A Wearable Open-Source electrical impedance tomography device.

Electrical impedance tomography (EIT) is medical imaging technique in which small electrical signals are used to map the electrical impedance distribution within the body. It is safe and non-invasive, which make it attractive for use in continuous monitoring or outpatient applications, but the high cost of commercial devices is an impediment to its adoption. Over the last 10 years, many research groups have developed their own EIT devices, but few designs for open-source EIT hardware are available. In this work, we present a complete open-source EIT system that is designed to be suitable for monitoring the lungs of free breathing subjects. The device is low-cost, wearable, and is designed to comply with the industry accepted safety standard for EIT. The device has been tested in two regimes: Firstly in terms of measurement uncertainty as a voltage measurement system, and secondly against a set of measures that have been proposed specifically for EIT hardware. The voltage measurement uncertainty of the device was measured to be - 0.7 % ± 0.36 mV. The EIT specific performance was measured in a phantom test designed to be as physiologically representative as practicable, and the device performed similarly to other published devices. This work will contribute to increased accessibility of EIT for study and will contribute to consensus on testing methodology for EIT devices.

A pneumatic reconfigurable socket for transtibial amputees.

Many transtibial amputees rate the fit between their residual limb and prosthetic socket as the most critical factor in satisfaction with using their prosthesis. This study aims to address the issue of prosthetic socket fit by reconfiguring the socket shape at the interface of the residual limb and socket. The proposed reconfigurable socket shifts pressure from sensitive areas and compensates for residual limb volume fluctuations, the most important factors in determining a good socket fit. Computed tomography scan images are employed to create the phantom limb of an amputee and to manufacture the reconfigurable socket. The performance of the reconfigurable socket was evaluated both experimentally and numerically using finite element modelling. The study showed that the reconfigurable socket can reduce interface pressure at targeted areas by up to 61%.

A novel two-dimensional phantom for electrical impedance tomography using 3D printing.

Electrical impedance tomography (EIT) is an imaging method that can be used to image electrical impedance contrasts within various tissues of the body. To support development of EIT measurement systems, a phantom is required that represents the electrical characteristics of the imaging domain. No existing type of EIT phantom combines good performance in all three characteristics of resistivity resolution, spatial resolution, and stability. Here, a novel EIT phantom concept is proposed that uses 3D printed conductive material. Resistivity is controlled using the 3D printing infill percentage parameter, allowing arbitrary resistivity contrasts within the domain to be manufactured automatically. The concept of controlling resistivity through infill percentage is validated, and the manufacturing accuracy is quantified. A method for making electrical connections to the 3D printed material is developed. Finally, a prototype phantom is printed, and a sample EIT analysis is performed. The resulting phantom, printed with an Ultimaker S3, has high reported spatial resolution of 6.9 µm, 6.9 µm, and 2.5 µm for X, Y, and Z axis directions, respectively (X and Y being the horizontal axes, and Z the vertical). The number of resistivity levels that are manufacturable by varying infill percentage is 15 (calculated by dividing the available range of resistivities by two times the standard deviation of the manufacturing accuracy). This phantom construction technique will allow assessment of the performance of EIT devices under realistic physiological scenarios.

Quantifying changes in shoulder orientation between the prone and supine positions from magnetic resonance imaging.

BACKGROUND: Predicting breast tissue motion using biomechanical models can provide navigational guidance during breast cancer treatment procedures. These models typically do not account for changes in posture between procedures. Difference in shoulder position can alter the shape of the pectoral muscles and breast. A greater understanding of the differences in the shoulder orientation between prone and supine could improve the accuracy of breast biomechanical models. METHODS: 19 landmarks were placed on the sternum, clavicle, scapula, and humerus of the shoulder girdle in prone and supine breast MRIs (N = 10). These landmarks were used in an optimization framework to fit subject-specific skeletal models and compare joint angles of the shoulder girdle between these positions. FINDINGS: The mean Euclidean distance between joint locations from the fitted skeletal model and the manually identified joint locations was 15.7 mm ± 2.7 mm. Significant differences were observed between prone and supine. Compared to supine position, the shoulder girdle in the prone position had the lateral end of the clavicle in more anterior translation (i.e., scapula more protracted) (P < 0.05), the scapula in more protraction (P < 0.01), the scapula in more upward rotation (associated with humerus elevation) (P < 0.05); and the humerus more elevated (P < 0.05) for both the left and right sides. INTERPRETATION: Shoulder girdle orientation was found to be different between prone and supine. These differences would affect the shape of multiple pectoral muscles, which would affect breast shape and the accuracy of biomechanical models.

