ESR dosimetry using inorganic materials: a case study of Li2CO3 and CaSO4:Dy as prospective dosimeters.

The CO2- radical ion, detected by ESR technique in bones and teeth enamel, was proved to be invaluable in high level and retrospective dosimetry. In these matrices, impurity carbonate (at phosphate sites) was the precursor to CO2-. With a view to investigate the possibility of using inorganic materials such as lithium carbonate as ESR dosimeters, studies were carried out on gamma-irradiated Li2CO3. The intensity of radiation-induced ESR signals of Li2CO3 at g = 2.0036 (CO3-) and g = 2.0006 (CO2-) was followed as a function of gamma dose in the low dose range of 1-1350 Gy. It was observed that the intensity of the ESR signal at g = 2.0036 (CO3-) was in a linear relation with the radiation dose in the dose range 10-800 Gy and the signal at g = 2.0006 (CO2-) showed linear response in the dose range 5-800 Gy. The lowest dose that could be detected in the present studies using the signal of CO2- in Li2CO3 powder samples (approximately 50 mg) is 3.2 Gy. ESR studies were also carried out on the widely used TL dosimetric material CaSO4:Dy and in pure CaSO4 after gamma irradiation. The TL materials were used in powder as well as pellet forms. The linearity of ESR response with dose for powder and pellet forms of CaSO4: Dy was also studied using the signals at g = 2.0030 (SO3-) and at g = 2.0139 (SO4-). It was observed that the range of linearity of dose response extended between 20 and 1200 Gy, for SO3- signals. The results of dosimetric study indicate that the ESR-Li2CO3 system could be used in dosimetric applications in radiotherapy. However, for the actual applications further advancement is needed to lower the detection limit. The TL phosphor, CaSO4:Dy in powder and pellet forms, could be used as ESR dosimeter in the dose range 20-600 Gy.     

K-band ESR spectra of calcite stalagmites from southeast and south Brazil.

Samples of calcite stalagmites from Caverna Santana (Sao Paulo State) and Caverna Botuvera (Santa Catarina State), southeastern and southern Brazil, respectively, were studied by electron spin resonance (ESR). The more common microwave frequency (X-Band, 9.5 GHz) as well as higher frequency K-band, 24 GHz were employed for the determination of the age of the samples. Even after extensive signal averaging, the dosimetric signal is not very well defined in the X-band (9.5 GHz). Using the K-band spectrometer it was possible to clearly identify the 6 hyperfine lines of Mn2+ and other paramagnetic centers in the g=2 region: SO2- and CO2- radicals. The use of high microwave frequency gives better S/N and spectral resolution making the identification of the dosimetric signal easier. The total dose (TD) or equivalent dose (ED) deposited in the samples was 2.3+/-0.3 Gy and 1.7+/-0.4 Gy for Caverna Botuvera samples and 2.6+/-0.7 Gy for the sample of Caverna Santana, giving an age of 2.9+/-0.7 ky, 2.1+/-0.8 ky and 3+/-1 ky, respectively. These first results are compatible with U/Th analysis. Due to the low S/N precision, measurements were possible only with the use of secondary standard composed on Mn2+ lines, naturally present in this sample.     

NMR and ESR study of liposome delivery of Mn2+ to murine liver

The mechanism of tissue relaxation of liposome-delivered Mn2+ as a contrast agent for magnetic resonance imaging (MRI) was examined using magnetic resonance and electron spin resonance (ESR) techniques. It is known that liposomes of the size and composition used in this study are taken up by fixed liver macrophages (Kupffer cells). It was determined that Mn2+ must be released from the liposomes in order to affect the water proton relaxation rate in the liver. As long as the Mn2+ was confined to the Kupffer cells, no substantial changes in the relaxation of the majority of the liver water were observed. Unlike other contrast agents delivered to the Kupffer cells (for example, Gd-starch microspheres or magnetite), once the Mn2+ is delivered and released into the Kupffer cells, it can diffuse from the Kupffer cells and be rapidly taken up by the hepatocytes. This seems to be the mechanism for selective relaxation enhancement in the liver. A consequence of this behavior is that the time at which maximum contrast enhancement occurs for MRI can be varied by the choice of liposome phospholipid composition. ESR techniques were used to directly determine the state of Mn2+ and the integrity of liposomes in various stages of processing.     

