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M O Leach

Publications and source records attributed to M O Leach.

At least 19 recordsLinked to original sources
PubMed1992

Rapid localization of concave volumes by conformal NMR spectroscopy.

"Conformal" spectroscopy is a method for the acquisition of accurately localized NMR spectra from noncuboidal regions with optimum signal-to-noise ratio, and is based upon the localization of volumes defined by a number of oblique intersecting selected slices. We have previously demonstrated conformal localization of volumes with convex surfaces. In this paper we extend the technique to the localization of concave volumes.

Humans↗
PubMed1992

Fast and accurate measurements of T1 using a multi-readout single inversion-recovery sequence.

TOMROP is a multiple readout single inversion-recovery sequence which may potentially allow the measurement of multi-exponential T1 recoveries in vivo by NMR imaging. It is shown that several important modifications must be made to this sequence to permit T1 to be measured accurately and reliably. With these modifications it is possible to measure T1 with a mean systematic error of -1.5% (-0.3% for samples with T1 greater than 300 ms), a mean accuracy of 3.1% (2.1% for samples with T1 greater than 300 ms) and a mean repeatability of 1.4% (1.4% for samples with T1 greater than 300 ms), using data collected in 6.4 min from sixteen 128 x 128 matrix images.

Algorithms↗
PubMed1992

Radial diffusion coefficient mapping.

The two-dimensional mapping of the effective diffusion coefficient of water in tissues may provide a useful method of tissue characterization to complement T1 and T2 relaxation time studies for diagnostic purposes. Current diffusion techniques rely on the application of large gradient strengths and long echo times to achieve the required sensitivity. This, in turn, limits the applicability of the technique to tissues having long T2s with rapid water diffusion. In addition, the inherent directionality of these methods results in only the partial encoding of diffusion information. A modified diffusion sequence is presented, radial diffusion mapping (RAD), which provides enhanced sensitivity diffusion maps by employing gradient sensitization in three orthogonal directions. Results in both phantoms and volunteers are presented, together with an investigation of the effects of T2 on the measurement accuracy. Using RAD, a two- to five-fold improvement in sensitivity was achieved, thus significantly enhancing the dynamic range of the method and allowing more accurate in vivo diffusion measurements to be carried out.

Acetone↗
PubMed1991

The water resonance as an alternative pH reference: relevance to in vivo 31P NMR localized spectroscopy studies.

pH measurements require a suitable pH reference within the 31P NMR spectrum with respect to which the chemical shift of Pi, and hence pH, may be calculated. In muscle spectra PCr is prominent and provides a reference frequency. However, recent localized tumor studies have reported the absence of PCr, for example, in breast tumors. The use of the alpha-, beta-, and gamma-ATP peaks as suitable references has been suggested, but the position of the beta- and gamma-ATP peaks is dependent upon the intracellular Mg2+ concentration. The alpha-ATP is not affected by ionic concentrations; however, it contains UDPG and NAD+, the presence of which can lead to peak-shape distortion. This paper considers the use of the H2O resonance from the proton spectrum used for shimming as a suitable pH reference, provided this is also localized to the same region of interest, using a sequence giving rise to eddy current effects comparable to those of the 31P NMR sequence. Localized in vivo measurements in the muscle and brain of volunteers indicate good agreement between the proton and phosphorus chemical shifts, allowing the PCr position to be predicted to within 0.01 ppm in all cases.

Body Water↗
PubMed1991

A quantitative analysis of the accuracy of in vivo pH measurements with 31P NMR spectroscopy: assessment of pH measurement methodology.

31P NMR spectroscopy provides a means of monitoring intracellular pH (pHi). In order to determine the significance of observed pH changes, an assessment of the measurement uncertainty is required. This paper considers the possible sources of error involved, firstly in chemical shift assignment and, secondly, in relating chemical shift to pH. A statistical analysis of these errors is presented and an expression for the accuracy of pH measurements obtained using in vivo 31P NMR spectroscopy is derived. Computer simulations and clinical measurements are considered to determine the likely error in clinical measurements. A comparison of pH measurement methodology using a centre-of-gravity calculation, Gaussian and Lorentzian fitting is also presented and discussed.

Humans↗
PubMed1991

The effect of intra-tumour heterogeneity on the distribution of phosphorus-containing metabolites within human breast tumours: an in vitro study using 31P NMR spectroscopy.

