Microultraound and small bowel inflammation:Tissue phantom studies

Capsule endoscopy represents a highly convenient but limited means of imaging inflammatory conditions of the small bowel. The inclusion of high frequency microultrasound into a capsule endoscope has the potential to enhance diagnostic capabilities with subsurface imaging of the bowel wall. Experimental studies on abattoir-obtained porcine small bowel have been carried out as an ethical means to characterize healthy and altered tissue in a preclinical setting as well as to explore other means of imaging pathology. Samples of small bowel were cannulated and perfused with phosphate buffered saline followed by variable dilutions of polystyrene microspheres. All samples were scanned with a purpose built step scanner employing a 47 MHz single element transducer. Results indicated that tissue high frequency ultrasound demonstrated sufficient sensitivity to detect the disruption normal histology with microsphere infusion. The combination of microultrasound and capsule endoscopy has the potential to enhance the diagnostic capabilities with improved qualitative and quantitative dimensions

Design and Simulation of a Ring-Shaped Linear Array for Microultrasound Capsule Endoscopy

Video capsule endoscopy (VCE) has significantly advanced visualization of the gastrointestinal tract (GI tract) since its introduction in the last 20 years. Work is now under way to combine VCE with microultrasound imaging. However, small maximum capsule dimensions, coupled with the electronics required to integrate ultrasound imaging capabilities, pose significant design challenges. This paper describes a simulation process for testing transducer geometries and imaging methodologies to achieve satisfactory imaging performance within the physical limitations of the capsule size and outlines many of the trade-offs needed in the design of this new class of ultrasound capsule endoscopy (USCE) device. A hybrid MATLAB model is described, incorporating KLM circuit elements and digitizing and beamforming elements to render a grey-scale B-mode. This model is combined with a model of acoustic propagation to generate images of point scatterers. The models are used to demonstrate the performance of a USCE transducer configuration comprising a single, unfocused transmit ring of radius 5 mm separated into eight segments for electrical impedance control and a 512-element receive linear array, also formed into a ring. The MATLAB model includes an ultrasonic pulser circuit connected to a piezocrystal composite transmit transducer with a center frequency of 25 MHz. B-scan images are simulated for wire target phantoms, multilayered phantoms, and a gut wall model. To demonstrate the USCE system’s ability to image tissue, a digital phantom was created from single-element ultrasonic transducer scans of porcine small bowel ex vivo obtained at a frequency of 45 MHz

Twisting waves increase the visibility of nonlinear behaviour

Nonlinear behaviour for acoustic systems is readily measured at high acoustic pressures in gasses or bulk materials. However, at low acoustic pressures non-linear effects are not commonly observed. We find that by phase structuring acoustics beams, one observes evidence of non-linear behaviour at an acoustic pressure of 66.78 dB lower than non-structured beams in room temperature air. A bespoke 28-element ultrasonic phased array antenna was developed to generate short pulses that carry orbital angular momentum and are propagated over a short air channel. When sampling small areas of the wavefront, we observed a distinctive change in the frequency components near phase singularities. At these phase singularities the local propagation path is screwed, resulting in the collection signals from pulses traveling along different paths across the aperture of a microphone. The usually negligible frequency chirping that arises from nonlinear behaviour in air interfere at these singularity points and produce a distinctive distortion of the acoustic pulse. Simple physical movement in the system or super-sonic wave speeds do not yield similar results. Such distortions in measured frequency response near phase singularities could lead to errors for SONAR or acoustic communication systems, where received signals are integrated over a finite-area detector. With further development this behaviour could potentially lead to accurate measurement techniques for determining a material's nonlinear properties at lower acoustic pressure

Integrated Front End Circuitry for Microultrasound Capsule Endoscopy

Video capsule endoscopy (VCE) was originally developed to address the limitation of conventional endoscopy in accessing the small bowel as a remote part of the gastrointestinal tract. To further enhance the diagnostic ability of VCE, microultrasound capsule endoscopy is under development for identification of disease at an earlier stage and visualisation of subsurface tissue features. This paper presents an evaluation of two approaches to improve signal to noise ratio (SNR) in rapid prototyped capsule endoscopes. First, noise reduction techniques are applied to the integrated front-end circuits in the prototype capsules. Secondly, multiple types of coded excitation transmission are tested and benchmarked with respect to non-coded transmission. Results are presented for both bench top phantom imaging and in vivo translational trial imaging

