Strain-Photoacoustic Imaging as a Potential Tool for Characterizing Intestinal Fibrosis
2019; Elsevier BV; Volume: 157; Issue: 5 Linguagem: Inglês
10.1053/j.gastro.2019.07.061
ISSN1528-0012
AutoresYunhao Zhu, Laura A. Johnson, Jonathan M. Rubin, Henry D. Appelman, Linyu Ni, Jie Yuan, Xueding Wang, Peter Higgins, Guan Xu,
Tópico(s)Ultrasound Imaging and Elastography
ResumoThe accurate diagnosis of the composition of intestinal strictures is critical in the management of Crohn's disease,1Rieder F. Lawrance I.C. Leite A. et al.Predictors of fibrostenotic Crohn's disease.Inflam Bowel Dis. 2011; 17: 2000-2007Crossref PubMed Scopus (55) Google Scholar Because inflammatory strictures may respond to anti-inflammatory therapy, but late-stage fibrotic strictures require surgical resection. In addition, the intestinal expression of extracellular matrix genes, that is, fibrosis, is an important predictor of future complicated and obstructive Crohn's disease.2Kugathasan S. Denson L.A. Walters T.D. et al.Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study.Lancet. 2017; 389: 1710-1718Abstract Full Text Full Text PDF PubMed Scopus (335) Google Scholar Mucosal biopsies are limited by sampling depth, rarely reaching the muscular layers where fibrosis occurs. Conventional imaging modalities can identify the presence of intestinal strictures by structural changes.3Stidham R.W. Higgins D. Imaging of intestinal fibrosis: current challenges and future methods.United European Gastroenterol J. 2016; 4: 515-522Crossref PubMed Scopus (26) Google Scholar However, none of the modalities can assess the pathological markers of fibrosis in contrast to inflammation.3Stidham R.W. Higgins D. Imaging of intestinal fibrosis: current challenges and future methods.United European Gastroenterol J. 2016; 4: 515-522Crossref PubMed Scopus (26) Google Scholar Previous studies by us and other groups have examined detecting collagen deposition in intestinal fibrosis using magnetization transfer magnetic resonance imaging4Wolff S.D. Eng J. Balaban R.S. Magnetization transfer contrast: method for improving contrast in gradient-recalled-echo images.Radiology. 1991; 179: 133-137Crossref PubMed Scopus (134) Google Scholar and photoacoustic (PA) imaging.5Lei H. Johnson L.A. Liu S. et al.Characterizing intestinal inflammation and fibrosis in Crohn's disease by photoacoustic imaging: feasibility study.Biomedical Optics Express. 2016; 7: 2837-2848Crossref PubMed Scopus (31) Google Scholar, 6Zhu Y. Johnson L.A. Huang Z. et al.Identifying intestinal fibrosis and inflammation by spectroscopic photoacoustic imaging: an animal study in vivo.Biomedical Optics Express. 2018; 9: 1590-1600Crossref PubMed Scopus (20) Google Scholar, 7Lei H. Johnson L.A. Eaton K.A. et al.Characterizing intestinal strictures of Crohn's disease in vivo by endoscopic photoacoustic imaging.Biomedical Optics Express. 2019; 10: 2542-2555Crossref PubMed Scopus (19) Google Scholar Our pilot study using ultrasound (US) elastography has demonstrated that the increased stiffness is a mechanical biomarker of intestinal fibrosis.8Stidham R.W. Xu J. Johnson L.A. et al.Ultrasound elasticity imaging for detecting intestinal fibrosis and inflammation in rats and humans with Crohn's Disease.Gastroenterology. 2011; 141: 819-826.e811Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar A challenge in quantitative elastography of the intestinal stricture is that the stress components are difficult to measure in deep abdomen. This study introduces an alternative approach of quantifying the stiffness of intestinal strictures without the necessity of stress measurement using PA-US parallel imaging. We have successfully identified increased hemoglobin content in inflammatory intestinal strictures and collagen deposition in fibrotic intestinal strictures using spectroscopic PA imaging in animals in vivo.5Lei H. Johnson L.A. Liu S. et al.Characterizing intestinal inflammation and fibrosis in Crohn's disease by photoacoustic imaging: feasibility study.Biomedical Optics Express. 2016; 7: 2837-2848Crossref PubMed Scopus (31) Google Scholar, 6Zhu Y. Johnson L.A. Huang Z. et al.Identifying intestinal fibrosis and inflammation by spectroscopic photoacoustic imaging: an animal study in vivo.Biomedical Optics Express. 2018; 9: 1590-1600Crossref PubMed Scopus (20) Google Scholar, 7Lei H. Johnson L.A. Eaton K.A. et al.Characterizing intestinal strictures of Crohn's disease in vivo by endoscopic photoacoustic imaging.Biomedical Optics Express. 