Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1267_Библиотеки_им_академика_М_И_Перельмана.pdf
12 Clinical, Cellular andSerologic Biomarkers ofIntestinal Fibrosis
177
in CD [25]. Likewise, the pro-angiogenic/pro-brogenic PDGF, known to increase
collagen production by myobroblasts and smooth muscle cells, is enhanced in
the serum of IBD patients [29].
A number of anti-microbial antibodies thought to originate from an abnormal
immune response directed to the microora [30], have been detected in the serum of
CD patients and encompass anti-Escherichia coli outer membrane protein C antibodies (anti-OmpC), anti-Pseudomonas-associated sequence I2 antibodies (anti I2), anti-bacterial agellin CBir1 antibodies (anti-CBir1), and anti-glycan antibodies,
including ASCA, anti-chitobioside carbohydrate IgA antibodies (ACCA), anti-mannobioside carbohydrate IgG antibodies (AMCA), anti- laminaribioside IgG antibodies (ALCA), anti-laminarin carbohydrate antibodies (anti-L), and anti-chitin
carbohydrate antibodies (anti-C) [31–34]. These antibodies are quantitatively and
qualitatively associated with a much more complicated clinical course of CD, such
as stricturing and stulizing phenotype, either in adult or in pediatric patients [3].
Conversely, none of the anti-glycan antibodies ASCA, AMCA, ACCA, ALCA, antiL and anti-C has been recently shown to correlate with disease behavior [35]. ASCA
are the most extensively studied antibodies in IBD due to their ability to distinguish
CD from UC with a sensitivity of 56% and a specicity of 88% [36]. In addition, CD
patients positive for ASCA evolve towards brostenosing or penetrating behavior
with a sensitivity of 70% and a specicity of 48%, and more often have an ileal or
ileo-colonic involvement with a subsequent higher need for intestinal resection [36,
37]. CD patients with serological positivity for ASCA frequently have perianal dis-
ease and an early disease onset [37]. As far as the other anti-glycan antibodies are
concerned, ACCA are those more often associated with a stricturing or penetrating
behavior with lower sensitivity (43%) but higher specicity (75%) than ASCA [36].
Additionally, ASCA, AMCA and anti-L positivity correlates with an increased rate
of early occurrence of complications and surgery [38], whereas ASCA, AMCA,
ACCA and anti-L positivity predict a more quick evolution into complications or
surgery [32]. The risk of developing strictures and/or stulas is 11-fold higher in CD
children with anti-CBir1, anti-OmpC, anti-I2 and ASCA positivity than in seronegative children [39]. A following larger prospective study conrmed these ndings on
CD children with serological positivity for anti-CBir1, anti-OmpC and ASCA [40].
An Irish study reported a signicant association of serum anti-CBir1 positivity with
both a complicated disease behavior and ileal location, but not with high need for
intestinal resection [41]. ASCA IgG have been shown to be the only antibodies signicantly associated with a stricturing/penetrating phenotype in a multivariate analysis in a population-based cohort of CD patients [42]. Recently, a meta-analysis on
11 studies and based on four antibodies-ASCA, anti-OmpC, anti-I2 and antiCBir1,
showed that ASCA are the antibodies with the highest sensitivity and anti-OmpC are
those with the highest specicity for complications and surgery [43]. The use of at
least two anti-microbial antibodies rather than any single one predicted more effectively CD progression towards disabling disease [43]. All these anti-microbial antibodies are suitable for predicting CD complications, but not for differentiating
stricturing phenotype from other behaviors. New prospective studies are necessary
to establish whether circulating antibodies, alone or together with other biomarkers,
are able to predict the clinical course and stricture development in IBD.
