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M O Leach

Publications and source records attributed to M O Leach.

At least 37 records · Page 2Linked to original sources
PubMed2004

Measurement of the three-dimensional distribution of radiation dose in grid therapy.

A single large dose of megavoltage x-rays delivered through a grid is currently being utilized by some centres for palliative radiotherapy treatments of large tumours. In this note, we investigate the dosimetry of grid therapy using two-dimensional film dosimetry and three-dimensional gel dosimetry. It is shown that the radiation dose is attenuated more rapidly with depth in a grid field than an open field, and that even shielded regions receive approximately 25% of the dose to the unshielded areas.

Dose Fractionation, Radiation↗
PubMed2004

Investigations in vivo of the effects of carbogen breathing on 5-fluorouracil pharmacokinetics and physiology of solid rodent tumours.

PURPOSE: We have shown previously that carbogen (95% 0(2), 5% CO(2)) breathing by rodents can increase uptake of anticancer drugs into tumours. The aim of this study was to extend these observations to other rodent models using the anticancer drug 5-fluorouracil (5FU). 5FU pharmacokinetics in tumour and plasma and physiological effects on the tumour by carbogen were investigated to determine the locus of carbogen action on augmenting tumour uptake of 5FU. METHODS: Two different tumour models were used, rat GH3 prolactinomas xenografted s.c. into nude mice and rat H9618a hepatomas grown s.c. in syngeneic Buffalo rats. Uptake and metabolism of 5FU in both tumour models with or without host carbogen breathing was studied non-invasively using fluorine-19 magnetic resonance spectroscopy ((19)F-MRS), while plasma samples from Buffalo rats were used to construct a NONMEM pharmacokinetic model. Physiological effects of carbogen on tumours were studied using (31)P-MRS for energy status (NTP/Pi) and pH, and gradient-recalled echo magnetic resonance imaging (GRE-MRI) for blood flow and oxygenation. RESULTS: In both tumour models, carbogan-induced GRE-MRI signal intensity increases of approximately 60% consistent with an increase in tumour blood oxygenation and/or flow. In GH3 xenografts, (19)F-MRS showed that carbogen had no significant effect on 5FU uptake and metabolism by the tumours, and (31)P-MRS showed there was no change in the NTP/Pi ratio. In H9618a hepatomas, (19)F-MRS showed that carbogen had no effect on tumour 5FU uptake but significantly ( p=0.0003) increased 5FU elimination from the tumour (i.e. decreased the t(1/2)) and significantly ( p=0.029) increased (53%) the rate of metabolism to cytotoxic fluoronucleotides (FNuct). The pharmacokinetic analysis showed that carbogen increased the rate of tumour uptake of 5FU from the plasma but also increased the rate of removal. (31)P-MRS showed there were significant ( p<or=0.02) increases in the hepatoma NTP/Pi ratio of 49% and transmembrane pH gradient of 0.11 units. CONCLUSIONS: We suggest that carbogen can transiently increase tumour blood flow, but this effect alone may not increase uptake of anticancer drugs without a secondary mechanism operating. In the case of the hepatoma, the increase in tumour energy status and pH gradient may be sufficient to augment 5FU metabolism to cytotoxic FNuct, while in the GH3 xenografts this was not the case. Thus carbogen breathing does not universally lead to increased uptake of anticancer drugs.

Animals↗
PubMed2004

The use of gel dosimetry for verification of electron and photon treatment plans in carcinoma of the scalp.

