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1.  Forced oscillations and respiratory system modeling in adults with cystic fibrosis 
The Forced Oscillation Technique (FOT) has the potential to increase our knowledge about the biomechanical changes that occur in Cystic Fibrosis (CF). Thus, the aims of this study were to investigate changes in the resistive and reactive properties of the respiratory systems of adults with CF.
The study was conducted in a group of 27 adults with CF over 18 years old and a control group of 23 healthy individuals, both of which were assessed by the FOT, plethysmography and spirometry. An equivalent electrical circuit model was also used to quantify biomechanical changes and to gain physiological insight.
Results and discussion
The CF adults presented an increased total respiratory resistance (p < 0.0001), increased resistance curve slope (p < 0.0006) and reduced dynamic compliance (p < 0.0001). In close agreement with the physiology of CF, the model analysis showed increased peripheral resistance (p < 0.0005) and reduced compliance (p < 0.0004) and inertance (p < 0.005). Significant reasonable to good correlations were observed between the resistive parameters and spirometric and plethysmographic indexes. Similar associations were observed for the reactive parameters. Peripheral resistance, obtained by the model analysis, presented reasonable (R = 0.35) to good (R = 0.64) relationships with plethysmographic parameters.
The FOT adequately assessed the biomechanical changes associated with CF. The model used provides sensitive indicators of lung function and has the capacity to differentiate between obstructed and non-obstructed airway conditions. The FOT shows great potential for the clinical assessment of respiratory mechanics in adults with CF.
PMCID: PMC4334397
Respiratory system modeling; Biomedical instrumentation; Diagnosis; Cystic fibrosis; Adults; Respiratory biomechanics; Forced oscillation technique
2.  Automated system for lung nodules classification based on wavelet feature descriptor and support vector machine 
Lung cancer is a leading cause of death worldwide; it refers to the uncontrolled growth of abnormal cells in the lung. A computed tomography (CT) scan of the thorax is the most sensitive method for detecting cancerous lung nodules. A lung nodule is a round lesion which can be either non-cancerous or cancerous. In the CT, the lung cancer is observed as round white shadow nodules. The possibility to obtain a manually accurate interpretation from CT scans demands a big effort by the radiologist and might be a fatiguing process. Therefore, the design of a computer-aided diagnosis (CADx) system would be helpful as a second opinion tool.
The stages of the proposed CADx are: a supervised extraction of the region of interest to eliminate the shape differences among CT images. The Daubechies db1, db2, and db4 wavelet transforms are computed with one and two levels of decomposition. After that, 19 features are computed from each wavelet sub-band. Then, the sub-band and attribute selection is performed. As a result, 11 features are selected and combined in pairs as inputs to the support vector machine (SVM), which is used to distinguish CT images containing cancerous nodules from those not containing nodules.
The clinical data set used for experiments consists of 45 CT scans from ELCAP and LIDC. For the training stage 61 CT images were used (36 with cancerous lung nodules and 25 without lung nodules). The system performance was tested with 45 CT scans (23 CT scans with lung nodules and 22 without nodules), different from that used for training. The results obtained show that the methodology successfully classifies cancerous nodules with a diameter from 2 mm to 30 mm. The total preciseness obtained was 82%; the sensitivity was 90.90%, whereas the specificity was 73.91%.
The CADx system presented is competitive with other literature systems in terms of sensitivity. The system reduces the complexity of classification by not performing the typical segmentation stage of most CADx systems. Additionally, the novelty of the algorithm is the use of a wavelet feature descriptor.
PMCID: PMC4329222
CADx system; Lung nodules; CT scan; Wavelet feature descriptor; Gray level co-ocurrence matrix; Support vector machine; Texture
4.  Experimental study of hemodynamics in the circle of willis 
BioMedical Engineering OnLine  2015;14(Suppl 1):S10.
The Circle of Willis (CoW) is an important collateral pathway of the cerebral blood flow. An experimental study of the cerebral blood flow (CBF) distribution in different anatomical variations may help to a better understanding of the collateral mechanism of the CoW.
An in-vitro test rig was developed to simulate the physiological cerebral blood flow in the CoW. Ten anatomical variations were considered in this study, include a set of different degrees of stenosis in L-ICA and L-ICA occlusion coexist with common anatomical variations. Volume flow rates of efferent arteries and pressure signals at the end of communicating arteries of each case were recorded. Physiological pressure waveforms were applied as inlet boundary condition.
In the development of L-ICA stenosis, the total CBF decreases with the increase of stenosis degree. The blood supply of ipsilateral middle cerebral artery (MCA) was affected most by the stenosis of L-ICA. Anterior communicating artery (ACoA) and ipsilateral posterior communicating artery (PCoA) function as important collateral pathways of cerebral collateral circulation when unilateral stenosis occurred. The blood supply of anterior cerebral circulation was compensated by the posterior cerebral circulation through ipsilateral PCoA when L-ICA stenosis degree is greater than 40% and the affected side was compensated immediately by the unaffected side through ACoA. Blood flow of the anterior circulation and the total CBF reached the minimum among all cases studied when L-ICA occlusion coexist with the absence of PCoA.
