Near real-time retroflexion detection in colonoscopy.

Colonoscopy is the most popular screening tool for colorectal cancer. Recent studies reported that retroflexion during colonoscopy helped to detect more polyps. Retroflexion is an endoscope maneuver that enables visualization of internal mucosa along the shaft of the endoscope, enabling visualization of the mucosa area that is difficult to see with typical forward viewing. This paper describes our new method that detects the retroflexion during colonoscopy. We propose region shape and location (RSL) features and edgeless edge cross-section profile (ECSP) features that encapsulate important properties of endoscope appearance and edge information during retroflexion. Our experimental results on 50 colonoscopy test videos show that a simple ensemble classifier using both ECSP and RSL features can effectively identify retroflexion in terms of analysis time and detection rate.

Novel information theory based method for superimposition of lateral head radiographs and cone beam computed tomography images.

OBJECTIVES: The aim was to introduce a novel alignment criterion, focus mutual information (FMI), for the superimposition of lateral cephalometric radiographs and three dimensional (3D) cone beam computed images as well as the assessment of the alignment characteristics of the new method and comparison of the novel methodology with the region of interest (ROI) approach. METHODS: Implementation of a FMI criterion-based methodology that only requires the approximate indication of stable structures in one single image. The robustness of the method was first addressed in a phantom experiment comparing the new technique with a ROI approach. Two consecutive cephalometric radiographs were then obtained, one before and one after functional twin block application. These images were then superimposed using alignment by FMI where the following were focused on, in several ways: (1) cranial base and acoustic meatus, (2) palatal plane and (3) mandibular symphysis. The superimposed images were subtracted and coloured. The applicability to cone beam CT (CBCT) is illustrated by the alignment of CBCT images acquired before and after craniofacial surgery. RESULTS: The phantom experiment clearly shows superior alignment when compared to the ROI approach (Wilcoxon n = 17, Z = -3.290, and P = 0.001), and robustness with respect to the choice of parameters (one-sample t-test n = 50, t = -12.355, and P = 0.000). The treatment effects are revealed clearly in the subtraction image of well-aligned cephalometric radiographs. The colouring scheme of the subtraction image emphasises the areas of change and visualizes the remodelling of the soft tissue. CONCLUSIONS: FMI allows for cephalometry without tracing, it avoids the error inherent to the use of landmarks and the interaction of the practitioner is kept to a minimum. The robustness to focal distribution variations limits the influence of possible examiner inaccuracy.

2D image registration using focused mutual information for application in dentistry.

Spatial alignment of image data is a common task in computer vision and medical imaging. This should preferentially be done with minimal intervention of an operator. Similarity measures with origin in the information theory such as mutual information (MI) have proven to be robust registration criteria for this purpose. Intra-oral radiographs can be considered images of piecewise rigid objects. Teeth and jaws are rigid but can be displaced with respect to each other. Therefore MI criteria combined with affine deformations tend to fail, when teeth and jaws move with respect to each other between image acquisitions. In this paper, we consider a focused weighing of pixels in the reference image. The resulting criterion, focused mutual information (FMI) is an adequate tool for the registration of rigid parts of a scene. We also show that the use of FMI is more robust for the subtraction of lateral radiographs of teeth, than MI confined to a region of interest. Furthermore, the criterion allows the follow-up of small carious lesions when upper and lower jaw moved between the acquisition of test and reference image.

A WBAN System for Ambulatory Monitoring of Physical Activity and Health Status: Applications and Challenges.

Recent technological advances in sensors, low-power integrated circuits, and wireless communications have enabled the design of low-cost, miniature, lightweight, intelligent physiological sensor platforms that can be seamlessly integrated into a body area network for health monitoring. Wireless body area networks (WBANs) promise unobtrusive ambulatory health monitoring for extended periods of time and near real-time updates of patients' medical records through the Internet. A number of innovative systems for health monitoring have recently been proposed. However, they typically rely on custom communication protocols and hardware designs, lacking generality and flexibility. The lack of standard platforms, system software support, and standards makes these systems expensive. Bulky sensors, high price, and frequent battery changes are all likely to limit user compliance. To address some of these challenges, we prototyped a WBAN utilizing a common off-the-shelf wireless sensor platform with a ZigBee-compliant radio interface and an ultra low-power microcontroller. The standard platform interfaces to custom sensor boards that are equipped with accelerometers for motion monitoring and a bioamplifier for electrocardiogram or electromyogram monitoring. Software modules for on-board processing, communication, and network synchronization have been developed using the TinyOS operating system. Although the initial WBAN prototype targets ambulatory monitoring of user activity, the developed sensors can easily be adapted to monitor other physiological parameters. In this paper, we discuss initial results, implementation challenges, and the need for standardization in this dynamic and promising research field.

