Adequacy of an early arterial phase low-volume contrast protocol in 64-detector computed tomography angiography for aortoiliac aneurysms

PURPOSE: This retrospective study was conducted to determine whether a low-volume contrast medium protocol provides sufficient enhancement for 64-detector computed tomography angiography (CTA) in patients with aortoiliac aneurysms. METHODS: Evaluated were 45 consecutive patients (6 women; mean age, 72 +/- 6 years) who were referred for aortoiliac computed tomography angiography between October 2005 and January 2007. Group A (22 patients; creatinine clearance, 64.2 +/- 8.1 mL/min) received 50 mL of the contrast agent. Group B (23 patients; creatinine clearance, 89.4 +/- 7.3 mL/min) received 100 mL of the contrast agent. The injection rate was 3.5 mL/s, followed by 30 mL of saline at 3.5 mL/s. Studies were performed on the same 64-detector computed tomography scanner using a real-time bolus-tracking technique. Quantitative analysis was performed by determination of mean vascular attenuation at 10 regions of interest from the suprarenal aorta to the common femoral artery by one reader blinded to type and amount of contrast agent and compared using the Student t test. Image quality according to a 4-point scale was assessed in consensus by two readers blinded to type and amount of contrast medium and compared using the Mann-Whitney test. Multivariable adjustments were performed using ordinal regression analysis. RESULTS: Mean total attenuation did not differ significantly between both groups (196.5 +/- 33.0 Hounsfield unit [HU] in group A and 203.1 +/- 44.2 HU in group B; P = .57 by univariate and P > .05 by multivariable analysis). Accordingly, attenuation at each region of interest was not significantly different (P > .35). Image quality was excellent or good in all patients. No significant differences in visual assessment were found comparing both contrast medium protocols (P > .05 by univariate and by multivariable analysis). CONCLUSIONS: Aortoiliac aneurysm imaging can be performed with substantially reduced amounts of contrast medium using 64-detector computed tomography angiography technology.

Contrast Formation in Kelvin Probe Force Microscopy of Single π-Conjugated Molecules

We report the contrast formation in the local contact potential difference (LCPD) measured by Kelvin probe force microscopy (KPFM) on single charge-transfer complexes (CTCs) on a NaCl bilayer on Cu(111). At different tip heights, we found quantitatively different LCPD contrasts that characterize different properties of the molecule. In the small distance regime, the tip penetrates the electron density of the molecule, and the contrast is related to the size and topography of the electron shell of the molecule. For larger distances, the LCPD contrast corresponds to the electrostatic field above the molecule. However, in the medium-distance regime, that is, for tip heights similar to the size of the molecule, the nonspherical distribution of π- and σ-electrons often conceals the effect of the partial charges within the molecule. Only for large distances does the LCPD map converge toward the simple field of a dipole for a polar molecule.

Absolute polarity determination of teeth cementum by phase sensitive second harmonic generation microscopy

The absolute sign of local polarity in relation to the biological growth direction has been investigated for teeth cementum using phase sensitive second harmonic generation microscopy (PS-SHGM) and a crystal of 2-cyclooctylamino-5-nitropyridine (COANP) as a nonlinear optic (NLO) reference material. A second harmonic generation (SHG) response was found in two directions of cementum: radial (acellular extrinsic fibers that are oriented more or less perpendicular to the root surface) and circumferential (cellular intrinsic fibers that are oriented more or less parallel to the surface). A mono-polar state was demonstrated for acellular extrinsic cementum. However, along the different parts of cementum in circumferential direction, two corresponding domains were observed featuring an opposite sign of polarity indicative for a bi-polar microscopic state of cellular intrinsic cementum. The phase information showed that the orientation of radial collagen fibrils of cementum is regularly organized with the donor (D) groups pointing to the surface. Circumferential collagen molecules feature orientational disorder and are oriented up and down in random manner showing acceptor or donor groups at the surface of cementum. Considering that the cementum continues to grow in thickness throughout life, we can conclude that the cementum is growing circumferentially in two opposite directions and radially in one direction. A Markov chain type model for polarity formation in the direction of growth predicts D-groups preferably appearing at the fiber front.