Evaluation of polyaza macrocyclic methylene phosphonate chelates of Gd3+ ions as MRI contrast agents

Gd(DTPA)2- (diethylenetriaminepentaacetic acid) and the polyaza macrocyclic Gd(DOTA)- (1,4,7,10-tetraazacyclododecane-N,N',N',N') are paradigms of general purpose paramagnetic complexes useful for enhancing contrast in magnetic resonance imaging (MRI). It is of both fundamental and practical interest to determine how one might modify the chemical structure of these chelate complexes to improve their utility for MRI in specific circumstances. In the present work, we investigated polyaza methylene phosphonate complexes of Gd3+ ions to compare their NMRD profiles with those of their carboxylate analogs and with Gd(DTPA)2-. We find that the number q of exchangeable water molecules coordinated directly to the Gd3+ ions tends to be smaller in the phosphonates, in principle reducing their utility in MRI. However, these phosphonates have a tendency to oligomerize, and the resulting decrease in rotational mobility of the paramagnetic oligomers increases their relaxivity at higher fields, offsetting the effect of decreases in q. In particular, Gd(DOTRP)3- (1,5,9-triazacyclododecane-N,N',N',-tris(methylenephosphonic++ + acid] would be an increasingly effective contrast agent above approximately 10 MHz if the oligomerization was stable in vivo (and the Gd3+ ions were sufficiently well bound). At lower fields, the relaxivity of these small chelate complexes is dominated by tau S0, the relaxation time of the spin moments of the paramagnetic ions. We find this to be favorably long for complexes of Gd3+ with the macrocyclic phosphonate ligands, as was found earlier by us for Gd(DOTA)-. This situation, ostensibly related to the relatively high symmetry and rigidity of the macrocyclic complexes, can increase the low-field relaxivity of the phosphonates almost a factor of 2 beyond that of Gd(DTPA)2-.     

Magnetic field dependence of solvent proton relaxation rates induced by Gd3+ and Mn2+ complexes of various polyaza macrocyclic ligands: implications for NMR imaging

The magnetic field dependence of the solvent water proton longitudinal relaxation rate 1/T1 (the NMRD profile) has been measured for solutions of chelates of Gd3+ and Mn2+ ions with two different polyaza macrocyclic ligands: 1,4,7-triazacyclononane-N,N',N",-triacetic acid (NOTA) and 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA). Studies were carried out mainly near physiological pH, but the pH dependence was also examined in some cases. The results are compared with published data for complexes of Gd3+ and Mn2+ ions with ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA). Competition experiments for the NOTA and DOTA chelates with EDTA and DTPA were also performed. It is found that, over the field range in which NMR imaging is currently being done, different symmetries of otherwise similar chemical ligands can alter 1/T1 of solvent protons by factors of up to three. The ligand environment can influence the relaxation times of the electronic spin moments of the ions, as well as their coordination number, thereby changing both the inner and outer sphere contributions to the relaxivities of the complexes. The relevance of these results to questions of efficiency and toxicity of these chelates as agents for enhancement of contrast in NMR images is discussed.     

Nuclear magnetic relaxation dispersion profiles of aqueous solutions of a series of Gd(NOTA) analogs.

Nuclear magnetic relaxation dispersion (NMRD) profiles and ESR linewidths have been measured for a series of neutral Gd(3+)-triazamacrocyclic complexes and compared with previous data for the simplest member of the macrocyclic triaza series, Gd(NOTA), and for the widely studied linear triaza complex, Gd(DTPA)2-. Water proton relaxivities and their temperature dependence were found to vary widely with the size of the triaza macrocycle and the identity of the side-chain chelating groups. The number of rapidly exchanging water molecules directly coordinated to the Gd3+ ion (q) was found to vary from 2 to 4 for eight of the ten complexes examined and a linear relationship between the 50-MHz relaxivity value and integral values of q is presented for this series of complexes. tau s values derived from ESR linewidths for some of the complexes are in reasonable agreement with those derived from their NMRD profiles; however, those complexes which either tended to form aggregates in solution or gave evidence for multiple averaged solution structures showed broad, near Lorentzian linewidths which were clearly not dominated by the electron spin relaxation time (tau s).     

