Clustering of samples with a tree-shaped dependence structure, with an application to microscopic time lapse imaging.

MOTIVATION: Recent imaging technologies allow for high-throughput tracking of cells as they migrate, divide, express fluorescent markers and change their morphology. The interpretation of these data requires unbiased, efficient statistical methods that model the dynamics of cell phenotypes. RESULTS: We introduce treeHFM, a probabilistic model which generalizes the theory of hidden Markov models to tree structured data. While accounting for the entire genealogy of a cell, treeHFM categorizes cells according to their primary phenotypic features. It models all relevant events in a cell's life, including cell division, and thereby enables the analysis of event order and cell fate heterogeneity. Simulations show higher accuracy in predicting correct state labels when modeling the more complex, tree-shaped dependency of samples over standard HMM modeling. Applying treeHFM to time lapse images of hematopoietic progenitor cell differentiation, we demonstrate that progenitor cells undergo a well-ordered sequence of differentiation events. AVAILABILITY AND IMPLEMENTATION: The treeHFM is implemented in C++. We provide wrapper functions for the programming languages R (CRAN package, https://CRAN.R-project.org/package=treeHFM) and Matlab (available at Mathworks Central, http://se.mathworks.com/matlabcentral/fileexchange/57575-treehfml). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

G-EYE advanced colonoscopy for improved polyp detection rates - a randomized tandem pilot study with different endoscopists.

BACKGROUND AND AIMS: The most commonly missed polyps in colonoscopy are those located behind haustral folds. The G-EYE system is a standard colonoscope consisting of re-processable balloon at its distal tip. The G-EYE balloon improves the detection of polyps by straightening the haustral folds. In our back-to-back tandem study, we aimed to determine whether and to what extent the G-EYE system could reduce adenoma miss rates in screening colonoscopy. METHODS: Patients referred to colonoscopy were randomized into 2 groups. Group A underwent a standard colonoscopy (SC) followed by balloon colonoscopy (BC), and Group B underwent BC followed by SC. In this randomized tandem study, the investigator's level of training and the endoscopists themselves were changed after each withdrawal. Each endoscopist was blinded to the results of the first withdrawal. RESULTS: Fifty-eight patients were enrolled and randomized into 2 groups with similar baseline characteristics. Nine patients were excluded from the study. Twenty-five patients underwent SC followed by BC while 24 underwent BC followed by SC. The adenoma miss rate for SC was 41 %, with an additional detection rate of 69 % for BC (ratio 1.69). The overall miss rate for polyps was 60 % for SC, with an additional detection rate of 150 % for BC (ratio 2.5). Experienced investigators who used BC were able to identify an additional 7 polyps while inexperienced investigators. CONCLUSIONS: Although our results could not clearly confirm that BC improves adenoma detection, the investigator's experience appears to be a major determinant of the adenoma detection rate.

Efficacy of SpyGlass(TM)-directed biopsy compared to brush cytology in obtaining adequate tissue for diagnosis in patients with biliary strictures.

AIM: To evaluate the diagnostic yield (inflammatory activity) and efficiency (size of the biopsy specimen) of SpyGlass(TM)-guided biopsy vs standard brush cytology in patients with and without primary sclerosing cholangitis (PSC). METHODS: At the University Medical Center Mainz, Germany, 35 consecutive patients with unclear biliary lesions (16 patients) or long-standing PSC (19 patients) were screened for the study. All patients underwent a physical examination, lab analyses, and abdominal ultrasound. Thirty-one patients with non-PSC strictures or with PSC were scheduled to undergo endoscopic retrograde cholangiography (ERC) and subsequent peroral cholangioscopy (POC). Standard ERC was initially performed, and any lesions or strictures were localized. POC was performed later during the same session. The Boston Scientific SpyGlass System(TM) (Natick, MA, United States) was used for choledochoscopy. The biliary tree was visualized, and suspected lesions or strictures were biopsied, followed by brush cytology of the same area. The study endpoints (for both techniques) were the degree of inflammation, tissue specimen size, and the patient populations (PSC vs non-PSC). Inflammatory changes were divided into three categories: none, low activity, and high activity. The specimen quantity was rated as low, moderate, or sufficient. RESULTS: SpyGlass(TM) imaging and brush cytology with material retrieval were performed in 29 of 31 (93.5%) patients (23 of the 29 patients were male). The median patient age was 45 years (min, 20 years; max, 76 years). Nineteen patients had known PSC, and 10 showed non-PSC strictures. No procedure-related complications were encountered. However, for both methods, tissues could only be retrieved from 29 patients. In cases of inflammation of the biliary tract, the diagnostic yield of the SpyGlass(TM)-directed biopsies was greater than that using brush cytology. More tissue material was obtained for the biopsy method than for the brush cytology method (P = 0.021). The biopsies showed significantly more inflammatory characteristics and greater inflammatory activity compared to the cytological investigation (P = 0.014). The greater quantity of tissue samples proved useful for both PSC and non-PSC patients. CONCLUSION: SpyGlass(TM) imaging can be recommended for proper inflammatory diagnosis in PSC patients. However, its value in diagnosing dysplasia was not addressed in this study and requires further investigation.