Centrally administered butyrate improves gut barrier function, visceral sensation and septic lethality in rats.

Short chain fatty acids readily crosses the gut-blood and blood-brain barrier and acts centrally to influence neuronal signaling. We hypothesized that butyrate, a short-chain fatty acid produced by bacterial fermentation, in the central nervous system may play a role in the regulation of intestinal functions. Colonic permeability and visceral sensation was evaluated in rats. Septic lethality was evaluated in a sepsis model induced by subcutaneous administration of both lipopolysaccharide and colchicine. Intracisternal butyrate dose-dependently improved colonic hyperpermeability and visceral nociception. In contrast, subcutaneous injection of butyrate failed to change it. Intracisternal orexin 1 receptor antagonist or surgical vagotomy blocked the central butyrate-induced improvement of colonic hyperpermeability. The improvement of intestinal hyperpermeability by central butyrate or intracisternal orexin-A was blocked by cannabinoid 1 or 2 receptor antagonist. Intracisternal butyrate significantly improved survival period in septic rats. These results suggest that butyrate acts in the central nervous system to improve gut permeability and visceral nociception through cannabinoid signaling. Endogenous orexin in the brain may mediate the reduction of intestinal hyperpermeability by central butyrate through the vagus nerve. We would suggest that improvement of leaky gut by central butyrate may induce visceral antinociception and protection from septic lethality.

The sea cucumber genome provides insights into morphological evolution and visceral regeneration.

Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs.

Understanding tissue expression evolution: from expression phylogeny to phylogenetic network.

Our understanding of tissue expression evolution in multi-cellular model organisms has been considerably advanced with the help of high-throughput technologies from EST, microarray to RNA-seq. Yet, many controversies remained unsolved, ranging from the evolutionary patterns of tissue expressions to expression phylogenetic analysis. Moreover, despite numerous reports published, it is desirable to have a general framework for study of tissue expression evolution. In this article, we first provide an up-to-date and concise review for the study of tissue expression evolution in multi-cellular organisms. While the expression phylogeny of the same tissues sampled from closely or intermediately related species largely reflects the species phylogeny, we demonstrate that phylogenetic network approach may shed some lights for our understanding of the developmental similarity and evolutionary relatedness during the multi-tissue evolution.

Near-infrared spectroscopy is a promising noninvasive technique for monitoring the effects of feeding regimens on the cerebral and splanchnic regions.

AIM: The effects of different milk and, or, administration regimens on cerebro-splanchnic perfusion are still a matter of debate. We investigated the effects of the bolus administration of breast milk or formula on cerebro-splanchnic oximetry, function and perfusion, assessed by near-infrared spectroscopy (NIRS). METHODS: This observational study of 30 infants fed with breast (n = 15) or formula (n = 15) milk, and matched for gestational age and birth weight, was carried out in the neonatal intensive care unit of the C Arrigo Children's Hospital, Alessandria, Italy, a tertiary-level referral centre, from October 2015 to December 2016. NIRS monitoring parameters, such as cerebral and splanchnic oximetry, fraction of tissue oxygen extraction and the cerebral-splanchnic ratio, were recorded before, during and after feeding. RESULTS: Breast milk led to a significant increase in cerebro-splanchnic oximetry and tissue oxygen extraction (p < 0.001) during and after feeding, and the cerebro-splanchnic perfusion ratio was significantly higher (p < 0.001) in the breast than formula group. CONCLUSION: Our study results suggest that breast milk was better tolerated than formula, requiring lower energy expenditure and lower cerebro-splanchnic haemodynamic redistribution. The findings could prompt investigations using NIRS as a promising noninvasive tool for cerebral and splanchnic longitudinal monitoring during neonatal feeding.

Evidence of viscerally-mediated cold-defence thermoeffector responses in man.