The results demonstrated the flow distribution patterns of the CoW under anatomical variations and clarified the collateral mechanism of the CoW. The flow ACoA is the most sensitive indexes to the morphology change of ipsilateral ICA. The relative independence of the circulation in anterior and posterior sections of the CoW is not broken and the function of ipsilateral PCoA is not activated until a severe stenosis of unilateral ICA occurs. PCoA is the most important collateral pathway of the collateral circulation and the missing of PCoA has the highest risk of stroke when the ipsilateral ICA has severe stenosis. These findings may provide the basis for future therapeutic and diagnosis applications.
PMCID: PMC4306098  PMID: 25603138
5.  A 3D numerical study of the collateral capacity of the circle of Willis with anatomical variation in the posterior circulation 
BioMedical Engineering OnLine  2015;14(Suppl 1):S11.
The Circle of Willis (CoW) is the most important collateral pathway of the cerebral artery. The present study aims to investigate the collateral capacity of CoW with anatomical variation when unilateral internalcarotid artery (ICA) is occluded.
Basing on MRI data, we have reconstructed eight 3D models with variations in the posterior circulation of the CoW and set four different degrees of stenosis in the right ICA, namely 24%, 43%, 64% and 79%, respectively. Finally, a total of 40 models are performed with computational fluid dynamics simulations. All of the simulations share the same boundary condition with static pressure and the volume flow rate (VFR) are obtained to evaluate their collateral capacity.
As for the middle cerebral artery (MCA) and the anterior cerebral artery (ACA), the transitional-type model possesses the best collateral capacity. But for the posterior cerebral artery (PCA), unilateral stenosis of ICA has the weakest influence on the unilateral posterior communicating artery (PCoA) absent model. We also find that the full fetal-type posterior circle of Willis is an utmost dangerous variation which must be paid more attention.
The results demonstrate that different models have different collateral capacities in coping stenosis of unilateral ICA and these differences can be reflected by different outlets. The study could be used as a reference for neurosurgeon in choosing the best treatment strategy.
PMCID: PMC4306100  PMID: 25603312
6.  Visual fatigue caused by watching 3DTV: an fMRI study 
BioMedical Engineering OnLine  2015;14(Suppl 1):S12.
The objective of this study is to observe the visual fatigue caused by watching 3DTV using the method of functional magnetic resonance imaging (fMRI). The data of fMRI during three kinds of visual stimulation tasks were obtained from twenty subjects. At first, blood-oxygen-level dependent (BOLD) signal changes during stimuli of checkerboard task were compared before and after one-hour watching 3D/2DTV, and subjective evaluation was conducted based on the questionnaire simultaneously. Then 3D and 2D images were used to stimulate healthy individuals to measure brain activities that correlated with stereoscopic vision. Finally, the relationship between front or back depth of field images and visual fatigue was investigated. The results reveal that the 3D group shows more significant differences of brain activities in BA8, BA17, BA18 and BA19 than the 2D group during the checkerboard stimulation. BA5, BA6, BA7 and BA8 were testified to have close relationship with stereoscopic perception via the 2D/3D images stimulation. Furthermore, the front depth of field image was proven to impose a more serious impact on visual fatigue than the back one. These conclusions are useful for healthy and reasonable 3DTV watching as well as properly designing of 3D scenes.
PMCID: PMC4306101  PMID: 25603496
Visual fatigue; fMRI; 3DTV; Stereoscopic images
7.  Establishment and ultrasound characteristics of atherosclerosis in rhesus monkey 
BioMedical Engineering OnLine  2015;14(Suppl 1):S13.
Atherosclerosis is one of the main risk factors cause acute cerebral-cardio vascular diseases. It's of great significance to establish an atherosclerosis animal model that can mimic the characteristics and nature course of human patients. Therefore, a rhesus monkey model was induced by high-fat diet to monitor their lipid profile and intima-media thickness (IMT) of artery walls and study atherosclerosis progression.
Fifty male rhesus monkeys were enrolled in this study. All of these monkeys were aged 7 to 14 years with BMI >30 kg/m2. They were fed with high-fat diet containing 10% of fat for the first 48 weeks. Use ultrasound to measure the IMT at bilateral common carotid arteries and their bifurcations and aorta (AO) of the monkeys, and screen out the individuals with thickened IMT for the next phase. In the next 48 weeks, some of these monkeys (n = 4) were fed with standard diet containing 3% fat. Meanwhile the other monkeys (n = 5) were fed with high-fat diet for another 48 weeks. Their serum lipid level was monitored and arterial IMT was also determined periodically.
Serum lipid level of all 50 monkeys elevated after fed with high-fat diet for the first 48 weeks. IMT thickening at right common carotid bifurcation and aorta (AO) was thickened in 9 monkeys. Furthermore, 4 of these 9 monkeys were fed with standard diet and other 5 monkeys were fed with high-fat diet in the following 48 weeks. The serum lipid level of the 4 monkeys recovered and their IMT at RBIF and AO did not progress. However, the lipid level of other 5 monkeys remained high, and their IMT thickening of AO progressed, and plaques and calcification focuses were found at the anterior wall of aorta near the bifurcation of common iliac artery.