Ultrasound capsule endoscopy:sounding out the future

Video capsule endoscopy (VCE) has been of immense benefit in the diagnosis and management of gastrointestinal (GI) disorders since its introduction in 2001. However, it suffers from a number of well recognized deficiencies. Amongst these is the limited capability of white light imaging, which is restricted to analysis of the mucosal surface. Current capsule endoscopes are dependent on visual manifestation of disease and limited in regards to transmural imaging and detection of deeper pathology. Ultrasound capsule endoscopy (USCE) has the potential to overcome surface only imaging and provide transmural scans of the GI tract. The integration of high frequency microultrasound (µUS) into capsule endoscopy would allow high resolution transmural images and provide a means of both qualitative and quantitative assessment of the bowel wall. Quantitative ultrasound (QUS) can provide data in an objective and measurable manner, potentially reducing lengthy interpretation times by incorporation into an automated diagnostic process. The research described here is focused on the development of USCE and other complementary diagnostic and therapeutic modalities. Presently investigations have entered a preclinical phase with laboratory investigations running concurrently

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

LRH-1 drives colon cancer cell growth by repressing the expression of the <i>CDKN1A</i> gene in a p53-dependent manner

Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor that has been implicated in the progression of breast, pancreatic and colorectal cancer (CRC). To determine mechanisms underlying growth promotion by LRH-1 in CRC, we undertook global expression profiling following siRNA-mediated LRH-1 knockdown in HCT116 cells, which require LRH-1 for growth and in HT29 cells, in which LRH-1 does not regulate growth. Interestingly, expression of the cell cycle inhibitor p21 (CDKN1A) was regulated by LRH-1 in HCT116 cells. p21 regulation was not observed in HT29 cells, where p53 is mutated. p53 dependence for the regulation of p21 by LRH-1 was confirmed by p53 knockdown with siRNA, while LRH-1-regulation of p21 was not evident in HCT116 cells where p53 had been deleted. We demonstrate that LRH-1-mediated p21 regulation in HCT116 cells does not involve altered p53 protein or phosphorylation, and we show that LRH-1 inhibits p53 recruitment to the p21 promoter, likely through a mechanism involving chromatin remodelling. Our study suggests an important role for LRH-1 in the growth of CRC cells that retain wild-type p53

Ultrasound Capsule Endoscopy With a Mechanically Scanning Micro-ultrasound:A Porcine Study

Wireless capsule endoscopy has been used for the clinical examination of the gastrointestinal (GI) tract for two decades. However, most commercially available devices only utilise optical imaging to examine the GI wall surface. Using this sensing modality, pathology within the GI wall cannot be detected. Micro-ultrasound (μUS) using high-frequency (>20 MHz) ultrasound can provide a means of transmural or cross-sectional image of the GI tract. Depth of imaging is approximately 10 mm with a resolution of between 40–120 μm that is sufficient to differentiate between subsurface histologic layers of the various regions of the GI tract. Ultrasound capsule endoscopy (USCE) uses a capsule equipped with μUS transducers that are capable of imaging below the GI wall surface, offering thereby a complementary sensing technique to optical imaging capsule endoscopy. In this work, a USCE device integrated with a ∼30 MHz ultrasonic transducer was developed to capture a full 360° image of the lumen. The performance of the device was initially evaluated using a wire phantom, indicating an axial resolution of 69.0 μm and lateral resolution of 262.5 μm. Later, in vivo imaging performance was characterised in the oesophagus and small intestine of anaesthetized pigs. The reconstructed images demonstrate clear layer differentiation of the lumen wall. The tissue thicknesses measured from the B-scan images show good agreement with ex vivo images from the literature. The high-resolution ultrasound images in the in vivo porcine model achieved with this device is an encouraging preliminary step in the translation of these devices toward future clinical use