Stability constants for Gd3+ binding to model DTPA-conjugates and DTPA-proteins: implications for their use as magnetic resonance contrast agents

Five DTPA-amide and ester derivatives have been synthesized and their Gd3+ stability constants have been measured using a simple spectrophotometric method. These results are compared to stability constants measured for Gd3+ binding to two different DTPA-conjugated proteins. Although the thermodynamic constants for Gd3+ binding to DTPA-monopropylamide and DTPA-monopropylester relative to Gd(DTPA)2- decrease by log K = 2.6 and 3.4, respectively, the blood pH conditional constants differ from Gd(DTPA)2- only by log K = 1.2 and 1.9, respectively. The corresponding dipropylamide and ester conjugates of DTPA show considerably lower thermodynamic and conditional constants. This has important implications in the covalent attachment of chelates to macromolecules for use in magnetic resonance imaging. The measured binding constants for Gd(DTPA)-IgG and Gd(DTPA)-BSA suggest that many of the DTPA molecules in these systems, prepared under our experimental conditions, are disconjugated. The model compound results indicate that it is important to use methods in attaching DTPA to macromolecules which preclude dionjugation of the chelate. Otherwise, their affinity for Gd3+ and consequently their usefulness as MRI contrast agents may be severely compromised.     

LiSr4(BO3)3:Ce3+ phosphor as a new material for ESR dosimetry

LiSr₄(BO₃)₃:0.01Ce³⁺ phosphor was investigated to assess its potential as a material for measurements of radiotherapeutic doses with electron spin resonance (ESR). The ESR spectrum of the phosphor irradiated with ⁶⁰Co features five ESR signals. An isochronal annealing experiment has shown that the strongest of these signals is associated with the same trap center as the 473 K peak on the TL glow curve of this material. The dose–response is linear in the studied range from 0.89 to 90.30 Gy. Fading of the signal was also investigated.     

Contrast material-enhanced visualization of the ablation medium for magnetic resonance-monitored ethanol injection therapy: imaging and safety aspects

PURPOSE: This study was performed to test whether the dissociation rate of free Gd3+ ions from gadoterate meglumine is significantly increased when the contrast agent is dissolved in ethanol and whether the magnetic resonance (MR) signal of gadolinium/ethanol solutions is enhanced to a degree that promises reliable detection during MR imaging-guided intralesional administration, such as for the treatment of low-flow venous malformations. MATERIALS AND METHODS: The apparent gadoterate meglumine-induced enhancement of the longitudinal proton relaxation rate of sterile ethanol/water solutions, stored at a temperature of 24 degrees C +/- 5 degrees C in the dark, was monitored for 2 weeks. The content of dissociated Gd3+ ions was determined after 6 and 8.5 months of storage. The signal difference between contrast agent/ethanol solutions and muscle tissue was assessed with imaging at 0.5 T and 1.5 T. RESULTS: Commercialized gadoterate meglumine diluted with 94% ethanol was not shown to have released toxic Gd3+ during storage times that exceed its physiologic circulation and excretion times after intravenous injection by a factor of more than 100. A maximum dissociation rate of 0.05% per month was estimated from the detection limit of the analysis. The apparent molar relaxivity of the contrast agent in the mixtures varied by less than 0.1 L/mmol per second with no temporal trend. Gradient-echo ethanol/muscle contrast increased with Gd concentrations to maximums of 15 mmol/L (at 0.5 T) and 25 mmol/L (at 1.5 T). CONCLUSIONS: Neither limited solubility nor release of Gd3+ ions could be identified as a general safety hazard associated with the application of gadoterate meglumine/ethanol solutions at Gd concentrations of 0.5-25 mmol/L, and such ablation mixtures could be efficiently and reliably visualized.     