178
A. Di Sabatino and P. Giuffrida
12.5 Other Factors
Fibroblast activation protein (FAP), which is a glycoprotein expressed by activated
broblasts during tissue remodeling, is up-regulated in idiopathic pulmonary brosis and liver cirrhosis [44, 45]. Serum FAP has been suggested as an index of liver
brosis [46], but there are no results on serum FAP as a biomarker of intestinal
brosis in IBD patients. Likewise, FAP is enhanced in the submucosa and in the
muscle layer of CD strictures, whereas the probrogenic cytokines transforming
growth factor (TGF)-β1 and TNF-α increases FAP expression on intestinal myobroblasts isolated from stricturing CD [47]. The blockade of FAP induces an ex vivo
reduction of type I collagen and TIMP-1 expression in strictured ileum of CD
patients [48].
12.6 Conclusions
Advances in understanding the mechanisms underlying intestinal brosis have
occurred over the last years. Nevertheless, there is not sufcient indication to support the diagnostic and prognostic power of any brogenic biomarker in clinical
practice. This is partly due to several limitations, including (1) the long-lasting progression of intestinal brosis, that requires studies of long duration and recruiting
large patients’ cohorts, (2) the frequent overlap of clinical phenotypes along the
natural history [49], and (3) the impact of concomitant immunomodulatory drugs
on serum biomarker levels. Additionally, the complexity of the pathophysiological
mechanisms underlying the brogenic process in the gut suggests that a panel of
biomarkers would be more accurate than a single factor, as it happens in liver brosis for the ELF panel [12]. Serum biomarkers of intestinal brosis have been used
so far in a phase 1 open label trial on CD patients with inammatory behavior
undergoing an oral treatment with GED-0301, a Smad7 antisense oligonucleotide,
whose action restores the anti-inammatory TGF-β signaling [50]. As TGF-β is also
implicated in the brogenic process in CD [51], in order to rule out a hypothetical
pro-brogenic effect of GED-0301, serum bFGF and YKL-40 were measured at
baseline and after 6months [50]. No signicant change was identied for both the
biomarkers, this in keeping with the absence of bowel thickness modications evaluated through ultrasonography [50].
References
1. Giuffrida P, Pinzani M, Corazza GR, etal. Biomarkers of intestinal brosis- one step towards
clinical trials for stricturing inammatory bowel disease. United European Gastroenterol J.
2016;4:523–30.
12 Clinical, Cellular andSerologic Biomarkers ofIntestinal Fibrosis
2. Rieder F, de Bruyn JR, Pham BT, etal. Results of the 4th scientic workshop of the ECCO
(Group II): markers of intestinal brosis in inammatory bowel disease. J Crohns Colitis.
2014;8:1166–78.
3. Rieder F, Lawrance IC, Leite A, etal. Predictors of brostenotic Crohn’s disease. Inamm
Bowel Dis. 2011;17:2000–7.
4. Beaugerie L, Seksik P, Nion-Larmurier I, etal. Predictors of Crohn’s disease. Gastroenterology.
2006;130:650–6.
5. Lichtenstein GR, Olson A, Travers S, et al. Factors associated with the development of
intestinal strictures or obstructions in patients with Crohn’s disease. Am J Gastroenterol.
2006;101:1030–8.
6. Moeller A, Gilpin SE, Ask K, etal. Circulating brocytes are an indicator of poor prognosis in
idiopathic pulmonary brosis. Am J Respir Crit Care Med. 2009;179:588–94.
7. Sazuka S, Katsuno T, Nakagawa T, etal. Fibrocytes are involved in inammation as well as
brosis in the pathogenesis of Crohn’s disease. Dig Dis Sci. 2014;59:760–8.
8. De Simone M, Ciulla MM, Ciof U, et al. Effects of surgery on peripheral N-terminal
propeptide of type III procollagen in patients with Crohn’s disease. J Gastrointest Surg.
2007;11:1361–4.
9. Kjeldsen J, Schaffalitzky de Muckadell OB, et al. Seromarkers of collagen I and III
metabolism in active Crohn’s disease. Relation to disease activity and response to therapy.
Gut. 1995;37:805–10.
10. Di Sabatino A, Jackson CL, Pickard KM, etal. Transforming growth factor beta signalling
and matrix metalloproteinases in the mucosa overlying Crohn’s disease strictures. Gut.
2009;58:777–89.
