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M O Leach

Publications and source records attributed to M O Leach.

At least 19 recordsLinked to original sources
PubMed2006

Reproducibility of reference tissue quantification of dynamic contrast-enhanced data: comparison with a fixed vascular input function.

Reference tissues are currently used to analyse dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data. The assessment of tumour response to treatment with anti-cancer drugs is a particularly important application of this type of analysis and requires a measure of reproducibility to define a level above which a significant change due to therapy can be inferred. This study compares the reproducibility of such quantification strategies with that found using a published, group-averaged uptake curve. It is shown that reference tissue quantification gives poorer reproducibility for most parameters than that found using a group-averaged plasma curve (a change in K(trans) of greater than 41.8% and 16.4% would be considered significant in the two approaches, respectively), but successfully incorporates some of the variability observed in plasma kinetics between visits and provides vascular input functions that, across the group, are comparable with the group-averaged curve. This study therefore provides an indirect validation of the methodology.

Antineoplastic Agents↗
PubMed2006

Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging vs X-ray mammography of women at a high familial risk of breast cancer.

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1-7 individual annual screening events. Women aged 35-49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was pound28 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to pound11 731 (CE MRI vs mammography) and pound15 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

Adult↗
PubMed2006

Parametric mapping of the hepatic perfusion index with gadolinium-enhanced volumetric MRI.

The purpose of this study was to adapt the hepatic perfusion index (HPI) methodology previously developed for MRI to derive 3D parametric maps of HPI, and to investigate apparent differences in HPI maps between a group of colorectal cancer patients and controls. To achieve this, a new and simpler approach to HPI calculation which does not require measurements from the aorta or portal vein is introduced, and assessed with large liver regions of interest (ROIs) in patients and controls. Several example HPI maps showing localized variation are then presented. The subject group consisted of 12 patients with known colorectal metastases, and 13 control subjects referred for routine contrast-enhanced spine imaging with no history of neoplastic disease. HPI was evaluated from serial T1 volume acquisitions acquired over the course of a Gd-DTPA bolus injection. Regions of abnormal perfusion were visible on the HPI maps derived for the patient group, manifested as areas of locally increased HPI extending around the visible margins of known metastases evident on the conventional contrast-enhanced images. This method for MR voxel-based parametric mapping of HPI has the potential to demonstrate regional variations in perfusion at the segmental and subsegmental level.

Adult↗
PubMed2006

Evaluation of response to treatment using DCE-MRI: the relationship between initial area under the gadolinium curve (IAUGC) and quantitative pharmacokinetic analysis.

The initial area under the gadolinium curve (IAUGC) is often used in addition to or as an alternative to parameters derived from pharmacokinetic modelling of T1-weighted dynamic contrast-enhanced (DCE) MRI data in the assessment of response to treatment of cancer. However, the physiological meaning of the IAUGC has not been rigorously defined with respect to model-based parameters. Here, simulations of DCE-MRI data were used to investigate the relationship between IAUGC and the parameters K(trans) (transfer constant), v(e) (fractional extravascular extracellular volume) and v(p) (fractional plasma volume), using two vascular input functions. It is shown that IAUGC is a mixed parameter that can display correlation with K(trans), v(e) and v(p) and ultimately has an intractable relationship with all three. Furthermore, it is demonstrated that the range over which IAUGC is taken and the nature of the vascular input function do not significantly affect this relationship.

Contrast Media↗
PubMed2006

Magnetic resonance spectroscopy (MRS) in the investigation of cancer at The Royal Marsden Hospital and The Institute of Cancer Research.

Developments in magnetic resonance spectroscopy (MRS) at The Royal Marsden Hospital and The Institute of Cancer Research are reviewed in the context of preceding developments in nuclear magnetic resonance (NMR) and MRS, and some of the early developments in this field, particularly those leading to human measurements. The early development of technology, and associated techniques for human measurement and assessment will be discussed, with particular reference to experience at out institutions. Applications using particular nuclei will then be described and related to other experimental work where appropriate. Contributions to the development of MRS that have been published in Physics in Medicine and Biology will be discussed.