KEY POINTS: Visceral thermoreceptors that modify thermoregulatory responses are widely accepted in animal but not human thermoregulation models. Recently, we have provided evidence of viscerally-mediated sweating alterations in humans during exercise brought about by warm and cool fluid ingestion. In the present study, we characterize the modification of shivering and whole-body thermal sensation during cold stress following the administration of a graded thermal stimuli delivered to the stomach via fluid ingestion at 52, 37, 22 and 7°C. Despite no differences in core and skin temperature, fluid ingestion at 52°C rapidly decreased shivering and sensations of cold compared to 37°C, whereas fluid ingestion at 22 and 7°C led to equivalent increases in these responses. Warm and cold fluid ingestion independently modifies cold defence thermoeffector responses, supporting the presence of visceral thermoreceptors in humans. However, the cold-defence thermoeffector response patterns differed from previously identified hot-defence thermoeffectors. ABSTRACT: Sudomotor activity is modified by both warm and cold fluid ingestion during heat stress, independently of differences in core and skin temperatures, suggesting independent viscerally-mediated modification of thermoeffectors. The present study aimed to determine whether visceral thermoreceptors modify shivering responses to cold stress. Ten males (mean ± SD: age 27 ± 5 years; height 1.73 ± 0.06 m, weight 78.4 ± 10.7 kg) underwent whole-body cooling via a water perfusion suit at 5°C, on four occasions, to induce a steady-state shivering response, at which point two aliquots of 1.5 ml kg-1 (SML) and 3.0 ml kg-1 (LRG), separated by 20 min, of water at 7, 22, 37 or 52°C were ingested. Rectal, mean skin and mean body temperature (Tb ), electromyographic activity (EMG), metabolic rate (M) and whole-body thermal sensation on a visual analogue scale (WBTS) ranging from 0 mm (very cold) to 200 mm (very hot) were all measured throughout. Tb was not different between all fluid temperatures following SML fluid ingestion (7°C: 35.7 ± 0.5°C; 22°C: 35.6 ± 0.5°C; 37°C: 35.5 ± 0.4°C; 52°C: 35.5 ± 0.4°C; P = 0.27) or LRG fluid ingestion (7°C: 35.3 ± 0.6°C; 22°C: 35.3 ± 0.5°C; 37°C: 35.2 ± 0.5°C; 52°C: 35.3 ± 0.5°C; P = 0.99). With SML fluid ingestion, greater metabolic rates and cooler thermal sensations were observed with ingestion at 7°C (M: 179 ± 55 W, WBTS: 29 ± 21 mm) compared to 52°C (M: 164 ± 34 W, WBTS: 51 ± 28 mm; all P < 0.05). With LRG ingestion, compared to shivering and thermal sensations with ingestion at 37°C (M: 215 ± 47 W, EMG: 3.9 ± 2.5% MVC, WBTS: 33 ± 2 mm), values were different (all P < 0.05) following ingestion at 7°C (M: 269 ± 77 W, EMG: 5.5 ± 0.9% MVC, WBTS: 14 ± 12 mm), 22°C (M: 270 ± 86 W, EMG: 5.6 ± 1.0% MVC, WBTS: 18 ± 19 mm) and 52°C (M: 179 ± 34 W, EMG: 3.3 ± 2.1% MVC, WBTS: 53 ± 28 mm). In conclusion, fluid ingestion at 52°C decreased shivering and the sensation of coolness, whereas fluid ingestion at 22 and 7°C increased shivering and sensations of coolness to similar levels, independently of core and skin temperature.

Nutritional status-dependent endocannabinoid signalling regulates the integration of rat visceral information.

