Louis W. C. Liu

CMOS Image Sensors for High Speed Applications

Recent advances in deep submicron CMOS technologies and improved pixel designs have enabled CMOS-based imagers to surpass charge-coupled devices (CCD) imaging technology for mainstream applications. The parallel outputs that CMOS imagers can offer, in addition to complete camera-on-a-chip solutions due to being fabricated in standard CMOS technologies, result in compelling advantages in speed and system throughput. Since there is a practical limit on the minimum pixel size (4∼5 μm) due to limitations in the optics, CMOS technology scaling can allow for an increased number of transistors to be integrated into the pixel to improve both detection and signal processing. Such smart pixels truly show the potential of CMOS technology for imaging applications allowing CMOS imagers to achieve the image quality and global shuttering performance necessary to meet the demands of ultrahigh-speed applications. In this paper, a review of CMOS-based high-speed imager design is presented and the various implementations that target ultrahigh-speed imaging are described. This work also discusses the design, layout and simulation results of an ultrahigh acquisition rate CMOS active-pixel sensor imager that can take 8 frames at a rate of more than a billion frames per second (fps).

Development of pacemaker activity and interstitial cells of cajal in the neonatal mouse small intestine

Intestinal motor patterns are not well developed in premature infants. Similarly, in neonatal mice, irregular motor patterns were observed. Pacemaker cells, identified in the small intestine as interstitial cells of Cajal (ICCs) associated with Auerbachs plexus (ICC‐APs), contribute to the generation of peristaltic movements. The objective of the present study was to assess the hypothesis that abnormal gut motor activity in (preterm) newborns can be associated with underdeveloped ICCs. Specifically, the aim was to identify at which point the electrical pacemaker activity is fully developed and whether or not the development of pacemaker activity has a structural correlation with the developmental stage of ICCs. Pacemaker activity was identified as that component of the slow wave that is insensitive to L‐type calcium (Ca2+) channel blockers and displays a characteristic reduction in frequency in the presence of cyclopiazonic acid (CPA), a specific inhibitor of the endoplasmic reticulum Ca2+ pump. In newborn, unfed neonates, action potentials occurred that were irregular in frequency and amplitude and sensitive to verapamil. CPA (5 μM) abolished all action potentials. Quiescent spots were observed in approximately 50% of impalements. Six hours after birth, slow‐wave activity appeared at a regular frequency and amplitude, and a well‐defined plateau phase was observed. Verapamil did not affect the frequency, 5 μM CPA decreased it. The effect of CPA on the pacemaker frequency 2 days after birth was identical to that observed in adult mice. In 2‐hr‐old neonates, ICCs could be identified through selective uptake of methylene blue, but ultrastructural features were not fully developed. At 48 hr, a complete ICC network covering Auerbachs plexus was formed, confirmed by electron microscopy. In summary, the pacemaker component of the slow waves can be identified in neonates as early as 6 hr after birth. The pacemaker component was fully developed 2 days after birth. These electrophysiological observations correlated with the development of full network characteristics of ICC‐APs and the development of fully differentiated ICC‐APs from “blast‐like” cells. Dev. Dyn. 1998;213:271–282.

Injection of Botulinum Toxin a to Upper Esophageal Sphincter for Oropharyngeal Dysphagia in Two Patients with Inclusion Body Myositis

Inclusion body myositis (IBM) is a progressive degenerative skeletal muscle disease leading to weakening and atrophy of both proximal and distal muscles. Dysphagia is reported in up to 86% of IBM patients. Surgical cricopharyngeal myotomy may be effective for cricopharyngeal dysphagia and there is one published report that botulinum toxin A, injected into the cricopharyngeus muscle using a hypopharyngoscope under general anesthesia, relieved IBM-associated dysphagia. This report presents the first documentation of botulinum toxin A injection into the upper esophageal sphincter using a flexible esophagogastroduodenoscope under conscious sedation, to reduce upper esophageal sphincter pressure and successfully alleviate oropharyngeal dysphagia in two IBM patients.

