Size and environment: The effect of phonon localization on micro-Brillouin imaging.

Specifically designed samples have been analyzed to test the ability of Brillouin spectroscopy to provide reliable mechanical characterization of micro and nano-objects. The selected samples are polymeric films, whose transversal sizes from hundreds of nano- to some micro-meters cover the entire range of length-scales relevant in Brillouin scattering process. The experimental data highlight how, the size of the extended collective oscillation (acoustic phonons, in brief) is the lowest spatial resolution reachable in Brillouin mechanical characterization. Conversely, in the limit condition of phonon confinement, the technique provides the mechanical properties of nano-objects whose characteristic size is comparable with the phonon wavelength (⁓300 nm). Investigating acoustically heterogeneous materials, both size of heterogeneity and acoustic mismatch between adjacent regions are shown to be relevant in shaping the Brillouin response. In particular, a transition from a confined to a non-confined condition is obtained modulating the acoustic mismatch between the micro-objects and their local environment. The provided results and the derived analytic models for the data analysis will guide the interpretation of Brillouin spectra acquired in complex nano-structured samples such as cells, tissues or biomimetic materials. Our analysis can therefore generate new insights to tackle fundamental problems in mechanobiology or to characterize new bioengineered materials.

Large-Area SiPM Pixels (LASiPs): A cost-effective solution towards compact large SPECT cameras.

Single Photon Emission Computed Tomography (SPECT) scanners based on photomultiplier tubes (PMTs) are still largely employed in the clinical environment. A standard camera for full-body SPECT employs ~50-100 PMTs of 4-8 cm diameter and is shielded by a thick layer of lead, becoming a heavy and bulky system that can weight a few hundred kilograms. The volume, weight and cost of a camera can be significantly reduced if the PMTs are replaced by silicon photomultipliers (SiPMs). The main obstacle to use SiPMs in full-body SPECT is the limited size of their sensitive area. A few thousand channels would be needed to fill a camera if using the largest commercially-available SiPMs of 6 × 6 mm2. As a solution, we propose to use Large-Area SiPM Pixels (LASiPs), built by summing individual currents of several SiPMs into a single output. We developed a LASiP prototype that has a sensitive area 8 times larger than a 6 × 6 mm2 SiPM. We built a proof-of-concept micro-camera consisting of a 40 × 40 × 8 mm3 NaI(Tl) crystal coupled to 4 LASiPs. We evaluated its performance in a central region of 15×15 mm2, where we were able to reconstruct images of a 99mTc capillary with an intrinsic spatial resolution of ~2 mm and an energy resolution of ~11.6% at 140 keV. We used these measurements to validate Geant4 simulations of the system. This can be extended to simulate a larger camera with more and larger pixels, which could be used to optimize the implementation of LASiPs in large SPECT cameras. We provide some guidelines towards this implementation.

High-performance computing and networking as tools for accurate emission computed tomography reconstruction.

It is well known that the quantitative potential of emission computed tomography (ECT) relies on the ability to compensate for resolution, attenuation and scatter effects. Reconstruction algorithms which are able to take these effects into account are highly demanding in terms of computing resources. The reported work aimed to investigate the use of a parallel high-performance computing platform for ECT reconstruction taking into account an accurate model of the acquisition of single-photon emission tomographic (SPET) data. An iterative algorithm with an accurate model of the variable system response was ported on the MIMD (Multiple Instruction Multiple Data) parallel architecture of a 64-node Cray T3D massively parallel computer. The system was organized to make it easily accessible even from low-cost PC-based workstations through standard TCP/IP networking. A complete brain study of 30 (64x64) slices could be reconstructed from a set of 90 (64x64) projections with ten iterations of the conjugate gradients algorithm in 9 s, corresponding to an actual speed-up factor of 135. This work demonstrated the possibility of exploiting remote high-performance computing and networking resources from hospital sites by means of low-cost workstations using standard communication protocols without particular problems for routine use. The achievable speed-up factors allow the assessment of the clinical benefit of advanced reconstruction techniques which require a heavy computational burden for the compensation effects such as variable spatial resolution, scatter and attenuation. The possibility of using the same software on the same hardware platform with data acquired in different laboratories with various kinds of SPET instrumentation is appealing for software quality control and for the evaluation of the clinical impact of the reconstruction methods.

World Wide Web interface for advanced SPECT reconstruction algorithms implemented on a remote massively parallel computer.