Gamma dose response of synthetic A-type carbonated apatite in comparison with the response of tooth enamel.

Synthetic A-type carbonated apatite samples were irradiated at room temperature with 60Co gamma rays. Their ESR spectra consist of the lines of CO2- and CO3- radicals of orthorhombic and axial symmetry. The measurements carried out immediately after sample irradiation showed that CO2- species are produced by decomposition of CO3- radicals. Intensity of the CO2- lines in the synthetic and enamel samples increases during the first 400 and 200 h after irradiation, respectively. The dependence of the EPR signal on the dose varies with carbonate content of the sample. The dose response curve for tooth enamel is steeper for the synthetic material.     

稀土元素La、Gd和Ce对培养大鼠细胞生物学效应的研究

目的 在细胞水平上研究稀土元素（REE）La,Gd和Ce对培养大鼠细胞的生物学作用及机。方法 采用同位素示踪、质子激发X荧光分析（PIXE）结合生化及细胞学等技术观察La对细胞的生物学作用,La,Gd及Ce的亚细胞分布及Gd,Ce对细胞钙含量及钙内流的影响。结果 La^3 在10^－10（或10^-9)-10^-6mol/L时促进细胞蛋白质合成、线粒体琥珀酸脱氢酶活性增加、DNA合成以及S期细胞比率增加,但La^2 在高剂量时（10^-4-10^-3mol/L)降低平滑肌细胞总蛋白质含量、抑制线粒体琥珀酸脱氢酶酸活性以及S期细胞比率减少。通过PIXE发现La,Gd,Ce可进入细胞,且在核内含量最高,其次为胞膜。Gd和Ce使细胞内钙含量增加,促进细胞钙内流。结论（1）La^3 对细胞有明显剂量－效应关系,在10^-10(或10^-19)-10^-6mol/L剂量范围内有促进细胞增殖作用。在10^-4-10^-3mol/L时有细胞毒性作用。（2）REE可进入细胞,且在核内富集。（3）REE可促进细胞外钙进入细胞。     

Manganese-enhanced MRI of the optic visual pathway and optic nerve injury in adult rats

PURPOSE: To evaluate manganese (Mn2+)-enhanced MRI in a longitudinal study of normal and injured rat visual projections. MATERIALS AND METHODS: MRI was performed 24 hours after unilateral intravitreal injection of MnCl2 (150 nmol) into adult Fischer rats that were divided into four groups: 1) controls (N = 5), 2) dose-response (N = 10, 0.2-200 nmol), 3) time-response with repeated MRI during 24-168 hours post injection (N = 4), and 4) optic nerve crush (ONC) immediately preceding the MnCl2 injection (N = 7). Control and ONC animals were reinjected with MnCl2 20 days after the first injection, and MRI was performed 24 hours later. RESULTS: In the control group, the optic projection was visualized from the retina to the superior colliculus, with indications of transsynaptic transport to the cortex. There was a semilogarithmic relationship between the Mn2+ dose and Mn2+ enhancement from 4 to 200 nmol, and the enhancement decayed gradually to 0 by 168 hours. No Mn2+-enhanced signal was detected distal to the ON crush site. In the control group, similar enhancement was obtained after the first and second MnCl2 injections, while in the ONC group the enhancement proximal to the crush site was reduced 20 days post lesion (20 dpl). CONCLUSION: Mn2+-enhanced MRI is a viable method for temporospatial visualization of normal and injured ON in the adult rat. The observed reduction in the Mn2+ signal proximal to the ONC is probably a result of retrograde damage to the retinal ganglion cells, and not of Mn2+ toxicity.     