11. Kapsoritakis AN, Kapsoritaki AI, Davidi IP, et al. Imbalance of tissue inhibitors of
metalloproteinases (TIMP) - 1 and - 4 serum levels, in patients with inammatory bowel
disease. BMC Gastroenterol. 2008;8:55.
12. Rosenberg WM, Voelker M, Thiel R, etal. Serum markers detect the presence of liver brosis:
a cohort study. Gastroenterology. 2004;127:1704–13.
13. Vesterhus M, Hov JR, Holm A, etal. Enhanced liver brosis score predicts transplant-free
survival in primary sclerosing cholangitis. Hepatology. 2015;62:188–97.
14. Koutroubakis IE, Petinaki E, Dimoulios P, etal. Serum laminin and collagen IV in inamma-
tory bowel disease. J Clin Pathol. 2003;56:817–20.
15. Verspaget HW, Biemond I, Allaart CF, et al. Assessment of plasma bronectin in Crohn’s
disease. Hepatogastroenterology. 1991;38:231–4.
16. Allan A, Wyke J, Allan RN, et al. Plasma bronectin in Crohn’s disease. Gut. 1989;
30:627–33.
17. Giuffrida P, Biancheri P, MacDonald TT. Proteases and small intestinal barrier function in
health and disease. Curr Opin Gastroenterol. 2014;30:147–53.
18. Vassiliadis E, Oliveira CP, Alvares-da-Silva MR, et al. Circulating levels of citrullinated
and MMP-degraded vimentin [VICM] in liver brosis related pathology. Am J Transl Res.
2012;4:403–14.
19. Vassiliadis E, Veidal SS, Barascuk N, et al. Measurement of matrix metalloproteinase
9- mediated collagen type III degradation fragment as a marker of skin brosis. BMC Dermatol.
2011;11:6.
20. Veidal SS, Karsdal MA, Nawrocki A, et al. Assessment of proteolytic degradation of the
basement membrane: a fragment of type IV collagen as a biochemical marker for liver brosis.
Fibrogenesis Tissue Repair. 2011;4:22.
21. Mortensen JH, Godskesen LE, Jensen MD, et al. Fragments of citrullinated and MMP-
degraded vimentin and MMP-degraded type III collagen are novel serological biomarkers to
differentiate Crohn’s disease from ulcerative colitis. J Crohns Colitis. 2015;9:863–72.
22. Mortensen JH, Manon-Jensen T, Jensen MD, etal. Ulcerative colitis, Crohn’s disease, and
irritable bowel syndrome have different proles of extracellular matrix turnover, which also
reects disease activity in Crohn’s disease. PLoS One. 2017;12:e0185855.
179
180
23. Bousvaros A, Zurakowski D, Fishman SJ, et al. Serum basic broblast growth factor in
pediatric Crohn’s disease. Implications for wound healing. Dig Dis Sci. 1997;42:378–86.
24. Di Sabatino A, Ciccocioppo R, Benazzato L, etal. Iniximab downregulates basic broblast
growth factor and vascular endothelial growth factor in Crohn’s disease patients. Aliment
Pharmacol Ther. 2004;19:1019–24.
25. Di Sabatino A, Ciccocioppo R, Armellini E, etal. Serum bFGF and VEGF correlate respec-
tively with bowel wall thickness and intramural blood ow in Crohn’s disease. Inamm Bowel
Dis. 2004;10:573–7.
26. Koutroubakis IE, Petinaki E, Dimoulios P, etal. Increased serum levels of YKL-40in patients
with inammatory bowel disease. Int J Colorectal Dis. 2003;18:254–9.
27. Erzin Y, Uzun H, Karatas A, etal. Serum YKL-40 as a marker of disease activity and stricture
formation in patients with Crohn’s disease. J Gastroenterol Hepatol. 2008;23:e357–62.
28. Pinzani M. Fibrosis in the GI tract: pathophysiology, diagnosis and treatment options. In:
Mayerle J, Tilg H, editors. Clinical update on inammatory disorders of the gastrointestinal
tract, Frontiers of gastrointestinal research. Basel: Karger; 2010. p.15–31.