Application of the specular and diffuse reflection analysis for in vitro diagnostics of dental erosion: correlation with enamel softening, roughness, and calcium release

We present assembly and application of an optical reflectometer for the analysis of dental erosion. The erosive procedure involved acid-induced softening and initial substance loss phases, which are considered to be difficult for visual diagnosis in a clinic. Change of the specular reflection signal showed the highest sensitivity for the detection of the early softening phase of erosion among tested methods. The exponential decrease of the specular reflection intensity with erosive duration was compared to the increase of enamel roughness. Surface roughness was measured by optical analysis, and the observed tendency was correlated with scanning electron microscopy images of eroded enamel. A high correlation between specular reflection intensity and measurement of enamel softening (r(2) ? -0.86) as well as calcium release (r(2) ? -0.86) was found during erosion progression. Measurement of diffuse reflection revealed higher tooth-to-tooth deviation in contrast to the analysis of specular reflection intensity and lower correlation with other applied methods (r(2) = 0.42-0.48). The proposed optical method allows simple and fast surface analysis and could be used for further optimization and construction of the first noncontact and cost-effective diagnostic tool for early erosion assessment in vivo.

The presence of iodinated contrast agents amplifies DNA radiation damage in computed tomography

The purpose of this study was to determine the influence of iodinated contrast agents on the formation of DNA double-strand breaks in vitro in lymphocytes and to verify these results in patients undergoing diagnostic computed tomography examinations. Blood samples were irradiated in vitro in the presence of iodinated X-ray contrast agent. Controls were irradiated without contrast agent. Fourteen patients were investigated using contrast-enhanced computed tomography (CT), and 14 other patients with unenhanced CT. Blood samples were taken prior to and 5 min and 1, 2 and 24 h after the CT examination. In these blood samples the average number of γH2Ax-foci per lymphocyte was enumerated by fluorescence microscopy. Statistical differences between foci numbers developed in the presence and absence of contrast agent were tested using an independent sample t-test. In vitro foci numbers after irradiation were significantly higher when contrast agent was present during irradiation. In vivo, γH2Ax-foci levels were 58% higher in patients undergoing contrast-enhanced CT compared with those undergoing unenhanced CT. In the presence of iodinated contrast agents DNA, damage is increased and the radiation dose is not the only factor affecting the amount of DNA damage. Individual patient characteristics and biological dosimetry applications, e.g. the analysis of γH2Ax-foci, have to be considered.

Intravital microscopy reveals endothelial dysfunction in resistance arterioles in Angiotensin II-induced hypertension

It is known that hypertension is associated with endothelial dysfunction and that Angiotensin II (Ang II) is a key player in the pathogenesis of hypertension. We aimed to elucidate whether endothelial dysfunction is a specific feature of Ang II-mediated hypertension or a common finding of hypertension, independently of underlying etiology. We studied endothelial-dependent vasorelaxation in precapillary resistance arterioles and in various large-caliber conductance arteries in wild-type mice with Ang II-dependent hypertension (2-kidney 1-clip (2K1C) model) or Ang II-independent (volume overload) hypertension (1-kidney 1-clip model (1K1C)). Normotensive sham mice were used as controls. Aortic mechanical properties were also evaluated. Intravital microscopy of precapillary arterioles revealed a significantly impaired endothelium-dependent vasorelaxation in 2K1C mice compared with sham mice, as quantified by the ratio of acetylcholine (ACh)-induced over S-nitroso-N-acetyl-D,L-penicillamine (SNAP)-induced vasorelaxation (2K1C: 0.49±0.12 vs. sham: 0.87±0.11, P=0.018). In contrast, the ACh/SNAP ratio in volume-overload hypertension 1K1C mice was not significantly different from sham mice, indicating no specific endothelial dysfunction (1K1C: 0.77±0.27 vs. sham: 0.87±0.11, P=0.138). Mechanical aortic wall properties and endothelium-dependent vasorelaxation, assessed ex vivo in rings of large-caliber conductance (abdominal and thoracic aorta, carotid and femoral arteries), were not different between 2K1C, 1K1C and sham mice. Endothelial dysfunction is an early feature of Ang II- but not volume-overload-mediated hypertension. This occurs exclusively at the level of precapillary arterioles and not in conduit arteries. Our findings, if confirmed in clinical studies, will provide a better understanding of the pathophysiological mechanisms of hypertension.