Toward a Miniaturized Wireless Fluorescence-Based Diagnostic Imaging System

Fluorescence-based spectroscopy and imaging techniques provide qualitative and quantitative diagnostic information on biological systems. In this paper, we report on the design, fabrication, and testing of a miniaturized wireless fluorescence imaging device for noninvasive clinical diagnosis and screening of diseases in the gastrointestinal tract. The system includes three submodules: optical imaging, electronics control and image acquisition, and information processing and transmission. These modules were individually developed and tested before being integrated into a battery-powered wireless device. The final integrated system is mounted in a customized, compact cylindrical housing. The performance of each individual module and the overall integrated system has been evaluated using fluorescent phantoms. It has been demonstrated that the miniaturized device can acquire spectrally resolved fluorescence images and transmit the image stream wirelessly. An important outcome of this feasibility study is the identification of important technological issues and pathways for future prototype development.

Interstitial cells of Cajal: mediators of communication between circular and longitudinal muscle layers of canine colon

Abstract The network of interstitial cells of Cajal associated with Auerbach’s (myenteric) plexus in the canine colon was investigated to determine its role in facilitating communication between circular and longitudinal muscle layers. Electrical coupling between the muscle layers was demonstrated by propagating extracellularly evoked electrotonic pulses from circular muscle cells to nearby longitudinal muscle cells. The likelihood of cytoplasmic continuity across Auerbach’s plexus was further demonstrated by the ability of neurobiotin to spread between the interstitial cells and the circular and longitudinal muscle cells. Importantly, direct neurobiotin spread between circular and longitudinal muscle cells was not observed even when they were in close proximity as determined by confocal microscopy. When neurobiotin did spread across the two muscle layers, the intervening interstitial cells were always neurobiotin-positive. In regions where circular and longitudinal muscle cells approach each other closely, electron microscopy revealed the presence of close appositions between interstitial cells and smooth muscle cells. Gap junctions between interstitial cells and smooth muscle cells of both layers, as judged by electron microscopy, were extremely rare. Neither gap junctions nor close appositions were observed between longitudinal and circular muscle cells. The special arrangement for electrotonic coupling across Auerbach’s plexus through interstitial cells of Cajal suggests controlled coupling between the two muscle layers, explaining the preservation of their distinct electrical activities.

Intercellular communication in smooth muscle

The functioning of a group of cells as a tissue depends on intercellular communication; an example is the spread of action potentials through intestinal tissue resulting in synchronized contraction. Recent evidence for cell heterogeneity within smooth muscle tissues has renewed research into cell coupling.Electrical coupling is essential for propagation of action potentials in gastrointestinal smooth muscle.Metabolic coupling may be involved in generation of pacemaker activity. This review deals with the role of cell coupling in tissue function and some of the issues discussed are the relationship between electrical synchronization and gap junctions, metabolic coupling, and the role of interstitial cells of Cajal in coupling.

CMOS imaging for biomedical applications

CMOS photodetectors and imaging systems have shown that they possess adequate performance characteristics to replace CCDs or PMTs in some biomedical applications, thereby providing low power, portable, and cheap integrated bioimaging systems. Some advanced solutions, like novel active pixel sensors that detect ultra-low light levels, and avalanche photodiodes that are integrated in CMOS and perform single photon detection, are addressed in this paper.

Linaclotide: A New Option for the Treatment of Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation in Adults

Chronic idiopathic constipation (CC) and irritable bowel syndrome with predominant constipation (IBS-C) are the 2 most common conditions among functional gastrointestinal disorders. Despite current multiple therapeutic options, treatment remains challenging and dissatisfactory to many patients. Linaclotide is a novel therapeutic agent, which is a guanylate cyclase receptor agonist that stimulates water secretion from the intestinal epithelium by promoting chloride and bicarbonate efflux into the lumen through activation of the cystic fibrosis transmembrane conductance regulator. Clinical trials have demonstrated that linaclotide is effective, safe and well tolerated in patients with CC and IBS-C. This review article highlights the mechanism of action of linaclotide, reviews published literature based on a search of databases, including MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), up to February 2013, and compares its utility with other currently available agents.

