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Biomedical subjects

M O Leach

Publications and source records attributed to M O Leach.

At least 127 records · Page 7Linked to original sources
PubMed1996

MRI in the evaluation of late bone marrow changes following bone marrow transplantation.

Measurements of MR spin-lattice (T1), and spin-spin (T2) relaxation times in lumbar vertebrae have been performed in a pilot study on six adult patients, treated for acute myeloid leukaemia (AML). All patients were treated with initial chemotherapy and then proceeded to bone marrow transplantation (BMT), conditioned with Melphalan and total body irradiation (TBI). MR measurements were made between 21 and 89 months after TBI. The relaxation times in the six patients were compared with those in six healthy age-matched volunteers to establish whether there were differences between the two groups. Average T1 values in the vertebrae of the treated patients are significantly shorter (p < 0.01) than in the healthy volunteers. This is consistent with the observation of a relatively hyperintense vertebral bone marrow in the T1 weighted images and is likely to be a consequence of treatment induced fatty replacement of marrow. Shorter T1 values tend to be distributed within the centre of the lumbar vertebrae compatible with observations, made by others, which suggest that the peripheral zone of the vertebral body has been repopulated with bone marrow cells whereas the central zone, around the basivertebral vein, is predominantly fat. Histogram displays of vertebral body relaxation time distributions (T1, T2) for both patients and healthy age-matched volunteers are similar in that both patients and volunteers give histograms that are only slightly skewed. This similarity is probably a reflection of the fact that the patients have been in remission for over a year and have generally healthy bone marrow.

Acute Disease↗
PubMed1995

Calculation of sensitivity correction factors for surface coil MRS.

Quantification of MRS signals obtained with surface coils is difficult due to the inhomogeneous response of these coils. This inhomogeneity results in the measured signal from a defined volume of interest (VOI) being spatially dependent. To account for the sensitivity variation with position from the surface coil, we have developed a method of calculating correction factors for defined VOIs based on an experimentally obtained 3D sensitivity coil map. These factors may then be applied to spectra obtained from these VOIs to accurately take into consideration the varying coil sensitivity resulting in a reduction of measured signal. This method is demonstrated here to be able to correct for the inhomogeneity of surface coils over a range of two coil radii to within 4% accuracy.

Humans↗
PubMed1995

Pharmacokinetics of the 13C labeled anticancer agent temozolomide detected in vivo by selective cross-polarization transfer.

The anticancer agent temozolomide labeled with 13C (8-Carbamoyl-3-13C-methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4-(3H)-o ne), was noninvasively detected in subcutaneous RIF-1 tumors by a selective cross polarization 13C NMR method, at a field strength of 9.4T. Pharmacokinetics of the drug, at a dose of 150 mg/kg, were determined for intravenous and intraperitoneal models of administration (three animals per mode). The half-life of the drug in the tumors was approximately 60 min. The uptake and clearance of the drug, however, varied significantly between individual hosts, for both modes of administration. These results demonstrate the feasibility of obtaining pharmacokinetics of anticancer agents for individual tumors without the need for a label that might modify drug activity (e.g., fluorine). The variability of the in vivo measurements, even within the same tumor model, demonstrates the necessity of directly monitoring the tumor to evaluate drug pharmacokinetics.

Animals↗
PubMed1995

Increased NOE enhancement in 1H decoupled 31P MRS.

1H decoupling using the WALTZ-4 decoupling scheme is a popular means of improving spectral resolution in 31P NMR spectroscopy. At the same time, sensitivity in the proton decoupled 31P spectra is enhanced by the nuclear Overhauser effect. The authors show that when using WALTZ-4 decoupling in a uniform decoupler RF field, the degree of sensitivity enhancement is critically dependent on whether the decoupling interval contains an odd or an even number of WALTZ decoupling elements. This effect is demonstrated both in phantoms and in vivo.

Humans↗
PubMed1995

Quality assessment in in vivo NMR spectroscopy: II. A protocol for quality assessment. EEC Concerted Research Project.

A protocol has been developed for quality assessment in in vivo NMR spectroscopy (MRS) on whole body and animal systems. The protocol, which has been evaluated in a series of international trials, defines procedures, objects and substances to evaluate the localisation of common slice and volume selection sequences, and to assess other relevant aspects of system performance, including: signal-to-noise; signal loss; relation between signal strength, concentration and volume; selective suppression of spectral lines; spectrometer stability.

Animals↗
PubMed1995

Quality assessment in in vivo NMR spectroscopy: III. Clinical test objects: design, construction, and solutions.

Based on the requirements of test protocols developed to evaluate clinical MRS single slice and volume localisation sequences, two clinical test objects, STO1 and STO2 have been developed. The properties of a range of potential construction materials have been assessed, demonstrating that the water/Perspex interface produced minimum susceptibility effects. The design of the objects has been evaluated in trials on different magnetic resonance instruments, with size and loading being adjusted to allow use on currently available equipment. Appropriate test solutions for 31P and 1H measurements have been developed and their properties evaluated.

Magnetic Resonance Spectroscopy↗
PubMed1995

Quality assessment in in vivo NMR spectroscopy: IV. A multicentre trial of test objects and protocols for performance assessment in clinical NMR spectroscopy.

A multicentre trial of test objects and protocols for performance assessment in single volume and slice selective magnetic resonance spectroscopy (MRS) was conducted by the European Community Concerted Action on MRI and MRS. The trial assessed phosphorus and proton localisation techniques implemented on commercially available MR systems at ten sites in Europe. At each site, a number of parameters devised by the Concerted Action were measured using prototype test objects. Some of these parameters related to the quality of localisation and others to the overall performance of the spectrometer. Results were obtained for the ISIS, DRESS, STEAM, and PRESS sequences with a range of acquisition parameters, allowing evaluation of the assessment methodology and comparison of the efficacy of various implementations of these localisation techniques. The results of this trial have been important in the development of the Concerted Action's final recommendations for MRS performance assessment, and demonstrate that such assessment provides valuable information in the comparison of spectroscopy data from different sites and in the development of new localisation sequences, and provides a means of quality assurance in MRS.

Magnetic Resonance Spectroscopy↗
PubMed1995

On doubling the signal in localised stimulated echo measurements.

Stimulated echo (STEAM) localisation yields up to 50% of the full magnetisation. It is shown that given the good magnetic field homogeneity now obtained in clinical MRS, and with a slight modification to the gradient pattern, the localised signal may be nearly doubled, although at the expense of introducing a frequency-dependent amplitude for peaks in the final spectrum. A two-step phase cycle is also required. The principle is demonstrated on a clinical MR system, and the relative merits of the sequence are discussed.

Magnetic Resonance Spectroscopy↗
PubMed1995

Quantification of signal selection efficiency, extra volume suppression and contamination for ISIS, STEAM and PRESS localized 1H NMR spectroscopy using an EEC localization test object.

The three most widely used single-volume NMR localization techniques (ISIS, STEAM and PRESS) are assessed quantitatively for 1H spectroscopy using an EEC localization test object. Signal selection efficiency, suppression of outer volume signals and contamination are measured on a 1.5 T whole-body Siemens GBS1 system. The ISIS signal selection efficiency (volume of interest (VOI), 1-125 cm3) ranged from 90% to 95%, with T1 relaxation during the sequence shown to account for the observed 5-10% signal loss. Contamination for ISIS was found to be higher for smaller VOIS and ranged from approximately 45% (VOI = 1 cm3) to approximately 9% (VOI = 125 cm3). For PRESS, contamination ranged from 7% to 12% and it was between 3% and 8% for STEAM. However, the maximum signal selection efficiency for the latter two techniques (echo time, 270 ms) was relatively low (10-17%), and limited by T2 losses and the non-rectangular slice profiles of sinc pulses.

Humans↗
PubMed1994

A gradient scheme suitable for localized shimming and in vivo 1H/31P STEAM and ISIS NMR spectroscopy.

A gradient scheme is presented which may be used for STEAM or ISIS localization. One application of the scheme is to perform single-shot STEAM shimming prior to data acquisition with STEAM and ISIS, using identical gradient amplitudes and durations. Using conventional STEAM to shim for ISIS can produce line-shape distortions induced by different eddy currents in the two sequences; with this gradient scheme the problem is minimized. Line-shape improvements of STEAM and ISIS localized data obtained after volume localized shimming with the proposed STEAM sequence are demonstrated. The localization performance of the STEAM and ISIS sequences are demonstrated on phantoms and in vivo for 1H and 31P metabolites.

Brain↗
PubMed1994

In vivo monitoring of fluoropyrimidine metabolites: magnetic resonance spectroscopy in the evaluation of 5-fluorouracil.

Since 5-fluorouracil (5-FU) was synthesized in the late 1950s it has become an important component of many anticancer treatment regimens. The increasing volume of literature accumulating about this drug is evidence that the optimal administration schedule and its combination with modulators has yet to be determined. Much of the investigation of 5-FU, particularly in the clinical setting, has been in the development of administration schedules based on plasma pharmacokinetic data. Particularly with the development of modulators of 5-FU, investigators are looking more closely at its intracellular tissue pharmacology and metabolism. To study the tissue metabolism of 5-FU (and other drugs), patients often have to be willing to undergo invasive procedures, sometimes with significant discomfort, usually with little direct benefit to their management. The ability to conduct an investigation of the cellular effects of a drug in both tumor and normal tissue non-invasively will not only be more acceptable to patients, resulting in better compliance to protocols, but will give information about the in situ tissue which is not subject to the problems of invasive sampling techniques. Magnetic resonance spectroscopy is a non-invasive technique that has recently started to show potential in the area of investigating 5-FU metabolism and its impact on tumor and patient outcome. Further development of this method may ultimately have an impact on the investigation of any new anticancer agent.

