke work and the pulsatile work fraction in pulmonary hypertension.

PubMed

Chemla, Denis; Castelain, Vincent; Zhu, Kaixian; Papelier, Yves; Creuzé, Nicolas; Hoette, Susana; Parent, Florence; Simonneau, Gérald; Humbert, Marc; Herve, Philippe

2013-05-01

The mean pulmonary artery pressure (mPAP) replaces mean systolic ejection pressure (msePAP) in the classic formula of right ventricular stroke work (RVSW) = (mPAP - RAP) × stroke volume, where RAP is mean right atrial pressure. Only the steady work is thus taken into account, not the pulsatile work, whereas pulmonary circulation is highly pulsatile. Our retrospective, high-fidelity pressure study tested the hypothesis that msePAP was proportional to mPAP, and looked at the implications for RVSW. Eleven patients with severe, precapillary pulmonary hypertension (PH) (six patients with idiopathic pulmonary arterial hypertension and five with chronic thromboembolic PH; mPAP = 57 ± 10 mm Hg) were studied at rest and during mild to moderate exercise. Eight non-PH control subjects were also studied at rest (mPAP = 16 ± 2 mm Hg). The msePAP was averaged from end diastole to dicrotic notch. In the full data set (53 pressure-flow points), mPAP ranged from 14 to 99.5 mm Hg, cardiac output from 2.38 to 11.1 L/min, and heart rate from 53 to 163 beats/min. There was a linear relationship between msePAP and mPAP (r² = 0.99). The msePAP matched 1.25 mPAP (bias, -0.5 ± 2.6 mm Hg). Results were similar in the resting non-PH group and in resting and the exercising PH group. This implies that the classic formula markedly underestimates RVSW and that the pulsatile work may be a variable 20% to 55% fraction of RVSW, depending on RAP and mPAP. At rest, RVSW in patients with PH was twice as high as that of the non-PH group (P < .05), but pulsatile work fraction was similar between the two groups (26 ± 4% vs 24 ± 1%) because of the counterbalancing effects of high RAP (11 ± 5 mm Hg vs 4 ± 2 mm Hg), which increases the fraction, and high mPAP, which decreases the fraction. Our study favored the use of an improved formula that takes into account the variable pulsatile work fraction: RVSW = (1.25 mPAP - RAP) × stroke volume. Increased RAP and increased mPAP have opposite effects on the pulsatile work fraction.

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

PubMed

Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

2016-01-01

Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients' compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box-Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box-Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box-Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms.

Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

PubMed

Bayram, N; van Wely, M; van der Veen, F

2004-01-01

In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in women with polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in these women. Although ovulation and pregnancy have been achieved, the effectiveness of pulsatile GnRH in women with PCOS has not been clearly demonstrated. To assess the effectiveness of pulsatile GnRH administration in women with polycystic ovary syndrome (PCOS), in terms of ongoing pregnancy, ovulation, clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, miscarriage, and multifollicular growth. We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched 13 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, August 2001), MEDLINE (January 1966 to August 2003), EMBASE (January 1985 to August 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. All relevant published randomised clinical trials were selected for inclusion if treatment consisted of pulsatile GnRH administration versus another treatment for ovulation induction in subfertile women with PCOS. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. All trials were screened and analysed for predetermined quality criteria. 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto method. Four randomised clinical trials involving 57 women were identified comparing four different treatments: GnRH versus HMG, GnRH and FSH versus FSH, GnRH following pretreatment with GnRH agonist (GnRHa) versus GnRH only, GnRH following pretreatment with GnRHa versus clomiphene citrate. This means that there was only one trial in any one comparison. In two studies, data of pre- and post-crossover were not described separately. All trials were small and of too short duration to show any significant differences in pregnancy results. The odds ratio for ongoing pregnancy, only described in one trial, was 7.5 (95% CI 0.44 to 127) in the comparison GnRH following pretreatment with GnRHa versus GnRH only in favour of the first group. Multiple pregnancies were not seen. Ovarian hyperstimulation syndrome was seen only in women allocated to ovulation induction with HMG. The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Design and validation of a pulsatile perfusion bioreactor for 3D high cell density cultures.

PubMed

Chouinard, Julie A; Gagnon, Serge; Couture, Marc G; Lévesque, Alain; Vermette, Patrick

2009-12-15

This study presents the design and validation of a pulsatile flow perfusion bioreactor able to provide a suitable environment for 3D high cell density cultures for tissue engineering applications. Our bioreactor system is mobile, does not require the use of traditional cell culture incubators and is easy to sterilize. It provides real-time monitoring and stable control of pH, dissolved oxygen concentration, temperature, pressure, pulsation frequency, and flow rate. In this bioreactor system, cells are cultured in a gel within a chamber perfused by a culture medium fed by hollow fibers. Human umbilical vein endothelial cells (HUVEC) suspended in fibrin were found to be living, making connections and proliferating up to five to six times their initial seeding number after a 48-h culture period. Cells were uniformly dispersed within the 14.40 mm x 17.46 mm x 6.35 mm chamber. A larger fraction of the cells suspended in 6.35-mm thick gels and cultured in a traditional CO(2) incubator were found to be round and dead [corrected]. In control experiments carried out in a traditional cell culture incubator, the scarcely found living cells were mostly on top of the gels, while cells cultured under perfusion bioreactor conditions were found to be alive and uniformly distributed across the gel. 2009 Wiley Periodicals, Inc.

Fluid Dynamic Characterization of a Polymeric Heart Valve Prototype (Poli-Valve) tested under Continuous and Pulsatile Flow Conditions

PubMed Central

De Gaetano, Francesco; Serrani, Marta; Bagnoli, Paola; Brubert, Jacob; Stasiak, Joanna; Moggridge, Geoff D.; Costantino, Maria Laura

2016-01-01

Introduction Only mechanical and biological heart valve prostheses are currently commercially available. The former show longer durability but require anticoagulant therapy, the latter display better fluid dynamic behaviour but do not have adequate durability. New Polymeric Heart Valves (PHVs) could potentially combine the haemodynamic properties of biological valves with the durability of mechanical valves. This work presents a hydrodynamic evaluation of two groups of newly developed supra-annular tri-leaflet prosthetic heart valves made from styrenic block copolymers (SBC): Poli-Valves. Methods Two types of Poli-Valves made of SBC differing in polystyrene fraction content were tested under continuous and pulsatile flow conditions as prescribed by ISO 5840 Standard. An ad - hoc designed pulse duplicator allowed the valve prototypes to be tested at different flow rates and frequencies. Pressure and flow were recorded; pressure drops, effective orifice area (EOA), and regurgitant volume were computed to assess the valve’s behaviour. Results Both types Poli-Valves met the minimum requirements in terms of regurgitation and EOA as specified by ISO 5840 Standard. Results were compared with five mechanical heart valves (MHVs) and five tissue heart valves (THVs), currently available on the market. Conclusion Based on these results, polymeric heart valves based on styrenic block copolymers, as Poli-Valves are, can be considered as promising alternative for heart valve replacement in near future. PMID:26689146

Fluid dynamic characterization of a polymeric heart valve prototype (Poli-Valve) tested under continuous and pulsatile flow conditions.

PubMed

De Gaetano, Francesco; Serrani, Marta; Bagnoli, Paola; Brubert, Jacob; Stasiak, Joanna; Moggridge, Geoff D; Costantino, Maria Laura

2015-11-01

Only mechanical and biological heart valve prostheses are currently commercially available. The former show longer durability but require anticoagulant therapy; the latter display better fluid dynamic behavior but do not have adequate durability. New Polymeric Heart Valves (PHVs) could potentially combine the hemodynamic properties of biological valves with the durability of mechanical valves. This work presents a hydrodynamic evaluation of 2 groups of newly developed supra-annular, trileaflet prosthetic heart valves made from styrenic block copolymers (SBC): Poli-Valves. 2 types of Poli-Valves made of SBC and differing in polystyrene fraction content were tested under continuous and pulsatile flow conditions as prescribed by ISO 5840 Standard. A pulse duplicator designed ad hoc allowed the valve prototypes to be tested at different flow rates and frequencies. Pressure and flow were recorded; pressure drops, effective orifice area (EOA), and regurgitant volume were computed to assess the behavior of the valve. Both types of Poli-Valves met the minimum requirements in terms of regurgitation and EOA as specified by the ISO 5840 Standard. Results were compared with 5 mechanical heart valves (MHVs) and 5 tissue heart valves (THVs), currently available on the market. Based on these results, PHVs based on styrenic block copolymers, as are Poli-Valves, can be considered a promising alternative for heart valve replacement in the near future.

Tomographic PIV behind a prosthetic heart valve

NASA Astrophysics Data System (ADS)

Hasler, D.; Landolt, A.; Obrist, D.

2016-05-01

The instantaneous three-dimensional velocity field past a bioprosthetic heart valve was measured using tomographic particle image velocimetry. Two digital cameras were used together with a mirror setup to record PIV images from four different angles. Measurements were conducted in a transparent silicone phantom with a simplified geometry of the aortic root. The refraction indices of the silicone phantom and the working fluid were matched to minimize optical distortion from the flow field to the cameras. The silicone phantom of the aorta was integrated in a flow loop driven by a piston pump. Measurements were conducted for steady and pulsatile flow conditions. Results of the instantaneous, ensemble and phase-averaged flow field are presented. The three-dimensional velocity field reveals a flow topology, which can be related to features of the aortic valve prosthesis.

Urethral anatomy and semen flow during ejaculation

NASA Astrophysics Data System (ADS)

Kelly, Diane

2016-11-01

Ejaculation is critical for reproductive success in many animals, but little is known about its hydrodynamics. In mammals, ejaculation pushes semen along the length of the penis through the urethra. Although the urethra also carries urine during micturition, the flow dynamics of micturition and ejaculation differ: semen is more viscous than urine, and the pressure that drives its flow is derived primarily from the rhythmic contractions of muscles at the base of the penis, which produce pulsatile rather than steady flow. In contrast, Johnston et al. (2014) describe a steady flow of semen through the crocodilian urethral groove during ejaculation. Anatomical differences of tissues associated with mammalian and crocodilian urethral structures may underlie these differences in flow behavior.

Doppler ultrasonography of the pectinis oculi artery in harpy eagles (Harpia harpyja)

PubMed Central

de Moraes, Wanderlei; Ferreira, Thiago A.C.; Somma, André T.; Cubas, Zalmir S.; Moore, Bret A.; Montiani-Ferreira, Fabiano

2017-01-01

Twenty harpy eagles (Harpia harpyja) without systemic or ocular diseases were examined to measure blood velocity parameters of the pectinis oculi artery using Doppler ultrasonography. Pectinate artery resistive index (RI) and pulsatility index (PI) were investigated using ocular Doppler ultrasonography. The mean RI and PI values across all eyes were 0.44±0.10 and 0.62±0.20 respectively. Low RI and PI values found in the harpy eagle´s pectinis oculi artery compared with the American pekin ducks one and other tissue suggest indeed a high metabolic activity in pecten oculi and corroborates the hypothesis of a nutritional function and/or intraocular pressure regulation. PMID:28540254

Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

USDA-ARS?s Scientific Manuscript database

Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have previously shown that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in...

Concentric Rings K-Space Trajectory for Hyperpolarized 13C MR Spectroscopic Imaging

PubMed Central

Jiang, Wenwen; Lustig, Michael; Larson, Peder E.Z.

2014-01-01

Purpose To develop a robust and rapid imaging technique for hyperpolarized 13C MR Spectroscopic Imaging (MRSI) and investigate its performance. Methods A concentric rings readout trajectory with constant angular velocity is proposed for hyperpolarized 13C spectroscopic imaging and its properties are analyzed. Quantitative analyses of design tradeoffs are presented for several imaging scenarios. The first application of concentric rings on 13C phantoms and in vivo animal hyperpolarized 13C MRSI studies were performed to demonstrate the feasibility of the proposed method. Finally, a parallel imaging accelerated concentric rings study is presented. Results The concentric rings MRSI trajectory has the advantages of acquisition timesaving compared to echo-planar spectroscopic imaging (EPSI). It provides sufficient spectral bandwidth with relatively high SNR efficiency compared to EPSI and spiral techniques. Phantom and in vivo animal studies showed good image quality with half the scan time and reduced pulsatile flow artifacts compared to EPSI. Parallel imaging accelerated concentric rings showed advantages over Cartesian sampling in g-factor simulations and demonstrated aliasing-free image quality in a hyperpolarized 13C in vivo study. Conclusion The concentric rings trajectory is a robust and rapid imaging technique that fits very well with the speed, bandwidth, and resolution requirements of hyperpolarized 13C MRSI. PMID:25533653

Motion Tolerant Unfocused Imaging of Physiological Waveforms for Blood Pressure Waveform Estimation Using Ultrasound.

PubMed

Seo, Joohyun; Pietrangelo, Sabino J; Sodini, Charles G; Lee, Hae-Seung

2018-05-01

This paper details unfocused imaging using single-element ultrasound transducers for motion tolerant arterial blood pressure (ABP) waveform estimation. The ABP waveform is estimated based on pulse wave velocity and arterial pulsation through Doppler and M-mode ultrasound. This paper discusses approaches to mitigate the effect of increased clutter due to unfocused imaging on blood flow and diameter waveform estimation. An intensity reduction model (IRM) estimator is described to track the change of diameter, which outperforms a complex cross-correlation model (C3M) estimator in low contrast environments. An adaptive clutter filtering approach is also presented, which reduces the increased Doppler angle estimation error due to unfocused imaging. Experimental results in a flow phantom demonstrate that flow velocity and diameter waveforms can be reliably measured with wide lateral offsets of the transducer position. The distension waveform estimated from human carotid M-mode imaging using the IRM estimator shows physiological baseline fluctuations and 0.6-mm pulsatile diameter change on average, which is within the expected physiological range. These results show the feasibility of this low cost and portable ABP waveform estimation device.

Flow Visualization of Three-Dimensionality Inside the 12 cc Penn State Pulsatile Pediatric Ventricular Assist Device

PubMed Central

Roszelle, Breigh N.; Deutsch, Steven; Manning, Keefe B.

2010-01-01

In order to aid the ongoing concern of limited organ availability for pediatric heart transplants, Penn State has continued development of a pulsatile Pediatric Ventricular Assist Device (PVAD). Initial studies of the PVAD observed an increase in thrombus formation due to differences in flow field physics when compared to adult sized devices, which included a higher degree of three-dimensionality. This unique flow field brings into question the use of 2D planar particle image velocimetry (PIV) as a flow visualization technique, however the small size and high curvature of the PVAD make other tools such as stereoscopic PIV impractical. In order to test the reliability of the 2D results, we perform a pseudo-3D PIV study using planes both parallel and normal to the diaphragm employing a mock circulatory loop containing a viscoelastic fluid that mimics 40% hematocrit blood. We find that while the third component of velocity is extremely helpful to a physical understanding of the flow, particularly of the diastolic jet and the development of a desired rotational pattern, the flow data taken parallel to the diaphragm is sufficient to describe the wall shear rates, a critical aspect to the study of thrombosis and design of such pumps. PMID:19936926

Pulsatility Index as a Diagnostic Parameter of Reciprocating Wall Shear Stress Parameters in Physiological Pulsating Waveforms

PubMed Central

Avrahami, Idit; Kersh, Dikla

2016-01-01

Arterial wall shear stress (WSS) parameters are widely used for prediction of the initiation and development of atherosclerosis and arterial pathologies. Traditional clinical evaluation of arterial condition relies on correlations of WSS parameters with average flow rate (Q) and heart rate (HR) measurements. We show that for pulsating flow waveforms in a straight tube with flow reversals that lead to significant reciprocating WSS, the measurements of HR and Q are not sufficient for prediction of WSS parameters. Therefore, we suggest adding a third quantity—known as the pulsatility index (PI)—which is defined as the peak-to-peak flow rate amplitude normalized by Q. We examine several pulsating flow waveforms with and without flow reversals using a simulation of a Womersley model in a straight rigid tube and validate the simulations through experimental study using particle image velocimetry (PIV). The results indicate that clinically relevant WSS parameters such as the percentage of negative WSS (P[%]), oscillating shear index (OSI) and the ratio of minimum to maximum shear stress rates (min/max), are better predicted when the PI is used in conjunction with HR and Q. Therefore, we propose to use PI as an additional and essential diagnostic quantity for improved predictability of the reciprocating WSS. PMID:27893801

Tactile communication using a CO(2) flux stimulation for blind or deafblind people.

PubMed

da Cunha, Jose Carlos; Bordignon, Luiz Alberto; Nohama, Percy

2010-01-01

This paper describes a tactile stimulation system for producing nonvisual image patterns to blind or deafblind people. The stimulator yields a CO(2) pulsatile flux directed to the user's skin throughout a needle that is coupled to a 2-D tactile plotter. The fluxtactile plotter operates with two step motor mounted on a wood structure, controlled by a program developed to produce alphanumerical characters and geometric figures of different size and speed, which will be used to investigate the psychophysical properties of this kind of tactile communication. CO(2) is provided by a cylinder that delivers a stable flux, which is converted to a pulsatile mode through a high frequency solenoid valve that can chop it up to 1 kHz. Also, system temperature is controlled by a Peltier based device. Tests on the prototype indicate that the system is a valuable tool to investigate the psychophysical properties of the skin in response to stimulation by CO(2) jet, allowing a quantitative and qualitative analysis as a function of stimulation parameters. With the system developed, it was possible to plot the geometric figures proposed: triangles, rectangles and octagons, in different sizes and speeds, and verify the control of the frequency of CO(2) jet stimuli.

Clinical characteristics of pulsatile tinnitus caused by sigmoid sinus diverticulum and wall dehiscence: a study of 54 patients.

PubMed

Wang, Guo-Peng; Zeng, Rong; Liu, Zhao-Hui; Liang, Xi-Hong; Xian, Jun-Fang; Wang, Zhen-Chang; Gong, Shu-Sheng

2014-01-01

CT angiography (CTA) and digital subtraction angiography (DSA) are valuable tools in imaging work-ups for the diagnosis of sigmoid sinus diverticulum (SSD) and sigmoid sinus wall dehiscence (SSWD). The development of pulsatile tinnitus (PT) resulting from SSD and SSWD may be associated with the dominance of venous systems. Our goal was to evaluate the clinical characteristics of PT caused by SSD and SSWD. This was a retrospective chart review undertaken in a tertiary academic referral center. Fifty-four patients with PT due to SSD and SSWD were recruited. Hospital files of these patients were assessed. Data included medical history, physical examinations, auxiliary examinations, and radiographic findings of CTA and DSA. The study population comprised 51 females and 3 males. Most patients with PT caused by SSD and SSWD were middle-aged women. All had normal otoscopy results. Anomalies occurred in or adjacent to the region of the transverse-sigmoid sinus junction in 52 patients. Half of the patients (27/54) presented abnormal results of examination of blood lipids. There were 57.41% (31/54) cases with ipsilateral dominance of the venous system, 9.26% (5/54) cases with contralateral dominance, and 33.33% (18/54) cases with co-dominance of the venous system.

Flow Patterns in the Jugular Veins of Pulsatile Tinnitus Patients

PubMed Central

Kao, Evan; Kefayati, Sarah; Amans, Matthew R.; Faraji, Farshid; Ballweber, Megan; Halbach, Van; Saloner, David

2017-01-01

Pulsatile Tinnitus (PT) is a pulse-synchronous sound heard in the absence of an external source. PT is often related to abnormal flow in vascular structures near the cochlea. One vascular territory implicated in PT is the internal jugular vein (IJV). Using computational fluid dynamics (CFD) based on patient-specific Magnetic Resonance Imaging (MRI), we investigated the flow within the IJV of seven subjects, four symptomatic and three asymptomatic of PT. We found that there were two extreme anatomic types classified by the shape and position of the jugular bulbs: elevated and rounded. PT patients had elevated jugular bulbs that led to a distinctive helical flow pattern within the proximal internal jugular vein. Asymptomatic subjects generally had rounded jugular bulbs that neatly redirected flow from the sigmoid sinus directly into the jugular vein. These two flow patterns were quantified by calculating the length-averaged streamline curvature of the flow within the proximal jugular vein: 130.3 ± 8.1 m-1 for geometries with rounded bulbs, 260.7 ± 29.4 m-1 for those with elevated bulbs (P < 0.005). Our results suggest that variations in the jugular bulb geometry lead to distinct flow patterns that are linked to PT, but further investigation is needed to determine if the vortex pattern is causal to sound generation. PMID:28057349

The effect of a simulation training package on skill acquisition for duplex arterial stenosis detection.

PubMed

Jaffer, Usman; Normahani, Pasha; Singh, Prashant; Aslam, Mohammed; Standfield, Nigel J

2015-01-01

In vascular surgery, duplex ultrasonography is a valuable diagnostic tool in patients with peripheral vascular disease, and there is increasing demand for vascular surgeons to be able to perform duplex scanning. This study evaluates the role of a novel simulation training package on vascular ultrasound (US) skill acquisition. A total of 19 novices measured predefined stenosis in a simulated pulsatile vessel using both peak systolic velocity ratio (PSVR) and diameter reduction (DR) methods before and after a short period of training using a simulated training package. The training package consisted of a simulated pulsatile vessel phantom, a set of instructional videos, duplex ultrasound objective structured assessment of technical skills (DUOSATS) tool, and a portable US scanner. Quantitative metrics (procedure time, percentage error using PSVR and DR methods, DUOSAT scores, and global rating scores) before and after training were compared. Subjects spent a median time of 144 mins (IQR: 60-195) training using the simulation package. Subjects exhibited statistically significant improvements when comparing pretraining and posttraining DUOSAT scores (pretraining = 17 [16-19.3] vs posttraining = 30 [27.8-31.8]; p < 0.01), global rating score (pretraining = 1 [1-2] vs posttraining = 4 [3.8-4]; p < 0.01), percentage error using both the DR (pretraining = 12.6% [9-29.6] vs posttraining = 10.3% [8.9-11.1]; p = 0.03) and PSVR (pretraining = 60% [40-60] vs posttraining = 20% [6.7-20]; p < 0.01) methods. In this study, subjects with no previous practical US experience developed the ability to both acquire and interpret arterial duplex images in a pulsatile simulated phantom following a short period of goal direct training using a simulation training package. A simulation training package may be a valuable tool for integration into a vascular training program. However, further work is needed to explore whether these newly attained skills are translated into clinical assessment. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Effect of non-Newtonian and pulsatile blood flow on mass transport in the human aorta.

PubMed

Liu, Xiao; Fan, Yubo; Deng, Xiaoyan; Zhan, Fan

2011-04-07

To investigate the effects of both non-Newtonian behavior and the pulsation of blood flow on the distributions of luminal surface LDL concentration and oxygen flux along the wall of the human aorta, we numerically compared a non-Newtonian model with the Newtonian one under both steady flow and in vivo pulsatile flow conditions using a human aorta model constructed from MRI images. The results showed that under steady flow conditions, although the shear thinning non-Newtonian nature of blood could elevate wall shear stress (WSS) in most regions of the aorta, especially areas with low WSS, it had little effect on luminal surface LDL concentration (c(w)) in most regions of the aorta. Nevertheless, it could significantly enhance c(w) in areas with high luminal surface LDL concentration through the shear dependent diffusivity of LDLs. For oxygen transport, the shear thinning non-Newtonian nature of blood could slightly reduce oxygen flux in most regions of the aorta, but this effect became much more apparent in areas with already low oxygen flux. The pulsation of blood flow could significantly reduce c(w) and enhance oxygen flux in these disturbed places. In most other regions of the aorta, the oxygen flux was also significantly higher than that for the steady flow simulation. In conclusion, the shear shining non-Newtonian nature of blood has little effect on LDL and oxygen transport in most regions of the aorta, but in the atherogenic-prone areas where luminal surface LDL concentration is high and oxygen flux is low, its effect is apparent. Similar is for the effect of pulsatile flow on the transport of LDLs. But, the pulsation of blood flow can apparently affect oxygen flux in the aorta, especially in areas with low oxygen flux. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cardiac-driven Pulsatile Motion of Intracranial Cerebrospinal Fluid Visualized Based on a Correlation Mapping Technique.

PubMed

Yatsushiro, Satoshi; Sunohara, Saeko; Hayashi, Naokazu; Hirayama, Akihiro; Matsumae, Mitsunori; Atsumi, Hideki; Kuroda, Kagayaki

2018-04-10

A correlation mapping technique delineating delay time and maximum correlation for characterizing pulsatile cerebrospinal fluid (CSF) propagation was proposed. After proofing its technical concept, this technique was applied to healthy volunteers and idiopathic normal pressure hydrocephalus (iNPH) patients. A time-resolved three dimensional-phase contrast (3D-PC) sampled the cardiac-driven CSF velocity at 32 temporal points per cardiac period at each spatial location using retrospective cardiac gating. The proposed technique visualized distributions of propagation delay and correlation coefficient of the PC-based CSF velocity waveform with reference to a waveform at a particular point in the CSF space. The delay time was obtained as the amount of time-shift, giving the maximum correlation for the velocity waveform at an arbitrary location with that at the reference location. The validity and accuracy of the technique were confirmed in a flow phantom equipped with a cardiovascular pump. The technique was then applied to evaluate the intracranial CSF motions in young, healthy (N = 13), and elderly, healthy (N = 13) volunteers and iNPH patients (N = 13). The phantom study demonstrated that root mean square error of the delay time was 2.27%, which was less than the temporal resolution of PC measurement used in this study (3.13% of a cardiac cycle). The human studies showed a significant difference (P < 0.01) in the mean correlation coefficient between the young, healthy group and the other two groups. A significant difference (P < 0.05) was also recognized in standard deviation of the correlation coefficients in intracranial CSF space among all groups. The result suggests that the CSF space compliance of iNPH patients was lower than that of healthy volunteers. The correlation mapping technique allowed us to visualize pulsatile CSF velocity wave propagations as still images. The technique may help to classify diseases related to CSF dynamics, such as iNPH.

Differences in aortic vortex flow pattern between normal and patients with stroke: qualitative and quantitative assessment using transesophageal contrast echocardiography.

PubMed

Son, Jang-Won; Hong, Geu-Ru; Hong, Woosol; Kim, Minji; Houle, Helene; Vannan, Mani A; Pedrizzetti, Gianni; Chung, Namsik

2016-06-01

The flow in the aorta forms a vortex, which is a critical determinant of the flow dynamics in the aorta. Arteriosclerosis can alter the blood flow pattern of the aorta and cause characteristic alterations of the vortex. However, this change in aortic vortex has not yet been studied. This study aimed to characterize aortic vortex flow pattern using transesophageal contrast echocardiography in normal and stroke patients. A total of 85 patients who diagnosed with ischemic stroke and 16 normal controls were recruited for this study. The 16 normal control subjects were designated as the control group, and the 85 ischemic stroke patients were designated as the stroke group. All subjects underwent contrast transesophageal echocardiography (TEE), and particle image velocimetry was used to assess aortic vortex flow. Qualitative and quantitative analyses of vortex flow morphology, location, phasic variation, and pulsatility were undertaken and compared between the groups. In the control group, multiple irregularly-shaped vortices were observed in a peripheral location in the descending thoracic aorta. In contrast, the stroke group had a single, round, merged, and more centrally located aortic vortex flow. In the quantitative analysis of vortex, vortex depth, which represents the location of the major vortex in the aorta, was significantly higher in the control group than in the stroke group (0.599 ± 0.159 vs. 0.522 ± 0.101, respectively, P = 0.013). Vortex relative strength, which is the pulsatility parameter of the vortex itself, was significantly higher in the stroke group than in the control group (0.367 ± 0.148 vs. 0.304 ± 0.087, respectively, P = 0.025). It was feasible to visualize and quantify the characteristic morphology and pulsatility of the aortic vortex flow using contrast TEE, and aortic vortex pattern significantly differed between normal and stroke patients.

Augmentative effect of pulsatility on the wall shear stress in tube flow.

PubMed

Nakata, M; Tatsumi, E; Tsukiya, T; Taenaka, Y; Nishimura, T; Nishinaka, T; Takano, H; Masuzawa, T; Ohba, K

1999-08-01

Wall shear stress (WSS) has been considered to play an important role in the physiological and metabolic functions of the vascular endothelial cells. We investigated the effects of the pulse rate and the maximum flow rate on the WSS to clarify the influence of pulsatility. Water was perfused in a 1/2 inch transparent straight cylinder with a nonpulsatile centrifugal pump and a pulsatile pneumatic ventricular assist device (VAD). In nonpulsatile flow (NF), the flow rate was changed 1 to 6 L/min by 1 L/min increments to obtain standard values of WSS at each flow rate. In pulsatile flow (PF), the pulse rate was controlled at 40, 60, and 80 bpm, and the maximum flow rate was varied from 3.3 to 12.0 L/min while the mean flow rate was kept at 3 L/min. The WSS was estimated from the velocity profile at measuring points using the laser illuminated fluorescence method. In NF, the WSS was 12.0 dyne/cm2 at 3 L/min and 33.0 dyne/cm2 at 6 L/min. In PF, the pulse rate change with the same mean, and the maximum flow rate did not affect WSS. On the other hand, the increase in the maximum flow rate at the constant mean flow rate of 3 L/min augmented the mean WSS from 13.1 to 32.9 dyne/cm2. We concluded that the maximum flow rate exerted a substantial augmentative effect on WSS, and the maximum flow rate was a dominant factor of pulsatility in this effect.

Male sexual behavior contributes to the maintenance of high LH pulsatility in anestrous female goats.

PubMed

Vielma, Jesús; Chemineau, Philippe; Poindron, Pascal; Malpaux, Benoît; Delgadillo, José Alberto

2009-10-01

The objective of this study was to determine the importance of male sexual behavior in stimulating LH secretion in anovulatory female goats. Two groups of females (n=10 per group) were each exposed to a buck in sexual rest and submitted to natural daylength. In one group, the buck was awake, whereas in the other group, it was sedated to prevent its sexual behavior. Two other groups of goats (n=10 per group) were exposed to sexually active bucks that had been exposed to 2.5 months of long days. In one group, the buck was awake, and in the other group, it was sedated. LH secretion was determined every 15 min from 4 h before introducing the bucks to 8 h after, then every 15 min again from 20 to 24 h after introducing the bucks. The bucks submitted to natural daylength did not stimulate LH secretion (P>0.05), whether they were sedated or not. In contrast, both the awake and the sedated light-treated bucks induced an increase (P<0.05) of LH pulsatility in the first 4 h following their introduction. However, pulsatility remained elevated until 24 h in the females exposed to the light-treated awake buck, whereas in the group with the light-treated sedated buck, pulsatility diminished (P<0.05) after the first 4 h of stimulation by the buck. In conclusion, the sexual behavior of males contributes to the maintenance of a high LH pulsatility up to 24 h after introduction into a group of anovulatory goats.

Numerical solutions of pulsating flow and heat transfer characteristics in a channel with a backward-facing step

NASA Astrophysics Data System (ADS)

Valencia, A.; Hinojosa, L.

The incompressible laminar flow of air and heat transfer in a channel with a backward-facing step is studied for steady cases and for pulsatile inlet conditions. For steady flows the influence of the inlet velocity profile, the height of the step and the Reynolds number on the reattachment length is investigated. A parabolic entrance profile was used for pulsatile flow. It was found with amplitude of oscillation of one by Re=100 that the primary vortex breakdown through one pulsatile cycle. The wall shear rate in the separation zone varied markedly with pulsatile flows and the wall heat transfer remained relatively constant. The time-average pulsatile heat transfer at the walls was greater as with steady flow with the same mean Reynolds number. Zusammenfassung Es wird eine zweidimensionale numerische Untersuchung des instationären Wärmeübergangs und Druckverlustes im laminar durchströmten Spaltkanal mit einer plötzlichen Kanalerweiterung dargelegt und zwar für stationäre und periodische Geschwindigkeitsprofile am Eintritt des Kanals. Für stationäre Strömungen wurden die Form des Eintrittsprofils, die Reynoldszahl und die Kanalerweiterung variiert. Als Lösung der Navier/Stokes-und der Energiegleichungen mit periodischen Randbedingungen resultiert eine oszillierende Strömung, die das Aufplatzen des Primärwirbels in einer Schwingungsperiode zur Folge hat. Der Einfluß dieser Oszillation auf den Wärmeübergang und den Strömungsverlust wurde für die maximale Amplitude und für Re=100 eingehend untersucht.

Quantitative clinical nonpulsatile and localized visible light oximeter: design of the T-Stat tissue oximeter

NASA Astrophysics Data System (ADS)

Benaron, David A.; Parachikov, Ilian H.; Cheong, Wai-Fung; Friedland, Shai; Duckworth, Joshua L.; Otten, David M.; Rubinsky, Boris E.; Horchner, Uwe B.; Kermit, Eben L.; Liu, Frank W.; Levinson, Carl J.; Murphy, Aileen L.; Price, John W.; Talmi, Yair; Weersing, James P.

2003-07-01

We report the development of a general, quantitative, and localized visible light clinical tissue oximeter, sensitive to both hypoxemia and ischemia. Monitor design and operation were optimized over four instrument generations. A range of clinical probes were developed, including non-contact wands, invasive catheters, and penetrating needles with injection ports. Real-time data were collected (a) from probes, standards, and reference solutions to optimize each component, (b) from ex vivo hemoglobin solutions co-analyzed for StO2% and pO2 during deoxygenation, and (c) from normoxic human subject skin and mucosal tissue surfaces. Results show that (a) differential spectroscopy allows extraction of features with minimization of the effects of scattering, (b) in vitro oximetry produces a hemoglobin saturation binding curve of expected sigmoid shape and values, and (c) that monitoring human tissues allows real-time tissue spectroscopic features to be monitored. Unlike with near-infrared (NIRS) or pulse oximetry (SpO2%) methods, we found non-pulsatile, diffusion-based tissue oximetry (StO2%) to work most reliably for non-contact reflectance monitoring and for invasive catheter- or needle-based monitoring, using blue to orange light (475-600 nm). Measured values were insensitive to motion artifact. Down time was non-existent. We conclude that the T-Stat oximeter design is suitable for the collection of spectroscopic data from human subjects, and that the oximeter may have application in the monitoring of regional hemoglobin oxygen saturation in the capillary tissue spaces of human subjects.

Collective pulsatile expansion and swirls in proliferating tumor tissue

NASA Astrophysics Data System (ADS)

Yang, Taeseok Daniel; Kim, Hyun; Yoon, Changhyeong; Baek, Seung-Kuk; Lee, Kyoung J.

2016-10-01

Understanding the dynamics of expanding biological tissues is essential to a wide range of phenomena in morphogenesis, wound healing and tumor proliferation. Increasing evidence suggests that many of the relevant phenomena originate from complex collective dynamics, inherently nonlinear, of constituent cells that are physically active. Here, we investigate thin disk layers of proliferating, cohesive, monoclonal tumor cells and report the discovery of macroscopic, periodic, soliton-like mechanical waves with which cells are collectively ratcheting, as in the traveling-wave chemotaxis of dictyostelium discodium amoeba cells. The relevant length-scale of the waves is remarkably large (∼1 mm), compared to the thickness of a mono-layer tissue (∼ 10 μ {{m}}). During the tissue expansion, the waves are found to repeat several times with a quite well defined period of approximately 4 h. Our analyses suggest that the waves are initiated by the leading edge that actively pulls the tissue in the outward direction, while the cells within the bulk tissue do not seem to generate a strong self-propulsion. Subsequently, we demonstrate that a simple mathematical model chain of nonlinear springs that are constantly pulled in the outward direction at the leading edge recapitulates the observed phenomena well. As the areal cell density becomes too high, the tissue expansion stalls and the periodic traveling waves yield to multiple swirling vortices. Cancer cells are known to possess a broad spectrum of migration mechanisms. Yet, our finding has established a new unusual mode of tumor tissue expansion, and it may be equally applicable for many different expanding thin layers of cell tissues.

Imaging complex nutrient dynamics in mycelial networks.