Separate visualization of endolymphatic space,perilymphatic space and bone by a single pulse sequence; 3D-inversion recovery imaging utilizing real reconstruction after intratympanic Gd-DTPA administration at 3 Tesla

Twenty-four hours after intratympanic administration of gadolinium contrast material (Gd), the Gd was distributed mainly in the perilymphatic space. Three-dimensional FLAIR can differentiate endolymphatic space from perilymphatic space, but not from surrounding bone. The purpose of this study was to evaluate whether 3D inversion-recovery turbo spin echo (3D-IR TSE) with real reconstruction could separate the signals of perilymphatic space (positive value), endolymphatic space (negative value) and bone (near zero) by setting the inversion time between the null point of Gd-containing perilymph fluid and that of the endolymph fluid without Gd. Thirteen patients with clinically suspected endolymphatic hydrops underwent intratympanic Gd injection and were scanned at 3 T. A 3D FLAIR and 3D-IR TSE with real reconstruction were obtained. In all patients, low signal of endolymphatic space in the labyrinth on 3D FLAIR was observed in the anatomically appropriate position, and it showed negative signal on 3D-IR TSE. The low signal area of surrounding bone on 3D FLAIR showed near zero signal on 3D-IR TSE. Gd-containing perilymphatic space showed high signal on 3D-IR TSE. In conclusion, by optimizing the inversion time, endolymphatic space, perilymphatic space and surrounding bone can be separately visualized on a single image using a 3D-IR TSE with real reconstruction.     

Longitudinal proton relaxation rates in rabbit tissues after intravenous injection of free and chelated Mn2+

The factors that determine the field-dependent increase in 1/T1 of tissue water protons were investigated for MnCl2 and Mn2+ (PDTA) (1,3-propylenediamine-N,N',N',N'-tetraacetic acid) introduced intravenously into rabbits. Mn2+ was used in preference to other paramagnetic ions in part because of the distinct NMRD profiles (magnetic field dependence of 1/T1) of free Mn2+ ions, their small chelate complexes, and their macromolecular conjugates, and in part because the relatively low toxicity of Mn2+ is favorable for animal studies. Tissue content of Mn2+ was determined in all samples by inductively coupled plasma analyses the state of Mn2+ in excised tissues was determined from the form of the 1/T1 NMRD profile of water protons; and distribution of contrast agent within tissue and access of water on a T1 time scale were determined by double-exponential analyses of proton relaxation behavior in intact doped tissue, as well as by the change of single-exponential relaxation rates and proton signal intensity upon gentle disruption of the tissue. MnCl2 is found in all tissues, except fat and skeletal muscle, but liver is most avid at low dose, and Mn2+ accumulates in spleen after high doses. Chelation targets Mn2+ to liver and kidney, saturating the liver chemically at relatively low dose. We suggest that pronounced increase in tissue relaxivity results from irrotationally bound Mn2+, ostensibly associated with the polar head groups of cell membranes. Compartmentalization of contrast agent and restricted diffusion of tissue water influences the maximum relaxation rates attainable, so that there is an optimal dose of these contrast agents which is rather low.     

Are the Local Blood Oxygen Level–Dependent (BOLD) Signals Caused by Neural Stimulation Response Dependent on Global BOLD Signals Induced by Hypercapnia in the Functional MR Imaging Experiment? Experiments of Long-Duration Hypercapnia and Multilevel Carbon Dioxide Concentration

BACKGROUND AND PURPOSE: The relationship between the local blood oxygen level-dependent (BOLD) signals caused by neural stimulation (fBOLD) and the global BOLD signals induced by hypercapnia (hBOLD) has not been fully investigated. In this study, we examine whether fBOLD is modulated by hBOLD signals, by means of experiments using a relatively wide range of inhaled carbon dioxide (CO(2)) for a long duration of 5 minutes. MATERIALS AND METHODS: Ten healthy volunteers were recruited, each undergoing 6 separate experiments by inhaling gas mixtures with different fractions of CO(2) (room air, 3%-7%). Each experiment contained 3 phases, prehypercapnic, hypercapnic, and posthypercapnic, during which boxcar visual stimulus was given. The local fBOLD signals were measured from areas showing activation patterns highly correlated with the visual stimulus paradigm, whereas the global hBOLD signals were measured from areas showing no visual activations. Percentage changes in fBOLD during transient-state hypercapnia and steady-state hypercapnia were both investigated in response to varying degrees of hypercapnic perturbations. RESULTS: The hBOLD signals increased with increase of inhaled CO(2) fractions. The duration for the hBOLD signals to reach steady state prolonged with increase of inhaled CO(2) fractions. Normalized fBOLD ratio was inversely related to the inhaled CO(2) during steady-state hypercapnia but showed positive association with hBOLD during transient-state hypercapnia. CONCLUSION: Our study concludes that the steady-state fBOLD signal intensity is dependent on and inversely related to the hBOLD signals. Previous reports documenting independent and additive relationships between hBOLD and fBOLD may likely be due to transient-state observations.     

