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M O Leach

Publications and source records attributed to M O Leach.

At least 91 records · Page 5Linked to original sources

Optimized MR imaging for polyacrylamide gel dosimetry.

Polyacrylamide gels are a powerful tool to measure radiation dose by quantifying the NMR T2 relaxation times of the irradiated gel. The exploitation of these radiation sensitive gels in clinical radiotherapy requires accurate mapping of T2 values. This paper describes the optimization strategy used to identify accurate and practical methods of measuring the range of T2 values typical of gel dosimeters (140-700 ms). The MR imaging techniques used to measure T2 values and the choice of image acquisition parameters are described. Four sequences are compared and the results are analysed in terms of accuracy, signal-to-noise ratio and acquisition time. A multiple spin echo sequence was found to yield the most accurate results (98.9%). Single spin echo sequences, such as Hahn spin echo and EPI spin echo, were found to measure gel T2 values with an accuracy of 90.1%. This paper reports the importance of careful selection and optimization of the MR imaging sequences for accurate and reliable polyacrylamide gel dosimetry.

Echo-Planar Imaging↗

The reproducibility of polyacrylamide gel dosimetry applied to stereotactic conformal radiotherapy.

The reproducibility of polyacrylamide gel (PAG) dosimetry has been evaluated when used to verify two radiotherapy treatment plans of increasing complexity. The plans investigated were a three-field coplanar arrangement, using the linac jaws for field shaping, and a four-field, conformal, non-coplanar plan using precision-cast lead alloy shielding blocks. Each treatment was performed three times using phantoms and calibration gels manufactured in-house. Two phantoms were specially designed for this work to aid accurate positioning of the gels for irradiation and imaging. All gels were imaged post-irradiation using a Siemens Vision 1.5T MR scanner. T2 relaxation images were calibrated to absorbed dose distributions using a number of smaller calibration vessels to produce distribution maps of relative dose. The relative dose distributions were found to be reproducible, with the standard deviation on the mean areas enclosed by the > or = 50% isodose lines measured in three orthogonal planes being 6.4% and 4.1% for the coplanar and non-coplanar plans respectively. The measured distributions were also consistent with those planned, with isodose lines generally agreeing to within a few millimetres. However, the measured absolute doses were on average 23.5% higher than those planned. Although the polyacrylamide gel dosimetry technique has some limitations, particularly when calibrating distributions to absolute dose, the ability to resolve sharp dose gradients in three dimensions with millimetre precision is invaluable when verifying complex conformal treatment plans, where avoidance of proximal, critical structures is a treatment criterion.

Acrylic Resins↗

Implications of respiratory motion for the quantification of 2D MR spectroscopic imaging data in the abdomen.

Magnetic resonance spectroscopic imaging (MRSI) studies in the abdomen or breast are acquired in the presence of respiratory motion. This modifies the point spread function (PSF) and hence the reconstructed spectra. We evaluated the quantitative effects of both periodic and aperiodic motion on spectra localized by MRSI. Artefactual signal changes, both the modification of native to a voxel and spurious signals arising elsewhere, depend primarily upon the motion amplitude relative to the voxel dimension. A similar dependence on motion amplitude was observed for simple harmonic motion (SHM), quasi-periodic motion and random displacements. No systematic dependence upon the period or initial phase of SHM or on the array size was found. There was also no significant variation with motion direction relative to the internal and external phase-encoding directions. In measured excursion ranges of 20 breast and abdominal tumours, 70% moved < or = 5 mm, while 30% moved 6-23 mm. The diaphragm and fatty tissues in the gut typically moved approximately 15-20 mm. While tumour/organ excursions less than half the voxel dimension do not substantially affect native signals, the bleeding in of strong lipid signals will be problematic in 1H studies. MRSI studies in the abdomen, even of relatively well-anchored tumours, are thus likely to benefit from the addition of respiratory triggering or other motion compensation strategies.

Abdomen↗

Radiotherapy planning of the pelvis using distortion corrected MR images: the removal of system distortions.

Image distortion is an important consideration in the use of magnetic resonance (MR) images for radiotherapy planning. The distortion is a consequence of system distortion (arising from main magnetic field inhomogeneity and nonlinearities in the applied magnetic field gradients) and of effects arising from the object/patient being imaged. A two stage protocol has been developed to correct both system and object-induced distortion in pelvic images which incorporates measures to maintain the quality, accuracy and consistency of the imaging and correction procedures. The first stage of the correction procedure is described here and involves the removal of system distortion. Object- (patient-) induced effects will be described in a subsequent work. Images are acquired with the patient lying on a flat rigid bed, which reproduces treatment conditions. A frame of marker tubes surrounding the patient and attached to the bed provides quality assurance data in each image. System distortions in the three orthogonal planes are mapped using a separate phantom, which fits closely within the quality control frame. Software has been written which automates the measurement and checking of the many marker positions which the test objects generate and which ensures that patient data are acquired using a consistent imaging protocol. Results are presented which show that the scanner and the phantoms used in measuring distortion give highly reproducible results with mean changes of the order of 0.1 mm between repeated measurements of marker positions in the same imaging session. Effective correction for in plane components of system distortion is demonstrated.