PubMed

Fricker, M D; Lee, J A; Bebber, D P; Tlalka, M; Hynes, J; Darrah, P R; Watkinson, S C; Boddy, L

2008-08-01

Transport networks are vital components of multi-cellular organisms, distributing nutrients and removing waste products. Animal cardiovascular and respiratory systems, and plant vasculature, are branching trees whose architecture is thought to determine universal scaling laws in these organisms. In contrast, the transport systems of many multi-cellular fungi do not fit into this conceptual framework, as they have evolved to explore a patchy environment in search of new resources, rather than ramify through a three-dimensional organism. These fungi grow as a foraging mycelium, formed by the branching and fusion of threadlike hyphae, that gives rise to a complex network. To function efficiently, the mycelial network must both transport nutrients between spatially separated source and sink regions and also maintain its integrity in the face of continuous attack by mycophagous insects or random damage. Here we review the development of novel imaging approaches and software tools that we have used to characterise nutrient transport and network formation in foraging mycelia over a range of spatial scales. On a millimetre scale, we have used a combination of time-lapse confocal imaging and fluorescence recovery after photobleaching to quantify the rate of diffusive transport through the unique vacuole system in individual hyphae. These data then form the basis of a simulation model to predict the impact of such diffusion-based movement on a scale of several millimetres. On a centimetre scale, we have used novel photon-counting scintillation imaging techniques to visualize radiolabel movement in small microcosms. This approach has revealed novel N-transport phenomena, including rapid, preferential N-resource allocation to C-rich sinks, induction of simultaneous bi-directional transport, abrupt switching between different pre-existing transport routes, and a strong pulsatile component to transport in some species. Analysis of the pulsatile transport component using Fourier techniques shows that as the colony forms, it self-organizes into well demarcated domains that are identifiable by differences in the phase relationship of the pulses. On the centimetre to metre scale, we have begun to use techniques borrowed from graph theory to characterize the development and dynamics of the network, and used these abstracted network models to predict the transport characteristics, resilience, and cost of the network.

An intriguing design concept to enhance the pulsatile fatigue life of self-expanding stents.

PubMed

Hsiao, Hao-Ming; Yin, Ming-Ting

2014-02-01

Intravascular stenting has emerged as the primary treatment for vascular diseases and has received great attention from the medical community since its introduction two decades ago. The endovascular self-expanding stent is used to treat peripheral artery diseases; however, once implanted, these stents suffer from various cyclic motions caused by pulsatile blood pressure and daily activities. Due to this challenging environment, fatigue performance has become a critical issue for stent design. In this paper, a simple yet intriguing concept of stent design aimed at enhancing pulsatile fatigue life is investigated. The concept of this design is to shift the highly concentrated stresses/strains away from the crown and re-distribute them along the stress-free bar arm by tapering its strut width. Finite element models were developed to evaluate the mechanical integrity and pulsatile fatigue resistance of the stent to various loading conditions. Results show that the fatigue safety factor jumped to 2.5-3.0 times that of the standard stent with constant strut width. This is astonishing considering that the stent profile and scaffolding were not compromised. The findings of this paper provide an excellent approach to the optimization of future stent design to greatly improve stent fatigue performance.

A durability study of a paracorporeal pulsatile electro-mechanical pneumatic biventricular assist device.

PubMed

Choi, Hyuk; Lee, Heung-Man; Nam, Kyoung Won; Choi, Jaesoon; Lee, Jung-Joo; Kim, Ho Chul; Song, Seung Joon; Ahn, Chi Bum; Son, Ho Sung; Lim, Choon Hak; Son, Kuk Hui; Park, Yong Doo; Jeong, Gi Seok; Sun, Kyung

2011-06-01

In 2002, the paracorporeal pulsatile electro-mechanical pneumatic ventricular assist device (VAD) began to be developed by the Korea Artificial Organ Center at Korea University under a Health & Medical Technology Research and Development program which finished in 2008. In vitro durability testing was conducted on the paracorporeal pulsatile pneumatic VAD to determine device durability and to evaluate device failures. The 1- and 2-year reliability of the paracorporeal pulsatile pneumatic VAD was shown to be 91.2% and 54.9%, respectively, with an 80% confidence level. Failure modes were analyzed using fault tree analysis, with customized software continuously acquiring data during the test period. After this period, 21 in vivo animal tests were done, with 14 cases of left atrium to left ventricle (LV) inflow cannulation (36Fr)/outflow grafting to descending aorta, and seven cases of apex cannulation of LV to descending aorta (12 mm). The longest postoperative day (182 days) in Korea was recently recorded in in vivo animal testing (bovine, 90 kg, male, 3.5-4.0 L/min flow rate, and 55 bpm). © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

The effect of prenatally administered vaginal progesterone on uterine artery Doppler in asymptomatic twin pregnancies.

PubMed

Agra, Isabela K R; Brizot, Maria L; Miyadahira, Mariana Y; Carvalho, Mário H B; Francisco, Rossana P V; Zugaib, Marcelo

2016-10-01

This study investigated the influence of vaginal progesterone on uterine circulation in asymptomatic twin gestations. This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. We included all trial participants who had undergone uterine artery pulsatility index evaluation at the time of randomization. During each ultrasound examination, the uterine artery pulsatility index was evaluated transabdominally. The mean uterine artery pulsatility index between the progesterone and placebo groups were compared for each gestational age, starting between 18 to 34 weeks and 6days and were analyzed at three (Time 1), six (Time 2) and nine (Time 3) weeks after randomization. The final analysis included 128 women in the progesterone group and 122 women in the placebo group. The baseline characteristics were similar in both groups. No difference in the mean uterine artery pulsatility index was observed between the progesterone and placebo groups at each week of gestation or throughout gestation. In twin pregnancies, the use of vaginal progesterone in the second half of pregnancy does not influence uterine circulation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nanoscaffold matrices for size-controlled, pulsatile transdermal testosterone delivery: nanosize effects on the time dimension

NASA Astrophysics Data System (ADS)

Malik, Ritu; Tondwal, Shailesh; Venkatesh, K. S.; Misra, Amit

2008-10-01

Pulsatile transdermal testosterone (T) has applications in hormone supplementation and male contraception. Pulsatile T delivery was achieved by assembling crystalline and nanoparticulate T in nucleation-inhibiting polymer matrices of controlled porosity. Different interference patterns observed from various polymeric films containing T were due to the various particle sizes of T present in the polymer matrices. Scanning electron microscopy was used to determine the size and shape of T crystals. Skin-adherent films containing T nanoparticles of any size between 10-500 nm could be prepared using pharmaceutically acceptable vinylic polymers. Drug release and skin permeation profiles were studied. The dissolution-diffusion behavior of nanoparticles differed from crystalline and molecular states. Nanosize may thus be used to engineer chronopharmacologically relevant drug delivery.

[Ovulation induction by pulsatile GnRH therapy in 2014: literature review and synthesis of current practice].

PubMed

Gronier, H; Peigné, M; Catteau-Jonard, S; Dewailly, D; Robin, G

2014-10-01

The hypogonadotropic hypogonadism is an easily treatable form of female infertility. The most common cause of hypogonadotropic hypogonadism is functional hypothalamic amenorrhea. The GnRH pump is a simple and effective treatment to restore fertility of patients with hypothalamic amenorrhea: cumulative pregnancy rate is estimated between 70 and 100% after 6 cycles, compared to a low rate of complications and multiple pregnancies. While only 2.8 cycles are on average required to achieve a pregnancy with a pump, this induction of ovulation stays underused in France. The objective of this paper is to propose a practical manual of pulsatile GnRH, in order to improve the accessibility of pulsatile GnRH for patients with hypogonadotropic hypogonadism. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Fatigue and In Vivo Validation of a Peritoneum-Lined Self-Expanding Nitinol Stent-Graft

PubMed Central

Bastijanic, Jennifer M.; Etscheidt, Jordan; Sattiraju, Mallika; Bonsignore, Craig; Kopchok, George; White, Rodney; Sarac, Timur P.

2014-01-01

Purpose To assess the fatigue and in vivo performance of a new stent-graft incorporating bovine peritoneum lining that is designed for application in peripheral vascular occlusive disease. Methods Bovine peritoneum-lined stent-grafts were subjected to accelerated in vitro pulsatile fatigue and axial/torsional fatigue testing designed to simulate 10 years of physiological strain on the devices. At specified times the devices were evaluated for stent fracture, suture failure, or tissue tearing. Seven dogs underwent bilateral common iliac artery (CIA) balloon angioplasty injury with unilateral placement of the peritoneum-lined stent-graft. Angiography and intravascular ultrasound were performed prior to treatment, after treatment, and prior to sacrifice at 30 days. Vessels were perfusion fixed and histologically evaluated at 5 regions: above stent, proximal stent, mid stent, distal stent, and below stent. Results No evidence of stent, suture, or tissue failure was present during or after pulsatile and axial/torsional fatigue testing. At 30±0.3 days after implantation, all vessels were patent. The average lumen area at explantation across stented vessels was 25.45 mm2. Lumen areas tended to be reduced above (23.57 mm2) and below (24.17 mm2) the stent. Lumen areas were consistent across stented regions at explantation (proximal stent 27.80 mm2, mid stent 25.88 mm2, and distal stent 25.81 mm2). The mean neointimal area in peritoneum-lined stents was 2.02±1.52 mm2, with a neointima:media ratio of 1.03±0.50. These values were significantly lower in the above and below stent areas than in the stented regions, but there was no difference in either measure within the proximal, mid, or distal stent. Conclusion The custom-designed peritoneum-lined stent-graft is promising for clinical peripheral applications due to its ability to resist relevant long-term physiological stresses and outstanding short-term patency rates in canine implantations. PMID:25290804

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling

PubMed Central

Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

2016-01-01

Background Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients’ compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. Methods The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box–Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Results and Discussion Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box–Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. Conclusions This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box–Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms. PMID:27479702

The association of endothelial function and tone by digital arterial tonometry with MRI left ventricular mass in African Americans: the Jackson Heart Study.

PubMed

Tripathi, Avnish; Benjamin, Emelia J; Musani, Solomon K; Hamburg, Naomi M; Tsao, Connie W; Saraswat, Arti; Vasan, Ramachandran S; Mitchell, Gary F; Fox, Ervin R

2017-05-01

Peripheral vascular endothelial dysfunction assessed by digital peripheral arterial tonometry (PAT) has been associated with risk for adverse cardiovascular events. We examined the relations of peripheral microvascular dysfunction and left ventricular mass in a community-based cohort of African Americans. We examined participants of the Jackson Heart Study who had PAT and cardiac magnetic resonance imaging evaluations between 2007 and 2013. Consistent with pertinent literature, left ventricular mass index (LVMI) was adjusted for body size by indexing to height 2.7 . Pearson's correlation and general linear regression analyses were used to relate reactive hyperemia index, baseline pulse amplitude (BPA), and augmentation index (markers of microvascular vasodilator function, baseline vascular pulsatility, and relative wave reflection, respectively) to LVMI after adjusting for traditional cardiovascular risk factors. A total of 440 participants (mean age 59 ± 10 years, 60% women) were included. Age- and sex-adjusted Pearson's correlation analysis suggested that natural log transformed LVMI was negatively correlated with reactive hyperemia index (coefficient: -0.114; P = .02) and positively correlated with BPA (coefficient: 0.272; P < .001). In multivariable analyses, higher log e LVMI was associated with higher BPA (β: 0.210; P = .03) after accounting for age, sex, body mass index, diabetes, hypertension, ratio of total cholesterol and high-density lipoprotein cholesterol, smoking, and history of cardiovascular disease. In a community-based sample of African Americans, higher baseline pulsatility measured by PAT was associated with higher LVMI by cardiac magnetic resonance imaging after adjusting for traditional risk factors. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Design and efficacy of a single-use bioreactor for heart valve tissue engineering.

PubMed

Converse, Gabriel L; Buse, Eric E; Neill, Kari R; McFall, Christopher R; Lewis, Holley N; VeDepo, Mitchell C; Quinn, Rachael W; Hopkins, Richard A

2017-02-01

Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system for nondestructive valve seeding and mechanical conditioning. Here we report the design for manufacture and the production of full scale, functional prototypes of such a system. To evaluate the efficacy of this bioreactor as a tool for seeding, ovine aortic valves were decellularized and subjected to seeding with human mesenchymal stem cells (hMSC). The effects of pulsatile conditioning using cyclic waveforms tuned to various negative and positive chamber pressures were evaluated, with respect to the seeding of cells on the decellularized leaflet and the infiltration of seeded cells into the interstitium of the leaflet. Infiltration of hMSCs into the aortic valve leaflet was observed following 72 h of conditioning under negative chamber pressure. Additional conditioning under positive pressure improved cellular infiltration, while retaining gene expression within the MSC-valve interstitial cell phenotype lineage. This protocol resulted in a subsurface pilot population of cells, not full tissue recellularization. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 249-259, 2017. © 2015 Wiley Periodicals, Inc.

Intraoperative laser speckle contrast imaging for monitoring cerebral blood flow: results from a 10-patient pilot study

NASA Astrophysics Data System (ADS)

Richards, Lisa M.; Weber, Erica L.; Parthasarathy, Ashwin B.; Kappeler, Kaelyn L.; Fox, Douglas J.; Dunn, Andrew K.

2012-02-01

Monitoring cerebral blood flow (CBF) during neurosurgery can provide important physiological information for a variety of surgical procedures. Although multiple intraoperative vascular monitoring technologies are currently available, a quantitative method that allows for continuous monitoring is still needed. Laser speckle contrast imaging (LSCI) is an optical imaging method with high spatial and temporal resolution that has been widely used to image CBF in animal models in vivo. In this pilot clinical study, we adapted a Zeiss OPMI Pentero neurosurgical microscope to obtain LSCI images by attaching a camera and a laser diode. This LSCI adapted instrument has been used to acquire full field flow images from 10 patients during tumor resection procedures. The patient's ECG was recorded during acquisition and image registration was performed in post-processing to account for pulsatile motion artifacts. Digital photographs confirmed alignment of vasculature and flow images in four cases, and a relative change in blood flow was observed in two patients after bipolar cautery. The LSCI adapted instrument has the capability to produce real-time, full field CBF image maps with excellent spatial resolution and minimal intervention to the surgical procedure. Results from this study demonstrate the feasibility of using LSCI to monitor blood flow during neurosurgery.

Motion Artifact Reduction in Ultrasound Based Thermal Strain Imaging of Atherosclerotic Plaques Using Time Series Analysis

PubMed Central

Dutta, Debaditya; Mahmoud, Ahmed M.; Leers, Steven A.; Kim, Kang

2013-01-01

Large lipid pools in vulnerable plaques, in principle, can be detected using US based thermal strain imaging (US-TSI). One practical challenge for in vivo cardiovascular application of US-TSI is that the thermal strain is masked by the mechanical strain caused by cardiac pulsation. ECG gating is a widely adopted method for cardiac motion compensation, but it is often susceptible to electrical and physiological noise. In this paper, we present an alternative time series analysis approach to separate thermal strain from the mechanical strain without using ECG. The performance and feasibility of the time-series analysis technique was tested via numerical simulation as well as in vitro water tank experiments using a vessel mimicking phantom and an excised human atherosclerotic artery where the cardiac pulsation is simulated by a pulsatile pump. PMID:24808628

Strain measurement of abdominal aortic aneurysm with real-time 3D ultrasound speckle tracking.

PubMed

Bihari, P; Shelke, A; Nwe, T H; Mularczyk, M; Nelson, K; Schmandra, T; Knez, P; Schmitz-Rixen, T

2013-04-01

Abdominal aortic aneurysm rupture is caused by mechanical vascular tissue failure. Although mechanical properties within the aneurysm vary, currently available ultrasound methods assess only one cross-sectional segment of the aorta. This study aims to establish real-time 3-dimensional (3D) speckle tracking ultrasound to explore local displacement and strain parameters of the whole abdominal aortic aneurysm. Validation was performed on a silicone aneurysm model, perfused in a pulsatile artificial circulatory system. Wall motion of the silicone model was measured simultaneously with a commercial real-time 3D speckle tracking ultrasound system and either with laser-scan micrometry or with video photogrammetry. After validation, 3D ultrasound data were collected from abdominal aortic aneurysms of five patients and displacement and strain parameters were analysed. Displacement parameters measured in vitro by 3D ultrasound and laser scan micrometer or video analysis were significantly correlated at pulse pressures between 40 and 80 mmHg. Strong local differences in displacement and strain were identified within the aortic aneurysms of patients. Local wall strain of the whole abdominal aortic aneurysm can be analysed in vivo with real-time 3D ultrasound speckle tracking imaging, offering the prospect of individual non-invasive rupture risk analysis of abdominal aortic aneurysms. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men with age-related low testosterone.

PubMed

Dias, Jenny Pena; Veldhuis, Johannes D; Carlson, Olga; Shardell, Michelle; Chia, Chee W; Melvin, Denise; Egan, Josephine M; Basaria, Shehzad

2017-04-01

Growth hormone is the major regulator of growth and body composition. Pulsatile GH secretion declines exponentially with age. Testosterone replacement is being increasingly offered to older men with age-related low testosterone. Testosterone administration has been shown to stimulate GH secretion. However, little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men. This randomized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone. Thirty-seven men, ≥65years with total testosterone <350ng/dL were randomized to 5g transdermal testosterone gel (TT), 1mg oral aromatase inhibitor (AI) or placebo daily for 12months. Primary outcome was deconvolution and approximate entropy analyses of pulsatile including basal and entropic modes of secretion performed at baseline and 3months. Secondary outcomes included IGF-1 evaluated at baseline, 3 and 6months. At 3months, mean GH and in IGF-1 were similar between the three groups. At 6months, IGF-1 significantly increased by Δ 15.3±10.3ng/ml in the TT-group compared to placebo (P=0.03). Both intervention groups significantly increased GH pulse frequency (TT-group, P=0.04; AI-group, P=0.05) compared to placebo. The GH secretory-burst mode (duration) significantly decreased in the TT-group (P=0.0018) compared to placebo while it remained unchanged in the AI-group (P=0.059). In older men, testosterone increases GH pulse frequency while the aromatization to estradiol is involved in the rise of IGF-1 levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Implantable physiologic controller for left ventricular assist devices with telemetry capability.

PubMed

Asgari, Siavash S; Bonde, Pramod

2014-01-01

Rotary type left ventricular assist devices have mitigated the problem of durability associated with earlier pulsatile pumps and demonstrated improved survival. However, the compromise is the loss of pulsatility due to continuous flow and retained percutaneous driveline leading to increased mortality and morbidity. Lack of pulsatility is implicated in increased gastrointestinal bleeding, aortic incompetence, and diastolic hypertension. We present a novel, wirelessly powered, ultra-compact, implantable physiologic controller capable of running a left ventricular assist device in a pulsatile mode with wireless power delivery. The schematic of our system was laid out on a circuit board to wirelessly receive power and run a left ventricular assist device with required safety and backup measures. We have embedded an antenna and wireless network for telemetry. Multiple signal processing steps and controlling algorithm were incorporated. The controller was tested in in vitro and in vivo experiments. The controller drove left ventricular assist devices continuously for 2 weeks in an in vitro setup and in vivo without any failure. Our controller is more power efficient than the current Food and Drug Administration-approved left ventricular assist device controllers. When used with electrocardiography synchronization, the controller allowed on-demand customization of operation with instantaneous flow and revolutions per minute changes, resulting in a pulsatile flow with adjustable pulse pressure. Our test results prove the system to be remarkably safe, accurate, and efficient. The unique combination of wireless powering and small footprint makes this system an ideal totally implantable physiologic left ventricular assist device system. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Effect of acute high-intensity resistance exercise on optic nerve sheath diameter and ophthalmic artery blood flow pulsatility.

PubMed

Lefferts, W K; Hughes, W E; Heffernan, K S

2015-12-01

Exertional hypertension associated with acute high-intensity resistance exercise (RE) increases both intravascular and intracranial pressure (ICP), maintaining cerebrovascular transmural pressure. Carotid intravascular pressure pulsatility remains elevated after RE. Whether ICP also remains elevated after acute RE in an attempt to maintain the vessel wall transmural pressure is unknown. Optic nerve sheath diameter (ONSD), a valid proxy of ICP, was measured in 20 participants (6 female; 24 ± 4 yr, 24.2 ± 3.9 kg m(-)(2)) at rest (baseline), following a time-control condition, and following RE (5 sets, 5 repetition maximum bench press, 5 sets 10 repetition maximum biceps curls) using ultrasound. Additionally, intracranial hemodynamic pulsatility index (PI) was assessed in the ophthalmic artery (OA) by using Doppler. Aortic pulse wave velocity (PWV) was obtained from synthesized aortic pressure waveforms obtained via a brachial oscillometric cuff and carotid pulse pressure was measured by using applanation tonometry. Aortic PWV (5.2 ± 0.5-6.0 ± 0.7 m s(-1), P < 0.05) and carotid pulse pressure (45 ± 17-59 ± 19 mm Hg, P < 0.05) were significantly elevated post RE compared with baseline. There were no significant changes in ONSD (5.09 ± 0.7-5.09 ± 0.7 mm, P > 0.05) or OA flow PI (1.35 ± 0.2-1.38 ± 0.3, P > 0.05) following acute RE. In conclusion, during recovery from acute high-intensity RE, there are increases in aortic stiffness and extracranial pressure pulsatility in the absence of changes in ICP and flow pulsatility. These findings may have implications for alterations in cerebral transmural pressure and cerebral aneurysmal wall stress following RE.

Comparison of a low-pressure and a high-pressure pulsatile lavage during débridement for orthopaedic implant infection.

PubMed

Muñoz-Mahamud, E; García, S; Bori, G; Martínez-Pastor, J C; Zumbado, J A; Riba, J; Mensa, J; Soriano, A

2011-09-01

The aim of our study was to compare the effectiveness of high-pressure pulsatile lavage and low-pressure lavage in patients with an orthopaedic implant infection treated with open débridement followed by antibiotic treatment. Patients with an orthopaedic implant infection requiring open débridement from January 2008 to August 2009 were randomized prospectively to a low-pressure or a high-pressure pulsatile lavage arm. Relevant information about demographics, co-morbidity, type of implant, microbiology data, surgical treatment, and outcome were recorded. Comparison of proportions was made using χ(2) test or Fisher exact test when necessary. The Kaplan-Meier survival method was used to estimate the cumulative probability of treatment failure from open débridement to the last visit. Seventy-nine patients were included. There were no differences between the main characteristics between both groups (p > 0.05). Mean (SD) age of the whole cohort was 70.2 (11.9) years. There were 46 infections on knee prosthesis, 17 on hip prosthesis, 7 on hip hemiarthroplasties and 9 on osteosynthesis devices. There were 69 acute post-surgical infections, 8 acute haematogenous infections and 2 chronic infections. The most common microorganisms isolated were coagulase-negative Staphylococci in 34 cases, Staphylococcus aureus in 26 and Escherichia coli in 19 cases. There were 30 polymicrobial infections. A total of 42 and 37 patients were randomized to a high-pressure pulsatile or a low-pressure lavage, respectively. There was no difference in the success rate between both arms (80.9 vs. 86.5%, p = 0.56). The use of a high-pressure pulsatile lavage during open débridement of implant infections had a similar success rate as a low-pressure lavage.

[Personal experience in the use of magnetotherapy in diseases of the musculoskeletal system].

PubMed

Sadlonova, J; Korpas, J

1999-12-01

Therapeutic application of pulsatile electromagnetic field in disorders of motility is recently becoming more frequent. Despite this fact information about the effectiveness of this therapy in the literature are rare. The aim of this study was therefore the treatment of 576 patients who suffered from vertebral syndrome, gonarthritis and coxarthritis. For application of pulsatile electromagnetic field MTU 500H Therapy System was used. Pulsatile electromagnetic field had a frequency valve of 4.5 mT in all studied groups and magnetic induction valve 12.5-18.75 mT in the 1st group. In the 2nd group the intensity was 5.8-7.3 mT and in the 3rd group it was 7.6-11.4 mT. The time of inclination/declination in the 1st group was 20/60 ms, in the 2nd group 40/80 ms and in the 3rd group 40/90 ms. The electromagnetic field was applied during 10 days. In the 1st-3rd day during 20 minutes and in the 4th-10th day during 30 minutes. The therapy was repeated in every patient after 3 months with values of intensity higher by 50%. In the time of pulsatile electro-magnetotherapy the patients were without pharmacotherapy or other physiotherapy. The application of pulsatile electromagnetic field is a very effective therapy of vertebral syndrome, gonarthritis and coxarthritis. The results have shown that the therapy was more effective in patients suffering from gonarthrosis, than in patients with vertebral syndrome and least effective in patients with coxarthosis. Owing to regression of oedema and pain relieve the motility of patients improved. (Tab. 3, Ref. 19.)

The reversibility of reduced cortical vein compliance in normal-pressure hydrocephalus following shunt insertion.

PubMed

Bateman, G A

2003-02-01

Superficial cortical venous compression secondary to alterations in craniospinal compliance is implicated in the pathogenesis of normal pressure hydrocephalus (NPH). A reduction in the pulsation in the outflow of the cortical veins would be expected to occur following compression of these veins and this has been shown in NPH. If cortical vein compression is a causative factor in NPH, it would be expected that cortical vein compliance as measured by pulsatility would be significantly altered by a curative procedure i.e. shunt tube insertion. My purpose is to compare the blood flow pulsatility characteristics in a group of patients with NPH before and after shunt tube insertion. I initially studied 18 subjects without pathology with MRI flow quantification studies of the cerebral arteries and veins to define the range of normality. The main study involved 18 patients with idiopathic dementia and mild leukoaraiosis who served as controls and seven patients with NPH studied before and after shunt insertion. Arterial, superior sagittal and straight sinus pulsatility was not significantly different between the patients with idiopathic dementia and those NPH patients before or after shunting. Cortical vein pulsatility before shunting in the patients with NPH was 43% lower than in those with idiopathic dementia ( P=0.006). Following shunting, cortical vein pulsatility increased by 186% ( P=0.007). There is thus reduced compliance in cortical veins in NPH which is significantly increased in patients who respond to insertion of a shunt tube. These findings suggest that reversible elevation in cortical vein pressure and reversal of the normal absorption pathway for cerebrospinal fluid may be behind the pathophysiology of NPH.

Use of patient specific 3D printed neurovascular phantoms to evaluate the clinical utility of a high resolution x-ray imager

NASA Astrophysics Data System (ADS)

Setlur Nagesh, S. V.; Russ, M.; Ionita, C. N.; Bednarek, D.; Rudin, S.

2017-03-01

Modern 3D printing technology can fabricate vascular phantoms based on an actual human patient with a high degree of precision facilitating a realistic simulation environment for an intervention. We present two experimental setups using 3D printed patient-specific neurovasculature to simulate different disease anatomies. To simulate the human neurovasculature in the Circle of Willis, patient-based phantoms with aneurysms were 3D printed using a Objet Eden 260V printer. Anthropomorphic head phantoms and a human skull combined with acrylic plates simulated human head bone anatomy and x-ray attenuation. For dynamic studies the 3D printed phantom was connected to a pulsatile flow loop with the anthropomorphic phantom underneath. By combining different 3D printed phantoms and the anthropomorphic phantoms, different patient pathologies can be simulated. For static studies a 3D printed neurovascular phantom was embedded inside a human skull and used as a positional reference for treatment devices such as stents. To simulate tissue attenuation acrylic layers were added. Different combinations can simulate different patient treatment procedures. The Complementary-Metal-Oxide-Semiconductor (CMOS) based High Resolution Fluoroscope (HRF) with 75μm pixels offers an advantage over the state-of-the-art 200 μm pixel Flat Panel Detector (FPD) due to higher Nyquist frequency and better DQE performance. Whether this advantage is clinically useful during an actual clinical neurovascular intervention can be addressed by qualitatively evaluating images from a cohort of various cases performed using both detectors. The above-mentioned method can offer a realistic substitute for an actual clinical procedure. Also a large cohort of cases can be generated and used for a HRF clinical utility determination study.

4D spiral imaging of flows in stenotic phantoms and subjects with aortic stenosis.

PubMed

Negahdar, M J; Kadbi, Mo; Kendrick, Michael; Stoddard, Marcus F; Amini, Amir A

2016-03-01

The utility of four-dimensional (4D) spiral flow in imaging of stenotic flows in both phantoms and human subjects with aortic stenosis is investigated. The method performs 4D flow acquisitions through a stack of interleaved spiral k-space readouts. Relative to conventional 4D flow, which performs Cartesian readout, the method has reduced echo time. Thus, reduced flow artifacts are observed when imaging high-speed stenotic flows. Four-dimensional spiral flow also provides significant savings in scan times relative to conventional 4D flow. In vitro experiments were performed under both steady and pulsatile flows in a phantom model of severe stenosis (one inch diameter at the inlet, with 87% area reduction at the throat of the stenosis) while imaging a 6-cm axial extent of the phantom, which included the Gaussian-shaped stenotic narrowing. In all cases, gradient strength and slew rate for standard clinical acquisitions, and identical field of view and resolution were used. For low steady flow rates, quantitative and qualitative results showed a similar level of accuracy between 4D spiral flow (echo time [TE] = 2 ms, scan time = 40 s) and conventional 4D flow (TE = 3.6 ms, scan time = 1:01 min). However, in the case of high steady flow rates, 4D spiral flow (TE = 1.57 ms, scan time = 38 s) showed better visualization and accuracy as compared to conventional 4D flow (TE = 3.2 ms, scan time = 51 s). At low pulsatile flow rates, a good agreement was observed between 4D spiral flow (TE = 2 ms, scan time = 10:26 min) and conventional 4D flow (TE = 3.6 ms, scan time = 14:20 min). However, in the case of high flow-rate pulsatile flows, 4D spiral flow (TE = 1.57 ms, scan time = 10:26 min) demonstrated better visualization as compared to conventional 4D flow (TE = 3.2 ms, scan time = 14:20 min). The feasibility of 4D spiral flow was also investigated in five normal volunteers and four subjects with mild-to-moderate aortic stenosis. The approach achieved TE = 1.68 ms and scan time = 3:44 min. The conventional sequence achieved TE = 2.9 ms and scan time = 5:23 min. In subjects with aortic stenosis, we also compared both MRI methods with Doppler ultrasound (US) in the measurement of peak velocity, time to peak systolic velocity, and eject time. Bland-Altman analysis revealed that, when comparing peak velocities, the discrepancy between Doppler US and 4D spiral flow was significantly less than the discrepancy between Doppler and 4D Cartesian flow (2.75 cm/s vs. 10.25 cm/s), whereas the two MR methods were comparable (-5.75 s vs. -6 s) for time to peak. However, for the estimation of eject time, relative to Doppler US, the discrepancy for 4D conventional flow was smaller than that of 4D spiral flow (-16.25 s vs. -20 s). Relative to conventional 4D flow, 4D spiral flow achieves substantial reductions in both the TE and scan times; therefore, utility for it should be sought in a variety of in vivo and complex flow imaging applications. © 2015 Wiley Periodicals, Inc.

Sigmoid sinus cortical plate dehiscence induces pulsatile tinnitus through amplifying sigmoid sinus venous sound.

PubMed

Tian, Shan; Wang, Lizhen; Yang, Jiemeng; Mao, Rui; Liu, Zhaohui; Fan, Yubo

2017-02-08

Sigmoid sinus cortical plate dehiscence (SSCPD) is common in pulsatile tinnitus (PT) patients, and is treated through SSCPD resurfacing surgery in clinic, but the bio-mechanism is not clear as so far. This study aimed to clarify the bio-mechanism of PT sensation induced by SSCPD, and quantify the relationship of cortical plate (CP) thickness and PT sensation intensity. It was hypothesized that SSCPD would induce PT through significantly amplifying sigmoid sinus (SS) venous sound in this study. Finite element (FE) analysis based on radiology data of typical patient was used to verify this hypothesis, and was validated with clinical reports. In cases with different CP thickness, FE simulations of SS venous sound generation and propagation procedure were performed, involving SS venous flow field, vibration response of tissue overlying dehiscence area (including SS vessel wall and CP) and sound propagation in temporal bone air cells. It was shown in results that SS venous sound at tympanic membrane was 56.9dB in SSCPD case and -45.2dB in intact CP case, and was inaudible in all thin CP cases. It was concluded that SSCPD would directly induce PT through significantly amplifying SS venous sound, and thin CP would not be the only pathophysiology of PT. This conclusion would provide a theoretical basis for the design of SSCPD resurfacing surgery for PT patients with SSCPD or thin CP. Copyright © 2017 Elsevier Ltd. All rights reserved.

SDOCT Doppler velocimetry for investigating the morphological influences on blood flow in the developing chick embryo heart

NASA Astrophysics Data System (ADS)

Davis, Anjul M.; Rothenberg, Florence G.; Law, Tzuo H.; Taber, Larry A.; Izatt, Joseph A.

2007-02-01

The onset of congenital heart disease (CHD) is believed to occur at very early stages of development. Investigations in the initiation and development of CHD has been hampered by the inability to image early stage heart structure and function, in vivo. Imaging small animals using optical coherence tomography (OCT) has filled a niche between the limited penetration depth of confocal microscopy and insufficient resolution from ultrasound. Previous demonstrations of chick heart imaging using OCT have entailed excision of, or arresting the heart to prevent motion artifacts. In this summary, we introduce SDOCT Doppler velocimetry as an enhancement of Doppler OCT for in vivo measurement of localized temporal blood flow dynamics. With this technique, dynamic velocity waveforms were measured in the outflow tract of the heart tube. These flow dynamics correlate to a finite element model of pulsatile flow and may lead to a further understanding of morphological influences on early heart development.

Cerebrospinal fluid bulk flow is driven by the cardiac cycle

NASA Astrophysics Data System (ADS)

Tithof, Jeffrey; Mestre, Humberto; Thomas, John; Nedergaard, Maiken; Kelley, Douglas

2017-11-01

Recent discoveries have uncovered a cerebrospinal fluid (CSF) transport system in the perivascular spaces (PVS) of the mammalian brain which clears excess extracellular fluid and protein waste products. The oscillatory pattern of CSF flow has long been attributed to arterial pulsations due to cardiac contractility but limitations in imaging techniques have impeded quantitative measurement of flow rates within the PVS. In this talk, we describe quantitative measurements from the first ever direct imaging of CSF flow in the PVS of a mouse brain. We perform particle tracking velocimetry to obtain time-resolved velocity measurements. To identify the cardiac and/or respiratory dependence of the flow, while imaging, we simultaneously record the mouse's electrocardiogram and respiration. Our measurements conclusively indicate that CSF pulsatility in the arterial PVS is directly driven by the cardiac cycle and not by the respiratory cycle or cerebral vasomotion. These results offer a substantial step forward in understanding bulk flow of CSF in the mammalian brain and may have important implications related to neurodegenerative diseases.

Evaluation of pulsatility index and diameter of the jugular vein and superficial body temperature as physiological indices of temperament in weaned beef calves: relationship with serum cortisol concentrations, rectal temp..

USDA-ARS?s Scientific Manuscript database

The relationship between temperament, pulsatility index and diameter of the jugular vein, and body temperature was assessed in Angus crossbred calves (262±24.9 days old). Temperament scores were used to classify calves as calm (n=31), intermediate (n=32), or temperamental (n=28). Blood samples were ...

Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol.

PubMed

Jagdale, Swati C; Bari, Nilesh A; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 3² full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

Power consumption of rotary blood pumps: pulsatile versus constant-speed mode.

PubMed

Pirbodaghi, Tohid; Cotter, Chris; Bourque, Kevin

2014-12-01

We investigated the power consumption of a HeartMate III rotary blood pump based on in vitro experiments performed in a cardiovascular simulator. To create artificial-pulse mode, we modulated the pump speed by decreasing the mean speed by 2000 rpm for 200 ms and then increasing speed by 4000 rpm (mean speeds plus 2000 rpm) for another 200 ms, creating a square waveform shape. The HeartMate III was connected to a cardiovascular simulator consisting of a hydraulic pump system to simulate left ventricle pumping action, arterial and venous compliance chambers, and an adjustable valve for peripheral resistance to facilitate the desired aortic pressure. The simulator operated based on Suga's elastance model to mimic the Starling response of the heart, thereby reproducing physiological blood flow and pressure conditions. We measured the instantaneous total electrical current and voltage of the pump to evaluate its power consumption. The aim was to answer these fundamental questions: (i) How does pump speed modulation affect pump power consumption? (ii) How does the power consumption vary in relation to external pulsatile flow? The results indicate that speed modulation and external pulsatile flow both moderately increase the power consumption. Increasing the pump speed reduces the impact of external pulsatile flow. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol

PubMed Central

Jagdale, Swati C.; Bari, Nilesh A.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form. PMID:24367788

Influence of pulsatile flow on LDL transport in the arterial wall.

