Flexible and directional fibre optic ultrasound transmitters using photostable dyes

All-optical ultrasound transducers are well-suited for use in imaging during minimally invasive surgical procedures. This requires highly miniaturised and flexible devices. Here we present optical ultrasound transmitters for imaging applications based on modified optical fibre distal tips which allow for larger transmitter element sizes, whilst maintaining small diameter proximal optical fibre. Three optical ultrasound transmitter configurations were compared; a 400 µm core optical fibre, a 200 µm core optical fibre with a 400 µm core optical fibre distal tip, and a 200 µm core optical fibre with a 400 µm core capillary distal tip. All the transmitters used a polydimethylsiloxane-dye composite material for ultrasound generation. The material comprised a photostable infra-red absorbing dye to provide optical absorption for the ultrasound transduction. The generated ultrasound beam profile for the three transmitters was compared, demonstrating similar results, with lateral beam widths <1.7 mm at a depth of 10 mm. The composite material demonstrates a promising alternative to previously reported materials, generating ultrasound pressures exceeding 2 MPa, with corresponding bandwidths ca. 30 MHz. These highly flexible ultrasound transmitters can be readily incorporated into medical devices with small lateral dimensions

Fibre optic intravascular measurements of blood flow: A review

Fibre optic sensors are well suited to measuring fluid flow in many contexts, and recently there has been burgeoning interest in their application to direct, invasive measurement of blood flow within human vasculature. Depending on the sensing method used and assumptions made, these intravascular measurements of blood flow can provide information about local blood velocity, volumetric flow, and flow-derived parameters. Fibre optic sensors can be readily integrated into medical devices, which are positioned into arteries and veins to obtain measurements that are inaccessible or cumbersome using non-invasive imaging modalities. Measurements of flow within coronary arteries is a particularly promising application of fibre optic sensing; recent studies have demonstrated the clinical utility of certain flow-based parameters, such as the coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). In this review, research and development of fibre optic flow sensors relevant to intravascular flow measurements are reviewed, with a particular focus on biomedical clinical translation

Optically Generated Ultrasound for Intracoronary Imaging

Conventional intravascular ultrasound (IVUS) devices use piezoelectric transducers to electrically generate and receive US. With this paradigm, there are numerous challenges that restrict improvements in image quality. First, with miniaturization of the transducers to reduce device size, it can be challenging to achieve the sensitivities and bandwidths required for large tissue penetration depths and high spatial resolution. Second, complexities associated with manufacturing miniaturized electronic transducers can have significant cost implications. Third, with increasing interest in molecular characterization of tissue in-vivo, it has been challenging to incorporate optical elements for multimodality imaging with photoacoustics (PA) or near-infrared spectroscopy (NIRS) whilst maintaining the lateral dimensions suitable for intracoronary imaging. Optical Ultrasound (OpUS) is a new paradigm for intracoronary imaging. US is generated at the surface of a fiber optic transducer via the photoacoustic effect. Pulsed or modulated light is absorbed in an engineered coating on the fiber surface and converted to thermal energy. The subsequent temperature rise leads to a pressure rise within the coating, which results in a propagating ultrasound wave. US reflections from imaged structures are received with optical interferometry. With OpUS, high bandwidths (31.5 MHz) and pressures (21.5 MPa) have enabled imaging with axial resolutions better than 50 μm and at depths >20 mm. These values challenge those of conventional 40 MHz IVUS technology and show great potential for future clinical application. Recently developed nanocomposite coating materials, that are highly transmissive at light wavelengths used for PA and NIRS light, can facilitate multimodality imaging, thereby enabling molecular characterization

A Survey on the Current Status and Future Challenges Towards Objective Skills Assessment in Endovascular Surgery

Minimally-invasive endovascular interventions have evolved rapidly over the past decade, facilitated by breakthroughs in medical imaging and sensing, instrumentation and most recently robotics. Catheter based operations are potentially safer and applicable to a wider patient population due to the reduced comorbidity. As a result endovascular surgery has become the preferred treatment option for conditions previously treated with open surgery and as such the number of patients undergoing endovascular interventions is increasing every year. This fact coupled with a proclivity for reduced working hours, results in a requirement for efficient training and assessment of new surgeons, that deviates from the “see one, do one, teach one” model introduced by William Halsted, so that trainees obtain operational expertise in a shorter period. Developing more objective assessment tools based on quantitative metrics is now a recognised need in interventional training and this manuscript reports the current literature for endovascular skills assessment and the associated emerging technologies. A systematic search was performed on PubMed (MEDLINE), Google Scholar, IEEXplore and known journals using the keywords, “endovascular surgery”, “surgical skills”, “endovascular skills”, “surgical training endovascular” and “catheter skills”. Focusing explicitly on endovascular surgical skills, we group related works into three categories based on the metrics used; structured scales and checklists, simulation-based and motion-based metrics. This review highlights the key findings in each category and also provides suggestions for new research opportunities towards fully objective and automated surgical assessment solutions

Micron resolution, high-fidelity three-dimensional vascular optical imaging phantoms