Behaviour of alanine dosimeters in an ozone environment

Polymer-alanine dosimeters (PADs) have been irradiated, in air with a concentration of 5 ppm of ozone, with doses up to 10 kGy, by means of a ⁹⁰Sr source. The electron spin resonance (ESR) signals were compared with the signals obtained after irradiations in normal air, and the amplitude reduction was found to be negligible. The evolution of the ESR signal of PADs irradiated in normal air and thereafter stored in air with 5 ppm ozone concentration was also investigated. No change was observed over a period of 2 months.     

Comparison of gamma- and UV-light-induced EPR spectra of enamel from deciduous molar teeth.

From previous work, it is known that CO2- radicals in tooth enamel are induced by gamma as well as by UV-light exposure. The parameters of the EPR signal of the CO2- radical were found to be independent of the source of exposure. However, it would be desirable for retrospective dosimetry to identify other characteristic features of the EPR spectrum of tooth enamel, which would allow differentiation between the two sources of exposure. In the present work, enamel of deciduous molars was exposed to gamma-radiation from a 60Co-source and 254 nm UV-light from a low-pressure mercury lamp. The resulting EPR spectra were deconvoluted, and the native spectrum simulated from spectra of the CO2- radical, and two further EPR lines. Both EPR signals of the native spectrum were located at g=2.0046, but were different in line shape and width. One was a 1 mT wide isotropic signal of Gaussian line shape while the other was a 0.7 mT wide axial signal of Lorentzian line shape. A comparable study of the amplitudes of the native and CO2- signals was done before and after gamma- and UV-light exposure. While the native signals were found to be only slightly sensitive to gamma-radiation, their amplitude increased significantly on UV-light exposure. Feasibilities are discussed to distinguish different radiation sources by exposure-induced alterations of the native EPR spectrum.     

Nitrogen dioxide (NO2) created by gamma-rays in Antarctic ice and rime ice.

Antarctic ice and rime ice after gamma-irradiation at 77 K were studied by electron spin resonance (ESR). The signal of nitrogen dioxide (NO2) was detected in both ices. The NO2 in the Antarctic ice, in particular, may be created from NO3- by reactions associated with intrinsic OH radicals. The detection limit of NO2 in solid samples was estimated to be approximately 0.02 ppm with ESR. The analysis using ESR in natural ice has a potential to trace environmental NO2.     

Number of inner-sphere water molecules in Gd3+ and Eu3+ complexes of DTPA-amide and -ester conjugates

The inner-sphere water coordination number for Eu3+ and Gd3+ complexed with five DTPA analogs, in which one or two terminal carboxylate groups are functionalized as propyl amides or propyl esters, have been studied using phosphorescence lifetime and nuclear magnetic relaxation dispersion (NMRD) measurements. Both methods show that the water coordination number does not increase above that observed for the analogous DTPA complexes. The phosphorescence lifetime results indicate that all five Eu3+ complexes have one inner-sphere water molecule at 25 degrees C. The NMRD profiles for three of the Gd3+ complexes at 25 degrees C are also consistent with one inner-sphere water molecule, whereas two complexes have profiles consistent only with a mixture of complexes, 50% containing a single water molecule and 50% with none. Lowering the temperature alters the population of these species such that all five Gd3+ complexes have significantly less bound water on average at 5 degrees C. These results explain the anomalous temperature dependencies of the NMRD curves reported previously for the Gd(DTPA)-protein conjugates. We suggest that the Gd(DTPA)-conjugate systems have a fluxional coordination sphere whereby the amount of inner-sphere coordinated water varies from near zero at 5 degrees C to a high of two near 37 degrees C.