PubMed

Sun, Nanfeng; Wood, Nigel B; Hughes, Alun D; Thom, Simon A M; Xu, X Yun

2007-10-01

The accumulation of low-density lipoprotein (LDL) is one of the important factors in atherogenesis. Two different time scales may influence LDL transport in vivo: (1) LDL transport is coupled to blood flow with a pulse cycle of around 1 s in humans; (2) LDL transport within the arterial wall is mediated by transmural flow in the order of 10(-8) m/s. Most existing models have assumed steady flow conditions and overlooked the interactions between physical phenomena with different time scales. The objective of this study was to investigate the influence of pulsatile flow on LDL transport and examine the validity of steady flow assumption. The effect of pulsatile flow on transmural transport was incorporated by using a lumen-free cyclic (LFC) and a lumen-free time-averaged (LFTA) procedures. It is found that the steady flow simulation predicted a focal distribution in the post-stenotic region, differing from the diffuse distribution pattern produced by the pulsatile flow simulation. The LFTA procedure, in which time-averaged shear-dependent transport properties calculated from instantaneous wall shear stress (WSS) were used, predicted a similar distribution pattern to the LFC simulations. We conclude that the steady flow assumption is inadequate and instantaneous hemodynamic conditions have important influence on LDL transmural transport in arterial geometries with disturbed and complicated flow patterns.

Development of a gastroretentive pulsatile drug delivery platform.

PubMed

Thitinan, Sumalee; McConville, Jason T

2012-04-01

To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Arteriolymphatic Fistula: An Unusual Cause of Spontaneous Swelling in the Left Supraclavicular Region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karuppiah Viswanathan, Ashok Mithra, E-mail: ashokmithrakv@gmail.com; Irodi, Aparna; Keshava, Shyamkumar N., E-mail: aparna-shyam@yahoo.com

2016-09-15

An abnormal fistulous communication between an artery and lymphatic system is a rare occurrence. We report a 38-year-old male presenting with sudden onset, spontaneous, pulsatile swelling in the left supraclavicular region following a recent cardiac catheterisation via right femoral arterial access. On evaluation, he was found to have a femoral arteriolymphatic fistula. He was managed conservatively with ultrasound-guided compression with complete resolution of symptoms at follow-up. This case describes a hitherto unknown complication of percutaneous vascular cannulation presenting in an unusual manner, diagnosed with Doppler Ultrasonography and CT angiography and managed effectively with a non-invasive therapeutic image-guided manoeuvre.

Endovascular Treatment of Pulsatile Tinnitus by Sigmoid Sinus Aneurysm: Technical Note and Review of the Literature.

PubMed

Cuellar, Hugo; Maiti, Tanmoy; Patra, Devi Prasad; Savardekar, Amey; Sun, Hai; Nanda, Anil

2018-05-01

Pulse-synchronous tinnitus is rare, and it almost always points toward a vascular pathology. We encountered a 56-year-old patient presenting with a 3-month history of right-side tinnitus who was found to have a sigmoid sinus aneurysm after initial imaging. The patient was managed successfully with dual endovascular access and stent placement across the aneurysm, with a subsequent complete symptomatic relief. Description of the endovascular management of sigmoid sinus aneurysm is not infrequent in the literature. This report provides a brief review of the available literature specifically addressing the management strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

The Hit and Away technique: optimal usage of the ultrasonic scalpel in laparoscopic gastrectomy.

PubMed

Irino, Tomoyuki; Hiki, Naoki; Ohashi, Manabu; Nunobe, Souya; Sano, Takeshi; Yamaguchi, Toshiharu

2016-01-01

Thermal injury and unexpected bleeding caused by ultrasonic scalpels can lead to fatal complications in laparoscopic gastrectomy (LG), such as postoperative pancreatic fistulas (POPF). In this study, we developed the "Hit and Away" protocol for optimal usage of the ultrasonic scalpel, which in essence involves dividing tissues and vessels in batches using the tip of the scalpel to control tissue temperature. To assess the effectiveness of the technique, the surface temperature of the mesocolon of female swine after ultrasonic scalpel activations was measured, and tissue samples were collected to evaluate microscopic thermal injury to the pancreas. In parallel, we retrospectively surveyed 216 patients who had undergone LG before or after the introduction of this technique and assessed the ability of this technique to reduce POPF. The tissue temperature of the swine mesocolon reached 43 °C, a temperature at which adipose tissue melted but fibrous tissue, including vessels, remained intact. The temperature returned to baseline within 3 s of turning off the ultrasonic scalpel, demonstrating the advantage of using ultrasonic scalpel in a pulsatile manner. Tissue samples from the pancreas demonstrated that the extent of thermal injury post-procedure was limited to the capsule of the pancreas. Moreover, with respect to the clinical outcomes before and after the introduction of this technique, POPF incidence decreased significantly from 7.8 to 1.0% (p = 0.021). The "Hit and Away" technique can reduce blood loss and thermal injury to the pancreas and help to ensure the safety of lymph node dissection in LG.

Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

NASA Astrophysics Data System (ADS)

Israel, Jean-Marc; Cabelguen, Jean-Marie; Le Masson, Gwendal; Oliet, Stéphane H.; Ciofi, Philippe

2014-02-01

The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-α. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.

Endocrine dynamics during pulsatile GnRH administration in patients with hypothalamic amenorrhea and polycystic ovarian disease.

PubMed

Rossmanith, W G; Wirth, U; Benz, R; Wolf, A S

1989-01-01

The LH secretory patterns and ovarian endocrine responses have been determined during pulsatile gonadotropin-releasing hormone (GnRH) administration for induction of ovulation in patients with hypothalamic amenorrhea (HA). However, until now these endocrine dynamics during GnRH therapy have not been thoroughly investigated in patients with polycystic ovarian disease (PCOD). Seven patients with HA and 4 patients with PCOD have therefore been studied to determine changes in LH pulsatile activity and in serum sex steroid levels in response to chronic intermittent GnRH stimulation. GnRH was administered intravenously (5-10 micrograms/90 minutes) by means of a portable infusion pump. Blood samples were obtained at 15-minute intervals for 4 hours on the day before the start of GnRH stimulation (control day) and on treatment days 5, 10 and 15. LH was determined in all samples and FSH, serum androgens and estrogens were measured in baseline samples by RIA. While 8 (62%) ovulations and 5 conceptions were observed in 13 treatment cycles in patients with HA, no ovulations were achieved during 9 treatment cycles in patients with PCOD. On the control day significantly (p less than 0.05) higher basal LH and testosterone (T) levels and significantly (p less than 0.05) lower FSH levels were found in the PCOD patients. The LH pulsatile profiles of the PCOD patients showed significantly (p less than 0.05) higher pulse amplitudes and areas under the curve (integrated responses). Pulsatile GnRH administration induced a significant (p less than 0.05) increase in LH pulse amplitudes in both HA and PCOD patients, and also increased (p less than 0.05) the integrated responses in patients with HA. During the GnRH stimulation, the LH interpulse intervals of both HA and PCOD patients were found to be similar to the frequency in which exogenous GnRH was administered. FSH levels rose continuously (p less than 0.001) during stimulation in patients with HA, but remained unchanged in patients with PCOD. In HA patients, T, androstenedione (AD) and estrone (E1) did not change during the GnRH treatment, but estradiol (E2) rose so that the ratios of aromatized estrogens to non-aromatized androgens (E1/AD, E2/T) increased. In contrast, T and AD increased significantly (p less than 0.05 or less) and E2 remained unchanged during stimulations in PCOD patients, which resulted in decreasing ratios of estrogens to androgens. These observations confirm that pulsatile GnRH administration can successfully induce ovulation in patients with HA by restoring the ovarian physiology. The data also demonstrate that pulsatile GnRH administration can influence the LH secretory patterns in PCOD patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute severe hemorrhage secondary to arterial invasion in a dog with thyroid carcinoma.

PubMed

Slensky, Kimberly A; Volk, Susan W; Schwarz, Tobias; Duda, Lili; Mauldin, Elizabeth A; Silverstein, Deborah

2003-09-01

A 7-year-old spayed female Labrador Retriever was referred because of progressive swelling and bruising of the neck, hemothorax, a possible mediastinal mass, and stridor. At the time of admission, the dog was recumbent, mentally dull, tachycardic, and hypothermic. Fluid therapy with hydroxyethyl starch and a balanced electrolyte solution was administered because of presumed hypovolemic shock secondary to hemorrhage; multiple units of packed RBCs and fresh frozen plasma were also administered. On the basis of the computed tomographic images, extensive subcutaneous, subfascial, and cranial mediastinal hemorrhage; hemothorax; prescapular lymphadenopathy; and a contrast-enhancing mass in the left cranioventral aspect of the neck were diagnosed. Exploratory surgery of the neck was performed. All subcutaneous structures were encased in a large blood clot. During dissection of the clot, pulsatile bleeding was observed just caudal to and to the left of the larynx; ligation of the left common carotid artery resulted in immediate cessation of the pulsatile bleeding. Further surgical exploration revealed a 2.5 x 2.5-cm mass adhered to the left common carotid artery at the level of the branching to the left cranial thyroid artery. The mass was removed; the histologic diagnosis was thyroid carcinoma. Three weeks after surgery, treatment with a combination of radiation and chemotherapy (doxorubicin and carboplatin) was begun. Thirteen months after surgery, the dog continued to be free from clinical signs of disease.

Analysis of flow disturbance in a stenosed carotid artery bifurcation using two-equation transitional and turbulence models.

PubMed

Tan, F P P; Soloperto, G; Bashford, S; Wood, N B; Thom, S; Hughes, A; Xu, X Y

2008-12-01

In this study, newly developed two-equation turbulence models and transitional variants are employed for the prediction of blood flow patterns in a diseased carotid artery where the growth, progression, and structure of the plaque at rupture are closely linked to low and oscillating wall shear stresses. Moreover, the laminar-turbulent transition in the poststenotic zone can alter the separation zone length, wall shear stress, and pressure distribution over the plaque, with potential implications for stresses within the plaque. Following the validation with well established experimental measurements and numerical studies, a magnetic-resonance (MR) image-based model of the carotid bifurcation with 70% stenosis was reconstructed and simulated using realistic patient-specific conditions. Laminar flow, a correlation-based transitional version of Menter's hybrid k-epsilon/k-omega shear stress transport (SST) model and its "scale adaptive simulation" (SAS) variant were implemented in pulsatile simulations from which analyses of velocity profiles, wall shear stress, and turbulence intensity were conducted. In general, the transitional version of SST and its SAS variant are shown to give a better overall agreement than their standard counterparts with experimental data for pulsatile flow in an axisymmetric stenosed tube. For the patient-specific case reported, the wall shear stress analysis showed discernable differences between the laminar flow and SST transitional models but virtually no difference between the SST transitional model and its SAS variant.

Hydrodynamic Forces on Microbubbles under Ultrasound Excitation

NASA Astrophysics Data System (ADS)

Clark, Alicia; Aliseda, Alberto

2014-11-01

Ultrasound (US) pressure waves exert a force on microbubbles that can be used to steer them in a flow. To control the motion of microbubbles under ultrasonic excitation, the coupling between the volume oscillations induced by the ultrasound pressure and the hydrodynamic forces needs to be well understood. We present experimental results for the motion of small, coated microbubbles, with similar sizes and physico-chemical properties as clinically-available ultrasound contrast agents (UCAs). The size distribution for the bubbles, resulting from the in-house manufacturing process, was characterized by analysis of high magnification microscopic images and determined to be bimodal. More than 99% of the volume is contained in microbubbles less than 10 microns in diameter, the size of a red blood cell. The motion of the microbubbles in a pulsatile flow, at different Reynolds and Womersley numbers, is studied from tracking of high-speed shadowgraphy. The influence of ultrasound forcing, at or near the resonant frequency of the bubbles, on the hydrodynamic forces due to the pulsatile flow is determined from the experimental measurements of the trajectories. Previous evidence of a sign reversal in Saffman lift is the focus of particular attention, as this is frequently the only hydrodynamic force acting in the direction perpendicular to the flow pathlines. Application of the understanding of this physical phenomenon to targeted drug delivery is analyzed in terms of the transport of the microbubbles. NSF GRFP.

Usefulness of B-mode and doppler sonography for the diagnosis of severe acute viral hepatitis A.

PubMed

Shin, Sang Wook; Kim, Tae Yeob; Jeong, Woo Kyoung; Kim, Yongsoo; Kim, Jinoo; Kim, Young Hwan; Park, Hwan Cheol; Sohn, Joo Hyun

2015-01-01

To investigate B-mode and Doppler ultrasonography (US) features correlating with laboratory findings for the diagnosis of severe acute hepatitis (SAH) in patients with hepatitis A virus infection. Thirty-nine consecutive serologically proven patients were enrolled. Decreased parenchymal echotexture, periportal tracking, gallbladder wall change, and splenomegaly were assessed on B-mode images. Blood flow velocities were measured in the main portal (V(PORTAL)) and in the hepatic veins, and the hepatic venous pulsatility index was calculated. SAH was defined as high model for end-stage liver disease (MELD) score ≥ 15 with or without coagulopathy. The relationship between US features and laboratory findings was assessed, and SAH diagnosis was evaluated. Serum alanine transaminase and prothrombin time were significantly different depending on the presence of gallbladder wall change and splenomegaly (p < 0.05). V(PORTAL) was inversely correlated with MELD score (r = -0.485) and several laboratory markers. The hepatic venous waveform and hepatic venous pulsatility index were significantly correlated with MELD score. For the diagnosis of SAH, the area under the receiver operating characteristic curve of V(PORTAL) was 0.798. It reached 0.869 in the patients with typical GB change. Both B-mode and Doppler US correlated well with several laboratory variables and may be helpful to diagnose SAH in patients with hepatitis A virus infection. © 2014 Wiley Periodicals, Inc.

A translating stage system for µ-PIV measurements surrounding the tip of a migrating semi-infinite bubble.

PubMed

Smith, B J; Yamaguchi, E; Gaver, D P

2010-01-01

We have designed, fabricated and evaluated a novel translating stage system (TSS) that augments a conventional micro particle image velocimetry (µ-PIV) system. The TSS has been used to enhance the ability to measure flow fields surrounding the tip of a migrating semi-infinite bubble in a glass capillary tube under both steady and pulsatile reopening conditions. With conventional µ-PIV systems, observations near the bubble tip are challenging because the forward progress of the bubble rapidly sweeps the air-liquid interface across the microscopic field of view. The translating stage mechanically cancels the mean bubble tip velocity, keeping the interface within the microscope field of view and providing a tenfold increase in data collection efficiency compared to fixed-stage techniques. This dramatic improvement allows nearly continuous observation of the flow field over long propagation distances. A large (136-frame) ensemble-averaged velocity field recorded with the TSS near the tip of a steadily migrating bubble is shown to compare well with fixed-stage results under identical flow conditions. Use of the TSS allows the ensemble-averaged measurement of pulsatile bubble propagation flow fields, which would be practically impossible using conventional fixed-stage techniques. We demonstrate our ability to analyze these time-dependent two-phase flows using the ensemble-averaged flow field at four points in the oscillatory cycle.

Dual regression physiological modeling of resting-state EPI power spectra: Effects of healthy aging.

PubMed

Viessmann, Olivia; Möller, Harald E; Jezzard, Peter

2018-02-02

Aging and disease-related changes in the arteriovasculature have been linked to elevated levels of cardiac cycle-induced pulsatility in the cerebral microcirculation. Functional magnetic resonance imaging (fMRI), acquired fast enough to unalias the cardiac frequency contributions, can be used to study these physiological signals in the brain. Here, we propose an iterative dual regression analysis in the frequency domain to model single voxel power spectra of echo planar imaging (EPI) data using external recordings of the cardiac and respiratory cycles as input. We further show that a data-driven variant, without external physiological traces, produces comparable results. We use this framework to map and quantify cardiac and respiratory contributions in healthy aging. We found a significant increase in the spatial extent of cardiac modulated white matter voxels with age, whereas the overall strength of cardiac-related EPI power did not show an age effect. Copyright © 2018. Published by Elsevier Inc.

Microvascular Branching as a Determinant of Blood Flow by Intravital Particle Imaging Velocimetry

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia; McKay, Terri L.; Vickerman, Mary B.; Wernet, Mark P.; Myers, Jerry G.; Radhakrishnan, Krishnan

2007-01-01

The effects of microvascular branching on blood flow were investigated in vivo by microscopic particle imaging velocimetry (micro-PIV). We use micro-PIV to measure blood flow by tracking red blood cells (RBC) as the moving particles. Velocity flow fields, including flow pulsatility, were analyzed for the first four branching orders of capillaries, postcapillary venules and small veins of the microvascular network within the developing avian yolksac at embryonic day 5 (E5). Increasing volumetric flowrates were obtained from parabolic laminar flow profiles as a function of increasing vessel diameter and branching order. Maximum flow velocities increased approximately twenty-fold as the function of increasing vessel diameter and branching order compared to flow velocities of 100 - 150 micron/sec in the capillaries. Results from our study will be useful for the increased understanding of blood flow within anastomotic, heterogeneous microvascular networks.

Real-time optical monitoring of permanent lesion progression in radiofrequency ablated cardiac tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Singh-Moon, Rajinder P.; Hendon, Christine P.

2016-02-01

Despite considerable advances in guidance of radiofrequency ablation (RFA) therapies for atrial fibrillation, success rates have been hampered by an inability to intraoperatively characterize the extent of permanent injury. Insufficient lesions can elusively create transient conduction blockages that eventually reconduct. Prior studies suggest significantly greater met-myoglobin (Mmb) concentrations in the lesion core than those in the healthy myocardium and may serve as a marker for irreversible tissue damage. In this work, we present real-time monitoring of permanent injury through spectroscopic assessment of Mmb concentrations at the catheter tip. Atrial wedges (n=6) were excised from four fresh swine hearts and submerged under pulsatile flow of warm (37oC) phosphate buffered saline. A commercial RFA catheter inserted into a fiber optic sheath allowed for simultaneous measurement of tissue diffuse reflectance (DR) spectra (500-650nm) during application of RF energy. Optical measurements were continuously acquired before, during, and post-ablation, in addition to healthy neighboring tissue. Met-myoglobin, oxy-myoglobin, and deoxy-myoglobin concentrations were extracted from each spectrum using an inverse Monte Carlo method. Tissue injury was validated with Masson's trichrome and hematoxylin and eosin staining. Time courses revealed a rapid increase in tissue Mmb concentrations at the onset of RFA treatment and a gradual plateauing thereafter. Extracted Mmb concentrations were significantly greater post-ablation (p<0.0001) as compared to healthy tissue and correlated well with histological assessment of severe thermal tissue destruction. On going studies are aimed at integrating these findings with prior work on near infrared spectroscopic lesion depth assessment. These results support the use of spectroscopy-facilitated guidance of RFA therapies for real-time permanent injury estimation.

Point-of-Care Ultrasonography to Assess Portal Vein Pulsatility and the Effect of Inhaled Milrinone and Epoprostenol in Severe Right Ventricular Failure: A Report of 2 Cases.

PubMed

Tremblay, Jan-Alexis; Beaubien-Souligny, William; Elmi-Sarabi, Mahsa; Desjardins, Georges; Denault, André Y

2017-10-15

This article describes 2 patients with severe acute right ventricular failure causing circulatory shock. Portal vein pulsatility assessed by bedside ultrasonography suggested clinically relevant venous congestion. Management included cardiac preload reduction and combined inhalation of milrinone and epoprostenol to reduce right ventricular afterload. Portal vein ultrasonography may be useful in assessing right ventricular function in the acutely ill patient.

Pulsatile flow and mass transport over an array of cylinders: gas transfer in a cardiac-driven artificial lung.

PubMed

Chan, Kit Yan; Fujioka, Hideki; Bartlett, Robert H; Hirschl, Ronald B; Grotberg, James B

2006-02-01

The pulsatile flow and gas transport of a Newtonian passive fluid across an array of cylindrical microfibers are numerically investigated. It is related to an implantable, artificial lung where the blood flow is driven by the right heart. The fibers are modeled as either squared or staggered arrays. The pulsatile flow inputs considered in this study are a steady flow with a sinusoidal perturbation and a cardiac flow. The aims of this study are twofold: identifying favorable array geometry/spacing and system conditions that enhance gas transport; and providing pressure drop data that indicate the degree of flow resistance or the demand on the right heart in driving the flow through the fiber bundle. The results show that pulsatile flow improves the gas transfer to the fluid compared to steady flow. The degree of enhancement is found to be significant when the oscillation frequency is large, when the void fraction of the fiber bundle is decreased, and when the Reynolds number is increased; the use of a cardiac flow input can also improve gas transfer. In terms of array geometry, the staggered array gives both a better gas transfer per fiber (for relatively large void fraction) and a smaller pressure drop (for all cases). For most cases shown, an increase in gas transfer is accompanied by a higher pressure drop required to power the flow through the device.

Long-Term Durability Test for the Left Ventricular Assist System EVAHEART under the Physiologic Pulsatile Load.

PubMed

Kitano, Tomoya; Iwasaki, Kiyotaka

The EVAHEART Left Ventricular Assist System (LVAS) was designed for the long-term support of a patient with severe heart failure. It has an original water lubrication system for seal and bearing and wear on these parts was considered one of its critical failure modes. A durability test focusing on wear was designed herein. We developed a mock loop, which generates a physiologic pulsatile flow and is sufficiently durable for a long-term test. The pulsatile load and the low fluid viscosity enable the creation of a severe condition for the mechanical seal. A total of 18 EVAHEART blood pumps completed 2 years of operation under the pulsatile condition without any failure. It indicated the EVAHEART blood pump had a greater than 90% reliability with a 88% confidence level. The test was continued with six blood pumps and achieved an average of 8.6 years, which was longer than the longest clinical use in Japan. The test result showed that no catastrophic, critical, marginal, or minor failures of the blood pump or their symptoms were observed. The seal performance was maintained after the test. Moreover, the surface roughness did not change, which showed any burn or abnormal wear occurred. The original water lubrication system equipped in EVAHEART LVAS prevent severe wear on the seal and the bearing, and it can be used in the bridge to transplant and destination therapy.

Increased Atherosclerosis Correlates with Subjective Tinnitus Severity.

PubMed

Yüksel, Fatih; Karataş, Duran; Türkdoğan, Figen Tunalı; Yüksel, Özlem

2018-03-01

The aim of the present study was to investigate whether increased intima media thickness was associated with the severity of subjective non-pulsatile tinnitus and hearing loss. Data of the patients who came to Otorhinolaryngology Department of Isparta Government Hospital with subjective non-pulsatile tinnitus complaint, between January 2012 and June 2013, were evaluated retrospectively. A total of 215 patients were included in the present study. Hearing tests, biochemical analysis, tinnitus handicap inventory (THI), visual analogue scale (VAS) and doppler ultrasonography results of the patients were reviewed and recorded. The patients were classified into two groups as those having an increased intima media thickness and those having a normal intima media thickness. The said groups were compared with respect to age, gender, THI, VAS, hearing test findings and lipid values. Moreover, THI and VAS groups were compared with respect to intima-media thickness. In the group having increased intima-media thickness, THI and VAS average, frequency of hypertension, total cholesterol, low density lipoprotein and triglyceride averages and mean frequencies obtained by hearing test were significantly higher. Comparison of THI and VAS groups showed that intima-media thickness was significantly different between those having a mild tinnitus and those having a severe tinnitus. Increased intima-media thickness was associated with the severity of subjective non-pulsatile tinnitus and hearing loss. For this reason, the carotid system should be examined in subjective non-pulsatile tinnitus patients.

Closing in on the Mechanisms of Pulsatile Insulin Secretion.

PubMed

Bertram, Richard; Satin, Leslie S; Sherman, Arthur S

2018-03-01

Insulin secretion from pancreatic islet β-cells occurs in a pulsatile fashion, with a typical period of ∼5 min. The basis of this pulsatility in mouse islets has been investigated for more than four decades, and the various theories have been described as either qualitative or mathematical models. In many cases the models differ in their mechanisms for rhythmogenesis, as well as other less important details. In this Perspective, we describe two main classes of models: those in which oscillations in the intracellular Ca 2+ concentration drive oscillations in metabolism, and those in which intrinsic metabolic oscillations drive oscillations in Ca 2+ concentration and electrical activity. We then discuss nine canonical experimental findings that provide key insights into the mechanism of islet oscillations and list the models that can account for each finding. Finally, we describe a new model that integrates features from multiple earlier models and is thus called the Integrated Oscillator Model. In this model, intracellular Ca 2+ acts on the glycolytic pathway in the generation of oscillations, and it is thus a hybrid of the two main classes of models. It alone among models proposed to date can explain all nine key experimental findings, and it serves as a good starting point for future studies of pulsatile insulin secretion from human islets. © 2018 by the American Diabetes Association.

An in vitro test bench reproducing coronary blood flow signals.

PubMed

Chodzyński, Kamil Jerzy; Boudjeltia, Karim Zouaoui; Lalmand, Jacques; Aminian, Adel; Vanhamme, Luc; de Sousa, Daniel Ribeiro; Gremmo, Simone; Bricteux, Laurent; Renotte, Christine; Courbebaisse, Guy; Coussement, Grégory

2015-08-07

It is a known fact that blood flow pattern and more specifically the pulsatile time variation of shear stress on the vascular wall play a key role in atherogenesis. The paper presents the conception, the building and the control of a new in vitro test bench that mimics the pulsatile flows behavior based on in vivo measurements. An in vitro cardiovascular simulator is alimented with in vivo constraints upstream and provided with further post-processing analysis downstream in order to mimic the pulsatile in vivo blood flow quantities. This real-time controlled system is designed to perform real pulsatile in vivo blood flow signals to study endothelial cells' behavior under near physiological environment. The system is based on an internal model controller and a proportional-integral controller that controls a linear motor with customized piston pump, two proportional-integral controllers that control the mean flow rate and temperature of the medium. This configuration enables to mimic any resulting blood flow rate patterns between 40 and 700 ml/min. In order to feed the system with reliable periodic flow quantities in vivo measurements were performed. Data from five patients (1 female, 4 males; ages 44-63) were filtered and post-processed using the Newtonian Womersley's solution. These resulting flow signals were compared with 2D axisymmetric, numerical simulation using a Carreau non-Newtonian model to validate the approximation of a Newtonian behavior. This in vitro test bench reproduces the measured flow rate time evolution and the complexity of in vivo hemodynamic signals within the accuracy of the relative error below 5%. This post-processing method is compatible with any real complex in vivo signal and demonstrates the heterogeneity of pulsatile patterns in coronary arteries among of different patients. The comparison between analytical and numerical solution demonstrate the fair quality of the Newtonian Womersley's approximation. Therefore, Womersley's solution was used to calculate input flow rate for the in vitro test bench.

Turbulence detection in a stenosed artery bifurcation by numerical simulation of pulsatile blood flow using the low-Reynolds number turbulence model.

PubMed

Ghalichi, Farzan; Deng, Xiaoyan

2003-01-01

The pulsatile blood flow in a partially blocked artery is significantly altered as the flow regime changes through the cardiac cycle. This paper reports on the application of a low-Reynolds turbulence model for computation of physiological pulsatile flow in a healthy and stenosed carotid artery bifurcation. The human carotid artery was chosen since it has received much attention because atherosclerotic lesions are frequently observed. The Wilcox low-Re k-omega turbulence model was used for the simulation since it has proven to be more accurate in describing transition from laminar to turbulent flow. Using the FIDAP finite element code a validation showed very good agreement between experimental and numerical results for a steady laminar to turbulent flow transition as reported in a previous publication by the same authors. Since no experimental or numerical results were available in the literature for a pulsatile and turbulent flow regime, a comparison between laminar and low-Re turbulent calculations was made to further validate the turbulence model. The results of this study showed a very good agreement for velocity profiles and wall shear stress values for this imposed pulsatile laminar flow regime. To explore further the medical aspect, the calculations showed that even in a healthy or non-stenosed artery, small instabilities could be found at least for a portion of the pulse cycle and in different sections. The 40% and 55% diameter reduction stenoses did not significantly change the turbulence characteristics. Further results showed that the presence of 75% stenoses changed the flow properties from laminar to turbulent flow for a good portion of the cardiac pulse. A full 3D simulation with this low-Re-turbulence model, coupled with Doppler ultrasound, can play a significant role in assessing the degree of stenosis for cardiac patients with mild conditions.

Neuropeptide action in insects and crustaceans.

PubMed

Mykles, Donald L; Adams, Michael E; Gäde, Gerd; Lange, Angela B; Marco, Heather G; Orchard, Ian

2010-01-01

Physiological processes are regulated by a diverse array of neuropeptides that coordinate organ systems. The neuropeptides, many of which act through G protein-coupled receptors, affect the levels of cyclic nucleotides (cAMP and cGMP) and Ca(2+) in target tissues. In this perspective, their roles in molting, osmoregulation, metabolite utilization, and cardiovascular function are highlighted. In decapod crustaceans, inhibitory neuropeptides (molt-inhibiting hormone and crustacean hyperglycemic hormone) suppress the molting gland through cAMP- and cGMP-mediated signaling. In insects, the complex movements during ecdysis are controlled by ecdysis-triggering hormone and a cascade of downstream neuropeptides. Adipokinetic/hypertrehalosemic/hyperprolinemic hormones mobilize energy stores in response to increased locomotory activity. Crustacean cardioacceleratory (cardioactive) peptide, proctolin, and FMRFamide-related peptides act on the heart, accessory pulsatile organs, and excurrent ostia to control hemolymph distribution to tissues. The osmoregulatory challenge of blood gorging in Rhodnius prolixus requires the coordinated release of serotonin and diuretic and antidiuretic hormones acting on the midgut and Malpighian tubules. These studies illustrate how multiple neuropeptides allow for flexibility in response to physiological challenges.

Channeled Scaffolds for Engineering Myocardium with Mechanical Stimulation

PubMed Central

Zhang, Ting; Wan, Leo Q.; Xiong, Zhuo; Marsano, Anna; Maidhof, Robert; Park, Miri; Yan, Yongnian; Vunjak-Novakovic, Gordana

2011-01-01

The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) are critically important for engineering functional myocardial tissue. We report the development of chitosan-collagen scaffolds with micro-pores and an array of parallel channels (~200 μm in diameter) that were specifically designed for cardiac tissue engineering with mechanical stimulation. The scaffolds were designed to have the structural and mechanical properties similar to those of the native human heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom-designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1–2 mm thick) consisted of metabolically active cells and started to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stresses promoted cell alignment, elongation, and the expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs. PMID:22081518

Channelled scaffolds for engineering myocardium with mechanical stimulation.

PubMed

Zhang, Ting; Wan, Leo Q; Xiong, Zhuo; Marsano, Anna; Maidhof, Robert; Park, Miri; Yan, Yongnian; Vunjak-Novakovic, Gordana

2012-10-01

The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) of the heart are important characteristics in the engineering of functional myocardial tissue. This study reports on the development of chitosan-collagen scaffolds with micropores and an array of parallel channels (~ 200 µm in diameter) that were specifically designed for cardiac tissue engineering using mechanical stimulation. The scaffolds were designed to have similar structural and mechanical properties of those of native heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1-2 mm thick) consisted of metabolically active cells that began to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stress promoted cell alignment, elongation, and expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs. Copyright © 2011 John Wiley & Sons, Ltd.

A novel endobronchial approach to massive hemoptysis complicating silicone Y-stent placement for tracheobronchomalacia: A case report.

PubMed

Ryu, Changwan; Boffa, Daniel; Bramley, Kyle; Pisani, Margaret; Puchalski, Jonathan

2018-02-01

Airway stabilization for severe, symptomatic tracheobronchomalacia (TBM) may be accomplished by silicone Y-stent placement. Common complications of the Y-stent include mucus plugging and granulation tissue formation. We describe a rare case of massive hemoptysis originating from a silicone Y-stent placed for TBM. An emergent bronchoscopy showed an actively bleeding, pulsatile vessel at the distal end of the left bronchial limb of the Y-stent. It was felt that the bleeding was caused by, or at least impacted by, the distal left bronchial limb of the Y-stent eroding into the airway wall. We hypothesized that placement of oxidized regenerated cellulose (ORC) would provide initial hemostasis, and the subsequent placement of a biocompatible surgical sealant would lead to definitive resolution. ORC provided sufficient hemostasis and the subsequent synthetic polymer reinforced the tissue for complete cessation of the bleed. The combined use of ORC and a biocompatible surgical sealant provided long-term management for life-threatening hemoptysis, and potentially morbid procedures such as embolization or surgery were avoided by advanced endobronchial therapy.

A novel endobronchial approach to massive hemoptysis complicating silicone Y-stent placement for tracheobronchomalacia

PubMed Central

Ryu, Changwan; Boffa, Daniel; Bramley, Kyle; Pisani, Margaret; Puchalski, Jonathan

2018-01-01

Abstract Rationale: Airway stabilization for severe, symptomatic tracheobronchomalacia (TBM) may be accomplished by silicone Y-stent placement. Common complications of the Y-stent include mucus plugging and granulation tissue formation. Patient concerns: We describe a rare case of massive hemoptysis originating from a silicone Y-stent placed for TBM. Diagnoses: An emergent bronchoscopy showed an actively bleeding, pulsatile vessel at the distal end of the left bronchial limb of the Y-stent. It was felt that the bleeding was caused by, or at least impacted by, the distal left bronchial limb of the Y-stent eroding into the airway wall. Interventions: We hypothesized that placement of oxidized regenerated cellulose (ORC) would provide initial hemostasis, and the subsequent placement of a biocompatible surgical sealant would lead to definitive resolution. Outcomes: ORC provided sufficient hemostasis and the subsequent synthetic polymer reinforced the tissue for complete cessation of the bleed. Lessons: The combined use of ORC and a biocompatible surgical sealant provided long-term management for life-threatening hemoptysis, and potentially morbid procedures such as embolization or surgery were avoided by advanced endobronchial therapy. PMID:29465600

Cardiovascular microbubble transport in vessel bifurcations with pulsatile flow: experimental model and theory

NASA Astrophysics Data System (ADS)

Valassis, Doug; Dodde, Robert; Eshpuniyani, Brijesh; Fowlkes, J. Brian; Bull, Joseph

2008-11-01

The behavior of long gas bubbles suspended in liquid flowing through successive bifurcations was investigated experimentally and theoretically as a model of cardiovascular bubble transport in gas embolotherapy. In this developmental cancer therapy, perflurocarbon droplets are vaporized in the vasculature and travel through a bifurcating network of vessels before lodging. The homogeneity of tumor necrosis is directly correlated with the transport and lodging of the emboli. An experimental model was used to explore the effects of flow pulsatility, frequency, gravity, and bifurcation roll angle on bubble splitting and lodging. At a bifurcation roll angle of 45-degrees, the most distinct difference in splitting ratios between three physiologic frequencies (1, 1.5, 2 Hz) was observed. As roll angle increased, lodged bubble volume in the first generation channel increased while bubble volume beyond the second bifurcation proportionately decreased. A corresponding time-dependent one-dimensional theoretical model was also developed. The results elucidate the effects of pulsatile flow and suggest the potential of gas embolotherapy to occlude blood flow to tumors.

Performance characterization of a rotary centrifugal left ventricular assist device with magnetic suspension.

PubMed

Jahanmir, Said; Hunsberger, Andrew Z; Heshmat, Hooshang; Tomaszewski, Michael J; Walton, James F; Weiss, William J; Lukic, Branka; Pae, William E; Zapanta, Conrad M; Khalapyan, Tigran Z

2008-05-01

The MiTiHeart (MiTiHeart Corporation, Gaithersburg, MD, USA) left ventricular assist device (LVAD), a third-generation blood pump, is being developed for destination therapy for adult heart failure patients of small to medium frame that are not being served by present pulsatile devices. The pump design is based on a novel, patented, hybrid passive/active magnetic bearing system with backup hydrodynamic thrust bearing and exhibits low power loss, low vibration, and low hemolysis. Performance of the titanium alloy prototype was evaluated in a series of in vitro tests with blood analogue to map out the performance envelop of the pump. The LVAD prototype was implanted in a calf animal model, and the in vivo pump performance was evaluated. The animal's native heart imparted a strong pulsatility to the flow rate. These tests confirmed the efficacy of the MiTiHeart LVAD design and confirmed that the pulsatility does not adversely affect the pump performance.

Pulsatile crizotinib treatment for brain metastasis in a patient with non-small-cell lung cancer.

PubMed

Wang, S; Chen, J; Xie, Z; Xia, L; Luo, W; Li, J; Li, Q; Yang, Z

2017-10-01

Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is a distinct subtype with patients showing peculiar clinicopathological features and dramatic responses to the ALK tyrosine kinase inhibitor crizotinib. Patients with this cancer variant have a dismal prognosis and limited treatment options when it has progressed to intracranial metastasis because of inadequate drug penetration into the central nervous system (CNS). Factors associated with response to TKI therapy have been reported to include pharmacokinetic and biodynamic resistance phenomena. In our NSCLC patient with multiple intracranial metastases, we administered high-dose pulsatile crizotinib therapy (1000 mg/d) on a one-day-on/one-day-off basis. A significant central nervous system (CNS) response was achieved, and time to neurological progression was prolonged to 6 months. High-dose pulsatile therapy may be an effective dosing strategy for crizotinib in NSCLC showing progression to metastasis in the brain. © 2017 John Wiley & Sons Ltd.