Microscopic and mesoscale optical imaging techniques allow for three-dimensional (3-D) imaging of biological tissue across millimeter-scale regions, and imaging phantom models are invaluable for system characterization and clinical training. Phantom models that replicate complex 3-D geometries with both structural and molecular contrast, with resolution and lateral dimensions equivalent to those of imaging techniques (<20  μm), have proven elusive. We present a method for fabricating phantom models using a combination of two-photon polymerization (2PP) to print scaffolds, and microinjection of tailored tissue-mimicking materials to simulate healthy and diseased tissue. We provide a first demonstration of the capabilities of this method with intravascular optical coherence tomography, an imaging technique widely used in clinical practice. We describe the design, fabrication, and validation of three types of phantom models: a first with subresolution wires (5- to 34-μm diameter) arranged circumferentially, a second with a vessel side-branch, and a third containing a lipid inclusion within a vessel. Silicone hybrid materials and lipids, microinjected within a resin framework created with 2PP, served as tissue-mimicking materials that provided realistic optical scattering and absorption. We demonstrate that optical phantom models made with 2PP and microinjected tissue-mimicking materials can simulate complex anatomy and pathology with exquisite detail

Dynamic physiological temperature and pressure sensing with phase-resolved low-coherence interferometry

We report the development and characterisation of highly miniaturised fibre-optic sensors for simultaneous pressure and temperature measurement, and a compact interrogation system with a high sampling rate. The sensors, which have a maximum diameter of 250 µm, are based on multiple low-finesse optical cavities formed from polydimethylsiloxane (PDMS), positioned at the distal ends of optical fibres, and interrogated using phase-resolved low-coherence interferometry. At acquisition rates of 250 Hz, temperature and pressure changes of 0.0021 °C and 0.22 mmHg are detectable. An in vivo experiment demonstrated that the sensors had sufficient speed and sensitivity for monitoring dynamic physiological pressure waveforms. These sensors are ideally suited to various applications in minimally invasive surgery, where diminutive lateral dimensions, high sensitivity and low manufacturing complexities are particularly valuable

All-Optical Rotational Ultrasound Imaging

Miniaturised high-resolution imaging devices are valuable for guiding minimally invasive procedures such as vascular stent placements. Here, we present all-optical rotational B-mode pulse-echo ultrasound imaging. With this device, ultrasound transmission and reception are performed with light. The all-optical transducer in the probe comprised an optical fibre that delivered pulsed excitation light to an optical head at the distal end with a multi-walled carbon nanotube and polydimethylsiloxane composite coating. This coating was photoacoustically excited to generate a highly directional ultrasound beam perpendicular to the optical fibre axis. A concave Fabry-Pérot cavity at the distal end of an optical fibre, which was interrogated with a tuneable continuous-wave laser, served as an omnidirectional ultrasound receiver. The transmitted ultrasound had a −6 dB bandwidth of 31.3 MHz and a peak-to-peak pressure of 1.87 MPa, as measured at 1.5 mm from the probe. The receiver had a noise equivalent pressure <100 Pa over a 20 MHz bandwidth. With a maximum outer probe diameter of 1.25 mm, the probe provided imaging with an axial resolution better than 50 µm, and a real-time imaging rate of 5 frames per second. To investigate the capabilities of the probe, intraluminal imaging was performed in healthy swine carotid arteries. The results demonstrate that the all-optical probe is viable for clinical rotational ultrasound imaging

In vivo expression of innate immunity markers in patients with mycobacterium tuberculosis infection

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs), Coronin-1 and Sp110 are essential factors for the containment of <it>Mycobacterium tuberculosis </it>infection. The purpose of this study was to investigate the <it>in vivo </it>expression of these molecules at different stages of the infection and uncover possible relationships between these markers and the state of the disease.</p> <p>Methods</p> <p>Twenty-two patients with active tuberculosis, 15 close contacts of subjects with latent disease, 17 close contacts of subjects negative for mycobacterium antigens and 10 healthy, unrelated to patients, subjects were studied. Quantitative mRNA expression of Coronin-1, Sp110, TLRs-1,-2,-4 and -6 was analysed in total blood cells <it>vs </it>an endogenous house-keeping gene.</p> <p>Results</p> <p>The mRNA expression of Coronin-1, Sp110 and TLR-2 was significantly higher in patients with active tuberculosis and subjects with latent disease compared to the uninfected ones. Positive linear correlation for the expression of those factors was only found in the infected populations.</p> <p>Conclusions</p> <p>Our results suggest that the up-regulation of Coronin-1 and Sp110, through a pathway that also includes TLR-2 up-regulation may be involved in the process of tuberculous infection in humans. However, further studies are needed, in order to elucidate whether the selective upregulation of these factors in the infected patients could serve as a specific molecular marker of tuberculosis.</p

Computational Reverse-Engineering of a Spider-Venom Derived Peptide Active Against Plasmodium falciparum SUB1

merozoites and invasion into erythrocytes. As PfSUB1 has emerged as an interesting drug target, we explored the hypothesis that PcFK1 targeted PfSUB1 enzymatic activity. culture in a range compatible with our bioinformatics analysis. Using contact analysis and free energy decomposition we propose that residues A14 and Q15 are important in the interaction with PfSUB1.Our computational reverse engineering supported the hypothesis that PcFK1 targeted PfSUB1, and this was confirmed by experimental evidence showing that PcFK1 inhibits PfSUB1 enzymatic activity. This outlines the usefulness of advanced bioinformatics tools to predict the function of a protein structure. The structural features of PcFK1 represent an interesting protein scaffold for future protein engineering