Eyal Klang

Detection of Small Bowel Mucosal Healing and Deep Remission in Patients With Known Small Bowel Crohn’s Disease Using Biomarkers, Capsule Endoscopy, and Imaging

Objectives:Mucosal healing (MH) and deep remission (DR) are associated with improved outcomes in Crohn’s disease (CD). However, most of the current data pertain to colonic MH and DR, whereas the evidence regarding the prevalence and impact of small bowel (SB) MH is scarce. The aim of this study was to to evaluate the prevalence of SBMH and DR in quiescent SBCD.Methods:Patients with known SBCD in clinical remission (CDAI<150) or with mild symptoms (CDAI<220) were prospectively recruited and underwent video capsule endoscopy after verification of SB patency. Inflammation was quantified using the Lewis score (LS). SBMH was defined as LS<135, whereas a significant inflammation was defined as LS>790. Clinico-biomarker remission was defined as a combination of clinical remission and normal biomarkers. DR was defined as a combination of clinico-biomarker remission and MH.Results:Fifty-six patients with proven SB patency were enrolled; 52 (92.9%) patients were in clinical remission and 21 (40.4%) in clinico-biomarker remission. SBMH was demonstrated in 8/52 (15.4%) of patients in clinical remission. Moderate-to-severe SB inflammation was demonstrated in 11/52 (21.1%) of patients in clinical remission and in 1/21 (4.7%) of patients in clinical and biomarker remission. Only 7/52 (13.5%) patients were in DR.Conclusions:SB inflammation is detected in the majority of CD patients in clinical and biomarker remission. SBMH and DR were rare and were independent of treatment modality. Our findings represent the true inflammatory burden in quiescent patients with SBCD.

Fully Convolutional Network for Liver Segmentation and Lesions Detection

In this work we explore a fully convolutional network (FCN) for the task of liver segmentation and liver metastases detection in computed tomography (CT) examinations. FCN has proven to be a very powerful tool for semantic segmentation. We explore the FCN performance on a relatively small dataset and compare it to patch based CNN and sparsity based classification schemes. Our data contains CT examinations from 20 patients with overall 68 lesions and 43 livers marked in one slice and 20 different patients with a full 3D liver segmentation. We ran 3-fold cross-validation and results indicate superiority of the FCN over all other methods tested. Using our fully automatic algorithm we achieved true positive rate of 0.86 and 0.6 false positive per case which are very promising and clinically relevant results.

The impact of magnetic resonance enterography and capsule endoscopy on the re-classification of disease in patients with known Crohn’s disease: A PROSPECTIVE ISRAELI IBD RESEARCH NUCLEUS (IIRN) STUDY

BACKGROUND AND AIMS The classification of Crohns disease (CD) is usually determined at initial diagnosis and is frequently based on ileocolonoscopic and cross-sectional imaging data. Advanced endoscopic and imaging techniques such as small-bowel video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) may provide additional data regarding disease extent and phenotype. Our aim was to examine whether VCE or MRE performed after the initial diagnosis may alter the original disease classification. METHODS Consecutive patients with known small-bowel CD in clinical remission or mild disease were prospectively recruited and underwent MRE and VCE (if small-bowel patency was confirmed by a patency capsule (PC). Montreal classifications before and after evaluation were compared. RESULTS Seventy-nine patients underwent MRE and VCE was performed in 56. Previously unrecognized disease locations were detected with VCE and MRE in 51 and 25%, respectively (p < 0.01) and by both modalities combined in 44 patients (55%). Twenty-two patients (27%) were reclassified as having an advanced phenotype (B2/B3). MRE and VCE reclassified the phenotype in 26 and 11% of cases, respectively (p < 0.05). Overall, both modalities combined altered the original Montreal classification in 49/76 patients (64%). CONCLUSION VCE and MRE may lead to reclassification of the original phenotype in a significant percentage of CD patients in remission. VCE was more sensitive for detection of previously unrecognized locations, while MRE was superior for detection of phenotype shift. The described changes in the disease classification may have an important impact on both clinical management and long-term prognosis in these patients.

Magnetic resonance enterography versus capsule endoscopy activity indices for quantification of small bowel inflammation in Crohn's disease.

