Biomedical subjects

M O Leach

Publications and source records attributed to M O Leach.

At least 73 records · Page 4Linked to original sources

PubMed2000

Hyperpolarized 129Xe NMR as a probe for blood oxygenation.

Optically enhanced NMR with (129)Xe and (3)He is emerging as a novel and promising technique for medical imaging of lungs and other tissues. Here it is shown that hyperpolarized (129)Xe NMR provides a powerful means of measuring blood oxygenation quantitatively and noninvasively. The interaction of xenon with hemoglobin is responsible for an oxygen-dependent NMR shift of (129)Xe in red blood cells, in sharp contrast to the current model of xenon-hemoglobin binding. This effect could be exploited in brain functional studies, and in the assessment of conditions and diseases affected by blood oxygenation.

Humans↗

PubMed2000

Surface-coil polarization transfer for monitoring tissue metabolism in vivo.

Polarization transfer methods can substantially enhance NMR signals from nuclei of low gamma, which are J-coupled to nuclei of high gamma, but to date have had limited application for in vivo (31)P MRS studies. They require both accurate flip angles and good localization in order to achieve their potential. Described here is an implementation of the insensitive nuclei enhanced by polarization transfer (INEPT) polarization transfer method using segmented adiabatic BIR4 RF pulses. Localization uses ISIS, applied to the coupled (1)H spins. Detailed analysis is performed to evaluate the specific absorption rate power deposition when using surface coils. Polarization transfer, localization capability, and use with surface coils are demonstrated using suitable test objects. Finally, in vivo data are presented from the liver of a normal volunteer in which the signals from the phosphodiester peaks are substantially enhanced.

Cell Polarity↗

PubMed2000

Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high-dose methotrexate treatment for childhood cancer.

BACKGROUND: To avoid the late sequelae associated with cranial radiation therapy in childhood, intermediate- or high-dose intravenous methotrexate (HDMTX) has found increasing application as a means of preventing the development of overt central nervous system disease in childhood acute leukaemia. However, acute and chronic neurotoxicity has been described following HDMTX therapy, and the long-term intellectual outcome in children treated in this way is inadequately documented. Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain is a noninvasive, quantitative way of assessing aspects of cerebral metabolism, which has not previously been applied to the study of children undergoing central nervous system directed therapy. PROCEDURE: To evaluate the potential role of (1)H-MRS in the investigation of related neurotoxicity, 11 children who had received HDMTX (cumulative dose 6-96 g/m(2)) underwent localised (1)H-MRS, magnetic resonance imaging. Neuropsychological assessments were performed on the children who had more than 1 year of follow-up time since last methotrexate treatment. Control (1)H-MRS studies on 11 adult and 6 young volunteers were undertaken. Eight patients had spectra of adequate quality. Comparisons between (1)H-MRS metabolite ratios and normal controls were made. RESULTS: Patients had a low choline/water ratio compared to controls (P < 0.01). No differences between patient and control NAA/water, Cr/water, Naa/Cr, and Cho/Cr ratios were seen. Overall, 3 patients had abnormal white matter changes on MRI. The mean IQ of the patients (104.1) was in the normal range. CONCLUSIONS: It is postulated that choline depletion in the brains of these patients may reflect subclinical disturbances of myelin metabolism as a result of methotrexate therapy and may represent a possible avenue of treatment in patients with clinical chronic methotrexate-related neurotoxicity.

Adolescent↗

PubMed2000

On the oxygenation-dependent (129)Xe T (1) in blood.

The spin-lattice relaxation time, T(1), of hyperpolarized (129)Xe in blood is sensitive to blood oxygenation. In particular, it has been shown that (129)Xe T(1) is shorter in venous blood than in arterial blood. We have studied the T(1) of hyperpolarized (129)Xe dissolved in human blood as a function of blood oxygenation level, sO(2), in the physiological oxygenation range. We show that the (129)Xe relaxation rate, T(1)(-1), varies in a nonlinear fashion as a function of sO(2). This finding suggests that direct interaction of xenon with the paramagnetic heme group of deoxyhemoglobin is not the dominant oxygenation-dependent relaxation mechanism for (129)Xe in blood. These results corroborate the idea that the oxygenation-dependence of (129)Xe T(1) is determined by conformational changes of hemoglobin induced by oxygen binding.

Carbon Dioxide↗

PubMed2000

Intravenous delivery of hyperpolarized (129)Xe: a compartmental model.

There is an increasing interest in the use of hyperpolarized 129-xenon (HpXe) NMR for the measurement of tissue perfusion. In this paper we present a theoretical study designed to assess the merit of intravenous HpXe delivery compared with the existing respiration techniques. A compartmental model was created to describe the behavior of the injected bolus in the circulatory system and in the lungs. The dependence of the tissue concentration on the T(1) and solubility of the Xe in the various compartments, and on injection rate, were evaluated. By this process the critical loss mechanisms are identified. It is shown that the predicted tissue concentrations of HpXe in gray and white matter are comparable using respiration or injection techniques.