29. Matusiewicz M, Neubauer K, Mierzchala-Pasierb M, etal. Matrix metalloproteinase-9: its inter-
play with angiogenic factors in inammatory bowel diseases. Dis Markers. 2014;2014:643645.
30. Dotan I, Fishman S, Dgani Y, etal. Antibodies against laminaribioside and chitobioside are
novel serologic markers in Crohn’s disease. Gastroenterology. 2006;131:366–78.
31. Arnott ID, Landers CJ, Nimmo EJ, etal. Sero-reactivity to microbial components in Crohn’s
disease is associated with disease severity and progression, but not NOD2/CARD15 genotype.
Am J Gastroenterol. 2004;99:2376–84.
32. Reumaux D, Sendid B, Poulain D, etal. Serological markers in inammatory bowel diseases.
Best Pract Res Clin Gastroenterol. 2003;17:19–35.
33. Rieder F, Schleder S, Wolf A, etal. Serum anti-glycan antibodies predict complicated Crohn’s
disease behavior: a cohort study. Inamm Bowel Dis. 2010;16:1367–75.
34. van Schaik FD, Oldenburg B, Hart AR, etal. Serological markers predict inammatory bowel
disease years before the diagnosis. Gut. 2013;62:683–8.
35. Paul S, Boschetti G, Rinaudo-Gaujous M, et al. Association of anti-glycan antibodies and
inammatory bowel disease course. J Crohns Colitis. 2015;9:445–51.
36. Kaul A, Hutess S, Liu L, etal. Serum anti-glycan antibody biomarkers for inammatory
bowel disease diagnosis and progression: a systematic review and meta-analysis. Inamm
Bowel Dis. 2012;18:1872–84.
37. Zhang Z, Li C, Zhao X, et al. Anti-Saccharomyces cerevisiae antibodies associate with
phenotypes and higher risk for surgery in Crohn’s disease: a meta-analysis. Dig Dis Sci.
2012;57:2944–54.
38. Rieder F, Dirmeier A, Strauch U, et al. Association of the novel serologic anti-glycan
antibodies anti-laminarin and anti-chitin with complicated Crohn’s disease behavior. Inamm
Bowel Dis. 2010;16:263–74.
39. Dubinsky MC, Lin YC, Dutridge D, etal. Serum immune responses predict rapid disease
progression among children with Crohn’s disease: immune responses predict disease
progression. Am J Gastroenterol. 2006;101:360–7.
40. Dubinsky MC, Kugathasan S, Mei L, etal. Increased immune reactivity predicts aggressive
complicating Crohn’s disease in children. Clin Gastroenterol Hepatol. 2008;6:1105–11.
41. O’Donnell S, O’Sullivan M, O’Morain CA, etal. The clinical signicance of antimicrobial
serologic responses within an Irish Crohn’s disease population. Eur J Gastroenterol Hepatol.
2013;25:1464–9.
42. Ryan JD, Silverberg MS, Xu W, etal. Predicting complicated Crohn’s disease and surgery:
phenotypes, genetics, serology and psychological characteristics of a population-based cohort.
Aliment Pharmacol Ther. 2013;38:274–83.
43. Xiong Y, Wang GZ, Zhou JQ, etal. Serum antibodies to microbial antigens for Crohn’s disease
progression: a meta-analysis. Eur J Gastroenterol Hepatol. 2014;26:733–42.
44. Acharya PS, Zukas A, Chandan V, etal. Fibroblast activation protein: a serine protease expressed
at the remodeling interface in idiopathic pulmonary brosis. Hum Pathol. 2006;37:352–60.
A. Di Sabatino and P. Giuffrida
12 Clinical, Cellular andSerologic Biomarkers ofIntestinal Fibrosis
45. Levy MT, McCaughan GW, Abbott CA, etal. Fibroblast activation protein: a cell surface
dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling
interface in human cirrhosis. Hepatology. 1999;29:1768–78.