After high-fat diet induction for 96 weeks, serum lipid levels of rhesus monkeys elevated significantly, which subsequently caused IMT thickening and plaques formation. When IMT thickening occurred, further vascular injury may be prevented by reducing diet fat content. Our study indicates that vascular injury of high-fat diet induced rhesus monkey is similar to that of human in position and progression.
PMCID: PMC4306102  PMID: 25602196
8.  Magnetic microbubble-mediated ultrasound-MRI registration based on robust optical flow model 
BioMedical Engineering OnLine  2015;14(Suppl 1):S14.
As a dual-modality contrast agent, magnetic microbubbles (MMBs) can not only improve contrast of ultrasound (US) image, but can also serve as a contrast agent of magnetic resonance image (MRI). With the help of MMBs, a new registration method between US image and MRI is presented.
In this method, MMBs were used in both ultrasound and magnetic resonance imaging process to enhance the most important information of interest. In order to reduce the influence of the speckle noise to registration, semi-automatic segmentations of US image and MRI were carried out by using active contour model. After that, a robust optical flow model between US image segmentation (floating image) and MRI segmentation (reference image) was built, and the vector flow field was estimated by using the Coarse-to-fine Gaussian pyramid and graduated non-convexity (GNC) schemes.
Qualitative and quantitative analyses of multiple group comparison experiments showed that registration results using all methods tested in this paper without MMBs were unsatisfactory. On the contrary, the proposed method combined with MMBs led to the best registration results.
The proposed algorithm combined with MMBs contends with larger deformation and performs well not only for local deformation but also for global deformation. The comparison experiments also demonstrated that ultrasound-MRI registration using the above-mentioned method might be a promising method for obtaining more accurate image information.
PMCID: PMC4306103  PMID: 25602434
9.  A method of extending the depth of focus of the high-resolution X-ray imaging system employing optical lens and scintillator: a phantom study 
BioMedical Engineering OnLine  2015;14(Suppl 1):S15.
The high-resolution X-ray imaging system employing synchrotron radiation source, thin scintillator, optical lens and advanced CCD camera can achieve a resolution in the range of tens of nanometers to sub-micrometer. Based on this advantage, it can effectively image tissues, cells and many other small samples, especially the calcification in the vascular or in the glomerulus. In general, the thickness of the scintillator should be several micrometers or even within nanometers because it has a big relationship with the resolution. However, it is difficult to make the scintillator so thin, and additionally thin scintillator may greatly reduce the efficiency of collecting photons.
In this paper, we propose an approach to extend the depth of focus (DOF) to solve these problems. We develop equation sets by deducing the relationship between the high-resolution image generated by the scintillator and the degraded blur image due to defect of focus first, and then we adopt projection onto convex sets (POCS) and total variation algorithm to get the solution of the equation sets and to recover the blur image.
By using a 20 μm thick unmatching scintillator to replace the 1 μm thick matching one, we simulated a high-resolution X-ray imaging system and got a degraded blur image. Based on the algorithm proposed, we recovered the blur image and the result in the experiment showed that the proposed algorithm has good performance on the recovery of image blur caused by unmatching thickness of scintillator.
The method proposed is testified to be able to efficiently recover the degraded image due to defect of focus. But, the quality of the recovery image especially of the low contrast image depends on the noise level of the degraded blur image, so there is room for improving and the corresponding denoising algorithm is worthy for further study and discussion.
PMCID: PMC4306104  PMID: 25602532
10.  Numerical simulation on the effects of drug eluting stents at different Reynolds numbers on hemodynamic and drug concentration distribution 
BioMedical Engineering OnLine  2015;14(Suppl 1):S16.
The changes of hemodynamics and drug concentration distribution caused by the implantation of drug eluting stents (DESs) in curved vessels have significant effects on In-Stent Restenosis.
A 3D virtual stent with 90°curvature was modelled and the distribution of wall shear stress (WSS) and drug concentration in this model were numerically studied at Reynolds numbers of 200, 400, 600, 800.
The results showed that (1) the intensity of secondary flow at the 45° cross-section was stronger than that at the 90° cross-section; (2) As the Reynolds number increases, the WSS decreases. When the Reynolds number reaches 600, the low-WSS region only accounts for 3% of the total area. (3) The effects of Reynolds number on drug concentration in the vascular wall decreases in proportionally and then the blood velocity increased 4 times, the drug concentration in the vascular wall decreased by about 30%. (4) The size of the high drug concentration region is inversely proportional to the Reynolds number. As the blood velocity increases, the drug concentration in the DES decreases, especially at the outer bend.
It is beneficial for the patient to decrease vigorous activities and keep calm at the beginning of the stent implantation, because a substantial amount of the drug is released in the first two months of stent implantation, thus a calm status is conducive to drug release and absorption; Subsequently, appropriate exercise which increases the blood velocity is helpful in decreasing regions of low-WSS.
PMCID: PMC4306105  PMID: 25602685
DES; curved artery; secondary flow; Reynolds number; WSS; drug concentration
11.  Acute effect of cycling intervention on carotid arterial hemodynamics: basketball athletes versus sedentary controls 
BioMedical Engineering OnLine  2015;14(Suppl 1):S17.