Academies and Institutes↗
PubMed2006

Colorectal hepatic metastases: quantitative measurements using single-shot echo-planar diffusion-weighted MR imaging.

The purpose of this study was to obtain quantitative measurements of the apparent diffusion coefficient (ADC1), flow insensitive apparent diffusion coefficient (ADC2) and perfusion fraction (F) of colorectal hepatic metastases using DWI and to compare these measurements with those obtained in liver parenchyma. Forty patients with 66 hepatic metastases from colorectal carcinoma were prospectively evaluated using DWI with three b values. Quantitative maps of the ADC1 (using b = 0, 150, 500 s/mm2 images), ADC2 (using b = 150, 500 s/mm2 images) and fractional variation (F) between ADC1 and ADC2, which reflects perfusion fraction, were calculated. The ADC1, ADC2 and F derived from metastases and liver parenchyma were compared. The mean ADC1 values of liver parenchyma and metastases were significantly higher than the mean ADC2 values (P < 0.0001, paired t-test). Colorectal metastases were found to have higher mean ADC1 and ADC2 values compared with liver (P < 0.0001, Mann-Whitney test). However, the estimated F was found to be lower in metastases compared to liver (P = 0.03, Mann-Whitney test). Colorectal hepatic metastases were characterised by higher ADC1 and ADC2 values, but lower F values compared to liver.

Adult↗
PubMed2006

Evaluation of 31P high-resolution magic angle spinning of intact tissue samples.

The first detailed evaluation is presented of high-resolution (31)P MRS using magic angle spinning (MAS) of intact tissue samples and comparison with the conventional method of studying tissue extracts. The main motivation is that MAS leaves the sample intact at the end of the study for histopathological evaluation. While MAS of tissue samples has previously been demonstrated for (1)H MRS, (31)P MRS is better suited to study of the phospholipid metabolites of importance in cancer. Samples of rhabdomyosarcoma and RIF-1 experimental tumours were maintained at 4 degrees C, spun at 3 kHz and measured in 28-min acquisitions at 11.7 and 14 T. Metabolite stability was evaluated using four sequential 28-min acquisitions. High-resolution MRS was performed on extracts of the same tissue samples. (31)P HR-MAS yielded well-resolved high-resolution spectra, showing peaks from phosphoethanolamine (PE), phosphocholine (PC), inorganic phosphate, glycerophosphoethanolamine and glycerophosphocholine, with linewidths in the range 3-20 Hz. In tumour samples there was no significant change in peak areas over a 2-h period, while peaks sensitive to pH (inorganic phosphate, PE and PC) showed a small change in chemical shift, corresponding to a change of 0.13 +/- 0.06 pH units. Tissue metabolite concentrations showed good agreement with concentrations measured from extracts of the same pieces of tissue. For calculation of metabolite concentrations, the measurement of a reference compound in a separate measurement is more robust than using the signal from a reference compound in the rotor with the sample. Compared with performing tissue extracts, use of MAS of intact tissue samples requires less preparation, is quicker and permits the same sample to be used for subsequent histopathology. The methodology has particular application in studying phospholipid metabolism in cancer and in monitoring tumour response to treatment, where concentrations of phospholipid-related metabolites are found to alter following response to a wide range of anti-cancer therapies.

Animals↗
PubMed2006

In vivo 31P MR spectral patterns and reproducibility in cancer patients studied in a multi-institutional trial.