Computational solution of the velocity and wall shear stress distribution inside a left carotid artery under pulsatile flow conditions

NASA Astrophysics Data System (ADS)

Arslan, Nurullah; Turmuş, Hakan

2014-08-01

Stroke is still one of the leading causes for death after heart diseases and cancer in all over the world. Strokes happen because an artery that carries blood uphill from the heart to the head is clogged. Most of the time, as with heart attacks, the problem is atherosclerosis, hardening of the arteries, calcified buildup of fatty deposits on the vessel wall. In this study, the fluid dynamic simulations were done in a left carotid bifurcation under the pulsatile flow conditions computationally. Pulsatile flow waveform is given in the paper. In vivo geometry and boundary conditions were obtained from a patient who has stenosis located at external carotid artery (ECA) and internal carotid artery (ICA) of his common carotid artery (CCA). The location of critical flow fields such as low wall shear stress (WSS), stagnation regions and separation regions were detected near the highly stenosed region and at branching region.

Pulsatile flow in ventricular catheters for hydrocephalus

NASA Astrophysics Data System (ADS)

Giménez, Á.; Galarza, M.; Thomale, U.; Schuhmann, M. U.; Valero, J.; Amigó, J. M.

2017-05-01

The obstruction of ventricular catheters (VCs) is a major problem in the standard treatment of hydrocephalus, the flow pattern of the cerebrospinal fluid (CSF) being one important factor thereof. As a first approach to this problem, some of the authors studied previously the CSF flow through VCs under time-independent boundary conditions by means of computational fluid dynamics in three-dimensional models. This allowed us to derive a few basic principles which led to designs with improved flow patterns regarding the obstruction problem. However, the flow of the CSF has actually a pulsatile nature because of the heart beating and blood flow. To address this fact, here we extend our previous computational study to models with oscillatory boundary conditions. The new results will be compared with the results for constant flows and discussed. It turns out that the corrections due to the pulsatility of the CSF are quantitatively small, which reinforces our previous findings and conclusions. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

The Generation and Propagation of Arterial Murmurs from a Stenosed Artery: A Computational Study

NASA Astrophysics Data System (ADS)

Zhu, Chi; Seo, Jung-Hee; Bakhshaee, Hani; Mittal, Rajat

2015-11-01

Cardiac auscultation - the procedure of diagnosing cardiovascular conditions using the stethoscope - has been used effectively for over a hundred years but still, the flow mechanism(s) responsible for the generation of these murmurs, as well as the effect of intervening tissue on the propagation of these murmurs, is not well understood. In this study, a one-way coupled, hybrid approach is used to investigate the propagation of murmurs generated from the flow in a stenosed artery. Specifically, the flow in the modeled artery is solved by an incompressible Navier-Stokes solver with the immersed-boundary method. The structural wave propagation in the tissue is resolved by a high-order, linear viscoelastic wave solver, and a mathematical decomposition is applied to separate the compressional and shear component of the acoustic wave propagating through the tissue. The simulations suggest, somewhat counterintuitively, that the shear wave contributes a significant component to the signal picked up by a stethoscope, and that this component carries much of the information that characterizes the source of the murmur. The implications of this for cardiac auscultation and further modeling of hemoacoustics are discussed. The effect of the stenosis severity and the flow pulsatility will also be investigated. The authors would like to acknowledge the SCH for funding this project.

Heterogeneity of hypoxia in solid tumours and mechanochemical reactions with oxygen nanobubbles.

PubMed

Orel, V B; Zabolotny, M A; Orel, V E

2017-05-01

Tumour hypoxia leads to radio and chemotherapy resistance among cancer patients. The aim of this paper is to formulate a hypothesis on the heterogeneity of hypoxia in solid tumours. Tumour vasculature is known to be significantly variable. The great structural and functional abnormalities of tumour microcirculation cause spatial and temporal heterogeneity in its perfusion. Tumours have constantly been under the influence of pulsatile blood perfusion with variable pressure that initiates inhomogeneous erythrocyte deformation and following impact on oxygen disorder release from red blood cells into plasma within the blood vessel. Furthermore, stochastically released oxygen in tumour vessel, plasma and interstitial fluid may lead to heterogeneity of hypoxia. Under the influence of increased heterogeneity of hemodynamic force, the oxygen molecules dissolved in blood plasma are inclined to form nanobubbles (NBs) in tumour vessels. Considering the fact that tumour interstitial fluid pressure is increased compared to normal tissues, we assume that oxygen NBs may burst under the impact of shear stress. During the course of mechanochemical reaction, when a nanobubble (NB) bursts, both reactive oxygen species and ions form in various charged states. In consequence of a chain reaction, free radical oxygen molecules bind to proteins and lipids, thus reducing oxygen molecules in a chaotic manner within the tumour. The proposed hypothesis should be used as a methodical approach based on the simultaneous ultrasound imaging diagnostic techniques and therapy, regarding the mechanochemical effect on NB conglomerates with drugs in the tumour. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Clinical and experimental study of the production of renal hemodynamic effects of IABP-assisted pulsatile flow extracorporeal circulation].

PubMed

Moro, H

1992-01-01

Renal hemodynamics during IABP-assisted pulsatile flow extracorporeal circulation was assessed in terms of measurement values for intraoperative renal blood flow obtained by the local thermodilution method in human clinical patients. In addition, the effect of IABP on renal hemodynamics was investigated in an animal model of renal denervation in a study undertaken to elucidate the action mechanism of IABP. Eighteen patients with acquired heart disease were involved in the study and measured for the renal blood flow (RBF), cardiac output (CO), renal-systemic partition coefficient for blood flow (RBF/CO), renal vascular resistance (RVR) and perfusion pressure. In the pulsatile flow group, the RBF/CO increased as the number of pump runs increased, whole the RVR was conversely reduced with increasing pump runs. The experimental study without extracorporeal circulation was conducted on 19 mongrel dogs. During IABP runs RBF/CO increased, while the RVR decreased. After renal denervation, no noticeable influence of IABP upon renal hemodynamics was observed. Following a loading dose of noradrenaline (Norad), the RVR increased in a Norad concentration-dependent fashion, independently of IABP and renal denervation. These results indicate that IABP reduces the RVR and thereby exerts a favorable action on renal hemodynamics during pump times. The study thus warrants us to surmise that a mechanism involving the renal sympathetic nerves might play an important role in the production of favorable renal hemodynamic effects of IABP-assisted pulsatile flow extracorporeal circulation.

LONG-TERM MECHANICAL CIRCULATORY SUPPORT (DESTINATION THERAPY): ON TRACK TO COMPETE WITH HEART TRANSPLANTATIO?

PubMed Central

Kirklin, James K.; Naftel, David C.; Pagani, Francis D.; Kormos, Robert L.; Stevenson, Lynne; Miller, Marissa; Young, James B.

2012-01-01

Objective(s) Average two-year survival following cardiac transplantation is approximately 80%. The evolution and subsequent approval of larger pulsatile and, more recently, continuous flow mechanical circulatory support (MCS) technology for destination therapy (DT) offers the potential for triage of some patients awaiting cardiac transplantation to DT. Methods The National Heart, Lung and Blood Institute Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a national multi-institutional study of chronic mechanical circulatory support. Between June 2006 and December 2011, 127 pulsatile and 1160 continuous flow pumps (24% of total primary LVADs) carried an initial strategy of DT therapy. Results By multivariable analysis, risk factors (p<0.05) for mortality following DT included older age, larger body mass index, history of cancer, history of cardiac surgery, INTERMACS level I (cardiogenic shock), dialysis, increased BUN, use of a pulsatile flow device and use of a RVAD. Among continuous flow LVAD patients who were not in cardiogenic shock, a particularly favorable survival was associated with no cancer, patients not in cardiogenic shock, and BUN < 50, resulting in one and two year survival of 88 and 80%. Conclusions 1) Evolution from pulsatile to continuous flow technology has dramatically improved one and two year survival; 2) Destination Therapy is not appropriate for patients with rapid hemodynamic deterioration; or severe right ventricular failure 4) Important subsets of continuous flow DT patients now enjoy survival which is competitive with heart transplantation out to about two years. PMID:22795459

Development and evaluation of endurance test system for ventricular assist devices.

PubMed

Sumikura, Hirohito; Homma, Akihiko; Ohnuma, Kentaro; Taenaka, Yoshiyuki; Takewa, Yoshiaki; Mukaibayashi, Hiroshi; Katano, Kazuo; Tatsumi, Eisuke

2013-06-01

We developed a novel endurance test system that can arbitrarily set various circulatory conditions and has durability and stability for long-term continuous evaluation of ventricular assist devices (VADs), and we evaluated its fundamental performance and prolonged durability and stability. The circulation circuit of the present endurance test system consisted of a pulsatile pump with a small closed chamber (SCC), a closed chamber, a reservoir and an electromagnetic proportional valve. Two duckbill valves were mounted in the inlet and outlet of the pulsatile pump. The features of the circulation circuit are as follows: (1) the components of the circulation circuit consist of optimized industrial devices, giving durability; (2) the pulsatile pump can change the heart rate and stroke length (SL), as well as its compliance using the SCC. Therefore, the endurance test system can quantitatively reproduce various circulatory conditions. The range of reproducible circulatory conditions in the endurance test circuit was examined in terms of fundamental performance. Additionally, continuous operation for 6 months was performed in order to evaluate the durability and stability. The circulation circuit was able to set up a wide range of pressure and total flow conditions using the SCC and adjusting the pulsatile pump SL. The long-term continuous operation test demonstrated that stable, continuous operation for 6 months was possible without leakage or industrial device failure. The newly developed endurance test system demonstrated a wide range of reproducible circulatory conditions, durability and stability, and is a promising approach for evaluating the basic characteristics of VADs.

Design and evaluation of a dry coated drug delivery system with floating-pulsatile release.

PubMed

Zou, Hao; Jiang, Xuetao; Kong, Lingshan; Gao, Shen

2008-01-01

The objective of this work was to develop and evaluate a floating-pulsatile drug delivery system intended for chronopharmacotherapy. Floating-pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, we generated the system which consisted of three different parts, a core tablet, containing the active ingredient, an erodible outer shell and a top cover buoyant layer. The dry coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer which is responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with Methocel K4M, Carbopol 934P and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their buoyancy, dissolution and pharmacokinetic, as well gamma-scintigraphically. The results showed that a certain lag time before the drug released generally due to the erosion of the dry coated layer. Floating time was controlled by the quantity and composition of the buoyant layer. Both pharmacokinetic and gamma-scintigraphic data point out the capability of the system of prolonged residence of the tablets in the stomach and releasing drugs after a programmed lag time. (c) 2007 Wiley-Liss, Inc.

Comparison of Irrigation Times Using Gravity and High-Pressure Lavage.

PubMed

Muscatelli, Stefano; Howe, Andrea; O'Hara, Nathan N; O'Toole, Robert V; Sprague, Sheila A; Slobogean, Gerard P

2017-05-01

The benefits of high-pressure pulsatile lavage for open fracture irrigation have been controversial based on conflicting experimental animal research. Recently published data definitively demonstrated that irrigation pressure does not affect the incidence of reoperation for the treatment of open fractures. However, proponents of pulsatile lavage argue a faster irrigation time is an important benefit of the high-pressure treatment. The purpose of this study was to determine the difference in irrigation time between gravity and high-pressure lavage. The experimental setup was designed to mimic clinical practice and compared mean irrigation flow times for high-pressure pulsatile lavage and gravity flow with 2 commonly used tube diameters. Each irrigation setup was tested 5 times at 3 different irrigation bag heights. Analysis of variance and Student's t tests were used to compare the mean flow times of 3 irrigation methods at each height and among the 3 heights for each irrigation method. The mean irrigation flow time in the various experimental models ranged from 161 to 243 seconds. Gravity irrigation with wide tubing was significantly faster than pulsatile lavage or gravity with narrow tubing (P<.001). Increasing irrigation bag height had only a marginal effect on the overall flow times (<9% difference). The difference in mean flow time among the testing techniques was slightly longer than 1 minute, which is unlikely to have a material impact on procedural costs, operating times, and subsequent gains in patient safety. [Orthopedics. 2017; 40(3):e413-e416.]. Copyright 2017, SLACK Incorporated.

In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

PubMed

Ghimire, Manish; McInnes, Fiona J; Watson, David G; Mullen, Alexander B; Stevens, Howard N E

2007-09-01

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.

A Bayesian Model for Highly Accelerated Phase-Contrast MRI

PubMed Central

Rich, Adam; Potter, Lee C.; Jin, Ning; Ash, Joshua; Simonetti, Orlando P.; Ahmad, Rizwan

2015-01-01

Purpose Phase-contrast magnetic resonance imaging (PC-MRI) is a noninvasive tool to assess cardiovascular disease by quantifying blood flow; however, low data acquisition efficiency limits the spatial and temporal resolutions, real-time application, and extensions to 4D flow imaging in clinical settings. We propose a new data processing approach called Reconstructing Velocity Encoded MRI with Approximate message passing aLgorithms (ReVEAL) that accelerates the acquisition by exploiting data structure unique to PC-MRI. Theory and Methods ReVEAL models physical correlations across space, time, and velocity encodings. The proposed Bayesian approach exploits the relationships in both magnitude and phase among velocity encodings. A fast iterative recovery algorithm is introduced based on message passing. For validation, prospectively undersampled data are processed from a pulsatile flow phantom and five healthy volunteers. Results ReVEAL is in good agreement, quantified by peak velocity and stroke volume (SV), with reference data for acceleration rates R ≤ 10. For SV, Pearson r ≥ 0.996 for phantom imaging (n = 24) and r ≥ 0.956 for prospectively accelerated in vivo imaging (n = 10) for R ≤ 10. Conclusion ReVEAL enables accurate quantification of blood flow from highly undersampled data. The technique is extensible to 4D flow imaging, where higher acceleration may be possible due to additional redundancy. PMID:26444911

Killing me un-softly: Causes and mechanisms of arterial stiffness Recent Highlights of ATVB: Early Career Committee Contribution

PubMed Central

Lyle, Alicia N.; Raaz, Uwe

2017-01-01

The aorta is a blood vessel that provides a low resistance path for blood flow directed from the heart to peripheral organs and tissues. However, the aorta has another central hemodynamic function whereby the elastic nature of the aortic wall provides a significant biomechanical buffering capacity complementing the pulsatile cardiac blood flow and this is often referred to as Windkessel function. Stiffening of the arterial wall leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function. In this review article, we aim to provide a short general overview of some of the most common mechanisms that contribute to increased arterial stiffness, the consequences of arterial stiffening, and the clinical conditions in which arterial stiffness occurs with a focus on recent advancements in the field. PMID:28122777

Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

PubMed

Bayram, N; van Wely, M; Vandekerckhove, P; Lilford, R; van Der Veen, F

2000-01-01

In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in patients with PCOS. But, although ovulation and pregnancy has been achieved, the use of pulsatile GnRH in PCOS patients is controversial. To assess the effectiveness of pulsatile GnRH administration in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of ovulation induction, pregnancy, miscarriage, multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. All relevant published RCTs were selected. Non-randomised controlled trials were eligible for inclusion if treatment consisted of GnRH administration versus another treatment to induce ovulation in subfertile women with PCOS. A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. One RCT (Bringer 1985a) and one abstract (Coelingh 1983) were identified this way. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed for predetermined quality criteria. 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Three RCTs and one non-randomised comparative trial were identified comparing four different treatments: GnRH versus HMG, GnRH following GnRHa pre-treatment versus no pre-treatment, GnRH and FSH versus FSH, and GnRH following GnRHa pre-treatment versus GnRH following oral contraceptive pre-treatment. This means that there was only one trial in any one comparison. In the first two studies, data of pre- and post-cross-over were not described separately. Therefore, these results could not be included in the MetaView analysis. The odds ratio for ovulation rate was 16 (95 % CI: 1.1-239) in the study comparing GnRH and FSH with FSH. When GnRH after GnRHa pre-treatment was compared with GnRH after oral contraceptive pre-treatment, an odds ratio of 7.5 (95 % CI: 1.2-46) was obtained. All trials were small and of too short duration to show any significance in pregnancy results. Per study only one to four pregnancies occurred. Multiple pregnancies were not seen. OHSS was seen only in the patients stimulated with HMG. The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Influence of sodium valproate on medium-late luteal phase pulsatile LH secretion in normal women.

PubMed

Lado Abeal, J; Rey Losada, C; Cabezas Agricola, J M; Cabezas-Cerrato, J

1994-01-01

It is not known whether gamma-aminobutyric acid (GABA) is involved in control of pulsatile LH secretion in human beings. Previous work by our group has shown that manipulation of the GABAergic system with sodium valproate does not affect pulsatile LH secretion in normal women in the late follicular phase. However, it has been suggested that steroid levels are critical for the influence of GABA upon hormone secretion; in particular, progesterone has been said to enhance inhibition by GABA. In this work we studied the effect of sodium valproate on pulsatile LH secretion in medium-late luteal phase of normal women. Six normal young women were studied over an 8-hour period in two successive menstrual cycles. On each occasion blood samples were taken every 10 minutes between 1000 and 1800 h. We administered 400 mg of sodium valproate every 8 hours on the 7 days preceding their second cycle and additional 400 mg at 0900 and 1400 h on the day of the study. Ovulation day was estimated by means of serial ovarian ultrasound examinations and confirmed by serum progesterone concentrations. In each cycle, LH, oestradiol and progesterone were determined by radioimmunoassay and sodium valproate by repolarization fluorescence spectrophotometry. The series of LH levels was smoothed for 1-minute sampling periods by means of a spline function and analysed by means of a program developed in our laboratory and written in Fortran 77. The program deconvolved the signal and calculated the pulse area, pulse duration, interpulse interval and number of pulses. LH pulse identification on the deconvolved signals was performed using our own method based on Friedman's non-parametric statistic. The statistical significance of differences between parameters was estimated using the Mann-Whitney test and Wilcoxon signed rank test. There were no significant differences in LH pulse area, pulse duration, interpulse interval or number of pulses with the administration of sodium valproate. Activation of the GABAergic system with sodium valproate had no biologically significant effect on the mid-late luteal phase pulsatile LH secretion in normal women.

Study of endothelial cell apoptosis using fluorescence resonance energy transfer (FRET) biosensor cell line with hemodynamic microfluidic chip system.

PubMed

Yu, J Q; Liu, X F; Chin, L K; Liu, A Q; Luo, K Q

2013-07-21

To better understand how hyperglycemia induces endothelial cell dysfunction under the diabetic conditions, a hemodynamic microfluidic chip system was developed. The system combines a caspase-3-based fluorescence resonance energy transfer (FRET) biosensor cell line which can detect endothelial cell apoptosis in real-time, post-treatment effect and with a limited cell sample, by using a microfluidic chip which can mimic the physiological pulsatile flow profile in the blood vessel. The caspase-3-based FRET biosensor endothelial cell line (HUVEC-C3) can produce a FRET-based sensor protein capable of probing caspase-3 activation. When the endothelial cells undergo apoptosis, the color of the sensor cells changes from green to blue, thus sensing apoptosis. A double-labeling fluorescent technique (yo pro-1 and propidium iodide) was used to validate the findings revealed by the FRET-based caspase sensor. The results show high rates of apoptosis and necrosis of endothelial cells when high glucose concentration was applied in our hemodynamic microfluidic chip combined with an exhaustive pulsatile flow profile. The two apoptosis detection techniques (fluorescent method and FRET biosensor) are comparable; but FRET biosensor offers more advantages such as real-time observation and a convenient operating process to generate more accurate and reliable data. Furthermore, the activation of the FRET biosensor also confirms the endothelial cell apoptosis induced by the abnormal pulsatile shear stress and high glucose concentration is through caspase-3 pathway. A 12% apoptotic rate (nearly a 4-fold increase compared to the static condition) was observed when the endothelial cells were exposed to a high glucose concentration of 20 mM under 2 h exhaustive pulsatile shear stress of 30 dyne cm(-2) and followed with another 10 h normal pulsatile shear stress of 15 dyne cm(-2). Therefore, the most important finding of this study is to develop a novel endothelial cell apoptosis detection method, which combines the microfluidic chip system and FRET biosensor. This finding may provide new insight into how glucose causes endothelial cell dysfunction, which is the major cause of diabetes-derived complications.

Development of a microimpedance pump for pulsatile flow transport - Part : Flow characteristics of the microimpedance pump. Part 2: A systematic study of steady and pulsatile transport in microscale cavities

NASA Astrophysics Data System (ADS)

Rinderknecht, Derek

Microfluidics offers an effective means to carry out a wide range of transport processes within a controlled microenvironment by drawing on the benefits imparted by increasing surface area to volume ratio at the microscale. Critical to the impact of microfluidics on integrated devices in the fields of bioengineering and biomedicine is the ability to transport fluids and biomolecules effectively particularly at the size scales involved. In this context a bio-inspired pumping mechanism, the valveless impedance pump, was explored for applications in microfluidics ranging from micro total analysis systems to microchannel cooling. Adhering to the basic principles of the impedance pump mechanism, pumps have been constructed at a variety of size scales from a few centimeters to a few hundred microns. The micro impedance pump is valveless, bidirectional, and can be constructed simply from a wide range of materials. Depending on the size of the pump flow rates range from nL/min to mL/min and pressures can be generated that exceed 20 kPa. Another benefit of the impedance pump is the pulsatile flow output which can be used in the context of microfluidic applications to enhance transport at low Reynolds numbers as well as metering in drug delivery. Pulsatile flow was therefore investigated as a method of augmenting transport in microfluidic systems. Micro PIV was used to study the affect of both steady and pulsatile flows on transport at low Reynolds number was examined in microscale rectangular cavities. Ventilation of the cavity contents was examined in terms of the residence time or average time a particle remains in the cavity region. Lagrangian coherent structures (LCS) were applied to empirical velocity fields to determine the impact of unsteadiness on time dependent boundaries to fluid transport present in the flow. Experimental results show that there are both frequencies which are beneficial and detrimental to cavity ventilation as well as certain frequencies which more evenly distribute particles originating in the cavity throughout the freestream.

Relationship between Aortic Compliance and Impact of Cerebral Blood Flow Fluctuation to Dynamic Orthostatic Challenge in Endurance Athletes.

PubMed

Tomoto, Tsubasa; Imai, Tomoko; Ogoh, Shigehiko; Maeda, Seiji; Sugawara, Jun

2018-01-01

Aorta effectively buffers cardiac pulsatile fluctuation generated from the left ventricular (LV) which could be a mechanical force to high blood flow and low-resistance end-organs such as the brain. A dynamic orthostatic challenge may evoke substantial cardiac pulsatile fluctuation via the transient increases in venous return and stroke volume (SV). Particularly, this response may be greater in endurance-trained athletes (ET) who exhibit LV eccentric remodeling. The aim of this study was to determine the contribution of aortic compliance to the response of cerebral blood flow fluctuation to dynamic orthostatic challenge in ET and age-matched sedentary (SED) young healthy men. ET ( n = 10) and SED ( n = 10) underwent lower body negative pressure (LBNP) (-30 mmHg for 4 min) stimulation and release the pressure that initiates a rapid regain of limited venous return and consequent increase in SV. The recovery responses of central and middle cerebral arterial (MCA) hemodynamics from the release of LBNP (~15 s) were evaluated. SV (via Modeflow method) and pulsatile and systolic MCA (via transcranial Doppler) normalized by mean MCA velocity (MCAv) significantly increased after the cessation of LBNP in both groups. ET exhibited the higher ratio of SV to aortic pulse pressure (SV/ Ao PP), an index of aortic compliance, at the baseline compared with SED ( P < 0.01). Following the LBNP release, SV was significantly increased in SED by 14 ± 7% (mean ± SD) and more in ET by 30 ± 15%; nevertheless, normalized pulsatile, systolic, and diastolic MCAv remained constant in both groups. These results might be attributed to the concomitant with the increase in aortic compliance assessed by SV/ Ao PP. Importantly, the increase in SV/ Ao PP following the LBNP release was greater in ET than in SED ( P < 0.01), and significantly correlated with the baseline SV/ Ao PP ( r = 0.636, P < 0.01). These results suggest that the aortic compliance in the endurance athletes is able to accommodate the additional SV and buffer the potential increase in pulsatility at end-organs such as the brain.

Imaging Strategies for Tissue Engineering Applications

PubMed Central

Nam, Seung Yun; Ricles, Laura M.; Suggs, Laura J.

2015-01-01

Tissue engineering has evolved with multifaceted research being conducted using advanced technologies, and it is progressing toward clinical applications. As tissue engineering technology significantly advances, it proceeds toward increasing sophistication, including nanoscale strategies for material construction and synergetic methods for combining with cells, growth factors, or other macromolecules. Therefore, to assess advanced tissue-engineered constructs, tissue engineers need versatile imaging methods capable of monitoring not only morphological but also functional and molecular information. However, there is no single imaging modality that is suitable for all tissue-engineered constructs. Each imaging method has its own range of applications and provides information based on the specific properties of the imaging technique. Therefore, according to the requirements of the tissue engineering studies, the most appropriate tool should be selected among a variety of imaging modalities. The goal of this review article is to describe available biomedical imaging methods to assess tissue engineering applications and to provide tissue engineers with criteria and insights for determining the best imaging strategies. Commonly used biomedical imaging modalities, including X-ray and computed tomography, positron emission tomography and single photon emission computed tomography, magnetic resonance imaging, ultrasound imaging, optical imaging, and emerging techniques and multimodal imaging, will be discussed, focusing on the latest trends of their applications in recent tissue engineering studies. PMID:25012069

Cerebrospinal Fluid Mechanics and Its Coupling to Cerebrovascular Dynamics

NASA Astrophysics Data System (ADS)

Linninger, Andreas A.; Tangen, Kevin; Hsu, Chih-Yang; Frim, David

2016-01-01

Cerebrospinal fluid (CSF) is not stagnant but displays fascinating oscillatory flow patterns inside the ventricular system and reversing fluid exchange between the cranial vault and spinal compartment. This review provides an overview of the current knowledge of pulsatile CSF motion. Observations contradicting classical views about its bulk production and clearance are highlighted. A clinical account of diseases of abnormal CSF flow dynamics, including hydrocephalus, syringomyelia, Chiari malformation type 1, and pseudotumor cerebri, is also given. We survey medical imaging modalities used to observe intracranial dynamics in vivo. Additionally, we assess the state of the art in predictive models of CSF dynamics. The discussion addresses open questions regarding CSF dynamics as they relate to the understanding and management of diseases.

A Bayesian model for highly accelerated phase-contrast MRI.

PubMed

Rich, Adam; Potter, Lee C; Jin, Ning; Ash, Joshua; Simonetti, Orlando P; Ahmad, Rizwan

2016-08-01

Phase-contrast magnetic resonance imaging is a noninvasive tool to assess cardiovascular disease by quantifying blood flow; however, low data acquisition efficiency limits the spatial and temporal resolutions, real-time application, and extensions to four-dimensional flow imaging in clinical settings. We propose a new data processing approach called Reconstructing Velocity Encoded MRI with Approximate message passing aLgorithms (ReVEAL) that accelerates the acquisition by exploiting data structure unique to phase-contrast magnetic resonance imaging. The proposed approach models physical correlations across space, time, and velocity encodings. The proposed Bayesian approach exploits the relationships in both magnitude and phase among velocity encodings. A fast iterative recovery algorithm is introduced based on message passing. For validation, prospectively undersampled data are processed from a pulsatile flow phantom and five healthy volunteers. The proposed approach is in good agreement, quantified by peak velocity and stroke volume (SV), with reference data for acceleration rates R≤10. For SV, Pearson r≥0.99 for phantom imaging (n = 24) and r≥0.96 for prospectively accelerated in vivo imaging (n = 10) for R≤10. The proposed approach enables accurate quantification of blood flow from highly undersampled data. The technique is extensible to four-dimensional flow imaging, where higher acceleration may be possible due to additional redundancy. Magn Reson Med 76:689-701, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

[Value of MR imaging and MR angiography in the differential diagnosis of carotid space tumour].

PubMed

Liu, Pei-fang; Li, Xin; Bao, Run-xian; Liu, Jing-zu; Ge, Zheng-jin

2004-04-01

To determine the imaging features of magnetic resonance imaging (MRI) and 2D time of flight (TOF) MR angiography (MRA) and study the value in the differential diagnosis and surgical planning for carotid space tumors. Twenty-six patients with suspected pulsatile carotid space mass were imaged by MRI and 2D TOF MRA from 1996 to 2003. Its characteristic findings were analyzed for lesion shape, margin, signal intensity, angle of common carotid bifurcation, and the relationship between the great vessels and carotid space mass. Of the 26 patients, 22 were verified histopathologically, including 15 carotid body tumors (1 patient had bilateral carotid body tumors), 4 carotid artery aneurysms, 3 schwannomas, and 1 metastatic carcinoma. The rest four patients had clinical pseudomasses proved by MRI and MRA as considerable dilated or tortuous carotid artery as compared with the contralateral one. Combined MRI and MRA assessment of carotid body tumors and carotid artery aneurysm yielded an accuracy of 100%. It was also revealed that the anatomy shown on the MRI and axial MRA source images was consistent with that found by surgery. MRI in combination with MRA is considered as non-invasive imaging technique for the evaluation of carotid space tumor showing superiority to other modalities in the differential diagnosis between vascular versus non-vascular tumours. This method may take the place of traumatic carotid angiography.

[Effectiveness and safety of atosiban vs. pulsatile administration of fenoterol in the treatment of preterm labour].

PubMed

Nonnenmacher, A; Hopp, H; Dudenhausen, J

2009-10-01

The aim of this study was to compare the efficacy and side effects of atosiban with those of fenoterol (pulsatile administration) for acute tocolysis. A prospective, open-label, randomised controlled trial was performed. Patients in preterm labour at 24+0 to 33+6 weeks of gestation were randomised to receive atosiban (A) or fenoterol (F) pulsatile administration. Primary outcome was the arrest of preterm labour. The proportion of woman remaining undelivered at 48 hours (86.3% atosiban group and 79.6% fenoterol group) and at 7 days (78.4% vs. 66.7%) was comparable. The incidence of maternal cardiovascular side effects was lower in the atosiban group (4% vs. 78%, p=0.0). Tocolysis was terminated as a result of maternal adverse effects in the fenoterol group (9%). Fetal tachycardia was lower in the atosiban group (2% vs. 22%). The mean duration of tocolytic administration was lower in the atosiban group (19 h vs. 24.5 h, p<0.05). The adverse effects in the pulsatile administration of fenoterol for short duration were only dependent on the initial dosage for the arrest of preterm labour. Neonatal outcome were similar between the treatment groups and were rather related to the gestational age not to the tocolytic agent. Atosiban was comparable in clinical effectiveness and was associated with fewer maternal and fetal adverse effects, so that fenoterol cannot be recommended. Completion of tocolytic therapy 12 hours after arrest of preterm labour is effective and associated with a short mean duration. Georg Thieme Verlag KG Stuttgart-New York.

[Pulsatile total cavopulmonary shunt for hypoplastic right heart syndrome with abnormal systemic venous return--a case report].

PubMed

Oiwa, H; Kawauchi, M; Chikada, M; Yagyu, K; Kotsuka, Y; Furuse, A

1995-01-01

A pulsatile total cavopulmonary shunt was successfully performed on a 5-year-old girl with hypoplastic right heart syndrome associated with abnormal systemic venous return; at the same time, modified mitral valve replacement was performed for mitral regurgitation. The right atrium, tricuspid valve and right ventricle were all extremely dimunitive. The diameter of the tricuspid valve was 50% of normal and the volume of the right ventricle was 8.6% of normal. In addition, there were severe subpumonary stenosis, a restrictive ventricular septal defect (VSD) and an atrial septal defect (ASD). The bilateral superior venae cavae (SVCs) and the hepatic vein drained to the left atrium, and the inferior vena cava was infrahepatically interrupted with a hemiazygos connection to the left superior vena cava. At the operation, each SVC was anastomosed end-to-side to each branch of the pulmonary artery (PA). The restrictive ventricular septal defect and stenotic subpulmonary lesion were left. The diameter of the ASD was reduced from 12 mm to 7 mm. The main PA was neither divided nor banded. The pulsatile blood flow from the left heart to the PA was regurated by a native restrictive VSD and stenotic subpulmonary lesion, and that from the right heart via the ASD was limited by reducing the size of the ASD. These described anatomic arrangements produced adequate antegrade pulsatile flow in the PA, which might prevent the development of pulmonary arteriovenous fistulae and, besides permit transfer of drainage of the hepatic vein from the left to the right atrium via the ASD in future.

Acute impact of drinking coffee on the cerebral and systemic vasculature.

PubMed

Washio, Takuro; Sasaki, Hiroyuki; Ogoh, Shigehiko

2017-05-01

Previous studies have suggested that the risk of ischemic stroke increases immediately after drinking coffee. Indeed, drinking coffee, that is, caffeine, acutely increases arterial stiffness as well as blood pressure and peripheral vascular resistance. On the other hand, it has been reported that arterial stiffening is associated with elevation in the pulsatility index (PI) of cerebral blood flow (CBF), which increases the risk of brain disease. However, the effect of drinking coffee on the PI of the CBF and its interaction with arterial stiffness remain unknown. Against this background, we hypothesized that an acute increase in arterial stiffness induced by drinking coffee augments cerebral pulsatile stress. To test this hypothesis, in 10 healthy young men we examined the effects of drinking coffee on the PI of middle cerebral artery blood velocity (MCAv) and brachial-ankle pulse wave velocity (baPWV) as indices of cerebral pulsatile stress and arterial stiffness, respectively. Mean arterial blood pressure and baPWV were higher ( P  < 0.01 and P  = 0.02), whereas mean MCA V and mean cerebrovascular conductance index were lower upon drinking coffee ( P  = 0.02 and P  < 0.01) compared with a placebo (decaffeinated coffee). However, there was no difference in the PI of MCAv between drinking coffee and the placebo condition. These findings suggest that drinking coffee does not increase cerebral pulsatile stress acutely despite an elevation in arterial stiffness in the systemic circulation. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Rapid Speed Modulation of a Rotary Total Artificial Heart Impeller.

PubMed

Kleinheyer, Matthias; Timms, Daniel L; Tansley, Geoffrey D; Nestler, Frank; Greatrex, Nicholas A; Frazier, O Howard; Cohn, William E

2016-09-01

Unlike the earlier reciprocating volume displacement-type pumps, rotary blood pumps (RBPs) typically operate at a constant rotational speed and produce continuous outflow. When RBP technology is used in constructing a total artificial heart (TAH), the pressure waveform that the TAH produces is flat, without the rise and fall associated with a normal arterial pulse. Several studies have suggested that pulseless circulation may impair microcirculatory perfusion and the autoregulatory response and may contribute to adverse events such as gastrointestinal bleeding, arteriovenous malformations, and pump thrombosis. It may therefore be beneficial to attempt to reproduce pulsatile output, similar to that generated by the native heart, by rapidly modulating the speed of an RBP impeller. The choice of an appropriate speed profile and control strategy to generate physiologic waveforms while minimizing power consumption and blood trauma becomes a challenge. In this study, pump operation modes with six different speed profiles using the BiVACOR TAH were evaluated in vitro. These modes were compared with respect to: hemodynamic pulsatility, which was quantified as surplus hemodynamic energy (SHE); maximum rate of change of pressure (dP/dt); pulse power index; and motor power consumption as a function of pulse pressure. The results showed that the evaluated variables underwent different trends in response to changes in the speed profile shape. The findings indicated a possible trade-off between SHE levels and flow rate pulsatility related to the relative systolic duration in the speed profile. Furthermore, none of the evaluated measures was sufficient to fully characterize hemodynamic pulsatility. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Analysis of pressure head-flow loops of pulsatile rotodynamic blood pumps.

