Biomedical subjects

M O Leach

Publications and source records attributed to M O Leach.

179 records · Page 10Linked to original sources

PubMedDate not supplied

Quantitative magnetic resonance spectroscopy by optimized numerical curve fitting.

A technique is reported for generating the quantitative area under selected peaks within a 31P NMR spectrum. A numerical iterative method generates the fitted curve so as to minimize the RMS deviation between the fit and the experimental data. The curve is constructed from elemental grains of spectral density ('spexels'), each of which represents an elemental Lorentzian distribution, where the centre frequency and line width of the spexel may be varied within predetermined limits. This provides a fit that in principle is not restricted to a Lorentzian model. The method allows peak areas to be estimated, including the case of overlapping peaks. The method has been tested using simulated spectra containing six overlapping spectral lines each of known amplitude (ranging from 367 to 661 mV) and area; together with additional Gaussian noise with a standard deviation ranging from 30 to 646 mV. The results of fitting both unfiltered and filtered spectra were compared. The variation of quality of fit with spectral noise and filtering has been evaluated. In all cases, the method fitted the peak amplitudes to within 1% of the simulated value. The optimization processes provide an excellent non-linear spectrum filtering algorithm. Provided the noise in the spectra did not exceed ca 400 mV, prefiltered data could be adequately fitted.

Computer Simulation↗

PubMedDate not supplied

A two-point volume localized T1 measurement sequence for in vivo spectroscopy using a surface coil.

A technique for obtaining T1 values from well localized regions using surface coils and with a clinically practicable measurement time is described. The method uses a two-point Inversion-Recovery/Saturation-Recovery (IR/SR) sequence in conjunction with the image-selected in vivo spectroscopy localization scheme. T1 values are obtained by comparing the ratio of peak areas with those in a pre-computed look-up table. The method was tested by measuring the T1s of six calibrated water phantoms doped with different concentrations of gadolinium. This indicated an accuracy of 3% for T1 values in the range 400-1500 ms. 31P spectra and T1 values of Pi, phosphocreatine and alpha-, beta- and gamma-NTP metabolites from the calf muscle of healthy volunteers were obtained with the sequence employing beta 1-insensitive excitation pulses and a surface coil. The T1 values fall within the range of published values obtained by other techniques.

Data Interpretation, Statistical↗

PubMedDate not supplied

Threshold voltages for hyperbolic secant inversion pulses.

Spin inversion produced by hyperbolic secant RF pulses is independent of pulse amplitude once a threshold value is exceeded. A semi-empirical formula for these pulses has been derived by application of analytical solutions to the Bloch equations. This predicts the required coil voltages for inversion as a function of inversion bandwidth and side-to-width parameter mu, based on knowledge of a reference voltage for the loaded coil. The voltage required is shown to increase linearly with bandwidth but to fall with the mu, approximately as (1/mu)0.4. Experimental confirmation is presented, and factors affecting choice of pulse parameters are discussed.

Algorithms↗

PubMedDate not supplied

Practicalities of localization in animal and human tumours.

Factors affecting the selection and application of localization methods for measuring tumours by NMR spectroscopy are considered, with particular regard to the S/N ratio and to contaminating signal from outside the volume of interest. Methods of assessing the performance of localization techniques are considered, and their importance for quantitative measurements and comparative studies is discussed.

Animals↗

PubMedDate not supplied

The effect of oestrogen ablation on the phospholipid metabolite content of primary and transplanted rat mammary tumours.

The concentration of phospholipid metabolites was determined in chemical extracts from two types of rat mammary tumours and compared with proliferation data (S-phase fraction). One of the tumours was an oestrogen-sensitive transplanted tumour. In this tumour the concentration of phosphocholine (PC) and glycerophosphorylcholine (GPC) correlated strongly with the S-phase fraction but not with the number of cells actively synthesizing DNA. Oestrogen ablation resulted in tumour regression. Regressing tumours contained less PC and more GPC than those actively growing. The other tumour was induced in rats by intravenous administration of N-methyl N-nitrosourea. Phosphoethanolamine (PE), PC and GPC levels were not associated with the S-phase fraction in this tumour. Oestrogen ablation resulted in tumour regression. There was no significant difference between the regressing and growing tumours in PE, PC or GPC content.