The standardization and reproducibility of techniques required to acquire anatomically localized 31P MR spectra non-invasively while studying tumors in cancer patients in a multi-institutional group at 1.5 T are reported. This initial group of patients was studied from 1995 to 2000 to test the feasibility of acquiring in vivo localized 31P MRS in clinical MR spectrometers. The cancers tested were non-Hodgkin's lymphomas, sarcomas of soft tissue and bone, breast carcinomas and head and neck carcinomas. The best accrual and spectral quality were achieved with the non-Hodgkin's lymphomas. The initial analysis of the spectral values of the sum of phosphoethanolamine plus phosphocholine normalized by the content of nucleotide triphosphates in a homogeneous sample of 32 NHL patients studied by in vivo (31)P MRS showed good reproducibility among different institutions. No statistical differences were found between the institution with the largest number of cases accrued and the rest of the multi-institutional NHL data (2.28 +/- 0.64, mean +/- standard error; n = 17, vs 2.08 +/- 0.14, n = 15). The preliminary data reported demonstrate that the institutions involved in this trial are obtaining reproducible 31P MR spectroscopic data non-invasively from human tumors. This is a fundamental prerequisite for the international cooperative group to be able to demonstrate the clinical value of the normalized determination of phosphoethanolamine plus phosphocholine by 31P MRS as predictor for treatment response in cancer patients.

Biomarkers, Tumor↗
PubMed2006

Applications of magnetic resonance spectroscopy in radiotherapy treatment planning.

Following advances in conformal radiotherapy, a key problem now facing radiation oncologists is target definition. While MRI and CT provide images of excellent spatial resolution, they do not always provide sufficient contrast to identify tumour extent or to identify regions of high cellular activity that might be targeted with boost doses. Magnetic resonance spectroscopy (MRS) is an alternative approach that holds great promise for aiding target definition for radiotherapy treatment planning, and for evaluation of response and recurrence. MRS is able to detect signals from low molecular weight metabolites such as choline and creatine that are present at concentrations of a few mM in tissue. Spectra may be acquired from single voxels, or from a 2D or 3D array of voxels using spectroscopic imaging. The current state of the art achieves a spatial resolution of 6-10 mm in a scan time of about 10-15 min. Co-registered MR images are acquired in the same examination. The method is currently under evaluation, in particular in brain (where MRS has been shown to differentiate between many tumour types and grades) and in prostate (where cancer may be distinguished from normal tissue and benign prostatic hypertrophy). The contrast achieved with MRS, based on tissue biochemistry, therefore provides a promising alternative for identifying tumour extent and regions of high metabolic activity. It is anticipated that MRS will become an essential tool for treatment planning where other modalities lack the necessary contrast.

Brain Neoplasms↗
PubMed2005

Effects of platinum/taxane based chemotherapy on acute perfusion in human pelvic tumours measured by dynamic MRI.

Dynamic contrast enhanced MRI (DCE-MRI) is being used increasingly in clinical trials to demonstrate that vascular disruptive and antiangiogenic agents target tumour microcirculation. Significant reductions in DCE-MRI kinetic parameters are seen within 4-24 and 48 h of treatment with vascular disruptive and antiangiogenic agents, respectively. It is important to know whether cytotoxic agents also cause significant acute reductions in these parameters, for reliable interpretation of results. This study investigated changes in transfer constant (K(trans)) and the initial area under the gadolinium curve (IAUGC) following the first dose of chemotherapy in patients with mostly gynaecological tumours. A reproducibility analysis on 20 patients (using two scans performed on consecutive days) was used to determine the significance of DCE-MRI parameter changes 24 h after chemotherapy in 18 patients. In 11 patients who received platinum alone or with a taxane, there were no significant changes in K(trans) or IAUGC in either group or individual patient analyses. When the remaining seven patients (treated with a variety of agents including platinum and taxanes) were included (n=18), there were also no significant changes in K(trans). Therefore, if combination therapy does show changes in DCE-MRI parameters then the effects can be attributed to antivascular therapy rather than chemotherapy.

Adult↗
PubMed2005

Application of the chirp z-transform to MRI data.

