Flow Imaging Method Research Articles

Blood flow imaging of high frame rate two‐dimensional vector in cardiovascular ultrasound detection

Traditional cardiovascular ultrasound detection using focused ultrasound can cause a decrease in frame rate, which affects the results of the diagnosis. In order to improve the effect of cardiovascular ultrasound detection, this study used ultrasound vector blood flow imaging technology to improve the image frame rate and introduce planar high frame rate imaging technology. Simultaneously, this work studies the parameters of the image through parameter analysis and combines the advantages of various methods to improve the analysis. In addition, this work proposes a high frame rate blood flow imaging method, and designs simulation experiments to analyse the effectiveness of the method. The results show that the proposed algorithm has a certain effect in two-dimensional vector blood flow imaging, which can be applied to clinical practice, and can provide theoretical reference for subsequent related research.

Basic study on estimation method of wall shear stress in common carotid artery using blood flow imaging

In this paper, we propose a method for adaptive selection of the kernel size used in estimation of the wall shear stress (WSS) based on flow velocity profiles obtained by the blood flow imaging method based on enhancement of RF echo signals from blood cells using a singular value decomposition based clutter filter. Two simulation phantom experiments with the Field II program were performed to validate the proposed method. In the simulation experiments, the average bias error (BE) between the WSSs estimated by the conventional method and theoretical one was 16.5%. The proposed method could reduce the average BE to 12.3%. Also, the proposed method was applied to RF echo signals from a common carotid artery (CCA) of a healthy male subject. The WSSs in the CCA were estimated during one cardiac cycle and in a range similar to that in previous reports.

A novel gas/liquid two-phase flow imaging method through electrical resistance tomography with DDELM-AE sparse dictionary

PurposeThe purpose of this paper is to explore gas/liquid two-phase flow is widely existed in industrial fields, especially in chemical engineering. Electrical resistance tomography (ERT) is considered to be one of the most promising techniques to monitor the transient flow process because of its advantages such as fast respond speed and cross-section imaging. However, maintaining high resolution in space together with low cost is still challenging for two-phase flow imaging because of the ill-conditioning of ERT inverse problem.Design/methodology/approachIn this paper, a sparse reconstruction (SR) method based on the learned dictionary has been proposed for ERT, to accurately monitor the transient flow process of gas/liquid two-phase flow in a pipeline. The high-level representation of the conductivity distributions for typical flow regimes can be extracted based on denoising the deep extreme learning machine (DDELM) model, which is used as prior information for dictionary learning.FindingsThe results from simulation and dynamic experiments indicate that the proposed algorithm efficiently improves the quality of reconstructed images as compared to some typical algorithms such as Landweber and SR-discrete fourier transformation/discrete cosine transformation. Furthermore, the SR-DDELM has also used to estimate the important parameters of the chemical process, a case in point is the volume flow rate. Therefore, the SR-DDELM is considered an ideal candidate for online monitor the gas/liquid two-phase flow.Originality/valueThis paper fulfills a novel approach to effectively monitor the gas/liquid two-phase flow in pipelines. One deep learning model and one adaptive dictionary are trained via the same prior conductivity, respectively. The model is used to extract high-level representation. The dictionary is used to represent the features of the flow process. SR and extraction of high-level representation are performed iteratively. The new method can obviously improve the monitoring accuracy and save calculation time.

ART-TV Algorithm for Diffuse Correlation Tomography Blood Flow Imaging

Near-infrared diffuse correlation imaging (DCT) is an important method of tissue blood flow imaging for the prognosis and diagnosis of various diseases. A new solution of DCT that is based on the $N$ th-order linear (NL) algorithm, termed as NL-DCT, was proposed in our previous study to overcome the limitations of tissue geometry and heterogeneity. The NL-DCT converts the image reconstruction into linear equations, and this solution is an ill-posed problem in mathematics. To improve the accuracy and robustness of the DCT image reconstruction, a combination of algebra reconstruction technique (ART) and total variation (TV), namely ART-TV, is proposed in this study. After each ART iteration, the TV model is used as an a priori constraint to reduce noise. The validations from computer simulation and phantom experiments with different anomalies demonstrate that the proposed ART-TV algorithm is efficient in DCT blood flow image reconstruction.