Background: Video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) are the prime modalities for the evaluation of small bowel (SB) Crohn’s disease (CD). Mucosal inflammation on VCE is quantified using the Lewis score (LS). Diffusion-weighted (DW) magnetic resonance imaging (MRI) allows for accurate assessment of SB inflammation without administration of intravenous contrast material. The Magnetic Resonance Index of Activity (MaRiA) and the Clermont index are quantitative activity indices validated for contrast-enhanced MRE and DW-MRE, respectively. The aim of this study was to compare the quantification of distal SB inflammation by VCE and MR-related activity indices. Methods: Patients with known quiescent SB CD were prospectively recruited and underwent MRE and VCE. LS, MaRIA and Clermont scores were calculated for the distal SB. Results: Both MRI-based indices significantly correlated with the LS and the Clermont index (r = 0.50, p = 0.001 and r = 0.53, p = 0.001, respectively). Both MaRIA and Clermont scores were significantly lower in patients with mucosal healing (LS < 135). The area under the curve (AUC) with both MR scores was moderate for prediction of any mucosal inflammation (LS ⩾ 135) and excellent for prediction of moderate-to-severe inflammation (LS ⩾ 790) (0.71 and 0.74 versus 0.93 and 0.91 for MaRIA and Clermont score, respectively). Conclusions: Modest correlation between VCE- and MRE-based quantitative indices of inflammation in patients with quiescent SB CD was observed. Between-modality correlation was higher in patients with endoscopically severe disease. DW-MRE gauged by Clermont score was at least as accurate as contrast-enhanced MRE for quantification of SB inflammation.

Clinical Outcomes of Surgery Versus Endoscopic Balloon Dilation for Stricturing Crohn's Disease.

BACKGROUND: Endoscopic balloon dilation and surgery are commonly practiced in stricturing Crohn’s disease. Nonetheless, there are still scant data directly comparing these 2 strategies. OBJECTIVE: The aim of this study was to compare the short- and long-term outcomes of endoscopic balloon dilation versus surgical resection in symptomatic Crohn’s strictures. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a single tertiary center. PATIENTS: Seventy-nine patients were identified, 40 in the surgical group and 39 in the endoscopic balloon dilation group (mean age 42.8 ± 13.9 versus 38.5 ± 12.2 years). MAIN OUTCOME MEASURES: The outcomes of all patients referred for endoscopic balloon dilation were compared with patients referred to surgery because of stricturing disease between the years 2006 and 2013. The primary outcome was the need for reintervention (either endoscopic balloon dilation or surgery) for symptomatic Crohn’s disease during follow-up. RESULTS: The proportion of patients who required any reintervention during follow-up was significantly lower in the surgical group versus the endoscopic balloon dilation group (OR = 5.62 (95% CI, 1.66–19.01); p = 0.005). The need for surgery/resurgery during follow-up was also significantly lower in the surgically treated group (OR = 3.53 (95% CI, 1.01–12.29); p = 0.047). Reintervention-free survival and surgery-free survival were both significantly shorter in the endoscopically treated group in a Kaplan-Mayer analysis. The rate of major complications was similar in the endoscopically and surgically treated groups (7.6% versus 7.5%; p = 0.7). LIMITATIONS: The small cohort and the retrospective data collection were limitations of this study. CONCLUSIONS: In our cohort of patients with fibrostenotic Crohn’s disease, a direct comparison showed reduced need for reinterventions with a similar rate of immediate major complications after surgery compared with endoscopic balloon dilation.

Virtual PET Images from CT Data Using Deep Convolutional Networks: Initial Results

In this work we present a novel system for PET estimation using CT scans. We explore the use of fully convolutional networks (FCN) and conditional generative adversarial networks (GAN) to export PET data from CT data. Our dataset includes 25 pairs of PET and CT scans where 17 were used for training and 8 for testing. The system was tested for detection of malignant tumors in the liver region. Initial results look promising showing high detection performance with a TPR of 92.3% and FPR of 0.25 per case. Future work entails expansion of the current system to the entire body using a much larger dataset. Such a system can be used for tumor detection and drug treatment evaluation in a CT-only environment instead of the expansive and radioactive PET-CT scan.

Improved Patch-Based Automated Liver Lesion Classification by Separate Analysis of the Interior and Boundary Regions

The bag-of-visual-words (BoVW) method with construction of a single dictionary of visual words has been used previously for a variety of classification tasks in medical imaging, including the diagnosis of liver lesions. In this paper, we describe a novel method for automated diagnosis of liver lesions in portal-phase computed tomography (CT) images that improves over single-dictionary BoVW methods by using an image patch representation of the interior and boundary regions of the lesions. Our approach captures characteristics of the lesion margin and of the lesion interior by creating two separate dictionaries for the margin and the interior regions of lesions (“dual dictionaries” of visual words). Based on these dictionaries, visual word histograms are generated for each region of interest within the lesion and its margin. For validation of our approach, we used two datasets from two different institutions, containing CT images of 194 liver lesions (61 cysts, 80 metastasis, and 53 hemangiomas). The final diagnosis of each lesion was established by radiologists. The classification accuracy for the images from the two institutions was 99% and 88%, respectively, and 93% for a combined dataset. Our new BoVW approach that uses dual dictionaries shows promising results. We believe the benefits of our approach may generalize to other application domains within radiology.