Humans↗

Magnetic resonance spectroscopy in the evaluation of neurotoxicity following cranial irradiation for childhood cancer.

In order to evaluate the role of proton MR spectroscopy (1H-MRS) in the diagnosis and assessment of long-term radiation-related neurotoxicity, 14 children who had received cranial irradiation for the treatment of childhood leukaemia (n = 6) or brain tumours (n = 8) underwent 1H-MRS, MRI and neuropsychological assessment. Short-term effects at 2 months following treatment were studied in a further three patients. MRI abnormalities were observed in nine patients. No statistically significant differences between patients and controls (n = 17) were seen in any of the calculated 1H-MRS metabolite ratios, in any of the three patient groups. On multivariate logistic regression analysis there was a correlation between the choline/water ratio and a low IQ. It is concluded that any systematic radiation-induced changes in the 1H MRS metabolites must be below the detection threshold of this study.

Adolescent↗

Radiation dosimetry using polymer gels: methods and applications.

New, complex radiotherapy delivery techniques require dosimeters that are able to measure complex three-dimensional dose distributions accurately and with good spatial resolution. Polymer gel is an emerging new dosimeter being applied to these challenges. The aim of this review is to present a practical overview of polymer gel dosimetry, including gel manufacture, imaging, calibration and application to radiotherapy verification. The dosimeters consist of a gel matrix within which is suspended a solution of acrylic molecules. These molecules polymerize upon exposure to radiation, with the degree of polymerization being proportional to absorbed dose. The polymer distribution can be measured in two or three dimensions using MRI or optical tomography and, after calibration, the images can be converted into radiation dose distributions. Manufacture of the gel is reported to be reproducible, and measured dose in the range 0-10 Gy is accurate to within 3-5%. In-plane image resolution of 1 mm x 1 mm, with image slice thicknesses of between 2-5 mm, is typically achievable using clinical 1.5 T MR scanners and standard T2 weighted imaging sequences. The gels have been used to verify a number of conventional and novel radiotherapy modalities, including brachytherapy, intensity modulated radiotherapy and stereotactic radiosurgery. All the studies have confirmed the value and versatility of the dosimetry technique.

Acrylamide↗

Treatment of SW620 cells with Tomudex and oxaliplatin induces changes in 2-deoxy-D-glucose incorporation associated with modifications in glucose transport.

UNLABELLED: Many studies suggest that changes in the uptake of the glucose analog FDG after therapy, compared with pretreatment uptake, predicts tumor response to therapy. However, clinical interpretation is compromised by a limited understanding of the effect of therapy on FDG and 2-deoxy-D-glucose (DG) uptake at the tumor cell level. METHODS: Uptake of 2-deoxy-D-[1-(3)H]glucose (3H-DG) by SW620 colonic tumor cells was measured before and 8, 16, 24, and 48 h after treatment with the novel platinum drug oxaliplatin and the novel thymidylate synthase inhibitor Tomudex. Glucose transport was determined by measuring the initial rate of uptake of the nearly nonmetabolized glucose analog 3-O-methyl-D-[1-(3)H]glucose (3H-OMG). The effect of these drugs on cell cycle kinetics was determined using flow cytometry. RESULTS: Treatment of SW620 cells with oxaliplatin was found to decrease uptake of 3H-DG after up to 24 h, but uptake returned to control levels after longer treatment. The initial decrease in 3H-DG incorporation was associated with a lower rate of glucose transport. Treatment of cells with Tomudex induced an increase in 3H-DG uptake that depended on treatment duration. Both glucose transport and the volume of distribution of 3H-OMG were higher in Tomudex-treated cells than in control cells. Flow cytometry showed that oxaliplatin induced a G2 and M arrest, whereas a buildup of cells in the S phase was associated with Tomudex treatment. Both treatments induced apoptosis in SW620 cells. CONCLUSION: Changes in uptake of DG by SW620 colonic tumor cells responding to therapy is specific to the drug type. Modulation of glucose transport was associated with changes in 3H-DG uptake.

Antineoplastic Agents↗

Evaluating the effect of rectal distension and rectal movement on prostate gland position using cine MRI.