Synergy between medical informatics and bioinformatics: facilitating genomic medicine for future health care.

In this paper, we review the results of BIOINFOMED, a study funded by the European Commission (EC) with the purpose to analyse the different issues and challenges in the area where Medical Informatics and Bioinformatics meet. Traditionally, Medical Informatics has been focused on the intersection between computer science and clinical medicine, whereas Bioinformatics have been predominantly centered on the intersection between computer science and biological research. Although researchers from both areas have occasionally collaborated, their training, objectives and interests have been quite different. The results of the Human Genome and related projects have attracted the interest of many professionals, and introduced new challenges that will transform biomedical research and health care. A characteristic of the 'post genomic' era will be to correlate essential genotypic information with expressed phenotypic information. In this context, Biomedical Informatics (BMI) has emerged to describe the technology that brings both disciplines (BI and MI) together to support genomic medicine. In recognition of the dynamic nature of BMI, institutions such as the EC have launched several initiatives in support of a research agenda, including the BIOINFOMED study.

World-Wide Web-based graphical user interfaces for laboratory data.

OBJECTIVES: Electronic medical record systems permit collection of large amounts of medical information. Usually, information is presented in a fixed format, either as text or tables. Health care providers have to navigate this fixed format in order to find information useful for a specific patient-provider interaction. The main objective of this work was to allow the provider immediate access to specific laboratory information through the development of a highly customizable, graphical user interface to the Mayo Clinic laboratory information system. RESULTS: Here we describe this platform-independent, World-Wide-Web-based graphical user interface that allows the provider to see all or a predetermined panel of essential laboratory data in graphical format. Advantages include availability at internet-based workstations, immediate recognition of trends over time, ability to zoom in and out of specific periods of time, and detailed analysis of patient values in relationship to normal values. CONCLUSIONS: Web browser-based user interface allowing graphical display of laboratory data using Java technology was described. The connection to the Mayo Clinic laboratory information system combines cross-platform support for use on virtually any networked machine, interaction through a Web browser for ease of use, and a combination of the Perl and Java languages for powerful data processing and interactivity.

The prognostic value of histology in the assessment of patients with Budd-Chiari syndrome.

BACKGROUND/AIMS: It is unclear whether treatment of patients with Budd-Chiari syndrome (BCS) should be based on liver histology, as large histopathological studies have not been performed. We investigated the relationship between the histopathological findings and survival. METHODS: We studied the clinical features and findings on biopsy specimens in 45 patients with BCS who were admitted to four tertiary referral medical centers. Histological findings, i.e. congestion, necrosis, inflammation and fibrosis, were graded. Survival was assessed in relation to histological findings and clinical features at the time of diagnosis as well as in relation to subsequent treatment with or without portosystemic shunting. RESULTS: Centrilobular congestion, centrilobular necrosis, lobular inflammation and portal inflammation were not significantly related to survival. In addition, there was no association between either pericentral or periportal fibrosis and survival. Univariate analysis revealed that the prothrombin time and Child-Pugh score were significantly related to survival (P = 0.005 and Ptrend = 0.02, respectively). Multivariate analysis yielded the Child-Pugh score, serum alanine aminotransferase (ALT) and treatment with portosystemic shunting as independent prognostic indicators. CONCLUSIONS: We found no evidence for a relationship between early liver pathology and survival. Child-Pugh score, serum ALT and portosystemic shunting appeared to be prognostic indicators for patients with BCS.

The mitotic checkpoint protein hBUB3 and the mRNA export factor hRAE1 interact with GLE2p-binding sequence (GLEBS)-containing proteins.

The mRNA export factor RAE1 (also called GLE2) and the mitotic checkpoint protein BUB3 share extensive sequence homology in yeast as well as higher eukaryotes, although the biological relevance of their similarity is unclear. Previous work in HeLa cells has shown that human (h)RAE1 binds the nuclear pore complex protein hNUP98 via a short NUP98 motif called GLEBS (for GLE2p-binding sequence). Here we report that the two known binding partners of hBUB3, the mitotic checkpoint proteins hBUB1 and hBUBR1, both carry a region with remarkable similarity to the GLEBS motif of hNUP98. We show that the GLEBS-like motifs of mouse (m)BUB1 and mBUBR1 are sufficient for mBUB3 binding. mBUB3 lacks affinity for the hNUP98 GLEBS, demonstrating its binding specificity for GLEBS motifs of mitotic checkpoint proteins. Interestingly, mRAE1 does not exclusively bind to the GLEBS motif of hNUP98 and can cross-interact with the mBUB1 GLEBS. We show that full-length RAE1 and BUB1 proteins interact in mammalian cells and accumulate both at the kinetochores of prometaphase chromosomes. Our findings demonstrate that GLEBS motifs reside in mammalian nucleoporins and mitotic checkpoint proteins and apparently serve as specific binding sites for either BUB3, RAE1, or both.

Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience.

OBJECTIVES: The aims of this retrospective study were to assess the frequency with which we used different treatment modalities for patients with primary sclerosing cholangitis (PSC) and cholangiocellular carcinoma (CCA). METHODS: A total of 41 patients with known CCA complicating PSC with a median age of 49 yr (range, 27-75 yr) were identified from a group of 1009 patients (4%) with PSC seen over 10 yr at the Mayo Clinic. RESULTS: These patients received mainly five forms of treatment: 10 patients were treated with radiation therapy (RT) with or without 5-fluorouracil (5-FU) (seven with palliative and three with curative intent), nine with stent placement for cholestasis, 12 with conservative treatment, four with surgical resection (one of four received RT and 5-FU), and three patients with orthotopic liver transplantation and RT, with or without 5-FU. One patient was treated with 5-FU alone, one with photodynamic therapy, and one patient with somatostatin analog. A total of 36 patients died, whereas four (10%) patients survived (two with surgical resection, one with orthotopic liver transplantation and RT, and one with stent placement) during a median follow-up of 5.5 months (range, 1-75 months). One patient was lost to follow-up. CONCLUSIONS: In highly selective cases, resective surgery seems to be of benefit in PSC patients with CCA. However, these therapies are rarely applied to these patients because of the advanced nature of the disease at the time of diagnosis. Efforts should be directed at earlier identification of potential surgical candidates.

Endoscopic application of photodynamic therapy for cholangiocarcinoma.

BACKGROUND: Previous studies indicate that photodynamic therapy provides effective relief from biliary obstruction in advanced cholangiocarcinoma. This report describes a method of applying photodynamic therapy in the biliary tract by using accessories available in the United States. METHODS: Endoscopic retrograde cholangiography was performed to define the proximal and distal extent of intraductal tumor. Patients were injected with 2 mg/kg of sodium porfimer. Forty-eight hours later a commercially available cylindrical diffusing laser fiber was inserted into an 8F biliary catheter equipped with a 0.038 inch side-hole at its distal tip. After positioning of a 0.035 inch guidewire proximal to the biliary stricture, the preloaded catheter was advanced over the guidewire by using the monorail technique. Laser light was applied at a power of 400 mW/cm fiber for a total energy of 180 J/cm.(2) RESULTS: Fourteen treatments were performed on 6 patients with tumors of Bismuth types IV (n = 2), III (n = 3), or II (n = 1). By using the preloaded biliary catheter, adequate positioning of the laser fiber was achieved in all patients. A fracture of the diffuser tip occurred during 1 of the treatments. Two patients developed acute cholangitis and 2 patients experienced skin phototoxicity. CONCLUSIONS: Photodynamic therapy for cholangiocarcinoma is safe and technically feasible with a preloaded biliary catheter and a monorail technique for catheter positioning.

Improved diagnostic yield of endoscopic biliary brush cytology by digital image analysis.

OBJECTIVE: To evaluate the accuracy of digital image analysis (DIA) for distinguishing between benign and malignant strictures of the biliary tract. PATIENTS AND METHODS: Our pathology databank was used to identify all biliary brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography between June 1997 and June 1999. Corresponding medical records were reviewed to determine whether patients had benign or malignant strictures. Strictures were further classified into benign strictures with negative routine cytology, malignant strictures with negative routine cytology, and malignant strictures with positive routine cytology. Papanicolaou-stained smears of available brush cytology specimens were destained and then restained with Feulgen dye. Nuclear images were quantified for DNA content without knowledge of stricture type. DNA histograms were generated and ploidy results compared with the class of stricture. RESULTS: We analyzed 27 specimens from 69 confirmed benign or malignant strictures. Assuming that the presence of any aneuploid cells indicated malignancy, the sensitivity of DIA was 85%. Furthermore, aneuploid cells were detected by DIA in 13 of 16 specimens in which routine cytology was unrevealing. CONCLUSION: Ploidy assessment by DIA has potential to enhance the sensitivity of diagnosing malignant strictures compared with routine cytology alone.

Hepatic lymphangiomatosis mimicking polycystic liver disease.