Toward Development of a Portable System for 3D Fluorescence Lymphography.

Lymphoedema is a debilitating disease that results in chronic swelling of a body region due to a dysfunctional lymphatic system. Since a cure is yet to be identified for this disease, management is currently the best option for preventing disease progression and improving patient outcomes. Fluorescence lymphography is a popular approach for mapping the lymphatic vessels to provide information about the underlying lymphatic dysfunction. However, current clinical fluorescence lymphography tools do not enable the creation of comprehensive 3D maps of lymphatics throughout affected limbs. This work presents the development toward multi-camera 3D reconstruction with fluorescence imaging to overcome the current limitations in clinical tools. Pilot studies have been performed that identify suitable instrumentation for this multi-camera approach and techniques for creating a 3D fluorescence lymphography device are discussed.Clinical Relevance- This paper presents development toward new low-cost and portable clinical tools for lymphoedema diagnosis and to facilitate personalised treatment and self-management of this disease.

Measurement of Blood Dilution during Lancet-Free Blood Sampling.

In this paper, we report on a fluorescent and colorimetric system for measuring the dilution of capillary blood released by a needle-free jet injector. Jet injection uses a high-speed liquid jet to penetrate tissue, and in the process can release capillary blood that can be collected for performing blood tests. In this way, blood sampling can be performed without the use of a lancet. However, any injectate that mixes with the collected blood dilutes the sample and may significantly impact subsequent analyses. By adding the fluorescent marker indocyanine green to the injected liquid, the fraction of injectate mixed into the collected blood can be measured. The incorporation of colorimetry allows our system to also correct for the impact of hematocrit on fluorescence. The results from this system show that it can determine the dilution of blood that has been diluted by up to 10 %, the upper limit of dilution typically observed in lancet-free blood sampling via jet injection.Clinical Relevance- Blood samples can be collected by jet injection without significant dilution, avoiding the need for lancing.

An Instrument for High-throughput Testing of Heart Tissue In Vitro.

Cardiac trabeculae are small samples of heart muscle tissue that can be dissected and studied in vitro to better understand the underlying physiology of cardiac muscle. However, instruments for such experimentation often (1) involve delicate mounting of the muscle, (2) constrain investigations to one muscle at a time and, thus, (3) cannot retain the muscle in the same experimental configuration for post-experimental assessment including imaging analysis. Here, we present a novel device that allows trabeculae to be secured by a visible-light photo-initiated hydrogel, manipulated via a force sensor, and stimulated while being imaged. We use our robust, accurate image registration techniques to measure cantilever and gel deformation during trabecula contraction and thereby provide a measure of trabecula force production during twitches. A variety of experiments can then be conducted, with the potential for the trabecula to be fixed in place using hydrogel for further post-experiment analysis, as well as longitudinal evaluation. The device has multiple wells making it amenable to high-throughput testing.Clinical Relevance- These methods may allow longitudinal and high-throughput studies of cardiac tissue samples in health and disease.

Non-contact quantification of aortic stenosis and mitral regurgitation using carotid waveforms from skin displacements.

Objective. Early diagnosis of heart problems is essential for improving patient prognosis.Approach. We created a non-contact imaging system that calculates the vessel-induced deformation of the skin to estimate the carotid artery pressure displacement waveforms. We present a clinical study of the system in patients (n= 27) with no underlying condition, aortic stenosis (AS), or mitral regurgitation (MR).Main results. Displacement waveforms were compared to aortic catheter pressures in the same patients. The morphologies of the pressure and displacement waveforms were found to be similar, and pulse wave analysis metrics, such as our modified reflection indices (RI) and waveform duration proportions, showed no significant differences. Compared with the control group, AS patients displayed a greater proportion of time to peak (p= 0.026 andp= 0.047 for catheter and displacement, respectively), whereas augmentation index (AIx)was greater for the displacement waveform only (p= 0.030). The modified RI for MR (p= 0.047 andp= 0.004 for catheter and displacement, respectively) was lower than in the controls. AS and MR were also significantly different for the proportion of time to peak (p= 0.018 for the catheter measurements), RI (p= 0.045 andp= 0.002 for the catheter and displacement, respectively), and AIx (p= 0.005 for the displacement waveform).Significance. These findings demonstrate the ability of our system to provide insights into cardiac conditions and support further development as a diagnostic/telehealth-based screening tool.

