Laser Spectroscopy of Neutron-Rich

The mean-square charge radii of ^{207,208}Hg (Z=80, N=127, 128) have been studied for the first time and those of ^{202,203,206}Hg (N=122, 123, 126) remeasured by the application of in-source resonance-ionization laser spectroscopy at ISOLDE (CERN). The characteristic kink in the charge radii at the N=126 neutron shell closure has been revealed, providing the first information on its behavior below the Z=82 proton shell closure. A theoretical analysis has been performed within relativistic Hartree-Bogoliubov and nonrelativistic Hartree-Fock-Bogoliubov approaches, considering both the new mercury results and existing lead data. Contrary to previous interpretations, it is demonstrated that both the kink at N=126 and the odd-even staggering (OES) in its vicinity can be described predominately at the mean-field level and that pairing does not need to play a crucial role in their origin. A new OES mechanism is suggested, related to the staggering in the occupation of the different neutron orbitals in odd- and even-A nuclei, facilitated by particle-vibration coupling for odd-A nuclei.

Antimagnetic rotation band in nuclei: a microscopic description.

Covariant density functional theory and the tilted axis cranking method are used to investigate antimagnetic rotation (AMR) in nuclei for the first time in a fully self-consistent and microscopic way. The experimental spectrum as well as the B(E2) values of the recently observed AMR band in (105)Cd are reproduced very well. This gives a further strong hint that AMR is realized in specific bands in nuclei.

Isospin character of the pygmy dipole resonance in 124Sn.

The pygmy dipole resonance has been studied in the proton-magic nucleus 124Sn with the (α, α'γ) coincidence method at Eα=136 MeV. The comparison with results of photon-scattering experiments reveals a splitting into two components with different structure: one group of states which is excited in (α, α'γ) as well as in (γ, γ') reactions and a group of states at higher energies which is only excited in (γ, γ') reactions. Calculations with the self-consistent relativistic quasiparticle time-blocking approximation and the quasiparticle phonon model are in qualitative agreement with the experimental results and predict a low-lying isoscalar component dominated by neutron-skin oscillations and a higher-lying more isovector component on the tail of the giant dipole resonance.

Cerebral perfusion and cerebrovascular reactivity are reduced in white matter hyperintensities.

BACKGROUND AND PURPOSE: There is growing evidence that white matter hyperintensities (WMH) should not be considered as benign age-dependent changes on MR images but indicate pathological changes with clinical consequences. Previous studies comparing subjects with WMH to normal controls have reported global reductions in cerebral blood flow (CBF) and cerebral vascular reactivity. In this study, we examined localized hemodynamic status to compare WMH to normal appearing white matter (NAWM). METHODS: A group of 21 normal 85-year-old subjects were studied using dynamic contrast-enhanced MRI together with administration of acetazolamide. From a combination of anatomic images with different signal weighting, regions of interest were generated corresponding to gray and white matter and WMH. Localized measurements of CBF and cerebral blood volume (CBV) and mean transit time were obtained directly within WMH and NAWM. RESULTS: When comparing WMH to NAWM, measurements showed significantly lower CBF (P=0.004) and longer mean transit time (P< 0.001) in WMH but no significant difference in CBV (P=0.846). The increases in CBF and CBV induced by acetazolamide were significantly smaller in WMH than in NAWM (P=0.026, P<0.001). CONCLUSION: These results show that a change in the hemodynamic status is present within the WMH, making these areas more likely to be exposed to transient ischemia inducing myelin rarefaction. In the future, MRI may be used to examine the effect of therapeutic strategies designed to prevent or normalize vascular changes.

Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: I. Theory, error analysis, and stereologic comparison.

Limited spatial resolution of positron emission tomography (PET) can cause significant underestimation in the observed regional radioactivity concentration (so-called partial volume effect or PVE) resulting in systematic errors in estimating quantitative physiologic parameters. The authors have formulated four mathematical models that describe the dynamic behavior of a freely diffusible tracer (H215O) in a region of interest (ROI) incorporating estimates of regional tissue flow that are independent of PVE. The current study was intended to evaluate the feasibility of these models and to establish a methodology to accurately quantify regional cerebral blood flow (CBF) corrected for PVE in cortical gray matter regions. Five monkeys were studied with PET after IV H2(15)O two times (n = 3) or three times (n = 2) in a row. Two ROIs were drawn on structural magnetic resonance imaging (MRI) scans and projected onto the PET images in which regional CBF values and the water perfusable tissue fraction for the cortical gray matter tissue (hence the volume of gray matter) were estimated. After the PET study, the animals were killed and stereologic analysis was performed to assess the gray matter mass in the corresponding ROIs. Reproducibility of the estimated parameters and sensitivity to various error sources were also evaluated. All models tested in the current study yielded PVE-corrected regional CBF values (approximately 0.8 mL x min(-1) x g(-1) for models with a term for gray matter tissue and 0.5 mL x min(-1) x g(-1) for models with a term for a mixture of gray matter and white matter tissues). These values were greater than those obtained from ROIs tracing the gray matter cortex using conventional H2(15)O autoradiography (approximately 0.40 mL x min(-1) x g(-1)). Among the four models, configurations that included two parallel tissue compartments demonstrated better results with regards to the agreement of tissue time-activity curve and the Akaike's Information Criteria. Error sensitivity analysis suggested the model that fits three parameters of the gray matter CBF, the gray matter fraction, and the white matter fraction with fixed white matter CBF as the most reliable and suitable for estimating the gray matter CBF. Reproducibility with this model was 11% for estimating the gray matter CBF. The volume of gray matter tissue can also be estimated using this model and was significantly correlated with the results from the stereologic analysis. However, values were significantly smaller compared with those measured by stereologic analysis by 40%, which can not be explained by the methodologic errors. In conclusion, the partial volume correction was essential in quantitation of regional CBF. The method presented in this article provided the PVE-corrected regional CBF in the cortical gray matter tissue. This study also suggests that further studies are required before using MRI derived anatomic information for PVE correction in PET.

Immunoelectron microscopic demonstration of thyroglobulin and thyroid hormones in rat thyroid gland.

We have developed a post-embedding immunogold technique for electron microscopic localization and quantitation of thyroglobulin (TG), thyroxine (T4), and triiodothyronine (T3) in rat thyroid. Labeling for TG was located on rough endoplasmic reticulum, Golgi apparatus, exocytotic vesicles, luminal colloid, colloid droplets, and lysosomes, whereas labeling for thyroid hormones was located on luminal colloid, colloid droplets, and lysosomes. We tested different procedures of fixation, dehydration, embedding, polymerization, and immunoincubation to optimize ultrastructural preservation and immunolabeling. Fixation with glutaraldehyde and osmium was possible with retained antigenicity. Dehydration temperature and the choice of embedding resin were the two crucial factors for good immunolabeling. Low-temperature dehydration greatly improved immunolabeling and could be combined with embedding in the methacrylate LR White or the epoxide Agar 100 (equivalent of Epon 812) polymerized at 40-60 degrees C, as the temperature during subsequent embedding and polymerization was of little importance for the immunoreactivity. Labeling on LR White sections was always higher than on Agar 100 sections. Various etching procedures were tested without improved specific labeling. Etching with hydrochloric acid gave nonspecific labeling of certain cell compartments.

In vivo measurements of relaxation process in the human liver by MRI. The role of respiratory gating/triggering.

In vivo estimation of relaxation processes in the liver by magnetic resonance imaging (MRI) may be helpful for characterization of various pathological conditions in the liver. However, such measurements may be significantly hampered by movement of the liver with the respiration. The effect of synchronization of data acquisition to the respiratory cycle on measured T1- and T2-relaxation curves was studied in normal subjects, patients with diffuse liver disease, and patients with focal liver pathology. Multi spin echo sequences with five different repetition times were used. The measurements were carried out with and without respiratory gating/triggering. In the healthy subjects as well as in the patients with diffuse liver diseases respiratory synchronization did not alter the obtained relaxation curves. However, in the patients with focal pathology the relaxation curves were significantly different, when respiratory synchronization was employed. The results indicate that respiratory synchronization is only necessary for estimation of relaxation processes in the liver with focal pathology.

A software program for exchanging MR data.

In an MR multicenter project, data exchange is a problem because most MR scanners do not use the same data format or have data export facilities. In the COMAC-BME Concerted Action on Tissue Characterization by MRS and MRI, a subgroup of seven MR centers had a need for data exchange in the form of digital MR images of the human brain. Because there was no common data format, software package was developed for data exchange. This article describes the basic features of the developed software. The software package was written in the language of C and was successfully tested on an IBM-6150 UNIX workstation. The software is currently being tested on the following series of UNIX workstations: SUN SPARC, IBM RS6000, and HP 9000/700.

Quantification of gadolinium-DTPA concentrations for different inversion times using an IR-turbo flash pulse sequence: a study on optimizing multislice perfusion imaging.

The purpose of this study was to optimize an inversion-recovery (IR) turbo fast low-angle shot (FLASH) for multislice imaging by evaluating the accuracy of calculated the relaxation-rate (R1) for different inversion times (TI). This is important for tracer kinetic modeling because it requires a system responding linearly to input. R1 are linearly related to changes in the concentration of gadolinium (Gd)-diethylenetriaminepentaacetic acid (DTPA), and R1 is a parameter that can be derived from the magnetic resonance (MR) signal. The accuracy of calculated R1 using an IR turbo fast low-angle shot was evaluated in phantoms and for increasing TIs using spectroscopically measured R1 values as reference. Signal curves, obtained in vivo after a bolus injection of Gd-DTPA, were used in an analytical computer program to study the effect of different TI-values on accurate calculation of R1. Results show that TIeff should be <200 ms to measure the bolus-passage of Gd-DTPA in blood accurately, whereas the myocardial response can be measured correctly for TIeff < 870 ms at 1.5 T. The initial slope of the myocardial signal enhancement curve becomes steeper for larger TI values, whereas the calculated R1 curves were similar, indicating that these curves, rather than signal curves, are more suitable even for qualitative perfusion evaluation. It is concluded that the results can be incorporated in a multislice IR turbo fast low-angle shot using the first slice (with a short TI) for assessment of both the arterial input function and the tissue response and the second slice in another position for assessment of the tissue response alone.

MR-visible water content in human brain: a proton MRS study.

In vivo measurement of metabolite concentrations in the human brain by means of proton-MRS contributes significantly to the clinical evaluation of patients with diseases of the brain. The fully relaxed water signal has been proposed as an internal standard for calibration of the MRS measurements. The major drawbacks are the necessity to make the assumptions that the water concentrations in the brain and that all tissue water is MR-visible. A number of in vivo measurements were carried out to estimate the concentration of MR-visible water in the brain of healthy volunteers divided into four age groups: newborn (0-23 days), adolescents (10-15 yr), adults (22-28 yr), and elderly people (60-74 yr). The examinations were carried out using a Siemens Helicon SP 63/84 MR-scanner operating at 1.5 T. Except for the newborn, four regions were studied in each subject using stimulated echo (STEAM) sequences without water suppression. In vitro measurements on a standard phantom were used for calibration. The calculated water concentrations ranged between 35.8 and 39.6 (mean 36.9) mol.[kg wet weight]-1 in the three groups, whereas it was 51.5 mol.[kg wet weight]-1 in the newborn, p < .01. The observed water concentration of neither the four regions nor of the three oldest age groups were significantly different. Comparisons between the water concentrations measured and those expected based on estimation of the content of grey and white matter in the region of interest from T1-weighted images and biochemical data published, suggest that only a small fraction (< 5%) of the tissue water may be MR-invisible.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo measurements of proton relaxation times in human brain, liver, and skeletal muscle: a multicenter MRI study.

Quantitative magnetic resonance imaging may offer unique potential for tissue characterization in vivo. In this connection texture analysis of quantitative MR images may be of special importance. Because evaluation of texture analysis needs large data material, multicenter approaches become mandatory. Within the frame of BME Concerted Action on Tissue Characterization by MRI and MRS, a pilot multicenter study was launched in order to evaluate the technical problems including comparability of relaxation time measurements carried out in the individual sites. Human brain, skeletal muscle, and liver were used as models. A total of 218 healthy volunteers were studied. Fifteen MRI scanners with field strength ranging from 0.08 T to 1.5 T were induced. Measurement accuracy was tested on the Eurospin relaxation time test object (TO5) and the obtained calibration curve was used for correction of the in vivo data. The results established that, by following a standardized procedure, comparable quantitative measurements can be obtained in vivo from a number of MR sites. The overall variation coefficient in vivo was in the same order of magnitude as ex vivo relaxometry. Thus, it is possible to carry out international multicenter studies on quantitative imaging, provided that quality control with respect to measurement accuracy and calibration of the MR equipments are performed.

In vivo field dependence of proton relaxation times in human brain, liver and skeletal muscle: a multicenter study.

T1 and T2 relaxation times are fundamental parameters for signal contrast behaviour in MRI. A number of ex vivo relaxometry studies have dealt with the magnetic field dispersion of T1. By means of multicenter study within the frame of the COMAC BME Concerted Action on Tissue Characterization by MRI and MRS, the in vivo field dispersion of T1 and T2 has been measured in order to evaluate whether ex vivo data are representative for the in vivo situation. Brain, skeletal muscle, and liver of healthy human volunteers were studied. Fifteen MR units with a field strength ranging from 0.08 T to 1.5 T took part in the trial, which comprised 218 volunteers. All the MR systems were tested for measurement accuracy using the Eurospin TO5 test object. The measured relaxation data were subsequently corrected according to the obtained calibration curves. The results showed a clear field dispersion of T1, whereas no significant variations were seen for T2. Our in vivo data were generally in reasonable agreement with proposed models based on ex vivo measurements.

Multicentre magnetic resonance texture analysis trial using reticulated foam test objects.

Texture analysis in magnetic resonance imaging has the ability to provide useful diagnostic information with respect to the discrimination of disease states of a single tissue or the separation of different tissues. However, for widespread use it is necessary to determine how texture measurements carried out in one center relate to those carried out in another. To this end, a multicentre trial has been performed where reticulated foam test objects have been scanned in six European centers according to a fixed protocol. It has been concluded that texture measurements are not transportable between centers. Principal component models calculated from the texture parameters collected in one center do not fit the data collected in another. Further trials are to investigate whether the reticulated foam test objects may be used to normalize tissue texture data collected in different centers.

Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain.

We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20-35 years) determined using the internal water standard method were (mean+/-SD): [NAA]=10.0+/-3.4 mM (n=53), [tCho]=1.9+/-1.0 mM (n=51), [Cr + PCr]=6.5+/-3.7 mM (n=51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy.

Volumetric analysis of the normal infant brain and in intrauterine growth retardation.

Twenty-eight infants with postmenstrual ages (PMA) in the range of 32-80 weeks were investigated. Twenty were newborn; among these the observed birth weight divided by the expected weight ranged from 0.31 to 1.1. Axial magnetic resonance images were recorded with a triple spin-echo sequence and the volumes were determined by encircling each structure of interest on every slice. Segmentation into grey matter, white matter and CSF was done by semi-automatic discriminant analysis. Growth charts for the cerebrum, cerebellum, corpora striata, thalami, ventricles, and grey and white matter are provided for infants with appropriate birth weight. The striatal (P = 0.02) and thalamic (P < 0.001) percentage of the hemispheric volume decreased with age, whereas the ratio of grey matter to white matter (G/W-ratio) increased (P = 0.01). In the neonatal patients, brain volumes were independently associated with both PMA and the degree of growth retardation. It was calculated that the hemispheric volume was reduced by from 16% to 23% if the total bodyweight was reduced by 40%. The G/W-ratio was found to be independently associated with the PMA (P < 0.05) and the degree of IUGR (P < 0.1) suggesting that fetal growth retardation reduces grey matter volume more than white matter.

Validation of a method for the determination of zolpidem in human plasma using LC with fluorescence detection.

A sensitive and selective high-performance liquid chromatography (HPLC) method was developed for the determination of zolpidem in human plasma. Zolpidem and the internal standard (trazodone) were extracted from human plasma that had been made basic. The basic sample was loaded onto a conditioned Bond Elut C18 cartridge, rinsed with water and eluted with methanol. Forty microliters were then injected onto the LC system. Separation was achieved on a C18 column (150 x 4.6 mm, 5 microm) with a mobile phase composed of acetonitrile:50 mM potassium phosphate monobasic at pH 6.0 (4:6, v/v). Detection was by fluorescence, with excitation at 254 nm and emission at 400 nm. The retention times of zolpidem and internal standard were approximately 4.7 and 5.3 min, respectively. The LC run time was 8 min. The assay was linear in concentration range 1-400 ng/ml for zolpidem in human plasma. The analysis of quality control samples for zolpidem (3, 30, and 300 ng/ml) demonstrated excellent precision with relative standard deviations (RSD) of 3.7, 4.6, and 3.0%, respectively (n = 18). The method was accurate with all intraday (n = 6) and overall (n = 18) mean concentrations within 5.8% from nominal at all quality control sample concentrations. This method was also performed using a Gilson Aspec XL automated sample processor and autoinjector. The samples were manually fortified with internal standard and made basic. The aspec then performed the solid phase extraction and made injections of the samples onto the LC system. Using the automated procedure for analysis, quality control samples for zolpidem (3, 30, and 300 ng/ml) demonstrated acceptable precision with RSD values of 9.0, 4.9, and 5.1%, respectively (n = 12). The method was accurate with all intracurve (n = 4) and overall (n = 12) mean values being less than 10.8% from nominal at all quality control sample concentrations.

Validation of a method for the determination of (R)-warfarin and (S)-warfarin in human plasma using LC with UV detection.

A sensitive and selective chiral high-performance liquid chromatography (HPLC) method was developed for the determination of (R)-warfarin and (S)-warfarin in human plasma. (R)- and (S)-warfarin and the internal standard (oxybenzone) were extracted from human plasma that had been made acidic with 1 N sulfuric acid into ethyl ether. The ethyl ether layer was removed and evaporated, and the residue was reconstituted in 200 microl of acetonitrile. A 50-microl aliquot was injected onto the HPLC system. Separation was achieved on a beta-cyclodextrin column (250 x 4.6 mm, 5 microm) with a mobile phase composed of acetonitrile:glacial acetic acid:triethylamine (1000:3:2.5, v/v/v). Detection was by ultraviolet absorbance at 320 nm. Late-eluting peaks were diverted from the analytical column by using a beta-cyclodextrin precolumn (50 x 4.6 mm, 5 microm) and a column switching device. The retention times of (R)- and (S)-warfarin and the internal standard were approximately 7.7, 6.9 and 4.0 min, respectively. The run time was 15 min. The assay was linear in concentration ranges of 12.5-2500 ng/ml for (R)- and (S)-warfarin in human plasma. The analysis of quality control samples for (R)- and (S)-warfarin (25.0, 400 and 2000 ng/ml) demonstrated excellent precision with relative standard deviations (R.S.D.) for (R)-warfarin of 10.9, 2.8, and 2.8%, respectively (n = 18), and for (S)-warfarin of 7.0, 2.4 and 2.6%, respectively (n = 18). The method was accurate with all overall (n = 18) mean concentrations being less than 6.0% from nominal at all quality control sample concentrations.

Development and validation of a sensitive and robust LC-tandem MS method for the analysis of warfarin enantiomers in human plasma.

A liquid chromatography-tandem mass spectrometry method (LC-MS-MS) was developed and validated for measuring warfarin (WAR) enantiomers (R-WAR and S-WAR) in human EDTA plasma. Liquid-liquid extraction using ethyl ether was used to extract the analytes from the plasma. Baseline resolution of S- and R-WAR as well as the internal standard enantiomers (S- and R-p-ClWAR, S-IS and R-IS) was achieved on a beta-cyclodextrin column with a mobile phase of acetonitrile-acetic acid-triethylamine (1000:3:2.5, v/v/v). The retention times are 6.9, 8.0, 7.0, and 7.9 min for S-WAR, R-WAR, S-IS and R-IS, respectively. The detection was by monitoring S- and R-WAR at m/z 307-->161 and S- and R-IS at m/z 341-->161 using (-) ESI. The standard curve range was 1-100 ng ml(-1) for both S- and R-WAR. The inter-day precision and accuracy of the quality control (QC) samples were <7.3% relative standard deviation (RSD) and <7.3% bias for S-WAR, and <6.5% RSD and <5.8% bias for R-WAR, respectively. Analyte stability during sample processing and storage were established. Method ruggedness was demonstrated by the reproducible performance from analysis of clinical samples.

Osteosarcoma in association with total hip replacement.

The occurrence of an osteosarcoma at the site of a cobalt-chrome total hip replacement is described, and the possibility of the tumour arising as a result of the liberation of cobalt particles is discussed. The experimental and clinical evidence relating tumour formation to the presence of particulate metals, and to the presence of solid and particulate polyethylene, is presented. It is considered that the risk of tumour formation at the site of any total hip replacement is very small.

Osteolytic changes in the upper femoral shaft following porous-coated hip replacement.

Ten uncemented total hip replacements were performed in 1975 using an implant in which the cobalt-chrome femoral stem was coated to give a porous surface. In all but one case a high-density polyethylene head was used. The radiological changes in the upper femoral shafts were assessed between three and nine years later. Seven showed extensive stress-relieving changes, loss of calcar, stress fractures at the root of the lesser trochanter with subsequent detachment, and osteoporosis followed by avulsion of the greater trochanter. In these seven patients the lower part of the stem appeared to be soundly embedded, although in only one was there evidence of bony incorporation. It is suggested that if the fixation of a fully coated implant of this sort remains sound, gross atrophy of the upper femoral shaft develops after five years. This atrophy, associated with an implant which can be removed only at the expense of further bone destruction, presents substantial problems if revision is needed.