Increased stiffness and flow resistance of the inner wall of Schlemm’s canal in glaucomatous human eyes

The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-µm spherical tips to probe the stiffness of the inner wall of Schlemm's canal as a function of distance from the tissue surface in normal and glaucomatous postmortem human eyes, and 1-µm spherical AFM tips to probe the region immediately below the tissue surface. To localize flow resistance, perfusion and imaging methods were used to characterize the pressure drop in the immediate vicinity of the inner wall using giant vacuoles that form in Schlemm's canal cells as micropressure sensors. Tissue stiffness increased with increasing AFM indentation depth. Tissues from glaucomatous eyes were stiffer compared with normal eyes, with greatly increased stiffness residing within ∼1 µm of the inner-wall surface. Giant vacuole size and density were similar in normal and glaucomatous eyes despite lower flow rate through the latter due to their higher flow resistance. This implied that the elevated flow resistance found in the glaucomatous eyes was localized to the same region as the increased tissue stiffness. Our findings implicate pathological changes to biophysical characteristics of Schlemm's canal endothelia and/or their immediate underlying extracellular matrix as cause for ocular hypertension in glaucoma.

Vector Flow Imaging Compared with Digital Subtraction Angiography for Stenosis Assessment in the Superficial Femoral Artery - A Study of Vector Concentration, Velocity Ratio and Stenosis Degree Percentage.

PurposeStenosis of the superficial femoral artery (SFA) induces complex blood flow with increased velocities. Disease assessment is performed with Doppler ultrasound and digital subtraction angiography (DSA), but Doppler ultrasound is limited by angle dependency and DSA by ionizing radiation. An alternative is the vector flow imaging method based on transverse oscillation (TO), an angle-independent vector velocity technique using ultrasound. In this study, flow complexity and velocity measured with TO were compared with DSA for the assessment of stenosis in the SFA.Materials and MethodsThe vector concentration, a measure of flow complexity, and the velocity ratio obtained from the stenosis and a disease-free adjacent vessel segment, were estimated with TO in 11 patients with a total of 16 stenoses of the SFA. TO data were compared with the corresponding stenosis degree percentage obtained with DSA.ResultsThe correlation between the vector concentration and DSA was very strong (R=0.93; p<0.001; 95% confidence interval (CI): 0.81–0.98), while only moderate for velocity ratio and DSA (R=0.50; p<0.07; 95% CI: 0.00–0.80). The correlation coefficients that were found were significantly different (p<0.005) without overlapping CI.ConclusionThe study indicated that flow changes in the SFA induced by stenosis can be quantified with TO, and that stenosis grading may be improved by estimation of flow complexity instead of velocity ratio. TO is a potential diagnostic tool for the assessment of atherosclerosis and peripheral arterial disease.

Portable Vector Flow Imaging Compared With Spectral Doppler Ultrasonography

In this study, a vector flow imaging (VFI) method developed for a portable ultrasound scanner was used for estimating peak velocity values and variation in beam-to-flow angle over the cardiac cycle in vivo on healthy volunteers. Peak-systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) measured with VFI were compared to spectral Doppler ultrasonography (SDU). Seventeen healthy volunteers were scanned on the left and right common carotid arteries (CCAs). The standard deviation (SD) of VFI measurements averaged over the cardiac cycle was 7.3% for the magnitude and 3.84° for the angle. Bland-Altman plots showed a positive bias for the PSV measured with SDU (mean difference: 0.31 ms -1 ), and Pearson correlation analysis showed a highly significant correlation ( r = 0.6 ; ). A slightly positive bias was found for EDV and RI measured with SDU (mean difference: 0.08 ms -1 and -0.01 ms -1 , respectively). However, the correlation was low and not significant. The beam-to-flow angle was estimated over the systolic part of the cardiac cycle, and its variations were for all measurements larger than the precision of the angle estimation. The range spanned deviations from -25.2° (-6.0 SD) to 23.7° (4.2 SD) with an average deviation from -15.2° to 9.7°. This can significantly affect PSV values measured by SDU as the beam-to-flow angle is not constant and not aligned with the vessel surface. The study demonstrates that the proposed VFI method can be used in vivo for the measurement of PSV in the CCAs, and that angle variations across the cardiac cycle can lead to significant errors in SDU velocity estimates.

Photoacoustic speckle tracking for motion estimation and flow analysis.

