An iterative Bayesian reconstruction algorithm for limited view angle tomography, or ectomography, based on the three-dimensional total variation (TV) norm has been developed. The TV norm has been described in the literature as a method for reducing noise in two-dimensional images while preserving edges, without introducing ringing or edge artefacts. It has also been proposed as a 2D regularization function in Bayesian reconstruction, implemented in an expectation maximization algorithm (TV-EM). The TV-EM was developed for 2D single photon emission computed tomography imaging, and the algorithm is capable of smoothing noise while maintaining edges without introducing artefacts. The TV norm was extended from 2D to 3D and incorporated into an ordered subsets expectation maximization algorithm for limited view angle geometry. The algorithm, called TV3D-EM, was evaluated using a modelled point spread function and digital phantoms. Reconstructed images were compared with those reconstructed with the 2D filtered backprojection algorithm currently used in ectomography. Results show a substantial reduction in artefacts related to the limited view angle geometry, and noise levels were also improved. Perhaps most important, depth resolution was improved by at least 45%. In conclusion, the proposed algorithm has been shown to improve the perceived image quality.

1. Local skeletal muscle blood flow was monitored using the microdialysis ethanol technique and 133Xe clearance during intermittent isometric contractions (5 s on/10 s off) of the thigh at 0-60% of the maximal voluntary isometric contraction force. 2. A linear increase in blood flow over a 25-fold range was detected using both 133Xe clearance and the microdialysis ethanol technique. 3. The median correlation coefficient between percentage maximal voluntary isometric contraction force and the ethanol outflow/inflow ratio, a marker of blood flow, was r = -0.98 (-0.94 to -0.99) (median and range, n = 6). The corresponding correlation coefficient for 133Xe clearance was r = 0.97 (0.92-0.98), the correlation coefficient between the ethanol outflow/inflow ratio and 133Xe clearance being r = -0.92 (-0.89 to -0.94). 4. Dialysate glucose concentration, although affected by blood flow, was not always significantly correlated with blood flow changes (r = 0.70; 0.51-0.95). 5. It may be concluded that the ethanol technique provides a valid measure of changes in local skeletal muscle blood flow. The data furthermore show that a linear increase in thigh skeletal muscle blood flow exists during the studied protocol of intermittent isometric contractions.

The clinical need for bedside myocardial perfusion studies is obvious in the present era of revascularization. Animal and first clinical studies suggest that microbubbles can be used as intravascular tracers of perfusion in conjunction with echocardiography as an imaging modality. In order to fully appreciate the potential and limitations of this approach, the complex interactions of microbubbles within an acoustic field need to be elucidated. Most importantly, there is a strong dependence of bubble effects on the acoustic pressure. At low pressures, linear backscatter yields low signal intensities; at medium range of pressures, bubble resonance causes the reflection of nonlinear signals with harmonic frequencies; and at high pressures, spontaneous acoustic emission with high signal intensity occurs as a final signal of the bubble in its process of disintegration. Thus, in order to allow sufficient replenishment of bubbles to the imaging plane, triggered imaging should be used with one frame every second to eighth cardiac cycle. Traditional gray scale echocardiography was not successful as an imaging modality because of the similarity of gray shades between the myocardium and the contrast effect. Subsequently, second harmonic imaging was developed and was fairly successful in contrast detection, although inherent problems persisted due to the overlap of fundamental and harmonic frequencies in the filtered signals. Harmonic power Doppler imaging turned out as the most sensitive acquisition method, however, with an early dropout at medium range attenuation. In theory, the new technique of pulse inversion may be most promising as this bubble specific imaging modality should combine high sensitivity of detection with great tolerance for attenuation effects in humans. First in vitro studies have confirmed its superiority over harmonic power Doppler in combination with stabilized microbubbles such as SonoVuetrade mark. Thus, we will have to accomplish a lot more work and comparative studies in humans before myocardial contrast echocardiography can emerge as a reproducible technique for evaluating myocardial perfusion with high diagnostic accuracy.

IntroductionInflammation is an important risk-associated component of many diseases and can be diagnosed by molecular imaging of specific molecules. The aim of this study was to evaluate the possibility of targeting adhesion molecules on inflammation-activated endothelial cells and macrophages using an innovative multimodal polyvinyl alcohol-based microbubble (MB) contrast agent developed for diagnostic use in ultrasound, magnetic resonance, and nuclear imaging.MethodsWe assessed the binding efficiency of antibody-conjugated multimodal contrast to inflamed murine or human endothelial cells (ECs), and to peritoneal macrophages isolated from rats with peritonitis, utilizing the fluorescence characteristics of the MBs. Single-photon emission tomography (SPECT) was used to illustrate 99mTc-labeled MB targeting and distribution in an experimental in vivo model of inflammation.ResultsFlow cytometry and confocal microscopy showed that binding of antibody-targeted MBs to the adhesion molecules ICAM-1, VCAM-1, or E-selectin, expressed on cytokine-stimulated ECs, was up to sixfold higher for human and 12-fold higher for mouse ECs, compared with that of non-targeted MBs. Under flow conditions, both VCAM-1- and E-selectin-targeted MBs adhered more firmly to stimulated human ECs than to untreated cells, while VCAM-1-targeted MBs adhered best to stimulated murine ECs. SPECT imaging showed an approximate doubling of signal intensity from the abdomen of rats with peritonitis, compared with healthy controls, after injection of anti-ICAM-1-MBs.ConclusionsThis novel multilayer contrast agent can specifically target adhesion molecules expressed as a result of inflammatory stimuli in vitro, and has potential for use in disease-specific multimodal diagnostics in vivo using antibodies against targets of interest.Electronic supplementary materialThe online version of this article (doi:10.1007/s12195-018-00562-z) contains supplementary material, which is available to authorized users.

(-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [11C]norepinephrine indicates that enantiomerically pure (-)-[11C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium.