Noninvasive Ultrasound Elasticity Imaging (UEI) of Crohn's Disease: Animal Model

Abstract

Inflammation occurs in episodic flares in Crohn's disease, which are part of the waxing and waning course of the disease. Healing between flares allows the intestine to reconstitute its epithelium, but this healing results in the deposition of fibrotic scar tissue as part of the healing process. Repeated cycles of flares and healing often lead to clinically significant fibrosis and stenosis of the intestine. Patients are treated empirically with steroids, with their many side effects, in the hope that they will respond. Many patients would be better treated with surgery if we could identify which patients truly have intestinal fibrosis. Ultrasound elasticity imaging (UEI) offers the potential to radically improve the diagnosis and management of local tissue elastic property, particularly intestinal fibrosis. This method allows complete characterization of local intestine tissue with high spatial resolution. The feasibility of UEI on Crohn's disease is demonstrated by directly applying this technique to an animal model of inflammatory bowel disease (IBD). Five female Lewis rats (150-180g) were prepared with phosphate buffered solution (PBS) as a control group and six were prepared with repeated intrarectal administration of trinitrobenzenesulfonic acid (TNBS) as a disease group. Preliminary strain measurements differentiate the diseased colons from the normal colons (p < 0.0002) and compared well with direct mechanical measurements and histology (p < 0.0005). UEI provides a simple and accurate assessment of local severity of fibrosis. The preliminary results on an animal model also suggest the feasibility of translating this imaging technique directly to human subjects for both diagnosis and monitoring.

Characterizing intestinal inflammation and fibrosis in Crohn’s disease by photoacoustic imaging: feasibility study

“…Colon samples with gradually changed disease conditions will be tested in our future study for further understanding the sensitivity and specificity of PAI on characterizing the intestinal strictures. Although the pulse-echo US did not show significant differences between the samples, US elasticity imaging also under investigation by the authors has demonstrated promising results in distinguishing inflammatory and fibrotic intestinal strictures [22,23].…”

“…In addition, since hemoglobin and collagen have almost parallel optical spectra in 1300s nm, optical wavelengths within this range produce similar results as the major molecular components in the samples were limited to hemoglobin and collagen. Water component change in the two types of samples was not considered as we did not find diseased conditions correlated to water content change [22,23]. Water content within the sample holder is stringently controlled to be identical for all experiment cases and thereby does not contribute to the difference between the PA images of the samples.…”

“…One group received a single 10 mg intrarectal dose of TNBS using the method described in [23]. This procedure produces acute inflammation of the distal colon which peaks 2-3 days after administration.…”

“…One group (acute TNBS, pure inflammatory) received a single 10 mg intrarectal dose of TNBS as described above. The second group animals (chronic TNBS, mixed inflammation and fibrosis) received weekly escalating doses of TNBS from 10 mg to 60 mg over 6 weeks as previously described [22,23]. Acute animals were euthanized 2 days post administration.…”

“…Our PA-US parallel imaging system was initially used to demonstrate the capability of PAI in quantitatively differentiating ex vivo normal intestine colon tissues, fibrotic and inflammatory intestinal strictures from trinitrobenzene sulfonic acid (TNBS) model in rat [22][23][24]. Surgically removed human intestinal specimens were afterwards imaged in an ARPAM system.…”