Minimally invasive capillary blood sampling methods.

INTRODUCTION: Whole blood samples, including arterial, venous, and capillary blood, are regularly used for disease diagnosis and monitoring. The global Covid-19 pandemic has highlighted the need for a more resilient screening capacity. Minimally invasive sampling techniques, such as capillary blood sampling, are routinely used for point of care testing in the home healthcare setting and clinical settings such as the Intensive Care Unit with less pain and wounding than conventional venepuncture. AREAS COVERED: In this manuscript, we aim to provide a overview of state-of-the-art of techniques for obtaining samples of capillary blood. We first review both established and novel methods for releasing blood from capillaries in the skin. Next, we provide a comparison of different capillary blood sampling methods based on their mechanism, testing site, puncture size, cost, wound geometry, healing, and perceptions of pain. Finally, we overview established and new methods for enhancing capillary blood collection. EXPERT OPINION: We expect that microneedles will prove to be a preferred option for paediatric blood collection. The ability of microneedles to collect a capillary blood sample without pain will improve paediatric healthcare outcomes. Jet injection may prove to be a useful method for facilitating both blood collection and drug delivery.

Jet-Induced Blood Release From Human Fingertips: A Single-Blind, Randomized, Crossover Trial.

BACKGROUND: Lancet pricks are often poorly received by individuals with diabetes; jet injection may allow lancet-free blood sampling. We examine whether the technique of jet injection can release sufficient blood from the fingertip to enable measurement of blood glucose concentration. In addition, we assess the effect of jet shape and cross-sectional area on fluid release, blood dilution, and perceived pain. METHODS: A randomized, single-blind, crossover study was conducted on 20 healthy volunteers who received interventions on four fingertips: a lancet prick, and jet injection of a small quantity of saline solution through three differently shaped and sized nozzles. Released fluid volume, blood concentration, and glucose concentration were assessed immediately after the intervention. Pain perception and duration, and any skin reactions, were evaluated both immediately and 24 hours after the intervention. RESULTS: Jet injection released sufficient blood from the fingertip to conduct a glucose measurement. A slot-shaped nozzle released the most blood, although less than a lancet, with slightly higher pain. The blood glucose levels estimated from the extracted fluid showed a mean absolute percentage error of 25%. There was no consistent evidence that a jet injection leads to different skin reactions at the intervention site relative to a lancet prick. CONCLUSIONS: Fingertip penetration by jet injection can release a volume of fluid sufficient for blood glucose measurement. Jet injection with a slot-shaped nozzle and/or a nozzle with larger outlet area helps to release more fluid. This technique may enable blood sampling, glucose concentration measurement, and insulin delivery to be performed in a single device.

Work-loop contractions reveal that the afterload-dependent time course of cardiac Ca2+ transients is modulated by preload.

