Magnetization transfer phenomenon in the human brain at 7 T.

Magnetization transfer is an important source of contrast in magnetic resonance imaging which is sensitive to the concentration of macromolecules and other solutes present in the tissue. Magnetization transfer effects can be visualized in magnetization transfer ratio images or quantified via the z-spectrum. This paper presents methods of measuring the z-spectrum and of producing high-resolution MTR images and maps of z-spectrum asymmetry in vivo at 7 T, within SAR limits. It also uses a 3-compartment model to measure chemical exchange and magnetization transfer parameters from the z-spectrum data. The peak in the z-spectrum associated with chemical exchange between amide and water protons (amide proton transfer, APT, effects) is much more apparent at 7 T than at 3 T. Furthermore at 7 T quantitative APT results varied between the corpus callosum and other white matter structures, suggesting that quantitative APT imaging could be used as a method of measuring myelination. The results also suggest that chemical exchange is not responsible for the phase shift observed in susceptibility weighted images between grey matter and white matter.

Water proton T1 measurements in brain tissue at 7, 3, and 1.5 T using IR-EPI, IR-TSE, and MPRAGE: results and optimization.

METHOD: This paper presents methods of measuring the longitudinal relaxation time using inversion recovery turbo spin echo (IR-TSE) and magnetization-prepared rapid gradient echo (MPRAGE) sequences, comparing and optimizing these sequences, reporting T1 values for water protons measured from brain tissue at 1.5, 3, and 7 T. T1 was measured in cortical grey matter and white matter using the IR-TSE, MPRAGE, and inversion recovery echo planar imaging (IR-EPI) pulse sequences. RESULTS: In four subjects the T1 of white and grey matter were found to be 646+/-32 and 1,197+/-134 ms at 1.5 T, 838+/-50 and 1,607+/-112 ms at 3T, and 1,126+/-97, and 1,939+/-149 ms at 7 T with the MPRAGE sequence. The T1 of the putamen was found to be 1,084+/-63 ms at 1.5 T, 1,332+/-68 ms at 3T, and 1,644+/-167 ms at 7 T. The T1 of the caudate head was found to be 1,109+/- 66 ms at 1.5 T, 1,395+/-49 ms at 3T, and 1,684+/-76 ms at 7 T. DISCUSSION: There was a trend for the IR-TSE sequence to underestimate T1 in vivo. The sequence parameters for the IR-TSE and MPRAGE sequences were also optimized in terms of the signal-to-noise ratio (SNR) in the fitted T1. The optimal sequence for IR-TSE in terms of SNR in the fitted T1 was found to have five readouts at TIs of 120, 260, 563, 1,221, 2,647, 5,736 ms and TR of 7 s. The optimal pulse sequence for MPRAGE with readout flip angle = 8 degrees was found to have five readouts at TIs of 160, 398, 988, 2,455, and 6,102 ms and a TR of 9 s. Further optimization including the readout flip angle suggests that the flip angle should be increased, beyond levels that are acceptable in terms of power deposition and point-spread function.

Active acoustic control in gradient coils for MRI.

The new principles of active acoustic control in gradient coil design recently introduced by Mansfield and Haywood (MAGMA 1999;8(Suppl 1):55) are further developed theoretically for the far-field acoustic output for a single sector of a coil system comprising four or more flat rectangular coil sectors. Each sector consists of a split plate arrangement in which are embedded two windings, an outer primary winding and a narrow inner re-entrant loop control winding immediately adjacent to and surrounding the split or air gap. The wire spacing of the control winding is made small so as not to affect substantially the magnetic field created by the primary winding. Experimental results are presented for two sectors each made of a different readily available plastic material and tested over a range of frequencies. They both show substantial average reductions in acoustic output over the full output when the control winding is appropriately driven. New theoretical expressions are derived for particular frequencies based on normal mode expansions for the plate. This new approach is better able to explain the acoustic output difference between the full and reduced output modes. Empirical expressions are also developed which include longitudinal as well as transverse plate characteristics and used to fit the experimental acoustic output data as a function of frequency and indicate good agreement with regard to both the form and amplitude of the acoustic output response.

Liver transplantation for citrullinaemia improves intellectual function.