The concentration of phosphorus-containing metabolites was determined in extracts of multiple samples from six human breast tumours and in samples from normal and inflamed breast tissue. The degree of lymphoid infiltrate, necrotic fraction and tumour cell and normal tissue fraction were determined on sections taken from each of the tumour samples. In four of the tumours there was a very high degree of variation between samples in the absolute concentration of metabolites. Three of these tumours showed a high degree of intra-tumour variation in the distribution of tumour cells and of normal tissue. The other two tumours were relatively homogeneous with respect to both tumour cellularity and the distribution of phosphorus-containing metabolites. Samples from normal breast tissue was found to contain only low concentrations of phosphorus-containing metabolites. However one of the inflamed samples, which consisted predominantly of macrophages, contained high levels of such compounds. The effect of time delay between resection and freezing on the levels of metabolites in human breast tumours was also examined.

Breast↗
PubMed1991

A comparison of in vivo and in vitro 31P NMR spectra from human breast tumours: variations in phospholipid metabolism.

An in vivo 31P NMR spectrum was obtained from each of four human breast tumours. The phosphomonoester and phosphodiester region of each spectrum consisted of a broad peak. Chemical extracts from samples of each of the tumours obtained at resection were examined on a high field strength NMR system. The phosphomonoester region in the spectrum from each extract resolved into three peaks consisting of phosphocholine, phosphoethanolamine and a nucleoside monophosphate. The phosphodiester region resolved into two components, glycerophosphorylcholine and glycerophosphorylethanolamine. Comparing the in vivo and in vitro data from each tumour showed that the contribution of phosphodiester was much lower in the in vitro spectra. We believe this to be a consequence of phospholipid, which would not appear in the aqueous extract, contributing to the phosphodiester peak in vivo.

Breast Neoplasms↗
PubMed1991

A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer.

Lonidamine is a substituted indazole carboxylic acid with a unique mechanism of action and early clinical studies have reported anti-tumour activity. In a phase II study 32 patients with previously treated advanced breast cancer were given Lonidamine in a daily divided oral dose of 600 mg. Of 28 patients evaluable for response, three (11%) achieved a partial response (4-24+ months) and three (11%) a minor response. Two patients have stable disease (greater than 3 months) and 20 progressed. Toxicity was very mild. Sixteen (53%) of 31 patients had myalgia which lasted a median of 2 weeks. This was investigated with nuclear magnetic resonance spectroscopy in four patients but the changes were unrelated to the degree of myalgia. No other major side-effect was seen, and no dose reduction was required. Lonidamine pharmacokinetics have been investigated in 17 patients 1 month after the start of therapy. Lonidamine was detected in the plasma of all patients, but there was no clear relationship between Lonidamine levels and clinical response or toxicity. Lonidamine appears to be active against advanced breast cancer and its low toxicity would allow combination studies with chemotherapy.

Adenosine Triphosphate↗
PubMed1991

The phosphocholine and glycerophosphocholine content of an oestrogen-sensitive rat mammary tumour correlates strongly with growth rate.

An oestrogen sensitive rat mammary tumour was grown in two groups of female and one group of male hooded rats. The male group and one of the female groups were supplemented with oestrogen. The tumours grew most rapidly in the female supplemented group. When the tumours reached 1.5 cm in diameter they were harvested and the cell cycle distribution and number of cells actively synthesising DNA (bromodeoxyuridine (BrdU) labelling index) determined in each case. Chemical extracts were prepared from each tumour and the concentration of phosphorus-containing metabolites determined using high resolution NMR spectroscopy. The concentration of phosphocholine was found to correlate strongly with the number of cells in S-phase and the number of cells labelled with BrdU, whilst a highly significant negative correlation was observed between these two parameters and glycerophosphocholine. The concentration of phosphoethanolamine did not correlate with either of these measures of proliferation rate. The concentration of glycerophosphorylethanolamine showed a weak negative correlation with the number of cells in S-phase.

Animals↗
PubMed1990

An assessment of the sensitivity of in vivo 31P nuclear magnetic resonance spectroscopy as a means of detecting pH heterogeneity in tumours: a simulation study.