KEY POINTS: Vagal sensory inputs transmit information from the viscera to brainstem neurones located in the nucleus tractus solitarii to set physiological parameters. These excitatory synapses exhibit a CB1 endocannabinoid-induced long-term depression (LTD) triggered by vagal fibre stimulation. We investigated the impact of nutritional status on long-term changes in this long-term synaptic plasticity. Food deprivation prevents LTD induction by disrupting CB1 receptor signalling. Short-term refeeding restores the capacity of vagal synapses to express LTD. Ghrelin and cholecystokinin, respectively released during fasting and refeeding, play a key role in the control of LTD via the activation of energy sensing pathways such as AMPK and the mTOR and ERK pathways. ABSTRACT: Communication form the viscera to the brain is essential to set physiological homoeostatic parameters but also to drive more complex behaviours such as mood, memory and emotional states. Here we investigated the impact of the nutritional status on long-term changes in excitatory synaptic transmission in the nucleus tractus solitarii, a neural hub integrating visceral signals. These excitatory synapses exhibit a CB1 endocannabinoid (eCB)-induced long-term depression (LTD) triggered by vagal fibre stimulation. Since eCB signalling is known to be an important component of homoeostatic regulation of the body and is regulated during various stressful conditions, we tested the hypothesis that food deprivation alters eCB signalling in central visceral afferent fibres. Food deprivation prevents eCB-LTD induction due to the absence of eCB signalling. This loss was reversed by blockade of ghrelin receptors. Activation of the cellular fuel sensor AMP-activated protein kinase or inhibition of the mechanistic target of rapamycin pathway abolished eCB-LTD in free-fed rats. Signals associated with energy surfeit, such as short-term refeeding, restore eCB-LTD induction, which in turn requires activation of cholecystokinin receptors and the extracellular signal-regulated kinase pathway. These data suggest a tight link between eCB-LTD in the NTS and nutritional status and shed light on the key role of eCB in the integration of visceral information.

The performing animal: causes and consequences of body remodeling and metabolic adjustments in red knots facing contrasting thermal environments.

Using red knots (Calidris canutus) as a model, we determined how changes in mass and metabolic activity of organs relate to temperature-induced variation in metabolic performance. In cold-acclimated birds, we expected large muscles and heart as well as improved oxidative capacity and lipid transport, and we predicted that this would explain variation in maximal thermogenic capacity (Msum). We also expected larger digestive and excretory organs in these same birds and predicted that this would explain most of the variation in basal metabolic rate (BMR). Knots kept at 5°C were 20% heavier and maintained 1.5 times more body fat than individuals kept in thermoneutral conditions (25°C). The birds in the cold also had a BMR up to 32% higher and a Msum 16% higher than birds at 25°C. Organs were larger in the cold, with muscles and heart being 9-20% heavier and digestive and excretory organs being 21-36% larger than at thermoneutrality. Rather than the predicted digestive and excretory organs, the cold-induced increase in BMR correlated with changes in mass of the heart, pectoralis, and carcass. Msum varied positively with the mass of the pectoralis, supracoracoideus, and heart, highlighting the importance of muscles and cardiac function in cold endurance. Cold-acclimated knots also expressed upregulated capacity for lipid transport across mitochondrial membranes [carnitine palmitoyl transferase (CPT)] in their pectoralis and leg muscles, higher lipid catabolism capacity in their pectoralis muscles [ß-hydroxyacyl CoA-dehydrogenase (HOAD)], and elevated oxidative capacity in their liver and kidney (citrate synthase). These adjustments may have contributed to BMR through changes in metabolic intensity. Positive relationships among Msum, CPT, and HOAD in the heart also suggest indirect constraints on thermogenic capacity through limited cardiac capacity.

Magnetic susceptibility anisotropy outside the central nervous system.

Magnetic-susceptibility-based MRI has made important contributions to the characterization of tissue microstructure, chemical composition, and organ function. This has motivated a number of studies to explore the link between microstructure and susceptibility in organs and tissues throughout the body, including the kidney, heart, and connective tissue. These organs and tissues have anisotropic magnetic susceptibility properties and cellular organizations that are distinct from the lipid organization of myelin in the brain. For instance, anisotropy is traced to the epithelial lipid orientation in the kidney, the myofilament proteins in the heart, and the collagen fibrils in the knee cartilage. The magnetic susceptibility properties of these and other tissues are quantified using specific MRI tools: susceptibility tensor imaging (STI), quantitative susceptibility mapping (QSM), and individual QSM measurements with respect to tubular and filament directions determined from diffusion tensor imaging. These techniques provide complementary and supplementary information to that produced by traditional MRI methods. In the kidney, STI can track tubules in all layers including the cortex, outer medulla, and inner medulla. In the heart, STI detected myofibers throughout the myocardium. QSM in the knee revealed three unique layers in articular cartilage by exploiting the anisotropic susceptibility features of collagen. While QSM and STI are promising tools to study tissue susceptibility, certain technical challenges must be overcome in order to realize routine clinical use. This paper reviews essential experimental findings of susceptibility anisotropy in the body, the underlying mechanisms, and the associated MRI methodologies. Copyright © 2016 John Wiley & Sons, Ltd.