BACKGROUND: Arginosuccinic acid synthetase (ASA) (EC 6.3.4.5) deficiency (citrullinaemia) (McKusick 215700) is a well-recognized cause of neonatal hyperammonaemic coma with poor long-term intellectual function, despite good medical management. METHODS: Cadaveric hepatic transplantation was performed in a 12-year-old boy with citrullinaemia under poor biochemical control. Subsequent development of fulminant hepatic failure necessitated a second cadaveric transplant. Psychometric assessments before and after transplantation were performed using a variety of age-appropriate tests. RESULTS: Normalization of plasma ammonium in our patient post transplantation has resulted in dramatic improvement in mental functioning and well-being and he now enjoys a normal diet. Psychometric assessment confirmed decline in his abilities prior to transplantation with particular post-transplantation improvement in perceptual organization and visuospatial abilities; these did not, however, return to normal. His family report considerable reduction in stress associated with the unpredictable nature of previous hyperammonaemic crises and recurrent hospitalization. CONCLUSIONS: Liver transplantation should be considered as an early therapeutic option in children with citrullinaemia to prevent ongoing cerebral insult associated with hyperammonaemia.

Functional magnetic resonance imaging of single motor events reveals human presupplementary motor area.

Conventional functional imaging paradigms use periods of repetitive task performance to generate sustained functional signal changes. We have developed a technique of imaging the small, transient signal changes that occur after single cognitive events. The technique uses echo-planar imaging at 3 T to generate functional images of the whole brain with a temporal resolution of 3 seconds. It uses a signal averaging technique to create time sweeps of functional activity. After a single cognitive event, widely distributed patterns of brain activation can be detected and their time course measured. This technique enables the individual cognitive tasks that constitute a paradigm to be analyzed separately and compared. We describe the application of this new technique to separate the cognitive elements in a simple "go/no-go" motor paradigm. Comparison of activation patterns during "go" and "no-go" responses reveals hierarchical subdivision of the medial premotor cortex into an anterior region (presupplementary motor area) involved in movement decision making and a posterior region (supplementary motor area proper) directly involved in motor execution.

The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever.

Severe Jarisch Herxheimer reaction (J-HR) precipitated by antibiotic treatment of louse-borne relapsing fever (LBRF) is associated with a transient, marked rise in circulating tumour necrosis factor alpha (TNF alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). Ovine polyclonal anti-TNF alpha antibody fragments (Fab) were used in a randomized double blind placebo controlled trial in an attempt to prevent this reaction. Within 4 h after penicillin, in controls (n = 29), a several-fold rise in cytokines occurred, concomitant with a fall in spirochaetes and maximal clinical manifestations of the J-HR. An intravenous infusion of anti-TNF alpha Fab, 30 min before penicillin in 20 patients reduced peak plasma levels of IL-6 and IL-8 (but not IL-1 beta) compared with controls (p = 0.01 and < 0.001, respectively) and the incidence of the J-HR, indicating some neutralization of TNF alpha. An apparent fall in TNF alpha reflected interference of anti-TNF alpha in the immunoassay.

Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha.

BACKGROUND: In patients with louse-borne relapsing fever (Borrelia recurrentis infection), antimicrobial treatment is often followed by sudden fever, rigors, and persistent hypotension (Jarisch-Herxheimer reactions) that are associated with increases in plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6, and interleukin-8. We attempted to determine whether sheep polyclonal Fab antibody fragments against TNF-alpha (anti-TNF-alpha Fab) could suppress the Jarisch-Herxheimer reaction. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 49 patients with proven louse-borne relapsing fever. Immediately before the intramuscular injection of penicillin, the patients received an intravenous infusion of either anti-TNF-alpha Fab or a control solution. RESULTS: Ten of the 20 patients given anti-TNF-alpha Fab had Jarisch-Herxheimer reactions with rigors, as compared with 26 of the 29 control patients (P = 0.006). The controls had significantly greater mean maximal increases in temperature (1.5 vs. 0.8 degrees C, P < 0.001), pulse rate (31 vs. 13 per minute, P < 0.001), and systolic blood pressure (25 vs. 15 mm Hg, P < 0.003), as well as higher mean peak plasma concentrations of interleukin-6 (50 vs. 17 micrograms per liter) and interleukin-8 (2000 vs 205 ng per liter) (P < 0.001 for both comparisons). Levels of TNF-alpha were undetectable after treatment with anti-TNF-alpha Fab. CONCLUSIONS: Pretreatment with sheep anti-TNF-alpha Fab suppresses Jarisch-Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the associated increases in plasma concentrations of interleukin-6 and interleukin-8, and may be useful in other forms of sepsis.