A version of the chirp z-transform (CZT) enabling signal intensity and phase-preserving field-of-view scaling has been programmed. The algorithm is important for all single-point imaging sequences such as SPRITE when used with multiple data acquisition for T2* mapping or signal averaging. CZT has particular utility for SPRITE imaging of nuclei with short relaxation times such as sodium at high field. Here, a complete theory of the properties of CZT is given. This method operates entirely in k-space. It is compared with a conventional interpolation approach that works in image space after the application of a fast Fourier transformation.

Journal Article↗
PubMed2005

Dual-contrast echo planar imaging with keyhole: application to dynamic contrast-enhanced perfusion studies.

A new EPI-based method is presented which features optimized sampling of k-space enabling the integrated acquisition of two gradient echo images. The first of these images is predominantly T1 weighted and the second is T*2 weighted. The new method combines echo sharing of sparsely acquired high spatial frequency components with the keyhole technique and half-Fourier image reconstruction. The feasibility of acquiring high spatial and temporal resolution in vivo images for perfusion mapping is demonstrated. In contrast to most current perfusion methods, which acquire the T1- and T*2-weighted images in separate acquisitions, the need for image co-registration here is obviated since both sets of images are EPI-based and are acquired within the same measurement.

Brain↗
PubMed2005

The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations.

Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.

Angiogenesis Inhibitors↗
PubMed2005

The development of functional imaging in the diagnosis, management and understanding of childhood brain tumours.

Imaging plays a fundamental role in the management of children with brain tumours. A series of new techniques, commonly grouped under the heading functional imaging, promise to give information on the properties and biological characteristics of tissues thereby adding to the structural information available from current imaging. The EPSRC funded a workshop to bring together clinicians from the UK Children's Cancer Study Group and scientific experts in the field to identify clinical problems in childhood brain tumours that may be addressed by functional imaging and to develop a clinical test bed for applying, evaluating and developing this new technology. The presentations and discussion sessions from the workshop are summarised and a review of the current 'state of the art' for this rapidly developing area provided. A key output of the workshop was agreement on a series of hypotheses which can be tested in carefully designed clinical studies.

Brain Neoplasms↗
PubMed2005

Preliminary dose response study of a gel dosimeter using 2-Hydroxyethyl Methacrylate (HEMA).

In this work we present a gel dosimeter based on 2-Hydroxyethyl Methacrylate (HEMA). The gel dosimeter is manufactured in normal atmospheric oxygen (normoxic) and undergoes a measurable change after irradiation. The gel is shown to provide a signal to noise ratio of up to at least 35 and have a linear change in transverse relaxation rate up to 70 Gy when measured with magnetic resonance imaging.

Dose-Response Relationship, Radiation↗
PubMed2005

Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies: a new whole organ technique.

AIMS: To develop a method of processing non-formalin fixed prostate specimens removed at radical prostatectomy to obtain fresh tissue for research and for correlating diagnostic and molecular results with preoperative imaging. METHODS/RESULTS: The method involves a prostate slicing apparatus comprising a tissue slicer with a series of juxtaposed planar stainless steel blades linked to a support, and a cradle adapted to grip the tissue sample and receive the blades. The fresh prostate gland is held in the cradle and the blades are moved through the cradle slits to produce multiple 4 mm slices of the gland in a plane perpendicular to its posterior surface. One of the resulting slices is preserved in RNAlater. The areas comprising tumour and normal glands within this preserved slice can be identified by matching it to the haematoxylin and eosin stained sections of the adjacent slices that are formalin fixed and paraffin wax embedded. Intact RNA can be extracted from the identified tumour and normal glands within the RNAlater preserved slice. Preoperative imaging studies are acquired with the angulation of axial images chosen to be similar to the slicing axis, such that stained sections from the formalin fixed, paraffin wax embedded slices match their counterparts on imaging. CONCLUSIONS: A novel method of sampling fresh prostate removed at radical prostatectomy that allows tissue samples to be used both for diagnosis and molecular analysis is described. This method also allows the integration of preoperative imaging data with histopathological and molecular data obtained from the prostate tissue slices.

Biomedical Research↗