Humans↗

PubMed2000

1H decoupling for in vivo (19)F MRS studies using the time-share modulation method on a clinical 1.5 T NMR system.

Time-share modulation has been implemented successfully on a clinical 1.5 T nuclear magnetic resonance (NMR) system to perform in vivo (19)F[-(1)H] decoupling. It uses commercially available radiofrequency (RF) filters, a transistor-transistor logic (TTL)-controlled attenuator, and a double-resonant RF surface coil suitable for (19)F magnetic resonance spectroscopy (MRS) studies in vivo. This decoupling scheme gives a threefold improvement in signal-to-noise ratio performance compared with the conventional WALTZ-4 decoupling scheme, when significant interaction exists between the decoupler and the receiver. It can also eliminate receiver saturation (i.e., saturation due to coupling of the strong proton decoupling pulse to the (19)F coil) without the need for a high-isolation coil system, thus allowing flexibility in coil geometry. This method has been demonstrated in vivo in patients receiving 5-fluorouracil chemotherapy. Magn Reson Med 44:5-9, 2000.

Antimetabolites, Antineoplastic↗

PubMed2000

Initial measurements of ifosfamide and cyclophosphamide in patients using (31)P MRS: pulse-and-acquire, decoupling, and polarization transfer.

Ifosfamide and cyclophosphamide are (31)P-containing alkylating agents used widely in the treatment of cancer. In this communication it is demonstrated that signals from these agents may be detected in the livers of patients undergoing treatment using (31)P MRS at 1.5 T. In vitro, signals are enhanced 4-fold by use of (1)H-decoupling, with a B(1) field of 100 Hz at -150 Hz relative to water. Polarization transfer (BINEPT) enhances signals in vitro by a further factor of 5.5. Preliminary results using the double-resonance methods in vivo show that the technique is practicable although enhancements may be less than observed in vitro. Factors affecting signal enhancement in vivo are evaluated. Magn Reson Med 44:180-184, 2000.

Antineoplastic Agents, Alkylating↗

PubMed2000

Gallbladder localization of (19)F MRS catabolite signals in patients receiving bolus and protracted venous infusional 5-fluorouracil.

The hepatobiliary distribution of 5-fluorouracil (5FU) catabolites was investigated in nine patients. Using fluorine 3D-chemical shift imaging, four patients receiving protracted venous infusion of 5FU demonstrated catabolite localized to the gallbladder. No hepatobiliary fluorine signals were detected in three patients whose gallbladders were absent or abnormal. Signals from the gallbladder showed a 2.2-2.4 ppm high-frequency shift from alpha-fluoro-beta-alanine, suggesting the presence of alpha-fluoro-beta-alanine-bile-acid conjugates. 3D-chemical shift imaging of two patients receiving bolus 5FU revealed alpha-fluoro-beta-alanine to be localized to the liver within 1 hr of administration. In one patient examined 4 hr after bolus administration, catabolite signal was detected only in the gallbladder.

Aged↗

PubMed2000

SAR and tissue heating with a clinical (31)P MRS protocol using surface coils, adiabatic pulses, and proton-decoupling.

In MRS studies using surface transmit coils, accurate assessment of local SAR and RF heating represents a difficult problem involving the coil geometry and electromagnetic and geometric tissue properties. Methodologies to determine the optimum operating parameters for dual-resonant surface coil measurements are presented, based on a standardized coil and protocol used in a multicenter (31)P MRS clinical trial, using adiabatic pulses and bilevel proton decoupling. Spatial distributions of absorbed radiation in human calf and in a tissue-equivalent gel phantom were modeled using finite-element simulations and realistic conductivity and permittivity values. Local SAR in worst-case 1 cm(3) volumes of interest (VOIs) in calf is predicted to be below international guidelines, and the temperature at the skin surface was found to increase due to the RF by less than 2 degrees C and remain below 37 degrees C. The heating rate and maximum temperature in the gel, at positions guided by the simulations, were within guideline values for both extremities and trunk and in reasonable agreement with that predicted.

Adult↗

PubMed2000

Preclinical development of noninvasive vascular occlusion with focused ultrasonic surgery for fetal therapy.