Data from Single Photon Emission Computed Tomography (SPECT) studies are blurred by inevitable physical phenomena occurring during data acquisition. These errors may be compensated by means of reconstruction algorithms which take into account accurate physical models of the data acquisition procedure. Unfortunately, this approach involves high memory requirements as well as a high computational burden which cannot be afforded by the computer systems of SPECT acquisition devices. In this work the possibility of accessing High Performance Computing and Networking (HPCN) resources through a World Wide Web interface for the advanced reconstruction of SPECT data in a clinical environment was investigated. An iterative algorithm with an accurate model of the variable system response was ported on the Multiple Instruction Multiple Data (MIMD) parallel architecture of a Cray T3D massively parallel computer. The system was accessible even from low cost PC-based workstations through standard TCP/IP networking. A speedup factor of 148 was predicted by the benchmarks run on the Cray T3D. A complete brain study of 30 (64 x 64) slices was reconstructed from a set of 90 (64 x 64) projections with ten iterations of the conjugate gradients algorithm in 9 s which corresponds to an actual speed-up factor of 135. The technique was extended to a more accurate 3D modeling of the system response for a true 3D reconstruction of SPECT data; the reconstruction time of the same data set with this more accurate model was 5 min. This work demonstrates the possibility of exploiting remote HPCN resources from hospital sites by means of low cost workstations using standard communication protocols and an user-friendly WWW interface without particular problems for routine use.

Serum biochemical markers of bone turnover in healthy infants and children.

Serum osteocalcin (OC), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D [1,25(OH)2D] were measured in 241 normal infants and children (134 males and 107 females aged 1.9 months-14 years, 1.8 months-12 years, respectively). Regarding the analysis of data for children above 2 yrs, we chose data with the following normalization: data/body surface x standard body surface, to eliminate biological variations not exclusively related to chronological age. The increase in serum OC occurred at the expected age of growth spurts in both sexes: in the first year of life OC values (mean +/- SD) were 82.6 +/- 34.3 and 60.2 +/- 32.9 OC ng/ml in males and females, respectively; during puberty, peak values occurred at the age of 10-12 yrs in girls (76.6 +/- 25.8) and at the age of 12-14 yrs in boys (113 +/- 48.3). Furthermore, significant positive correlations with age were found for males from 2 to 14 yrs (p < 0.00001) and for females from 2 to 12 yrs (p < 0.001). Elevated levels of BAP occurred in the first year, 70.4 +/- 28.2 and 71.8 +/- 28.5, and in the second year, 69.4 +/- 26.7 and 67.4 +/- 33.8 ng/ml, for males and females, respectively. For children older than 2 yrs, a positive correlation with age (p < 0.01) was found for females only, with a peak value of 67.2 +/- 13.9 at the age of 10-12 yrs. For ages 2-14 yrs the reference values (mean +/- 2SD) were 15.5 - 90.3 and 17.2 - 95.2 ng/ml for males and females, respectively. The highest PICP levels (1354 +/- 680 ng/ml in males and 1041 +/- 766 in females) were observed in infants less than 1 year of age, decreasing by about 60% at the age of 2. There was no significant change in serum PICP for children older than 2 yrs with values covering a range (mean +/- 2SD) of 52 - 544 and 18 - 546 ng/ml in males and females, respectively. Similarly, the highest ICTP values were seen in infants younger than 1 year (29.7 +/- 11.7 and 29.5 +/- 20.1 ng/ml in males and females, respectively). In the ages from 2 to 14 yrs there did not seem to be any systematic age-correlated changes, with values covering a range (mean +/- 2SD) of 6.06 - 24.5 in boys and 6.84 - 22.9 ng/ml in girls. Serum PTH concentrations (mean +/- SD) in infancy were 27.2 +/- 19.3 pg/ml for males and 25.8 +/- 10.8 for females. Normal ranges (mean +/- 2SD) in the older group were 5.77 - 53.1 and 6.71 - 57.3 pg/ml for males and females, respectively. Serum 1,25(OH)2D presented values of 47.3 +/- 28.1 and 38.7 +/- 18.2 pg/ml under 2 yrs for males and females, respectively. The ranges (mean +/- 2SD) in children above 2 yrs were 9.5 - 101 pg/ml in boys and 10.9 - 88.4 in girls. The results of this study contribute to the establishment of reference values in normal children for these biochemical assays; these reference values are needed when the above biological markers will be applied in the monitoring of metabolic bone diseases.