Hepatic lymphangiomatosis is a rare disorder characterized by cystic dilatation of the lymphatic vessels in the hepatic parenchyma. It can occur in the liver alone, in the liver and spleen, or in multiple organs. Clinically, diagnosis can be difficult because of the rarity and protean manifestations of this disorder. We describe a 53-year-old woman with hepatic lymphangiomatosis in whom polycystic liver disease had been previously diagnosed. In addition, we review 12 cases of hepatic, splenic, and hepatosplenic lymphangiomatosis with or without systemic lymphangiomatosis and discuss the differential diagnosis.

Characterization and growth regulation of a rat intrahepatic bile duct epithelial cell line under hormonally defined, serum-free conditions.

Bile duct epithelial cells, or cholangiocytes, proliferate in vivo under a number of pathologic (i.e., partial hepatectomy) and pathophysiologic (i.e., bile duct ligation, malignant transformation) conditions. However, little is known about the possible growth factors that modulate these proliferative responses, in part because an in vitro model to study proliferation of nontransformed, normal cholangiocytes is not available. We report here the development of a rat cholangiocyte cell line (MMRC, minimal media-requiring rat cholangiocytes) that grows under hormonally defined, serum-free conditions on plastic and maintains a cholangiocyte phenotype. Morphologic as well as functional studies indicate that the cell line is polarized and actively transports fluid and electrolytes in an apical to basolateral direction. MMRC, when cultured for 24 mo. and passaged 80 times, have not undergone malignant transformation, because the cell line failed to grow under anchorage-independent conditions or in nude mice. Cellular proliferation is accelerated 2-8-fold by insulin, insulin-like growth factor 1, epidermal growth factor, and hepatocyte growth factor, growth factors known to stimulate tyrosine kinase receptors, and inhibited 2-10-fold by TGFbeta and IL-2. Glyco-conjugates of primary (i.e., cholic and chenodeoxycholic acid) and secondary bile acids (i.e., deoxycholic and lithocholic acid) do not alter proliferation at low concentration (1 microM), but are toxic at higher concentration (10 microM). In summary, we have developed and characterized a cholangiocyte cell line derived from normal rat liver, which grows under hormonally defined, serum-free conditions, maintains a nonmalignant, cholangiocyte phenotype, displays morphologic and functional features of polarity, and alters its proliferation rate in response to a variety of growth factors.

Applying World Wide Web technology to the study of patients with rare diseases.

Randomized, controlled trials of sporadic diseases are rarely conducted. Recent developments in communication technology, particularly the World Wide Web, allow efficient dissemination and exchange of information. However, software for the identification of patients with a rare disease and subsequent data entry and analysis in a secure Web database are currently not available. To study cholangiocarcinoma, a rare cancer of the bile ducts, we developed a computerized disease tracing system coupled with a database accessible on the Web. The tracing system scans computerized information systems on a daily basis and forwards demographic information on patients with bile duct abnormalities to an electronic mailbox. If informed consent is given, the patient's demographic and preexisting medical information available in medical database servers are electronically forwarded to a UNIX research database. Information from further patient-physician interactions and procedures is also entered into this database. The database is equipped with a Web user interface that allows data entry from various platforms (PC-compatible, Macintosh, and UNIX workstations) anywhere inside or outside our institution. To ensure patient confidentiality and data security, the database includes all security measures required for electronic medical records. The combination of a Web-based disease tracing system and a database has broad applications, particularly for the integration of clinical research within clinical practice and for the coordination of multicenter trials.

Cholangiocyte-specific rat liver proteins identified by establishment of a two-dimensional gel protein database.

The liver is composed of a variety of cells that form a functional unit involved in uptake, synthesis, metabolism, and secretion. Until recently, most studies examining liver function did not analyze the specific proteins expressed or functions performed by the multiple individual cell types that constitute the hepatic mass. In the last decade, novel isolation methods have been developed that allow the purification of liver cell populations highly enriched in one type of liver cell. Here, we present a detailed two-dimensional (2-D) protein map of rat bile duct epithelial cells (i.e., cholangiocytes) using a recently developed isolation procedure. In addition, we identify 27 major cholangiocyte proteins either by comparison to maps of known rat liver proteins (based on pI and Mr) or by tryptic digestion and microsequencing. Finally, we compare the relative abundance of individual proteins present in cholangiocytes to whole liver as well as hepatocyte-specific proteins. Our results show that cholangiocytes express a unique array of individual proteins. The cholangiocyte 2-D protein pattern is markedly different from that of isolated rat hepatocytes or whole rat liver, with high levels of proteins previously known to be expressed by cholangiocytes (e.g., cytokeratins, actins) as well as protein not previously demonstrated to be expressed at high levels (e.g., annexin V, selenium binding protein). We conclude that this cholangiocyte-derived, 2-D protein map will be a crucial resource for studies directed at our understanding of cholangiocyte physiology and pathobiology.