2019; 10: 2542-2555Crossref PubMed Scopus (19) Google Scholar In the meantime, we found that parallel PA-US imaging is capable of capturing the blood content reduction in intestinal stricture during compression of abdominal walls of animals. We define such observation strain-PA phenomenon, which reflects the stiffness of the observed tissue. In the video, we first briefly reviewed the physics of spectroscopic PA imaging and our previous studies on PA-US parallel imaging of intestinal strictures. Cineloops demonstrating the strain-PA phenomenon were shown. We spelled out our derivation of the mathematical expression mapping the strain-PA ratio to the strain-stress ratio. The mathematical expression was examined using trinitrobenzenesulfonic acid model in rats8Stidham R.W. Xu J. Johnson L.A. et al.Ultrasound elasticity imaging for detecting intestinal fibrosis and inflammation in rats and humans with Crohn's Disease.Gastroenterology. 2011; 141: 819-826.e811Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar in vivo. The animal model mimics the acute disease condition where the intestinal stricture only contains inflammation and the chronic condition where both intestinal fibrosis and inflammation present. The experiment was performed using a light-emitting diode (LED) based PA imaging system (AcousticX, Prexion, Japan). The sensor array of the system possesses a 10 MHz central frequency and 80.9% bandwidth. The LED light sources flashed at 4 kHz and 200 μJ per pulse. PA signals generated by 384 LED flashes were averaged for improved signal-to-noise ratio, producing an imaging frame rate of approximately 10 per second. A vertical translation stage slowly pushed the sensor array against the abdominal wall of the animals at approximately 0.4 mm/s for 25 seconds. Figure 1 shows the representative images captured in an acute and a chronic animal, and corresponding histology. In Figure 2A, the averaged PA signal magnitudes within the top quadrant of the bowel loop were plotted against the bowel wall strain measured by speckle tracking (Echoinsight, Epsilon Imaging Inc, Ann Arbor, MI) in the parallel US images. The descending trend of the strain–PA curves were quantified by fitting to linear models. The slopes of the linear models derived from the chronic (ie, fibrotic) animals are approximately 2 times of those derived from the acute (ie, inflammatory) ones (n = 14; P = 8 × 10-7), as shown in Figure 2B. The Young's moduli of the samples were solved from the strain–PA ratios using our mathematical expression. An approximately 2 times stiffness increase was observed in the chronic animals compared with the acute ones (n = 14; P = 4 × 10-5) in Figure 2C, which agrees with the conclusion in our previous study.8Stidham R.W. Xu J. Johnson L.A. et al.Ultrasound elasticity imaging for detecting intestinal fibrosis and inflammation in rats and humans with Crohn's Disease.Gastroenterology. 2011; 141: 819-826.e811Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar The video concludes with our vision for clinical translation of the presented technology and a preliminary feasibility study in human subjects.Figure 2Quantitative analysis of the strain-PA phenomenon. A, Normalized mean PA magnitude within the top quadrant of the intestinal stricture loops as a function of the strain of the stricture walls. As illustrated by the purple dashed line, the curves were fit to linear models. The slope of the linear model, ie, tanθ, is defined as strain-PA ratio. B Strain-PA ratios derived from A. C, The Young's moduli, ie, the stiffness, of the intestinal strictures derived from the strain-PA ratios in B.View Large Image Figure ViewerDownload Hi-res image Download (PPT) This video demonstrates the capability of PA-US parallel imaging in quantifying the mechanical properties of intestinal strictures, in addition to their molecular components. Such non-invasive and non-ionizing radiation imaging procedure is readily translatable to clinics for quick disease assessment and therapeutic planning. We thank Dr Thomas Wang at University of Michigan for his advice on revising this article. We thank Dr Ting Feng at Nanjing University of Technology for assisting in preparing the animations illustrating the experiment setup. We also thank Drs Sato Naoto and Toshitaka Agano with PreXion and Cyberdyne for providing the light-emitting diode–based photoacoustic ultrasound dual modality imaging system. https://www.gastrojournal.org/cms/asset/74a2a68b-6672-487d-8aed-ee04780fb255/mmc1.mp4Loading ... Download .mp4 (90.35 MB) Help with .mp4 files Video CME Exam 1: Strain-Photoacoustic Imaging as a Potential Tool for Characterizing Intestinal FibrosisGastroenterologyVol. 157Issue 5Preview Full-Text PDF
Referência(s)