46. Williams KH, Viera de Ribeiro AJ, Prakoso E, etal. Lower serum broblast activation protein
shows promise in the exclusion of clinically signicant liver brosis due to non-alcoholic fatty
liver disease in diabetes and obesity. Diabetes Res Clin Pract. 2015;108:466–72.
47. Rovedatti L, Di Sabatino A, Knowles CH, etal. Fibroblast activation protein expression in
Crohn’s disease strictures. Inamm Bowel Dis. 2011;17:1251–3.
48. Truf M, Sorrentino L, Monieri M, etal. Inhibition of broblast activation protein restores
a balanced extracellular matrix and reduces brosis in Crohn’s disease strictures ex vivo.
Inamm Bowel Dis. 2018;24(2):332–45.
49. Cosnes J, Cattan S, Blain A, etal. Long-term evolution of disease behavior of Crohn’s disease.
Inamm Bowel Dis. 2002;8:244–50.
50. Zorzi F, Calabrese E, Monteleone I, etal. A phase 1 open-label trial shows that smad7 antisense
oligonucleotide (GED0301) does not increase the risk of small bowel strictures in Crohn’s
disease. Aliment Pharmacol Ther. 2012;36:850–7.
51. Biancheri P, Giuffrida P, Docena GH, etal. The role of transforming growth factor (TGF)-β
in modulating the immune response and brogenesis in the gut. Cytokine Growth Factor Rev.
2014;25:45–55.
181
Chapter 13
Imaging inIntestinal Fibrosis. What Is State
oftheArt?
JordiRimola
Abstract Over the past decade, there has been increasing evidence that cross-
sectional imaging may be helpful in the evaluation and management of Crohn’s
disease patients. Multiple studies have analyzed the potentiality of these techniques
of detecting bowel wall brosis deposition in areas of stricturing disease, even in the
setting of superimposed inammation. Such knowledge may be incorporated in the
appropriate medical, endoscopical and surgical algorithm management of stricturing Crohn’s disease.
This chapter will review the different imaging modalities for assessing the bowel,
published evidence supporting the use of these techniques in Crohn’s disease
patients, potential roles in clinical practice, and likely challenges and obstacles to
future use in clinical practice and in research studies.
Keywords MR enterography · CT enterography · Bowel ultrasound ·
Elastography · Diffusion weighted imaging · Crohn’s disease
13.1 Introduction
Patients with Crohn’s disease (CD) often develop intestinal stenosis. Stenosis due to
acute inammation is potentially reversible with medical treatment. However, longterm stenosis due to intestinal brosis that accumulates from wound-healing mechanisms in response to transmural injury secondary to segmental bowel inammation
can currently only be treated with surgery. The proportion of patients who develop
long-term stenosis increases with the time from the onset of disease, and intestinal
stenosis is the main reason for surgery in CD patients [1]. Thus, the accurate determination of the extent of brosis accumulation in the bowel is key for the management of CD patients. However, differentiating between inammation and brosis as
the causes of stenosis is complex.
J. Rimola
IBD Unit, Radiology Department, Hospital Clínic de Barcelona, University of Barcelona,
Barcelona, Catalonia, Spain
e-mail: jrimola@clinic.cat
F. Rieder (ed.), Fibrostenotic Inammatory Bowel Disease,
https://doi.org/10.1007/978-3-319-90578-5_13
183© Springer International Publishing AG, part of Springer Nature 2018
184
Histopathologic analysis of endoscopic biopsy specimens is unreliable for determining the amount of brosis in the intestinal wall because they are not transmural
and brosis is unevenly distributed in stenotic segments and samples are often not
representative.
Not only can cross-sectional imaging modalities identify strictures in both the
small and large bowel, they can also detect signs of inammation and brosis. Thus,
given the transmural nature of the disease, cross-sectional imaging may enable a
more objective assessment of bowel injury [2, 3]. In recent years, novel techniques
linked to cross-sectional imaging modalities have been used in research and incorporated into radiologists’ daily practice with the aim of better characterizing stenosis through quantifying the degree of brosis in the bowel.
