•A centerline extraction and segmentation method is proposed for the small intestine.•A novel stochastic centerline tracking strategy improves performance.•Segmentation performance is improved by ...conditioning the method on centerlines.•Robustness of the method is assessed by evaluating on diseased intestines.
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Cine-MRI of the abdomen is a non-invasive imaging technique allowing assessment of small intestinal motility. This is valuable for the evaluation of gastrointestinal disorders. While 2D cine-MRI is increasingly used for this purpose in both clinical practice and in research settings, the potential of 3D cine-MRI has been largely underexplored. In the absence of image analysis tools enabling investigation of the intestines as 3D structures, the assessment of motility in 3D cine-images is generally limited to the evaluation of movement in separate 2D slices. Furthermore, while a segmentation map of the small intestine would be required for a number of automatic analysis tasks, deep learning based segmentation of the small intestine generally performs poorly due to the large variety in shapes, sizes and locations in the abdomen among different patients. Using a data set of 3D cine-MRI scans from 14 healthy volunteers, we developed a multi-task method that automatically tracks individual segments of the small intestine in a time-point from 3D cine-MRI scans, using a stochastic tracker built on top of a CNN-based orientation classifier. The method additionally performs segmentation, conditioned on the locations of intestinal centerlines. We demonstrate the benefit of our stochastic tracking strategy and we show that our proposed segmentation method performs significantly better than an identical network without centerline conditioning. Furthermore, we assess the robustness of the method through evaluation on a set of patients with severe bowel disease. In terms of centerline tracking, our method achieves a recall of 0.74±0.07, a precision of 0.80±0.06 and an F1 score of 0.77±0.05 in the set of healthy volunteers. In the set of patients, it achieves a recall of 0.76±0.12, a precision of 0.86±0.11 and an F1 score of 0.80±0.08. Segmentation achieves a Dice coefficient of 0.88±0.03 in the set of healthy volunteers and 0.79±0.09 in the set of patients. By extracting a structural representation of the small intestine, the presented method provides a major first step towards automatic detailed quantitative assessment of small intestinal motility in abdominal 3D cine-MRI.
Abstract Background There is an increasing need for objective treatment monitoring in perianal fistulising Crohn’s disease (pfCD). Therefore, the magnetic resonance novel index for fistula imaging in ...CD (MAGNIFI-CD) index has been designed and internally validated on the ADMIRE-CD trial cohort. The aim of this study was to externally validate the MAGNIFI-CD index to monitor response to medical and surgical treatment regimens in pfCD. Methods A retrospective longitudinal cohort was established of consecutive patients with complex pfCD treated with surgical and/or medical therapy and a baseline and follow-up MRI between January 2007 and May 2021. The MAGNIFI-CD index was scored by two independent, abdominal radiologists blinded for time points and clinical outcomes. Responsiveness, reliability, and test accuracy regarding clinically important improvement were assessed. Cut-offs for response and remission were selected classified on fistula drainage assessment and physician global assessment. Results A total of 65 patients (51% female, median age 32 years) were included. A clinically relevant responsiveness of the MAGNIFI-CD was shown, with a significant decrease in clinical remitters and responders with a median MAGNIFI-CD of 18.0 7.5–20.0 to 9.0 0.8–16.0 ( p < 0.001) and non-significant change in non-responders with a median MAGNIFI-CD of 20.0 12.0–23.0 to 18.0 13.0–21.0 ( p = 0.22). There was an ‘almost perfect’ interobserver agreement (ICC = 0.87; 95% CI 0.80–0.92) for the MAGNIFI-CD index. An optimal cut-off value was defined as a decrease of 2 points for clinical response, and a MAGNIFI-CD ≤ 6 for remission at follow-up MRI. Conclusion The MAGNIFI-CD index is a responsive and reliable MRI scoring instrument for treatment monitoring in perianal fistulising Crohn’s disease. Clinical relevance statement The MAGNIFI-CD index is a well-structured, responsive scoring instrument to assess fistula severity and activity that allows quantitative detection of changes in therapy response in patients with perianal fistulising Crohn’s disease, thereby facilitating endpoints in clinical trials. Key Points Well-defined cut-offs for response and remission are needed for objective treatment monitoring of perianal fistulising Crohn’s disease (pfCD) . Cut-off values for remission and for response at 6 months follow-up were defined. Interobserver agreement was good . The MAGNIFI-CD index is responsive and reliable for treatment monitoring and is suitable for use in clinical trials . Graphical Abstract
Vagus nerve stimulation (VNS), most likely via enteric neurons, prevents postoperative ileus (POI) by reducing activation of alpha7 nicotinic receptor (α7nAChR) positive
macrophages (mMφ) and ...dampening surgery-induced intestinal inflammation. Here, we evaluated if 5-HT4 receptor (5-HT4R) agonist prucalopride can mimic this effect in mice and human.
