Correction of errors caused by imperfect inversion pulses in MR imaging measurement of T1 relaxation times

Spin-lattice (T1) relaxation times were measured by an inversion-recovery magnetic resonance imaging method with a slice-selective inversion pulse (SIP), a non-selective rectangular inversion pulse (RIP), or a B1-insensitive adiabatic inversion pulse (AIP). Data analysis either assumed perfect inversion (two-parameter fit) or allowed for imperfect inversion (three-parameter fit). Imperfect inversion pulses caused low T1 values in phantoms with a two-parameter fit, while three-parameter T1 estimates were accurate over the range 430-2670 ms. A difference of approximately 10% between two-parameter and three-parameter T1 values in normal human brain tissue was attributed to B1 inhomogeneity with the slice-selective inversion pulse and rectangular inversion pulse, to the slice profile with the slice-selective inversion pulse, and to T2 effects for the adiabatic inversion pulse. Any T1 method that relies on accurate flip angles may have a significant systematic error in vivo. Phantom accuracy does not ensure accuracy in vivo, because phantoms may have a more homogeneous B1 field and a longer T2 than do biological samples.     

Further studies on the feasibility of one-day Salmonella detection by enzyme-linked immunosorbent assay

A model system previously developed for the rapid detection of Salmonella typhimurium in foods was improved and extended to many other Salmonella serotypes. The original protocol, which consisted of an overnight nonselective culture followed by a specific enzyme-linked immunosorbent assay (ELISA), was modified and improved. A sandwich ELISA which used polyclonal antibodies for the capture stage and a cocktail of monoclonal antibodies for the detector stage was developed. The assay recognized a wide range of Salmonella serotypes; S. enteritidis, the most important serotype in the United Kingdom had a detection limit in the ELISA of about 4 x 10(2) cells ml-1. The cultural stage prior to the ELISA was either a single nonselective broth (incubated for 28 h) or a preenrichment broth (incubated for 7 h) plus a selective broth (incubated for 21 h). Antibodies which bind to cells grown in the unfavorable conditions of a selective medium were selected. It was concluded that, in the future, the shortened protocols for the detection of Salmonella spp. in foods described here will be of considerable value.     

Changes of relaxation times (T1, T2) and apparent diffusion coefficient after permanent middle cerebral artery occlusion in the rat: temporal evolution, regional extent, and comparison with histology

The quantitative NMR parameters T1, T2, rho, and apparent diffusion coefficient (ADC) were determined during the 7 h after middle cerebral artery occlusion in rats. In the normal caudate-putamen (CP), 869 +/- 145 ms and 72 +/- 2 ms for T1 and for T2, respectively, were found; the corresponding values for cortex were 928 +/- 117 ms and 73 +/- 2 ms. The ADC showed significant dependence on gradient direction: diffusion along x resulted in 534 +/- 53 microns 2/s (CP) and 554 +/- 62 microns 2/s (cortex), and along y in 697 +/- 58 microns 2/s (CP) and 675 +/- 53 microns 2/s (cortex). In the ischemic territory, a continuous increase over time of both relaxation times was observed in the CP, leading to an increase of 29 +/- 20% (T1) and 51 +/- 41% (T2) above control level. ADC dropped to 63 +/- 15% of control in the CP and to 74 +/- 4% of control in the temporal cortex. No significant change was noted in proton density during the observation period. Strongest ADC reduction was in the center of the ischemic territory (< or = 60% of control) surrounded by a region of lesser reduction (< or = 80% of control). During the early part of the study, the area of reduced ADC was larger than that of elevated relaxation times. Toward the end of the experiment, the area of increased relaxation times approached that of decreased ADC at < or = 80% of control. Good agreement of histological presentation of infarct with the total area of decreased ADC (< or = 80%) was demonstrated.     