A comparison of pediatric and adult CT organ dose estimation methods.

BACKGROUND: Computed Tomography (CT) contributes up to 50% of the medical exposure to the United States population. Children are considered to be at higher risk of developing radiation-induced tumors due to the young age of exposure and increased tissue radiosensitivity. Organ dose estimation is essential for pediatric and adult patient cancer risk assessment. The objective of this study is to validate the VirtualDose software in comparison to currently available software and methods for pediatric and adult CT organ dose estimation. METHODS: Five age groups of pediatric patients and adult patients were simulated by three organ dose estimators. Head, chest, abdomen-pelvis, and chest-abdomen-pelvis CT scans were simulated, and doses to organs both inside and outside the scan range were compared. For adults, VirtualDose was compared against ImPACT and CT-Expo. For pediatric patients, VirtualDose was compared to CT-Expo and compared to size-based methods from literature. Pediatric to adult effective dose ratios were also calculated with VirtualDose, and were compared with the ranges of effective dose ratios provided in ImPACT. RESULTS: In-field organs see less than 60% difference in dose between dose estimators. For organs outside scan range or distributed organs, a five times' difference can occur. VirtualDose agrees with the size-based methods within 20% difference for the organs investigated. Between VirtualDose and ImPACT, the pediatric to adult ratios for effective dose are compared, and less than 21% difference is observed for chest scan while more than 40% difference is observed for head-neck scan and abdomen-pelvis scan. For pediatric patients, 2 cm scan range change can lead to a five times dose difference in partially scanned organs. CONCLUSIONS: VirtualDose is validated against CT-Expo and ImPACT with relatively small discrepancies in dose for organs inside scan range, while large discrepancies in dose are observed for organs outside scan range. Patient-specific organ dose estimation is possible using the size-based methods, and VirtualDose agrees with size-based method for the organs investigated. Careful range selection for CT protocols is necessary for organ dose optimization for pediatric and adult patients.

Association of sleep impairments and gastrointestinal disorders in the context of the visceral theory of sleep.

It was noticed long ago that sleep disorders or interruptions to the normal sleep pattern were associated with various gastrointestinal disorders. We review the studies which established the causal link between these disorders and sleep impairment. However, the mechanism of interactions between the quality of sleep and gastrointestinal pathophysiology remained unclear. Recently, the visceral theory of sleep was formulated. This theory proposes that the same brain structures, and particularly the same cortical sensory areas, which in wakefulness are involved in processing of the exteroceptive information, switch during sleep to the processing of information coming from various visceral systems. We review the studies which demonstrated that neurons of the various cortical areas (occipital, parietal, frontal) during sleep began to fire in response to activation coming from the stomach and small intestine. These data demonstrate that, during sleep, the computational power of the central nervous system, including all cortical areas, is engaged in restoration of visceral systems. Thus, the general mechanism of the interaction between quality of sleep and health became clear.

Transdifferentiation of mouse visceral yolk sac cells into parietal yolk sac cells in vitro.

The mouse embryonic yolk sac is an extraembryonic membrane that consists of a visceral yolk sac (VYS) and parietal yolk sac (PYS), and functions in hematopoietic-circulation in the fetal stage. The present study was undertaken to examine the normal development of both murine VYS and PYS tissues using various molecular markers, and to establish a novel VYS cell culture system in vitro for analyzing differentiation potentials of VYS cells. RT-PCR and immunohistochemical analyses of gene expression in VYS and PYS tissues during development revealed several useful markers for their identification: HNF1ß, HNF4α, Cdh1 (E-cadherin), Krt8 and Krt18 for VYS epithelial cells, and Stra6, Snail1, Thbd and vimentin for PYS cells. PYS cells exhibited mesenchymal characteristics in gene expression and morphology. When VYS cells at 11.5 days of gestation were cultured in vitro for 7 days, the number of HNF1ß-, HNF4α-, E-cadherin- and cytokeratin-positive VYS epithelial cells was significantly reduced and, instead, Stra6-and vimentin-positive PYS-like cells increased with culture. RT-PCR analyses also demonstrated that gene expression of VYS markers decreased, whereas that of PYS markers increased in the primary culture of VYS cells. These data indicate that VYS epithelial cells rapidly transdifferentiate into PYS cells having mesenchymal characteristics in vitro, which may provide a culture system suitable for studying molecular mechanisms of VYS transdifferentiation into PYS cells and also epithelial-mesenchymal transition.