PubMed

Jahren, Silje E; Ochsner, Gregor; Shu, Fangjun; Amacher, Raffael; Antaki, James F; Vandenberghe, Stijn

2014-04-01

The clinical importance of pulsatility is a recurring topic of debate in mechanical circulatory support. Lack of pulsatility has been identified as a possible factor responsible for adverse events and has also demonstrated a role in myocardial perfusion and cardiac recovery. A commonly used method for restoring pulsatility with rotodynamic blood pumps (RBPs) is to modulate the speed profile, synchronized to the cardiac cycle. This introduces additional parameters that influence the (un)loading of the heart, including the timing (phase shift) between the native cardiac cycle and the pump pulses, and the amplitude of speed modulation. In this study, the impact of these parameters upon the heart-RBP interaction was examined in terms of the pressure head-flow (HQ) diagram. The measurements were conducted using a rotodynamic Deltastream DP2 pump in a validated hybrid mock circulation with baroreflex function. The pump was operated with a sinusoidal speed profile, synchronized to the native cardiac cycle. The simulated ventriculo-aortic cannulation showed that the level of (un)loading and the shape of the HQ loops strongly depend on the phase shift. The HQ loops displayed characteristic shapes depending on the phase shift. Increased contribution of native contraction (increased ventricular stroke work [WS ]) resulted in a broadening of the loops. It was found that the previously described linear relationship between WS and the area of the HQ loop for constant pump speeds becomes a family of linear relationships, whose slope depends on the phase shift. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

Induction of ovulation with subcutaneous pulsatile gonadotropin-releasing hormone: correlation with body weight and other parameters.

PubMed

Thomas, A K; Mander, J; Hale, J; Walstab, J; Forrest, M S

1989-05-01

We treated 21 anovulatory infertile patients with subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administered via a syringe pump. Response to treatment was assessed by urinary estrogen excretion and ultrasound measurement of follicular growth. Ten patients ovulated and 8 subsequently conceived, for a total of 10 pregnancies. Human chorionic gonadotropin (hCG) was not administered routinely, but two patients required hCG to induce follicular rupture. The majority of the patients who conceived had a body mass index (BMI) of less than 21 and a luteinizing hormone (LH)/follicle-stimulating hormone ratio of less than 1. Conversely, those patients with either elevated BMI or LH or both generally failed to respond satisfactorily to this treatment. It is suggested that pulsatile GnRH is most likely to succeed in inducing ovulation if the BMI is less than 21 and the LH is normal, but is unlikely to be successful if there is both an elevated LH and a BMI of greater than 25. Between these two extremes, the response is variable and a therapeutic trial may be appropriate.

Induction of pulsatile secretion of leptin in horses following thyroidectomy.

PubMed

Buff, Preston R; Messer, Nat T; Cogswell, Andria M; Wilson, David A; Johnson, Philip J; Keisler, Duane H; Ganjam, Venkataseshu K

2007-02-01

Endocrine characteristics of Quarter Horse-type mares were determined during a 68 h feed deprivation and again in the same mares following surgical thyroidectomy (THX). A crossover experimental design was implemented, in which mares received brome hay available ad libitum (FED) or were food deprived (RES) for 68 h. Blood samples were collected every 20 min for 48 h, beginning 20 h after the onset of food deprivation. Concentrations of triiodothyronine and thyroxine were undetectable post-THX. Plasma concentrations of thyrotropin were greater post-THX versus pre-THX (P<0 x 001). Plasma concentrations of leptin were greater in the THX FED group than in the THX RES group (P<0 x 01). The existence of leptin pulse secretion was found only in post-THX compared with the same horses pre-THX (P=0 x 02). We theorize that non-pulsatile secretion of leptin may have contributed to the survival of this species, as it evolved in the regions of seasonal availability of food. Lack of pulsatile secretion of leptin may contribute to the accumulation of energy stores by modulating leptin sensitivity.

Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations.

PubMed

Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Warenik-Szymankiewicz, Alina; Genazzani, Andrea Riccardo

2008-01-01

Functional hypothalamic amenorrhea (FHA) is defined as a non-organic and reversible disorder in which the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion plays a key role. There are main three types of FHA: stress-related amenorrhea, weight loss-related amenorrhea and exercise-related amenorrhea. The spectrum of GnRH-luteinizing hormone (LH) disturbances in FHA is very broad and includes lower mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern and higher mean frequency of LH pulses. Precise mechanisms underlying the pathophysiology of FHA are very complex and unclear. Numerous neuropeptides, neurotransmitters and neurosteroids play important roles in the physiological regulation of GnRH pulsatile secretion and there is evidence that different neuropeptides may be involved in the pathophysiology of FHA. Particular attention is paid to such substances as allopregnanolone, neuropeptide Y, corticotropin-releasing hormone, leptin, ghrelin and beta-endorphin. Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA.

Gonadotropin-releasing hormone for infertility in women with primary hypothalamic amenorrhea. Toward a more-interventional approach.

PubMed

Kesrouani, A; Abdallah, M A; Attieh, E; Abboud, J; Atallah, D; Makhoul, C

2001-01-01

To assess the effectiveness of a protocol of pulsatile gonadotropin releasing-hormone (GnRH) in treating infertility in women with primary hypothalamic amenorrhea. Retrospective analysis of 44 cycles treated at an infertility center. Twenty-four patients with primary hypothalamic amenorrhea were treated intravenously with pulsatile GnRH using 5 micrograms per bolus every 90 minutes. Ultrasound monitoring and cervical assessment by Insler's scoring system allowed timed injection of human chorionic gonadotropin (hCG) and intrauterine insemination if needed. Luteal support was provided with hCG. The ovulation rate was 95% with the 5-microgram dose. A single follicle was produced in 91% of cycles. The overall pregnancy rate per ovulatory cycle was 45%, and the pregnancy rate per patient was 83%. In patients treated previously with exogenous gonadotropins, poor results were observed. Only one case of mild overstimulation was reported. Pulsatile GnRH is an effective and safe method of treating infertility in women with primary hypothalamic amenorrhea, thus simulating normal ovulation; however, more-interventional management, including the qualitative estrogenic response, may lead to optimal results and increase the pregnancy rate.

Correlation between vortices and wall shear stress in a curved artery model under pulsatile flow conditions

NASA Astrophysics Data System (ADS)

Cox, Christopher; Plesniak, Michael W.

2017-11-01

One of the most physiologically relevant factors within the cardiovascular system is the wall shear stress. The wall shear stress affects endothelial cells via mechanotransduction and atherosclerotic regions are strongly correlated with curvature and branching in the human vasculature, where the shear stress is both oscillatory and multidirectional. Also, the combined effect of curvature and pulsatility in cardiovascular flows produces unsteady vortices. In this work, our goal is to assess the correlation between multiple vortex pairs and wall shear stress. To accomplish this, we use an in-house high-order flux reconstruction Navier-Stokes solver to simulate pulsatile flow of a Newtonian blood-analog fluid through a rigid 180° curved artery model. We use a physiologically relevant flow rate and generate results using both fully developed and uniform entrance conditions, the latter motivated by the fact that flow upstream to a curved artery may not be fully developed. Under these two inflow conditions, we characterize the evolution of various vortex pairs and their subsequent effect on several wall shear stress metrics. Supported by GW Center for Biomimetics and Bioinspired Engineering.

High-cut characteristics of the baroreflex neural arc preserve baroreflex gain against pulsatile pressure.

PubMed

Kawada, Toru; Zheng, Can; Yanagiya, Yusuke; Uemura, Kazunori; Miyamoto, Tadayoshi; Inagaki, Masashi; Shishido, Toshiaki; Sugimachi, Masaru; Sunagawa, Kenji

2002-03-01

A transfer function from baroreceptor pressure input to sympathetic nerve activity (SNA) shows derivative characteristics in the frequency range below 0.8 Hz in rabbits. These derivative characteristics contribute to a quick and stable arterial pressure (AP) regulation. However, if the derivative characteristics hold up to heart rate frequency, the pulsatile pressure input will yield a markedly augmented SNA signal. Such a signal would saturate the baroreflex signal transduction, thereby disabling the baroreflex regulation of AP. We hypothesized that the transfer gain at heart rate frequency would be much smaller than that predicted from extrapolating the derivative characteristics. In anesthetized rabbits (n = 6), we estimated the neural arc transfer function in the frequency range up to 10 Hz. The transfer gain was lost at a rate of -20 dB/decade when the input frequency exceeded 0.8 Hz. A numerical simulation indicated that the high-cut characteristics above 0.8 Hz were effective to attenuate the pulsatile signal and preserve the open-loop gain when the baroreflex dynamic range was finite.

Prediction and control of neural responses to pulsatile electrical stimulation

NASA Astrophysics Data System (ADS)

Campbell, Luke J.; Sly, David James; O'Leary, Stephen John

2012-04-01

This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s-1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s-1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

An agent-based model of leukocyte transendothelial migration during atherogenesis.

PubMed

Bhui, Rita; Hayenga, Heather N

2017-05-01

A vast amount of work has been dedicated to the effects of hemodynamics and cytokines on leukocyte adhesion and trans-endothelial migration (TEM) and subsequent accumulation of leukocyte-derived foam cells in the artery wall. However, a comprehensive mechanobiological model to capture these spatiotemporal events and predict the growth and remodeling of an atherosclerotic artery is still lacking. Here, we present a multiscale model of leukocyte TEM and plaque evolution in the left anterior descending (LAD) coronary artery. The approach integrates cellular behaviors via agent-based modeling (ABM) and hemodynamic effects via computational fluid dynamics (CFD). In this computational framework, the ABM implements the diffusion kinetics of key biological proteins, namely Low Density Lipoprotein (LDL), Tissue Necrosis Factor alpha (TNF-α), Interlukin-10 (IL-10) and Interlukin-1 beta (IL-1β), to predict chemotactic driven leukocyte migration into and within the artery wall. The ABM also considers wall shear stress (WSS) dependent leukocyte TEM and compensatory arterial remodeling obeying Glagov's phenomenon. Interestingly, using fully developed steady blood flow does not result in a representative number of leukocyte TEM as compared to pulsatile flow, whereas passing WSS at peak systole of the pulsatile flow waveform does. Moreover, using the model, we have found leukocyte TEM increases monotonically with decreases in luminal volume. At critical plaque shapes the WSS changes rapidly resulting in sudden increases in leukocyte TEM suggesting lumen volumes that will give rise to rapid plaque growth rates if left untreated. Overall this multi-scale and multi-physics approach appropriately captures and integrates the spatiotemporal events occurring at the cellular level in order to predict leukocyte transmigration and plaque evolution.

An agent-based model of leukocyte transendothelial migration during atherogenesis

PubMed Central

Bhui, Rita; Hayenga, Heather N.

2017-01-01

A vast amount of work has been dedicated to the effects of hemodynamics and cytokines on leukocyte adhesion and trans-endothelial migration (TEM) and subsequent accumulation of leukocyte-derived foam cells in the artery wall. However, a comprehensive mechanobiological model to capture these spatiotemporal events and predict the growth and remodeling of an atherosclerotic artery is still lacking. Here, we present a multiscale model of leukocyte TEM and plaque evolution in the left anterior descending (LAD) coronary artery. The approach integrates cellular behaviors via agent-based modeling (ABM) and hemodynamic effects via computational fluid dynamics (CFD). In this computational framework, the ABM implements the diffusion kinetics of key biological proteins, namely Low Density Lipoprotein (LDL), Tissue Necrosis Factor alpha (TNF-α), Interlukin-10 (IL-10) and Interlukin-1 beta (IL-1β), to predict chemotactic driven leukocyte migration into and within the artery wall. The ABM also considers wall shear stress (WSS) dependent leukocyte TEM and compensatory arterial remodeling obeying Glagov’s phenomenon. Interestingly, using fully developed steady blood flow does not result in a representative number of leukocyte TEM as compared to pulsatile flow, whereas passing WSS at peak systole of the pulsatile flow waveform does. Moreover, using the model, we have found leukocyte TEM increases monotonically with decreases in luminal volume. At critical plaque shapes the WSS changes rapidly resulting in sudden increases in leukocyte TEM suggesting lumen volumes that will give rise to rapid plaque growth rates if left untreated. Overall this multi-scale and multi-physics approach appropriately captures and integrates the spatiotemporal events occurring at the cellular level in order to predict leukocyte transmigration and plaque evolution. PMID:28542193

The Involvement of PPARs in the Selective Regulation of Brain CYP2D by Growth Hormone.

PubMed

Zhang, Furong; Li, Jie; Na, Shufang; Wu, Juan; Yang, Zheqiong; Xie, Xianfei; Wan, Yu; Li, Ke; Yue, Jiang

2018-05-21

Brain CYP2D is responsible for the synthesis of endogenous neurotransmitters such as dopamine and serotonin. This study is to investigate the effects of cerebral CYP2D on mouse behavior and the mechanism whereby growth hormone regulates brain CYP2D. The inhibition of cerebellar CYP2D significantly affected the spatial learning and exploratory behavior of mice. CYP2D expression was lower in the brain in GHR-/- mice than that in WT mice; however, hepatic CYP2D levels were similar. Brain PPARα expression in male GHR-/- mice were markedly higher than those in WT mice, while brain PPARγ levels were decreased or unchanged in different regions. However, both hepatic PPARα and PPARγ in male GHR-/- mice were markedly higher than those in WT mice. Pulsatile GH decreased the PPARα mRNA level and increased the mRNA levels of CYP2D6 and PPARγ in SH-SY5Y cells. A luciferase assay showed that PPARγ activated the CYP2D6 gene promoter while PPARα inhibited its function. Pulsatile GH decreased the binding of PPARα to the CYP2D6 promoter by 40% and promoted the binding of PPARγ to the CYP2D6 promoter by approximately 60%. The male GH secretory pattern altered PPAR expression and the binding of PPARs to the CYP2D promoter, leading to the elevation of brain CYP2D in a tissue-specific manner. Growth hormone may alter the learning and memory functions in patients receiving GH replacement therapy via brain CYP2D. Copyright © 2018. Published by Elsevier Ltd.

Using the morphology of photoplethysmogram peaks to detect changes in posture.

PubMed

Linder, Stephen P; Wendelken, Suzanne M; Wei, Edward; McGrath, Susan P

2006-06-01

The morphology of the pulsatile component of the photoplethysmogram (PPG) has been shown to vary with physiology, but changes in the morphology caused by the baroreflex response to orthostatic stress have not been investigated. Using two FDA approved Nonin pulse oximeters placed on the finger and ear, we monitored 11 subjects, for three trials each, as they stood from a supine position. Each cardiac cycle was automatically extracted from the PPG waveform and characterized using statistics corresponding to normalized peak width, instantaneous heart rate, and amplitude of the pulsatile component of the ear PPG. A nonparametric Wilcoxon rank sum test was then used to detect in real-time changes in these features with p < 0.01. In all 33 trials, the standing event was detected as an abrupt change in at least two of these features, with only one false alarm. In 26 trials, an abrupt change was detected in all three features, with no false alarms. An increase in the normalize peak width was detected before an increase in heart rate, and in 21 trials a peak in the feature was detected before or as standing commenced. During standing, the pulse rate always increases, and then amplitude of the ear PPG constricts by a factor of two or more. We hypothesis that the baroreflex first reduces the percentage of time blood flow is stagnant during the cardiac cycle, then increases the hear rate, and finally vasoconstricts the peripheral tissue in order to reestablishing a nominal blood pressure. These three features therefore can be used as a detector of the baroreflex response to changes in posture or other forms of blood volume sequestration.

Near-infrared spectroscopic tissue imaging for medical applications

DOEpatents

Demos,; Stavros, Staggs [Livermore, CA; Michael, C [Tracy, CA

2006-03-21

Near infrared imaging using elastic light scattering and tissue autofluorescence are explored for medical applications. The approach involves imaging using cross-polarized elastic light scattering and tissue autofluorescence in the Near Infra-Red (NIR) coupled with image processing and inter-image operations to differentiate human tissue components.

Near-infrared spectroscopic tissue imaging for medical applications

DOEpatents

Demos, Stavros [Livermore, CA; Staggs, Michael C [Tracy, CA

2006-12-12

Near infrared imaging using elastic light scattering and tissue autofluorescence are explored for medical applications. The approach involves imaging using cross-polarized elastic light scattering and tissue autofluorescence in the Near Infra-Red (NIR) coupled with image processing and inter-image operations to differentiate human tissue components.

Locally optimal extracellular stimulation for chaotic desynchronization of neural populations.

PubMed

Wilson, Dan; Moehlis, Jeff

2014-10-01

We use optimal control theory to design a methodology to find locally optimal stimuli for desynchronization of a model of neurons with extracellular stimulation. This methodology yields stimuli which lead to positive Lyapunov exponents, and hence desynchronizes a neural population. We analyze this methodology in the presence of interneuron coupling to make predictions about the strength of stimulation required to overcome synchronizing effects of coupling. This methodology suggests a powerful alternative to pulsatile stimuli for deep brain stimulation as it uses less energy than pulsatile stimuli, and could eliminate the time consuming tuning process.

Rapid Response to High-Dose, Pulsatile Erlotinib in Afatinib-Refractory Leptomeningeal Carcinomatosis from Adenocarcinoma of the Lung: A Case Report.

PubMed

Fan, Frank S

2016-01-01

Leptomeningeal carcinomatosis occurred in an old female patient who was on a standard dose of afatinib for the treatment of her non-small cell lung cancer harboring an epidermal growth factor receptor gene mutation sensitive to tyrosine kinase inhibitors when extracranial lesions were still under control. Shifting to high-dose, pulsatile erlotinib dramatically saved her from the devastating condition in a very short period of time. Inadequate afatinib concentration in cerebrospinal fluid is reasonably suspected, and there is a call for clinical trials testing high-dose afatinib in leptomeningeal carcinomatosis.

Tissues segmentation based on multi spectral medical images

NASA Astrophysics Data System (ADS)

Li, Ya; Wang, Ying

2017-11-01

Each band image contains the most obvious tissue feature according to the optical characteristics of different tissues in different specific bands for multispectral medical images. In this paper, the tissues were segmented by their spectral information at each multispectral medical images. Four Local Binary Patter descriptors were constructed to extract blood vessels based on the gray difference between the blood vessels and their neighbors. The segmented tissue in each band image was merged to a clear image.

Acoustic radiation force impulse (ARFI) imaging: Characterizing the mechanical properties of tissues using their transient response to localized force

NASA Astrophysics Data System (ADS)

Nightingale, Kathryn R.; Palmeri, Mark L.; Congdon, Amy N.; Frinkely, Kristin D.; Trahey, Gregg E.

2004-05-01

Acoustic radiation force impulse (ARFI) imaging utilizes brief, high energy, focused acoustic pulses to generate radiation force in tissue, and conventional diagnostic ultrasound methods to detect the resulting tissue displacements in order to image the relative mechanical properties of tissue. The magnitude and spatial extent of the applied force is dependent upon the transmit beam parameters and the tissue attenuation. Forcing volumes are on the order of 5 mm3, pulse durations are less than 1 ms, and tissue displacements are typically several microns. Images of tissue displacement reflect local tissue stiffness, with softer tissues (e.g., fat) displacing farther than stiffer tissues (e.g., muscle). Parametric images of maximum displacement, time to peak displacement, and recovery time provide information about tissue material properties and structure. In both in vivo and ex vivo data, structures shown in matched B-mode images are in good agreement with those shown in ARFI images, with comparable resolution. Potential clinical applications under investigation include soft tissue lesion characterization, assessment of focal atherosclerosis, and imaging of thermal lesion formation during tissue ablation procedures. Results from ongoing studies will be presented. [Work supported by NIH Grant R01 EB002132-03, and the Whitaker Foundation. System support from Siemens Medical Solutions USA, Inc.

In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding.

PubMed

Nakayama, Yasuhide; Takewa, Yoshiaki; Sumikura, Hirohito; Yamanami, Masashi; Matsui, Yuichi; Oie, Tomonori; Kishimoto, Yuichiro; Arakawa, Mamoru; Ohmuma, Kentaro; Tajikawa, Tsutomu; Kanda, Keiichi; Tatsumi, Eisuke

2015-01-01

In-body tissue architecture--a novel and practical regeneration medicine technology--can be used to prepare a completely autologous heart valve, based on the shape of a mold. In this study, a three-dimensional (3D) printer was used to produce the molds. A 3D printer can easily reproduce the 3D-shape and size of native heart valves within several processing hours. For a tri-leaflet, valved conduit with a sinus of Valsalva (Biovalve type VII), the mold was assembled using two conduit parts and three sinus parts produced by the 3D printer. Biovalves were generated from completely autologous connective tissue, containing collagen and fibroblasts, within 2 months following the subcutaneous embedding of the molds (success rate, 27/30). In vitro evaluation, using a pulsatile circulation circuit, showed excellent valvular function with a durability of at least 10 days. Interposed between two expanded polytetrafluoroethylene grafts, the Biovalves (N = 3) were implanted in goats through an apico-aortic bypass procedure. Postoperative echocardiography showed smooth movement of the leaflets with minimal regurgitation under systemic circulation. After 1 month of implantation, smooth white leaflets were observed with minimal thrombus formation. Functional, autologous, 3D-shaped heart valves with clinical application potential were formed following in-body embedding of specially designed molds that were created within several hours by 3D printer. © 2014 Wiley Periodicals, Inc.

A thin film nitinol heart valve.

PubMed

Stepan, Lenka L; Levi, Daniel S; Carman, Gregory P

2005-11-01

In order to create a less thrombogenic heart valve with improved longevity, a prosthetic heart valve was developed using thin film nitinol (NiTi). A "butterfly" valve was constructed using a single, elliptical piece of thin film NiTi and a scaffold made from Teflon tubing and NiTi wire. Flow tests and pressure readings across the valve were performed in vitro in a pulsatile flow loop. Bio-corrosion experiments were conducted on untreated and passivated thin film nitinol. To determine the material's in vivo biocompatibility, thin film nitinol was implanted in pigs using stents covered with thin film NiTi. Flow rates and pressure tracings across the valve were comparable to those through a commercially available 19 mm Perimount Edwards tissue valve. No signs of corrosion were present on thin film nitinol samples after immersion in Hank's solution for one month. Finally, organ and tissue samples explanted from four pigs at 2, 3, 4, and 6 weeks after thin film NiTi implantation appeared without disease, and the thin film nitinol itself was without thrombus formation. Although long term testing is still necessary, thin film NiTi may be very well suited for use in artificial heart valves.

Comprehensive mechanical characterization of PLA fabric combined with PCL to form a composite structure vascular graft.

PubMed

Li, Chaojing; Wang, Fujun; Douglas, Graeham; Zhang, Ze; Guidoin, Robert; Wang, Lu

2017-05-01

Vascular grafts made by tissue engineering processes are prone to buckling and twisting, which can impede blood flow and lead to collapse of the vessel. These vascular conduits may suffer not only from insufficient tensile strength, but also from vulnerabilities related to compression, torsion, and pulsatile pressurization. Aiming to develop a tissue engineering-inspired blood conduit, composite vascular graft (cVG) prototypes were created by combining a flexible polylactic acid (PLA) knitted fabric with a soft polycaprolactone (PCL) matrix. The graft is to be populated in-situ with cellular migration and proliferation into the device. Comprehensive characterizations probed the relationship between structure and mechanical properties of the different cVG prototypes. The composite grafts exhibited major improvements in mechanical characteristics compared to single-material devices, with particular improvement in compression and torsional resistance. A commercial expanded polytetrafluoroethylene (ePTFE) vascular graft was used as a control against the proposed composite vascular grafts. CVG devices showed high tensile strength, high bursting strength, and improved suture retention. Compression, elastic recovery, and compliance were similar to those for the ePTFE graft. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigation of polymeric scaffold degradation for drug delivery and neovascularization applications

NASA Astrophysics Data System (ADS)

Bulusu, Kartik V.; Alibouzar, Mitra; Castro, Nathan J.; Zhang, Lijie G.; Sarkar, Kausik; Plesniak, Michael W.

2016-11-01

Degradable polymer-based prosthetics for the treatment of osseous tissue defects, maxillo-/cranio-facial trauma and brain injury face two common clinical obstacles impeding efficient tissue engraftment i.e., controlled material release and neovascularization. Ascertaining the time scales of polymer degradation for controlled delivery of drugs and nutrients is critical to treatment efficacy and strategy. We incorporated multiple experimental methodologies to understand the driving forces of transport mechanisms in polyvinyl alcohol-based (PVA) 3D-printed scaffolds of different porosity. Scaffold degradation was monitored various pulsatile flow conditions using MEMS-based pressure catheters and an ultrasonic flow rate sensor. Ultrasonic properties (bulk attenuation and sound velocity) were measured to monitor the degradation process in a static, alkaline medium. Viscosity and the absorption spectra variations with PVA-solute concentrations were measured using a rheometer and a spectrophotometer, respectively. A simple mathematical model based on Fick's law of diffusion provides the fundamental description of solute transport from the scaffold matrices. However, macroscopic material release could become anomalous or non-Fickian in complex polymeric scaffold matrices. Supported by the GW Center for Biomimetics and Bioinspired Engineering and NIH Director's New Innovator Award 1DP2EB020549-01.

Potential for Imaging Engineered Tissues with X-Ray Phase Contrast

PubMed Central

Appel, Alyssa; Anastasio, Mark A.

2011-01-01

As the field of tissue engineering advances, it is crucial to develop imaging methods capable of providing detailed three-dimensional information on tissue structure. X-ray imaging techniques based on phase-contrast (PC) have great potential for a number of biomedical applications due to their ability to provide information about soft tissue structure without exogenous contrast agents. X-ray PC techniques retain the excellent spatial resolution, tissue penetration, and calcified tissue contrast of conventional X-ray techniques while providing drastically improved imaging of soft tissue and biomaterials. This suggests that X-ray PC techniques are very promising for evaluation of engineered tissues. In this review, four different implementations of X-ray PC imaging are described and applications to tissues of relevance to tissue engineering reviewed. In addition, recent applications of X-ray PC to the evaluation of biomaterial scaffolds and engineered tissues are presented and areas for further development and application of these techniques are discussed. Imaging techniques based on X-ray PC have significant potential for improving our ability to image and characterize engineered tissues, and their continued development and optimization could have significant impact on the field of tissue engineering. PMID:21682604

Comprasion of ovarian stromal blood flow measured by color Doppler ultrasonography in polycystic ovary syndrome patients and healthy women with ultrasonographic evidence of polycystic.

PubMed

Ozdemir, Ozhan; Sari, Mustafa Erkan; Kalkan, Dilek; Koc, Esra Meltem; Ozdemir, Seyda; Atalay, Cemal Resat

2015-04-01

To compare ovarian stromal artery blood flows measured by Doppler ultrasonography of polycystic ovary syndrome (PCOS) patients and healthy women with polycystic ovarian image in ultrasonography. Forty-two patients diagnosed with PCOS according to the criteria of 2003 Rotterdam Concencus Conferance on PCOS and 38 healthy volunteers with polycystic ovarian image in ultrasonography were included in the study. Ovarian volumes and ovarian stromal artery blood flows were measured by 3-dimensional (3-D) ultrasonography and Doppler ultrasonography in all patients. In patients with PCOS, ovarian stromal artery pulsatility index (PI) and resistivity index (RI) were found significantly different from healthy women with polycystic ovarian image in ultrasonography (p < 0.05). 3-D ovarian volumes were found significantly higher in patients with PCOS (p < 0.05), and a negative correlation was also obtained between ovarian volumes and ovarian stromal artery resistivity indices. Ovarian stromal artery Doppler examination could have an importance to explain the pathophysiology of PCOS, but there are few publications in the literature about PCOS and the details of ovarian stromal artery Doppler parameters in patients with polycystic ovarian image only. We conclude that Doppler ultrasonography findings of PCOS patients might be helpful in understanding the clinical follow-up and etiology of the disease.

Evaluation of motion-correction methods for dual-gated cardiac positron emission tomography/computed tomography imaging.

PubMed

Klén, Riku; Noponen, Tommi; Koikkalainen, Juha; Lötjönen, Jyrki; Thielemans, Kris; Hoppela, Erika; Sipilä, Hannu; Teräs, Mika; Knuuti, Juhani

2016-09-01

Dual gating is a method of dividing the data of a cardiac PET scan into smaller bins according to the respiratory motion and the ECG of the patient. It reduces the undesirable motion artefacts in images, but produces several images for interpretation and decreases the quality of single images. By using motion-correction techniques, the motion artefacts in the dual-gated images can be corrected and the images can be combined into a single motion-free image with good statistics. The aim of the present study is to develop and evaluate motion-correction methods for cardiac PET studies. We have developed and compared two different methods: computed tomography (CT)/PET-based and CT-only methods. The methods were implemented and tested with a cardiac phantom and three patient datasets. In both methods, anatomical information of CT images is used to create models for the cardiac motion. In the patient study, the CT-only method reduced motion (measured as the centre of mass of the myocardium) on average 43%, increased the contrast-to-noise ratio on average 6.0% and reduced the target size on average 10%. Slightly better figures (51, 6.9 and 28%) were obtained with the CT/PET-based method. Even better results were obtained in the phantom study for both the CT-only method (57, 68 and 43%) and the CT/PET-based method (61, 74 and 52%). We conclude that using anatomical information of CT for motion correction of cardiac PET images, both respiratory and pulsatile motions can be corrected with good accuracy.

System and method for controlling depth of imaging in tissues using fluorescence microscopy under ultraviolet excitation following staining with fluorescing agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demos, Stavros; Levenson, Richard

The present disclosure relates to a method for analyzing tissue specimens. In one implementation the method involves obtaining a tissue sample and exposing the sample to one or more fluorophores as contrast agents to enhance contrast of subcellular compartments of the tissue sample. The tissue sample is illuminated by an ultraviolet (UV) light having a wavelength between about 200 nm to about 400 nm, with the wavelength being selected to result in penetration to only a specified depth below a surface of the tissue sample. Inter-image operations between images acquired under different imaging parameters allow for improvement of the imagemore » quality via removal of unwanted image components. A microscope may be used to image the tissue sample and provide the image to an image acquisition system that makes use of a camera. The image acquisition system may create a corresponding image that is transmitted to a display system for processing and display.« less

Pulsatile operation of a continuous-flow right ventricular assist device (RVAD) to improve vascular pulsatility

PubMed Central

Ng, Boon C.; Timms, Daniel; Cohn, William E.

2018-01-01

Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction. In addition, the performance of the speed modulation strategy has been assessed under different cardiovascular states, including variation in ventricular contractility and pulmonary arterial compliance. Our results indicated that the proposed pulse profile with optimised parameters (Apulse = 10000 rpm and ωmin = 3000 rpm) was able to generate pulmonary arterial pulse pressure within the physiological range (9–15 mmHg) while avoiding undesirable pump backflow under both co- and counter-pulsation modes. As compared to co-pulsation, stroke work was reduced by over 44% under counter-pulsation, suggesting that mechanical workload of the right ventricle can be efficiently mitigated through counter-pulsing the pump speed. Furthermore, our results showed that improved ventricular contractility could potentially lead to higher risk of ventricular suction and pump backflow, while stiffening of the pulmonary artery resulted in increased pulse pressure. In conclusion, the proposed speed modulation strategy produces pulsatile hemodynamics, which is more physiologic than continuous blood flow. The findings also provide valuable insight into the interaction between RVAD speed modulation and the pulmonary circulation under various cardiovascular states. PMID:29677212

Correlation between plasma pentosidine concentrations and retinal hemodynamics in patients with type 2 diabetes.

PubMed

Sato, Eiichi; Nagaoka, Taiji; Yokota, Harumasa; Takahashi, Atsushi; Yoshida, Akitoshi

2012-05-01

To investigate whether plasma pentosidine, a well-defined advanced glycation end product, is associated with retinal hemodynamic abnormalities in patients with type 2 diabetes. Prospective cross-sectional study. Forty-two eyes with type 2 diabetes mellitus were evaluated. The type 2 diabetic eyes were divided into 2 groups: 22 eyes (22 patients; mean age, 61 years) with nondiabetic retinopathy (NDR) and 20 eyes (20 patients; mean age, 61 years) with mild nonproliferative diabetic retinopathy (NPDR). We used a retinal laser Doppler system to measure the arterial diameter, velocity, and blood flow in the major temporal retinal arteries. The pulsatility ratio, a resistive index expressed as the peak systolic to the end diastolic velocity ratio, was calculated from the blood velocity traces. Plasma pentosidine was measured in 42 patients with diabetes using a commercially available competitive enzyme-linked immunosorbent assay. The pulsatility ratio significantly increased in patients with NPDR (4.8 ± 1.5) compared with patients with NDR (3.7 ± 0.8) (P = .0061). No differences in velocity, diameter, or blood flow were seen between the 2 groups. Plasma pentosidine levels also increased significantly (P = .0085) in patients with NPDR (0.057 ± 0.015) compared to patients with NDR (0.047 ± 0.012). The pulsatility ratio was correlated positively with the plasma pentosidine levels in patients with NPDR (Pearson correlation, r = 0.45, P = .044). Multiple regression analysis showed that the plasma pentosidine level was significantly associated with the pulsatility ratio (standardized coefficient, 0.62; P = .009). The vascular rigidity of the retinal arteries may increase with increasing plasma pentosidine in patients with type 2 diabetes with retinopathy. Copyright © 2012 Elsevier Inc. All rights reserved.

Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states.

PubMed

Chan, Jean L; Williams, Catherine J; Raciti, Patricia; Blakeman, Jennifer; Kelesidis, Theodore; Kelesidis, Iosif; Johnson, Michael L; Thorner, Michael O; Mantzoros, Christos S

2008-07-01

States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment. GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

Pulsatile LH secretion and ovarian follicular wave emergence and growth in anestrous ewes.

PubMed

Seekallu, Srinivas V; Barrett, David M W; Toosi, Behzad M; Clarke, Kelsey; Ewen, Kirk A; Duggavathi, Rajesha; Davies, Kate L; Pattullo, Kim M; Bagu, Edward T; Rawlings, Norman C

2010-10-01

The objective of this study was to determine if pulsatile LH secretion was needed for ovarian follicular wave emergence and growth in the anestrous ewe. In Experiment 1, ewes were either large or small (10 x 0.47 or 5 x 0.47 cm, respectively; n = 5/group) sc implants releasing estradiol-17 beta for 10 d (Day 0 = day of implant insertion), to suppress pulsed LH secretion, but not FSH secretion. Five sham-operated control ewes received no implants. In Experiment 2, 12 ewes received large estradiol-releasing implants for 12 d (Day 0 = day of implant insertion); six were given GnRH (200 ng IV) every 4 h for the last 6 d that the implants were in place (to reinitiate pulsed LH secretion) whereas six Control ewes were given saline. Ovarian ultrasonography and blood sampling were done daily; blood samples were also taken every 12 min for 6 h on Days 5 and 9, and on Days 6 and 12 of the treatment period in Experiments 1 and 2, respectively. Treatment with estradiol blocked pulsatile LH secretion (P < 0.001). In Experiment 1, implant treatment halted follicular wave emergence between Days 2 and 10. In Experiment 2, follicular waves were suppressed during treatment with estradiol, but resumed following GnRH treatment. In both experiments, the range of peaks in serum FSH concentrations that preceded and triggered follicular wave emergence was almost the same as control ewes and those given estradiol implants alone or with GnRH; mean concentrations did not differ (P < 0.05). We concluded that some level of pulsatile LH secretion was required for the emergence of follicular waves that were triggered by peaks in serum FSH concentrations in the anestrous ewe. (c) 2010 Elsevier Inc. All rights reserved.

Reduced nocturnal ACTH-driven cortisol secretion during critical illness

PubMed Central

Boonen, Eva; Meersseman, Philippe; Vervenne, Hilke; Meyfroidt, Geert; Guïza, Fabian; Wouters, Pieter J.; Veldhuis, Johannes D.

2014-01-01

Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P < 0.04). Pulsatile cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ≤ 0.03), as was ACTH-cortisol cross-approximate entropy (P ≤ 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness. PMID:24569590

An optimization formulation for characterization of pulsatile cortisol secretion.

PubMed

Faghih, Rose T; Dahleh, Munther A; Brown, Emery N

2015-01-01

Cortisol is released to relay information to cells to regulate metabolism and reaction to stress and inflammation. In particular, cortisol is released in the form of pulsatile signals. This low-energy method of signaling seems to be more efficient than continuous signaling. We hypothesize that there is a controller in the anterior pituitary that leads to pulsatile release of cortisol, and propose a mathematical formulation for such controller, which leads to impulse control as opposed to continuous control. We postulate that this controller is minimizing the number of secretory events that result in cortisol secretion, which is a way of minimizing the energy required for cortisol secretion; this controller maintains the blood cortisol levels within a specific circadian range while complying with the first order dynamics underlying cortisol secretion. We use an ℓ0-norm cost function for this controller, and solve a reweighed ℓ1-norm minimization algorithm for obtaining the solution to this optimization problem. We use four examples to illustrate the performance of this approach: (i) a toy problem that achieves impulse control, (ii) two examples that achieve physiologically plausible pulsatile cortisol release, (iii) an example where the number of pulses is not within the physiologically plausible range for healthy subjects while the cortisol levels are within the desired range. This novel approach results in impulse control where the impulses and the obtained blood cortisol levels have a circadian rhythm and an ultradian rhythm that are in agreement with the known physiology of cortisol secretion. The proposed formulation is a first step in developing intermittent controllers for curing cortisol deficiency. This type of bio-inspired pulse controllers can be employed for designing non-continuous controllers in brain-machine interface design for neuroscience applications.