New pulse sequences for T1- and T1/T2-contrast enhancing in NMR imaging

Improved pulse sequences DIFN (abbreviation of the words: DIFferentiation by N pulses), 90 degrees - tau1 - 180 degrees tau1 - . . . 180 degrees - tau1 with optimised time intervals tau1- for T1 measurement and contrast enhancing in NMR imaging are presented. The pulse sequences DIFN have a better sensitivity to T1 than the well-known pulse sequence SR. In contrast to the IR pulse sequence, the information given by the DIFN pulse sequence is more reliable, because the NMR signal does not change its sign. For a given time interval tau0 < or = (0.1 - 0.3) T(1) the DIFN pulse sequences serve as T1-filters. They pass the signal components with relatively short T1 < T(1) and suppress the components with relatively long T1 < T(1). The effects of the radiofrequency field inhomogeneity and inaccurate adjusting of pulse lengths are also considered. It is also proposed in this work to use the joint T1T2-contrast in NMR imaging obtained as a result of applying the DIFN pulse sequences in combination with the well-known Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence. The region of interest, where the contrast should be especially enhanced, is specified by the two times at which measurements are performed, which allow the amplitudes of pixels to reach some defined levels by spin-lattice and spin-spin relaxation.     

Comparison of conventional single echo and multi-echo sequences with a fast spin-echo sequence for quantitative T2 mapping: application to the prostate

The accuracy of water T2 maps generated from a fast spin-echo (FSE) sequence was compared with data obtained by conventional single and multi-echo spin-echo pulse sequences using a commercial gel phantom. Spatially localized stimulated echo acquisition mode (STEAM) proton spectroscopy was also used to confirm the reported water T2 values of the gels contained in the phantom. The FSE sequence was shown to be superior in accuracy to both the single and multi-echo spin echo sequences and comparable to STEAM, producing results that were within 10% of known values. The effectiveness of the FSE sequence was further demonstrated by generating T2 maps of the normal and diseased prostate in clinically acceptable imaging times, resulting in comparable T2 values to those obtained using STEAM. Accurate quantitative T2 maps can be produced with the FSE sequence.     

Improvements on an in vivo automatic shimming method [FASTERMAP]

Improvements on a localized, automatic shimming method described by Gruetter and Boesch (J. Magn. Reson. 96, 323-334 (1992)) and Gruetter (Magn. Reson. Med. 29, 804-811 (1993)) are presented. A spin-echo sequence employing a double sech refocusing scheme is used to acquire a field map along linear projections that improves the signal-to-noise ratio by at least a factor of two over the stimulated echo sequence previously used. To further improve the reliability of shim adjustments, a variance-weighted polynomial regression analysis is performed. This also extends the scope of application of this technique to global shimming. Localized 1H spectra of human brain shimmed by this method are presented.     

Measurement of magnetic resonance T2 for physiological experiments

The proton transverse relaxation time (T2) of human skeletal muscles has been increasingly used in magnetic resonance imaging experiments to examine muscle physiology and neuromuscular control. However, little attention has been paid to the experimental factors affecting the accuracy or sensitivity of the T2 measurement. We have explored theoretically and experimentally the structure of several magnetic resonance pulse sequences for measuring T2 of the first dorsal interosseous muscle and found that a multiecho imaging technique using non-slice-selective refocusing pulses (MENSS) produces more accurate T2 estimates than multiecho slice-selective (MESS) imaging methods that are commonly used. Using either technique we acquired four 5-mm-thick transverse images of the first dorsal interosseous muscle with a spatial resolution of 0.6 mm within 5 min. The T2 measured by the MENSS method was closer to the true T2 than was the T2 estimated by the MESS method. After a given amount of exercise, the MENSS technique revealed an average 28 +/- 10% increase in T2 compared with a 13 +/- 3% increase measured with an equivalent MESS technique. We conclude that the MENSS method is a more accurate and sensitive procedure for studying neuromuscular physiology compared with the more commonly used MESS method.     

Expansion of transplanted hepatocytes during liver regeneration

A method for volume selective proton spectroscopy is presented based on a multiecho sequence with short refocusing interval tcp. It is demonstrated, that by appropriate choice of tcp on the order of 4-6 ms, signals from overlapping multiplets like the glutamine and glutamate (Glu/Gln) resonances in spectra of the human brain are considerably increased compared with a conventional PRESS volume selection scheme. Thus proton spectra from J-coupled multiplet signals can be acquired with TE on the order of 20-30 ms avoiding the baseline problems arising at shorter echo times due to broad resonances. This allows to selectively acquire spectra from substances with longer T2 without the confounding effects from J-coupling occurring in conventional volume selection techniques.     