Quantitation of brain perfusion with 99mTc-bicisate and single SPECT scan: comparison with microsphere measurements.

This study describes and validates in a preliminary manner a method to measure the steady-state influx constant (Ki) of 99mTc-bicisate with one single photon emission computed tomography (SPECT) scan. The method is based on the analysis of the arterial concentration of the radioactivity. The results of this quantitation procedure were compared with regional CBF (rCBF) measurements made using 99mTc-microspheres (MI). Two quantitative indexes of perfusion, fractional brain uptake (FBU) and normalized (with cerebellum) brain uptake (NBU), were also evaluated. Two SPECT studies were performed on seven cardiovascular patients who had no signs of neurological disease. In the first of these, 99mTc-bicisate was used, while in the other, which was performed 2 days later, MI were injected into the left heart ventricle. The values of the FBU, NBU, and Ki of 99mTc-bicisate were calculated in several gray and white matter brain regions of interest (ROIs) and compared with the rCBF values measured with MI in coupled ROIs. Mean FBU values were 0.00008 +/- 0.00002 and 0.00004 +/- 0.00001 in the gray and the white matter, respectively. Mean NBU values were 0.99 +/- 0.04 and 0.54 +/- 0.05, mean Ki values were 0.36 +/- 0.06 and 0.19 +/- 0.03 ml g-1 min-1 and mean rCBF values were 0.51 +/- 0.04 and 0.27 +/- 0.04 ml g-1 min-1 in gray and white matter, respectively. Analysis of variance of the regression gave different F values for the regressions with rCBF of FBU (F = 19, n = 126), NBU (F = 289, n = 112), and Ki (F = 117, n = 126).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term ambulatory enterogastric reflux monitoring. Validation of a new fiberoptic technique.

A new technique for the long-term ambulatory detection of enterogastric and nonacid gastroesophageal reflux has been conceived, developed, and validated. It is based on the use of a fiberoptic sensor that utilizes the optical properties of bile. In vitro studies have shown good precision, good stability, sensitivity of 2.5 mumol/liter bilirubin concentration, as well as a useful working range of 2.5-100 mumol/liter bilirubin concentration. In vivo studies have been performed in 29 subjects. Simultaneous gastric aspirations have allowed a comparison of fiberoptic system measurements both with spectrophotometric analysis and bile acid concentrations of corresponding gastric juice samples. Linear correlations were shown between fiberoptic assessment and both spectrophotometric and bile acid concentration findings (P < 0.01). Simultaneous assessment of reflux with the fiberoptic system and cholescintigraphy has shown a 92.9% concordance as regards the presence or absence of reflux. Present results imply that the fiberoptic system is an important tool for the understanding of the clinical relevance of enterogastric and nonacid gastroesophageal reflux.

Change in glucose metabolism after long-term treatment with deflazacort and betamethasone.

We have compared the long-term effects of different corticosteroids on glucose metabolism by carrying out a 75 g oral glucose tolerance test in 27 subjects before and after the administration of deflazacort or betamethasone for two months in random balanced sequence. Fasting plasma glucose and insulin concentrations were significantly higher after betamethasone, whereas deflazacort increased only fasting plasma insulin. After oral glucose there were significant increases in blood glucose and insulin after betamethasone compared with deflazacort. These results suggest that the degree of glucose intolerance and insulin resistance depends on the steroid used and on the dose given, although long-term treatment with deflazacort has a smaller effect on glucose metabolism than betamethasone.

Marine biosurfactants, I. Screening for biosurfactants among crude oil degrading marine microorganisms from the North Sea.

Three bacterial strains of marine origin were isolated during a screening for biosurfactants among n-alkane degrading microorganisms. One strain-identified as Alcaligenes sp. MM1-produced a novel glucose lipid. In the case of Arthrobacter sp. EK 1 the well-known trehalose tetraester was found as major component. From another pure culture classified as Arthrobacter sp. SI 1, extracellular emulsifying agents with properties indicating high molecular weight substances were detected. Furthermore trehalose corynomycolates were found at up to 2 g/l. The isolated biosurfactants showed good interfacial and emulsifying properties.

Marine biosurfactants, II. Production and characterization of an anionic trehalose tetraester from the marine bacterium Arthrobacter sp. EK 1.