Using Ca
imaging, the effect of electrical field stimulation (EFS) and prucalopride was evaluated in situ on mMφ activation evoked by ATP in jejunal
tissue. Next, preoperative and postoperative administration of prucalopride (1-5 mg/kg) was compared with that of preoperative VNS in a model of POI in wild-type and α7nAChR knockout mice. Finally, in a pilot study, patients undergoing a Whipple procedure were preoperatively treated with prucalopride (n=10), abdominal VNS (n=10) or sham/placebo (n=10) to evaluate the effect on intestinal inflammation and clinical recovery of POI.
EFS reduced the ATP-induced Ca
response of mMφ, an effect that was dampened by neurotoxins tetrodotoxin and ω-conotoxin and mimicked by prucalopride. In vivo, prucalopride administered before, but not after abdominal surgery reduced intestinal inflammation and prevented POI in wild-type, but not in α7nAChR knockout mice. In humans, preoperative administration of prucalopride, but not of VNS, decreased
and
expression in the
and improved clinical recovery.
Enteric neurons dampen mMφ activation, an effect mimicked by prucalopride. Preoperative, but not postoperative treatment with prucalopride prevents intestinal inflammation and shortens POI in both mice and human, indicating that preoperative administration of 5-HT4R agonists should be further evaluated as a treatment of POI.
NCT02425774.
We evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study.
...Non-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API). A subject was considered a weekly responder for GRS if total or obvious relief was reported and a responder for API if the weekly average pain score was reduced by at least 30% vs baseline. The primary endpoints were the proportion of subjects who were weekly responders for at least 6 out of the 12 treatment weeks for both GRS and API ('GRS+API', composite endpoint) and for GRS and API separately.
202 participants (32±11 years, 68% female) were randomly allocated to receive ebastine (n=101) or placebo (n=101). Treatment with ebastine resulted in significantly more responders (12%, 12/92) for GRS+API compared with placebo (4%, 4/87, p=0.047) while the proportion of responders for GRS and API separately was higher for ebastine compared with placebo, although not statistically significant (placebo vs ebastine, GRS: 7% (6/87) vs 15% (14/91), p=0.072; API: 25% (20/85) vs 37% (34/92), p=0.081).
Our study shows that ebastine is superior to placebo and should be further evaluated as novel treatment for patients with non-constipated IBS.
The study protocol was approved by the local ethics committee of each study site (EudraCT number: 2013-001199-39; ClinicalTrials.gov identifier: NCT01908465).
Aim
Controversies on therapeutic strategy for large bowel obstruction by primary colorectal cancer mainly concern acute conditions, being essentially different from subacute obstruction. Clearly ...defining acute obstruction is important for design and interpretation of studies as well as for guidelines and daily practice. This systematic review aimed to evaluate definitions of obstruction by colorectal cancer in prospective studies.
Method
A systematic search was performed in PubMed, Embase and the Cochrane Library. Eligibility criteria included randomized or prospective observational design, publication between 2000 and 2019, and the inclusion of patients with an obstruction caused by colorectal cancer. Provided definitions of obstruction were extracted with assessment of common elements.
Results
A total of 16 randomized controlled trials (RCTs) and 99 prospective observational studies were included. Obstruction was specified as acute in 28 studies, complete/emergency in five, (sub)acute or similar terms in four and unspecified in 78. Five of 16 RCTs (31%) and 37 of 99 cohort studies (37%) provided a definition. The definitions included any combination of clinical symptoms, physical signs, endoscopic features and radiological imaging findings in 25 studies. The definition was only based on clinical symptoms in 11 and radiological imaging in six studies. Definitions included a radiological component in 100% of evaluable RCTs (5/5) vs. 54% of prospective observational studies (20/37, P = 0.07).