Effects of Anti-Hypertensive Monotherapy with Either Calcium Channel Blocker or Angiotensin Receptor Blocker on Arterial Stiffness, Central Hemodynamics, and Ventriculo-Arterial Coupling in Uncomplicated Hypertension Patients

PubMed Central

Lin, Heng-Hsu; Wang, Chia-Sung; Lin, Jiunn-Lee; Hwang, Juey-Jen; Lin, Lian-Yu

2013-01-01

Objectives This study is designed to investigate the effects of anti-hypertensive monotherapy [either calcium channel blocker (CCB) or angiotensin receptor blocker (ARB)] on pulsatile hemodynamic parameters in patients with uncomplicated hypertension. Methods This is a longitudinal observational study. For simplicity, we included patients with uncomplicated hypertension who receivedmono anti-hypertensive therapy with ARB or CCB. Hemodynamic parameters including central arterial pressure (CAP), aortic characteristic impedance (Zc), augmentation index (AI), brachial-ankle pulse wave velocity (baPWV), heart-ankle pulse wave velocity (haPWV), cardiac ultrasonographic parameters and ventriculo-arterial (VA) coupling were measured before, 1 month and 3 months after treatment. Results A total of 74 subjects were included in our study for analysis from 2007-2008. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and central systolic arterial pressure (CSAP) were significantly reduced 1 and 3 months after initiation of therapy. Among the pulsatile hemodynamic parameters, only the baPWV was significantly reduced (from1537.78 ± 200.63 cm/s to 1460.06 ± 186.09 cm/s to 1456.53 ± 196.03 cm/s, p for trend = 0.016). The haPWV only decreased with borderline significance (from 1015.38 ± 124.26 cm/s to 978.88 ± 126.55 cm/s to 967.99 ± 103.37 cm/s, p for trend = 0.041). The other pulsatile hemodynamic parameters remained unchanged before and after therapy. Subgroup analysis (age above or below52 years) showed that the baPWVwas significantly reduced only in the younger group. Conclusions Among the pulsatile hemodynamic parameters, only the baPWV was effectively reduced by either CCB or ARB. The improvement of PWV was more evident in younger subjects. PMID:27122681

A neurokinin 3 receptor-selective agonist accelerates pulsatile luteinizing hormone secretion in lactating cattle.

PubMed

Nakamura, Sho; Wakabayashi, Yoshihiro; Yamamura, Takashi; Ohkura, Satoshi; Matsuyama, Shuichi

2017-07-01

Pulsatile gonadotropin-releasing hormone (GnRH) secretion, which is indispensable for follicular development, is suppressed in lactating dairy and beef cattle. Neurokinin B (NKB) neurons in the arcuate nucleus of the hypothalamus are considered to play an essential role in generating the pulsatile mode of GnRH/luteinizing hormone (LH) secretion. The present study aimed to clarify the role of NKB-neurokinin 3 receptor (NK3R) signaling in the pulsatile pattern of GnRH/gonadotropin secretion in postpartum lactating cattle. We examined the effects of the administration of an NK3R-selective agonist, senktide, on gonadotropin secretion in lactating cattle. The lactating cattle, at approximately 7 days postpartum, were intravenously infused with senktide (30 or 300 nmol/min) or vehicle for 24 h. The administration of 30 or 300 nmol/min senktide significantly increased LH pulse frequency compared to in the control group during 0-4 or 20-24 h after infusion, respectively. Moreover, LH and follicle-stimulating hormone levels were gradually increased by 300 nmol/min administration of senktide during the 0-4-h sampling period. Ultrasonography of the ovaries was performed to identify the first postpartum ovulation in senktide-administered lactating cattle. The interval from calving to first postpartum ovulation was significantly shorter in the 300 nmol/min senktide-administered group than in the control group. Taken together, these findings suggest that senktide infusion elicits an increase in LH pulse frequency that may stimulate follicular development and, in turn, induce the first postpartum ovulation in lactating cattle. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Can time-averaged flow boundary conditions be used to meet the clinical timeline for Fontan surgical planning?

PubMed

Wei, Zhenglun Alan; Trusty, Phillip M; Tree, Mike; Haggerty, Christopher M; Tang, Elaine; Fogel, Mark; Yoganathan, Ajit P

2017-01-04

Cardiovascular simulations have great potential as a clinical tool for planning and evaluating patient-specific treatment strategies for those suffering from congenital heart diseases, specifically Fontan patients. However, several bottlenecks have delayed wider deployment of the simulations for clinical use; the main obstacle is simulation cost. Currently, time-averaged clinical flow measurements are utilized as numerical boundary conditions (BCs) in order to reduce the computational power and time needed to offer surgical planning within a clinical time frame. Nevertheless, pulsatile blood flow is observed in vivo, and its significant impact on numerical simulations has been demonstrated. Therefore, it is imperative to carry out a comprehensive study analyzing the sensitivity of using time-averaged BCs. In this study, sensitivity is evaluated based on the discrepancies between hemodynamic metrics calculated using time-averaged and pulsatile BCs; smaller discrepancies indicate less sensitivity. The current study incorporates a comparison between 3D patient-specific CFD simulations using both the time-averaged and pulsatile BCs for 101 Fontan patients. The sensitivity analysis involves two clinically important hemodynamic metrics: hepatic flow distribution (HFD) and indexed power loss (iPL). Paired demographic group comparisons revealed that HFD sensitivity is significantly different between single and bilateral superior vena cava cohorts but no other demographic discrepancies were observed for HFD or iPL. Multivariate regression analyses show that the best predictors for sensitivity involve flow pulsatilities, time-averaged flow rates, and geometric characteristics of the Fontan connection. These predictors provide patient-specific guidelines to determine the effectiveness of analyzing patient-specific surgical options with time-averaged BCs within a clinical time frame. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cerebral Hemodynamics in the Elderly: A Transcranial Doppler Study in the Einstein Aging Study Cohort.

PubMed

Yang, Dixon; Cabral, Digna; Gaspard, Emmanuel N; Lipton, Richard B; Rundek, Tatjana; Derby, Carol A

2016-09-01

We sought to describe the relationship between age, sex, and race/ethnicity with transcranial Doppler hemodynamic characteristics from major intracerebral arterial segments in a large elderly population with varying demographics. We analyzed 369 stroke-free participants aged 70 years and older from the Einstein Aging Study. Single-gate, nonimaging transcranial Doppler sonography, a noninvasive sonographic technique that assesses real-time cerebrovascular hemodynamics, was used to interrogate 9 cerebral arterial segments. Individual Doppler spectra and cerebral blood flow velocities were acquired, and the pulsatility index and resistive index were calculated by the device's automated waveform-tracking function. Multiple linear regression models were used to examine the independent associations of age, sex, and race/ethnicity with transcranial Doppler measures, adjusting for hypertension, history of myocardial infarction or revascularization, and history of diabetes. Among enrolled participants, 303 individuals had at least 1 vessel insonated (mean age [SD], 80 [6] years; 63% women; 58% white; and 32% black). With age, transcranial Doppler measures of mean blood flow velocity were significantly decreased in the basilar artery (P = .001) and posterior cerebral artery (right, P = .003; left, P = .02). Pulsatility indices increased in the left middle cerebral artery (P = .01) and left anterior cerebral artery (P = .03), and the resistive index was increased in the left middle cerebral artery (P = .007) with age. Women had higher pulsatility and resistive indices compared to men in several vessels. We report a decreased mean blood flow velocity and weakly increased arterial pulsatility and resistance with aging in a large elderly stroke-free population. These referential trends in cerebrovascular hemodynamics may carry important implications in vascular diseases associated with advanced age, increased risk of cerebrovascular disease, cognitive decline, and dementia.

Fluid-structure interaction of a pulsatile flow with an aortic valve model: A combined experimental and numerical study.

PubMed

Sigüenza, Julien; Pott, Desiree; Mendez, Simon; Sonntag, Simon J; Kaufmann, Tim A S; Steinseifer, Ulrich; Nicoud, Franck

2018-04-01

The complex fluid-structure interaction problem associated with the flow of blood through a heart valve with flexible leaflets is investigated both experimentally and numerically. In the experimental test rig, a pulse duplicator generates a pulsatile flow through a biomimetic rigid aortic root where a model of aortic valve with polymer flexible leaflets is implanted. High-speed recordings of the leaflets motion and particle image velocimetry measurements were performed together to investigate the valve kinematics and the dynamics of the flow. Large eddy simulations of the same configuration, based on a variant of the immersed boundary method, are also presented. A massively parallel unstructured finite-volume flow solver is coupled with a finite-element solid mechanics solver to predict the fluid-structure interaction between the unsteady flow and the valve. Detailed analysis of the dynamics of opening and closure of the valve are conducted, showing a good quantitative agreement between the experiment and the simulation regarding the global behavior, in spite of some differences regarding the individual dynamics of the valve leaflets. A multicycle analysis (over more than 20 cycles) enables to characterize the generation of turbulence downstream of the valve, showing similar flow features between the experiment and the simulation. The flow transitions to turbulence after peak systole, when the flow starts to decelerate. Fluctuations are observed in the wake of the valve, with maximum amplitude observed at the commissure side of the aorta. Overall, a very promising experiment-vs-simulation comparison is shown, demonstrating the potential of the numerical method. Copyright © 2017 John Wiley & Sons, Ltd.

Intracranial hypotension and hypertension in children and adolescents.

PubMed

Ozge, Aynur; Bolay, Hayrunnisa

2014-07-01

The specific aim of this review is to report the features of intracranial pressure changes [spontaneous intracranial hypotension (SIH) and idiopathic intracranial hypertension (IIH)] in children and adolescents, with emphasis on the presentation, diagnosis, and treatment modalities. Headache associated with intracranial pressure changes are relatively rare and less known in children and adolescents. SIH is a specific syndrome involving reduced intracranial pressure with orthostatic headache, frequently encountered connective tissue disorders, and a good prognosis with medical management, initial epidural blood patching, and sometimes further interventions may be required. IIH is an uncommon condition in children and different from the disease in adults, not only with respect to clinical features (likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus) but also different in outcome. Consequently, specific ICP changes of pediatric ages required specific attention both of exact diagnosis and entire management.

Evaluation of hemodynamics changes during interventional stent placement using Doppler optical coherence tomography

NASA Astrophysics Data System (ADS)

Vuong, Barry; Genis, Helen; Wong, Ronnie; Ramjist, Joel; Jivraj, Jamil; Farooq, Hamza; Sun, Cuiru; Yang, Victor X. D.

2015-03-01

Carotid atherosclerosis is a critical medical concern that can lead to ischemic stroke. Local hemodynamic patterns have also been associated with the development of atherosclerosis, particularly in regions with disturbed flow patterns such as bifurcations. Traditionally, this disease was treated using carotid endarterectomy, however recently there is an increasing trend of carotid artery stenting due to its minimally invasive nature. It is well known that this interventional technique creates changes in vasculature geometry and hemodynamic patterns due to the interaction of stent struts with arterial lumen, and is associated with complications such as distal emboli and restenosis. Currently, there is no standard imaging technique to evaluate regional hemodynamic patterns found in stented vessels. Doppler optical coherence tomography (DOCT) provides an opportunity to identify in vivo hemodynamic changes in vasculature using high-resolution imaging. In this study, blood flow profiles were examined at the bifurcation junction in the internal carotid artery (ICA) in a porcine model following stent deployment. Doppler imaging was further conducted using pulsatile flow in a phantom model, and then compared to computational fluid dynamics (CFD) simulation of a virtual bifurcation to assist with the interpretation of emphin vivo results.

CFD and PIV Analysis of Hemodynamics in a Growing Intracranial Aneurysm

PubMed Central

Raschi, Marcelo; Mut, Fernando; Byrne, Greg; Putman, Christopher M.; Tateshima, Satoshi; Viñuela, Fernando; Tanoue, Tetsuya; Tanishita, Kazuo; Cebral, Juan R.

2011-01-01

Hemodynamics is thought to be a fundamental factor in the formation, progression and rupture of cerebral aneurysms. Understanding these mechanisms is important to improve their rupture risk assessment and treatment. In this study we analyze the blood flow field in a growing cerebral aneurysm using experimental particle image velocimetry (PIV) and computational fluid dynamics (CFD) techniques. Patient-specific models were constructed from longitudinal 3D computed tomography angiography (CTA) images acquired at one-year intervals. Physical silicone models were constructed from the CTA images using rapid prototyping techniques and pulsatile flow fields were measured with PIV. Corresponding CFD models were created and run under matching flow conditions. Both flow fields were aligned, interpolated, and compared qualitatively by inspection and quantitatively by defining similarity measures between the PIV and CFD vector fields. Results showed that both flow fields were in good agreement. Specifically, both techniques provided consistent representations of the main intra-aneurysmal flow structures, and their change during the geometric evolution of the aneurysm. Despite differences observed mainly in the near wall region and the inherent limitations of each technique, the information derived is consistent and can be used to study the role of hemodynamics in the natural history of intracranial aneurysms. PMID:22548127

Magnetoacoustic imaging of human liver tumor with magnetic induction

NASA Astrophysics Data System (ADS)

Hu, Gang; Cressman, Erik; He, Bin

2011-01-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is an imaging technique under development to achieve imaging of electrical impedance contrast in biological tissues with spatial resolution close to ultrasound imaging. However, previously reported MAT-MI experimental results are obtained either from low salinity gel phantoms, or from normal animal tissue samples. In this study, we report the experimental study on the performance of the MAT-MI imaging method for imaging in vitro human liver tumor tissue. The present promising experimental results suggest the feasibility of MAT-MI to image electrical impedance contrast between the cancerous tissue and its surrounding normal tissues.

Objective breast tissue image classification using Quantitative Transmission ultrasound tomography

NASA Astrophysics Data System (ADS)

Malik, Bilal; Klock, John; Wiskin, James; Lenox, Mark

2016-12-01

Quantitative Transmission Ultrasound (QT) is a powerful and emerging imaging paradigm which has the potential to perform true three-dimensional image reconstruction of biological tissue. Breast imaging is an important application of QT and allows non-invasive, non-ionizing imaging of whole breasts in vivo. Here, we report the first demonstration of breast tissue image classification in QT imaging. We systematically assess the ability of the QT images’ features to differentiate between normal breast tissue types. The three QT features were used in Support Vector Machines (SVM) classifiers, and classification of breast tissue as either skin, fat, glands, ducts or connective tissue was demonstrated with an overall accuracy of greater than 90%. Finally, the classifier was validated on whole breast image volumes to provide a color-coded breast tissue volume. This study serves as a first step towards a computer-aided detection/diagnosis platform for QT.

Effects of short-term feed deprivation and melatonin implants on circadian patterns of leptin in the horse.

PubMed

Buff, P R; Morrison, C D; Ganjam, V K; Keisler, D H

2005-05-01

Leptin is a protein hormone produced by adipose tissue that influences hypothalamic mechanisms regulating appetite and energy balance. In species tested thus far, including horses, concentrations of leptin increase as animal fat mass increases. The variables and mechanisms that influence the secretion of leptin are not well known, nor is it known in equine species how the secretion of leptin is influenced by acute alterations in energy balance, circadian patterns, and/or reproductive competence. Our objectives were to determine in horses: 1) whether plasma concentrations of leptin are secreted in a circadian and/or a pulsatile pattern; 2) whether a 48-h period of feed restriction would alter plasma concentrations of leptin, growth hormone, or insulin; and 3) whether ovariectomy and/or a melatonin implant would affect leptin. In Exp. 1, mares exposed to ambient photoperiod of visible light (11 h, 33 min to 11 h, 38 min), received treatments consisting of a 48-h feed restriction (RES) or 48 h of alfalfa hay fed ad libitum (FED). Mares were maintained in a dry lot before sampling and were tethered to a rail during sampling. Analyses revealed that leptin was not secreted in a pulsatile manner, and that mean leptin concentrations were greater (P < 0.001) in FED vs. RES mares (17.20 +/- 0.41 vs. 7.29 +/- 0.41 ng/mL). Plasma growth hormone was pulsatile, and mean concentrations were greater in RES than FED mares (2.15 +/- 0.31 vs. 1.08 +/- 0.31 ng/mL; P = 0.05). Circadian patterns of leptin secretion were observed, but only in FED mares (15.39 +/- 0.58 ng/mL for morning vs. 19.00 +/- 0.58 ng/mL for evening; P < 0.001). In Exp. 2, mares that were ovariectomized or intact received either a s.c. melatonin implant or a sham implant. Thereafter, blood was sampled at weekly intervals at 1000 and 1700. Concentrations of leptin in samples collected at 1700 were greater (P < 0.001) than in those collected at 1000 (28.24 +/- 1.7 vs. 22.07 +/- 1.7 ng/mL). Neither ovariectomy nor chronic treatment with melatonin affected plasma concentrations of leptin or the circadian pattern of secretion. These data provide evidence that plasma leptin concentrations in the equine are sensitive to acute changes in nutritional status and vary in a circadian pattern that is sensitive to fasting but not to melatonin treatment or ovariectomy.

X-ray Phase Contrast Allows Three Dimensional, Quantitative Imaging of Hydrogel Implants

PubMed Central

Appel, Alyssa A.; Larson, Jeffery C.; Jiang, Bin; Zhong, Zhong; Anastasio, Mark A.; Brey, Eric M.

2015-01-01

Three dimensional imaging techniques are needed for the evaluation and assessment of biomaterials used for tissue engineering and drug delivery applications. Hydrogels are a particularly popular class of materials for medical applications but are difficult to image in tissue using most available imaging modalities. Imaging techniques based on X-ray Phase Contrast (XPC) have shown promise for tissue engineering applications due to their ability to provide image contrast based on multiple X-ray properties. In this manuscript, we investigate the use of XPC for imaging a model hydrogel and soft tissue structure. Porous fibrin loaded poly(ethylene glycol) hydrogels were synthesized and implanted in a rodent subcutaneous model. Samples were explanted and imaged with an analyzer-based XPC technique and processed and stained for histology for comparison. Both hydrogel and soft tissues structures could be identified in XPC images. Structure in skeletal muscle adjacent could be visualized and invading fibrovascular tissue could be quantified. There were no differences between invading tissue measurements from XPC and the gold-standard histology. These results provide evidence of the significant potential of techniques based on XPC for 3D imaging of hydrogel structure and local tissue response. PMID:26487123

TH-CD-206-01: Expectation-Maximization Algorithm-Based Tissue Mixture Quantification for Perfusion MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, H; Xing, L; Liang, Z

Purpose: To investigate the feasibility of estimating the tissue mixture perfusions and quantifying cerebral blood flow change in arterial spin labeled (ASL) perfusion MR images. Methods: The proposed perfusion MR image analysis framework consists of 5 steps: (1) Inhomogeneity correction was performed on the T1- and T2-weighted images, which are available for each studied perfusion MR dataset. (2) We used the publicly available FSL toolbox to strip off the non-brain structures from the T1- and T2-weighted MR images. (3) We applied a multi-spectral tissue-mixture segmentation algorithm on both T1- and T2-structural MR images to roughly estimate the fraction of eachmore » tissue type - white matter, grey matter and cerebral spinal fluid inside each image voxel. (4) The distributions of the three tissue types or tissue mixture across the structural image array are down-sampled and mapped onto the ASL voxel array via a co-registration operation. (5) The presented 4-dimensional expectation-maximization (4D-EM) algorithm takes the down-sampled three tissue type distributions on perfusion image data to generate the perfusion mean, variance and percentage images for each tissue type of interest. Results: Experimental results on three volunteer datasets demonstrated that the multi-spectral tissue-mixture segmentation algorithm was effective to initialize tissue mixtures from T1- and T2-weighted MR images. Compared with the conventional ASL image processing toolbox, the proposed 4D-EM algorithm not only generated comparable perfusion mean images, but also produced perfusion variance and percentage images, which the ASL toolbox cannot obtain. It is observed that the perfusion contribution percentages may not be the same as the corresponding tissue mixture volume fractions estimated in the structural images. Conclusion: A specific application to brain ASL images showed that the presented perfusion image analysis method is promising for detecting subtle changes in tissue perfusions, which is valuable for the early diagnosis of certain brain diseases, e.g. multiple sclerosis.« less

A painful pulsatile abdominal mass in a young man with elevated blood pressures: an unusual presentation of phaeochromocytoma.

PubMed

Lee, B M K; Ti, L K

2002-08-01

We report an unusual presentation of phaeochromocytoma in a young man with a painful, pulsatile abdominal mass and elevated blood pressures. This led to a delay in diagnosis and resulted in the administration of triggers of catecholamine release, possibly causing a catecholamine surge. This caused the development of catecholamine-induced cardiomyopathy and multiple organ failure, requiring inotropic and ventilatory support, intra-aortic balloon pump and dialysis. Fortunately, his condition reversed with supportive treatment and alpha-adrenergic blockade. This illustrates the importance of having a high index of suspicion of phaeochromocytoma, especially in young patients with elevated blood pressures.

Predictable pulsatile release of tramadol hydrochloride for chronotherapeutics of arthritis.

PubMed

Dabhi, Chandu; Randale, Shivsagar; Belgamwar, Veena; Gattani, Surendra; Tekade, Avinash

2010-07-01

The present investigation deals with the development of a pH and time-dependent press-coated pulsatile drug delivery system for delivering drugs into the colon. The system consists of a drug containing core, coated by a combination of natural polymer Delonix regia gum (DRG) and hydroxypropyl methylcellulose (HPMC K4M) in various proportions, which controls the onset of release. The whole system was coated with methacrylic acid copolymers, which not only prevents the drug release in the stomach, but also prolongs the lag time. Tramadol HCl was used as a model drug and varying combinations of DRG and HPMC K4M were used to achieve the desired lag time before rapid and complete release of the drug in the colon. It was observed that the lag time depends on the coating ratio of DRG to HPMC and also on press coating weight. Drug release was found to be increased by 15-30% in the presence of colonic microbial flora. The results showed the capability of the system in achieving pulsatile release for a programmable period of time and pH-dependent release to attain colon-targeted delivery.

The effects of the pulsatile period on the size of recirculation bubble in the vicinity of stent struts

NASA Astrophysics Data System (ADS)

Jiang, B.; Thondapu, V.; Barlis, P.; Poon, E. K. W.; Ooi, A. S. H.

2017-04-01

Incomplete stent apposition (ISA) is sometimes found in stent deployment at complex lesions, and it is considered to be one of the causes of post-stenting complications, such as late stent thrombosis and restenosis. The presence of ISA leads to large recirculation bubbles behind the stent struts, which can reduce shear stress at the arterial wall that retards neointimal formation process and thus lead to complications. Computational fluid dynamics (CFD) simulations are performed on simplified two-dimensional axisymmetric arterial models with stents struts of square and circular cross-sectional shapes at a malapposition distance of 120 μm from the arterial wall. To investigate the effects of pulsatile flow period on the dynamics of the recirculation bubbles, high fidelity simulations are carried out with pulsatile flows of period 0.4 s and 0.8 s. Under the condition of the same flow rate, both square and circular strut cases show that shorter period provides greater flow deceleration, leading to the formation of a larger recirculation bubble. With the same thickness, circular strut has a significant improvement over the square strut in terms of the size of the recirculation bubble, and therefore less likely to lead to complications.

Distinctive features of "chronotherapeutic" and "pulsatile" drug delivery systems negating the practice of their interchangeable terminology.

PubMed

Ali, Javed; Baboota, Sanjula; Ahuja, Alka; Saigal, Nitin

2010-07-01

The term pulsatile drug delivery has often been used as a synonym to chronotherapeutic drug delivery. This needs to be given a thought as both the drug delivery systems are entirely addressing different needs of the patients as well as the intentions of the formulators being different. Chronotherapeutic systems are based completely on circadian needs and response of the body and the need of the drug to be in its maximum concentrations at a particular time of the day, the fact being supported by endless list of ailments which elicit the related symptoms at a particular time of the day. Considering the formulation approach, one does not find major differences among site-specific chronotherapeutic systems and the basic and more conventional intestinal or colon targeted systems due to the mechanism and the site of landing of drug of both being almost similar even though the intention of the formulator being different. An ideal pulsatile system is the one delivering drug in different pulses with multiple troughs in release profile. The article explores the major differences in between the two systems and highlights the need of using appropriate terminology for these individual and distinct systems catering different needs.

Processing oscillatory signals by incoherent feedforward loops

NASA Astrophysics Data System (ADS)

Zhang, Carolyn; Wu, Feilun; Tsoi, Ryan; Shats, Igor; You, Lingchong

From the timing of amoeba development to the maintenance of stem cell pluripotency,many biological signaling pathways exhibit the ability to differentiate between pulsatile and sustained signals in the regulation of downstream gene expression.While networks underlying this signal decoding are diverse,many are built around a common motif, the incoherent feedforward loop (IFFL),where an input simultaneously activates an output and an inhibitor of the output.With appropriate parameters,this motif can generate temporal adaptation,where the system is desensitized to a sustained input.This property serves as the foundation for distinguishing signals with varying temporal profiles.Here,we use quantitative modeling to examine another property of IFFLs,the ability to process oscillatory signals.Our results indicate that the system's ability to translate pulsatile dynamics is limited by two constraints.The kinetics of IFFL components dictate the input range for which the network can decode pulsatile dynamics.In addition,a match between the network parameters and signal characteristics is required for optimal ``counting''.We elucidate one potential mechanism by which information processing occurs in natural networks with implications in the design of synthetic gene circuits for this purpose. This work was partially supported by the National Science Foundation Graduate Research Fellowship (CZ).

Behaviour of beta 2-adrenoceptors on lymphocytes under continuous and pulsatile tocolysis with Fenoterol.

PubMed

Schmidt-Rhode, Peter; Brunke, Björn; Schröer, Heinrich; Obert, Kirstin; Schlegel, Kerstin; Sturm, Gerhard; Schulz, Klaus-Dieter; von Wichert, Peter

2003-01-01

The present study investigates the population of beta 2-receptors on lymphocytes in pregnant women with premature labor between the 29th and 34th week of pregnancy. The population of receptors on lymphocytes correlates with that on the myometrium, which is not accessible for study during pregnancy. Fourteen patients received a pulsatile tocolysis, while ten women received a continuous tocolysis with Fenoterol. Assuming an equal population of receptors in both groups before commencement of therapy, the numbers of receptors in the patients with continuous tocolysis fell to about 35% of the initial value after 72 hours. Under pulsatile tocolysis, the numbers of receptors remained unchanged for a period of three days and was still only just below 70% of the initial value by the seventh day. Our data demonstrate that continuous administration of the short-acting beta 2-agonist Fenoterol resulted in a substantial loss of beta 2-adrenoceptors on lymphocytes. In contrast, intermittent administration of the same beta 2-adrenergic agonist prevented the onset of receptor down-regulation in pregnant women with preterm labor. Further studies are required to investigate the impact of the decreased loss of beta 2-adrenoceptor density on the good clinical experience with intermittent tocolysis.

Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation

PubMed Central

Lysyansky, Borys; Rosenblum, Michael; Pikovsky, Arkady; Tass, Peter A.

2017-01-01

High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson’s disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS. PMID:28273176

Physiological interpretation of Doppler shift waveforms: the femorodistal segment in combined disease.

PubMed

Campbell, W B; Baird, R N; Cole, S E; Evans, J M; Skidmore, R; Woodcock, J P

1983-01-01

A new method is presented for assessing the femorodistal segment in multisegmental arterial disease, using the Laplace transform technique of Doppler waveform analysis. Blood velocity/time waveforms were obtained at femoral and ankle levels in three groups of limbs--50 without arterial disease, 12 with isolated aortoiliac stenoses, and 32 with femoropopliteal occlusions, with and without proximal disease. The waveforms were analysed for Laplace transform and pulsatility index values. The omega 0 coefficients of the Laplace transform analysis at femoral and ankle levels were compared in each subject, as the omega 0 gradient (femoral/ankle omega 0): and pulsatility index damping factor (femoral/ankle P1) was also calculated. The omega 0 gradient was shown to detect femoropopliteal occlusion in the presence of multisegmental arterial disease and to give some indication of its haemodynamic significance. The diagnostic accuracy of the omega 0 gradient was superior to that of pulsatility index damping factor. When combined with its existing ability to detect aortoiliac stenosis, this new application of the Laplace transform method offers the possibility both of a system for complete localisation of significant arterial lesions, and potential for follow-up of vascular surgical procedures in the lower limb, from two simple Doppler recordings.

Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone.

PubMed

Czajkowski, Krzysztof; Sienko, Jacek; Mogilinski, Mariusz; Bros, Magdalena; Szczecina, Roman; Czajkowska, Anna

2007-03-01

To compare the influence of vaginal micronized progesterone and oral dydrogesterone supplementation on uteroplacental circulation in early pregnancy that is complicated by threatened abortion. Randomized, parallel group, double-blind, double dummy-controlled study. Tertiary care university hospital. Fifty-three patients with threatened abortion and a living embryo. Three hundred milligrams of micronized vaginal progesterone or 30 mg of oral dydrogesterone daily supplementation for 6 weeks, serial transvaginal Doppler ultrasound measurement of pulsatility index, resistance index, and systolic/diastolic ratio of the spiral arteries, the uterine arteries, and the intrachorionic area. Uteroplacental blood flow. The study demonstrated that vaginal progesterone administration, but not oral dydrogesterone treatment, results in the decrease in the spiral artery pulsatility and resistance index and systolic/diastolic ratio. Insignificant decrease in pulsatility index and resistance index of the uterine artery was observed at >9 weeks and was not associated with treatment regimen. Dydrogesterone treatment was only accompanied by the decrease in the uterine artery systolic/diastolic ratio. Vaginal progesterone and oral dydrogesterone supplementation have a different influence on the uteroplacental circulation in early pregnancy that is complicated by threatened abortion.

Processing Oscillatory Signals by Incoherent Feedforward Loops

PubMed Central

Zhang, Carolyn; You, Lingchong

2016-01-01

From the timing of amoeba development to the maintenance of stem cell pluripotency, many biological signaling pathways exhibit the ability to differentiate between pulsatile and sustained signals in the regulation of downstream gene expression. While the networks underlying this signal decoding are diverse, many are built around a common motif, the incoherent feedforward loop (IFFL), where an input simultaneously activates an output and an inhibitor of the output. With appropriate parameters, this motif can exhibit temporal adaptation, where the system is desensitized to a sustained input. This property serves as the foundation for distinguishing input signals with varying temporal profiles. Here, we use quantitative modeling to examine another property of IFFLs—the ability to process oscillatory signals. Our results indicate that the system’s ability to translate pulsatile dynamics is limited by two constraints. The kinetics of the IFFL components dictate the input range for which the network is able to decode pulsatile dynamics. In addition, a match between the network parameters and input signal characteristics is required for optimal “counting”. We elucidate one potential mechanism by which information processing occurs in natural networks, and our work has implications in the design of synthetic gene circuits for this purpose. PMID:27623175

3D on-chip microscopy of optically cleared tissue

NASA Astrophysics Data System (ADS)

Zhang, Yibo; Shin, Yoonjung; Sung, Kevin; Yang, Sam; Chen, Harrison; Wang, Hongda; Teng, Da; Rivenson, Yair; Kulkarni, Rajan P.; Ozcan, Aydogan

2018-02-01

Traditional pathology relies on tissue biopsy, micro-sectioning, immunohistochemistry and microscopic imaging, which are relatively expensive and labor-intensive, and therefore are less accessible in resource-limited areas. Low-cost tissue clearing techniques, such as the simplified CLARITY method (SCM), are promising to potentially reduce the cost of disease diagnosis by providing 3D imaging and phenotyping of thicker tissue samples with simpler preparation steps. However, the mainstream imaging approach for cleared tissue, fluorescence microscopy, suffers from high-cost, photobleaching and signal fading. As an alternative approach to fluorescence, here we demonstrate 3D imaging of SCMcleared tissue using on-chip holography, which is based on pixel-super-resolution and multi-height phase recovery algorithms to digitally compute the sample's amplitude and phase images at various z-slices/depths through the sample. The tissue clearing procedures and the lens-free imaging system were jointly optimized to find the best illumination wavelength, tissue thickness, staining solution pH, and the number of hologram heights to maximize the imaged tissue volume, minimize the amount of acquired data, while maintaining a high contrast-to-noise ratio for the imaged cells. After this optimization, we achieved 3D imaging of a 200-μm thick cleared mouse brain tissue over a field-of-view of <20mm2 , and the resulting 3D z-stack agrees well with the images acquired with a scanning lens-based microscope (20× 0.75NA). Moreover, the lens-free microscope achieves an order-of-magnitude better data efficiency compared to its lens-based counterparts for volumetric imaging of samples. The presented low-cost and high-throughput lens-free tissue imaging technique enabled by CLARITY can be used in various biomedical applications in low-resource-settings.

Application of gonadotropin releasing hormone in hypogonadotropic hypogonadism--diagnostic and therapeutic aspects.

PubMed

Delemarre-van de Waal, Henriette A

2004-11-01

Puberty is the result of reactivation of the gonadotropin releasing hormone (GnRH) pulse generator resulting in an increasing release of GnRH by the hypothalamus, which stimulates the gonadotropic cells of the pituitary to synthesize and secrete LH and FSH. Hypogonadotropic hypogonadism (HH) is often the result of GnRH deficiency. The clinical picture is characterized by the absence of pubertal development and infertility. It is difficult to differentiate HH from delayed puberty since low gonadotropin and low testosterone levels are found in both conditions. We hypothesized that long-term GnRH administration may differentiate between the two conditions by a difference in the increase of gonadotropins, the idea being that in normal delayed puberty the pituitary of the patient has been primed with GnRH during the fetal and early postnatal period. Seventeen adolescents suspected of having hypogonadotropic hypogonadism were treated with pulsatile GnRH for 7 days. At the present time, the diagnosis of these patients is known and the results of the long-term GnRH stimulation have been evaluated according to the present diagnosis. The results show that the increase in gonadotropins following GnRH treatment is similar in both conditions. Therefore, at a prepubertal age a normal delayed puberty cannot be distinguished from hypogonadotropic hypogonadism using long-term GnRH stimulation. Long-term pulsatile GnRH treatment is a physiological therapy for the induction of puberty. Unlike testosterone it has the advantage of stimulation of testicular growth and fertility, as well as virilization, in males. We have treated 68 male patients with HH with pulsatile GnRH. The results show testicular growth and virilization in all the patients and spermatogenesis in 58 patients. Wearing a portable pump is cumbersome. However, the patients were very motivated and adapted very easily to this inconvenience. When spermatogenesis had developed, GnRH treatment was changed to human chorionic gonadotropin (hCG) administration 1-2 times per week intramuscularly or subcutaneously. During hCG therapy spermatogenesis was maintained or even improved. At least ten patients fathered children. Pulsatile GnRH cannot distinguish between a normal delayed puberty and a hypothalamic defect in still prepubertal patients. Pulsatile GnRH offers an appropriate way to initiate testicular growth including virilization and fertility in males with hypogonadotropic hypogonadism.

A polarization sensitive hyperspectral imaging system for detection of differences in tissue properties

NASA Astrophysics Data System (ADS)

Peller, Joseph A.; Ceja, Nancy K.; Wawak, Amanda J.; Trammell, Susan R.

2018-02-01

Polarized light imaging and optical spectroscopy can be used to distinguish between healthy and diseased tissue. In this study, the design and testing of a single-pixel hyperspectral imaging system that uses differences in the polarization of light reflected from tissue to differentiate between healthy and thermally damaged tissue is discussed. Thermal lesions were created in porcine skin (n = 8) samples using an IR laser. The damaged regions were clearly visible in the polarized light hyperspectral images. Reflectance hyperspectral and white light imaging was also obtained for all tissue samples. Sizes of the thermally damaged regions as measured via polarized light hyperspectral imaging are compared to sizes of these regions as measured in the reflectance hyperspectral images and white light images. Good agreement between the sizes measured by all three imaging modalities was found. Hyperspectral polarized light imaging can differentiate between healthy and damaged tissue. Possible applications of this imaging system include determination of tumor margins during cancer surgery or pre-surgical biopsy.