In recent years there has been a large amount of research into the potential use of radiation sensitive gels for three-dimensional verification of clinical radiotherapy doses. In this paper we report the use of a MAGIC gel dosimeter (Fong et al 2001 Phys. Med. Biol. 46 3105) for the verification of a specific patient's radiation therapy dose distribution. A 69-year-old male patient presented with a squamous cell carcinoma extending approximately 180 degrees across the top of the scalp (anterior to posterior) and from just over midline to 90 degrees left of the skull. The patient's treatment was commenced using two electron fields. For gel dosimetry, phantoms were produced in which the outer surface spatially corresponded to the outer contours of the patient's anatomy in the region of irradiation. The phantoms were treated with either electrons or intensity modulated radiation therapy (IMRT) with photons. The results identified a hot spot between the matched electron fields and confirmed the more homogeneous dose distribution produced by the IMRT planning system. The IMRT plan was then clinically implemented. The application of a clinical dose to a phantom shaped to a specific patient as well as the ability to select a slice at will during phantom imaging means that gel dosimetry can no longer be considered to simply have potential alone, but is now in fact a useful dosimetric tool.

Aged↗
PubMed2004

Monitoring temozolomide treatment of low-grade glioma with proton magnetic resonance spectroscopy.

Assessment of low-grade glioma treatment response remains as much of a challenge as the treatment itself. Proton magnetic resonance spectroscopy ((1)H-MRS) and imaging were incorporated into a study of patients receiving temozolomide therapy for low-grade glioma in order to evaluate and monitor tumour metabolite and volume changes during treatment. Patients (n=12) received oral temozolomide (200 mg m(-2) day(-1)) over 5 days on a 28-day cycle for 12 cycles. Response assessment included baseline and three-monthly magnetic resonance imaging studies (pretreatment, 3, 6, 9 and 12 months) assessing the tumour size. Short (TE (echo time)=20 ms) and long (TE=135 ms) echo time single voxel spectroscopy was performed in parallel to determine metabolite profiles. The mean tumour volume change at the end of treatment was -33% (s.d.=20). The dominant metabolite in long echo time spectra was choline. At 12 months, a significant reduction in the mean choline signal was observed compared with the pretreatment (P=0.035) and 3-month scan (P=0.021). The reduction in the tumour choline/water signal paralleled tumour volume change and may reflect the therapeutic effect of temozolomide.

Administration, Oral↗
PubMed2004

Methodological standardization for a multi-institutional in vivo trial of localized 31P MR spectroscopy in human cancer research. In vitro and normal volunteer studies.

A multi-institutional group has been created to demonstrate the utility of in vivo 31P magnetic resonance spectroscopy (31P-MRS) to study human cancers in vivo. This review is concerned with the novel problems concerning quality control in this large multinational trial of 31P MRS. Our results show that the careful and systematic performance of the quality control tests depicted here (standardized dual 1H/31P tuned radiofrequency probe, quality control procedures, routine use of 1H irradiation while acquiring 31P MR signals) has ensured comparable results between the different institutions. In studies made in vitro, the root-mean-square error was 3.6 %, and in muscle of healthy volunteers in vivo the coefficients of variance for the ratios phosphocreatine/nucleotide-triphosphates, phosphocreatine/noise and nucleotide-triphosphate/noise were 12.2, 7.0 and 10.8 %, respectively. The standardization of the acquisition protocol for in vivo-localized 31P MR spectroscopy across the different institutions has resulted in comparable in vivo data, decreasing the possible problems related to a research study carried out under a multi-institutional setting.

Biomarkers, Tumor↗
PubMed2004

Investigation of microenvironmental factors influencing the longitudinal relaxation times of drugs and other compounds.

The aim of this study was to investigate the microenvironmental factors likely to influence the longitudinal relaxation time of MR visible drugs or compounds in vivo at 1.5 T. The relative influence that viscosity, albumin and paramagnetic contrast agent concentrations have on the observed longitudinal relaxation times of three 19F MR detectable drugs and compounds have been investigated. Our data show that for 5-fluorouracil, flucloxacillin and tetrafluorosuccinic acid-containing phantoms, the presence of albumin at normal physiological concentrations will have relaxation effects of the same order of magnitude as that of a commonly clinically administered contrast agent, gadolinium diethylenetriamine pentaacetic acid. The contribution of viscosity is shown, in the examples studied here, to be of minor importance, contributing less than 6.5% to the observed relaxation effects. It is also demonstrated that in the presence of competitive binding of other ligands for common binding sites on albumin, the 19F longitudinal relaxation time of 5-fluorouracil can increase by up to 340% from its value in the absence of the competing ligand. The relevance of the findings to in vivo studies is discussed.