To compare the acute effects of a cycling intervention on carotid arterial hemodynamics between basketball athletes and sedentary controls.
Ten young long-term trained male basketball athletes (BA) and nine age-matched male sedentary controls (SC) successively underwent four bouts of exercise on a bicycle ergometer at the same workload. Hemodynamic variables at right common carotid artery were determined at rest and immediately following each bout of exercise. An ANCOVA was used to compare differences between the BA and SC groups at rest and immediately following the cycling intervention. The repeated ANOVA was used to assess differences between baseline and each bout of exercise within the BA or SC group.
In both groups, carotid hemodynamic variables showed significant differences at rest and immediately after the cycling intervention. At rest, carotid arterial stiffness was significantly decreased and carotid arterial diameter was significantly increased in the BA group as compared to the SC group. Immediately following the cycling intervention, carotid arterial stiffness showed no obvious changes in the BA group but significantly increased in the SC group. It is worth noting that while arterial stiffness was lower in the BA group than in the SC group, the oscillatory shear index (OSI) was significantly higher in the BA group than in the SC group both at rest and immediately following the cycling intervention.
Long-term basketball exercise had a significant impact on common carotid arterial hemodynamic variables not only at rest but also after a cycling intervention. The role of OSI in the remodeling of arterial structure and function in the BA group at rest and after cycling requires clarification.
PMCID: PMC4306107  PMID: 25602805
Basketball athletes; cycling intervention; arterial stiffness; hemodynamics; common carotid artery
12.  Pulsatile arterial wall-blood flow interaction with wall pre-stress computed using an inverse algorithm 
BioMedical Engineering OnLine  2015;14(Suppl 1):S18.
The computation of arterial wall deformation and stresses under physiologic conditions requires a coupled compliant arterial wall-blood flow interaction model. The in-vivo arterial wall motion is constrained by tethering from the surrounding tissues. This tethering, together with the average in-vivo pressure, results in wall pre-stress. For an accurate simulation of the physiologic conditions, it is important to incorporate the wall pre-stress in the computational model. The computation of wall pre-stress is complex, as the un-loaded and un-tethered arterial shape with residual stress is unknown. In this study, the arterial wall deformation and stresses in a canine femoral artery under pulsatile pressure was computed after incorporating the wall pre-stresses. A nonlinear least square optimization based inverse algorithm was developed to compute the in-vivo wall pre-stress.
First, the proposed inverse algorithm was used to obtain the un-loaded and un-tethered arterial geometry from the unstressed in-vivo geometry. Then, the un-loaded, and un-tethered arterial geometry was pre-stressed by applying a mean in-vivo pressure of 104.5 mmHg and an axial stretch of 48% from the un-tethered length. Finally, the physiologic pressure pulse was applied at the inlet and the outlet of the pre-stressed configuration to calculate the in-vivo deformation and stresses. The wall material properties were modeled with an incompressible, Mooney-Rivlin model derived from previously published experimental stress-strain data (Attinger et al., 1968).
The un-loaded and un-tethered artery geometry computed by the inverse algorithm had a length, inner diameter and thickness of 35.14 mm, 3.10 mm and 0.435 mm, respectively. The pre-stressed arterial wall geometry was obtained by applying the in-vivo axial-stretch and average in-vivo pressure to the un-loaded and un-tethered geometry. The length of the pre-stressed artery, 51.99 mm, was within 0.01 mm (0.019%) of the in-vivo length of 52.0 mm; the inner diameter of 3.603 mm was within 0.003 mm (0.08%) of the corresponding in-vivo diameter of 3.6 mm, and the thickness of 0.269 mm was within 0.0015 mm (0.55%) of the in-vivo thickness of 0.27 mm. Under physiologic pulsatile pressure applied to the pre-stressed artery, the time averaged longitudinal stress was found to be 42.5% higher than the circumferential stresses. The results of this study are similar to the results reported by Zhang et al., (2005) for the left anterior descending coronary artery.
An inverse method was adopted to compute physiologic pre-stress in the arterial wall before conducting pulsatile hemodynamic calculations. The wall stresses were higher in magnitude in the longitudinal direction, under physiologic pressure after incorporating the effect of in-vivo axial stretch and pressure loading.
PMCID: PMC4306109  PMID: 25603022
13.  An assessment of intra-patient variability on observed relationships between wall shear stress and plaque progression in coronary arteries 
BioMedical Engineering OnLine  2015;14(Suppl 1):S2.
Wall shear stress (WSS) has been associated with sites of plaque localization and with changes in plaque composition in human coronary arteries. Different values have been suggested for categorizing WSS as low, physiologic or high; however, uncertainties in flow rates, both across subjects and within a given individual, can affect the classification of WSS and thus influence the observed relationships between local hemodynamics and plaque changes over time. This study examines the effects of uncertainties in flow rate boundary conditions upon WSS values and investigates the influence of this variability on the observed associations of WSS with changes in VH-IVUS derived plaque components.