Missed lung cancer on chest radiography and computed tomography: imaging and medicolegal issues

The solvent and temperature dependence of the rate constant for spin echo dephasing, 1/Tm, for 0.2 to 1.2 mM glassy solutions of chromyl bis(1-hydroxy-cyclohexanecarboxylic acid), CrO(HCA)-2; aquo vanadyl ion, VO2+ (aq), and vanadyl bis(trifluoroacetylacetonate), VO(tfac)2 were examined. At low temperatures where 1/T1 < 1/Tm, 1/Tm in 1:1 H2O:glycerol is dominated by solvent protons. At low temperature 1/Tm increases in the order 1:1 H2O:glycerol or 9:1 CF3CH2OH:ethyleneglycol (no methyl groups) < 9:1 i-PrOH:MeOH (hindered methyl groups) < 9:1 n-PrOH:MeOH (less hindered methyl groups). This solvent dependence of 1/Tm is similar to that observed for nitroxyl radicals, which indicates that the effect of solvent methyl groups on spin-echo dephasing at low temperature is quite general. At higher temperatures the echo dephasing is dominated by spin-lattice relaxation and is concentration dependent. As the glass softens, echo dephasing is dominated by the onset of molecular tumbling.     

Preferential activation of the complement system in the lower epidermis of patients with pemphigus vulgaris

A technique is described for acquiring phosphocreatine (PCr) images of skeletal muscle using a rapid acquisition with relaxation enhancement (RARE) pulse sequence. All of the phosphorus metabolites other than PCr are forced to dephase within the first few echoes, whereas the Carr-Purcell Meiboom-Gill (CPMG) pulse sequence maintains a high PCr signal long enough to acquire 64 echoes in a single shot. Axial PCr images of a human forearm with a signal-to-noise ratio of 9 were acquired in 2 min. The effect of the refocusing pulse section profile on the ratio of desired to undesired metabolite signal is demonstrated.     

Molecular evidence for multifocal papillary serous carcinoma of the peritoneum in patients with germline BRCA1 mutations

RATIONALE AND OBJECTIVES: The authors have investigated dysprosium [Dy]-DOTA-PAMAM, generation 5 (G = 5) dendrimers as a possible new class of macromolecular T2 contrast agents. The use of DOTA provides a metal complex with greater stability than can be achieved using DTPA as ligand, an important factor in the design of blood pool agents with long half-lives. METHODS: Generation 5 ammonia-core PAMAM dendrimers were linked to the bifunctional ligand p-SCN-Bz-DOTA. After determination of the number of conjugated DOTA molecules by 1H nuclear magnetic resonance, Dy3+ was titrated at a 90% molar ratio. For comparison, single ionic chelates of Dy-DTPA and Dy-DOTA also were prepared. Using a variable field relaxometer, T1 and T2 relaxation times were measured at 13 different field strengths from 0.05 to 1.5 T and temperatures of 3, 10, 20 and 37 degrees C. RESULTS: The synthesis resulted in a preparation with 76 DOTA and 68 Dy3+ ions per dendrimer molecule. The T1 relaxivity values for Dy-DTPA, Dy-DOTA, and the Dy-DOTA-based dendrimer all were independent of field strength, with values between 0.12 and 0.20 mM-1 sec-1. At lower fields (0.05-0.1 T), 1/T2 was identical to 1/T1. At higher fields, however, 1/T2 increased quadratically with field strength, with a strong dependence on temperature. The field-dependent component of 1/T2 was up to three times higher for the Dy-DOTA-based dendrimer compared with the single chelate molecules, with coefficients of 0.37 to 0.03 sec-1/Tesla2 for T = 3 to 37 degrees C. CONCLUSIONS: The results are interpreted with the "inner sphere" theory of susceptibility effects (Curie spin relaxation). The large temperature dependence suggests that the dominant mechanism of relaxation is the contact interaction effect, with the proton residence time as the primary time constant. This largely unexplored relaxation mechanism has the potential to create a new class of T2-selective contrast agents.     