This study explores photoacoustic (PA) speckle tracking to characterize flow as an alternative to ultrasound (US) speckle tracking or current PA flow imaging methods. In cases where tracking of submicrometer particles is required, the US signal-to-noise ratio and contrast might be low due to limited reflectivity of subwavelength size targets at low concentrations. However, it may be possible to perform more accurate velocimetry using PAs due to different contrast mechanisms utilized in PA imaging. Here, we introduce a PA-based speckle tracking method that overcomes the directional dependence of Doppler imaging and the limited field of view of current correlation-based methods used in PA flow imaging. The feasibility of this method is demonstrated in a potential application-minimally invasive diagnosis of ventricular shunt malfunction, where the velocity of optically absorbing particles was estimated in a shunt catheter using block matching of PA and US signals. Overall, our study demonstrates the potential of the PA-based motion tracking method under various flow rates where US imaging cannot be effectively used for specking tracking because of its low contrast and low signal-to-noise ratio.

Evaluation of Peak Reflux Velocities with Vector Flow Imaging and Spectral Doppler Ultrasound in Varicose Veins.

Purpose Spectral Doppler ultrasound (SDUS) is used for quantifying reflux in lower extremity varicose veins. The technique is angle-dependent opposed to the new angle-independent Vector Flow Imaging (VFI) method. The aim of this study was to compare peak reflux velocities obtained with VFI and SDUS in patients with chronic venous disease, i. e., pathological retrograde blood flow caused by incompetent venous valves. Materials and Methods 64 patients with chronic venous disease were scanned with VFI and SDUS in the great or the small saphenous vein, and reflux velocities were compared to three assessment tools for chronic venous disease. A flow rig was used to assess the accuracy and precision of the two methods. Results The mean peak reflux velocities differed significantly (VFI: 47.4 cm/s vs. SDUS: 62.0 cm/s, p<0.001). No difference in absolute precision (p=0.18) nor relative precision (p=0.79) was found. No correlation to disease severity, according to assessment tools, was found for peak reflux velocities obtained with either method. In vitro, VFI was more accurate but equally precise when compared to SDUS. Conclusion Both VFI and SDUS detected the pathologic retrograde flow in varicose veins but measured different reflux velocities with equal precision. VFI may play a role in evaluating venous disease in the future.

Collaborative Study for Analysis of Subvisible Particles Using Flow Imaging and Light Obscuration: Experiences in Japanese Biopharmaceutical Consortium

The evaluation of subvisible particles, including protein aggregates, in therapeutic protein products has been of great interest for both pharmaceutical manufacturers and regulatory agencies. To date, the flow imaging (FI) method has emerged as a powerful tool instead of light obscuration (LO) due to the fact that (1) protein aggregates contain highly transparent particles and thereby escape detection by LO and (2) FI provides detailed morphological characteristics of subvisible particles. However, the FI method has not yet been standardized nor listed in any compendium. In an attempt to assess the applicability of the standardization of the FI method, we conducted a collaborative study using FI and LO instruments in a Japanese biopharmaceutical consortium. Three types of subvisible particle preparations were shared across 12 laboratories and analyzed for their sizes and counts. The results were compared between the methods (FI and LO), inter-laboratories, and inter-instruments (Micro Flow Imaging and FlowCam). We clarified the marked difference between the detectability of FI and LO when counting highly transparent protein aggregates in the preparations. Although FlowCam provided a relatively higher number of particles compared with MFI, consistent results were obtained using the instrument from the same manufacturer in all 3 samples.

Label-Free, Flow-Imaging Methods for Determination of Cell Concentration and Viability

PurposeTo investigate the potential of two flow imaging microscopy (FIM) techniques (Micro-Flow Imaging (MFI) and FlowCAM) to determine total cell concentration and cell viability.MethodsB-lineage acute lymphoblastic leukemia (B-ALL) cells of 2 different donors were exposed to ambient conditions. Samples were taken at different days and measured with MFI, FlowCAM, hemocytometry and automated cell counting. Dead and live cells from a fresh B-ALL cell suspension were fractionated by flow cytometry in order to derive software filters based on morphological parameters of separate cell populations with MFI and FlowCAM. The filter sets were used to assess cell viability in the measured samples.ResultsAll techniques gave fairly similar cell concentration values over the whole incubation period. MFI showed to be superior with respect to precision, whereas FlowCAM provided particle images with a higher resolution. Moreover, both FIM methods were able to provide similar results for cell viability as the conventional methods (hemocytometry and automated cell counting).ConclusionFIM-based methods may be advantageous over conventional cell methods for determining total cell concentration and cell viability, as FIM measures much larger sample volumes, does not require labeling, is less laborious and provides images of individual cells.