Immunohistochemical demonstration of interleukin-1 beta induced changes in acute-phase proteins and albumin in rat liver

Interleukin-1 beta is a potent mediator of the acute-phase response. However, the effects of interleukin-1 beta administration on the topic in vivo production of acute-phase proteins and albumin are so far not well understood. Overnight fasted rats were subcutaneously injected with 0.2 mL 0.9% NaCl (control group) or 6.25 micrograms recombinant human interleukin-1 beta, and rectal temperature was measured at intervals up to 48 h. Livers were perfused-fixed in vivo prior to injection (base-line), and at 9, 24, and 48 h following the interleukin-1 beta injection. Fibrinogen, orosomucoid (alpha 1-acid glycoprotein) and albumin were immunostained using a streptavidin-biotin-immunoperoxidase technique. Rectal temperature peaked 5 h after the single interleukin-1 beta injection, and fell gradually to base-line values by 24 h. Prior to injection only a few hepatocytes, randomly scattered throughout the liver lobule, stained positive for fibrinogen and orosomucoid. In contrast, all hepatocytes stained uniformly positive for fibrinogen and orosomucoid 9 h after interleukin-1 beta injection, whereas at 24 h a predominant centrilobular staining pattern occurred. Due to fasting, albumin positive hepatocytes were already reduced at base-line in both groups. Interleukin-1 beta induced a further significant loss of albumin positive cells in the periportal zone (35 +/- 21%) at 9 h when compared with controls (58 +/- 11%, p = 0.037). In conclusion, subcutaneous interleukin-1 beta (probably by stimulation of interleukin-6) strongly induces fibrinogen and orosomucoid expression in rat liver, and suppresses immunohistochemically stainable albumin in a heterogenous way, mainly in the periportal zone.

Neonatal steroids induce a down-regulation of tenascin-C and elastin and cause a deceleration of the first phase and an acceleration of the second phase of lung alveolarization

Pre- and postnatal corticosteroids are often used in perinatal medicine to improve pulmonary function in preterm infants. To mimic this clinical situation, newborn rats were treated systemically with dexamethasone (Dex), 0.1-0.01 mg/kg/day on days P1-P4. We hypothesized that postnatal Dex may have an impact on alveolarization by interfering with extracellular matrix proteins and cellular differentiation. Morphological alterations were observed on 3D images obtained by high-resolution synchrotron radiation X-ray tomographic microscopy. Alveolarization was quantified stereologically by estimating the formation of new septa between days P4 and P60. The parenchymal expression of tenascin-C (TNC), smooth muscle actin (SMA), and elastin was measured by immunofluorescence and gene expression for TNC by qRT-PCR. After Dex treatment, the first phase of alveolarization was significantly delayed between days P6 and P10, whereas the second phase was accelerated. Elastin and SMA expressions were delayed by Dex treatment, whereas TNC expression was delayed and prolonged. A short course of neonatal steroids impairs the first phase of alveolarization, most likely by altering the TNC and elastin expression. Due to an overshooting catch-up during the second phase of alveolarization, the differences disappear when the animals reach adulthood.

Gas-phase Dissociation of homo-DNA Oligonucleotides

Synthetic modified oligonucleotides are of interest for diagnostic and therapeutic applications, as their biological stability, pairing selectivity, and binding strength can be considerably increased by the incorporation of unnatural structural elements. Homo-DNA is an oligonucleotide homologue based on dideoxy-hexopyranosyl sugar moieties, which follows the Watson-Crick A-T and G-C base pairing system, but does not hybridize with complementary natural DNA and RNA. Homo-DNA has found application as a bioorthogonal element in templated chemistry applications. The gas-phase dissociation of homo-DNA has been investigated by ESI-MS/MS and MALDI-MS/MS, and mechanistic aspects of its gas-phase dissociation are discussed. Experiments revealed a charge state dependent preference for the loss of nucleobases, which are released either as neutrals or as anions. In contrast to DNA, nucleobase loss from homo-DNA was found to be decoupled from backbone cleavage, thus resulting in stable products. This renders an additional stage of ion activation necessary in order to generate sequence-defining fragment ions. Upon MS(3) of the primary base-loss ion, homo-DNA was found to exhibit unspecific backbone dissociation resulting in a balanced distribution of all fragment ion series.

Intussusceptive angiogenesis: its role in embryonic vascular network formation

Intussusceptive angiogenesis is a novel mode of blood vessel formation and remodeling, which occurs by internal division of the preexisting capillary plexus without sprouting. In this study, the process is demonstrated in developing chicken eye vasculature and in the chorioallantoic membrane by methylmethacrylate (Mercox) casting, transmission electron microscopy, and in vivo observation. In a first step of intussusceptive angiogenesis, the capillary plexus expands by insertion of numerous transcapillary tissue pillars, ie, by intussusceptive microvascular growth. In a subsequent step, a vascular tree arises from the primitive capillary plexus as a result of intussusceptive pillar formation and pillar fusions, a process we termed "intussusceptive arborization." On the basis of the morphological observations, a 4-step model for intussusceptive arborization is proposed, as follows: phase I, numerous circular pillars are formed in rows, thus demarcating future vessels; phase II, formation of narrow tissue septa by pillar reshaping and pillar fusions; phase III, delineation, segregation, growth, and extraction of the new vascular entity by merging of septa; and phase IV, formation of new branching generations by successively repeating the process, complemented by growth and maturation of all components. In contrast to sprouting, intussusceptive angiogenesis does not require intense local endothelial cell proliferation; it is implemented primarily by rearrangement and attenuation of the endothelial cell plates. In summary, transcapillary pillar formation, ie, intussusception, is a central and probably widespread process, which plays a role not only in capillary network growth and expansion (intussusceptive microvascular growth), but also in vascular plexus remodeling and tree formation (intussusceptive arborization).