Within a screening for biosurfactants we could isolate various n-alkanes utilizing marine bacteria which were capable of synthesizing glycolipids. One strain was identified as Arthrobacter sp. EK 1 which produced trehalose lipids. After purification by column and thick layer chromatography the main fraction, an anionic 2,3,4,2'-trehalose tetraester, was obtained. The chain lengths of fatty acids ranged from 8 up to 14, furthermore succinate could be detected. Since the place of substitution of succinate has so far not been cited in literature, a definitive structural elucidation was carried out chemically by hydroboration and by 1H, 2D1H, 13C and 13C-1H correlation NMR measurements. All investigations confirmed the exact position of succinate at C 2 atom of trehalose. After improvement of growth conditions the production of the trehalose tetraester increased up to 4.8 milligrams during a fermentation in 20 l bioreactor under nitrogen limitation.

Physiological reactions during brush saw operation.

An experimental study of the physiological effects of brush saw operation was performed on eight professional agricultural workers. The experiments were carried out in the field under practical working conditions. Aesthesiometric thresholds (two-point discrimination and depth sense perception), manipulative dexterity, pinch grip force and fingertip skin temperature (FST) were measured before and after exposure to different combinations of static load (handle holding), noise and vibration by using new production brush saws for 5 to 15 min. The changes in the peripheral circulatory, sensorineural and muscular functions of the brush saw workers were not found to be significantly different under the various exposure conditions. Static load accounted for the major part of the changes in aesthesiometric thresholds, pinch grip force and FST after brush saw operation. With respect to baseline measurements, no significant difference in manipulative skill was observed after each exposure period. The weighted vibration accelerations from the right and left handles of a brush saw were 3.13 and 1.80 m/s2, respectively. The assessment of brush saw vibration exposure according to ISO 5349 and the results of FST measurements were consistent with the findings of some epidemiological surveys indicating a low risk of vibration-induced white finger among brush sawyers. This investigation pointed out that the increase in the aesthesiometric thresholds was mainly determined by handle holding, and that the reduction in gripping force during actual work was related to the duration of brush saw operation. Therefore, prolonged static overload on the nerves, muscles and joints of the hand-arm system could explain the increased risk of musculoskeletal and sensorineural disorders found among brush saw users.

A brain phantom for studying contrast recovery in emission computerized tomography.

A brain phantom is described that is characterized by a high anatomical definition and by the possibility of varying the internal contrast with the use of a single radioactive solution. The experimental work was done with a single-photon emission computerized tomographic (SPET) rotating camera. The phantom was used to study the contrast recovery of both the filtered back-projection and an iterative reconstruction algorithm. Moreover, it was also used to find a cross-calibration factor between activity concentrations in the SPET slices and an external reference.

Compensation of spatial system response in SPECT with conjugate gradient reconstruction technique.

A procedure for the determination of the system matrix in single photon emission tomography (SPECT) is described which uses the conjugate gradient reconstruction technique in order to take into account the variable system resolution of a camera equipped with parallel-hole collimators. The procedure involves the acquisition of the system line spread functions (LSF) in the region occupied by the object to be studied. Those data are used to generate a set of weighting factors based on the assumption that the LSFs of the collimated camera are of Gaussian shape with the full width at half maximum (FWHM) linearly dependent on the source depth in the span of image space. The factors are stored on a disc file for subsequent use in the reconstruction process. Afterwards the reconstruction is performed using the conjugate gradient method with the system matrix modified by the incorporation of these precalculated factors in order to take into account the variable geometrical system response. The set of weighting factors is regenerated whenever the acquisition conditions are changed (collimator, radius of rotation). In the case of an ultra high resolution (UHR) collimator 2000 weighting factors need to be calculated. The modification of the system matrix for the geometrical response allows the number of iterations to increase, considerably improving image definition without the appearance of noise artifacts. Moreover, phantom studies show that the number of iterations is less critical because of improved stability in the convergence to the solution. For brain studies of patients 10-15 iterations are usually performed. Studies with a single line source give a value between 7 and 8 mm for the FWHM of the point spread function (PSF) when the conjugate gradient method with modified system matrix is used on data acquired with a UHR collimator, whereas without the modification of the system matrix the result is 9 mm FWHM, if filtered backprojection (FBP) is used with the same filter as in the clinical studies the result is 15 mm FWHM. The results of this work show that proper definition of the system matrix using conjugate gradients influences the quality of the reconstruction remarkably. Nevertheless, further work has to be done in order to assess to what extent the system matrix is ill-conditioned and, eventually, to define a suitable regularization technique.