Animals↗

PubMedDate not supplied

Phospholipid metabolites, prognosis and proliferation in human breast carcinoma.

The content of the phospholipid metabolites, phosphocholine, phosphoethanolamine, glycerophosphorylcholine and glycerophosphorylethanolamine was measured in chemical extracts from 46 human breast carcinoma using 31P NMR spectroscopy. Some patients had received therapy prior to tumour resection. The data were therefore stratified into two groups: (i) all tumours; and (ii) untreated tumours. Three indices of tumour proliferation i.e., mitotic index, Ki67 and S-phase fraction were determined on tissue from the same tumours and were found not to correlate with the content of any of these metabolites. In addition oestrogen-receptor status and density, tumour grade and DNA ploidy were obtained on some tumours. The phosphocholine content was higher in high grade tumours when compared with low grade tumours. There was no apparent relationship between DNA ploidy and the content of any of these metabolites. Glycerophosphorylcholine content of oestrogen-receptor positive tumours correlated with receptor density. However, there was no significant difference between receptor positive and negative tumours in the content of any of the phospholipid metabolites measured.

Aneuploidy↗

PubMedDate not supplied

Antivascular cancer treatments: functional assessments by dynamic contrast-enhanced magnetic resonance imaging.

New anticancer therapeutics that target tumor blood vessels promise improved efficacy and tolerability in humans. Early phase 1 drug trials have shown that the maximum tolerated dose may be inappropriate for more advanced clinical studies with efficacy endpoints. More advanced clinical trials have demonstrated that morphologic assessments of tumor response are of limited value for gauging the efficacy of treatment. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can serve as pharmacodynamic indicator of biological activity for antivascular cancer drugs by helping to define the biologically active dose. DCE-MRI studies may also predict the efficacy of treatment on the basis of changes observed. If DCE-MRI is to be used for the selection of antivascular drugs that advance into efficacy trials, then it will be necessary to develop standardized approaches to measurement and robust analytic approaches with clear accepted endpoints specified prospectively that have biological validity. Such developments will be essential for multicenter trials in which it will be necessary to establish effective cross-site standardization of measurements and evaluation.

Angiogenesis Inhibitors↗

PubMedDate not supplied

Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS).

BACKGROUND: Women genetically predisposed to breast cancer often develop the disease at a young age when dense breast tissue reduces the sensitivity of X-ray mammography. Our aim was, therefore, to compare contrast enhanced magnetic resonance imaging (CE MRI) with mammography for screening. METHODS: We did a prospective multicentre cohort study in 649 women aged 35-49 years with a strong family history of breast cancer or a high probability of a BRCA1, BRCA2, or TP53 mutation. We recruited participants from 22 centres in the UK, and offered the women annual screening with CE MRI and mammography for 2-7 years. FINDINGS: We diagnosed 35 cancers in the 649 women screened with both mammography and CE MRI (1881 screens): 19 by CE MRI only, six by mammography only, and eight by both, with two interval cases. Sensitivity was significantly higher for CE MRI (77%, 95% CI 60-90) than for mammography (40%, 24-58; p=0.01), and was 94% (81-99) when both methods were used. Specificity was 93% (92-95) for mammography, 81% (80-83) for CE MRI (p<0.0001), and 77% (75-79) with both methods. The difference between CE MRI and mammography sensitivities was particularly pronounced in BRCA1 carriers (13 cancers; 92%vs 23%, p=0.004). INTERPRETATION: Our findings indicate that CE MRI is more sensitive than mammography for cancer detection. Specificity for both procedures was acceptable. Despite a high proportion of grade 3 cancers, tumours were small and few women were node positive. Annual screening, combining CE MRI and mammography, would detect most tumours in this risk group.

Adult↗

PubMedDate not supplied

Comparison and evaluation of rigid, affine, and nonrigid registration of breast MR images.