Design and demonstration of a pumpless 14 compartment microphysiological system.

We describe a human "Body-on-a-chip" device (or microphysiological system) that could be used to emulate drug distribution, metabolism, and action in the body. It is based upon a physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model, where multiple chambers representing different organs are connected with fluidic channels to mimic multi-organ interactions within the body. Here we describe a pumpless 14 chamber (13 organs) microfluidic cell culture device that provides a separation between barrier and nonbarrier types of cell cultures. Our barrier chamber layer (skin, GI tract, and lung) allows for direct access and/or exposures to chemical or biological reagents forcing these reagents to pass through a barrier of cells established on a microfabricated membrane before exposing the nonbarrier tissue chambers (fat, kidney, heart, adrenal glands, liver, spleen, pancreas, bone marrow, brain, muscle) or entering the microfluidic circulation within the device. Our nonbarrier tissue chambers were created as three-dimensional configurations by resuspending cells in hydrogel (PGMatrix). We used cell lines to represent five of these organs (barrier lines-A549 [lung] and Caco2 [GI]) (nonbarrier lines-HepG2 C3A [liver], Meg01 [bone marrow], and HK2 [kidney]). The dimensions of our straight duct-like channels to each organ chamber were designed to provide the appropriate flow of a culture medium. The organ volumes and organ flow rates that have been reported for an average human male were used to estimate the desired fluid retention times in each organ chamber. The flow through the channels was induced by gravity on a custom programmed rocker platform which enabled pumpless operation and minimized bubble entrapment. The purpose of this paper is to describe the design and operation of a 14 chamber multi-organ system representing 13 tissues/organs with both barrier and nonbarrier tissue chambers and to study the interactive responses among the various cell lines. We demonstrate that five different cell lines survived with high viability (above 85%) for 7 days. We compared the individual observed flow rates to the compartments to the desired or estimated flow rates. This work demonstrates the feasibility of constructing, operating and maintaining a simple, gravity-driven, multi-organ microphysiological system with the capability of measuring cellular functions such as CYP1A1 and CYP3A4 activities, albumin release, urea, maintenance of tight junctions, and presence of surfactant for a sustained period. Biotechnol. Bioeng. 2016;113: 2213-2227. © 2016 Wiley Periodicals, Inc.

Daily NO rhythms in peripheral clocks in aging male Wistar rats: protective effects of exogenous melatonin.

In mammals suprachiasmatic nucleus (SCN), acts as a light entrainable master clock and by generation of temporal oscillations regulates the peripheral organs acting as autonomous clocks resulting in overt behavioral and physiological rhythms. SCN also controls synthesis and release of melatonin (hormonal message for darkness) from pineal. Nitric Oxide (NO) acts as an important neurotransmitter in generating the phase shifts of circadian rhythms and participates in sleep-wake processes, maintenance of vascular tone as well as signalling and regulating inflammatory processes. Aging is associated with disruption of circadian timing system and decline in endogenous melatonin leading to several physiological disorders. Here we report the effect of aging on NO daily rhythms in various peripheral clocks such as kidney, intestine, liver, heart, lungs and testis. NO levels were measured at zeitgeber time (ZT) 0, 6, 12 and 18 in these tissues using Griess assay in male Wistar rats. Aging resulted in alteration of NO levels as well as phase of NO in both 12 and 24 months groups. Correlation analysis demonstrated loss of stoichiometric interaction between the various peripheral clocks with aging. Age induced alterations in NO daily rhythms were found to be most significant in liver and, interestingly least in lungs. Neurohormone melatonin, an endogenous synchroniser and an antiaging agent decreases with aging. We report further differential restoration with exogenous melatonin administration of age induced alterations in NO daily rhythms and mean levels in kidney, intestine and liver and the stoichiometric interactions between the various peripheral clocks.