Growth hormone treatment in pediatric burns: a safe therapeutic approach

In the recovery period after strenuous exercise, there is increased O2 uptake, termed the excess postexercise O2 consumption (EPOC). One of the mechanisms suggested to explain EPOC is activation of the triglyceride/fatty acid (TG/FA) cycle by catecholamines. The purpose of this study was to determine the effect of selective beta1- and nonselective beta-adrenoceptor blockade on EPOC and the TG/FA cycle. Seven healthy young men each participated in three control and three exercise experiments in a randomized and balanced sequence. In the exercise experiments, subjects exercised for 90 minutes at 58% +/- 2% (mean +/- SD) of maximal O2 uptake on a cycle ergometer, followed by a 4.5-hour bedrest. The control experiments followed the same protocol, but without exercise. In one control and one exercise experiment, the selective beta1-adrenoceptor antagonist atenolol (0.062 mg.kg(-1) body weight) was administered intravenously immediately after the exercise (EXAT) and at the corresponding time in the rest-control experiment (REAT). In a second set of control and exercise experiments, the nonselective beta-adrenoceptor antagonist propranolol (0.15 mg.kg(-1) body weight) was administered (REPRO and EXPRO). In a third set of rest and exercise experiments, an injection of saline was given instead of beta-antagonist (RE and EX). TG/FA cycling was calculated by combining results obtained with a two-stage glycerol infusion and indirect calorimetry. O2 uptake was significantly increased above control levels throughout the recovery period after exercise with the nonselective beta-adrenoceptor antagonist, beta1-adrenoceptor antagonist, and saline. However, there was no difference between the time course or magnitude of EPOC in the three situations. After 4.5 hours of bedrest, the mean increase in O2 uptake was 8% to 9% in all three conditions. TG/FA cycling was increased after exercise, but no effects of beta-antagonists were observed. We conclude that EPOC and the rate of TG/FA cycling are not attenuated by selective beta1- or nonselective beta-adrenoceptor blockade after an acute prolonged exercise protocol.     

Renal expression of interleukin-2 receptor mRNA in patients with crescentic glomerulonephritis

A microcolony assay was used in conjunction with fractionated gamma irradiation to determine the number of clonogens in murine intestinal crypts with varying doses of irradiation used in the determination. The experimental design allows direct comparison between two-dose methodologies, employing one and two (or two or four) equal dose fractions, and multiple-dose methodologies involving determination of the crypt survival curves for a number of fractionation regimens using equal doses per fraction. The two-dose methodology yielded estimates of clonogen number of between 3 and 4 at low delivered dose (single and double fractions each of 6.5-7.5 Gy), rising to around 40 at high biological doses (two and four fractions each of 5.75 or 6.5 Gy). The multifraction methodology yielded estimates of clonogen number which increased from 13 after a single fraction to values of 26 and 22 after three and four fractions. However, the latter values were reduced to 11 and 9, and showed little evidence of any dependence on fraction number, when data pertaining to high biologically effective doses were excluded. Hence it is concluded that the high values for clonogen number typically deduced from such multiple-dose protocols, compared with the generally lower (but dose-dependent) values obtained from two-dose protocols, may be explained at least partially by the higher biological doses generally employed in the multiple-dose protocols.     

Tracheal replacement with cryopreserved tracheal allograft: experiment in dogs

The purpose of this study was to assess the feasibility of a newly developed field inhomogeneity catheter for interventional MRI in vivo. Different prototypes of a field inhomogeneity catheter (pigtail and multipurpose configuration, balloon catheters) were investigated in pigs. The catheters were introduced in Seldinger technique via the femoral vessels over a guidewire on an interventional MR system (Philips Gyroscan NT combined with a C-arm fluoroscopy unit [Philips BV 212]). Catheters were placed in veins and arteries. The catheter position was controlled by a fast gradient-echo sequence (turbo field echo [TFE]). Catheters were introduced over a guidewire without complications in all cases. Using the field inhomogeneity concept, catheters were easily visualized in the inferior vena cava and the aorta by the fast gradient-echo technique on MR in all cases. Although aortic branches were successful cannulated, the catheters were not well displayed by the TFE technique due to the complex and tortuous anatomy. All animals survived the experiments without complications. MR-guided visualization of a field inhomogeneity catheter is a simple concept that can be realized on each MR scanner and may allow intravascular MR-guided interventions in future.     