Three patients with coronary artery disease underwent baseline and 12 month follow-up angiography and virtual histology-intravascular ultrasound (VH-IVUS) measurements. Coronary artery models were reconstructed from the data and models with and without side-branches were created. Patient-specific Doppler ultrasound (DUS) data were employed as inflow boundary conditions and computational fluid dynamics was used to calculate the WSS in each model. Further, the influence of representative coronary artery flow waveforms upon WSS values was investigated and the concept of treating WSS using relative, rather than actual, values was explored.
Models that included side-branch outflows and subject-specific DUS velocities were considered to be the reference cases. Hemodynamic differences were caused by the exclusion of side-branches and by imposing alternative velocity waveforms. One patient with fewer side-branches and a scaled generic waveform had little deviation from the reference case, while another patient with several side-branches excluded showed much larger departures from the reference situation. Differences between models and the respective reference cases were reduced when data were analyzed using relative, rather than actual, WSS.
When considering individual subjects, large variations in patient-specific flow rates and exclusion of multiple side-branches in computational models can cause significant differences in observed associations between plaque evolution and ranges of computed WSS. These differences may contribute to the large variability typically found among subjects in pooled populations. Relative WSS may be more useful than actual WSS as a correlative variable when there is a large degree of uncertainty in flow rate data.
PMCID: PMC4306111  PMID: 25603192
14.  Finite element analysis of mechanics of neovessels with intraplaque hemorrhage in carotid atherosclerosis 
BioMedical Engineering OnLine  2015;14(Suppl 1):S3.
Intraplaque hemorrhage is a widely known factor facilitating plaque instability. Neovascularization of plaque can be regarded as a compensatory response to the blood supply in the deep intimal and medial areas of the artery. Due to the physiological function, the deformation of carotid atherosclerotic plaque would happen under the action of blood pressure and blood flow. Neovessels are subject to mechanical loading and likely undergo deformation. The rupture of neovessels may deteriorate the instability of plaque. This study focuses on the local mechanical environments around neovessels and investigates the relationship between the biomechanics and the morphological specificity of neovessels.
Stress and stretch were used to evaluate the rupture risk of the neovessels in plaque. Computational structural analysis was performed based on two human carotid plaque slice samples. Two-dimensional models containing neovessels and other components were built according to the plaque slice samples. Each component was assumed to be non-linear isotropic, piecewise homogeneous and incompressible. Different mechanical boundary conditions, i.e. static pressures, were imposed in the carotid lumen and neovessels lumen respectively. Finite element method was used to simulate the mechanical conditions in the atherosclerotic plaque.
Those neovessels closer to the carotid lumen undergo larger stress and stretch. With the same distance to the carotid lumen, the longer the perimeter of neovessels is, the larger stress and the deformation of the neovessels will be. Under the same conditions, the neovessels with larger curvature suffer greater stress and stretch. Neovessels surrounded by red blood cells undergo a much larger stretch.
Local mechanical conditions may result in the hemorrhage of neovessels and accelerate the rupture of plaque. The mechanical environments of the neovessel are related to its shape, curvature, distance to the carotid lumen and the material properties of plaque.
PMCID: PMC4306113  PMID: 25603398
15.  Artery buckling affects the mechanical stress in atherosclerotic plaques 
BioMedical Engineering OnLine  2015;14(Suppl 1):S4.
Tortuous arteries are often seen in patients with hypertension and atherosclerosis. While the mechanical stress in atherosclerotic plaque under lumen pressure has been studied extensively, the mechanical stability of atherosclerotic arteries and subsequent effect on the plaque stress remain unknown. To this end, we investigated the buckling and post-buckling behavior of model stenotic coronary arteries with symmetric and asymmetric plaque.
Buckling analysis for a model coronary artery with symmetric and asymmetric plaque was conducted using finite element analysis based on the dimensions and nonlinear anisotropic materials properties reported in the literature.
Artery with asymmetric plaque had lower critical buckling pressure compared to the artery with symmetric plaque and control artery. Buckling increased the peak stress in the plaque and led to the development of a high stress concentration in artery with asymmetric plaque. Stiffer calcified tissue and severe stenosis increased the critical buckling pressure of the artery with asymmetric plaque.
Arteries with atherosclerotic plaques are prone to mechanical buckling which leads to a high stress concentration in the plaques that can possibly make the plaques prone to rupture.
PMCID: PMC4306115  PMID: 25603490
16.  Characterising human atherosclerotic carotid plaque tissue composition and morphology using combined spectroscopic and imaging modalities 
BioMedical Engineering OnLine  2015;14(Suppl 1):S5.
Calcification is a marked pathological component in carotid artery plaque. Studies have suggested that calcification may induce regions of high stress concentrations therefore increasing the potential for rupture. However, the mechanical behaviour of the plaque under the influence of calcification is not fully understood. A method of accurately characterising the calcification coupled with the associated mechanical plaque properties is needed to better understand the impact of calcification on the mechanical behaviour of the plaque during minimally invasive treatments. This study proposes a comparison of biochemical and structural characterisation methods of the calcification in carotid plaque specimens to identify plaque mechanical behaviour.