PURPOSE: A new nonrigid registration method, designed to reduce the effect of movement artifact in subtraction images from breast MR, is compared with existing rigid and affine registration methods. METHOD: Nonrigid registration was compared with rigid and affine registration methods and unregistered images using 54 gadolinium-enhanced 3D breast MR data sets. Twenty-seven data sets had been previously reported normal, and 27 contained a histologically proven carcinoma. The comparison was based on visual assessment and ranking by two radiologists. RESULTS: When analyzed by two radiologists independently, all three registration methods gave better-quality subtraction images than unregistered images (p < 0.01), but nonrigid registration gave significantly better results than the rigid and affine registration methods (p < 0.01). There was no significant difference between rigid and affine registration methods. CONCLUSION: Nonrigid registration significantly reduces the effects of movement artifact in subtracted contrast-enhanced breast MRI. This may enable better visualization of small tumors and those within a glandular breast.

Adult↗

PubMedDate not supplied

A rotate-translate CT scanner providing cross-sectional data suitable for planning the dosimetry of radiotherapy treatment.

An isotope scanner (J & P Engineering Multipoise scanner, Mk. III) has been converted to provide a simple transmission Ct scanning device, using a 137Cs gamma-ray source. The performance of the scanner has been evaluated by imaging a variety of phantoms and an anaesthetised rabbit. The relationship between the measured linear attenuation coefficient and the known electron density was found to be linear, for a range of materials with densities between those of bone and air. For reconstructed pixels of size 5 X 5 mm2 the percentage standard deviation of linear attenuation coefficient is typically 2.4% for bone and 3.6% for muscle. The spatial resolution of the device was measured and the performance of the scanner with the maximum design source strength was predicted. In the reconstruction of a cross section of the rabbit and of a human thorax phantom, air-muscle, lung-muscle, and muscle-bone interfaces are clearly visible. From experience gained with this scanner the role of simple CT scanning devices in radiotherapy treatment planning is considered. The resolution in linear attenuation coefficient and the spatial resolution available from the scanner are considered sufficient for radiotherapy treatment planning.

Animals↗

PubMedDate not supplied

Constrained deconvolution of SPECT liver tomograms by direct digital image restoration.

Several techniques for performing digital image restoration are reviewed and the problems associated with evaluating image processing are discussed. An application of constrained deconvulution to images of the liver produced by single-photon emission computed tomography is presented. Specific evaluation criteria are suggested and based on these, the choice of conditions best suited for processing liver images is proposed. Typically cold tumor contrast can be improved by a factor of greater than 2 whilst image mottle increases negligibly.

Filtration↗

PubMedDate not supplied

The development of high-efficiency cathode converters for a multiwire proportional chamber positron camera.

A high-efficiency cathode converter for 511-keV photons has been developed for incorporation into a multiwire proportional chamber (MWPC) positron camera. The converter consists of a honeycomb pattern produced in a 1-mm-thick lead sheet to leave lead walls with a thickness of approximately 60 micron. The converter also serves as the cathode of an MWPC, the gap between the converter and the anode wire plane being 2.5 mm. This small gap results in a high secondary electron extraction efficiency without the need for additional drift voltages. Measurements of the efficiencies of a plane converter and of two types of structured converters in a single section MWPC are described and the efficiency is found to increase in proportion to the converter surface area. This result justifies the use of a simple theoretical model whereby an extrapolation to the efficiency of a detector consisting of a stack of 20 MWPC sections, each section having two converters, is made. The efficiency of this proposed system is calculated to be 17% for 511-keV photons.

Beta Particles↗

PubMedDate not supplied

The design and use of a dual-frequency surface coil providing proton images for improved localization in 31P spectroscopy of small lesions.

Nuclear magnetic resonance (NMR) spectroscopy of small lesions is restricted by the difficulties of localizing the surface coil with respect to the lesion and the problem of ensuring that signal is only obtained from the lesion and not from surrounding tissue. A double-tuned coil has been developed that permits NMR proton images to be obtained from a region of interest, prior to carrying out 31P spectroscopy of the same region with the same coil, without the need for further adjustment. The coil provides a means of accurately localizing the region from which the 31P signal is obtained, whilst offering a means of accurately applying 31P signal localization methods, and the possibility of making corrections for the nonuniform sensitivity of a given surface coil. The coil makes use of two parallel resonant circuits, with independent rf connections, but sharing a common coil. Simulated shorted and open circuit lambda /4 cables are used, respectively, to open circuit each circuit at the resonant frequency of the other circuit and ensure that the simulated lambda /4 line is short circuited for each circuit at the circuit's resonant frequency. At 63.6 MHz, the Q of the coil was 190 unloaded and 90 loaded, and at 25.7 MHz the Q was 210 unloaded and 140 loaded, for a 4-cm-diam coil. The coil has been used to obtain proton images and 31P spectra. A circuit employing only one input was also developed.

