Diagnostic performance of MRI and histology in assessment of deep lipomatous tumours.

BACKGROUND: Deep lipomatous tumours can be benign lipomas or intermediate/locally recurring atypical lipomatous tumours (ALTs). Differentiating between these two entities clinically and radiologically is difficult. The aims of this study were to report a series of deep lipomatous tumours, comparing the clinical, radiological and pathological features of ALTs and lipomas; and to predict the likelihood of a lipomatous tumour being ALT based on anatomical site and MRI characteristics. METHODS: This was a retrospective review of patients with deep lipomatous tumours presenting over 6 years to a tertiary sarcoma centre, with preoperative MRI, and preoperative or postoperative histology including MDM2 gene analysis. Sensitivity, specificity, predictive values and accuracy in diagnosing ALT were calculated for MRI and histopathological features. RESULTS: Some 248 patients were included; 81 (32·7 per cent) had a final diagnosis of ALT. ALTs were larger than lipomas (median 19 versus 10 cm; P < 0·001); there was no ALT smaller than 5 cm. A tumour presenting in the lower limb was more likely to be an ALT than a lesion at any other site (48·4 versus 13·5 per cent; P < 0·001). In patients with lipomatous tumours at sites other than the lower limbs, MRI had a negative predictive value of 95 per cent for excluding ALT. CONCLUSION: Despite concern, most deep lipomatous tumours (nearly 70 per cent) are benign lipomas. Certain features imply that tumours are almost never ALT: smaller than 5 cm or located outside the lower limb with no suspicious characteristics on MRI. Tumours with these features might safely and confidently be managed outside tertiary sarcoma centres.

ANTECEDENTES: Los tumores lipomatosos profundos pueden ser lipomas benignos o tumores lipomatosos atípicos (atypical lipomatous tumour, ALT) con potencial de recidiva local/intermedia. Diferenciar estas dos entidades desde el punto de vista clínico es difícil. Los objetivos de este estudio fueron presentar una gran serie de tumores lipomatosos profundos, comparando las características clínicas, radiológicas y patológicas de los ALT y de los lipomas y predecir la probabilidad de que un tumor lipomatoso sea ALT según su localización anatómica y las características de la RNM. MÉTODOS: Revisión retrospectiva de pacientes con tumores lipomatosos profundos tratados en un centro terciario de sarcoma durante un período de 6 años, en los que se dispusiese de RNM preoperatoria y análisis MDM2 en el preoperatorio o postoperatorio. Se calculó la sensibilidad, la especificidad, el valor predictivo y la precisión diagnóstica de la RNM y de las características histopatológicas para el diagnóstico de ALT. RESULTADOS: Se incluyeron 248 pacientes, de los que en solo 81 (32,7%) se estableció un diagnóstico final de ALT. Los ALT fueron más grandes que los lipomas (19 versus 10 cm, P < 0,001) y no hubo ningún ALT de tamaño menor de 5 cm. Hubo una mayor probabilidad de que un tumor fuera ALT si se presentaba en las extremidades inferiores en comparación con cualquier otra localización (48,4% versus 13,5%, P < 0,001). En pacientes con tumores lipomatosos localizados en otros lugares que no fueran las extremidades inferiores, la RMN tuvo un valor predictivo negativo del 95,5% para excluir la ALT. CONCLUSIÓN: A pesar del recelo tradicional, la mayoría (70%) de los tumores lipomatosos profundos son lipomas benignos. Algunas características, como los tumores de menos de 5 cm y aquellos ubicados fuera de las extremidades inferiores sin características sospechosas por RNM, indican que los tumores casi nunca son ALT. Los tumores con esas características pueden tratarse de manera segura y con solvencia fuera de los centros de sarcomas terciarios. En casos seleccionados, puede ser útil la prueba genética MDM2 en la biopsia.

Modeling the sub-diffraction focusing phenomenon of light propagation through scattering medium.

