Controlled mechanical ventilation to detect regional lymph node metastases in esophageal cancer using USPIO-enhanced MRI; comparison of image quality.

BACKGROUND: Artifacts caused by respiratory motion or ventilation-induced chest movements are a major problem for thoracic MRI, as they can obscure important anatomical structures such as lymph node metastases. We compared image quality of routine breathhold with intermittent apnea during controlled mechanical ventilation of patients under general anesthesia as the ideal situation without respiratory motion in the detection and characterization of regional lymph nodes in esophageal cancer. METHODS: In this prospective study, 10 patients treated for esophageal cancer underwent ultrasmall superparamagnetic iron oxide (USPIO) enhanced MRI scans. Before neoadjuvant therapy, MRI scans were acquired with a routine breathhold technique. After neoadjuvant therapy, patients were scanned under general anesthesia immediately prior to surgery with controlled mechanical ventilation. The image quality was compared using a Likert scale questionnaire based on visibility of anatomical structures and image artifacts. RESULTS: MRI with controlled mechanical ventilation and prolonged controlled apnea of 4 min was safe and feasible. All cardio-respiratory monitoring parameters remained stable during the apnea phases. Mediastinal and upper abdominal lymph nodes down to 2 mm in size could be visualized with all sequences. All image quality criteria, including visibility of thoracic structures and regional lymph nodes were scored higher using the controlled ventilation sequences compared to the routine breathhold phase. CONCLUSION: USPIO-enhanced MRI with controlled mechanical ventilation is superior to routine breathhold MRI in visualizing lymph nodes, which warrants new motion reduction techniques to use MRI for the detection of lymph node metastases in patients with esophageal cancer.

Multi-center reproducibility of neurochemical profiles in the human brain at 7 T.

The purpose of this work was to harmonize data acquisition and post-processing of single voxel proton MRS ((1) H-MRS) at 7 T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7 T MR systems from two different vendors using an identical semi-localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations ('subject', 'institute' and 'random') were identified with a variance component analysis. Concentrations of 10-11 metabolites, which were corrected for T1 , T2 , magnetization transfer effects and partial volume effects, were obtained with mean Cramér-Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within-subject and system noise, except for total N-acetylaspartate, glutamine and glutathione, which were related to differences in signal-to-noise ratio and in shimming performance between vendors. After multi-center harmonization of acquisition and post-processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7 T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with (1) H-MRS at ultra-high magnetic field.

Image quality and cancer visibility of T2-weighted magnetic resonance imaging of the prostate at 7 Tesla.

OBJECTIVES: To assess the image quality of T2-weighted (T2w) magnetic resonance imaging of the prostate and the visibility of prostate cancer at 7 Tesla (T). MATERIALS & METHODS: Seventeen prostate cancer patients underwent T2w imaging at 7T with only an external transmit/receive array coil. Three radiologists independently scored images for image quality, visibility of anatomical structures, and presence of artefacts. Krippendorff's alpha and weighted kappa statistics were used to assess inter-observer agreement. Visibility of prostate cancer lesions was assessed by directly linking the T2w images to the confirmed location of prostate cancer on histopathology. RESULTS: T2w imaging at 7T was achievable with 'satisfactory' (3/5) to 'good' (4/5) quality. Visibility of anatomical structures was predominantly scored as 'satisfactory' (3/5) and 'good' (4/5). If artefacts were present, they were mostly motion artefacts and, to a lesser extent, aliasing artefacts and noise. Krippendorff's analysis revealed an α = 0.44 between three readers for the overall image quality scores. Clinically significant cancer lesions in both peripheral zone and transition zone were visible at 7T. CONCLUSION: T2w imaging with satisfactory to good quality can be routinely acquired, and cancer lesions were visible in patients with prostate cancer at 7T using only an external transmit/receive body array coil. KEY POINTS: • Satisfactory to good T2-weighted image quality of the prostate is achievable at 7T. • Periprostatic lipids appear hypo-intense compared to healthy peripheral zone tissue at 7T. • Prostate cancer is visible on T2-weighted MRI at 7T.

No effect of C-reactive protein on early atherosclerosis development in apolipoprotein E*3-leiden/human C-reactive protein transgenic mice.

OBJECTIVE: C-reactive protein (CRP) has been associated with risk of cardiovascular disease. It is not clear whether CRP is causally involved in the development of atherosclerosis. Mouse CRP is not expressed at high levels under normal conditions and increases in concentration only several-fold during an acute phase response. Because the dynamic range of human CRP is much larger, apolipoprotein E*3-Leiden (E3L) transgenic mice carrying the human CRP gene offer a unique model to study the role(s) of CRP in atherosclerosis development. METHODS AND RESULTS: Atherosclerosis development was studied in 15 male and 15 female E3L/CRP mice; E3L transgenic littermates were used as controls. The mice were fed a hypercholesterolemic diet to induce atherosclerosis development. Cholesterol exposure did not differ between E3L/CRP and E3L mice. Plasma CRP levels were on average 10.2+/-6.5 mg/L in male E3L/CRP mice, 0.2+/-0.1 mg/L in female E3L/CRP mice, and undetectable in E3L mice. Quantification of atherosclerosis showed that lesion area in E3L/CRP mice was not different from that in E3L mice. CONCLUSIONS: This study demonstrates that mildly elevated levels of CRP in plasma do not contribute to the development of early atherosclerosis in hypercholesterolemic E3L/CRP mice.

