Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

Abstract

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy

“…We seek to expand on this work through the use of quantitative analysis techniques to calculate key tissue properties and establish a healthy baseline. Quantitative µUS can detect pre-cancerous changes in tissue organization in isolated tissue in a laboratory environment [ 86 , 87 , 88 , 89 ]. Both acoustic impedance (Z) and backscattering coefficient (BSC) showed potential for detecting changes in cell and tissue architecture characteristic of early disease [ 86 ].…”

“…The incident wave amplitude can be obtained by reversing the calculation using the same transducer configuration and a material of known acoustic impedance as a reflector, in this case a quartz flat. The BSC was calculated using the same methodology as in previous studies [ 86 ], where the coefficient is broken down into terms based on the geometry of the transducer, a reference echo from a known quartz reflector and loss due to attenuation: where R q is the reflection coefficient of the quartz reflector, θ T is the half-angle subtended by the transducer face at the focal point, V s is the signal obtained from the interrogated sample, integrated over the time-gate of interest, V q is the amplitude of the signal obtained from the ground truth reference integrated over the full sample time, and d 1 and d 2 are the minimum and maximum depths of the tissue sample within the US image.…”

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

“…Since the layers are relatively thin (1-2 mm maximum), subsurface but still only superficial imaging is required. Although μUS signal attenuation with depth is often assumed to be prohibitive, the limited tissue penetration required makes capsule-based μUS imaging of the wall of the GI tract a viable technique [6].…”

Progress towards a multi-modal capsule endoscopy device featuring microultrasound imaging

“…Previous work has shown that it can allow differentiation of the layers of the GIT [4] as well as quantitative analysis of diseased tissue [5].…”