Postoperative evaluation of surgery for craniosynostosis based on image registration techniques

Craniosynostosis consists of a premature fusion of the sutures in an infant skull, which restricts the skull and brain growth. During the last decades there has been a rapid increase of fundamentally diverse surgical treatment methods. At present, the surgical outcome has been assessed using global variables such as cephalic index, head circumerence and intracranial volume. However, the variables have failed in describing the local deformations and morphological changes, which are proposed to more likely induce neurological disorders.

Methods for the measurement and characterization of erosion in enamel and dentine

The advantages, limitations and potential applications of available methods for studying erosion of enamel and dentine are reviewed. Special emphasis is placed on the influence of histological differences between the dental hard tissue and the stage of the erosive lesion. No method is suitable for all stages of the lesion. Factors determining the applicability of the methods are: surface condition of the specimen, type of the experimental model, nature of the lesion, need for longitudinal measurements and type of outcome. The most suitable and most widely used methods are: chemical analyses of mineral release and enamel surface hardness for early erosion, and surface profilometry and microradiography for advanced erosion. Morphological changes in eroded dental tissue have usually been characterised by scanning electron microscopy. Novel methods have also been used, but little is known of their potential and limitations. Therefore, there is a need for their further development, evaluation, consolidation and, in particular, validation.

Feature-invariant image registration method for quantification of surgical outcomes in patients with craniosynostosis: a preliminary study

Craniosynostosis consists of a premature fusion of the sutures in an infant skull that restricts skull and brain growth. During the last decades, there has been a rapid increase of fundamentally diverse surgical treatment methods. At present, the surgical outcome has been assessed using global variables such as cephalic index, head circumference, and intracranial volume. However, these variables have failed in describing the local deformations and morphological changes that may have a role in the neurologic disorders observed in the patients. This report describes a rigid image registration-based method to evaluate outcomes of craniosynostosis surgical treatments, local quantification of head growth, and indirect intracranial volume change measurements. The developed semiautomatic analysis method was applied to computed tomography data sets of a 5-month-old boy with sagittal craniosynostosis who underwent expansion of the posterior skull with cranioplasty. Quantification of the local changes between pre- and postoperative images was quantified by mapping the minimum distance of individual points from the preoperative to the postoperative surface meshes, and indirect intracranial volume changes were estimated. The proposed methodology can provide the surgeon a tool for the quantitative evaluation of surgical procedures and detection of abnormalities of the infant skull and its development.

Femoroacetabular impingement

Femoroacetabular impingement (FAI) is a pathomechanical concept describing the early and painful contact of morphological changes of the hip joint, both on the acetabular, and femoral head sides. These can lead clinically to symptoms of hip and groin pain, and a limited range of motion with labral, chondral and bony lesions. Pincer impingement generally involves the acetabular side of the joint where there is excessive coverage of the acetabulum, which may be focal or more diffuse. There is linear contact of the acetabulum with the head/neck junction. Cam impingement involves the femoral head side of the joint where the head is associated with bony excrescences and is aspheric. The aspheric femoral head jams into the acetabulum. Imaging appearances are reviewed below. This type is evident in young males in the second and third decades. The main features of FAI are described.

TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner

Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage.

Morphofunctional adaptations of the olfactory mucosa in postnatally developing rabbits

Rabbits are born blind and deaf and receive unusually limited maternal care. Consequently, their suckling young heavily rely on the olfactory cue for nipple attachment. However, the postnatal morphofunctional adaptations of olfactory mucosa (OM) are not fully elucidated. To clarify on the extent and the pattern of refinement of the OM following birth in the rabbit, morphologic and morphometric analysis of the mucosa were done at neonatal (0-1 days), suckling (2 weeks), weanling (4 weeks), and adult (6-8 months) stages of postnatal development. In all the age groups, the basic components of the OM were present. However, proliferative activity of cells of the mucosal epithelium decreased with increasing age as revealed by Ki-67 immunostaining. Diameters of axon bundles, packing densities of olfactory cells, and cilia numbers per olfactory cell knob increased progressively with age being 5.5, 2.1, and 2.6 times, respectively, in the adult as compared with the neonate. Volume fraction values for the bundles increased by 5.3% from birth to suckling age and by 7.4% from weaning to adulthood and the bundle cores were infiltrated with blood capillaries in all ages except in the adult where such vessels were lacking. The pattern of cilia projection from olfactory cell knobs also showed age-related variations, that is, arose as a tuft from the tips of the knobs in neonates and sucklings and in a radial pattern from the knob bases in weanlings and adults. These morphological changes may be attributed to the high olfactory functional demand associated with postnatal development in the rabbit.