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

The value of sildenafil as mode of stimulation in pharmaco-penile duplex ultrasonography.

The purpose of this work was to assess whether a single intracavernous injection (ICI) of a low dose of the combination of papaverine-phentolamine is replaceable by a high dose of the oral erectogenic agent sildenafil as mode of stimulation during pharmaco-penile duplex ultrasonography (PPDU). Eleven patients with complaints of erectile dysfunction were included in a crossover study. With an interval of two weeks the patients were exposed to ICI with papaverine/phentolamine (3.75 mg/0.125 mg) and oral administration with sildenafil (100 mg) preceding PPDU. Five patients started with ICI. Six patients started with sildenafil. In the sildenafil stimulation mode, visual erotic stimulation (VES) was used to initiate erection. VES was applied by personal LCD monitor. Cut-off values to define sufficient arterial response were: peak flow velocity (PSV) >25 cm/s and acceleration time (AT) <72 ms. Cut-off value to define sufficient veno-occlusion was a resistance index > or =1.00. Statistical analysis of PPDU parameters shows no significant difference between the two modes of stimulation for arterial response (PSV, AT), whereas the resistance index, as a parameter of veno-occlusive response was significantly higher in the sildenafil mode. This finding is confirmed in the clinical translation of the results: two patients with an insufficient arterial response to ICI had a sufficient arterial response to sildenafil and only one patient showed an insufficient arterial response following sildenafil, whereas the response following ICI was sufficient. Analysis of veno-occlusive responses shows remarkable differences between both modes of stimulation. Whereas following the administration of sildenafil all veno-occlusive responses were classified as sufficient, seven patients showed an insufficient veno-occlusive response following ICI. As mode of stimulation in PPDU, high dose sildenafil yields significantly less false positive diagnoses of 'veno-occlusive dysfunction' than intracavernous injection of the combination papaverine/phentolamine. No difference was found in the quality of the arterial response. Based on this study we conclude that sildenafil may replace ICI as mode of stimulation during PPDU.

Dental microwear and microstructure in early oligocene primates from the Fayum, Egypt: implications for diet.

Textbook descriptions usually portray the Fayum anthropoideans as frugivores, with Parapithecus grangeri including a folivorous component in its diet and Apidium a component of hard-object feeding. Recent work with modern mammals has shown that analyses of both dental microwear and dental microstructure may yield insights into diet and tooth use. The purpose of this study was to combine these two techniques to gain a better perspective on the paleobiology of the Fayum higher primates. Dental microwear analyses involved the use of high resolution epoxy casts of Aegyptopithecus, Parapithecus, and Apidium housed in the Duke University Primate Center. Scanning electron micrographs were taken at x500, and all microwear features in each micrograph were digitized. For microstructure analyses, molar teeth were sectioned in a variety of planes, lightly etched, and photographed in the SEM. Results of the dental microwear analyses indicate that the three Fayum anthropoideans all clustered with modern primate frugivores but that there were also significant differences between Aegyptopithecus and the other two Fayum genera. By contrast, dental microstructure analyses showed important differences between Apidium and the other two genera. The reason for these differences probably lies in a combination of body size and dietary differences, with Aegyptopithecus occasionally feeding on hard objects and Apidium maximizing wear resistance through a unique emphasis of radial (rather than decussating) enamel.

Enamel microstructure in Lemuridae (Mammalia, Primates): assessment of variability.

This study describes the molar enamel microstructure of seven lemurid primates: Hapalemur griseus, Varecia variegata, Lemur catta, Lemur macaco, Lemur fulvus rufus, Lemur fulvus fulvus, and Lemur fulvus albifrons. Contrary to earlier accounts, which reported little or no prism decussation in lemurid enamel, both Lemur and Varecia molars contain a prominent inner layer of decussating prisms (Hunter-Schreger bands), in addition to an outer radial prism layer, and a thin, nonprismatic enamel surface layer. In contrast, Hapalemur enamel consists entirely of radial and, near the surface, nonprismatic enamel. In addition, for all species, prism packing patterns differ according to depth from the tooth surface, and for all species but Varecia (which also has the thinnest enamel of any lemurid), average prism area increases from the enamel-dentine junction to the surface; this may be a developmental solution to the problem of accommodating a larger outer surface area with enamel deposited from a fixed number of cells. Finally, contradicting some previous reports, Pattern 1 prisms predominate only in the most superficial prismatic enamel. In the deeper enamel, prism cross-sections include both closed (Pattern 1) and arc-shaped (Pattern 2 or, most commonly, Pattern 3). This sequence of depth-related pattern change is repeated in all taxa. It should also be emphasized that all taxa can exhibit all three prism patterns in their mature enamel. The high degree of quantitative and qualitative variation in prism size, shape, and packing suggests that these features should be used cautiously in phylogenetic studies. Hapalemur is distinguished from the other lemurids by unique, medially constricted or rectangular prism cross-sections at an intermediate depth and the absence of prism decussation, but, without further assessment of character polarity, these differences do not clarify lemurid phylogenetic relations. Some characters of enamel microstructure may represent synapomorphies of Lemuridae, or of clades within Lemuridae, but homoplasty is likely to be common. Homoplasy of enamel characters may reflect functional constraints.