OBJECTIVE: This study was undertaken to investigate the ability of focused ultrasonic surgery to occlude blood flow in vivo. STUDY DESIGN: A 5-mm linear track exposure of 1.7-MHz focused ultrasound was applied across the femoral vessels for 5 seconds. Free field spatial peak intensities in the range of 1,000 to 4,660 W x cm(-2) were used. Vascular occlusion was confirmed after demonstration of an absent distal arterial pulse and an absent flow signal on magnetic resonance angiography and subtracted (after minus before) contrast-enhanced dual-echo steady-state sequences. RESULTS: The minimum intensity for consistent vascular occlusion was 1,690 W x cm(-2) at a focal depth of 5 mm when the transducer was moved at 1 mm x s(-1) orthogonal to the direction of blood flow. CONCLUSIONS: This study demonstrates that focused ultrasonic surgery can achieve reproducible vascular occlusion in vivo. Potential obstetric applications include noninvasive ultrasonographically guided occlusion of placental vessels mediating interfetal transfusion in monochorionic twins.

Animals↗

PubMed2000

High-resolution segmented EPI in a motor task fMRI study.

A high-resolution gradient echo, multi-slice segmented echo planar imaging method was used for functional MRI (fMRI) using a motor task at 1.5 Tesla. Functional images with an in-plane resolution of 1 mm and slice thickness of 4 mm were obtained with good white-gray matter contrast. The multi-shot approach, combined with a short total readout period of 82 ms, limits blurring effects for short T(2)(*) tissues (such as gray matter), assuring truly high-resolution images. In all subjects, motor functions were clearly depicted in the contralateral central sulcus over several slices and sometimes activation was detected in the supplementary motor area and/or ipsilateral central sulcus. The average signal change of 11+/-3% was much higher than in standard low-resolution fMRI EPI experiments, as a result of larger relative blood fractions.

Adult↗

PubMed2000

Magnetic resonance imaging screening in women at genetic risk of breast cancer: imaging and analysis protocol for the UK multicentre study. UK MRI Breast Screening Study Advisory Group.

The imaging and analysis protocol of the UK multicentre study of magnetic resonance imaging (MRI) as a method of screening for breast cancer in women at genetic risk is described. The study will compare the sensitivity and specificity of contrast-enhanced MRI with two-view x-ray mammography. Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for three years, with annual MRI and x-ray mammography continuing for up to 5 years. A symptomatic cohort will be measured in the first year to ensure consistent reporting between centres. The MRI examination comprises a high-sensitivity three-dimensional contrast-enhanced assessment, followed by a high-specificity contrast-enhanced study in equivocal cases. Multiparametric analysis will encompass morphological assessment, the kinetics of contrast agent uptake and determination of quantitative pharmacokinetic parameters. Retrospective analysis will identify the most specific indicators of malignancy. Sensitivity and specificity, together with diagnostic performance, diagnostic impact and therapeutic impact will be assessed with reference to pathology, follow-up and changes in diagnostic certainty and therapeutic decisions. Mammography, lesion localisation, pathology and cytology will be performed in accordance with the UK NHS Breast Screening Programme quality assurance standards. Similar standards of quality assurance will be applied for MR measurements and evaluation.

Adult↗

PubMed2000

Improving image quality and T(1) measurements using saturation recovery turboFLASH with an approximate K-space normalisation filter.

We present a method for reducing the image point-spread function and measuring T(1) using saturation recovery turboFLASH (SRTF) with centric-ordered k-space and a k-space correction filter designed to compensate for longitudinal magnetisation evolution during image acquisition. The method provides a two point T(1) measurement that reduces inaccuracies and image artefacts caused by longitudinal magnetisation evolution in conventional turboFLASH methods. The method is designed for use in rapid, quantitative measurements of contrast agent uptake in vivo.

Adult↗

PubMed2000

Dynamic contrast enhanced MRI of prostate cancer: correlation with morphology and tumour stage, histological grade and PSA.

AIM: To quantify MRI enhancement characteristics of normal and abnormal prostatic tissues and to correlate these with tumour stage, histological grade and tumour markers. MATERIALS AND METHODS: Quantitative gradient recalled echo MR images were obtained following bolus injection of gadopentetate dimeglumine in 48 patients with prostate cancer. Turbo spin-echo T2-weighted images at the same anatomical position were reviewed for the presence of tumours (45 regions), normal peripheral zone (33 regions), and normal appearing central gland (30 regions). Time-signal intensity parameters (onset time, mean gradient and maximal amplitude of enhancement and wash-out score) and modelling parameters (permeability surface area product, lesion leakage space and maximum gadolinium concentration) were correlated with tumour stage, histological grade (Gleason score) and serum prostatic specific antigen (PSA) levels. RESULTS: Significant differences were noted between peripheral zone and tumour with respect to signal intensity and modelling parameters (P = 0.0001), except onset time. No differences between central gland and tumour enhancement values were seen. There was weak correlation between MRI tumour stage and tumour vascular permeability (r(2) = 12%; P = 0.02) and maximum tumour gadolinium concentration (r(2) = 14%; P = 0.015). However, no significant correlations were seen with Gleason score or PSA levels. CONCLUSION: Quantification of MR contrast enhancement characteristics allows tissue discrimination in prostate cancer consistent with known variations in microvessel density estimates.