Optical techniques are assuming greater importance in biomedical applications, however, due to extreme complexity involved in light propagation through scattering medium, it is very challenging to analyze experimentally. Here we report a two-stage simulation technique to simulate phase-conjugated light propagation through scattering medium with macroscopic dimensions. The reported simulation yields accurate information with flexibility to access research parameters. The proposed simulation method is suitable for finite-difference time-domain (FDTD) technique, pseudospectral time-domain (PSTD) technique, and other simulation techniques based upon numerical solutions of Maxwell's equations. We demonstrate modeling phase-conjugated light propagation through a scattering medium. The reported simulation technique is applicable to model the propagation of continuous-wave (CW) light with specific amplitude and phase through a scattering medium of macroscopic dimensions. More importantly, the flexibility of simulation enables analysis of research factors that are challenging to access experimentally.

Modeling of carrier transport in organic light emitting diode with random dopant effects by two-dimensional simulation.

To model the carrier transport in organic light-emitting diodes (OLEDs) with random dopant effects in the emitting layer, two-dimensional simulation was used. By including the Gaussian shape density of states and field-dependent mobility in the Poisson and drift-diffusion solver, the carrier transport, trapping in the dopant state, and radiative recombination were accurately modeled. To examine the model, the current-voltage characteristics of organic light-emitting devices were compared. The host material in the emitting layer was 2,2-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)biphenyl (BImBP), which was doped with bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic) at various concentrations. By including the random doping model, the trend of mobility was altered and the radiative efficiency fitted experimental values well.

Cone-beam x-ray luminescence computed tomography (CB-XLCT) prototype development and performance evaluation.

This study developed a prototype for a rotational cone-beam x-ray luminescence computed tomography (CB-XLCT) system, considering its potential application in pre-clinical theranostic imaging. A geometric calibration method applicable to both imaging chains (XL and CT) was also developed to enhance image quality. The results of systematic performance evaluations were presented to assess the feasibility of commercializing XLCT technology. Monte Carlo GATE simulation was performed to determine the optimal imaging conditions for nanophosphor particles (NPs) irradiated by 70 kV x-rays. We acquired a low-dose transmission x-ray tube and designed a prone positioning platform and a rotating gantry, using mice as targets from commercial small animalµ-CT systems. We then employed the image cross-correlation (ICC) automatic geometric calibration method to calibrate XL and CT images. The performance of the system was evaluated through a series of phantom experiments with a linearity of 0.99, and the contrast-to-noise ratio (CNR) between hydroxyl-apatite (HA) and based epoxy resin is 19.5. The XL images of the CB-XLCT prototype achieved a Dice similarity coefficient (DICE) of 0.149 for a distance of 1 mm between the two light sources. Finally, the final XLCT imaging results were demonstrated using the Letter phantoms with NPs. In summary, the CB-XLCT prototype developed in this study showed the potential to achieve high-quality imaging with acceptable radiation doses for small animals. The performance of CT images was comparable to current commercial machines, while the XL images exhibited promising results in phantom imaging, but further efforts are needed for biomedical applications.

Corneal transparency and scleral opacity arises from the nanoarchitecture of the constituent collagen fibrils.

While human scleral and corneal tissues possess similar structural morphology of long parallel cylindrical collagen fibrils, their optical characteristics are markedly different. Using pseudospectral time-domain (PSTD) simulations of Maxwell's equations, we model light propagation through realistic representations of scleral and corneal nanoarchitecture and analyze the transmittance and spatial correlation in the near field. Our simulation results provide differing predictions for scleral opacity and corneal transparency across the vacuum ultraviolet to the mid-infrared spectral region in agreement with experimental data. The simulations reveal that the differences in optical transparency between these tissues arise through differences in light scattering emanating from the specific nanoscale arrangement and polydispersity of the constituent collagen fibrils.

Virtual and real-world implementation of deep-learning-based image denoising model on projection domain in digital tomosynthesis and cone-beam computed tomography data.