Accuracy and Precision of a Plane Wave Vector Flow Imaging Method in the Healthy Carotid Artery

The objective of the study described here was to investigate the accuracy and precision of a plane wave 2-D vector flow imaging (VFI) method in laminar and complex blood flow conditions in the healthy carotid artery. The approach was to study (i) the accuracy for complex flow by comparing the velocity field from a computational fluid dynamics (CFD) simulation to VFI estimates obtained from the scan of an anthropomorphic flow phantom and from an in vivo scan; (ii) the accuracy for laminar unidirectional flow in vivo by comparing peak systolic velocities from VFI with magnetic resonance angiography (MRA); (iii) the precision of VFI estimation in vivo at several evaluation points in the vessels. The carotid artery at the bifurcation was scanned using both fast plane wave ultrasound and MRA in 10 healthy volunteers. The MRA geometry acquired from one of the volunteers was used to fabricate an anthropomorphic flow phantom, which was also scanned using the fast plane wave sequence. The same geometry was used in a CFD simulation to calculate the velocity field. Results indicated that similar flow patterns and vortices were estimated with CFD and VFI in the phantom for the carotid bifurcation. The root-mean-square difference between CFD and VFI was within 0.12 m/s for velocity estimates in the common carotid artery and the internal branch. The root-mean-square difference was 0.17 m/s in the external branch. For the 10 volunteers, the mean difference between VFI and MRA was −0.17 m/s for peak systolic velocities of laminar flow in vivo. The precision in vivo was calculated as the mean standard deviation (SD) of estimates aligned to the heart cycle and was highest in the center of the common carotid artery (SD = 3.6% for velocity magnitudes and 4.5° for angles) and lowest in the external branch and for vortices (SD = 10.2% for velocity magnitudes and 39° for angles). The results indicate that plane wave VFI measures flow precisely and that estimates are in good agreement with a CFD simulation and MRA.

Manipulation-free cultures of human iPSC-derived cardiomyocytes offer a novel screening method for cardiotoxicity.

Induced pluripotent stem cell (iPSC)-based cardiac regenerative medicine requires the efficient generation, structural soundness and proper functioning of mature cardiomyocytes, derived from the patient's somatic cells. The most important functional property of cardiomyocytes is the ability to contract. Currently available methods routinely used to test and quantify cardiomyocyte function involve techniques that are labor-intensive, invasive, require sophisticated instruments or can adversely affect cell vitality. We recently developed optical flow imaging method analyses and quantified cardiomyocyte contractile kinetics from video microscopic recordings without compromising cell quality. Specifically, our automated particle image velocimetry (PIV) analysis of phase-contrast video images captured at a high frame rate yields statistical measures characterizing the beating frequency, amplitude, average waveform and beat-to-beat variations. Thus, it can be a powerful assessment tool to monitor cardiomyocyte quality and maturity. Here we demonstrate the ability of our analysis to characterize the chronotropic responses of human iPSC-derived cardiomyocytes to a panel of ion channel modulators and also to doxorubicin, a chemotherapy agent with known cardiotoxic side effects. We conclude that the PIV-derived beat patterns can identify the elongation or shortening of specific phases in the contractility cycle, and the obtained chronotropic responses are in accord with known clinical outcomes. Hence, this system can serve as a powerful tool to screen the new and currently available pharmacological compounds for cardiotoxic effects.

Tomographic Wire-Mesh Imaging of Water-Air Flow Based on Sparse Minimization

The wire-mesh sensor is widely used in the measurement of two-phase flow. Comparing with the other flow imaging methods, the wire-mesh method has the advantages of high temporal resolution, cost efficiency, and with high robustness against effects of flow patterns, but suffers from the comparatively low resolution. In this paper, a tomographic method was proposed to enhance the spatial resolution of the wire-mesh sensor. The wire-mesh image is refined through reconstruction with a linear observation model and the raw data from the wire-mesh sensor. The sparse minimization method with folded concave penalty was presented to solve the image reconstruction problem. The numerical and experimental results show that the proposed method can produce the resolution-enhanced wire-mesh images with less artifacts and distinct phase interfaces, and thus gives a theoretically possibility to observing the details of the target flow conditions.