Biochemical analysis, by Fourier Transform Infrared (FTIR) spectroscopy, was used to identify the key components, including calcification, in each plaque sample. However, FTIR has a finite penetration depth which may limit the accuracy of the calcification measurement. Therefore, this FTIR analysis was coupled with the identification of the calcification inclusions located internally in the plaque specimen using micro x-ray computed tomography (μX-CT) which measures the calcification volume fraction (CVF) to total tissue content. The tissue characterisation processes were then applied to the mechanical material plaque properties acquired from experimental circumferential loading of human carotid plaque specimen for comparison of the methods.
FTIR characterised the degree of plaque progression by identifying the functional groups associated with lipid, collagen and calcification in each specimen. This identified a negative relationship between stiffness and 'lipid to collagen' and 'calcification to collagen' ratios. However, μX-CT results suggest that CVF measurements relate to overall mechanical stiffness, while peak circumferential strength values may be dependent on specific calcification geometries. This study demonstrates the need to fully characterise the calcification structure of the plaque tissue and that a combination of FTIR and μX-CT provides the necessary information to fully understand the mechanical behaviour of the plaque tissue.
PMCID: PMC4306117  PMID: 25602176
17.  Influence of model boundary conditions on blood flow patterns in a patient specific stenotic right coronary artery 
BioMedical Engineering OnLine  2015;14(Suppl 1):S6.
In literature, the effect of the inflow boundary condition was investigated by examining the impact of the waveform and the shape of the spatial profile of the inlet velocity on the cardiac hemodynamics. However, not much work has been reported on comparing the effect of the different combinations of the inlet/outlet boundary conditions on the quantification of the pressure field and flow distribution patterns in stenotic right coronary arteries.
Non-Newtonian models were used to simulate blood flow in a patient-specific stenotic right coronary artery and investigate the influence of different boundary conditions on the phasic variation and the spatial distribution patterns of blood flow. The 3D geometry of a diseased artery segment was reconstructed from a series of IVUS slices. Five different combinations of the inlet and the outlet boundary conditions were tested and compared.
The temporal distribution patterns and the magnitudes of the velocity, the wall shear stress (WSS), the pressure, the pressure drop (PD), and the spatial gradient of wall pressure (WPG) were different when boundary conditions were imposed using different pressure/velocity combinations at inlet/outlet. The maximum velocity magnitude in a cardiac cycle at the center of the inlet from models with imposed inlet pressure conditions was about 29% lower than that from models using fully developed inlet velocity data. Due to the fact that models with imposed pressure conditions led to blunt velocity profile, the maximum wall shear stress at inlet in a cardiac cycle from models with imposed inlet pressure conditions was about 29% higher than that from models with imposed inlet velocity boundary conditions. When the inlet boundary was imposed by a velocity waveform, the models with different outlet boundary conditions resulted in different temporal distribution patterns and magnitudes of the phasic variation of pressure. On the other hand, the type of different boundary conditions imposed at the inlet and the outlet did not have significant effect on the spatial distribution patterns of the PD, the WPG and the WSS on the lumen surface, regarding the locations of the maximum and the minimum of each quantity.
The observations from this study indicated that the ways how pressure and velocity boundary conditions are imposed in computational models have considerable impact on flow velocity and shear stress predictions. Accuracy of in vivo measurements of blood pressure and velocity is of great importance for reliable model predictions.
PMCID: PMC4306119  PMID: 25602370
18.  Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results 
BioMedical Engineering OnLine  2015;14(Suppl 1):S7.
Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue.
Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue.
Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen.
Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large discrepancies, future studies should seek to employ vessel-appropriate material models to simulate the response of diseased femoral tissue in order to obtain the most accurate numerical results.
PMCID: PMC4306121  PMID: 25602515
19.  Right ventricle-pulmonary circulation dysfunction: a review of energy-based approach 
BioMedical Engineering OnLine  2015;14(Suppl 1):S8.
Patients with repaired or palliated right heart congenital heart disease (CHD) are often left with residual lesions that progress and can result in significant morbidity. However, right ventricular-pulmonary arterial evaluation and the timing of reintvervention is still subjective. Currently, it relies on symptomology, or RV imaging-based metrics from echocardiography or MR derived parameters including right ventricular (RV) ejection fraction (EF), end-systolic pressure (ESP), and end-diastolic volume (EDV). However, the RV is coupled to the pulmonary vasculature, and they are not typically evaluated together. For example, the dysfunctional right ventricular-pulmonary circulation (RV-PC) adversely affects the RV myocardial performance resulting in decreased efficiency. Therefore, comprehensive hemodynamic assessment should incorporate changes in RV-PC and energy efficiency for CHD patients.
The ventricular pressure-volume relationship (PVR) and other energy-based endpoints derived from PVR, such as stroke work (SW) and ventricular elastance (Ees), can provide a measure of RV performance. However, a detailed explanation of the relationship between RV performance and pulmonary arterial hemodynamics is lacking. More importantly, PVR is impractical for routine longitudinal evaluation in a clinical setting, because it requires invasive catheterization. As an alternative, analytical methods and computational fluid dynamics (CFD) have been used to compute energy endpoints, such as power loss or energy dissipation, in abnormal physiologies.