Reducing the radiation dose will cause severe image noise and artifacts, and degradation of image quality will also affect the accuracy of diagnosis. To find a solution, we comprise a 2D and 3D concatenating convolutional encoder-decoder (CCE-3D) and the structural sensitive loss (SSL), via transfer learning (TL) denoising in the projection domain for low-dose computed tomography (LDCT), radiography, and tomosynthesis. The simulation and real-world practicing results show that many of the figures-of-merit (FOMs) increase in both projections (2-3 times) and CT imaging (1.5-2 times). From the PSNR and structural similarity index of measurement (SSIM), the CCE-3D model is effective in denoising but keeps the shape of the structure. Hence, we have developed a denoising model that can be served as a promising tool to be implemented in the next generation of x-ray radiography, tomosynthesis, and LDCT systems.

CT diagnosis of ilioinguinal lymph node metastases in melanoma using radiological characteristics beyond size and asymmetry.

BACKGROUND: Diagnosis of lymph node (LN) metastasis in melanoma with non-invasive methods is challenging. The aim of this study was to evaluate the diagnostic accuracy of six LN characteristics on CT in detecting melanoma-positive ilioinguinal LN metastases, and to determine whether inguinal LN characteristics can predict pelvic LN involvement. METHODS: This was a single-centre retrospective study of patients with melanoma LN metastases at a tertiary cancer centre between 2008 and 2016. Patients who had preoperative contrast-enhanced CT assessment and ilioinguinal LN dissection were included. CT scans containing significant artefacts obscuring the pelvis were excluded. CT scans were reanalysed for six LN characteristics (extracapsular spread (ECS), minimum axis (MA), absence of fatty hilum (FH), asymmetrical cortical nodule (CAN), abnormal contrast enhancement (ACE) and rounded morphology (RM)) and compared with postoperative histopathological findings. RESULTS: A total of 90 patients were included. Median age was 58 (range 23-85) years. Eighty-eight patients (98 per cent) had pathology-positive inguinal disease and, of these, 45 (51 per cent) had concurrent pelvic disease. The most common CT characteristics found in pathology-positive inguinal LNs were MA greater than 10 mm (97 per cent), ACE (80 per cent), ECS (38 per cent) and absence of RM (38 per cent). In multivariable analysis, inguinal LN characteristics on CT indicative of pelvic disease were RM (odds ratio (OR) 3.3, 95 per cent c.i. 1.2 to 8.7) and ECS (OR 4.2, 1.6 to 11.3). Cloquet's node is known to be a poor predictor of pelvic spread. Pelvic LN disease was present in 50 per cent patients, but only 7 per cent had a pathology-positive Cloquet's node. CONCLUSION: Additional CT radiological characteristics, especially ECS and RM, may improve diagnostic accuracy and aid clinical decisions regarding the need for inguinal or ilioinguinal dissection.

PSTD Simulation of optical phase conjugation of light propagating long optical paths.

The phenomenon of Optical Phase Conjugation (OPC) can be rigorously simulated using the pseudospectral time-domain (PSTD) technique. However, with finite computational memory, it is infeasible to simulate light propagating long optical paths. We report a robust OPC simulation technique that can account for long optical path lengths by sequentially inverting the electromagnetic fields. Specifically, the ideal efficiency of OPC refocusing of light through scattering medium can be accurately determined.

Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma.

A prospective study explored the heterogeneous nature of metastatic melanoma using Multiplex immunohistochemistry (IHC) and flow cytometry (FACS). Multiplex IHC data quantitated immune subset number present intra-tumoral (IT) vs the tumor stroma, plus distance of immune subsets from the tumor margin (TM). In addition, mIHC showed a close association between the presence of IT CD8+ T cells and PDL1 expression in melanoma, which was more prevalent on macrophages than on melanoma cells. In contrast, FACS provided more detailed information regarding the T cell subset differentiation, their activation status and expression of immune checkpoint molecules. Interestingly, mIHC detected significantly higher Treg numbers than FACS and showed preferential CD4+ T cell distribution in the tumor stroma. Based on the mIHC and FACS data, we provide a model which defines metastatic melanoma immune context into four categories using the presence or absence of PDL1+ melanoma cells and/or macrophages, and their location within the tumor or on the periphery, combined with the presence or absence of IT CD8+ T cells. This model interprets melanoma immune context as a spectrum of tumor escape from immune control, and provides a snapshot upon which interpretation of checkpoint blockade inhibitor (CBI) therapy responses can be built.