Preload and afterload dictate the dynamics of the cyclical work-loop contraction that the heart undergoes in vivo. Cellular Ca2+ dynamics drive contraction, but the effects of afterload alone on the Ca2+ transient are inconclusive. To our knowledge, no study has investigated whether the putative afterload dependence of the Ca2+ transient is preload dependent. This study is designed to provide the first insight into the Ca2+ handling of cardiac trabeculae undergoing work-loop contractions, with the aim to examine whether the conflicting afterload dependency of the Ca2+ transient can be accounted for by considering preload under isometric and physiological work-loop contractions. Thus, we subjected ex vivo rat right-ventricular trabeculae, loaded with the fluorescent dye Fura-2, to work-loop contractions over a wide range of afterloads at two preloads while measuring stress, length changes, and Ca2+ transients. Work-loop control was implemented with a real-time Windkessel model to mimic the contraction patterns of the heart in vivo. We extracted a range of metrics from the measured steady-state twitch stress and Ca2+ transients, including the amplitudes, time courses, rates of rise, and integrals. Results show that parameters of stress were afterload and preload dependent. In contrast, the parameters associated with Ca2+ transients displayed a mixed dependence on afterload and preload. Most notably, its time course was afterload dependent, an effect augmented at the greater preload. This study reveals that the afterload dependence of cardiac Ca2+ transients is modulated by preload, which brings the study of Ca2+ transients during isometric contractions into question when aiming to understand physiological Ca2+ handling.NEW & NOTEWORTHY This study is the first examination of Ca2+ handling in trabeculae undergoing work-loop contractions. These data reveal that reducing preload diminishes the influence of afterload on the decay phase of the cardiac Ca2+ transient. This is significant as it reconciles inconsistencies in the literature regarding the influence of external loads on cardiac Ca2+ handling. Furthermore, these findings highlight discrepancies between Ca2+ handling during isometric and work-loop contractions in cardiac trabeculae operating at their optimal length.

High-Resolution Spatiotemporal Quantification of Intestinal Motility With Free-Form Deformation.

OBJECTIVE: To develop a method to quantify strain fields from in vivo intestinal motility recordings that mitigate accumulation of tracking error. METHODS: The deforming geometry of the intestine in video sequences was modeled by a biquadratic B-spline mesh. Green-Lagrange strain fields were computed to quantify the surface deformations. A nonlinear optimization scheme was applied to mitigate the accumulation of tracking error associated with image registration. RESULTS: The optimization scheme maintained the RMS strain error under 1% and reduced the rate of strain error by 97% during synthetic tests. The algorithm was applied to map 64 segmental, 12 longitudinal, and 23 propagating circular contractions in the jejunum. Coordinated activity of the two muscle layers could be identified and the strain fields were able to map and quantify the anisotropic contractions of the intestine. Frequency and velocity were also quantified, from which two types of propagating circular contractions were identified: (i) [Formula: see text] strain contractions that originated spontaneously and propagated at [Formula: see text] mm/s in two pigs, and (ii) cyclic propagating contractions of [Formula: see text] strain occurred at [Formula: see text] cpm and propagated at [Formula: see text] mm/s in a rabbit. CONCLUSION: The algorithm simultaneously mapped the circular, longitudinal activity of the intestine with high spatial resolution and quantified anisotropic contractions and relaxations. SIGNIFICANCE: The proposed algorithm can now be used to define the interactions of muscle layers during motility patterns. It can be integrated with high-resolution bioelectrical recordings to investigate the regulatory mechanisms of motility.

Jet-Induced Tissue Disruption for Blood Release.

OBJECTIVE: Needle-free jet injection is a drug delivery technique that uses the momentum of the fluid drug to break through the skin. This technique has recently also been applied to blood release, aiming to collect samples from capillaries in the skin without needing a lancet prick. This work provides new information about the wound geometry and tissue disruption caused by shallow jet injection with circular-shaped and slot-shaped jets. METHODS: We use histological analysis to compare the disruption of tissue, including blood vessels, caused by lancet-pricking and jet injection with a circular-shaped jet and a lancet-inspired slot-shaped jet. RESULTS: Intradermal injection into porcine skin using a slot-shaped jet disrupted more vascular endothelium in the tissue than a circular-shaped jet and did so at a smaller penetration depth with smaller wound volume. Our results suggest that shallow jet injections may have the potential to release more capillary blood than a lancet prick. CONCLUSION: These findings demonstrate that a reversible jet injector might be used in diabetes management as a device to release and collect blood samples, in addition to being used to deliver insulin. SIGNIFICANCE: Tissue disruption is crucial to consider when using jet injection to deliver drugs and release capillary blood.

Quantifying optical anisotropy in soft tissue membranes using Mueller matrix imaging.