Multi-phase liver lesions classification using relevant visual words based on mutual information

We present a novel method for automated diagnosis of liver lesions in multi-phase CT images. Our approach is a variant of the Bag-of-Visual-Words (BoVW) method. It improves the BoVW model by selecting the most relevant words to be used for the input representation using a mutual information based criterion. Additionally, we generate relevance maps to visualize and localize the decision of the automatic classification algorithm. We validated our algorithm on 85 multi-phase CT images of 4 categories: hemangiomas, Focal Nodular Hyper-plasia (FNH), Hepatic Cellular Carcinoma (HCC) and cholangiocarcinoma. The new algorithm suggested in this paper improves the classical BoVW method sensitivity by 7% and specificity by 3%. The shift from single-phase liver data to a multi-phase representation is shown to substantially improve classification results. Overall, the system presented reaches state-of-the-art classification results of 82.4% sensitivity and 92.7% specificity on the 4 category lesion data, a challenging clinical diagnosis task.

Diffusion-weighted imaging in quiescent Crohn's disease: correlation with inflammatory biomarkers and video capsule endoscopy

AIM To investigate the role of restricted diffusion in quiescent Crohns disease (CD) patients and its association with inflammatory biomarkers and endoscopic disease. MATERIAL AND METHODS Fifty-two quiescent CD patients prospectively underwent magnetic resonance enterography (MRE) and video capsule endoscopy (VCE) and were tested for the inflammatory biomarkers, faecal calprotectin (FCP) and C-reactive protein (CRP). Restricted diffusion in the distal ileum was qualitatively (absence/presence) and quantitatively (apparent diffusion coefficient [ADC]) assessed by two readers. The VCE-based Lewis score was calculated for the distal ileum. Restricted diffusion sensitivity and specificity for VCE ulcerations were assessed for patients with elevated (>100 μg/g) or normal (<100 μg/g) FCP. Receiver operating characteristic (ROC) curve was used to assess the ability of ADC to identify patients with concurrent VCE ulceration and elevated FCP. RESULTS The sensitivity and specificity of restricted diffusion for patients with VCE ulceration were higher in patients with elevated FCP (reader 1: 71.4%, 80%, reader 2: 76.2%, 100%, respectively) compared to patients with normal FCP (reader 1: 46.2%, 61.5%; reader 2: 15.4%, 76.9%, respectively). The ADC had a high diagnostic accuracy for identifying patients that had concurrent VCE ulceration and elevated FCP (reader 1: AUC=0.819, reader 2: AUC=0.832). CONCLUSION In quiescent CD patients, the presence of restricted diffusion is suggestive of an active inflammation, associated with elevated FCP. Thus, DWI may serve as a clinical tool in the follow-up of these patients, implying subclinical inflammatory flares.

Structural bowel damage in quiescent Crohn’s disease ☆

BACKGROUND Crohns disease is associated with accumulation of progressive structural bowel damage (SBD) leading to the development of stenotic and penetrating complications. The data pertaining to the course of progression of SBD is scarce. The Lemann index (LI) is a novel tool for evaluation of SBD that incorporates pan-enteric clinical, endoscopic and imaging data. AIMS To evaluate the progression of SBD in quiescent CD patients. METHODS Patients with known quiescent small bowel Crohns disease (CD) for at least 3 months (CDAI<220) were prospectively recruited and underwent repeated magnetic resonance enterographies (MRE) and video capsule endoscopies (VCE). Patients were assessed for SBD on initial and follow-up evaluation using relevant clinicopathological data, MRE and VCE results. Significant structural bowel damage (SBD) was identified as LI>4.8, and progression of SBD as LI>0.3. RESULTS Sixty one patients were enrolled in the study. Significant SBD was detected 13 (21.4%) on enrollment. Duration of disease (p=0.036) and history of CD-related surgery (p=0.0001) were associated with significant BD. Forty one patients underwent a follow-up MRE (14.8±2.5 months apart). LI was similar at baseline and follow-up. There was a negligible change in LI between the evaluations. CONCLUSIONS In patients with quiescent Crohns disease, structural bowel damage was stable over a median of 14 months follow-up.