Albumins↗
PubMed2003

Sliding window dual gradient echo (SW-dGRE): T1 and proton resonance frequency (PRF) calibration for temperature imaging in polyacrylamide gel.

The aim of the work is to evaluate a magnetic resonance imaging (MRI) thermometry sequence suitable for targeting of focused ultrasound (FUS) when used in vascular occlusion studies. A sliding window dual gradient echo (SW-dGRE) sequence was used. This sequence has the capability of monitoring both T1 relaxation and phase changes, which vary with temperature. Preliminary work involved quantification of the changes in T1 relaxation time with temperature and obtaining the PRF shift coefficient in polyacrylamide gel as it underwent an exothermic reaction during polymerization (avoiding the use of an external heat source). Temperature changes were visualized using thermal maps acquired with the sequence. For FUS guidance a thermal imaging technique is required with a temporal resolution <5 s, a spatial resolution of approximately 1 mm and a temperature resolution of approximately 5 degrees C. The sequence was optimized to improve the CNR (contrast to noise ratio) and SNR (signal to noise ratio) in the phase and magnitude images respectively. The PRF coefficient obtained for the polyacrylamide gel was -9.98 +/- 0.24 ppb degrees C(-1), whilst deltaT1 and temperature change were related by a proportionality factor, the T1 temperature coefficient, of 102.3 +/- 2.9 ms degrees C(-1). The sequence produces an image at every 1.4 s interval. In both magnitude and phase data, the in-plane resolution is +/- 1.2 mm and the temperature resolution is approximately 2 degrees C. The advantage of this sequence is that the temperature obtained from the magnitude data can be confirmed independently using the phase data and vice versa. Thus the sequence can essentially be crosschecked.

Acrylic Resins↗
PubMed2003

Polymer gel measurement of dose homogeneity in the breast: comparing MLC intensity modulation with standard wedged delivery.

Polymer gel dosimetry has been used to measure the radiotherapy dose homogeneity in a breast phantom for two different treatment methods. The first 'standard' method uses two tangential wedged fields while the second method has three static fields shaped by multileaf collimators (MLCs) in addition to the standard wedged fields to create intensity modulated fields. Gel dose distributions from the multileaf modulation treatment show an improved dose uniformity in comparison to the standard treatment with a decreased volume receiving doses over 105%.

Breast Neoplasms↗
PubMed2003

Increased tumour extracellular pH induced by Bafilomycin A1 inhibits tumour growth and mitosis in vivo and alters 5-fluorouracil pharmacokinetics.

The aim was to determine if a specific inhibitor of vacuolar H(+)-ATPases (V-ATPases), Bafilomycin A1 (BFM), could increase the low extracellular pH (pHe) typical of solid tumours and thus inhibit their growth in vivo. BFM inhibited the proliferation of various human cells and rat pituitary GH3 tumour cells in vitro (IC50: 2.5-19.2 nM), and flow cytometry on GH3 cells showed a marked increase in S and G2M phases after 16-48 h, but no evidence of increased apoptosis. BFM caused significant inhibition of GH3 xenograft growth, and histomorphometry showed a 30% decrease in mitosis but no change in apoptosis. 31P-magnetic resonance spectroscopy (MRS) in vivo of GH3 xenografts showed that BFM increased pHe, but did not affect pHi, resulting in a decrease in the negative pH gradient (-delta pH). BFM decreased lactate formation suggesting a reduction in glycolysis. We suggest that BFM reduces extracellular H(+)-transport by inhibition of V-ATPases leading to an increase in pHe and decreased glycolysis, and thus reduced tumour cell proliferation. 19F-MRS in vivo showed that a smaller -delta pH was associated with decreased retention of 5-fluorouracil (5FU) which was consistent with our previous data in vivo implying the -delta pH controls tumour retention of 5 FU.