Contribution of portal-drained viscera to heat production in Iberian gilts fed a low-protein diet: comparison to Landrace.

BACKGROUND: In terms of whole-body metabolism, visceral tissues have a disproportionate influence with respect to their masses, and under certain circumstances their high metabolic rate may compromise nutrient availability to the tissues of productive/economic interest. The low energy efficiency of Iberian compared to modern breeds could be partly explained by the contribution of portal-drained viscera to heat production. The objective of this study was to determine the relative contribution of portal-drained viscera heat production (PDVHP) to total heat production (THP) in Iberian and Landrace gilts fed a diet with low protein content. RESULTS: Compared to Landrace, Iberian gilts (29 ± 0.9 kg body weight) had lower pre- and postprandial portal vein blood flow (654 vs. 965, and 746 vs. 1133 mL min(-1) , respectively; P < 0.01), postprandial PDVHP (3.09 vs. 3.88 kJ h(-1) kg(-0.75) ; P < 0.01) and PDVHP/THP ratio (0.08 vs. 0.13; P < 0.05), and greater THP (38.5 vs. 31.8 kJ h(-1) kg(-0.75) ; P < 0.05), when offered 0.25 of their daily ration in a 6 h sampling period. CONCLUSION: In spite of the low energetic efficiency and growth rate of Iberian compared to modern breeds, the contribution of PDV energy expenditure relative to THP was lower in Iberian compared to Landrace gilts in the present study.

Specific features of adaptation of rats to chronic cold treatment.

Permanent exposure of rats to four-week cold treatment at +4ºC for 24 h/day resulted in increased weights of the brown adipose tissue, adrenals, and spleen and had no effect on the levels of cortisol and corticosterone in the blood serum. Similar data were observed after exposure of rats to intermittent four-week cold treatment at +4ºC for 8 h/day. After short-term exposure of rats to intermittent cold treatment at +4ºC for 1.5 h/day, all indices studied were similar to those observed in intact animals.

What is the Acupoint? A preliminary review of Acupoints.

BACKGROUND: According to traditional Chinese medicine (TCM) theory, acupoints are specifically chosen sites of acupuncture manipulation, and also the basis for studying the mechanism of acupuncture. Stimulating different acupoints on the body surface could provide various therapeutic benefits. However, what is the acupoint? This question is not clear. REVIEW SUMMARY: We focuse on examining the function of acupoints from different perspectives, including the local and the systemic effects of stimulating acupoints. For example, acupoints may release certain substances or incur some changes, which could adjust the function of organs, maintain homeostasis. Furthermore, the therapeutic effects of verum acupoints versus sham acupoints were discussed. However, due to insufficience in evidence and in current methodologies, research into mechanisms of acupuncture is still incomplete. CONCLUSION: This review might explain, to some extent, what an acupoint is. Further research into the identity of acupoints is warranted, and multidisciplinary methods using novel technologies may yield significant advances over existing knowledge.

Evaluation of dose conversion coefficients for an eight-year-old Iranian male phantom undergoing computed tomography.

In order to construct a library of Iranian pediatric voxel phantoms for radiological protection and dosimetry applications, an Iranian eight-year-old phantom was constructed from a series of CT images. Organ and effective dose conversion coefficients to this phantom were calculated for head, chest, abdominopelvis and chest-abdomen-pelvis scans at tube voltages of 80, 100 and 120 kVp. To validate the results, the organ and effective dose conversion coefficients obtained were compared with those of the University of Florida eight-year-old voxel female phantom as a function of examination type and anatomical scan area. For a detailed study, depth distributions of organs together with the thickness of surrounding tissues located in the beam path, which are shielding the internal organs, were determined for these two voxel phantoms. The relation between the anatomical differences and the level of delivered dose was investigated and the discrepancies among the results justified.

Real-time method for motion-compensated MR thermometry and MRgHIFU treatment in abdominal organs.