A survey of MRI-based medical image analysis for brain tumor studies

MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines.

Host cell responses of Salmonella typhimurium infected human dendritic cells

Live attenuated Salmonella are attractive vaccine candidates for mucosal application because they induce both mucosal immune responses and systematic immune responses. After breaking the epithelium barrier, Salmonella typhimurium is found within dendritic cells (DC) in the Peyer's patches. Although there are abundant data on the interaction of S. typhimurium with murine epithelial cells, macrophages and DC, little is known about its interaction with human DC. Live attenuated S. typhimurium have recently been shown to efficiently infect human DC in vitro and induce production of cytokines. In this study, we have analysed the morphological consequences of infection of human DC by the attenuated S. typhimurium mutant strains designated PhoPc, AroA and SipB and the wild-type strains of the American Type Culture Collection (Manassas, VA, USA), ATCC 14028 and ATCC C53, by electron microscopy at 30 min, 3 h and 24 h after exposure. Our results show that genetic background of the strains profoundly influence DC morphology following infection. The changes included (i) membrane ruffling; (ii) formation of tight or spacious phagosomes; (iii) apoptosis; and (iv) spherical, pedunculated membrane-bound microvesicles that project from the plasma membrane. Despite the fact that membrane ruffling was much more pronounced with the two virulent strains, all mutants were taken up by the DC. The microvesicles were induced by all the attenuated strains, including SipB, which did not induce apoptosis in the host cell. These results suggest that Salmonella is internalized by human DC, inducing morphological changes in the DC that could explain immunogenicity of the attenuated strains.

Antisense-mediated melanoma inhibitor of apoptosis protein downregulation sensitizes G361 melanoma cells to cisplatin

Malignant melanoma is an aggressive form of skin cancer that is highly resistant to conventional therapies. The melanoma inhibitor of apoptosis protein is a potent inhibitor of apoptosis and is overexpressed in melanoma cells, but undetectable in most normal tissues including melanocytes. We designed 20-mer phosphorothioate antisense oligonucleotides complementary to five putatively single-stranded sites on the melanoma inhibitor of apoptosis protein mRNA and investigated their ability to sensitize G361 melanoma cells to cisplatin. Inhibition of melanoma inhibitor of apoptosis protein mRNA and protein expression were measured by real-time polymerase chain reaction and immunoblotting. Cell viability and apoptosis were quantitated by colorimetric viability assays and by annexin V staining, respectively. Oligonucleotide M706 was identified as the most efficient antisense sequence which downregulated melanoma inhibitor of apoptosis protein mRNA and protein levels in G361 cells by 68 and 78%, respectively. The specificity of target downregulation was confirmed using scrambled sequence control oligonucleotides that only marginally decreased melanoma inhibitor of apoptosis protein expression. Whereas downregulation of melanoma inhibitor of apoptosis protein moderately inhibited cell growth by 26%, in combination with cisplatin, this resulted in a supra-additive effect with almost 57% reduction in G361 cell viability compared with cisplatin alone (17%) (P<0.05). Cell death was mainly due to apoptosis as demonstrated by a 3- to 4-fold increase in annexin V-positive cells and typical morphological changes compared with controls. In summary, we describe a new antisense oligonucleotide that efficiently downregulates melanoma inhibitor of apoptosis protein expression and sensitizes melanoma cells to cisplatin.