Animals↗
PubMed2003

Could assessment of glioma methylene lipid resonance by in vivo (1)H-MRS be of clinical value?

The potential clinical role of in vivo (1)H-MRS ((1)H-magnetic resonance spectroscopy) lipid methylene resonance measurements of human glioma has been assessed. 20 patients, 14 with low grade and 6 with high grade gliomas have been investigated using single voxel (1)H-MRS. Three of the low grade group had undergone transformation by clinical and imaging criteria. Short echo time (TE=20 ms, TR=2500 ms) single voxel Stimulated Echo Acquisition (STEAM) spectra with (acquisitions=64) and without (acquisitions=4) water suppression were acquired. Additionally, T(1) weighted (T(1)W) water spectra (TE=20 ms, TR=888 ms) were acquired pre- and post-injection of Gd-DTPA (0.2 mmol x kg(-1)). The T(1)W water spectra were used to determine the water proton enhancement occurring within the spectroscopic voxel. The enhancement expressed as a percentage was compared with the lipid methylene peak. All the high grade tumours had significantly higher levels of lipid than low grade tumours (p=0.002). Low grade tumours had significantly less water proton enhancement than transformers (p=0.04) and high grade tumours (p=0.001). The lipid methylene signal correlated strongly with the voxel water enhancement (r(2)=0.74, p<0.0001). The data support the view that the spectroscopically detected lipid methylene signal may be a useful criterion in grading glioma. The correlation of the lipid methylene signal with blood-brain barrier breakdown suggests that detection of a previously absent (1)H-MRS lipid methylene signal in low grade tumours might be an early indicator of transformation.

Biomarkers, Tumor↗
PubMed2003

Non-invasive study of human gall bladder bile in vivo using (1)H-MR spectroscopy.

The sampling of gall bladder bile for analytical studies remains an invasive procedure. We demonstrate the application of the non-invasive methodology of (1)H-MR spectroscopy to the qualitative and quantitative assessment of human gall bladder bile in vivo. Spectral profiles in vivo are shown in relation to model and porcine gall bladder bile and the quantitation in man of the trimethylamine (choline) and lecithin concentrations were estimated to range from 25.9 mM to 48.4 mM (mean: 35.8 mM, standard deviation: 9.8). The composition of human gall bladder bile together with the quantitation of various constituents can be studied non-invasively in vivo.

Adult↗
PubMed2002

A model to assess SAR for surface coil magnetic resonance spectroscopy measurements.

Surface coils are widely used in magnetic resonance (MR) studies due to their superior signal to noise properties. Application of excessive power levels to transmit surface coils may result in local tissue damage. A homogeneous muscle tissue model for the conservative prediction of surface coil specific absorption rate (SAR) is introduced. Based on this model, sequence parameters can be limited to provide operational levels within safety guidelines. It is demonstrated that this model provides worst-case SAR estimates at MR frequencies of 25.75 MHz and 63.6 MHz. The dependence of SAR on model structure and geometry is analysed and conclusions on the relationship between SAR levels and local anatomy are drawn. By making a worst-case assumption for the tissue parameters the model provides safe operational levels for all tissue types. Power-demanding proton-decoupled 31P magnetic resonance spectroscopy experiments are possible based on the SAR estimates provided. To date SAR values are calculated for 1 g of tissue. Changes in regulations to calculate SAR values for 10 g tissue masses, and the according averaging of local SAR over a larger volume, have been proposed by the International Electrotechnical Commission. A comparative study shows that up to 100% more energy may be applied to surface coils if SAR values are determined for 10 g tissue masses rather than 1 g tissue masses.

Algorithms↗
PubMed2002

Consecutive projections onto convex sets.