J. Rimola
13.2 Challenges toAssessing Fibrosis by Imaging Techniques
Cross-sectional imaging is highly accurate in detecting inammatory lesions. One
key feature indicating the presence of active disease is mucosal enhancement on a
thickened bowel segment. When evidence of mucosal enhancement or hypervascularity is lacking on computed tomography (CT), ultrasound (US), or magnetic resonance imaging (MRI) of the bowel, brosis is often assumed. However, brosis is
closely linked to inammation, and both components are frequently superimposed
in stenotic segments; therefore, standard imaging modalities might be unable to differentiate between them [4–6].
This chapter discusses the potential and the limitations of cross-sectional imaging techniques for assessing bowel brosis in patients with CD.
13.3 Bowel Ultrasound
Classically, a stratied bowel echo pattern (identication of different bowel wall
layers) in a stenotic segment on bowel ultrasound was associated with collagen
deposition, but this association has not been validated [7]. Furthermore, this
approach does not allow the degree of brosis to be quantied, so additional analyses are required.
Adding contrast-enhanced US has limited value for assessing brosis. In a
single- center study correlating US ndings with histopathologic ndings in which
stenosis was classied as predominantly inammatory or predominantly brotic,
the percentage of bowel enhancement together with Doppler US and presence of a
penetrating complication was associated with stenosis with a predominantly inammatory component but not with stenosis with a predominantly brotic component.
However, the only US nding associated with brosis was a low Doppler signal [8].
Strain elastography can add information to gray-scale US by assessing tissue
elasticity. This noninvasive imaging modality assesses tissue mechanical properties
13 Imaging inIntestinal Fibrosis. What Is State oftheArt?
185
and stiffness by measuring strain (i.e., the degree of compression of a material in
response to a force applied to a xed area). Hard materials or tissues (e.g., brosis)
exhibit low strain in response to a xed stress and are commonly described as stiffer.
The deposition of extracellular brotic matrix together with muscle hypertrophy in
the bowel wall contributes to changes in the mechanical properties of brostenotic
intestinal damage. Table13.1 summarizes the different studies evaluating US elastography in animal models and in humans.
Initial studies [9] provided evidence that elastography was able to measure the
‘hardness’ or ‘softness’ of a tissue in a trinitrobenzenesulfonic acid model of intestinal injury in rats. Bowel segments were stratied in different degrees between
early phase inammation and late phase brosis. Using a two-dimensional speckle
tracking technique to quantify tissue elasticity, the strain assessment was able to
differentiate segments with an inammatory component from those with a brotic
component. The same study also evaluated 7 human subjects with CD, nding signicant differences in stiffness between stenotic bowel segments and adjacent normal small bowel in (−0.87 vs. −1.99Kpa; p=0.0008); moreover, this measurement
Table 13.1 Main studies evaluating US elastography of the bowel as surrogate marker of brosis
using histopathology as reference standard
Author/publication
Stidham,
Gastroenterology
2011; 141: 819–826
Dillman, Radiology
2013
Dillman, Ultrasound
2014
Baumgart, Radiology
2015
Fraquelli, IBD 2015 Shear-wave real
TNBS trinitrobenzenesulfonic acid, ARFI acoustic radiation force impulse
Elastography
modality Population Relevant data
Twodimensional
Speckle
tracking
technique
Real-time
elastography
(ARFI)
Real-time
elastography
(ARFI)
Shear-wave real
time
elastography
time
elastography
Lewis rats after
TNBS-induced
colitis
Human pilot
study (n=7)
Lewis rats after
TNBS-induced
colitis (n=13)
Lewis rats after
TNBS-induced
colitis (n=17)
Humans
(n=10)
Humans
(n=23)
Rats: distinguish inamed from
brotic inammatory tissue (2.07 vs.