PURPOSE: Magnetic resonance-guided high-intensity focused ultrasound is considered to be a promising treatment for localized cancer in abdominal organs such as liver, pancreas, or kidney. Abdominal motion, anatomical arrangement, and required sustained sonication are the main challenges. METHODS: MR acquisition consisted of thermometry performed with segmented gradient-recalled echo echo-planar imaging, and a segment-based one-dimensional MR navigator parallel to the main axis of motion to track the organ motion. This tracking information was used in real-time for: (i) prospective motion correction of MR thermometry and (ii) HIFU focal point position lock-on target. Ex vivo experiments were performed on a sheep liver and a turkey pectoral muscle using a motion demonstrator, while in vivo experiments were conducted on two sheep liver. RESULTS: Prospective motion correction of MR thermometry yielded good signal-to-noise ratio (range, 25 to 35) and low geometric distortion due to the use of segmented EPI. HIFU focal point lock-on target yielded isotropic in-plane thermal build-up. The feasibility of in vivo intercostal liver treatment was demonstrated in sheep. CONCLUSION: The presented method demonstrated in moving phantoms and breathing sheep accurate motion-compensated MR thermometry and precise HIFU focal point lock-on target using only real-time pencil-beam navigator tracking information, making it applicable without any pretreatment data acquisition or organ motion modeling.

The severity of irritable bowel syndrome or the presence of fibromyalgia influencing the perception of visceral and somatic stimuli.

BACKGROUND: Fibromyalgia Syndrome (FMS) is a frequent comorbidity in Irritable Bowel Syndrome (IBS) patients with a higher functional bowel disorder severity index (FBDSI). We tested the possibility that mild to severe IBS patients without FMS would have a graduated visceral and somatic perception, and the presence of FMS would further enhance somatic, but conversely attenuate visceral perception.Our aim was to study visceral and somatic sensitivity in mild IBS patients and in severe IBS patients with or without FMS. METHODS: Eleven mild IBS and 19 severe IBS with and without FMS patients were studied. Somatic and visceral stimuli were applied in each patient by means of electrical stimulations at active and control sites and by means of an electronic barostat in the rectum. Thresholds for discomfort and perception cumulative scores were measured. RESULTS: Mild and severe IBS patients without FMS demonstrated a significantly lower somatic perception cumulative score than severe IBS patients with FMS at active site. Conversely only severe IBS patients without FMS had significantly lower visceral thresholds for discomfort than mild IBS patients and severe IBS patients with FMS. CONCLUSIONS: The presence of co-existing FMS or greater FBDSI affects somatic and visceral perception in a graded fashion across IBS patients.

Effects of preceding stimulation on brain activation in response to colonic distention in humans.

OBJECTIVE: It has been suggested that the pattern of distension (moderate following mild and vice versa) might influence brain activation and the experience of hypersensitivity, offset analgesia, and anticipation. Nevertheless, how the pattern of stimulation affects sensitization and/or desensitization to visceral stimulation remains unknown. METHODS: In 45 nonclinical healthy participants (12 women, 33 men; 20-26 years old), brain processing of visceral sensation induced by colonic distension was examined using H2(15)O positron emission tomography. Subjective feelings regarding the stimuli were also measured. The descending colon was stimulated using six patterns of three bag pressures (0, 20, and 40 mm Hg). To evaluate the neural sensitization to visceral stimulation arising from the precedence effect, the effects of a 20- or 40-mm Hg distention after a sham or 20- or 40-mm Hg distension were analyzed using statistical parametric mapping. The level of significance was set at a voxelwise level of p < .0001, with cluster extent sizes of k > 50. RESULTS: The midbrain, insula, and cerebellum, were more strongly activated by a 20-mm Hg distension with a preceding 40-mm Hg distention than by a 20-mm Hg distention without a preceding stimulation (p < .0001). Conversely, a sham stimulation after the experience of an intense stimulation activated the midcingulate cortex, compared with a sham stimulation without the experience of actual visceral stimulation (p < .0001). CONCLUSIONS: By directly comparing different patterns of visceral stimuli, preceding visceral stimuli may affect neural sensitization and/or desensitization in humans, including elevated midbrain, insula, and midcingulate cortex.