Light extraction efficiency enhancement of flip-chip blue light-emitting diodes by anodic aluminum oxide.

We produced an anodic aluminum oxide (AAO) structure with periodic nanopores on the surface of flip-chip blue light-emitting diodes (FC-BLEDs). The nanopores had diameters ranging from 73 to 85 nm and were separated by distances ranging from approximately 10 to 15 nm. The light extraction efficiency enhancement of the FC-BLEDs subjected to different durations of the second pore-widening process was approximately 1.6-2.9%. The efficiency enhancement may be attributed to the following mechanism: periodic nanopores on the surface of FC-BLEDs reduce the critical angle of total reflection and effective energy transfer from a light emitter into a surface plasmon mode produced by AAO.

2-D PSTD Simulation of optical phase conjugation for turbidity suppression.

Turbidity Suppression via Optical Phase Conjugation (TS-OPC) is an optical phenomenon that uses the back propagation nature of optical phase conjugate light field to undo the effect of tissue scattering. We use the computationally efficient and accurate pseudospectral time-domain (PSTD) simulation method to study this phenomenon; a key adaptation is the volumetric inversion of the optical wavefront E-field as a means for simulating a phase conjugate mirror. We simulate a number of scenarios and demonstrate that TS-OPC deteriorates with increased scattering in the medium, or increased mismatch between the random medium and the phase conjugate wave during reconstruction.

Facilitation of calcium blocking and membrane effects by intrinsic sympathomimetic activity.

The interactions between ICI 118, 587 (Corwin) a beta 1-selective partial adrenergic agonist, and atenolol (Tenormin), propranolol (Inderal) and verapamil were examined first in anaesthetised dogs pretreated with syrosingopine and vagotomised. ICI 118, 587 was administered iv in cumulative doses of 0.1 to 1000 micrograms X kg-1. In four animals, heart rate increased from 102 +/- 4 to 188 +/- 12 beats X min-1 with a KA of 2.5 +/- 0.9 micrograms X kg-1. ICI 118, 587 was then administered to five groups each of four animals pretreated with atenolol (250 micrograms X kg-1 and 500 micrograms X kg-1iv), propranolol (250 micrograms X kg-1 and 500 micrograms X kg-1) or verapamil (200 micrograms X kg-1 plus 5 micrograms X kg-1 X min-1 iv). Both atenolol and propranolol shifted the dose response curve to the right but verapamil did not. Atenolol did not lower the maximal heart rate response to ICI 118,587. Both propranolol and verapamil slowed heart rate significantly (P less than 0.05) after, but not before, ICI 118,587. Further studies were then carried out in vitro. Cat papillary muscles were superfused with physiological saline at pH 7.4 and with either atenolol or ICI 118,587 at 5 X 10(-5) mol X litre-1. Tension was recorded at Lmax over a [Ca2+] range of 0.5 to 8 X 10(-3)mol X litre-1. The pA2 for verapamil against Ca2+ in the presence of atenolol and ICI 118,587 was 5.25 +/- 0.10 and 6.57 +/- 0.22 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

2-D PSTD Simulation of focusing monochromatic light through a macroscopic scattering medium via optical phase conjugation.

By employing the pseudospectral time-domain (PSTD) simulation technique, we analyze the propagation of monochromatic light through a macroscopic scattering medium. Simulation results show that, monochromatic light can be directed through a scattering medium and focus into a narrow peak; a range of wavelengths has been simulated. Furthermore, we compare: i) focusing monochromatic light through a macroscopic scattering medium, and, ii) focusing monochromatic light through vacuum. Based upon numerical solutions of Maxwell's equations, we demonstrate: with a fully-surrounding wavefront of specific amplitude and phase, sub-diffraction focusing can be achieved with monochromatic light, with or without the presence of a scattering medium.

