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.

Transdermal nitroglycerin in angina pectoris: efficacy of intermittent application.

Continuous application of transdermal nitroglycerin appears to result in tolerance to the antianginal effect. In a double-blind study the effects of continuous (24 h/day) and intermittent (16 h/day) application of transdermal nitroglycerin in a dosage of 10 mg/day were compared with the effects of placebo in 12 patients with chronic stable angina receiving treatment with beta-adrenergic blocking or calcium channel blocking agents. Exercise performance was assessed 2 to 4 hours after initial application and after 1 week of each treatment given in random order with a 3 day interval between treatments. Exercise time to onset of angina, total exercise duration and time to 1 mm ST segment depression were all significantly increased after initial application during the continuous and intermittent treatment periods. These increases were maintained after 1 week of intermittent but not continuous treatment. Thus the benefit of initial application of transdermal nitroglycerin is maintained with intermittent treatment and a daily nitrate-free interval, whereas tolerance to antianginal effect occurs with continuous treatment.

Hemodynamic effects of intermittent transdermal nitroglycerin in chronic congestive heart failure.

The hemodynamic effects of intermittent and continuous treatment with transdermal nitroglycerin, 10 mg/24 hours, were compared in 10 patients with chronic congestive heart failure (CHF). Eight patients responded to initial application with more than a 20% reduction in mean pulmonary artery wedge pressure. Cardiac index increased from a control value of 2.1 +/- 0.5 to 2.4 +/- 0.6 liters/min/m2 at 2 hours (p less than 0.05) and mean pulmonary wedge pressure was reduced from 22 +/- 5 to 16 +/- 6 mm Hg (p less than 0.01). The 2 nonresponders had the largest left ventricular volumes on 2-dimensional echocardiograms. Responders were randomized to intermittent (16 hours/day) or continuous (24 hours/day) treatment for 1 month followed by a month of the alternate treatment. After 1 month of intermittent treatment, the hemodynamic response after reapplication was similar to the initial response. After another month of continuous treatment, hemodynamic values 24 hours after application were similar to initial control values and there was no change after removal and reapplication. Thus, the moderate vasodilator effect of transdermal nitroglycerin in CHF is maintained with intermittent treatment, whereas tolerance develops with continuous treatment.

Effect of reducing atrial pressure on atrial natriuretic factor and vasoactive hormones in congestive heart failure secondary to ischemic and nonischemic dilated cardiomyopathy.

The effect of an acute and sustained reduction in atrial pressure on atrial natriuretic factor (ANF) and vasoactive hormone secretion was studied in 9 patients with congestive heart failure (CHF). Intravenous nitroglycerin was titrated to reduce the pulmonary artery wedge pressure by 30 to 50% and maintain this reduction for 4 hours. After 60 minutes of nitroglycerin administration, the mean decrement in wedge pressure was 10.0 +/- 1.7 (standard error) mm Hg (35%) and plasma ANF was 65.3 +/- 13.9 pmol/liter (35%). The initial decrease, sustained reduction and later increase in plasma ANF levels closely paralleled the changes in pulmonary arterial wedge (r = 0.94, p less than 0.0001) and right atrial pressures (r = 0.91, p less than 0.0001) during and immediately after the nitroglycerin infusion. Plasma aldosterone and cortisol levels increased during the first 2 hours of the nitroglycerin infusion, but there was little change in plasma norepinephrine or plasma renin activity. Although levels were elevated in CHF, plasma ANF still responded rapidly to changes in atrial pressure. A sustained reduction in pressure produced a sustained reduction in ANF levels. These findings provide further support for a regulatory role of ANF, even in chronic CHF.

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.

Development of a simple, fluoroimmunoassay for paraquat.

High affinity populations of antibodies to paraquat were produced in high concentrations in the sera of immunised sheep. A simple fluoroimmunoassay was developed for rapid measurement of plasma paraquat. Fluorescein-labelled paraquat was added to sample or standard (20 microliter) followed by premixed first and second antisera. Equilibrium was reached within 2 min and results were available within 20 min. Correlation with weighed-in paraquat gave a regression line (r) of 0.997. All reagents proved stable and are suitable for general distribution.

Design of the immunogen and label for use in a fluoroimmunoassay for paracetamol.

The design of immunogens for raising antisera containing antibodies specifically directed against paracetamol is discussed. A derivative of the drug with minimal structural alteration was synthesised, coupled to the carrier protein key-hole limpet haemocyanin, and used to immunise sheep. The evaluation of the resulting antisera is described. Preparation of a fluorescent label with reduced bridge-binding then allowed the development of a polarisation fluoroimmunoassay for paracetamol in buffer, suitable for conversion to a direct serum assay.

Development of a specific polarisation fluoroimmunoassay for paracetamol in serum.

A specific polarisation fluoroimmunoassay for the measurement of paracetamol levels in serum has been developed for use in emergency toxicological screening. It is based on the use of a fluorescein-labelled analogue and a sheep antiserum and exploits the rapid dissociation kinetics of the hapten-antibody complex to enable the label and antiserum to be combined as a single reagent. Paracetamol levels are determined by adding 5 microL of serum to 1.5 mL of the single reagent, incubation at ambient temperature for a few minutes and measurement of fluorescence polarisation. In addition to its speed and simplicity, the assay is both accurate and precise and the results obtained correlate closely with those from the commonly used chemical and enzymatic techniques.

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.

Improvements in snap-shot nuclear magnetic resonance imaging.

New variants of the ultra-high-speed echo-planar imaging technique have been used to obtain snap-shot images of adult patients and volunteers at 0.1 T. Modified pulsed-gradient sequences together with non-linear signal sampling and activity screened gradients have greatly improved the image quality obtainable by single-shot methods. A particular variant, modulus blipped echo-planar single-pulse technique (MBEST), although slightly slower than the blipped echo-planar single-pulse technique (BEST), is experimentally more robust and incorporates intrinsic T2 weighting. An account of these improvements together with some experimental results is presented.

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.

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.

Development of a radioimmunoassay for idazoxan hydrochloride.

To facilitate the measurement of idazoxan in clinical trials an immunoassay capable of detecting low ng ml-1 concentrations was required. A stable derivative was prepared which, after linking to keyhole limpet hemocyanin (KLH), was subsequently immunized into sheep. Early assay development was carried out with both fluorescent (1-FITC) and iodinated (I-125) labels. The assay methodology was the same in both cases, using magnetizable solid-phase particles to which the antibody was linked. The sensitivity of the assay was such that a large sample volume was required, which in turn, led to problems of increased protein interference. The use of pepsin to digest the protein was used effectively after several blocking agents were unsuccessfully used. The limit of detection was in the region of 3 ng ml-1. Cross-reactivity studies showed that the antibody was specific for idazoxan. Intra- and inter-assay precision was 7 and 12%, respectively. Correlation with the analytical GC-MSD method was in the order of 0.90.

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.

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.

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.