Aged↗

PubMed2000

Rationale for a national multi-centre study of magnetic resonance imaging screening in women at genetic risk of breast cancer.

In 1994, the UK National Health Service identified as a research priority that magnetic resonance imaging (MRI) should be assessed as a screening tool for young, pre-menopausal women who are at a high genetic risk of developing breast cancer. In 1997 a national multicentre study was established to compare MRI with X-ray mammography as a method for screening for breast cancer in this group of women. This paper reviews the relevant literature and describes the rationale that led to the setting up of this study.

Journal Article↗

PubMed2000

Protocol for a national multi-centre study of magnetic resonance imaging screening in women at genetic risk of breast cancer.

The protocol of the national multicentre study of Magnetic Resonance Imaging (MRI) as a method of screening for breast cancer in women at genetic risk is described. The sensitivity and specificity of contrast-enhanced MRI will be compared with two-view X-ray mammography in a comparative trial. Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for 3 years, with annual MRI and X-ray examination continuing for up to 5 years. A symptomatic cohort will be measured in the initial phase of the study to ensure consistent reporting between centres. The MRI examination will comprise an initial high-sensitivity screening measurement, followed by a high-specificity measurement in equivocal cases. Retrospective analysis will identify the most specific indicators of malignancy. Sensitivity and specificity, together with diagnostic performance, diagnostic impact and therapeutic impact will be assessed with reference to pathology, follow-up and changes in diagnostic certainty and therapeutic decisions. The psychological impact of screening in this high-risk group will be ascertained.

Journal Article↗

PubMed2000

A modified polymer gel for radiotherapy dosimetry: assessment by MRI and MRS.

The characteristics of a new formulation of polymer gel are assessed for MRI-based radiotherapy dosimetry. The gel, based on the first BANG gel formulation, replaces acrylamide with the less toxic monomer sodium methacrylate. The relationship between MR T2 relaxation time and radiation dose for the gel formulation was studied using spin-echo imaging. Proton magnetic resonance spectroscopy was also used to assess the gel composition as a function of dose. The effect of gel pH on the dose-response and baseline R2 was then investigated. A calibration performed on gel without pH modulation (pH = 6.6) revealed a dose-response of 0.14 s(-1) Gy(-1) within the range 0-8 Gy. The baseline R2 increases with pH above neutrality, rising from 1.2 s(-1) at pH = 5.1 to 5.0 s(-1) at pH = 10.1. The dose-response is also pH dependent, having a minimum value of 0.09 s(-1) Gy(-1) at pH = 10.1 and peaking at 0.21 s(-1) Gy(-1) at pH = 7.7. Undertaking proton spectroscopy on the gels enabled resonances associated with the monomer and co-monomer to be studied. By integrating the peaks from the respective monomers and normalizing to the signal at 0 Gy it was shown that only 50% of the methacrylate monomer was used at 10 Gy, whereas 80% of the co-monomer was used at this dose. The data indicate that this gel has a reduced toxicity and a comparable dose response to the previously reported BANG gel. In addition, the performance of the gel can be optimized by controlling the pH. MR spectroscopy revealed that the crosslinking co-monomer is consumed more readily than the monomer, which is in agreement with previous compositional studies.

Calibration↗

PubMed2000

Proton spectroscopic imaging of polyacrylamide gel dosimeters for absolute radiation dosimetry.

Proton spectroscopy has been evaluated as a method for quantifying radiation induced changes in polyacrylamide gel dosimeters. A calibration was first performed using BANG-type gel samples receiving uniform doses of 6 MV photons from 0 to 9 Gy in 1 Gy intervals. The peak integral of the acrylic protons belonging to acrylamide and methylenebisacrylamide normalized to the water signal was plotted against absorbed dose. Response was approximately linear within the range 0-7 Gy. A large gel phantom irradiated with three, coplanar 3 x 3 cm square fields to 5.74 Gy at isocentre was then imaged with an echo filter technique to map the distribution of monomers directly. The image, normalized to the water signal, was converted into an absolute dose map. At the isocentre the measured dose was 5.69 Gy (SD = 0.09) which was in good agreement with the planned dose. The measured dose distribution elsewhere in the sample shows greater errors. A T2 derived dose map demonstrated a better relative distribution but gave an overestimate of the dose at isocentre of 18%. The data indicate that MR measurements of monomer concentration can complement T2-based measurements and can be used to verify absolute dose. Compared with the more usual T2 measurements for assessing gel polymerization, monomer concentration analysis is less sensitive to parameters such as gel pH and temperature, which can cause ambiguous relaxation time measurements and erroneous absolute dose calculations.

Calibration↗