Echo-volumar imaging (EVI) of the brain at 3.0 T: first normal volunteer and functional imaging results.

OBJECTIVE: Our goal was to present the first echo-volumar brain images obtained at 3.0 T, together with the first functional imaging results using echo volumar imaging. MATERIALS AND METHODS: The results presented were obtained on volunteers using an in-house designed and constructed 3.0 T echo-planar/volumar imager. RESULTS: The results demonstrate the feasibility of obtaining snapshot volumar images comprising up to 64 x 64 x 8 voxels corresponding to a spatial resolution of 3.0 x 3.0 x 2.5 mm3. Results are also presented showing local cortical changes in signal in response to an external visual stimulus for both the left and the right brain hemispheres. CONCLUSION: The snapshot acquisition of a whole-volume data set has a number of advantages when considering motional effects or functional image changes that may involve time delays or phase effects within different cortical regions. Instantaneous acquisition of the whole data set means accurate phase information may be straightforwardly obtained.

Anti-tumor necrosis factor-alpha prevents decreased ventricular contractility in endotoxemic pigs.

It is not known how the decrease in left ventricular contractility following endotoxin exposure is mediated, or whether this decrease is preventable by antibodies to tumor necrosis factor-alpha (TNF alpha). Four groups of six anesthetized and instrumented pigs were pretreated with ovine polyclonal antibody to human TNF alpha (anti-TNF alpha), nonspecific IgG, or saline, and then treated with either endotoxin or saline. We measured hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter). Left ventricular contractility was assessed using the slope (Emax) of the end-systolic pressure-volume relationship. Four hours after the start of endotoxin infusion in the nonspecific IgG pretreated group, Emax had decreased by 44 +/- 6% (p < 0.05), mean arterial pressure had decreased from 115 +/- 7 mm Hg to 70 +/- 10 mm Hg (p < 0.05), and cardiac output was rapidly decreasing after an initial increase (p < 0.05). Anti-TNF alpha significantly reduced the decrease in Emax (11 +/- 9%, p < 0.05), and the systemic hypotension (108 +/- 15 mm Hg to 99 +/- 6 mm Hg, p < 0.05), at 4 h, and prevented the late decrease in cardiac output. This suggests that TNF alpha is an important early mediator in sepsis leading to decreased left ventricular contractility.

Active acoustic screening: reduction of noise in gradient coils by Lorentz force balancing.

We have designed and constructed a quiet gradient set with restricted access for the combined purposes of evaluating the principles of active acoustic screening, recently introduced by Mansfield, Glover, and Bowtell, and for EPI studies of the head at 3.0 T. The design utilizes the return paths of the conductors in a closed arc loop arrangement to eliminate net Lorentz forces thereby attenuating acoustic noise especially at low frequency. This design should significantly reduce the dangers to patients of high noise levels, especially in high field magnetic resonance imaging systems.

Echo-planar imaging of the brain at 3.0 T: first normal volunteer results.

OBJECTIVE: To present the first echo-planar brain images of diagnostic quality obtained at 3.0 T and to point out some of the problems experienced in performing it. MATERIALS AND METHODS: The results presented were obtained on volunteers using an in-house designed and constructed 3.0 T EPI imager. RESULTS: The results demonstrate the feasibility of obtaining snapshot imaging comprising up to 256 x 256 pixels and corresponding to a spatial resolution of 0.75 x 0.75 mm2 with a slice thickness of 2.5 mm. CONCLUSION: Potentially augmented diagnostic information can be obtained with high field EPI of the brain. Some susceptibility artifact is apparent at the bone-air interfaces as expected at 3.0 T.

Prolonged monitoring of the upper gastrointestinal tract using echo planar magnetic resonance imaging.

