Progress Towards a Multi-Modal Capsule Endoscopy Device Featuring Microultrasound Imaging

Current clinical standards for endoscopy in the gastrointestinal (GI) tract combine high definition optics and ultrasound imaging to view the lumen superficially and through its thickness. However, these instruments are limited to the length of an endoscope and the only clinically available, autonomous devices able to travel the full length of the GI tract easily offer only video capsule endoscopy (VCE). Our work seeks to overcome this limitation with a device (“Sonopill”) for multimodal capsule endoscopy, providing optical and microultrasound (μUS) imaging and supporting sensors1. μUS transducers have been developed with multiple piezoelectric materials operating across a range of centre frequencies to study viability in the GI tract. Because of the combined constraints of μUS imaging and the low power / heat tolerance of autonomous devices, a hybrid approach has been taken to the transducer design, with separate transmit and receive arrays allowing multiple manufacturing approaches to maximise system efficiency. To explore these approaches fully, prototype devices have been developed with PVDF, high-frequency PZT and PMN-PT composites, and piezoelectric micromachined ultrasonic transducer arrays. Test capsules have been developed using 3D printing to investigate issues including power consumption, heat generation / dissipation, acoustic coupling, signal strength and capsule integrity. Because of the high functional density of the electronics in our proposed system, application specific integrated circuits (ASICs) have been developed to realise the ultrasound transmit and receive circuitry along with white-light and autofluorescence imaging with single-photon avalanche detectors (SPADs). The ultrasound ASIC has been developed and the SPAD electronics and optical subsystem have been validated experimentally. The functionality of various transducer materials has been examined as a function of frequency and ultrasound transducers have been developed to operate at centre frequencies in the range 15 - 50 MHz. Ex vivo testing of porcine tissue has been performed, generating images of interest to the clinical community, demonstrating the viability of the Sonopill concept

Activation of optimally and unfavourably oriented faults in a uniform local stress field during the 2011 Prague, Oklahoma, sequence

The orientations of faults activated relative to the local principal stress directions can provide insights into the role of pore pressure changes in induced earthquake sequences. Here, we examine the 2011 M 5.7 Prague earthquake sequence that was induced by nearby wastewater disposal. We estimate the local principal compressive stress direction near the rupture as inferred from shear wave splitting measurements at spatial resolutions as small as 750 m. We find that the dominant azimuth observed is parallel to previous estimates of the regional compressive stress with some secondary azimuths oriented subparallel to the strike of the major fault structures. From an extended catalogue, we map ten distinct fault segments activated during the sequence that exhibit a wide array of orientations. We assess whether the five near-vertical fault planes are optimally oriented to fail in the determined stress field. We find that only two of the fault planes, including the M   5.7 main shock fault, are optimally oriented. Both the M 4.8 foreshock and M   4.8 aftershock occur on fault planes that deviate 20–29° from the optimal orientation for slip. Our results confirm that induced event sequences can occur on faults not optimally oriented for failure in the local stress field. The results suggest elevated pore fluid pressures likely induced failure along several of the faults activated in the 2011 Prague sequence

In-Vivo Evaluation of Microultrasound and Thermometric Capsule Endoscopes

Clinical endoscopy and colonoscopy are commonly used to investigate and diagnose disorders in the upper gastrointestinal tract and colon respectively. However, examination of the anatomically remote small bowel with conventional endoscopy is challenging. This and advances in miniaturization led to the development of video capsule endoscopy (VCE) to allow small bowel examination in a non-invasive manner. Available since 2001, current capsule endoscopes are limited to viewing the mucosal surface only due to their reliance on optical imaging. To overcome this limitation with submucosal imaging, work is under way to implement microultrasound (μUS) imaging in the same form as VCE devices. This paper describes two prototype capsules, termed Sonocap and Thermocap, which were developed respectively to assess the quality of μUS imaging and the maximum power consumption that can be tolerated for such a system. The capsules were tested in vivo in the oesophagus and small bowel of porcine models. Results are presented in the form of μUS B-scans and safe temperature readings observed up to 100 mW in both biological regions. These results demonstrate that acoustic coupling and μUS imaging can be achieved in vivo in the lumen of the bowel and the maximum power consumption that is possible for miniature μUS systems