SIGNIFICANCE: A non-destructive technique for accurately characterizing the spatial distribution of optical properties of soft tissue membranes may give improved outcomes in many tissue engineering applications. AIM: This study aimed to develop a non-destructive macroscopic imaging technique that is sensitive to optical anisotropy, typical of fibrous components in soft tissue membranes, and can address some of the difficulties caused by the complex turbid nature of these tissues. APPROACH: A near-infrared Mueller matrix imaging polarimeter employing logarithm decomposition was developed and used to conduct transmission measurements of all the polarization properties across the full thickness of bovine pericardium tissue. RESULTS: The full Mueller matrix was measured across a 70 mm × 70 mm sample of calf bovine pericardium and revealed significant retardance (linear and circular) and depolarization in this tissue. Regions with a uniform axis of optical anisotropy were identified. Mueller matrix imaging demonstrated that the exhibited circular retardance was sufficient to lead to possible misinterpretation of apparent fiber orientation when using conventional polarization imaging techniques for such tissues. CONCLUSIONS: Mueller matrix imaging can identify regional distributions of optical anisotropy in calf bovine pericardium. This new capability is a promising development in non-destructive imaging for tissue selection.

Simultaneous Brightfield, Fluorescence, and Optical Coherence Tomographic Imaging of Contracting Cardiac Trabeculae Ex Vivo.

In cardiac muscle, intracellular Ca2+ transients activate contractile myofilaments, causing contraction, macroscopic shortening, and geometric deformation. Our understanding of the internal relationships between these events has been limited because we can neither 'see' inside the muscle nor precisely track the spatio-temporal nature of excitation-contraction dynamics. To resolve these problems, we have constructed a device that combines a suite of imaging modalities. Specifically, it integrates a brightfield microscope to measure local changes of sarcomere length and tissue strain, a fluorescence microscope to visualize the Ca2+ transient, and an optical coherence tomograph to capture the tissue's geometric changes throughout the time-course of a cardiac cycle. We present here the imaging infrastructure and associated data collection framework. Data are collected from isolated rod-like tissue structures known as trabeculae carneae. In our instrument, a pair of position-controlled platinum hooks hold each end of an ex vivo muscle sample while it is continuously superfused with nutrient-rich saline solution. The hooks are under independent control, permitting real-time control of muscle length and force. Lengthwise translation enables the piecewise scanning of the sample, overcoming limitations associated with the relative size of the microscope imaging window (540 µm by 540 µm) and the length of a typical trabecula (>2000 µm). Platinum electrodes at either end of the muscle chamber stimulate the trabecula at a user-defined rate. We exploit the stimulation signal as a trigger for synchronizing the data from each imaging window to reconstruct the entire sample twitching under steady-state conditions. Applying image-processing techniques to these brightfield imaging data provides tissue displacement and sarcomere length maps. Such a collection of data, when incorporated into an experiment-modeling pipeline, will provide a deeper understanding of muscle contractile homogeneity and heterogeneity in physiology and pathophysiology.

Using codesign to develop a mobile application for pelvic floor muscle training with an intravaginal device (femfit®).

AIMS: The aim of this project was to use codesign to develop a mobile application (app) for pelvic floor muscle training, with an intravaginal device (femfit®). The objective was to obtain user feedback to guide the design and development of a mobile app, consistent with the Mobile Application Rating Scale (MARS) framework. METHODS: Twenty-six women (22-62 years) provided mobile app feedback using a Design Thinking framework and grounded theory approach. Four focus groups (2 h each) and two sets of one-to-one interviews (1 h each) were held from May 2018 to October 2019. The researchers debriefed the focus groups and interviews, and undertook analysis based on project objectives and key questions. RESULTS: Recurring themes throughout the study aligned with sections of the MARS: (A) engagement (e.g., progress tracking), (B) functionality (e.g., intuitive interface), (C) aesthetics (e.g., smart graphics and colors), (D) information (e.g., clear, concise information). An internal preliminary assessment determined a MARS Quality Mean Score of 4.1 of 5 (engagement: 3.6 of 5; functionality: 4 of 5; aesthetics: 4.3 of 5: information: 4.4 of 5). CONCLUSIONS: The development of the mobile app is on track to meet MARS requirements, and to be a fun, motivating app for women. Future work is required to investigate its efficacy.

Assessing vaginal pressure profiles before and after prolapse surgery using an intravaginal pressure sensor (femfit®).