Beta-adrenoceptor stimulant properties of amidoalkylamino-substituted 1-aryl-2-ethanols and 1-(aryloxy)-2-propanols.

Parallel series of 2-[(2-amidoethyl)amino]-1-arylethanols and 1-[(2-amidoethyl)amino]-3-(aryloxy)-2-propanols have been prepared, and the compounds were tested as beta-adrenoceptor stimulants on the heart and circulation of the dog. The corresponding 2-(alkylamino)-1-arylethanols and 3-(alkylamino)-2-propanols have been tested for comparison and the structure-activity relationships (SAR) examined. The arylethanols are potent full agonists, showing selectivity for the heart relative to blood vessels, while the (aryloxy)propanols are even more cardioselective and are partial agonists. Within a narrow series of 1-[(amidoethyl)amino]-3-(4-hydroxyphenoxy)-2-propanols, careful examination of the SAR of the amide group showed that great variation in cardioselectivity and degree of agonism may be produce. From this study ICI 118587, N-[20[[2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethyl]-4-morpholinecarboxamide, was selected for its high cardioselectivity and 50% agonist properties. This compound in under clinical evaluation as a cardiac stimulant.

The cardiovascular effects of ICI 118,587: A beta 1-adrenoceptor partial agonist.

1 In a preparation in which cardiovascular reflexes were prevented from occurring, ICI 118,587 (1-(p-hydroxyphenoxy)-3-beta-(morpholinocarbonamido) ethylamino-2-propranol fumarate) caused dose-dependent positive chronotropic and inotropic effects upon the dog heart. 2 The increase in heart rate brought about by ICI 118,587 was about 43% of the maximum increase produced by isoprenaline. 3 For a given chronotropic effect produced by either ICI 118,587 or isoprenaline, each compound produced a similar inotropic effect as indicated by an increase in LV dp/dtmax. 4 In contrast to the direct stimulant action of ICI 118,587 on the heart no direct effects on vascular smooth muscle were observed. 5 ICI 118,587 was shown to be a competitive antagonist of the chronotropic and vasodilator effects of isoprenaline on the heart and blood vessels and of the chronotropic effects of noradrenaline on the heart. 6 It is concluded that ICI 118,587 is a selective beta 1-adrenoceptor partial agonist.

The effects of three beta-adrenoceptor blocking drugs on isolated preparations of skeletal and cardiac muscle.

1 The effects of propranolol, oxprenolol and practolol on the isometric twitch responses to electrical stimulation of isolated diaphragm muscles from the rat and of isolated papillary muscles from the rabbit are described.2 Depression of the twitch responses of the diaphragm muscle was produced by propranolol (20 mug/ml), by oxprenolol (100 mug/ml) and by practolol (500 mug/ml).3 Depression of the twitch responses of the papillary muscles was produced by propranolol (20 mug/ml) by oxprenolol (100 mug/ml) and by practolol (200 mug/ml).4 No increase of twitch tension was produced by oxprenolol or practolol on either tissue.5 It is concluded that propranolol, oxprenolol and practolol produce negative inotropic actions on isolated cardiac muscle by a mechanism unrelated to blockade of beta-adrenoceptors and which occurs at doses which are well in excess of those doses required to produce beta-blockade.

Interaction between the effects of 5-hydroxytryptamine and adrenaline on the growth of platelet thrombi in the coronary artery of the anaesthetized dog.