Methane Emission in a Specific Riparian-Zone Sediment Decreased with Bioelectrochemical Manipulation and Corresponded to the Microbial Community Dynamics

Dissimilatory metal-reducing bacteria are widespread in terrestrial ecosystems, especially in anaerobic soils and sediments. Thermodynamically, dissimilatory metal reduction is more favorable than sulfate reduction and methanogenesis but less favorable than denitrification and aerobic respiration. It is critical to understand the complex relationships, including the absence or presence of terminal electron acceptors, that govern microbial competition and coexistence in anaerobic soils and sediments, because subsurface microbial processes can effect greenhouse gas emissions from soils, possibly resulting in impacts at the global scale. Here, we elucidated the effect of an inexhaustible, ferrous-iron and humic-substance mimicking terminal electron acceptor by deploying potentiostatically poised electrodes in the sediment of a very specific stream riparian zone in Upstate New York state. At two sites within the same stream riparian zone during the course of six weeks in the spring of 2013, we measured CH4 and N2/N2O emissions from soil chambers containing either poised or unpoised electrodes, and we harvested biofilms from the electrodes to quantify microbial community dynamics. At the upstream site, which had a lower vegetation cover and highest soil temperatures, the poised electrodes inhibited CH4 emissions by ~45% (when normalized to remove temporal effects). CH4 emissions were not significantly impacted at the downstream site. N2/N2O emissions were generally low at both sites and were not impacted by poised electrodes. We did not find a direct link between bioelectrochemical treatment and microbial community membership; however, we did find a correspondence between environment/function and microbial community dynamics

Translational trial outcomes for capsule endoscopy test devices

Current clinical standards in the endoscopic diagnosis of gastrointestinal diseases are primarily based on the use of optical systems. Ultrasound has established diagnostic credibility in the form of endoscopic ultrasound (EUS), however it is limited to examination of the upper gastrointestinal tract (oesophagus, stomach and upper (proximal) small bowel). Access to the remainder of the small bowel is currently limited to optical capsule endoscopes and a limited number of other modalities as these capsules are restricted to visual examination of the surface or mucosa of the gut wall. Ultrasound capsule endoscopy has been proposed to integrate microultrasound imaging capabilities into the existing capsule format and extend examination capabilities beyond the mucosa. To establish the ability of high frequency ultrasound to resolve the histological structure of the gastrointestinal tract, ex vivo scans of pig and human tissue were performed. This was done using 25 and 34 MHz single element, physically focused composite transducers mechanically scanned along the tissue. Tethered prototype devices were then developed with 30 MHz physically focused polyvinylidene fluoride (PVDF) single element transducers embedded for use in initial translational trials in the small bowel of porcine subjects. B-scan images from the ex vivo model validation and the in vivo trials are presented

Impaired phagocytosis of apoptotic cells by macrophages in chronic granulomatous disease is reversed by IFN-γ in a nitric oxide-dependent manner