Magnetic resonance imaging protocol optimization for evaluation of hyaline cartilage in the distal interphalangeal joint of fingers

RATIONALE AND OBJECTIVES: To identify a single magnetic resonance imaging (MRI) protocol that will provide optimal signal-to-noise ratio, resolution, and image contrast with minimal susceptibility artifacts and that will allow clear delineation and visualization of cartilage, fluid, bone, tendons, and ligaments within the distal interphalangeal (DIP) joint of the human hand. METHODS: A highly optimized 2.4 T MRI system was constructed from a 31-cm horizontal bore magnet, using a solenoid radiofrequency coil. This was used to study the DIP joints of 16 healthy, asymptomatic volunteers. RESULTS: A range of image contrast protocols were explored, including spin-echo T1 and T2, field echo, chemical shift suppression to give water only images, and magnetization transfer. Susceptibility variations were explored by changing the field strength from 0.6 to 2.4 T. A spin-echo protocol with TR = 1500 msec and TE = 30 msec can routinely produce images with resolution 0.075 x 0.150 for a slice thickness of 1 mm in 13 minutes. That protocol can visualize simultaneously compact and trabecular bone, two layers of cartilage, synovial fluid, and synovium within the joint, tendons and ligaments, and the volar plate. CONCLUSIONS: Although the contrast is not fully optimized for any one tissue, the spin echo protocol (TR = 1500, TE = 30) provides sagittal MR images, which clearly delineate the major structures of interest within the DIP joint, and which will be used in future studies to compare changes in the DIP joint because of aging or osteoarthritis. Experience gained by applying the above methods to a total of 16 healthy, asymptomatic volunteers has enabled a single sequence to be identified, which although not optimized for any one tissue, nevertheless visualized simultaneously and clearly delineated compact and trabecular bone, two layers of cartilage, synovial fluid, and synovium within the joint.     

Lesbians, bisexual women, and body image: an investigation of gender roles and social group affiliation

In our previous study, we demonstrated that chronic ethanol (EtOH) exposure down-regulated the cannabinoid receptors (CB1) in mouse brain synaptic plasma membrane (SPM) (Basavarajappa et al., Brain Res. 793 (1998) 212-218). In the present study, we investigated the effect of chronic EtOH (4-day inhalation) on the CB1 agonist stimulated guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTP gamma S) binding in SPM from mouse. Our results indicate that the net CP55,940 stimulated [35S]GTP gamma S binding was increased with increasing concentrations of CP55,940 and GDP. This net CP55,940 (1.5 microM) stimulated [35S]GTP gamma S binding was reduced significantly (-25%) in SPM from chronic EtOH group (175 +/- 5.25%, control; 150 +/- 8.14%, EtOH; P < 0.05). This effect occurs without any significant changes on basal [35S]GTP gamma S binding (152.1 +/- 10.7 for control, 147.4 +/- 5.0 fmol/mg protein for chronic EtOH group, P > 0.05). Non-linear regression analysis of net CP55,940 stimulated [35S]GTP gamma S binding in SPM showed that the Bmax of cannabinoid stimulated binding was significantly reduced in chronic EtOH exposed mouse (Bmax = 7.58 +/- 0.22 for control; 6.42 +/- 0.20 pmol/mg protein for EtOH group; P < 0.05) without any significant changes in the G-protein affinity (Kd = 2.68 +/- 0.24 for control; 3.42 +/- 0.31 nM for EtOH group; P > 0.05). The pharmacological specificity of CP55,940 stimulated [35S]GTP gamma S binding in SPM was examined with CB1 receptor antagonist, SR141716A and these studies indicated that CP55,940 stimulated [35S]GTP gamma S binding was blocked by SR141716A with a decrease (P < 0.05) in the IC50 values in the SPM from chronic EtOH group. These results suggest that the observed down-regulation of CB1 receptors by chronic EtOH has a profound effect on desensitization of cannabinoid-activated signal transduction and possible involvement of CB1 receptors in EtOH tolerance and dependence.     