The Research on Flow Imaging and Flow Profile Interpretation Method in Shale Gas Horizontal Well Multiphase Flow

Multiphase flow state is complex in shale gas horizontal well. Using foreign array probe tools to accurately monitor fluid production location and flowrate is very important, but at present domestic flow imaging and flow profile interpretation technology is still immature. In this paper, based on analysis the structure and characteristics of Schlumberger FSI (Flow Scanning Imager), firstly, the multiphase flow in shale gas horizontal wells was numerically simulated by Fluent software, and the velocity and pressure distributions were obtained. Compared with the typical horizontal well gas-water two-phase flow pattern classification, the two methods are in good agreement. Secondly, using the methods of gridding and simple inverse distance interpolation, the calculation of holdup and average velocity are carried out. After that, considering the deviation and flow pattern, the calculation method of key parameters was deduced such as the apparent velocity, phase distribution coefficient and drift velocity. What’s more, Flow profile interpretation model is established in horizontal air-water two-phase. In the end, the field test data show that three-dimensional flow imaging effect and interpretation precision is good for stratified flow.

Spiral Flow Phantom for Ultrasound Flow Imaging Experimentation.

As new ultrasound flow imaging methods are being developed, there is a growing need to devise appropriate flow phantoms that can holistically assess the accuracy of the derived flow estimates. In this paper, we present a novel spiral flow phantom design whose Archimedean spiral lumen naturally gives rise to multi-directional flow over all possible angles (i.e., from 0° to 360°). Developed using lost-core casting principles, the phantom geometry comprised a three-loop spiral (4-mm diameter and 5-mm pitch), and it was set to operate in steady flow mode (3 mL/s flow rate). After characterizing the flow pattern within the spiral vessel using computational fluid dynamics (CFD) simulations, the phantom was applied to evaluate the performance of color flow imaging (CFI) and high-frame-rate vector flow imaging. Significant spurious coloring artifacts were found when using CFI to visualize flow in the spiral phantom. In contrast, using vector flow imaging (least-squares multi-angle Doppler based on a three-transmit and three-receive configuration), we observed consistent depiction of flow velocity magnitude and direction within the spiral vessel lumen. The spiral flow phantom was also found to be a useful tool in facilitating demonstration of dynamic flow visualization based on vector projectile imaging. Overall, these results demonstrate the spiral flow phantom's practical value in analyzing the efficacy of ultrasound flow estimation methods.

A Vector Flow Imaging Method for Portable Ultrasound Using Synthetic Aperture Sequential Beamforming.

This paper presents a vector flow imaging method for the integration of quantitative blood flow imaging in portable ultrasound systems. The method combines directional transverse oscillation (TO) and synthetic aperture sequential beamforming to yield continuous velocity estimation in the whole imaging region. Six focused emissions are used to create a high-resolution image (HRI), and a dual-stage beamforming approach is used to lower the data throughput between the probe and the processing unit. The transmit/receive focal points are laterally separated to obtain a TO in the HRI that allows for the velocity estimation along the lateral and axial directions using a phase-shift estimator. The performance of the method was investigated with constant flow measurements in a flow rig system using the SARUS scanner and a 4.1-MHz linear array. A sequence was designed with interleaved B-mode and flow emissions to obtain continuous data acquisition. A parametric study was carried out to evaluate the effect of critical parameters. The vessel was placed at depths from 20 to 40 mm, with beam-to-flow angles of 65°, 75°, and 90°. For the lateral velocities at 20 mm, a bias between -5% and -6.2% was obtained, and the standard deviation (SD) was between 6% and 9.6%. The axial bias was lower than 1% with an SD around 2%. The mean estimated angles were 66.70° ± 2.86°, 72.65° ± 2.48°, and 89.13° ± 0.79° for the three cases. A proof-of-concept demonstration of the real-time processing and wireless transmission was tested in a commercial tablet obtaining a frame rate of 27 frames/s and a data rate of 14 MB/s. An in vivo measurement of a common carotid artery of a healthy volunteer was finally performed to show the potential of the method in a realistic setting. The relative SD averaged over a cardiac cycle was 4.33%.

Abstract 3008: Preclinical characterization of AMG 900, a pan-aurora kinase inhibitor, alone and in combination with taxanes in ovarian cancer