Imaging biological tissues with electrical conductivity contrast below 1 S m−1 by means of magnetoacoustic tomography with magnetic induction

PubMed Central

Hu, Gang; Li, Xu; He, Bin

2010-01-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is a recently introduced imaging modality for noninvasive electrical impedance imaging, with ultrasound imaging resolution and a contrast reflecting the electrical conductivity properties of tissues. However, previous MAT-MI systems can only image samples that are much more conductive than real human or animal tissues. To image real biological tissue samples, a large-current-carrying coil that can give stronger magnetic stimulations and stronger MAT-MI acoustic signals is employed in this study. The conductivity values of all the tissue samples employed in this study are also directly measured using a well calibrated four-electrode system. The experimental results demonstrated the feasibility to image biological tissues with electrical conductivity contrast below 1.0 S∕m using the MAT-MI technique with safe level of electromagnetic energy applied to tissue samples. PMID:20938494

Imaging biological tissues with electrical conductivity contrast below 1 S m-1 by means of magnetoacoustic tomography with magnetic induction

NASA Astrophysics Data System (ADS)

Hu, Gang; Li, Xu; He, Bin

2010-09-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is a recently introduced imaging modality for noninvasive electrical impedance imaging, with ultrasound imaging resolution and a contrast reflecting the electrical conductivity properties of tissues. However, previous MAT-MI systems can only image samples that are much more conductive than real human or animal tissues. To image real biological tissue samples, a large-current-carrying coil that can give stronger magnetic stimulations and stronger MAT-MI acoustic signals is employed in this study. The conductivity values of all the tissue samples employed in this study are also directly measured using a well calibrated four-electrode system. The experimental results demonstrated the feasibility to image biological tissues with electrical conductivity contrast below 1.0 S/m using the MAT-MI technique with safe level of electromagnetic energy applied to tissue samples.

High resolution microendoscopy with structured illumination and Lugol's iodine staining for evaluation of breast cancer architecture

NASA Astrophysics Data System (ADS)

Dobbs, Jessica; Kyrish, Matthew; Krishnamurthy, Savitri; Grant, Benjamin; Kuerer, Henry; Yang, Wei; Tkaczyk, Tomasz; Richards-Kortum, Rebecca

2016-03-01

Intraoperative margin assessment to evaluate resected tissue margins for neoplastic tissue is performed to prevent reoperations following breast-conserving surgery. High resolution microendoscopy (HRME) can rapidly acquire images of fresh tissue specimens, but is limited by low image contrast in tissues with high optical scattering. In this study we evaluated two techniques to reduce out-of-focus light: HRME image acquisition with structured illumination (SI-HRME) and topical application of Lugol's Iodine. Fresh breast tissue specimens from 19 patients were stained with proflavine alone or Lugol's Iodine and proflavine. Images of tissue specimens were acquired using a confocal microscope and an HRME system with and without structured illumination. Images were evaluated based on visual and quantitative assessment of image contrast. The highest mean contrast was measured in confocal images stained with proflavine. Contrast was significantly lower in HRME images stained with proflavine; however, incorporation of structured illumination significantly increased contrast in HRME images to levels comparable to that in confocal images. The addition of Lugol's Iodine did not increase mean contrast significantly for HRME or SI-HRME images. These findings suggest that structured illumination could potentially be used to increase contrast in HRME images of breast tissue for rapid image acquisition.

Deep Tissue Fluorescent Imaging in Scattering Specimens Using Confocal Microscopy

PubMed Central

Clendenon, Sherry G.; Young, Pamela A.; Ferkowicz, Michael; Phillips, Carrie; Dunn, Kenneth W.

2015-01-01

In scattering specimens, multiphoton excitation and nondescanned detection improve imaging depth by a factor of 2 or more over confocal microscopy; however, imaging depth is still limited by scattering. We applied the concept of clearing to deep tissue imaging of highly scattering specimens. Clearing is a remarkably effective approach to improving image quality at depth using either confocal or multiphoton microscopy. Tissue clearing appears to eliminate the need for multiphoton excitation for deep tissue imaging. PMID:21729357

Multiview hyperspectral topography of tissue structural and functional characteristics

NASA Astrophysics Data System (ADS)

Zhang, Shiwu; Liu, Peng; Huang, Jiwei; Xu, Ronald

2012-12-01

Accurate and in vivo characterization of structural, functional, and molecular characteristics of biological tissue will facilitate quantitative diagnosis, therapeutic guidance, and outcome assessment in many clinical applications, such as wound healing, cancer surgery, and organ transplantation. However, many clinical imaging systems have limitations and fail to provide noninvasive, real time, and quantitative assessment of biological tissue in an operation room. To overcome these limitations, we developed and tested a multiview hyperspectral imaging system. The multiview hyperspectral imaging system integrated the multiview and the hyperspectral imaging techniques in a single portable unit. Four plane mirrors are cohered together as a multiview reflective mirror set with a rectangular cross section. The multiview reflective mirror set was placed between a hyperspectral camera and the measured biological tissue. For a single image acquisition task, a hyperspectral data cube with five views was obtained. The five-view hyperspectral image consisted of a main objective image and four reflective images. Three-dimensional topography of the scene was achieved by correlating the matching pixels between the objective image and the reflective images. Three-dimensional mapping of tissue oxygenation was achieved using a hyperspectral oxygenation algorithm. The multiview hyperspectral imaging technique is currently under quantitative validation in a wound model, a tissue-simulating blood phantom, and an in vivo biological tissue model. The preliminary results have demonstrated the technical feasibility of using multiview hyperspectral imaging for three-dimensional topography of tissue functional properties.

Detection of the multiphoton signals in stained tissue using nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Zeng, Yaping; Xu, Jian; Kang, Deyong; Lin, Jiangbo; Chen, Jianxin

2016-10-01

Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) imaging, has become a powerful, important tool for tissue imaging at the molecular level. Recently, MPM is also used to image hematoxylin and eosin (H and E)-stained sections in cancer diagnostics. However, several studies have showed that the MPM images of tissue stained with H and E are significantly different from unstained tissue sections. Our aim was to detect of the multiphoton signals in stained tissue by using MPM. In this paper, MPM was used to image histological sections of esophageal invasive carcinoma tissues stained with H, E, H and E and fresh tissue. To detect of the multiphoton signals in stained tissue, the emission spectroscopic of tissue stained with H, E, H and E were obtained. For comparison, the fresh tissues were also investigated. Our results showed that the tissue stained with H, E, H and E could be detected by their TPEF signals. While the tissue stained with H and fresh tissue could be detected by their TPEF and SHG signals. In this work, we detect of the multiphoton signals in stained tissue. These findings will be useful for choosing suitable staining method so to improve the quality of MPM imaging in the future.

Application of hyperosmotic agent to determine gastric cancer with optical coherence tomography ex vivo in mice

NASA Astrophysics Data System (ADS)

Xiong, Honglian; Guo, Zhouyi; Zeng, Changchun; Wang, Like; He, Yonghong; Liu, Songhao

2009-03-01

Noninvasive tumor imaging could lead to the early detection and timely treatment of cancer. Optical coherence tomography (OCT) has been reported as an ideal diagnostic tool for distinguishing tumor tissues from normal tissues based on structural imaging. In this study, the capability of OCT for functional imaging of normal and tumor tissues based on time- and depth-resolved quantification of the permeability of biomolecules through these tissues is investigated. The orthotopic graft model of gastric cancer in nude mice is used, normal and tumor tissues from the gastric wall are imaged, and a diffusion of 20% aqueous solution of glucose in normal stomach tissues and gastric tumor tissues is monitored and quantified as a function of time and tissue depth by an OCT system. Our results show that the permeability coefficient is (0.94+/-0.04)×10-5 cm/s in stomach tissues and (5.32+/-0.17)×10-5 cm/s in tumor tissues, respectively, and that tumor tissues have a higher permeability coefficient compared to normal tissues in optical coherence tomographic images. From the results, it is found that the accurate and sensitive assessment of the permeability coefficients of normal and tumor tissues offers an effective OCT image method for detection of tumor tissues and clinical diagnosis.

High Resolution X-ray Phase Contrast Imaging with Acoustic Tissue-Selective Contrast Enhancement

DTIC Science & Technology

2008-06-01

Imaging with Acoustic Tissue-Selective Contrast Enhancement PRINCIPAL INVESTIGATOR: Gerald J. Diebold, Ph.D. CONTRACTING... Contrast Imaging with Acoustic Tissue-Selective Contrast Enhancement 5b. GRANT NUMBER W81XWH-04-1-0481 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...additional phase contrast features are visible at the interfaces of soft tissues as slight contrast enhancements . The image sequence in Fig. 2 shows an image

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

PubMed

Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

2016-05-01

High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

Acoustic Radiation Force Elasticity Imaging in Diagnostic Ultrasound

PubMed Central

Doherty, Joshua R.; Trahey, Gregg E.; Nightingale, Kathryn R.; Palmeri, Mark L.

2013-01-01

The development of ultrasound-based elasticity imaging methods has been the focus of intense research activity since the mid-1990s. In characterizing the mechanical properties of soft tissues, these techniques image an entirely new subset of tissue properties that cannot be derived with conventional ultrasound techniques. Clinically, tissue elasticity is known to be associated with pathological condition and with the ability to image these features in vivo, elasticity imaging methods may prove to be invaluable tools for the diagnosis and/or monitoring of disease. This review focuses on ultrasound-based elasticity imaging methods that generate an acoustic radiation force to induce tissue displacements. These methods can be performed non-invasively during routine exams to provide either qualitative or quantitative metrics of tissue elasticity. A brief overview of soft tissue mechanics relevant to elasticity imaging is provided, including a derivation of acoustic radiation force, and an overview of the various acoustic radiation force elasticity imaging methods. PMID:23549529

Acoustic radiation force elasticity imaging in diagnostic ultrasound.

PubMed

Doherty, Joshua R; Trahey, Gregg E; Nightingale, Kathryn R; Palmeri, Mark L

2013-04-01

The development of ultrasound-based elasticity imaging methods has been the focus of intense research activity since the mid-1990s. In characterizing the mechanical properties of soft tissues, these techniques image an entirely new subset of tissue properties that cannot be derived with conventional ultrasound techniques. Clinically, tissue elasticity is known to be associated with pathological condition and with the ability to image these features in vivo; elasticity imaging methods may prove to be invaluable tools for the diagnosis and/or monitoring of disease. This review focuses on ultrasound-based elasticity imaging methods that generate an acoustic radiation force to induce tissue displacements. These methods can be performed noninvasively during routine exams to provide either qualitative or quantitative metrics of tissue elasticity. A brief overview of soft tissue mechanics relevant to elasticity imaging is provided, including a derivation of acoustic radiation force, and an overview of the various acoustic radiation force elasticity imaging methods.

Multimodal tissue perfusion imaging using multi-spectral and thermographic imaging systems applied on clinical data

NASA Astrophysics Data System (ADS)

Klaessens, John H. G. M.; Nelisse, Martin; Verdaasdonk, Rudolf M.; Noordmans, Herke Jan

2013-03-01

Clinical interventions can cause changes in tissue perfusion, oxygenation or temperature. Real-time imaging of these phenomena could be useful for surgical strategy or understanding of physiological regulation mechanisms. Two noncontact imaging techniques were applied for imaging of large tissue areas: LED based multispectral imaging (MSI, 17 different wavelengths 370 nm-880 nm) and thermal imaging (7.5 to 13.5 μm). Oxygenation concentration changes were calculated using different analyzing methods. The advantages of these methods are presented for stationary and dynamic applications. Concentration calculations of chromophores in tissue require right choices of wavelengths The effects of different wavelength choices for hemoglobin concentration calculations were studied in laboratory conditions and consequently applied in clinical studies. Corrections for interferences during the clinical registrations (ambient light fluctuations, tissue movements) were performed. The wavelength dependency of the algorithms were studied and wavelength sets with the best results will be presented. The multispectral and thermal imaging systems were applied during clinical intervention studies: reperfusion of tissue flap transplantation (ENT), effectiveness of local anesthetic block and during open brain surgery in patients with epileptic seizures. The LED multispectral imaging system successfully imaged the perfusion and oxygenation changes during clinical interventions. The thermal images show local heat distributions over tissue areas as a result of changes in tissue perfusion. Multispectral imaging and thermal imaging provide complementary information and are promising techniques for real-time diagnostics of physiological processes in medicine.

Comparison of irrigation solutions and devices in a contaminated musculoskeletal wound survival model.

PubMed

Owens, Brett D; White, Daniel W; Wenke, Joseph C

2009-01-01

There is much to learn about the effectiveness of different methods currently used for the irrigation of open wounds. The purpose of this study was to compare various approaches in a survival animal model. We used an established goat model involving the creation of a reproducible complex musculoskeletal wound followed by inoculation with Pseudomonas aeruginosa (lux) bacteria. This genetically altered luminescent bacterium provides the ability for quantitative analysis with a photon-counting camera system. For Study 1, wound irrigation was performed six hours after the injury and inoculation; the goats were assigned to four treatment groups: normal saline solution, bacitracin solution, castile soap, and benzalkonium chloride. All wounds received sharp débridement and irrigation with use of a pulsatile lavage device (19 psi). Images and photon counts were obtained prior to irrigation, after irrigation, and forty-eight hours after injury and inoculation. For Study 2, we used the same animal model and compared bulb syringe and pulsatile lavage irrigation with saline solution. In Study 1, the irrigation treatment lowered the bacterial counts in all treatment groups. The greatest reduction was seen with castile soap, which lowered the photon count to 13% of the pretreatment level. This was followed by benzalkonium chloride, bacitracin, and saline solution at 18%, 22%, and 29%, respectively. At forty-eight hours, imaging showed a rebound in bacterial counts in every group. The highest rebound was measured in the castile soap group, which rebounded to 120% of the pretreatment level. The benzalkonium chloride group experienced a rebound to 94% of the pretreatment level. These were followed by bacitracin solution (89%) and normal saline solution (68%). In Study 2, both treatment methods were effective in removing 75% of the bacteria initially. At forty-eight hours, the bacterial levels in the pulsed lavage group rebounded to 94% of the original levels (compared with 48% in the bulb syringe group). The difference in the mean photon count ratios at forty-eight hours was significant (p = 0.048). Approaches used to remove bacteria from wounds, such as irrigants other than saline solution or high-pressure devices, may not have the best clinical outcome.

X-ray Phase Contrast Allows Three Dimensional, Quantitative Imaging of Hydrogel Implants

DOE PAGES

Appel, Alyssa A.; Larson, Jeffrey C.; Jiang, Bin; ...

2015-10-20

Three dimensional imaging techniques are needed for the evaluation and assessment of biomaterials used for tissue engineering and drug delivery applications. Hydrogels are a particularly popular class of materials for medical applications but are difficult to image in tissue using most available imaging modalities. Imaging techniques based on X-ray Phase Contrast (XPC) have shown promise for tissue engineering applications due to their ability to provide image contrast based on multiple X-ray properties. In this manuscript we describe results using XPC to image a model hydrogel and soft tissue structure. Porous fibrin loaded poly(ethylene glycol) hydrogels were synthesized and implanted inmore » a rodent subcutaneous model. Samples were explanted and imaged with an analyzer-based XPC technique and processed and stained for histology for comparison. Both hydrogel and soft tissues structures could be identified in XPC images. Structure in skeletal muscle adjacent could be visualized and invading fibrovascular tissue could be quantified. In quantitative results, there were no differences between XPC and the gold-standard histological measurements. These results provide evidence of the significant potential of techniques based on XPC for 3D imaging of hydrogel structure and local tissue response.« less

Multiview hyperspectral topography of tissue structural and functional characteristics

NASA Astrophysics Data System (ADS)

Liu, Peng; Huang, Jiwei; Zhang, Shiwu; Xu, Ronald X.

2016-01-01

Accurate and in vivo characterization of structural, functional, and molecular characteristics of biological tissue will facilitate quantitative diagnosis, therapeutic guidance, and outcome assessment in many clinical applications, such as wound healing, cancer surgery, and organ transplantation. We introduced and tested a multiview hyperspectral imaging technique for noninvasive topographic imaging of cutaneous wound oxygenation. The technique integrated a multiview module and a hyperspectral module in a single portable unit. Four plane mirrors were cohered to form a multiview reflective mirror set with a rectangular cross section. The mirror set was placed between a hyperspectral camera and the target biological tissue. For a single image acquisition task, a hyperspectral data cube with five views was obtained. The five-view hyperspectral image consisted of a main objective image and four reflective images. Three-dimensional (3-D) topography of the scene was achieved by correlating the matching pixels between the objective image and the reflective images. 3-D mapping of tissue oxygenation was achieved using a hyperspectral oxygenation algorithm. The multiview hyperspectral imaging technique was validated in a wound model, a tissue-simulating blood phantom, and in vivo biological tissue. The experimental results demonstrated the technical feasibility of using multiview hyperspectral imaging for 3-D topography of tissue functional properties.

Multiphoton Microscopy of Prostate and Periprostatic Neural Tissue: A Promising Imaging Technique for Improving Nerve-Sparing Prostatectomy

PubMed Central

Yadav, Rajiv; Mukherjee, Sushmita; Hermen, Michael; Tan, Gerald; Maxfield, Frederick R.; Webb, Watt W.

2009-01-01

Abstract Background and Purpose Various imaging modalities are under investigation for real-time tissue imaging of periprostatic nerves with the idea of improving the results of nerve-sparing radical prostatectomy. We explored multiphoton microscopy (MPM) for real-time tissue imaging of the prostate and periprostatic neural tissue in a male Sprague-Dawley rat model. The unique advantage of this technique is the acquisition of high-resolution images without necessitating any extrinsic labeling agent and with minimal phototoxic effect on tissue. Materials and Methods The prostate and cavernous nerves were surgically excised from male Sprague-Dawley rats. The imaging was carried out using intrinsic fluorescence and scattering properties of the tissues without any exogenous dye or contrast agent. A custom-built MPM, consisting of an Olympus BX61WI upright frame and a modified MRC 1024 scanhead, was used. A femtosecond pulsed titanium/sapphire laser at 780-nm wavelength was used to excite the tissue; laser power under the objective was modulated via a Pockels cell. Second harmonic generation (SHG) signals were collected at 390 (±35 nm), and broadband autofluorescence was collected at 380 to 530 nm. The images obtained from SHG and from tissue fluorescence were then merged and color coded during postprocessing for better appreciation of details. The corresponding tissues were subjected to hematoxylin and eosin staining for histologic confirmation of the structures. Results High-resolution images of the prostate capsule, underlying acini, and individual cells outlining the glands were obtained at varying magnifications. MPM images of adipose tissue and the neural tissues were also obtained. Histologic confirmation and correlation of the prostate gland, fat, cavernous nerve, and major pelvic ganglion validated the findings of MPM. Conclusion Real-time imaging and microscopic resolution of prostate and periprostatic neural tissue using MPM is feasible without the need for any extrinsic labeling agents. Integration of this imaging modality with operative technique has the potential to improve the precision of nerve-sparing prostatectomy. PMID:19425823

Thick tissue diffusion model with binding to optimize topical staining in fluorescence breast cancer margin imaging

NASA Astrophysics Data System (ADS)

Xu, Xiaochun; Kang, Soyoung; Navarro-Comes, Eric; Wang, Yu; Liu, Jonathan T. C.; Tichauer, Kenneth M.

2018-03-01

Intraoperative tumor/surgical margin assessment is required to achieve higher tumor resection rate in breast-conserving surgery. Though current histology provides incomparable accuracy in margin assessment, thin tissue sectioning and the limited field of view of microscopy makes histology too time-consuming for intraoperative applications. If thick tissue, wide-field imaging can provide an acceptable assessment of tumor cells at the surface of resected tissues, an intraoperative protocol can be developed to guide the surgery and provide immediate feedback for surgeons. Topical staining of margins with cancer-targeted molecular imaging agents has the potential to provide the sensitivity needed to see microscopic cancer on a wide-field image; however, diffusion and nonspecific retention of imaging agents in thick tissue can significantly diminish tumor contrast with conventional methods. Here, we present a mathematical model to accurately simulate nonspecific retention, binding, and diffusion of imaging agents in thick tissue topical staining to guide and optimize future thick tissue staining and imaging protocol. In order to verify the accuracy and applicability of the model, diffusion profiles of cancer targeted and untargeted (control) nanoparticles at different staining times in A431 tumor xenografts were acquired for model comparison and tuning. The initial findings suggest the existence of nonspecific retention in the tissue, especially at the tissue surface. The simulator can be used to compare the effect of nonspecific retention, receptor binding and diffusion under various conditions (tissue type, imaging agent) and provides optimal staining and imaging protocols for targeted and control imaging agent.

Functional and morphological ultrasonic biomicroscopy for tissue engineers

NASA Astrophysics Data System (ADS)

Mallidi, S.; Aglyamov, S. R.; Karpiouk, A. B.; Park, S.; Emelianov, S. Y.

2006-03-01

Tissue engineering is an interdisciplinary field that combines various aspects of engineering and life sciences and aims to develop biological substitutes to restore, repair or maintain tissue function. Currently, the ability to have quantitative functional assays of engineered tissues is limited to existing invasive methods like biopsy. Hence, an imaging tool for non-invasive and simultaneous evaluation of the anatomical and functional properties of the engineered tissue is needed. In this paper we present an advanced in-vivo imaging technology - ultrasound biomicroscopy combined with complementary photoacoustic and elasticity imaging techniques, capable of accurate visualization of both structural and functional changes in engineered tissues, sequential monitoring of tissue adaptation and/or regeneration, and possible assistance of drug delivery and treatment planning. The combined imaging at microscopic resolution was evaluated on tissue mimicking phantoms imaged with 25 MHz single element focused transducer. The results of our study demonstrate that the ultrasonic, photoacoustic and elasticity images synergistically complement each other in detecting features otherwise imperceptible using the individual techniques. Finally, we illustrate the feasibility of the combined ultrasound, photoacoustic and elasticity imaging techniques in accurately assessing the morphological and functional changes occurring in engineered tissue.

Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection

NASA Astrophysics Data System (ADS)

Tate, Tyler; Baggett, Brenda; Rice, Photini; Watson, Jennifer; Orsinger, Gabe; Nymeyer, Ariel C.; Welge, Weston A.; Keenan, Molly; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth; Chambers, Setsuko; Black, John; Utzinger, Urs; Barton, Jennifer

2015-03-01

With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

Pulsatile and steady-state hemodynamics of the human patella bone by diffuse optical spectroscopy.

PubMed

Farzam, Parisa; Zirak, Peyman; Binzoni, Tiziano; Durduran, Turgut

2013-08-01

The cardiac cycle related pulsatile behavior of the absorption and scattering coefficients of diffuse light and the corresponding alterations in hemoglobin concentrations in the human patella was studied. The pulsations in scattering is considerably smaller than absorption. The difference in amplitude of absorption coefficient pulsations for different wavelengths was translated to pulsations in oxygenated and deoxygenated hemoglobin, which leads to strong pulsations in the total hemoglobin concentration and oxygen saturation. The physiological origin of the observed signals was confirmed by applying a thigh-cuff. Moreover, we have investigated the optical and physiological properties of the patella bone and their changes in response to arterial cuff occlusion.

Evaluation of exercise-respiratory system modifications and integration schemes for physiological systems

NASA Technical Reports Server (NTRS)

Gallagher, R. R.

1974-01-01

Exercise subroutine modifications are implemented in an exercise-respiratory system model yielding improvement of system response to exercise forcings. A more physiologically desirable respiratory ventilation rate in addition to an improved regulation of arterial gas tensions and cerebral blood flow is observed. A respiratory frequency expression is proposed which would be appropriate as an interfacing element of the respiratory-pulsatile cardiovascular system. Presentation of a circulatory-respiratory system integration scheme along with its computer program listing is given. The integrated system responds to exercise stimulation for both nonstressed and stressed physiological states. Other integration possibilities are discussed with respect to the respiratory, pulsatile cardiovascular, thermoregulatory, and the long-term circulatory systems.

Particle Image Velocimetry studies of bicuspid aortic valve hemodynamics

NASA Astrophysics Data System (ADS)

Saikrishnan, Neelakantan; Yap, Choon-Hwai; Yoganathan, Ajit P.

2010-11-01

Bicuspid aortic valves (BAVs) are a congenital anomaly of the aortic valve with two fused leaflets, affecting about 1-2% of the population. BAV patients have much higher incidence of valve calcification & aortic dilatation, which may be related to altered mechanical forces from BAV hemodynamics. This study aims to characterize BAV hemodynamics using Particle Image Velocimetry(PIV). BAV models are constructed from normal explanted porcine aortic valves by suturing two leaflets together. The valves are mounted in an acrylic chamber with two sinuses & tested in a pulsatile flow loop at physiological conditions. 2D PIV is performed to obtain flow fields in three planes downstream of the valve. The stenosed BAV causes an eccentric jet, resulting in a very strong vortex in the normal sinus. The bicuspid sinus vortex appears much weaker, but more unstable. Unsteady oscillatory shear stresses are also observed, which have been associated with adverse biological response; characterization of the hemodynamics of BAVs will provide the first step to understanding these processes better. Results from multiple BAV models of varying levels of stenosis will be presented & higher stenosis corresponded to stronger jets & increased aortic wall shear stresses.

The Manifestation of Vortical and Secondary Flow in the Cerebral Venous Outflow Tract: An In Vivo MR Velocimetry Study

PubMed Central

Kefayati, Sarah; Amans, Matthew; Faraji, Farshid; Ballweber, Megan; Kao, Evan; Ahn, Sinyeob; Meisel, Karl; Halbach, Van; Saloner, David

2016-01-01

Aberrations in flow in the cerebral venous outflow tract (CVOT) have been implicated as the cause of several pathologic conditions including idiopathic intracranial hypertension (IIH), multiple sclerosis (MS), and pulsatile tinnitus (PT). The advent of 4D Flow magnetic resonance imaging (4D-Flow MRI) has recently allowed researchers to evaluate blood flow patterns in the arterial structures with great success. We utilized similar imaging techniques and found several distinct flow characteristics in the CVOT of subjects with and without lumenal irregularities. We present the flow patterns of 8 out of 38 subjects who have varying heights of the internal jugular bulb and varying lumenal irregularities including stenosis and diverticulum. In the internal jugular vein (IJV) with an elevated jugular bulb (JB), 4DFlow MRI revealed a characteristic spiral flow that was dependent on the level of JB elevation. Vortical flow was also observed in the diverticula of the venous sinuses and IJV. The diversity of flow complexity in the CVOT illustrates the potential importance of hemodynamic investigations in elucidating venous pathologies. PMID:27894675

Characterization of human oral tissues based on quantitative analysis of optical coherence tomography images

NASA Astrophysics Data System (ADS)

Salehi, Hassan S.; Kosa, Ali; Mahdian, Mina; Moslehpour, Saeid; Alnajjar, Hisham; Tadinada, Aditya

2017-02-01

In this paper, five types of tissues, human enamel, human cortical bone, human trabecular bone, muscular tissue, and fatty tissue were imaged ex vivo using optical coherence tomography (OCT). The specimens were prepared in blocks of 5 x 5 x 3 mm (width x length x height). The OCT imaging system was a swept source OCT system operating at wavelengths ranging between 1250 nm and 1360 nm with an average power of 18 mW and a scan rate of 50 to 100 kHz. The imaging probe was placed on top of a 2 x 2 cm stabilizing device to maintain a standard distance from the samples. Ten image samples from each type of tissue were obtained. To acquire images with minimum inhomogeneity, imaging was performed multiple times at different points. Based on the observed texture differences between OCT images of soft and hard tissues, spatial and spectral features were quantitatively extracted from the OCT images. The Radon transform from angles of 0 deg to 90 deg was computed, averaged over all the angles, normalized to peak at unity, and then fitted with Gaussian function. The mean absolute values of the spatial frequency components of the OCT image were considered as a feature, where 2-D fast Fourier transform (FFT) was done to OCT images. These OCT features can reliably differentiate between a range of hard and soft tissues, and could be extremely valuable in assisting dentists for in vivo evaluation of oral tissues and early detection of pathologic changes in tissues.

3D imaging of optically cleared tissue using a simplified CLARITY method and on-chip microscopy

PubMed Central

Zhang, Yibo; Shin, Yoonjung; Sung, Kevin; Yang, Sam; Chen, Harrison; Wang, Hongda; Teng, Da; Rivenson, Yair; Kulkarni, Rajan P.; Ozcan, Aydogan

2017-01-01

High-throughput sectioning and optical imaging of tissue samples using traditional immunohistochemical techniques can be costly and inaccessible in resource-limited areas. We demonstrate three-dimensional (3D) imaging and phenotyping in optically transparent tissue using lens-free holographic on-chip microscopy as a low-cost, simple, and high-throughput alternative to conventional approaches. The tissue sample is passively cleared using a simplified CLARITY method and stained using 3,3′-diaminobenzidine to target cells of interest, enabling bright-field optical imaging and 3D sectioning of thick samples. The lens-free computational microscope uses pixel super-resolution and multi-height phase recovery algorithms to digitally refocus throughout the cleared tissue and obtain a 3D stack of complex-valued images of the sample, containing both phase and amplitude information. We optimized the tissue-clearing and imaging system by finding the optimal illumination wavelength, tissue thickness, sample preparation parameters, and the number of heights of the lens-free image acquisition and implemented a sparsity-based denoising algorithm to maximize the imaging volume and minimize the amount of the acquired data while also preserving the contrast-to-noise ratio of the reconstructed images. As a proof of concept, we achieved 3D imaging of neurons in a 200-μm-thick cleared mouse brain tissue over a wide field of view of 20.5 mm2. The lens-free microscope also achieved more than an order-of-magnitude reduction in raw data compared to a conventional scanning optical microscope imaging the same sample volume. Being low cost, simple, high-throughput, and data-efficient, we believe that this CLARITY-enabled computational tissue imaging technique could find numerous applications in biomedical diagnosis and research in low-resource settings. PMID:28819645

Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients.

PubMed

Siravegna, Giulia; Mussolin, Benedetta; Buscarino, Michela; Corti, Giorgio; Cassingena, Andrea; Crisafulli, Giovanni; Ponzetti, Agostino; Cremolini, Chiara; Amatu, Alessio; Lauricella, Calogero; Lamba, Simona; Hobor, Sebastijan; Avallone, Antonio; Valtorta, Emanuele; Rospo, Giuseppe; Medico, Enzo; Motta, Valentina; Antoniotti, Carlotta; Tatangelo, Fabiana; Bellosillo, Beatriz; Veronese, Silvio; Budillon, Alfredo; Montagut, Clara; Racca, Patrizia; Marsoni, Silvia; Falcone, Alfredo; Corcoran, Ryan B; Di Nicolantonio, Federica; Loupakis, Fotios; Siena, Salvatore; Sartore-Bianchi, Andrea; Bardelli, Alberto

2015-07-01

Colorectal cancers (CRCs) evolve by a reiterative process of genetic diversification and clonal evolution. The molecular profile of CRC is routinely assessed in surgical or bioptic samples. Genotyping of CRC tissue has inherent limitations; a tissue sample represents a single snapshot in time, and it is subjected to spatial selection bias owing to tumor heterogeneity. Repeated tissue samples are difficult to obtain and cannot be used for dynamic monitoring of disease progression and response to therapy. We exploited circulating tumor DNA (ctDNA) to genotype colorectal tumors and track clonal evolution during treatment with the epidermal growth factor receptor (EGFR)-specific antibodies cetuximab or panitumumab. We identified alterations in ctDNA of patients with primary or acquired resistance to EGFR blockade in the following genes: KRAS, NRAS, MET, ERBB2, FLT3, EGFR and MAP2K1. Mutated KRAS clones, which emerge in blood during EGFR blockade, decline upon withdrawal of EGFR-specific antibodies, indicating that clonal evolution continues beyond clinical progression. Pharmacogenomic analysis of CRC cells that had acquired resistance to cetuximab reveals that upon antibody withdrawal KRAS clones decay, whereas the population regains drug sensitivity. ctDNA profiles of individuals who benefit from multiple challenges with anti-EGFR antibodies exhibit pulsatile levels of mutant KRAS. These results indicate that the CRC genome adapts dynamically to intermittent drug schedules and provide a molecular explanation for the efficacy of rechallenge therapies based on EGFR blockade.

Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering.

PubMed

Parvizi, Mojtaba; Bolhuis-Versteeg, Lydia A M; Poot, André A; Harmsen, Martin C

2016-07-01

Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-β1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-β1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well-aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre-differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-β1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Coupled to Shear Force Microscopy

NASA Astrophysics Data System (ADS)

Nguyen, Son N.; Sontag, Ryan L.; Carson, James P.; Corley, Richard A.; Ansong, Charles; Laskin, Julia

2018-02-01

Constant mode ambient mass spectrometry imaging (MSI) of tissue sections with high lateral resolution of better than 10 μm was performed by combining shear force microscopy with nanospray desorption electrospray ionization (nano-DESI). Shear force microscopy enabled precise control of the distance between the sample and nano-DESI probe during MSI experiments and provided information on sample topography. Proof-of-concept experiments were performed using lung and brain tissue sections representing spongy and dense tissues, respectively. Topography images obtained using shear force microscopy were comparable to the results obtained using contact profilometry over the same region of the tissue section. Variations in tissue height were found to be dependent on the tissue type and were in the range of 0-5 μm for lung tissue and 0-3 μm for brain tissue sections. Ion images of phospholipids obtained in this study are in good agreement with literature data. Normalization of nano-DESI MSI images to the signal of the internal standard added to the extraction solvent allowed us to construct high-resolution ion images free of matrix effects.

Hyperspectral imaging based on compressive sensing to determine cancer margins in human pancreatic tissue ex vivo

NASA Astrophysics Data System (ADS)

Peller, Joseph; Thompson, Kyle J.; Siddiqui, Imran; Martinie, John; Iannitti, David A.; Trammell, Susan R.

2017-02-01

Pancreatic cancer is the fourth leading cause of cancer death in the US. Currently, surgery is the only treatment that offers a chance of cure, however, accurately identifying tumor margins in real-time is difficult. Research has demonstrated that optical spectroscopy can be used to distinguish between healthy and diseased tissue. The design of a single-pixel imaging system for cancer detection is discussed. The system differentiates between healthy and diseased tissue based on differences in the optical reflectance spectra of these regions. In this study, pancreatic tissue samples from 6 patients undergoing Whipple procedures are imaged with the system (total number of tissue sample imaged was N=11). Regions of healthy and unhealthy tissue are determined based on SAM analysis of these spectral images. Hyperspectral imaging results are then compared to white light imaging and histological analysis. Cancerous regions were clearly visible in the hyperspectral images. Margins determined via spectral imaging were in good agreement with margins identified by histology, indicating that hyperspectral imaging system can differentiate between healthy and diseased tissue. After imaging the system was able to detect cancerous regions with a sensitivity of 74.50±5.89% and a specificity of 75.53±10.81%. Possible applications of this imaging system include determination of tumor margins during surgery/biopsy and assistance with cancer diagnosis and staging.

Tissue Equivalent Phantom Design for Characterization of a Coherent Scatter X-ray Imaging System

NASA Astrophysics Data System (ADS)

Albanese, Kathryn Elizabeth

Scatter in medical imaging is typically cast off as image-related noise that detracts from meaningful diagnosis. It is therefore typically rejected or removed from medical images. However, it has been found that every material, including cancerous tissue, has a unique X-ray coherent scatter signature that can be used to identify the material or tissue. Such scatter-based tissue-identification provides the advantage of locating and identifying particular materials over conventional anatomical imaging through X-ray radiography. A coded aperture X-ray coherent scatter spectral imaging system has been developed in our group to classify different tissue types based on their unique scatter signatures. Previous experiments using our prototype have demonstrated that the depth-resolved coherent scatter spectral imaging system (CACSSI) can discriminate healthy and cancerous tissue present in the path of a non-destructive x-ray beam. A key to the successful optimization of CACSSI as a clinical imaging method is to obtain anatomically accurate phantoms of the human body. This thesis describes the development and fabrication of 3D printed anatomical scatter phantoms of the breast and lung. The purpose of this work is to accurately model different breast geometries using a tissue equivalent phantom, and to classify these tissues in a coherent x-ray scatter imaging system. Tissue-equivalent anatomical phantoms were designed to assess the capability of the CACSSI system to classify different types of breast tissue (adipose, fibroglandular, malignant). These phantoms were 3D printed based on DICOM data obtained from CT scans of prone breasts. The phantoms were tested through comparison of measured scatter signatures with those of adipose and fibroglandular tissue from literature. Tumors in the phantom were modeled using a variety of biological tissue including actual surgically excised benign and malignant tissue specimens. Lung based phantoms have also been printed for future testing. Our imaging system has been able to define the location and composition of the various materials in the phantom. These phantoms were used to characterize the CACSSI system in terms of beam width and imaging technique. The result of this work showed accurate modeling and characterization of the phantoms through comparison of the tissue-equivalent form factors to those from literature. The physical construction of the phantoms, based on actual patient anatomy, was validated using mammography and computed tomography to visually compare the clinical images to those of actual patient anatomy.

Seeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing

PubMed Central

Berke, Ian M.; Miola, Joseph P.; David, Michael A.; Smith, Melanie K.; Price, Christopher

2016-01-01

In situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues. Drawing inspiration from recent developments in the deep-tissue imaging field, we describe the application of immersion based optical clearing techniques, which utilize the principle of refractive index (RI) matching between the clearing/mounting media and tissue under observation, to improve the deep, in situ imaging of musculoskeletal tissues. To date, few optical clearing techniques have been applied specifically to musculoskeletal tissues, and a systematic comparison of the clearing ability of optical clearing agents in musculoskeletal tissues has yet to be fully demonstrated. In this study we tested the ability of eight different aqueous and non-aqueous clearing agents, with RIs ranging from 1.45 to 1.56, to optically clear murine knee joints and cortical bone. We demonstrated and quantified the ability of these optical clearing agents to clear musculoskeletal tissues and improve both macro- and micro-scale imaging of musculoskeletal tissue across several imaging modalities (stereomicroscopy, spectroscopy, and one-, and two-photon confocal microscopy) and investigational techniques (dynamic bone labeling and en bloc tissue staining). Based upon these findings we believe that optical clearing, in combination with advanced imaging techniques, has the potential to complement classical musculoskeletal analysis techniques; opening the door for improved in situ investigation and quantification of musculoskeletal tissues. PMID:26930293

Seeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing.

PubMed

Berke, Ian M; Miola, Joseph P; David, Michael A; Smith, Melanie K; Price, Christopher

2016-01-01

In situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues. Drawing inspiration from recent developments in the deep-tissue imaging field, we describe the application of immersion based optical clearing techniques, which utilize the principle of refractive index (RI) matching between the clearing/mounting media and tissue under observation, to improve the deep, in situ imaging of musculoskeletal tissues. To date, few optical clearing techniques have been applied specifically to musculoskeletal tissues, and a systematic comparison of the clearing ability of optical clearing agents in musculoskeletal tissues has yet to be fully demonstrated. In this study we tested the ability of eight different aqueous and non-aqueous clearing agents, with RIs ranging from 1.45 to 1.56, to optically clear murine knee joints and cortical bone. We demonstrated and quantified the ability of these optical clearing agents to clear musculoskeletal tissues and improve both macro- and micro-scale imaging of musculoskeletal tissue across several imaging modalities (stereomicroscopy, spectroscopy, and one-, and two-photon confocal microscopy) and investigational techniques (dynamic bone labeling and en bloc tissue staining). Based upon these findings we believe that optical clearing, in combination with advanced imaging techniques, has the potential to complement classical musculoskeletal analysis techniques; opening the door for improved in situ investigation and quantification of musculoskeletal tissues.

The Use of Fluid Mechanics to Predict Regions of Microscopic Thrombus Formation in Pulsatile VADs.

PubMed

Topper, Stephen R; Navitsky, Michael A; Medvitz, Richard B; Paterson, Eric G; Siedlecki, Christopher A; Slattery, Margaret J; Deutsch, Steven; Rosenberg, Gerson; Manning, Keefe B

2014-03-01

We compare the velocity and shear obtained from particle image velocimetry (PIV) and computational fluid dynamics (CFD) in a pulsatile ventricular assist device (VAD) to further test our thrombus predictive methodology using microscopy data from an explanted VAD. To mimic physiological conditions in vitro , a mock circulatory loop is used with a blood analog that matched blood's viscoelastic behavior at 40% hematocrit. Under normal physiologic pressures and for a heart rate of 75 bpm, PIV data is acquired and wall shear maps are produced. The resolution of the PIV shear rate calculations are tested using the CFD and found to be in the same range. A bovine study, using a model of the 50 cc Penn State V-2 VAD, for 30 days at a constant beat rate of 75 beats per minute (bpm) provides the microscopic data whereby after the 30 days, the device is explanted and the sac surface analyzed using scanning electron microscopy (SEM) and, after immunofluorescent labeling for platelets and fibrin, confocal microscopy. Areas are examined based on PIV measurements and CFD, with special attention to low shear regions where platelet and fibrin deposition are most likely to occur. Data collected within the outlet port in a direction normal to the front wall of the VAD shows that some regions experience wall shear rates less than 500 s -1 , which increases the likelihood of platelet and fibrin deposition. Despite only one animal study, correlations between PIV, CFD, and in vivo data show promise. Deposition probability is quantified by the thrombus susceptibility potential, a calculation to correlate low shear and time of shear with deposition.

The influence of non-planar geometry on the flow within a distal end-to-side anastomosis

NASA Astrophysics Data System (ADS)

Sherwin, S. J.; Doorly, D. J.; Peiro, J.; Caro, C. G.

1998-11-01

The pattern of the flow in arteries is strongly influenced by the three-dimensional shape of the geometry. Curvature and torsion of the wall geometry alters the axial velocity distribution, and introduces cross flow velocity components. In this investigation we have considered flow in a model geometry of a fully occluded 45^o distal end-to-side anastomosis. Previous investigations have typically focused on planar end-to-side anastomoses where the bypass and host vessels have a plane of symmetry. We have increased the complexity of the model by considering a non-planar geometry produced by deforming the bypass vessel out of the plane of symmetry. The flows have been numerically and experimentally investigated using a spectral/hp element algorithm and magnetic resonance imaging. The significant effect of the non-planar geometry is to introduce a bulk rotation of the two secondary flow cells present in flow within a planar geometry. A reduction in wall shear stress is observed at the bed of the anastomosis and a larger absolute flux of velocity is seen within the occluded region proximal to the anastomosis. Current investigations have considered the role of pulsatility in the form of a non-reversing sinusoidal oscillation. In this case a separation bubble, not present in the steady case, is seen at the toe of the anastomosis during the systolic part of the cycle. The role of geometry and pulsatility on particle motion has also been addressed with a view to determining the shear exposure on particle within these types of flows.

[Evaluation and Optimization of Microvascular Arterial Anastomoses by Transit Time Flow Measurement].

PubMed

Herberhold, S; Röttker, J; Bartmann, D; Solbach, A; Keiner, S; Welz, A; Bootz, F; Laffers, W

2016-03-01

INDRODUCTION: The regular application of transit time flow measurement in microvascular anastomoses during heart surgery has lead to improvements of the outcome of coronary artery bypass grafts. Our study was meant to discover whether this measurement method was also applicable for evaluation and optimization of microvascular arterial anastomoses of radial forearm flaps. In this prospective examination a combining ultrasound imaging and transit time flow measurement device (VeriQ, MediStim) was used during surgery to assess anastomotic quality of 15 radial forearm flaps. Pulsatility index (PI) and mean blood flow were measured immediately after opening the arterial anastomosis as well as 15 min afterwards. Furthermore, application time and description of handling were recorded seperately for every assessment. Mean blood flow immediately after opening the anastomosis and 15 min later were 3.9 and 3.4 ml/min resepectively showing no statistically significant difference (p=0.96). There was no significance in the increase of pulsatility index from 22.1 to 27.2 (p=0.09) during the same time range, either. Due to measurement results showing atypical pulse curves in 2 cases decision for surgical revision of the anastomoses was made. All forearm flaps showed good vascularisation during follow-up. Time for device set up, probe placement and measurements was about 20 min. Handling was described to be uncomplicated without exception. There were no noteworthy problems. Transit time flow measurement contributes to the improvement of anastomotic quality and therefore to the overall outcome of radial forearm flaps. The examined measurement method provides objective results and is useful for documentation purposes. © Georg Thieme Verlag KG Stuttgart · New York.

Magnetic resonance imaging 4-D flow-based analysis of aortic hemodynamics in Turner syndrome.

PubMed

Arnold, Raoul; Neu, Marie; Hirtler, Daniel; Gimpel, Charlotte; Markl, Michael; Geiger, Julia

2017-04-01

Cardiovascular surveillance is important in Turner syndrome because of the increased risk of aortic dilation and dissection with consecutively increased mortality. To compare 4-D flow MRI for the characterization of aortic 3-D flow patterns, dimensions and vessel wall parameters in pediatric patients with Turner syndrome and age-matched controls. We performed 4-D flow MRI measuring in vivo 3-D blood flow with coverage of the thoracic aorta in 25 patients with Turner syndrome and in 16 female healthy controls (age mean ± standard deviation were 16 ± 5 years and 17 ± 4 years, respectively). Blood flow was visualized by time-resolved 3-D path lines. Visual grading of aortic flow in terms of helices and vortices was performed by two independent observers. Quantitative analysis included measurement of aortic diameters, quantification of peak systolic wall shear stress, pulsatility index and oscillatory shear index at eight defined sites. Patients with Turner syndrome had significantly larger aortic diameters normalized to BSA, increased vortices in the ascending aorta and elevated helix flow in the ascending and descending aorta compared to controls (all P<0.03). Patients with abnormal helical or vortical flow in the ascending aorta had significantly larger diameters of the ascending aorta (P<0.03). Peak systolic wall shear stress, pulsatility index and oscillatory shear index were significantly lower in Turner patients compared to controls (p=0.02, p=0.002 and p=0.01 respectively). Four-dimensional flow MRI provides new insights into the altered aortic hemodynamics and wall shear stress that could have an impact on the development of aortic dissections.

Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig.

PubMed

Turan, Sifa; Aberdeen, Graham W; Thompson, Loren P

2017-10-01

Placental hypoxia is associated with maternal hypertension, placental insufficiency, and fetal growth restriction. In the pregnant guinea pig, prenatal hypoxia during early gestation inhibits cytotrophoblast invasion of spiral arteries, increases maternal blood pressure, and induces fetal growth restriction. In this study the impact of chronic maternal hypoxia on fetal heart structure was evaluated using four-dimensional echocardiography with spatiotemporal image correlation and tomographic ultrasound, and uterine and umbilical artery resistance/pulsatility indexes and fetal heart function were evaluated using pulsed-wave Doppler ultrasound. Pregnant guinea pigs were exposed to normoxia ( n = 7) or hypoxia (10.5% O 2 , n = 9) at 28-30 days gestation, which was maintained until full term (65 days). At full term, fetal heart structure and outflow tracts were evaluated in the four-chamber view. Fetal heart diastolic function was assessed by E wave-to-A wave diastolic filling ratios (E/A ratios) of both ventricles and systolic function by the myocardial performance index (or Tie) of left ventricles of normoxic ( n = 21) and hypoxic ( n = 17) fetuses. There were no structural abnormalities in fetal hearts. However, hypoxia induced asymmetric fetal growth restriction and increased the placental/fetal weight compared with normoxic controls. Hypoxia increased Doppler resistance and pulsatility indexes in the uterine, but not umbilical, arteries, had no effect on the Tie index, and increased the E/A ratio in left, but not right, ventricles. Thus, prolonged hypoxia, starting at midgestation, increases uterine artery resistance and generates fetal growth restriction at full term. Furthermore, the enhanced cardiac diastolic filling with no changes in systolic function or umbilical artery resistance suggests that the fetal guinea pig systemic circulation undergoes a compensated, adaptive response to prolonged hypoxia exposure. Copyright © 2017 the American Physiological Society.

Pulsatile flows and wall-shear stresses in models simulating normal and stenosed aortic arches

NASA Astrophysics Data System (ADS)

Huang, Rong Fung; Yang, Ten-Fang; Lan, Y.-K.

2010-03-01

Pulsatile aqueous glycerol solution flows in the models simulating normal and stenosed human aortic arches are measured by means of particle image velocimetry. Three transparent models were used: normal, 25% stenosed, and 50% stenosed aortic arches. The Womersley parameter, Dean number, and time-averaged Reynolds number are 17.31, 725, and 1,081, respectively. The Reynolds numbers based on the peak velocities of the normal, 25% stenosed, and 50% stenosed aortic arches are 2,484, 3,456, and 3,931, respectively. The study presents the temporal/spatial evolution processes of the flow pattern, velocity distribution, and wall-shear stress during the systolic and diastolic phases. It is found that the flow pattern evolving in the central plane of normal and stenosed aortic arches exhibits (1) a separation bubble around the inner arch, (2) a recirculation vortex around the outer arch wall upstream of the junction of the brachiocephalic artery, (3) an accelerated main stream around the outer arch wall near the junctions of the left carotid and the left subclavian arteries, and (4) the vortices around the entrances of the three main branches. The study identifies and discusses the reasons for the flow physics’ contribution to the formation of these features. The oscillating wall-shear stress distributions are closely related to the featured flow structures. On the outer wall of normal and slightly stenosed aortas, large wall-shear stresses appear in the regions upstream of the junction of the brachiocephalic artery as well as the corner near the junctions of the left carotid artery and the left subclavian artery. On the inner wall, the largest wall-shear stress appears in the region where the boundary layer separates.

Periprosthetic Artifact Reduction Using Virtual Monochromatic Imaging Derived From Gemstone Dual-Energy Computed Tomography and Dedicated Software.

PubMed

Reynoso, Exequiel; Capunay, Carlos; Rasumoff, Alejandro; Vallejos, Javier; Carpio, Jimena; Lago, Karen; Carrascosa, Patricia

2016-01-01

The aim of this study was to explore the usefulness of combined virtual monochromatic imaging and metal artifact reduction software (MARS) for the evaluation of musculoskeletal periprosthetic tissue. Measurements were performed in periprosthetic and remote regions in 80 patients using a high-definition scanner. Polychromatic images with and without MARS and virtual monochromatic images were obtained. Periprosthetic polychromatic imaging (PI) showed significant differences compared with remote areas among the 3 tissues explored (P < 0.0001). No significant differences were observed between periprosthetic and remote tissues using monochromatic imaging with MARS (P = 0.053 bone, P = 0.32 soft tissue, and P = 0.13 fat). However, such differences were significant using PI with MARS among bone (P = 0.005) and fat (P = 0.02) tissues. All periprosthetic areas were noninterpretable using PI, compared with 11 (9%) using monochromatic imaging. The combined use of virtual monochromatic imaging and MARS reduced periprosthetic artifacts, achieving attenuation levels comparable to implant-free tissue.

Phase contrast imaging of buccal mucosa tissues-Feasibility study

NASA Astrophysics Data System (ADS)

Fatima, A.; Tripathi, S.; Shripathi, T.; Kulkarni, V. K.; Banda, N. R.; Agrawal, A. K.; Sarkar, P. S.; Kashyap, Y.; Sinha, A.

2015-06-01

Phase Contrast Imaging (PCI) technique has been used to interpret physical parameters obtained from the image taken on the normal buccal mucosa tissue extracted from cheek of a patient. The advantages of this method over the conventional imaging techniques are discussed. PCI technique uses the X-ray phase shift at the edges differentiated by very minute density differences and the edge enhanced high contrast images reveal details of soft tissues. The contrast in the images produced is related to changes in the X-ray refractive index of the tissues resulting in higher clarity compared with conventional absorption based X-ray imaging. The results show that this type of imaging has better ability to visualize microstructures of biological soft tissues with good contrast, which can lead to the diagnosis of lesions at an early stage of the diseases.

Mathematical modeling of pulsatile flow of non-Newtonian fluid in stenosed arteries

NASA Astrophysics Data System (ADS)

Sankar, D. S.; Lee, Usik

2009-07-01

The pulsatile flow of blood through mild stenosed artery is studied. The effects of pulsatility, stenosis and non-Newtonian behavior of blood, treating the blood as Herschel-Bulkley fluid, are simultaneously considered. A perturbation method is used to analyze the flow. The expressions for the shear stress, velocity, flow rate, wall shear stress, longitudinal impedance and the plug core radius have been obtained. The variations of these flow quantities with different parameters of the fluid have been analyzed. It is found that, the plug core radius, pressure drop and wall shear stress increase with the increase of yield stress or the stenosis height. The velocity and the wall shear stress increase considerably with the increase in the amplitude of the pressure drop. It is clear that for a given value of stenosis height and for the increasing values of the stenosis shape parameter from 3 to 6, there is a sharp increase in the impedance of the flow and also the plots are skewed to the right-hand side. It is observed that the estimates of the increase in the longitudinal impedance increase with the increase of the axial distance or with the increase of the stenosis height. The present study also brings out the effects of asymmetric of the stenosis on the flow quantities.

Biomathematical modeling of pulsatile hormone secretion: a historical perspective.

PubMed

Evans, William S; Farhy, Leon S; Johnson, Michael L

2009-01-01

Shortly after the recognition of the profound physiological significance of the pulsatile nature of hormone secretion, computer-based modeling techniques were introduced for the identification and characterization of such pulses. Whereas these earlier approaches defined perturbations in hormone concentration-time series, deconvolution procedures were subsequently employed to separate such pulses into their secretion event and clearance components. Stochastic differential equation modeling was also used to define basal and pulsatile hormone secretion. To assess the regulation of individual components within a hormone network, a method that quantitated approximate entropy within hormone concentration-times series was described. To define relationships within coupled hormone systems, methods including cross-correlation and cross-approximate entropy were utilized. To address some of the inherent limitations of these methods, modeling techniques with which to appraise the strength of feedback signaling between and among hormone-secreting components of a network have been developed. Techniques such as dynamic modeling have been utilized to reconstruct dose-response interactions between hormones within coupled systems. A logical extension of these advances will require the development of mathematical methods with which to approximate endocrine networks exhibiting multiple feedback interactions and subsequently reconstruct their parameters based on experimental data for the purpose of testing regulatory hypotheses and estimating alterations in hormone release control mechanisms.

Estimation of the radial force using a disturbance force observer for a magnetically levitated centrifugal blood pump.

PubMed

Pai, C N; Shinshi, T; Shimokohbe, A

2010-01-01

Evaluation of the hydraulic forces in a magnetically levitated (maglev) centrifugal blood pump is important from the point of view of the magnetic bearing design. Direct measurement is difficult due to the absence of a rotor shaft, and computational fluid dynamic analysis demands considerable computational resource and time. To solve this problem, disturbance force observers were developed, using the radial controlled magnetic bearing of a centrifugal blood pump, to estimate the radial forces on the maglev impeller. In order to design the disturbance observer, the radial dynamic characteristics of a maglev impeller were evaluated under different working conditions. It was observed that the working fluid affects the additional mass and damping, while the rotational speed affects the damping and stiffness of the maglev system. Based on these results, disturbance force observers were designed and implemented. The designed disturbance force observers present a bandwidth of 45 Hz. In non-pulsatile conditions, the magnitude of the estimated radial thrust increases in proportion to the flowrate, and the rotational speed has little effect on the force direction. At 5 l/min against 100 mmHg, the estimated radial thrust is 0.95 N. In pulsatile conditions, this method was capable of estimating the pulsatile radial thrust with good response.

The induction of ovulation by pulsatile administration of GnRH: an appropriate method in hypothalamic amenorrhea.

PubMed

Christou, Fotini; Pitteloud, Nelly; Gomez, Fulgencio

2017-08-01

The induction of ovulation by the means of a pump which assures the pulsatile administration of GnRH is a well-known method that applies to women suffering from amenorrhea of hypothalamic origin. Although a simple and efficient method to establish fertility, it is underused. Twelve patients suffering from this condition, 1 Kallmann syndrome, 4 normosmic isolated hypogonadotropic hypogonadism, and 7 functional hypothalamic amenorrhea desiring pregnancy were treated. They underwent one or more cycles of pulsatile GnRH, at a frequency of 90 minutes, either by the intravenous or the subcutaneous route. An initial dose of 5 μg per pulse in the intravenous route was administered and of 15 μg per pulse in the subcutaneous route. The treatment was monitored by regular dosing of gonadotropins, estradiol and progesterone, and the development of follicles and ovulation was monitored by intra-vaginal ultrasonography. All the patients had documented ovulation, after a mean of 17 days on pump stimulation. Single ovulation occurred in 30 of 33 treatment cycles, irrespective of the route of administration. Ovulation resulted in 10 pregnancies over 7 patients (2 pregnancies in 3 of them), distributed in the 3 diagnostic categories. For comparison, a patient with PCOS treated similarly, disclosed premature LH surge without ovulation.

Methicillin Resistant Staphylococcus Aureus Biofilm Formation Over A Separated Flow Region Under Steady And Pulsatile Flow Conditions

NASA Astrophysics Data System (ADS)

Salek, M. Mehdi; Martinuzzi, Robert

2012-02-01

Several researchers have observed that the formation, morphology and susceptibility of bacterial biofilms are affected by the local hydrodynamic condition and, in particular, shear stresses acting on the fluid-biofilm interface. A backwards facing step (BFS) experimental model has been widely utilized as an in vitro model to examine and characterize the effect of flow separation and recirculation zones comparable to those present within various medical devices as well as those observed in vivo. The specific geometry of BFS covers a vide range of flow features observed in physiological or environmental conditions. The hypothesis of this study is that the flow behavior and structures can effectively contribute to the transport and attachment of cells and affecting the morphology of adhered colonies as well as suspended structures (i.e. biofilm streamers). Hence, the formation of the recirculation region occurring within a backward facing step (BFS) under steady and pulsatile conditions as well as three-dimensional flow structures arising close to the side walls are investigated to correlate to biofilms behavior. This hypothesis is investigated using a backward facing step incorporated into a flow cell under steady and pulsatile flow regimes to study the growth of methicillin resistant Staphylococcus aureus (MRSA) UC18 as the study microorganism.

The relationship between pulsatile GnRH secretion and cAMP production in immortalized GnRH neurons.

PubMed

Frattarelli, John L; Krsmanovic, Lazar Z; Catt, Kevin J

2011-06-01

In perifused immortalized GnRH neurons (GT1-7), simultaneous measurements of GnRH and cAMP revealed that the secretory profiles for both GnRH and cAMP are pulsatile. An analysis of GnRH and cAMP pulses in 16 independent experiments revealed that 25% of pulses coincide. Inversion of the peak and nadir levels was found in 33% and random relationship between GnRH and cAMP found in 42% of analyzed pulses. The random relation between GnRH and cAMP pulse resets to synchronous after an inverse relation between pulses occurred during the major GnRH release, indicating that GnRH acts as a switching mechanism to synchronize cAMP and GnRH release in perifused GT1-7 neurons. Activation of GnRH receptors with increasing agonist concentrations caused a biphasic change in cAMP levels. Low nanomolar concentrations increased cAMP production, but at high concentrations the initial increase was followed by a rapid decline to below the basal level. Blockade of the GnRH receptors by peptide and nonpeptide antagonists generated monotonic nonpulsatile increases in both GnRH and cAMP production. These findings indicate that cAMP positively regulates GnRH secretion but does not participate in the mechanism of pulsatile GnRH release.

Stokes-polarimetry imaging of tissue

NASA Astrophysics Data System (ADS)

Wu, Paul J.

A novel Stokes-polarimetry imaging system and technique was developed to quantify fully the polarization properties of light remitted from tissue. The uniqueness of the system and technique is established in the incident polarization. Here, the diffuse illumination is varied and controlled with the intention to improve the visibility of tissue structures. Since light retains some polarization even after multiple-scattering events, the polarization of remitted light depends upon the interactions within the material. Differentiation between tissue structures is accomplished by two-dimensional mapping of the imaged area using metrics such as the degree of linear polarization, degree of circular polarization, ellipticity, and Stokes parameters. While Stokes-polarimetry imaging can be applied to a variety of tissues and conditions, this thesis focuses on tissue types associated with the disease endometriosis. The current standard in diagnosing endometriosis is visual laparoscopy with tissue biopsy. The documented correlation between laparoscopy inspection and histological confirmation of suspected lesions was at best 67%. Endometrial lesions vary greatly in their appearance and depth of infiltration. Although laparoscopy permits tissue to be assessed by color and texture, to advance beyond the state-of-the-art, a new imaging modality involving polarized light was investigated; in particular, Stokes-polarimetry imaging was used to determine the polarization signature of light that interacted with tissue. Basic science studies were conducted on rat tails embedded within turbid gelatin. The purpose of these experiments was to determine how identification of sub-surface structures could be improved. Experimental results indicate image contrast among various structures such as tendon, soft tissue and intervertebral discs. Stokes-polarimetry imaging experiments were performed on various tissues associated with endometriosis to obtain a baseline characterization for each tissue type. Structures such as birefringent collagen, smooth-muscle fiber-bundles, and nerve bundles were visualized that were otherwise not observable with unpolarized light imaging. Finally, a study of cutaneous scars indicated the feasibility of using Stokes-polarimetry imaging in the detection of atypical tissue. A relationship between incident linear polarization angle and skin anatomy was determined so as to obtain maximum contrast between scar tissue and normal skin.

Various clinical application of phase contrast X-ray

NASA Astrophysics Data System (ADS)

Oh, Chilhwan; Park, Sangyong; Ha, Seunghan; Park, Gyuman; Lee, Gunwoo; Lee, Onseok; Je, Jungho

2008-02-01

In biomedical application study using phase contrast X-ray, both sample thickness or density and absorption difference are very important factors in aspects of contrast enhancement. We present experimental evidence that synchrotron hard X-ray are suitable for radiological imaging of biological samples down to the cellular level. We investigated the potential of refractive index radiology using un-monochromatized synchrotron hard X-rays for the imaging of cell and tissue in various diseases. Material had been adopted various medical field, such as apoE knockout mouse in cardiologic field, specimen from renal and prostatic carcinoma patient in urology, basal cell epithelioma in dermatology, brain tissue from autosy sample of pakinson's disease, artificially induced artilrtis tissue from rabbits and extracted tooth from patients of crack tooth syndrome. Formalin and paraffin fixed tissue blocks were cut in 3 mm thickness for the X-ray radiographic imaging. From adjacent areas, 4 μm thickness sections were also prepared for hematoxylin-eosin staining. Radiographic images of dissected tissues were obtained using the hard X-rays from the 7B2 beamline of the Pohang Light Source (PLS). The technique used for the study was the phase contrast images were compared with the optical microscopic images of corresponding histological slides. Radiographic images of various diseased tissues showed clear histological details of organelles in normal tissues. Most of cancerous lesions were well differentiated from adjacent normal tissues and detailed histological features of each tumor were clearly identified. Also normal microstructures were identifiable by the phase contrast imaging. Tissue in cancer or other disease showed clearly different findings from those of surrounding normal tissue. For the first time we successfully demonstrated that synchrotron hard X-rays can be used for radiological imaging of relatively thick tissue samples with great histological details.

Autofluorescence detection and imaging of bladder cancer realized through a cystoscope

DOEpatents

Demos, Stavros G [Livermore, CA; deVere White, Ralph W [Sacramento, CA

2007-08-14

Near infrared imaging using elastic light scattering and tissue autofluorescence and utilizing interior examination techniques and equipment are explored for medical applications. The approach involves imaging using cross-polarized elastic light scattering and/or tissue autofluorescence in the Near Infra-Red (NIR) coupled with image processing and inter-image operations to differentiate human tissue components.

ACR Appropriateness Criteria® Tinnitus.

PubMed

Kessler, Marcus M; Moussa, Marwan; Bykowski, Julie; Kirsch, Claudia F E; Aulino, Joseph M; Berger, Kevin L; Choudhri, Asim F; Fife, Terry D; Germano, Isabelle M; Kendi, A Tuba; Kim, Jeffrey H; Luttrull, Michael D; Nunez, Diego; Shah, Lubdha M; Sharma, Aseem; Shetty, Vilaas S; Symko, Sophia C; Cornelius, Rebecca S

2017-11-01

Tinnitus is the perception of sound in the absence of an external source. It is a common symptom that can be related to hearing loss and other benign causes. However, tinnitus may be disabling and can be the only symptom in a patient with a central nervous system process disorder. History and physical examination are crucial first steps to determine the need for imaging. CT and MRI are useful in the setting of pulsatile tinnitus to evaluate for an underlying vascular anomaly or abnormality. If there is concomitant asymmetric hearing loss, neurologic deficit, or head trauma, imaging should be guided by those respective ACR Appropriateness Criteria ® documents, rather than the presence of tinnitus. Imaging is not usually appropriate in the evaluation of subjective, nonpulsatile tinnitus that does not localize to one ear. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Comparison of phase-contrast MR imaging and endovascular sonography for intracranial blood flow velocity measurements.

PubMed

Schneiders, J J; Ferns, S P; van Ooij, P; Siebes, M; Nederveen, A J; van den Berg, R; van Lieshout, J; Jansen, G; vanBavel, E; Majoie, C B

2012-10-01

Local hemodynamic information may help to stratify rupture risk of cerebral aneurysms. Patient-specific modeling of cerebral hemodynamics requires accurate data on BFV in perianeurysmal arteries as boundary conditions for CFD. The aim was to compare the BFV measured with PC-MR imaging with that obtained by using intra-arterial Doppler sonography and to determine interpatient variation in intracranial BFV. In 10 patients with unruptured intracranial aneurysms, BFV was measured in the cavernous ICA with PC-MR imaging in conscious patients before treatment, and measured by using an intra-arterial Doppler sonography wire when the patient was anesthetized with either propofol (6 patients) or sevoflurane (4 patients). Both techniques identified a pulsatile blood flow pattern in cerebral arteries. PSV differed >50 cm/s between patients. A mean velocity of 41.3 cm/s (95% CI, 39.3-43.3) was measured with PC-MR imaging. With intra-arterial Doppler sonography, a mean velocity of 29.3 cm/s (95% CI, 25.8-32.8) was measured with the patient under propofol-based intravenous anesthesia. In patients under sevoflurane-based inhaled anesthesia, a mean velocity of 44.9 cm/s (95% CI, 40.6-49.3) was measured. We showed large differences in BFV between patients, emphasizing the importance of using patient-specific hemodynamic boundary conditions in CFD. PC-MR imaging measurements of BFV in conscious patients were comparable with those obtained with the intra-arterial Doppler sonography when the patient was anesthetized with a sevoflurane-based inhaled anesthetic.

Imaging pulse wave velocity in mouse retina using swept-source OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Song, Shaozhen; Wei, Wei; Wang, Ruikang K.

2016-03-01

Blood vessel dynamics has been a significant subject in cardiology and internal medicine, and pulse wave velocity (PWV) on artery vessels is a classic evaluation of arterial distensibility, and has never been ascertained as a cardiovascular risk marker. The aim of this study is to develop a high speed imaging technique to capture the pulsatile motion on mouse retina arteries with the ability to quantify PWV on any arterial vessels. We demonstrate a new non-invasive method to assess the vessel dynamics on mouse retina. A Swept-source optical coherence tomography (SS-OCT) system is used for imaging micro-scale blood vessel motion. The phase-stabilized SS-OCT provides a typical displacement sensitivity of 20 nm. The frame rate of imaging is ~16 kHz, at A-line rate of ~1.62 MHz, which allows the detection of transient pulse waves with adequate temporal resolution. Imaging volumes with repeated B-scans are obtained on mouse retina capillary bed, and the mouse oxymeter signal is recorded simultaneously. The pulse wave on artery and vein are resolved, and with the synchronized heart beat signal, the temporal delay on different vessel locations is determined. The vessel specific measurement of PWV is achieved for the first time with SS-OCT, for pulse waves propagating more than 100 cm/s. Using the novel methodology of retinal PWV assessment, it is hoped that the clinical OCT scans can provide extended diagnostic information of cardiology functionalities.

Real-time three-dimensional optical coherence tomography image-guided core-needle biopsy system.

PubMed

Kuo, Wei-Cheng; Kim, Jongsik; Shemonski, Nathan D; Chaney, Eric J; Spillman, Darold R; Boppart, Stephen A

2012-06-01

Advances in optical imaging modalities, such as optical coherence tomography (OCT), enable us to observe tissue microstructure at high resolution and in real time. Currently, core-needle biopsies are guided by external imaging modalities such as ultrasound imaging and x-ray computed tomography (CT) for breast and lung masses, respectively. These image-guided procedures are frequently limited by spatial resolution when using ultrasound imaging, or by temporal resolution (rapid real-time feedback capabilities) when using x-ray CT. One feasible approach is to perform OCT within small gauge needles to optically image tissue microstructure. However, to date, no system or core-needle device has been developed that incorporates both three-dimensional OCT imaging and tissue biopsy within the same needle for true OCT-guided core-needle biopsy. We have developed and demonstrate an integrated core-needle biopsy system that utilizes catheter-based 3-D OCT for real-time image-guidance for target tissue localization, imaging of tissue immediately prior to physical biopsy, and subsequent OCT imaging of the biopsied specimen for immediate assessment at the point-of-care. OCT images of biopsied ex vivo tumor specimens acquired during core-needle placement are correlated with corresponding histology, and computational visualization of arbitrary planes within the 3-D OCT volumes enables feedback on specimen tissue type and biopsy quality. These results demonstrate the potential for using real-time 3-D OCT for needle biopsy guidance by imaging within the needle and tissue during biopsy procedures.

Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins

PubMed Central

Mueller, Jenna L.; Harmany, Zachary T.; Mito, Jeffrey K.; Kennedy, Stephanie A.; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G.; Willett, Rebecca M.; Brown, J. Quincy; Ramanujam, Nimmi

2013-01-01

Purpose To develop a robust tool for quantitative in situ pathology that allows visualization of heterogeneous tissue morphology and segmentation and quantification of image features. Materials and Methods Tissue excised from a genetically engineered mouse model of sarcoma was imaged using a subcellular resolution microendoscope after topical application of a fluorescent anatomical contrast agent: acriflavine. An algorithm based on sparse component analysis (SCA) and the circle transform (CT) was developed for image segmentation and quantification of distinct tissue types. The accuracy of our approach was quantified through simulations of tumor and muscle images. Specifically, tumor, muscle, and tumor+muscle tissue images were simulated because these tissue types were most commonly observed in sarcoma margins. Simulations were based on tissue characteristics observed in pathology slides. The potential clinical utility of our approach was evaluated by imaging excised margins and the tumor bed in a cohort of mice after surgical resection of sarcoma. Results Simulation experiments revealed that SCA+CT achieved the lowest errors for larger nuclear sizes and for higher contrast ratios (nuclei intensity/background intensity). For imaging of tumor margins, SCA+CT effectively isolated nuclei from tumor, muscle, adipose, and tumor+muscle tissue types. Differences in density were correctly identified with SCA+CT in a cohort of ex vivo and in vivo images, thus illustrating the diagnostic potential of our approach. Conclusion The combination of a subcellular-resolution microendoscope, acriflavine staining, and SCA+CT can be used to accurately isolate nuclei and quantify their density in anatomical images of heterogeneous tissue. PMID:23824589

Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins.

PubMed

Mueller, Jenna L; Harmany, Zachary T; Mito, Jeffrey K; Kennedy, Stephanie A; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G; Willett, Rebecca M; Brown, J Quincy; Ramanujam, Nimmi

2013-01-01

To develop a robust tool for quantitative in situ pathology that allows visualization of heterogeneous tissue morphology and segmentation and quantification of image features. TISSUE EXCISED FROM A GENETICALLY ENGINEERED MOUSE MODEL OF SARCOMA WAS IMAGED USING A SUBCELLULAR RESOLUTION MICROENDOSCOPE AFTER TOPICAL APPLICATION OF A FLUORESCENT ANATOMICAL CONTRAST AGENT: acriflavine. An algorithm based on sparse component analysis (SCA) and the circle transform (CT) was developed for image segmentation and quantification of distinct tissue types. The accuracy of our approach was quantified through simulations of tumor and muscle images. Specifically, tumor, muscle, and tumor+muscle tissue images were simulated because these tissue types were most commonly observed in sarcoma margins. Simulations were based on tissue characteristics observed in pathology slides. The potential clinical utility of our approach was evaluated by imaging excised margins and the tumor bed in a cohort of mice after surgical resection of sarcoma. Simulation experiments revealed that SCA+CT achieved the lowest errors for larger nuclear sizes and for higher contrast ratios (nuclei intensity/background intensity). For imaging of tumor margins, SCA+CT effectively isolated nuclei from tumor, muscle, adipose, and tumor+muscle tissue types. Differences in density were correctly identified with SCA+CT in a cohort of ex vivo and in vivo images, thus illustrating the diagnostic potential of our approach. The combination of a subcellular-resolution microendoscope, acriflavine staining, and SCA+CT can be used to accurately isolate nuclei and quantify their density in anatomical images of heterogeneous tissue.