Lung volume, breathing pattern and ventilation inhomogeneity in preterm and term infants

BACKGROUND: Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques. METHODOLOGY/PRINCIPAL FINDINGS: We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t(PTEF)/t(E)) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity. CONCLUSIONS: Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process.

Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

BACKGROUND: Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R) injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells. METHODS: Rats were randomly assigned to a control, Celsior (CE) or Celsior + surfactant (CE+S) group (n = 5 each). In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4 degrees C and 50 min of reperfusion at 37 degrees C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups) or immediately after sacrifice (Control), the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells. RESULTS: Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation): CE: 160 mm3 (0.61) vs. CE+S: 4 mm3 (0.75); p < 0.05) and the development of atelectases (CE: 342 mm3 (0.90) vs. CE+S: 0 mm3; p < 0.05) but led to a higher degree of peribronchovascular edema (CE: 89 mm3 (0.39) vs. CE+S: 268 mm3 (0.43); p < 0.05). Alveolar type II cells were similarly swollen in CE (423 microm3(0.10)) and CE+S (481 microm3(0.10)) compared with controls (323 microm3(0.07); p < 0.05 vs. CE and CE+S). The number of lamellar bodies was increased and the mean lamellar body volume was decreased in both CE groups compared with the control group (p < 0.05). CONCLUSION: Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of peribronchovascular edema. Morphological changes of alveolar type II cells due to I/R are not affected by surfactant treatment. The beneficial effects of exogenous surfactant therapy are related to the intraalveolar activity of the exogenous surfactant.

Effects of carbonation on the mineral composition of cement kiln dust

Due to their relatively high calcium oxide content, industrial mineral oxide wastes are potential candidates for mineral sequestration of carbon dioxide (CO2). Cement kiln dust (CKD), a byproduct of cement manufacturing contains 20-60% CaO making it a possible candidate for CO2 sequestration. In this study, three types of CKD are characterized, before and after carbonation, using environmental scanning electron microscopy and energy dispersive x-ray microanalysis to determine the mineralogical and morphological changes occurring due to carbonation. The reactants, products, and precipitation mechanisms were investigated to enhance understanding of the governing processes and allow better utilization of CKD for CO2 sequestration. The results of multiple independent analyses confirmed the formation of CaCO3 during carbonation. Examinations of the reaction pathways found that CaO and calcium hydroxide (Ca(OH)2) were the major reactants. Three types of CaCO3 precipitation mechanisms were observed: (1) diffusion of CO2 into Ca(OH)2 particles causing precipitation in the pores of the particle and the growth of a CaCO3 ring from the outside inward, (2) precipitation onto existing particles, and (3) precipitation from aqueous solution. The growth of a CaCO3 ring on the outside of a particle may slow further diffusion of CO2 into a particle slowing iv the overall sequestration rate. Additionally, changes caused by carbonation in the solubility of trace metals were studied by mixing pre- and post-carbonated CKD with water and analyzing the solution using inductively coupled plasma mass spectrometry. Decreases in the leaching of chromium, lead, and copper were observed, and is an incentive for use of CKD for CO2 sequestration. Equilibrium modeling using PHREEQC confirmed that CaO and Ca(OH)2 would carbonate readily and form CaCO3.

Influence of traumatic impaction and pathological loading on knee menisci

Nearly half of the US population faces the risk of developing knee osteoarthritis (OA). Both in vitro and in vivo studies can aid in a better understanding of the etiology, progression, and advancement of this debilitating disorder. The knee menisci are fibrocartilagenous structures that aid in the distribution of load, attenuation of shock, alignment and lubrication of the knee. Little is known about the biochemical and morphological changes associated with knee menisci following altered loading and traumatic impaction, and investigations are needed to further elucidate how degradation of this soft tissue advances over time. The biochemical response of porcine meniscal explants was investigated following a single bout of dynamic compression with and without the treatment of the pharmaceutical drug, anakinra (IL-1RA). Dynamic loading led to a strain-dependent response in both anabolic and catabolic gene expression of meniscal explants. By inhibiting the Interleukin-1 pathway with IL-1RA, a marked decrease in several catabolic molecules was found. From these studies, future developments in OA treatments may be developed. The implementation of an in vivo animal model contributes to the understanding of how the knee joint behaves as a whole. A novel closed-joint in vivo model that induces anterior cruciate ligament (ACL) rupture has been developed to better understand how traumatic injury leads to OA. The menisci of knees from three different groups (healthy, ACL transected, and traumatically impacted) were characterized using histomorphometry. The acute and chronic changes within the knee following traumatic impaction were investigated. The works presented in this dissertation have focused on the characterization, implementation, and development of mechanically-induced changes to the knee menisci.