1. The interaction between adrenaline and 5-hydroxytryptamine (5-HT) has been quantitated on the rate of thrombus formation, in the stenosed coronary artery with damaged endothelium of the anaesthetized dog. 2. Changes in the plasma concentration of adrenaline were produced by varying the rate of an intravenous infusion of adrenaline and in the effects of 5-HT, by intravenous injections of the selective 5-HT2 receptor antagonist, ICI 170809. 3. Increases in the plasma concentration of adrenaline, which did not cause significant changes in blood pressure and heart rate, increased the rate of thrombus formation. 4. Antagonism of the 5-HT2 receptor by ICI 170809, in the absence of an infusion of adrenaline, abolished thrombus formation (mean ED50 0.41 microgram kg-1, i.v.). 5. The effects of adrenaline were non-competitively antagonized by ICI 170809; maximum effects were obtained in the dose-range 50-200 micrograms kg-1, i.v., when the mean dose-ratio increase in adrenaline required to restore equivalent rates of thrombus formation was 39 fold. 6. These results are consistent with a synergism between adrenaline and 5-HT and emphasize the importance of both on thrombus formation.

Redirection of arachidonic acid metabolism by ICI D1542: effects on thrombus formation in the coronary artery of the anaesthetized dog.

1. The effects of simultaneous redirection of arachidonic acid metabolism, by inhibition of thromboxane A2 (TXA2) synthase and blockade of the platelet thromboxane A2 receptor (TP-receptor), was examined on the rate of thrombus formation in a stenosed coronary artery with damaged endothelium in an anaesthetized dog. 2. Redirection of arachidonic acid metabolism was achieved by intravenous doses of ICI D1542, a selective and potent inhibitor of TXA2 synthase and the TP-receptor. 3. Redirection of arachidonic acid metabolism was demonstrated in whole blood, stimulated ex vivo by collagen. The ED50 for inhibition of TXB2 production was 7.1 micrograms kg-1, i.v.; there were corresponding increases in the production of the eicosanoids prostaglandin D2 (PGD2), PGE2 and PGF2 alpha. 4. Thrombus formation was inhibited by D1542 (ED50 0.55 micrograms kg-1, i.v.), but could be restarted by an intravenous infusion of adrenaline (0.2-38 micrograms kg-1 min-1, i.v.). In the presence of the maximum effective dose of D1542 (1 mg kg-1, i.v.) a 190 fold increase in the infusion rate of adrenaline was required to restore thrombus formation. 5. In the presence of D1542, removal of endoperoxide metabolites by inhibition of cyclo-oxygenase with aspirin (5 mg kg-1, i.v.) caused thrombus formation to restart, indicating the ability of the endoperoxide metabolites to inhibit thrombus formation in vivo. 6. These results indicate that, in the stenosed and damaged coronary artery of the dog, redirection of arachidonic acid metabolism by D1542 is more effective at preventing thrombus formation than inhibition of cyclo-oxygenase by aspirin.

The harmful effects of aqueous contrast agents on the gastrointestinal tract: a study of mechanism and means of counteraction.

The effect of mildly and strongly hypertonic solutions on intestinal tone and motility was tested with aqueous contrast solutions and with mannitol as a control in 15 dogs. These experiments were repeated in animals premedicated with atropine sulfate and/or methysergide maleate. Intestinal motility was recorded on serial x-ray films. Tone and motility were estimated by variations of intestinal caliber and rate of transit of contrast solution, respectively. The results obtained contradict the currently accepted mechanism of action of iodinated contrast media on the intestinal tract, which assumes that the effect is osmotic like that of a saline laxative. Solutions of different osmolarity produce hyperperistalsis of the same magnitude. This effect begins rapidly after the onset of gastric emptying and much sooner than a significant osmotic fluid shift occurs. Atropine sulfate and methysergide maleate (serotonin blocker), when given individually, are incapable of completely inhibiting hyperperistalsis induced by hypertonic solutions. However, when these agents are given in combination, motility is completely inhibited. The evidence supports a serotonin role in the hyperperistalsis induced by hypertonic solutions, partly by direct action of serotonin on the smooth muscle cells and partly by indirect action on the intramural cholinergic ganglion cells. This concept offers a possible means of eliminating one of the adverse effects of aqueous contrast media on the gastrointestinal tract.