Upper gastrointestinal motility and transit has been studied in five human volunteers with the ultra high speed, magnetic resonance imaging (MRI) technique MBEST (Modulus Blipped Echo-planar Single pulse Technique), a variant of echo planar imaging. Snapshot images requiring a data acquisition time of only 64-128 msec allowed visualisation of peristalsis in the antrum and duodenum in real time, without motional image degradation, as would normally be seen using conventional MRI. Gastroduodenal flow of the luminal contents was visualised using water as a contrast medium, with appropriate adjustment of the time constant (T2) weighting of the system. Rapid (0.3 Hz) imaging of gastroduodenal motility in both transverse and coronal planes was achieved by respiratory gating to the imaging frequency, allowing repetition rates of up to 20 frames per minute for 2-3 hours. Fast replay of stored images, to produce a 'movie loop', allowed identification of fasting motility patterns of the gastric antrum and proximal small intestine, with depiction of the phases of the migrating motor complex. Images of the fed patterns after the ingestion of a test meal showed good separation of solid and liquid particulate matter and mixing waves in the gastric body. The potential for quantitative measurements with this new imaging modality of the gastrointestinal tract is under development, which will allow us to measure transit and correlate this with motility data.

Urinary cotinine fluoroimmunoassay for smoking status screening adapted to an automated analyser.

A polarization fluoroimmunoassay for cotinine, a major metabolite of nicotine, has been adapted for fully automated screening of urine samples on the Abbott TDx analyser. The method has sensitivity and specificity suitable for the discrimination of active smokers from non-smokers (including passive smokers) by application of a cut-off at 0.5 mg l-1 of total urinary cotinine. Most active smokers' urine gave results over 1 mg l-1, whereas apparent levels in non-smokers were 0.08 mg l-1 or lower. A result for one sample can be obtained in about 5 min and a throughput of 80 samples h-1 can be maintained for large-scale screening applications.

Observation of cerebrospinal fluid flow with echo-planar magnetic resonance imaging.

Using echo-planar (EP) magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) flow patterns have been demonstrated in the normal subject and patients with pathological conditions including communicating hydrocephalus, aqueduct stenosis and syringohydromyelia. Snap-shot imaging times of 128 ms allow detailed demonstration of transient intraventricular CSF flow patterns, which is not possible with conventional MRI. The potential of EPI as a method for qualitative and quantitative assessment of CSF dynamics is illustrated.

Echo planar imaging of the human fetus in utero at 0.5 T.

The snap-shot capability of the echo-planar imaging technique is used to freeze motion effectively in human fetal studies in utero. These first results obtained at 0.5 T demonstrate diagnostic quality images without the need for averaging. Although averaging improves the image signal to noise ratio, it is shown that significant image blurring is produced even when only eight separate images are averaged over a period of a few seconds. Results are presented showing anatomical detail of the internal organs of the fetus. Some pathology is also demonstrated. These results were obtained using the modulus blipped echo-planar single-pulse technique (MBEST). Running at 10 frames/second, the modulus version of the fast low-angle excitation echo-planar technique (FLEET) is used to produce ungated fetal cardiac movies.

Study of internal structure of the human fetus in utero by echo-planar magnetic resonance imaging.

The ultrafast echo-planar magnetic resonance imaging technology, developed and built in Nottingham, has been used to produce the first snapshot images of the human fetus in utero. The imager, operating at a proton resonance frequency of 22 MHz, produces transaxial views in 64 or 128 milliseconds. These images comprise either 64 x 128 or 128 x 128 pixels with an in-plane resolution of 3 x 3 mm2. The slice thickness is 10 mm. Fetal scans of up to 32 contiguous slices are produced in a few minutes. These have been used to study the internal structure of the uterus and the fetus in a range of cases with gestations ranging from 26 weeks to term. Echo-planar imaging seems particularly suitable as an imaging modality since its high speed obviates image blurring arising from fetal motion.

Echo planar imaging of an infant with pectus excavatum.

Echo planar imaging has enabled us to image safely and without sedation the thorax of an infant with pectus excavatum deformity. The heart was displaced into the left side of the thorax, and the right lung was calculated to be 1.6 times larger than the left lung.

Ultrafast magnetic resonance scanning of the liver with echo-planar imaging.

Echo-planar imaging (EPI) is a magnetic resonance imaging (MRI) technique which provides MR images in, typically, 50-100 ms. The potential of EPI as an imaging modality for the liver has been investigated in volunteers and patients with liver disease. Images with improved quality are presented. Obtained at a field strength of 0.52 Tesla, these true unaveraged snap-shot images have larger data arrays, comprising 128 X 128 pixels.