OPTiSPIM: integrating optical projection tomography in light sheet microscopy extends specimen characterization to nonfluorescent contrasts.

Mesoscopic 3D imaging has become a widely used optical imaging technique to visualize intact biological specimens. Selective plane illumination microscopy (SPIM) visualizes samples up to a centimeter in size with micrometer resolution by 3D data stitching but is limited to fluorescent contrast. Optical projection tomography (OPT) works with fluorescent and nonfluorescent contrasts, but its resolution is limited in large samples. We present a hybrid setup (OPTiSPIM) combining the advantages of each technique. The combination of fluorescent and nonfluorescent high-resolution 3D data into integrated datasets enables a more extensive representation of mesoscopic biological samples. The modular concept of the OPTiSPIM facilitates incorporation of the transmission OPT modality into already established light sheet based imaging setups.

Synthesis of bone-like micro-porous calcium phosphate/iota-carrageenan composites by gel diffusion

Brushite and octacalcium phosphate (OCP) crystals are well-known precursors of hydroxylapatite (HAp), the main mineral found in bone. In this report, we present a new method for biomimicking brushite and OCP using single and double diffusion techniques. Brushite and OCP crystals were grown in an iota-carrageenan gel. The aggregates were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), infrared spectroscopy (IR) and thermal gravimetric analysis (TGA). SEM revealed different morphologies of brushite crystals from highly porous aggregates to plate-shaped forms. OCP crystals grown in iota-carrageenan showed a porous spherical shape different from brushite growth forms. The XRD method demonstrated that the single-diffusion method favors the formation of monoclinic brushite. In contrast, the double diffusion method was found to promote the formation of the triclinic octacalcium phosphate OCP phase. By combining the different parameters for crystal growth in carrageenan, such as ion concentration, gel pH and gel density, it is possible to modify the morphology of composite crystals, change the phase of calcium phosphate and modulate the amount of carrageenan inclusion in crystals. This study suggests that iota-carrageenan is a high-molecular-weight polysaccharide that is potentially applicable for controlling calcium phosphate crystallization.

Pitfalls in post-mortem CT-angiography--intravascular contrast induces post-mortem pericardial effusion

We present a case where multi-phase post-mortem computed tomography angiography (PMCTA) induced a hemorrhagic pericardial effusion during the venous phase of angiography. Post-mortem non-contrast CT (PMCT) suggested the presence of a ruptured aortic dissection. This diagnosis was confirmed by PMCTA after pressure controlled arterial injection of contrast. During the second phase of multi-phase PMCTA the presence of contrast leakage from the inferior cava vein into the pericardial sac was noted. Autopsy confirmed the post-mortem nature of this vascular tear. This case teaches us an important lesson: it underlines the necessity to critically analyze PMCT and PMCTA images in order to distinguish between artifacts, true pathologies and iatrogenic findings. In cases with ambiguous findings such as the case reported here, correlation of imaging findings with autopsy is elementary.

Multi-phase postmortem CT angiography: recognizing technique-related artefacts and pitfalls

BACKGROUND AND PURPOSE Multi-phase postmortem CT angiography (MPMCTA) is increasingly being recognized as a valuable adjunct medicolegal tool to explore the vascular system. Adequate interpretation, however, requires knowledge about the most common technique-related artefacts. The purpose of this study was to identify and index the possible artefacts related to MPMCTA. MATERIAL AND METHODS An experienced radiologist blinded to all clinical and forensic data retrospectively reviewed 49 MPMCTAs. Each angiographic phase, i.e. arterial, venous and dynamic, was analysed separately to identify phase-specific artefacts based on location and aspect. RESULTS Incomplete contrast filling of the cerebral venous system was the most commonly encountered artefact, followed by contrast agent layering in the lumen of the thoracic aorta. Enhancement or so-called oedematization of the digestive system mucosa was also frequently observed. CONCLUSION All MPMCTA artefacts observed and described here are reproducible and easily identifiable. Knowledge about these artefacts is important to avoid misinterpreting them as pathological findings.