A scanning electron-microscopic study of in vitro abrasion of mammalian tooth enamel under compressive loads.

Microscopic tooth-wear (microwear) patterns can be an important tool for assessing modes and rates of abrasive tooth wear, but their analysis and interpretation is complicated by the fact that microwear is influenced by many factors. Three of these factors were here tested under conditions of compressive loading: (1) species differences in enamel structure, (2) abrasive particle size and (3) magnitude of force. Teeth of four species (Homo sapiens, Lemur fulvus, Ovis aries and Crocodylus rhombifer) were abraded in vitro using three sizes of abrasive silicon-carbide grit (average diameters 73, 23 and 14 microns), at two loads (50 and 100 kg). Microwear features were assessed by scanning electron microscopy of lightly etched enamel surfaces and epoxy replicas. Microwear pits (length:width < 4:1) were the predominant feature type. Factorial analysis of variance of rank-transformed, feature-area measurements demonstrated that, under conditions of compressive loading, the size of abrasive particles was the primary determinant of microwear size. These results contrast with previous experimental tests of abrasion by predominantly shearing loads, where feature size was influenced by interaction among experimental factors, including the microscopic orientation of enamel crystallites. Although magnitude of compressive force was not a factor in microwear size variation, it may be a critical factor in explaining the presence or absence of microwear on tooth surfaces. The relatively small compressive bite force generated during typical chewing may not consistently produce abrasive pitting. These experiments demonstrate that, as the same abrasive regime can produce both large and small pits, the mechanism by which wear features are formed (i.e. compression or adhesion) cannot be determined from the size of features alone. Nevertheless, the dependence of pit size on abrasive particle size demonstrates that metrical variation in wear features can elucidate important attributes of an animal's diet.

Enamel microstructure and molar wear in the greater galago, Otolemur crassicaudatus (Mammalia, Primates).

This study describes the molar enamel microstructure of the greater galago, based on SEM study of four individuals. Galago molar enamel consists primarily of radially oriented Pattern 1 prisms. However, the most superficial enamel is characterized by regions of poorly developed prisms or nonprismatic enamel, and Pattern 3 prisms can be found at depths intermediate and deep to the enamel surface. Orientations of prism long axes relative to wear surfaces differ among functionally distinct regions (cuspal facets, Phase I/II facets, and crushing basins). Consequently, orientations of enamel crystallites relative to these surfaces also differ. Because crystallites are the structural unit involved in enamel abrasion, these differences in orientation may have important effects on molar wear patterns. Crystallite orientations differ most between cuspal facets and Phase I/II facet surfaces. Cuspal facets are characterized by near surface-parallel interprismatic and surface-oblique prismatic crystallites. Previous experimental studies suggest that this arrangement is most resistant to wear when surface-normal (compressive) loads predominate. In contrast, prismatic and interprismatic crystallites intercept Phase I/II facet surfaces obliquely, an arrangement expected to resist abrasion when surface-parallel (shearing) loads predominate. Superficial enamel is preserved at most basin surfaces, indicating that these regions are subject to comparatively little abrasive wear. These results support the hypothesis that galago occlusal enamel is organized so as to resist abrasion of different functional regions, a property that may prove important in maintaining functional efficiency. However, this largely reflects constraints of occlusal topography on a microstructure typical of many mammals and thus does not appear to represent a structural innovation.

Enamel structure and microwear: an experimental study of the response of enamel to shearing force.

The anisotropic fracturing and differential wear properties of enamel microstructure represent factors that can obscure the predictive relationship between dental microwear and diet. To assess the impact of enamel structure on microwear, this in vitro experimental study examines the relative contributions to wear of three factors: 1) species differences in microstructure, 2) direction of shearing force relative to enamel prisms and crystallites, and 3) size of abrasive particles. Teeth of Lemur, Ovis, Homo, and Crocodylus, representing, respectively, the structural categories of prismatic patterns 1, 2, and 3 and nonprismatic enamel, were abraded by shearing forces (forces having a component directed parallel to abraded surfaces) and examined by scanning electron microscopy. Striation width increased with particle size for nonprismatic, but not for prismatic, specimens. Direction of shear relative to prism and crystallite orientation had a significant influence on striation width in only some prismatic enamels. The different responses of prismatic and nonprismatic enamels to abrasion reflect the influence of structure, but at the level of organization of crystallites rather than prisms per se. Such interactions explain in part the inability of striation width to discriminate among animals with different dietary habits. Heteroscedasticity and deviations from normality also may confound parametric analyses of microwear variables. Variation in crystallite orientation in prismatic enamels may contribute to optimal dental function through the property of differential wear in functionally distinct regions of teeth.