Conclusion
In this systematic review, the majority of prospective studies did not define obstruction by colorectal cancer and its urgency, whereas provided definitions varied hugely. Radiological confirmation seems to be an essential component in defining acute obstruction.
Background
Creeping fat is a pathological feature of small bowel Crohn’s disease (CD), with literature suggesting that bowel resection with extended mesenteric resection is related to less ...postoperative recurrences. Conventional imaging is unable to accurately quantify the disease involvement (
i.e.
, fibrosis) of creeping fat. Quantification of disease involvement could be useful in decision-making for additional extended mesenteric resection. We investigated the feasibility of magnetic resonance elastography (MRE) of the mesentery and if MRE is capable to detect fibrotic disease involvement of mesentery in active CD.
Methods
Multifrequency MRE yielded spatial stiffness (shear wave speed, SWS, |G*|) and fluidity maps (φ). Viscoelastic properties of seven CD patients’ mesentery were compared to age- and sex-matched healthy volunteers (HV) (Mann–Whitney
U
-test). Within CD patients, the affected and “presumably” unaffected mesentery were compared (Wilcoxon-signed rank test). Repeatability was tested in 15 HVs (Bland–Altman analysis, coefficient of variation CoV). Spearman rank correlations were used to investigate the relation between microscopically scored amount of mesenteric fibrosis and viscoelastic parameters.
Results
SWS, |G*|, and
φ
of affected mesentery in CD were higher compared to HV (
p
= 0.017,
p
= 0.001,
p
= 0.017). Strong correlations were found between percentage of area of mesenteric fibrosis and SWS and |G*| (
p
< 0.010). No differences were found within CD between affected and presumably unaffected mesentery. Repeatability of SWS showed 95% limits of agreement of (-0.09, 0.13 m/s) and within-subject CoV of 5.3%.
Conclusion
MRE may have the potential to measure fibrotic disease involvement of the mesentery in CD, possibly guiding clinical decision-making with respect to extended mesenteric resection.
Trial registration
Dutch trial register,
NL9105
, registered 7 December 2020.
Relevance statement
MRE may have the potential to measure the amount of mesenteric fibrosis of the affected mesenteric fat in active Crohn’s disease, giving more insight into disease progression and could potentially play a role in clinical decision-making for extended mesenteric resection.
Key points
• MRE of the mesentery in patients with active CD is feasible.
• Fluidity and stiffness of the mesentery increase in active CD, while stiffness correlates with the histopathological amount of mesenteric fibrosis.
• MRE provides biomarkers to quantify mesenteric disease activity in active CD.
Graphical Abstract
Up to 20% of people worldwide develop gastrointestinal symptoms following a meal
, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both ...the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H
-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.
The balance between antioxidants, such as ascorbate (ASC) and glutathione, and oxidative reactive oxygen species (ROS) is known to play a pivotal role in the response of plant cells to abiotic ...stress. Here cell cultures of Arabidopsis thaliana were investigated with regard to their response to elevated levels of cadmium. At concentrations <100 μM, Cd induces a rapid and concentration-dependent H2O2 accumulation. This response could be inhibited by diphenylene iodonium (DPI, 20 μM). Reverse transcription-PCR analysis of three RBOH (respiratory burst oxidase homologues) genes showed an increased transcription of RBOHF after 15 min. No change in ASC concentration was observed during the first 3 h after Cd addition. In contrast, glutathione levels completely diminished within 1 h. This drop could be attributed to an increase in phytochelatin 4. At the plasma membrane, Cd further induced a significant decrease in dehydroascorbate (DHA) uptake activity (up to 90% inhibition after 4 h). This decrease is not present when cells are treated with LaCl3 before exposure to CdCl2. LaCl3 is a typical inhibitor of Ca channels and prevents Cd uptake in these cells as well as the Cd-induced ROS production. Therefore, these results appear to indicate that Cd uptake is a prerequisite for the change in DHA transport activity. However, DPI did not prevent the drop in DHA uptake activity present in Cd-treated Arabidopsis cells, indicating that this response seems to be independent of the Cd-induced H2O2 production.
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