In this note we describe and evaluate the performance of a novel approach to information recovery that involves consecutive projection onto convex sets (POCS). The method is applied to a time series of medical image data and the results are compared to images reconstructed using the standard POCS reconstruction method. The consecutive POCS method converges in a desired step-wise manner producing reconstructed images of superior quality compared to the standard scheme and can speed up the reconstruction process. The proposed method is of value for many finite sampling imaging problems including, in particular, fast-scan magnetic resonance imaging applications.

Algorithms↗
PubMed2002

Apoptosis is associated with triacylglycerol accumulation in Jurkat T-cells.

Magnetic resonance spectroscopy is increasingly used as a non-invasive method to investigate apoptosis. Apoptosis was induced in Jurkat T-cells by Fas mAb. (1)H magnetic resonance spectra of live cells showed an increase in methylene signal as well as methylene/methyl ratio of fatty acid side chains at 5 and 24 h following induction of apoptosis. To explain this observation, (1)H magnetic resonance spectra of cell extracts were investigated. These demonstrated a 70.0+/-7.0%, 114.0+/-8.0% and 90.0+/-5.0% increase in the concentration of triacylglycerols following 3, 5 and 7 h of Fas mAb treatment (P<0.05). Confocal microscopy images of cells stained with the lipophilic dye Nile Red demonstrated the presence of lipid droplets in the cell cytoplasm. Quantification of the stained lipids by flow cytometry showed a good correlation with the magnetic resonance results (P > or =0.05 at 3, 5 and 7 h). (31)P magnetic resonance spectra showed a drop in phosphatidylcholine content of apoptosing cells, indicating that alteration in phosphatidylcholine metabolism could be the source of triacylglycerol accumulation during apoptosis. In summary, apoptosis is associated with an early accumulation of mobile triacylglycerols mostly in the form of cytoplasmic lipid droplets. This is reflected in an increase in the methylene/methyl ratio which could be detected by magnetic resonance spectroscopy.

Apoptosis↗
PubMed2002

An algorithm for the optimum combination of data from arbitrary magnetic resonance phased array probes.

When summing the spectra acquired with phased array coils, signals with low signal-to-noise ratio or wrongly corrected phase may degrade the overall signal-to-noise ratio (SNR). Here we present a mathematical expression predicting the dependence of combined SNR on the signal-to-noise ratios and errors in phase correction of composite signals. Based on this equation, signals that do not lead to an overall increase in signal-to-noise ratio can be identified and excluded from the weighted sum of signals. This tool is particularly useful for the combination of large numbers of signals. Additionally, a simple and robust algorithm for calculating the complex weighting factors necessary for the signal-to-noise weighted combination of spectroscopic data is presented. Errors in the calculation and correction of relative phase differences between composite spectra are analysed. The errors have a negligible effect on the overall spectral SNR for typical clinical magnetic resonance spectroscopy (MRS). The signal combination routine developed here has been applied to the first in vivo MRS study of human rectal adenocarcinomas at 1.5 T (Dzik-Jurasz A S K, Murphy P S, George M, Prock T, Collins D J, Swift I and Leach M O 2001 Magn. Reson. Med. at press), showing improvements of combined spectral SNR of up to 34% over the maximum SNR from a single element.

Adenocarcinoma↗
PubMed2002

Human rectal adenocarcinoma: demonstration of 1H-MR spectra in vivo at 1.5 T.

This study was designed to determine whether 1H-MR spectra of locally advanced human rectal adenocarcinoma could be acquired in vivo at 1.5 T. Despite the relatively large size of these neoplasms, only six out of 21 tumors accommodated a voxel size of 8 cm3. This was due to air pockets within the tumor mass, which limited voxel positioning. Localized proton spectra were acquired at short (20 ms) and long (135 ms) echo times (TEs) using a single-voxel technique. The most commonly detected metabolites were choline and lipid.

Adenocarcinoma↗