Animals↗
PubMed1994

Technical note: reducing motion artifacts in in vivo magnetic resonance imaging measurements of relaxation times.

Robust and accurate methods of measuring relaxation times on commercial scanners have recently been developed. Such methods overcome many machine and sequence dependent errors, but are still subject to errors arising from motion artifacts. This paper considers methods of decreasing the effect of motion artifacts in in vivo T1 and T2 measurements. Three conventional techniques for reducing such artifacts are assessed for their use with relaxation time measurement sequences. It is shown that these techniques do not adversely affect the accuracy of phantom T1 measurements made with the spin echo/inversion recovery sequence, and of T2 measurements made using the PHAPS sequence. For in vivo measurements of T1 it is also shown that these techniques reduce the standard deviation of T1 measurements in regions of interest and improve the reproducibility of such measurements overall. Two other techniques for reducing motion artifacts were found not to be compatible with the accurate measurement of relaxation times.

Adipose Tissue↗
PubMed1994

Magnetic resonance spectroscopy applied to clinical oncology.

Magnetic resonance spectroscopy provides a means of non-invasively measuring the behaviour of a range of compounds of biochemical significance. With the development of a range of spatial localization and mapping techniques, the method has a range of promising applications in oncology. 31P and 1H spectroscopy are of value in observing the metabolism of both tumours and normal tissues. 19F spectroscopy has been used to monitor the metabolism of fluorine containing anticancer drugs, and 13C may find application in this field, particularly in pre-clinical studies. In vivo clinical measurements are complemented by pre-clinical studies, high resolution measurements of extracts from tissue samples and also the measurement of biofluids, which can provide additional metabolic and pharmacokinetic information. The application of these techniques to oncology is reviewed, with particular emphasis on their clinical role.

Clinical Trials as Topic↗
PubMed1993

A rapid interleaved method for measuring signal intensity curves in both blood and tissue during contrast agent administration.

A method has been developed that uses dynamic MR imaging to measure simultaneously the changes in signal intensity due to paramagnetic contrast agent in blood and tissue, using interleaved single-angle projection and imaging sequences. The basic projection/image sequence has a projection time resolution of 50 ms and can measure rapid changes in the blood signal intensity. Variants with a tissue suppression slab have time resolutions of 57 or 75 ms. Orientation of the projection and image planes can be defined independently. This technique will facilitate functional measurements using MR contrast agents, allowing the blood input function to be determined with excellent time resolution.

Animals↗
PubMed1993

The non-invasive monitoring of low dose, infusional 5-fluorouracil and its modulation by interferon-alpha using in vivo 19F magnetic resonance spectroscopy in patients with colorectal cancer: a pilot study.

BACKGROUND: 5-Fluorouracil (5-FU) is the most widely used cytotoxic drug in oncology and the only one useful in the management of colorectal cancer - a leading cause of cancer death worldwide. Recent studies of 5-FU have focused on increasing efficacy and reducing toxicity by varying the delivery schedule and combining it with modulators. With the development of whole body magnetic resonance systems it is now possible to examine the metabolism of 5-FU in vivo by exploiting the magnetic properties of the fluorine atom which is an integral component of the drug. PATIENTS AND METHODS: Magnetic Resonance Spectroscopy (MRS) was used to non-invasively monitor the metabolism of 5-FU in the liver metastases of colorectal cancer patients. The patients were treated with a continuous low dose intravenous infusion of 5-FU until the point of refractory disease, at which time interferon-alpha was added with the objective of modulating 5-FU activity. MRS was performed at specific phases of the treatment. RESULTS: Twenty-six patients were treated with 5-FU, 11 (42%) achieving partial response. Of the 15 given interferon when disease became refractory to 5-FU, 4 showed signs of further response. In patients observed by MRS during the first 8 weeks of 5-FU treatment, those with a visible 5-FU signal were likely to respond to treatment (p = 0.017). At the time of interferon-alpha addition, MRS showed that 7 patients developed new or increased 5-FU signals, and 4 patients showed a signal from the active metabolites of 5-FU. The patients who exhibited a new or increased 5-FU signal were more likely to show further response to interferon-alpha (p = 0.007). CONCLUSIONS: MRS is a powerful technique for monitoring intratumoural metabolism and modulation of 5-FU enabling prediction of tumour outcome. Direct metabolic information may facilitate the rapid development of optimal clinical schedules for 5-FU and its modulators, thus maximising antitumour effect and minimising toxicity to the patient. This technique may be applied to other areas of clinical medicine where knowledge of the tissue metabolism of a fluorinated drug is of interest.

Antineoplastic Combined Chemotherapy Protocols↗