Immunodeficiency in chronic granulomatous disease (CGD) is well characterized. Less understood are exaggerated sterile inflammation and autoimmunity associated with CGD. Impaired recognition and clearance of apoptotic cells resulting in their disintegration may contribute to CGD inflammation. We hypothesized that priming of macrophages (Ms) with IFN-γ would enhance impaired engulfment of apoptotic cells in CGD. Diverse M populations from CGD (gp91(phox)(-/-)) and wild-type mice, as well as human Ms differentiated from monocytes and promyelocytic leukemia PLB-985 cells (with and without mutation of the gp91(phox)), demonstrated enhanced engulfment of apoptotic cells in response to IFN-γ priming. Priming with IFN-γ was also associated with increased uptake of Ig-opsonized targets, latex beads, and fluid phase markers, and it was accompanied by activation of the Rho GTPase Rac. Enhanced Rac activation and phagocytosis following IFN-γ priming were dependent on NO production via inducible NO synthase and activation of protein kinase G. Notably, endogenous production of TNF-α in response to IFN-γ priming was critically required for inducible NO synthase upregulation, NO production, Rac activation, and enhanced phagocytosis. Treatment of CGD mice with IFN-γ also enhanced uptake of apoptotic cells by M in vivo via the signaling pathway. Importantly, during acute sterile peritonitis, IFN-γ treatment reduced excess accumulation of apoptotic neutrophils and enhanced phagocytosis by CGD Ms. These data support the hypothesis that in addition to correcting immunodeficiency in CGD, IFN-γ priming of Ms restores clearance of apoptotic cells and may thereby contribute to resolution of exaggerated CGD inflammation

Holocene depositional history inferred from single-grain luminescence ages in southern California, North America.

Significant sediment flux and deposition in a sedimentary system are influenced by climate changes, tectonics, lithology, and the sedimentary system’s internal dynamics. Identifying the timing of depositional periods from stratigraphic records is a first step to critically evaluating the controls of sediment flux and deposition. Here, we show that ages of single-grain K-feldspar luminescence subpopulations may provide information on the timing of previous major depositional periods. We analyzed 754 K-feldspar single-grains from 17 samples from the surface to ~9 m-depth in a trench located downstream of the Mission Creek catchment. Single-grain luminescence subpopulation ages significantly overlap at least eight times since ~12.0 ka indicating a common depositional history. These depositional periods correspond reasonably well with the wetter climate periods based on hydroclimatic proxies from nearby locations. Our findings imply a first-order climatic control on sediment depositional history in southern California on a millennial timescale

Refractive-index sensing with ultra-thin plasmonic nanotubes

We study the refractive-index sensing properties of plasmonic nanotubes with a dielectric core and ultra-thin metal shell. The few-nm thin metal shell is described by both the usual Drude model and the nonlocal hydrodynamic model to investigate the effects of nonlocality. We derive an analytical expression for the extinction cross section and show how sensing of the refractive index of the surrounding medium and the figure-of-merit are affected by the shape and size of the nanotubes. Comparison with other localized surface plasmon resonance sensors reveals that the nanotube exhibits superior sensitivity and comparable figure-of-merit

New paradigm for macromolecular crystallography experiments at SSRL: automated crystal screening and remote data collection

Through the combination of robust mechanized experimental hardware and a flexible control system with an intuitive user interface, SSRL researchers have screened over 200 000 biological crystals for diffraction quality in an automated fashion. Three quarters of SSRL researchers are using these data-collection tools from remote locations

In Vivo Characterization of a Wireless Telemetry Module for a Capsule Endoscopy System Utilizing a Conformal Antenna

This paper describes the design, fabrication, packaging, and performance characterization of a conformal helix antenna created on the outside of a 10 mm ×30 mm capsule endoscope designed to operate at a carrier frequency of 433 MHz within human tissue. Wireless data transfer was established between the integrated capsule system and an external receiver. The telemetry system was tested within a tissue phantom and in vivo porcine models. Two different types of transmission modes were tested. The first mode, replicating normal operating conditions, used data packets at a steady power level of 0 dBm, while the capsule was being withdrawn at a steady rate from the small intestine. The second mode, replicating the worst-case clinical scenario of capsule retention within the small bowel, sent data with stepwise increasing power levels of –10, 0, 6, and 10 dBm, with the capsule fixed in position. The temperature of the tissue surrounding the external antenna was monitored at all times using thermistors embedded within the capsule shell to observe potential safety issues. The recorded data showed, for both modes of operation, a low error transmission of 10−3 packet error rate and 10−5 bit error rate and no temperature increase of the tissue according to IEEE standards