Postoperative sella: evaluation with fast spin echo T2-weighted high-resolution imaging

OBJECTIVE: The purpose of this study was to investigate the magnetic resonance features of the postoperative sella with fast spin echo (FSE) T2-weighted high-resolution imaging and to evaluate the benefits of the sequence using a follow-up magnetic resonance imaging protocol after transsphenoidal surgery. METHODS: Coronal spin echo (SE) T1-weighted and FSE T2-weighted images were prospectively obtained in 24 patients after surgery for pituitary adenomas. We observed the signals and the contour of normal structures, fluid collection, implanted materials, and mass lesions, including granulation tissue and adenoma. RESULTS: The pituitary gland was delineated in 51 of 59 FSE T2-weighted images, 90.2% of which presented clear boundaries. Whereas the gland was detected in 49 of 58 SE T1-weighted images, only 20.4% showed the boundaries. A mass lesion was identified in each of 12 patients with good resolution on FSE T2-weighted images. SE T1-weighted images detected mass lesions in 7 of 12 patients without distinctive boundaries. Contrast enhancement had little advantage in clarifying the boundaries between normal and abnormal structures. For the detection of mass lesions in the sella, the kappa values for interobserver agreement were 0.8 for FSE T2-weighted images and 0.25 for SE T1-weighted images. CONCLUSION: FSE T2-weighted imaging is a reliable method with which to assess the sella with sufficient resolution after transsphenoidal surgery. The combination of unenhanced SE T1-weighted and FSE T2-weighted images may reduce the use of contrast material after pituitary surgery.     

Assessment of bacterial viability status by flow cytometry and single cell sorting

Cardiac echo-planar imaging suffers invariably from regions of severe distortion and T*2 decay in the myocardium. The purpose of this work was to perform local measurements of T*2 and field inhomogeneities in the myocardium and to identify the sources of focal signal loss and distortion. Field inhomogeneity maps and T*2 were measured in five normal volunteers in short-axis slices spanning from base to apex. It was found that T*2 ranged from 26 ms (SD = 7 ms, n = 5) to 41 ms (SD = 11 ms, n = 5) over most of the heart, and peak-to-peak field inhomogeneity differences were 71 Hz (SD = 14 Hz, n = 5). In all hearts, regions of severe signal loss were consistently adjacent to the posterior vein of the left ventricle; T*2 in these regions was 12 ms (SD = 2 ms, n = 5), and the difference in resonance frequency with the surrounding myocardium was 70-100 Hz. These effects may be caused by increased magnetic susceptibility from deoxygenated blood in these veins.     

Contrast-agent phase effects: an experimental system for analysis of susceptibility, concentration, and bolus input function kinetics

A system is presented for experimental arterial input function (AIF) simulation and for accurate measurement of the concentration, susceptibility effects, and magnetic moment of paramagnetic MR contrast agents. Signal effects of contrast agents are evaluated with a stable, well-characterized, and precise experimental setup. A cylindrical phantom and a closed-loop circulating flow system were designed for AIF simulation, assessment of the physical determinants of contrast-agent phase effects, and measurement of contrast-agent properties under controlled conditions. A mathematical model of the AIF dynamics is proposed. From the experimental phase shift (delta phi), either the concentration or molar susceptibility, chiM, is determined. The linear dependence of delta phi on concentration and echo time (TE), the orientation dependence, and the lack of dependence on T1, T2, and diffusion time are proven precisely for water solutions under a wide variety of conditions. The measured effective magnetic moment of Gd+3, mu(eff), was 7.924 +/- 0.015 Bohr magnetons in agreement with the theoretical value of 7.937.     

Improving MR quantification of regional blood volume with intravascular T1 contrast agents: accuracy, precision, and water exchange

The goal of this work was to develop a comprehensive understanding of the relationship between vascular proton exchange rates and the accuracy and precision of tissue blood volume estimates using intravascular T1 contrast agents. Using computer simulations, the effects of vascular proton exchange and experimental pulse sequence parameters on measurement accuracy were quantified. T1 and signal measurements made in a rat model implanted with R3230 mammary adenocarcinoma tumors demonstrated that the theoretical findings are biologically relevant; data demonstrated that over-simplified exchange models may result in measures of tumor, muscle, and liver blood volume fractions that depend on experimental parameters such as the vascular contrast concentration. As a solution to the measurement of blood volume in tissues with exchange that is unknown, methods that minimize exchange rate dependence were examined. Simulations that estimated both the accuracy and precision of such methods indicated that both the inversion recovery and the transverse-spoiled gradient echo methods using a "no-exchange" model provide the best trade-off between accuracy and precision.