INTRODUCTION AND HYPOTHESIS: The impact of surgery on pelvic floor muscle (PFM) function remains uncertain. There is a pressure differential along the length of the vagina, influenced by surrounding active and passive tissue structures, giving rise to a pressure profile. The aim of this study is to determine if an intravaginal pressure sensor, femfit®, can measure differences in pressure profiles before and after surgery for pelvic organ prolapse (POP). METHODS: This pilot study includes 22 women undergoing POP surgery. Intravaginal pressure profiles were measured with femfit® pre- and post-surgery and differences tested using paired Student's t-tests. Patients completed validated questionnaires for vaginal, bowel, and urinary incontinence symptoms pre- and post-POP surgery and a femfit® usability questionnaire. RESULTS: Sixteen sets of vaginal pressure data were analysed. The highest pressure generated was identified as the peak PFM pressure, whilst all sensor measurements provided a pressure profile. Intra-abdominal pressure (IAP) was measured by the most distal sensor, 8. On average, the difference between peak PFM pressure and IAP was significantly greater post-surgery (p < 0.01). Urinary and vaginal symptom questionnaire scores were significantly improved after POP surgery. Femfit® usability questionnaires demonstrated high levels of patient acceptability. CONCLUSIONS: Women generate higher peak PFM pressures compared to IAP post-POP surgery, with pressure profiles that are comparable to women without POP. This metric might be useful to assess the outcome of POP surgery and encourage women to maintain this profile via PFM training, potentially reducing POP recurrence risk.

A miniature mechanical testing device for testing hydrogel-based biomaterials in a confocal microscope.

Cardiac muscle cells are the fundamental building blocks of the heart, yet little is known about their mechanical properties in either healthy or diseased states. While many have explored unloaded myocyte behavior under a variety of interventions, methods for force measurements are limited due to cell fragility. Here, we present a custom device for manipulation and mechanical testing of hydrogels embedded with delicate cardiac muscle cells. Consisting of a custom disposable flexure, which is easily interchangeable, the device has the potential for high throughput testing of cell-gel constructs. Additionally, the mechanical testing device is the size of a microscope slide - appropriate for use in most microscopes, for simultaneous imaging of the sample. The mechanical properties of a gelatin-methacryloyl hydrogel sample were assessed, and 3D volumes of gel imaged using a confocal microscope. The Young's modulus of the gel was found to be 33kPa.Clinical Relevance- High-throughput testing provides the potential to gain insight into cardiac cell mechanics. Experimentation under the influence of a variety of pharmacological interventions could improve the rate at which treatments for cardiac disease are developed. Furthermore, methods may be extended to other embedded biological tissues.

Blood Collection from The Porcine Ear Using a Jet Injector.

We present a new lancet-free method of capillary blood collection for the measurement of blood glucose concentration using a needle-free jet injector. This technique is tested on living animals and directly compared to the current best practice, lancet prick. Shallow jet injection into porcine outer-ear was performed using a portable needle-free jet injector with a slot-shaped nozzle. The jet injections presented used about 25 µL of injectate to penetrate porcine skin to about 1.4 mm, which is within the WHO standards for capillary blood sampling. The blood and fluid released by the jet injections and lancet pricks was collected. The volume and colour of these samples were analysed. The results demonstrate that jet injection is a feasible technique for the collection of capillary blood, despite the small volume of blood samples retrieved from all four pigs. Jet injection may be used in the future to retrieve capillary blood samples from human fingertips.

CellML 2.0.

We present here CellML 2.0, an XML-based language for describing and exchanging mathematical models of physiological systems. MathML embedded in CellML documents is used to define the underlying mathematics of models. Models consist of a network of reusable components, each with variables and equations giving relationships between those variables. Models may import other models to create systems of increasing complexity. CellML 2.0 is defined by the normative specification presented here, prescribing the CellML syntax and the rules by which it should be used. The normative specification is intended primarily for the developers of software tools which directly consume CellML syntax. Users of CellML models may prefer to browse the informative rendering of the specification (https://cellml.org/specifications/cellml_2.0/) which extends the normative specification with explanations of the rules combined with examples of their usage.