In this review, we review the causes of RV-PA failure and the limitation of current clinical parameters to quantify RV-PC dysfunction. Then, we describe the advantage of currently available energy-based endpoints and emerging energy endpoints, such as energy loss in the Pas or kinetic energy, obtained from a new non-invasive imaging technique, i.e. 4D phase contrast MRI.
PMCID: PMC4306123  PMID: 25602641
20.  MRI-based strain and strain rate analysis of left ventricle: a modified hierarchical transformation model 
BioMedical Engineering OnLine  2015;14(Suppl 1):S9.
Different from other indicators of cardiac function, such as ejection fraction and transmitral early diastolic velocity, myocardial strain is promising to capture subtle alterations that result from early diseases of the myocardium. In order to extract the left ventricle (LV) myocardial strain and strain rate from cardiac cine-MRI, a modified hierarchical transformation model was proposed.
A hierarchical transformation model including the global and local LV deformations was employed to analyze the strain and strain rate of the left ventricle by cine-MRI image registration. The endocardial and epicardial contour information was introduced to enhance the registration accuracy by combining the original hierarchical algorithm with an Iterative Closest Points using Invariant Features algorithm. The hierarchical model was validated by a normal volunteer first and then applied to two clinical cases (i.e., the normal volunteer and a diabetic patient) to evaluate their respective function.
Based on the two clinical cases, by comparing the displacement fields of two selected landmarks in the normal volunteer, the proposed method showed a better performance than the original or unmodified model. Meanwhile, the comparison of the radial strain between the volunteer and patient demonstrated their apparent functional difference.
The present method could be used to estimate the LV myocardial strain and strain rate during a cardiac cycle and thus to quantify the analysis of the LV motion function.
PMCID: PMC4306125  PMID: 25602778
21.  Interactive simulator for e-Learning environments: a teaching software for health care professionals 
There is an established tradition of cardiovascular simulation tools, but the application of this kind of technology in the e-Learning arena is a novel approach. This paper presents an e-Learning environment aimed at teaching the interaction of cardiovascular and lung systems to health-care professionals. Heart-lung interaction must be analyzed while assisting patients with severe respiratory problems or with heart failure in intensive care unit. Such patients can be assisted by mechanical ventilatory assistance or by thoracic artificial lung.
“In silico” cardiovascular simulator was experimented during a training course given to graduate students of the School of Specialization in Cardiology at ‘Sapienza’ University in Rome.
The training course employed CARDIOSIM©: a numerical simulator of the cardiovascular system. Such simulator is able to reproduce pathophysiological conditions of patients affected by cardiovascular and/or lung disease. In order to study the interactions among the cardiovascular system, the natural lung and the thoracic artificial lung (TAL), the numerical model of this device has been implemented. After having reproduced a patient’s pathological condition, TAL model was applied in parallel and hybrid model during the training course.
Results obtained during the training course show that TAL parallel assistance reduces right ventricular end systolic (diastolic) volume, but increases left ventricular end systolic (diastolic) volume. The percentage changes induced by hybrid TAL assistance on haemodynamic variables are lower than those produced by parallel assistance. Only in the case of the mean pulmonary arterial pressure, there is a percentage reduction which, in case of hybrid assistance, is greater (about 40%) than in case of parallel assistance (20-30%).
At the end of the course, a short questionnaire was submitted to students in order to assess the quality of the course. The feedback obtained was positive, showing good results with respect to the degree of students’ learning and the ease of use of the software simulator.
PMCID: PMC4280694  PMID: 25522902
e-Learning; Numerical model; Cardiovascular system; Thoracic artificial lung assistance; Haemodynamic; Ontologies
22.  Real-time estimation of respiratory rate from a photoplethysmogram using an adaptive lattice notch filter 
Many researchers have attempted to acquire respiratory rate (RR) information from a photoplethysmogram (PPG) because respiration affects the waveform of the PPG. However, most of these methods were difficult to operate in real-time because of their complexity or computational requirements. From these needs, we attempted to develop a method to estimate RR from a PPG with a light computational burden.
To obtain RR information, we adopt a sequential filtering structure and frequency estimation technique, which extracts a dominant frequency from a given signal. In particular, we used an adaptive lattice notch filter (ALNF) to estimate RR from a PPG along with an additional heart rate that is utilized as an adaptation parameter of our method. Furthermore, we designed a sequential infinite impulse response (IIR) notch filtering system (i.e., harmonic IIR notch filter) to eliminate the cardiac component and its harmonics from the PPG. We compared the proposed method with Burg’s AR modeling method, which is widely used to estimate RR from a PPG, using open-source data and measured data.
By using a statistical test, it was determined that our adaptive lattice-type respiratory rate estimator (ALRE) was significantly more accurate than Burg’s AR model method (p <0.0001). Furthermore, the ALRE’s tracking performance was better than that of Burg’s method, and the variances of its estimates were smaller than those of Burg’s method.
In short, our method showed a better performance than Burg’s AR modeling method for real-time applications.