Abstract BACKGROUND: Aurora kinases (AK) A and B play essential roles in multiple stages of mitosis and are frequently overexpressed in a subset of human cancers, including ovarian cancer (OC). AMG 900, a potent and highly selective small molecule inhibitor of AKs, showed promising single-agent activity in heavily pretreated patients with advanced OC in a Phase 1b clinical trial. In this study, we report the preclinical effects of AMG 900 in a panel of well-characterized human cancer cell lines representing clinically-relevant OC subtypes. METHODS: The anti-proliferative effects of AMG 900 were evaluated using a 5-day cell count assay. Cell lines were classified as sensitive to AMG 900 when lethality was &amp;gt; 15% at 10 nM. Molecular markers were profiled including TP53 mutation status, AURKA, CCNE1, MYC copy number, and p53, p21 and cyclin E1 protein by reverse phase protein array. Flow cytometry and imaging methods were used to evaluate the mechanism of action of AMG 900 alone and in combination with chemotherapy. The combination of AMG 900 plus docetaxel was evaluated in an IGROV-1 ovarian endometrioid carcinoma xenograft model. RESULTS: One third of the cell lines (11 of 35) were classified as sensitive to AMG 900 and showed enrichment for TP53 mutations and serous OC subtype. However, 10 of 24 resistant cell lines harbored TP53 mutations, indicating that TP53 mutational status alone was not sufficient for predicting AMG 900 sensitivity. Inhibition of AK activity by AMG 900 in OC cells resulted in aborted cell division leading to polyploidy and cell death (suggestive of aurora-B dominant phenotype). Re-plating of remnant cells after AMG 900 treatment showed an attenuation of cell regrowth, where TP53mut IGROV-1 cells showed minimal regrowth compared to TP53wt OVCAR-5 cells. AMG 900 inhibited proliferation at low nanomolar concentrations in the majority of OC cell lines and enhanced the effects of paclitaxel, carboplatin, and doxorubicin in IGROV-1 cells. In tumor-bearing mice, administration of AMG 900 at 7.5 mg/kg (PO) for two days per week or docetaxel at 10 mg/kg (IP) weekly for four cycles significantly inhibited the growth of IGROV-1 tumor xenografts (P &amp;lt; .0001 vs. vehicle alone). Notably, co-administration of AMG 900 with docetaxel enhanced efficacy and induced a delay in tumor regrowth compared to docetaxel alone. Single-agent-treated mice showed minimal body weight loss (BWL), whereas combination-treated mice showed moderate BWL (average &amp;lt; 10%) that was largely reversible (2 of 12 animals removed due to toxicity). CONCLUSIONS: AMG 900 alone or in combination with chemotherapy such as paclitaxel may be a promising clinical strategy to treat patients with ovarian cancer. Citation Format: Ondrej Kalous, Dylan Conklin, Kanthinh Manivong, William Wayne, Kelly Hanestad, Jude Canon, Robert Loberg, Gregory Friberg, Erick Gamelin, Florian D. Vogl, Gloria Juan, Angela Coxon, Dennis Slamon, Richard Finn, Marc Payton. Preclinical characterization of AMG 900, a pan-aurora kinase inhibitor, alone and in combination with taxanes in ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3008.

Development of Flow Imaging Analysis for Subvisible Particle Characterization in Glatiramer Acetate

Proteins, peptides, colloids, and polymers present a rapidly growing field of pharmaceutical industry. Bringing these products into market, however, is a huge regulatory challenge, especially because many of these therapeutics are intended for parenteral administration. Physicochemical properties of such products--size, shape, surface potential, and extent of particle-particle interaction-have to be well understood and monitored throughout manufacturing, release, and stability testing. First and foremost, size distribution of subvisible particles (SVP) in these products should be reliably measured. We present development of a flow imaging method to assess SVP in the polypeptide injectable therapeutic product-glatiramer acetate (Copaxone(®)). Flow imaging comprises optical inspection of a flowing liquid and allows quantitation of particles in the range of 1-500 μm. The challenges of method development are discussed and the method performance characteristics--accuracy, precision, linearity, and specificity--are demonstrated.

Thermal imaging of the skin blood flow oscillations in extremities: modification of the spectral components

Objective. The aim of the study was description of the method of skin blood flow imaging via spectral processing of the dynamic thermograms of extremities. Materials and methods. The method realized by decomposition of the temperature signal into spectral components, modification of the spectral components and inverse transform of the spectral components into a new signal, which is considered as blood flow. Modification of spectral components was accomplished taking into account skin properties, and intended for the compensation of attenuation and time lag of temperature spectral components relative to blood flow components. Results. Blood flow maps of hands during arm cuff test have been demonstrated. Blood flow values calculated from the dynamic thermogram have been validated by photoplethysmography. The technique allows restoring of the blood flow oscillations at any point of the thermogram of the object. Benefits of thermal imaging of blood flow are the following: results are not depended from the ambient light, the method not critical to the camera angle, and blood flow maps can be registered both from the whole body and small areas. The method of blood flow imaging, in a long view, applicable for the monitoring of the skin microcirculation in progression and treatment of diabetic foot syndrome, Raynaud's syndrome, as well as burn, frostbite, mechanical injury, and atherosclerosis.