The presence of hypoxia and low pH in tumours is known to influence several treatment modalities including radiotherapy, chemotherapy and hyperthermia. Hypoxic and acidic regions have been demonstrated in tumours using pH and pO2 microelectrodes. The technique has shown marked heterogeneity within individual tumours. A non-invasive measure of intracellular pH is provided by 31P nuclear magnetic resonance (NMR) spectroscopy from determination of the chemical shift of inorganic phosphate, and is being increasingly applied to the study of human tumours in vivo. Based upon the assumption that hypoxic cells are also acidic, we have assessed the ability of a whole-body NMR spectrometer to detect acidic subpopulations within a tumour using simulated tumour spectra. In these simulations the size of the acidic subpopulation, assigned pH values from 5.0 to 7.0, was varied between 5% and 50% of the neutral "control" population. Gaussian noise was added to the simulated spectra giving signal-to-noise ratios for the neutral control inorganic phosphate peak of 3, 5 and 7, which are typical of values encountered in human tumour measurements. From the results of the simulations it seems unlikely that human hypoxic, and presumably acidic, cell fractions, typically 1-15%, will be detected by this method in the presence of signal-to-noise levels characteristic of current equipment. Therefore, whole-body in vivo 31P NMR spectroscopy may fail to identify significant pH heterogeneity within human tumours. Improvements in signal-to-noise and line separation owing to improvements in technique and higher field strength instruments may improve sensitivity to heterogeneous populations.

Cell Hypoxia↗
PubMed1990

Comparison of 5-fluorouracil pharmacokinetics following intraperitoneal and intravenous administration using in vivo 19F magnetic resonance spectroscopy.

Intrahepatic pharmacokinetic studies of 5-Fluorouracil (5 FU) metabolism following intravenous and intraperitoneal administration have been undertaken in four patients using in vivo 19F nuclear magnetic resonance spectroscopy. Following intravenous administration, 5 FU decayed with "half times" ranging from 5 to 17 min. There was considerable variation of 5 FU pharmacokinetics between patients following intraperitoneal administration. Peritoneal contamination by infused 5 FU was considered to be a significant problem in one patient. A technique for providing superficial signal suppression was therefore investigated and its efficacy for excluding signal from the peritoneal space has been demonstrated. Owing to the potential for contamination from peritoneal 5 FU, the accumulation of fluoro-beta-alanine (FBAL) is a more reliable indicator of drug catabolism than the measurement of unlocalized "hepatic" 5 FU. Rapid intrahepatic catabolism of 5 FU to FBAL was demonstrated in all patients. However, there was greater pharmacokinetic variation following intraperitoneal administration than following intravenous administration. Therapeutic implications of intravenous compared with intraperitoneal administration of 5 FU are discussed.

Fluorouracil↗
PubMed1989

Conformal NMR spectroscopy: accurate localization to noncuboidal volumes with optimum SNR.

"Conformal Spectroscopy" is a general method for the acquisition of accurately localized NMR spectra from noncuboidal regions with optimum signal-to-noise ratio (SNR). The method is based upon the localization of volumes defined by a number of intersecting oblique slices and may be implemented using standard imager hardware. Conformal techniques can enhance many existing localization sequences such as ISIS (31P) and STEAM (1H) resulting in typical SNR improvements of around 1.8, equivalent to a more than threefold reduction in acquisition time. Applications include in vivo tumor spectroscopy.

Breast Neoplasms↗
PubMed1989

The use of an improved inversion pulse with the spin-echo/inversion-recovery sequence to give increased accuracy and reduced imaging time for T1 measurements.

The hyperbolic secant inversion pulse has been incorporated into the interleaved saturation-recovery/inversion-recovery sequence to provide T1 measurements combining high precision with a significantly reduced imaging time (a mean accuracy of 2% over a T1 range of 300 to 1650 ms for standard gel phantoms, with Tr1 = Tr2 = 2.0 s, Ti = 0.67 s).

Humans↗
PubMed1978

In vivo measurement of calcium by the 37Ar method: a study of the effect of recirculating breath collection systems on the exhalation rate.

A study has been made of the effect that different methods of breath collection have on the measurement of calcium in vivo by the 40Ca(n,alpha) 37Ar method. The effect of open and rebreathing breath collection methods has been examined by using intravenous injections of 133Xe. This study has indicated that comparison of calcium measurements between individuals and between centres is likely to be accurate only if breath is collected on 'open circuit'.

Argon↗
PubMed1978

Problems in the interpretation of the in vivo measurement of calcium by the argon-37 method: an investigation of inert-gas elimination in humans.

An investigation has been made of some physiological problems associated with the interpretation of in-vivo measurements of calcium by the argon-37 method. Inert-gas elimination in humans over a period of several days was studied using i.v. injections of Xe-133. The results imply that the exhalation rate of A-37 formed in bone will be affected by the individual's composition, in particular body fat. Comparison of calcium measurements between individuals and between laboratories is meaningful only if corrections are made for differing individual composition.

Argon↗