Role of Calcium Channels in Pharmacological Modulation of Gastrointestinal Motility

Synchronized circumferential contractions and propagating phasic contractile activity are important components of gastrointestinal motility involved in propulsion of food and food residues. These contractions are initiated and regulated by electrical activity (slow-wave-type action potentials or slow waves) of the smooth muscle cell membranes (1). Periodically electrical pacemaker potentials are generated by specialized pacemaker cells [a network of interstitial cells of Cajal (ICC) and smooth muscle cells] and propagated into the rest of the smooth muscle layer. Slow-wave-type action potentials generated in the smooth muscle layers consist of an upstroke phase and a plateau phase with or without superimposed spikes. Calcium channels play a role in both the initiation of the slow-wave and in the generation of the plateau phase, the latter being associated with generation and regulation of contraction. Pharmacological manipulation of calcium channel activity may therefore influence the slow wave frequency and propagation, determining the characteristics of propulsion and synchronization, as well as the duration and amplitude of the slow wave plateau phase, determining the force of the individual phasic contractions. One objective of this chapter is to discuss involvement of calcium channels in the generation of the slow-wave-type action potentials in the colon with the canine colon as primary model. Another objective is to discuss the role of calcium channels in the pharmacological control of colonic motility.

Mo2013 Predictability of Functional Defecation Disorder in Patients With Chronic Constipation Using a Standardized Constipation Symptom Questionnaire

Introduction Anorectal manometry is a commonly used technique to assess patients with fecal incontinence, but is known to have low reproducibility and poor validation in assessment of anal sphincter function. We report a pilot study on a novel technique using Functional Lumen Imaging Probe (FLIP) to improve assessment. Although FLIP has been used in upper GI studies its use in anorectal region is limited to three published studies, all of which used a 16 cm probe (as in upper GI studies). We used a purpose built shorter catheter to demonstrate bio-mechanical properties of the anus. Methods 19 healthy volunteers were recruited (9 females), mean age 34 (20-75). Catheters were purpose built, incorporating an anal and rectal balloon, each with its own separate inflation point. Anal canal balloon was made in three different sizes (2, 3 and 4cm long). Appropriate sized catheter corresponding to the length of subjects anal canal (based on manometry) was used. 3 cross sectional area (CSA) readings were obtained with 2cm balloon, 5 with 3cm and 10 with 4cm balloon. In order to obtain meaningful results, the anal canal balloon was required to be touching the lumen wall. This was achieved by varying inflation volumes according to the balloon size. Results Participants underwent standard water-perfused anal manometry followed by FLIP on the same day. To test repeatability the FLIP was repeated after 30 minutes on the same day. The parameters checked for repeatability included CSA during rest, squeeze, endurance squeeze and cough in addition to the intra balloon pressure during these phases. Anal canal was divided into three partsdistal, mid and proximal based on anatomy and preliminary data analysis. Study established the test-retest and intra-observer repeatability for CSA using Bland-Altman plot and Intra-class correlation coefficient (ICC). Pearson correlation coefficient (PCC) was used to establish correlation between CSA and pressure. Bland Altmans plots showed measurement points for all parameters to be within 2 SD of line of equality. ICC calculated individually for each part of anal canal showed high levels of repeatability for CSA measurements (Table 1). Pressure readings were also repeatable (Table 1). Pearson correlation coefficient showed a negative correlation, between CSA and pressure, at all the balloon volumes apart from the highest (Table 2). Conclusions By allowing determination of serial CSAs during distension EndoFLIP allows detailed and segmental description of geometric and mechanical properties of the anal canal. The CSA and pressure reading were repeatable and lower CSA was associated with higher pressure across all balloon volumes apart from the highest. Possible cause for this was excessive distension of anal canal at higher balloon volumes. Validity and repeatability of EndoFLIP has been proved by this study. Intra-class correlation coefficient values