Humans↗

PubMedDate not supplied

Installation of an ambient-temperature control system in a 1.5-tesla whole body system to facilitate animal studies.

An ambient-temperature control system, designed to maintain small, anaesthetized animals at physiological temperatures during long examination times, is described. The system is suitable for installation in large bore, whole-body magnets and can be positioned close to the animal under study. Design details and a description of the equipment used is given. The system proved to be satisfactory in maintaining mice at physiological temperatures.

Animals↗

PubMedDate not supplied

MRIW: parametric analysis software for contrast-enhanced dynamic MR imaging in cancer.

A software package called the Magnetic Resonance Imaging Workbench has been developed to characterize contrast agent uptake in vivo following T1-weighted magnetic resonance (MR) imaging with qualitative analysis of changes in signal intensity or quantitative analysis of changes in contrast agent concentration over time. Various descriptors may be calculated from the analysis of dynamic contrast agent-enhanced MR studies and visualized as false-color overlays, which allow the immediate display and interpretation of information taken from a series of images acquired over time. Qualitative descriptors include onset of enhancement, initial gradient, mean gradient, maximum enhancement, and washout. These parameters can be particularly useful in the investigation of multifocal or widespread disease. Quantitative descriptors include capillary permeability-surface area product, extracellular volume, and T1 and may be used to monitor changes in the disease state and to assess the efficacy of treatment. In addition, they allow comparison of data obtained from different patients, from independent MR studies, or from studies performed with different modalities. Analysis of contrast enhancement during MR imaging in terms of such qualitative or quantitative parameters is a promising new method of data analysis in radiology.

Computer Graphics↗

PubMedDate not supplied

Phosphocholine and choline content of rat sarcoma cells grown in the presence and absence of serum.

Rat sarcoma cells were grown in vitro in tissue culture medium (DMEM) supplemented with 10% foetal calf serum for 5 to 8 days followed by serum withdrawal to produce populations of cells with a variety of cell cycle distributions. Phosphocholine (PCho) and choline content and S + G2 fraction were determined. The phosphocholine content of faster growing populations of serum supplemented cells was higher than the slower growing populations. Choline content was not consistently associated with S + G2 fraction. Serum deprivation was accompanied by a decrease in S + G2 fraction after 24 hours but even after 48 hours PCho content was only slightly decreased.

Animals↗

PubMedDate not supplied

Introduction to in vivo MRS of cancer: new perspectives and open problems.

Measurements of tumour extracts and tumour cell lines using 1H and 31P MRS have demonstrated the potential of the technique to distinguish different types of tumour, and in a range of tumours to provide information on degree of malignancy, grade and prognosis. In vivo studies have shown that changes in the energetic status of tumours, and in the phospholipid metabolites, correlate with the response of tumours to treatment, providing the potential to monitor the effectiveness of cancer treatment. Routine application of these techniques in clinical measurements depends upon the development of robust equipment and measurement methods to aid clinical measurements. Considerable advances have been made. Imaging can now be performed very rapidly, and a range of localisation technique have been established. Equipment provides for automatic set up and shimming, and coils with increased sensitivity are available. Improvements in hardware provide more sensitive receive coils; and shielded gradients which provide for a more robust performance. 31P studies are being improved by the use of NOE enhancement and 1H decoupling, increasing the specificity and sensitivity of the techniques. These advances in instrumentation need to be complemented by advances in our understanding of the biochemical processes in tumours giving rise to the observed spectral changes. In this paper, recent reports of NMR spectroscopy in cancer are reviewed, together with the requirements for tumour measurements.

Humans↗