Computational and Biochemical Approaches to Molecular Epidemiology

Mining activity in Butte, Montana has taken place, or continues to take place, within the urban residence of Butte itself. This has led to urban areas with high concentrations of toxic metals such as arsenic, lead, copper, zinc, mercury and cadmium. Advances in protein study and gene sequencing has opened the possibility of finding molecular biomarkers whose presence, absence or morphological changes could indicate disease processes in populations exposed to environmental toxins. While in principle, biomarkers can be any chemicals or metabolites, as well as proteins and genes that are indicative of exposure to xenobiotics, this study seeks to identify changes in cellular pathways that suggest chronic (or acute) exposure to low-levels of metals associated with historical mining activities on the Butte Hill that could cause oxidative stress or other stress to the cell.

Two-Phase Flow In Microchannels: Morphology And Interface Phenomena

The existence and morphology, as well as the dynamics of micro-scale gas-liquid interfaces is investigated numerically and experimentally. These studies can be used to assess liquid management issues in microsystems such as PEMFC gas flow channels, and are meant to open new research perspectives in two-phase flow, particularly in film deposition on non-wetting surfaces. For example the critical plug volume data can be used to deliver desired length plugs, or to determine the plug formation frequency. The dynamics of gas-liquid interfaces, of interest for applications involving small passages (e.g. heat exchangers, phase separators and filtration systems), was investigated using high-speed microscopy - a method that also proved useful for the study of film deposition processes. The existence limit for a liquid plug forming in a mixed wetting channel is determined by numerical simulations using Surface Evolver. The plug model simulate actual conditions in the gas flow channels of PEM fuel cells, the wetting of the gas diffusion layer (GDL) side of the channel being different from the wetting of the bipolar plate walls. The minimum plug volume, denoted as critical volume is computed for a series of GDL and bipolar plate wetting properties. Critical volume data is meant to assist in the water management of PEMFC, when corroborated with experimental data. The effect of cross section geometry is assessed by computing the critical volume in square and trapezoidal channels. Droplet simulations show that water can be passively removed from the GDL surface towards the bipolar plate if we take advantage on differing wetting properties between the two surfaces, to possibly avoid the gas transport blockage through the GDL. High speed microscopy was employed in two-phase and film deposition experiments with water in round and square capillary tubes. Periodic interface destabilization was observed and the existence of compression waves in the gas phase is discussed by taking into consideration a naturally occurring convergent-divergent nozzle formed by the flowing liquid phase. The effect of channel geometry and wetting properties was investigated through two-phase water-air flow in square and round microchannels, having three static contact angles of 20, 80 and 105 degrees. Four different flow regimes are observed for a fixed flow rate, this being thought to be caused by the wetting behavior of liquid flowing in the corners as well as the liquid film stability. Film deposition experiments in wetting and non-wetting round microchannels show that a thicker film is deposited for wetting conditions departing from the ideal 0 degrees contact angle. A film thickness dependence with the contact angle theta as well as the Capillary number, in the form h_R ~ Ca^(2/3)/ cos(theta) is inferred from scaling arguments, for contact angles smaller than 36 degrees. Non-wetting film deposition experiments reveal that a film significantly thicker than the wetting Bretherton film is deposited. A hydraulic jump occurs if critical conditions are met, as given by a proposed nondimensional parameter similar to the Froude number. Film thickness correlations are also found by matching the measured and the proposed velocity derived in the shock theory. The surface wetting as well as the presence of the shock cause morphological changes in the Taylor bubble flow.