PMCID: PMC4277838  PMID: 25518918
23.  Simulation of in vivo dynamics during robot assisted joint movement 
Robots are very useful tools in orthopedic research. They can provide force/torque controlled specimen motion with high repeatability and precision. A method to analyze dissipative energy outcome in an entire joint was developed in our group. In a previous study, a sheep knee was flexed while axial load remained constant during the measurement of dissipated energy. We intend to apply this method for the investigation of osteoarthritis. Additionally, the method should be improved by simulation of in vivo knee dynamics. Thus, a new biomechanical testing tool will be developed for analyzing in vitro joint properties after different treatments.
Discretization of passive knee flexion was used to construct a complex flexion movement by a robot and simulate altering axial load similar to in vivo sheep knee dynamics described in a previous experimental study.
The robot applied an in vivo like axial force profile with high reproducibility during the corresponding knee flexion (total standard deviation of 0.025 body weight (BW)). A total residual error between the in vivo and simulated axial force was 0.16 BW. Posterior-anterior and medio-lateral forces were detected by the robot as a backlash of joint structures. Their curve forms were similar to curve forms of corresponding in vivo measured forces, but in contrast to the axial force, they showed higher total standard deviation of 0.118 and 0.203 BW and higher total residual error of 0.79 and 0.21 BW for posterior-anterior and medio-lateral forces respectively.
We developed and evaluated an algorithm for the robotic simulation of complex in vivo joint dynamics using a joint specimen. This should be a new biomechanical testing tool for analyzing joint properties after different treatments.
PMCID: PMC4279817  PMID: 25516427
24.  Examination of ceramic restoration adhesive coverage in cusp-replacement premolar using acoustic emission under fatigue testing 
This study investigates CAD/CAM ceramic cusp-replacing restoration resistance with and without buccal cusp replacement under static and dynamic cyclic loads, monitored using the acoustic emission (AE) technique.
The cavity was designed in a typical MODP (mesial-occlusal-distal-palatal) restoration failure shape when the palatal cusp has been lost. Two ceramic restorations [without coverage (WOC) and with (WC) buccal cuspal coverage with 2.0 mm reduction in cuspal height] were prepared to perform the fracture and fatigue tests with normal (200 N) and high (600 N) occlusal forces. The load versus AE signals in the fracture and fatigue tests were recorded to evaluate the restored tooth failure resistance.
The results showed that non-significant differences in load value in the fracture test and the accumulated number of AE signals under normal occlusal force (200 N) in the fatigue test were found between with and without buccal cuspal coverage restorations. The first AE activity occurring for the WOC restoration was lower than that for the WC restoration in the fracture test. The number of AE signals increased with the cyclic load number. The accumulated number of AE signals for the WOC restoration was 187, higher than that (85) for the WC restoration under 600 N in the fatigue test.
The AE technique and fatigue tests employed in this study were used as an assessment tool to evaluate the resistances in large CAD/CAM ceramic restorations. Non-significant differences in the tested fracture loads and accumulated number of AE signals under normal occlusal force (200 N) between different restorations indicated that aggressive treatment (with coverage preparation) in palatal cusp-replacing ceramic premolars require more attention for preserving and protecting the remaining tooth.
PMCID: PMC4273487  PMID: 25495010
Cuspal-coverage; Ceramic; Acoustic emission; Fatigue; CAD/CAM
25.  Computer modeling and ex vivo experiments with a (saline-linked) irrigated electrode for RF-assisted heating 
Externally irrigated radiofrequency (RF) electrodes have been widely used to thermally ablate tumors in surface tissue and to thermally coagulate the transection plane during a surgical resection. As far as we know, no mathematical model has yet been developed to study the electrical and thermal performance of these electrodes, especially the role of the saline layer that forms around the electrode.
Numerical models of a TissueLink device model DS3.0 (Salient Surgical Technologies, Portsmouth, NH, USA) were developed. Irrigation was modeled including a saline layer and a heat convection term in the governing equation. Ex vivo experiments based on fragments of bovine hepatic tissue were conducted to obtain information which was used in building the numerical model. We compared the 60°C isotherm of the computer results with the whitening contour in the heated samples.
Computer and experimental results were in fine agreement in terms of lesion depth (2.4 mm in the simulations and 2.4 ± 0.6 mm in the experiments). In contrast, the lesion width was greater in the simulation (9.6 mm vs. 7.8 ± 1.8 mm). The computer simulations allowed us to explain the role of the saline layer in creating the thermal lesion. Impedance gradually decreased as heating proceeded. The saline was not observed to boil. In the proximity of the electrode (around 1 mm) the thermal lesion was mainly created by the RF power in this zone, while at a further distance the thermal lesion was created by the hot saline on the tissue surface by simple thermal conduction. Including the heat convection term associated with the saline velocity in the governing equation was crucial to verifying that the saline layer had not reached boiling temperature.
The model reproduced thermal performance during heating in terms of lesion depth, and provided an explanation for: 1) the relationship between impedance, electrode insertion depth, and saline layer, and 2) the process of creating thermal lesions in the tissue with this type of electrode.
PMCID: PMC4271499  PMID: 25494912
Computer modeling; Irrigated electrode; Mathematical modeling; Radiofrequency ablation; Radiofrequency-assisted resection; Saline-linked technology

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