1.10, p=0.037)
Humans: differences between
stenotic bowel segments
(−0.87±0.22) vs. normal
(−1.99±0.53) (P=0.0008);
correlated with the presence of
brosis (r=0.81, p=0.008)
Distinguish brotic and
inammatory intestinal damage with
an area under the ROC of 0.971, and
a PPV and NPV of 95.0% and
92.9%, respectively
Area under receiver operating
characteristic curve of 0.91in
distinguishing between bowel
segments with low and high brosis
scores
Good agreement between invivo
real-time elastography and exvivo
mechanical induced elastography
Values for mild-moderate brosis
overlapped with those obtained in
non-stenotic inammatory segments
in a control group
186
J. Rimola
correlated well with exvivo elastometry (r=−0.81). However, an important limitation of these initial studies was that the bowel elastography technique was not performed in real time and required extensive image post-processing.
Nowadays, US elastography images of the bowel are acquired in real time using
dynamic strain imaging techniques or rapid attenuating shear waves (Fig.13.1).
When focused ultrasound beams from the probe displace tissue posteriorly, the
restorative force of the tissue propagates laterally, generating shear waves. Software
processes the signals to show the different degrees of strain in a color scale, and the
color-coded information about strain is displayed superimposed on the conventional
B-mode US image [10]. Real-time bowel elastography measurements acquired
invivo were similar to the measurements obtained using direct mechanical tensiometry in exvivo specimens [11].
Siemens’ acoustic radiation force impulse system allows the stiffness in a specic region of bowel wall to be measured and also allows the absolute value of stiffness to be determined. In a trinitrobenzenesulfonic acid rat model, Dillman etal.
[12] found this system distinguished between brotic and inammatory intestinal
damage with an area under the receiver operating characteristic curve of 0.971, with
a 95.0% positive predictive value and a 92.9% negative predictive value. Interestingly,
Baumgart etal. [11] applied this technique before, during, and after surgery in 10
CD patients undergoing intestinal resection. They found that elastography measurements were associated with the degree of muscularis thickness (p = 0.006), trichrome stain score (4 vs. 0; p<0.001), and western blot quantication of collagen
content (high vs. low) (2.01 vs. 0.87; p=0.009).
However, there are still concerns about the contribution of inammation to the
overall shear wave elastography measurement on the human bowel. In CD, the
inammatory component is usually superimposed on background brosis. Shear
wave speed is not signicantly different between bowel segments with high and low
inammation scores [11, 13]. Although Baumgart etal. [11] reported a modest correlation between shear wave elastography and histologic grade of brosis (r=0.60,
p=0.01), they found no signicant correlation with inammation.
Nevertheless, some studies obtained signicantly greater mean shear wave
velocity on segments with high brosis score than on segments with low brosis
score in exvivo bowel specimens [13]. However, these ndings are in conict with
those reported more recently by Fraquelli etal. [14] in a study of 23 human subjects,
where the strain ratio (strain of stenotic segment normalized by the strain of mesenteric fat within subjects) determined invivo on the terminal ileum was signicantly
different between mild-moderate brosis and severe brosis, but where values for
mild-moderate brosis overlapped with those obtained in non-stenotic inammatory segments in a control group.
Despite the promising results published recently, further evidence is needed
before US elastography can be incorporated into routine clinical care for patients
with CD. Unresolved issues include establishing reproducibility across vendors,
dening the dynamic range, and determining the technique’s ability to quantify intermediate grades of bowel brosis that could identify the progression or improvement
of brosis and ultimately predict the natural history and clinical outcomes of CD.
13 Imaging inIntestinal Fibrosis. What Is State oftheArt?
a
187
b
Fig. 13.1 Two examples of real time ultrasound elastography. (a) Corresponds to an image of
stenotic bowel wall in a longstanding CD patient. The color scale (from red—highest KPa to
blue—lowest KPa) shows the distribution of the elasticity within the region (box) of interest overlaid on grayscale images. (b) Corresponds to a 31-year old male patient with CD with stenotic
segment on the terminal ileum evaluated by Acoustic Radiation Force Image (ARFI). The ARFI,
or push pulse, displaces targeted tissue at a specied depth and estimates the shear wave velocity
on the area delineated by the box