PURPOSE: To evaluate the dynamic interrelationship between rectal distension and rectal movements, and to determine the effect of rectal movement on the position of the prostatic gland using cine magnetic resonance imaging (MRI). METHODS AND MATERIALS: Fifty-five patients with biopsy-proven or suspected prostate cancer were examined in the axial plane using repeated spoiled gradient-echo sequences every 10 seconds for 7 minutes. Twenty-four patients received bowel relaxants before imaging. Images were analyzed for the degree of rectal distension, for the incidence, magnitude, and number of rectal and prostate movements. RESULTS: Rectal movements were seen in 28 (51%) patients overall, in 10 (42%) of those receiving bowel relaxants and in 18 (58%) not receiving bowel relaxants. The incidence of rectal movements correlated with the degree of rectal distension (p = 0.0005), but the magnitude of rectal movements did not correlate with the degree of rectal distension. Eighty-six rectal movements resulting in 33 anterior-posterior (AP) prostate movements were seen. The magnitude of rectal movements correlated well with degree of prostate movements (p < 0.001). Prostate movements in the AP direction were seen in 16 (29%) patients, and in 9 (16%) patients the movement was greater than 5 mm. The median prostate AP displacement was anterior by 4.2 (-5 to +14 mm). CONCLUSIONS: Cine MRI is able to demonstrate near real time rectal and associated prostate movements. Rectal movements are related to rectal distension and result in significant displacements of the prostate gland over a time period similar to that used for daily fractionated radiotherapy treatments. Delivery of radiotherapy needs to take into account these organ movements.

Aged↗

Spin-lattice relaxation of laser-polarized xenon in human blood.

The nuclear spin polarization of 129Xe can be enhanced by several orders of magnitude by using optical pumping techniques. The increased sensitivity of xenon NMR has allowed imaging of lungs as well as other in vivo applications. The most critical parameter for efficient delivery of laser-polarized xenon to blood and tissues is the spin-lattice relaxation time (T1) of xenon in blood. In this work, the relaxation of laser-polarized xenon in human blood is measured in vitro as a function of blood oxygenation. Interactions with dissolved oxygen and with deoxyhemoglobin are found to contribute to the spin-lattice relaxation time of 129Xe in blood, the latter interaction having greater effect. Consequently, relaxation times of 129Xe in deoxygenated blood are shorter than in oxygenated blood. In samples with oxygenation equivalent to arterial and venous blood, the 129Xe T1s at 37 degrees C and a magnetic field of 1.5 T were 6.4 s +/- 0.5 s and 4.0 s +/- 0.4 s, respectively. The 129Xe spin-lattice relaxation time in blood decreases at lower temperatures, but the ratio of T1 in oxygenated blood to that in deoxygenated blood is the same at 37 degrees C and 25 degrees C. A competing ligand has been used to show that xenon binding to albumin contributes to the 129Xe spin-lattice relaxation in blood plasma. This technique is promising for the study of xenon interactions with macromolecules.

Arteries↗

Measurement of the extracellular pH of solid tumours in mice by magnetic resonance spectroscopy: a comparison of exogenous (19)F and (31)P probes.

Precise measurement of pH(e) in vivo may be of clinical value for both diagnosis and selection of therapy. pH(e) measurements made by the (31)P probe 3-aminopropylphosphonate (3-APP) were compared with those made by the (19)F probe, 3-[N-(4-fluor-2-trifluoromethylphenyl)-sulphamoyl]-propionic acid (ZK-150471) in three solid tumour types, human HT29 xenografts, murine RIF-1 fibrosarcomas and Lettre tumours grown subcutaneously in mice. No significant differences were observed when probe measurements of pH(e) were compared at 20-60 min post-administration, although very low pH(e) values (ca. 6.0) were recorded in two out of eight Lettre tumours by ZK-150471. The more rapid pH(e) measurements possible using ZK-150471 showed that during the first 20 min post-administration significant increases occurred in pH(e) which were greatest in the more necrotic tumours. Since isolated cell experiments showed that ZK-150471 was non-toxic and did not enter the cells, this early increase in pH(e) may reflect gradual penetration by ZK-150471 of the reportedly alkaline necrotic space in the tumours. The wide chemical shift range, improved signal-to-noise and absence of signal overlap allowed a more rapid and precise measurement of pH(e) by ZK-150471 compared to 3-APP. These characteristics suggest that ZK-150471 is currently the preferred pH(e) probe for non-invasive MRS.

Animals↗

Dynamic contrast-enhanced MRI in the differentiation of breast tumors: user-defined versus semi-automated region-of-interest analysis.

Dynamic contrast-enhanced MR mammography is an increasingly used method of evaluating breast pathology. The purpose of this study was to compare two semi-automated methods of region of interest (ROI) analysis with a user-defined method, in the discrimination of breast tumors using dynamic contrast-enhanced MRI. Results are presented from the retrospective analysis of 81 malignant and 36 benign breast lesions. The study demonstrates the importance of a consistent ROI strategy and also shows that semi-automated approaches offer a standardized method, which may improve the discrimination of primary breast tumors. J. Magn. Reson. Imaging 1999; 10:945-949.

Adenocarcinoma↗

Perfluorocarbon emulsions as intravenous delivery media for hyperpolarized xenon.

The use of perfluorooctyl bromide (PFOB) emulsions as delivery media for hyperpolarized xenon has been investigated. Emulsion droplet size was controlled by varying the content of egg yolk phospholipid (EYP), which served as an emulsifier. Hyperpolarized 129Xe nuclear magnetic resonance (NMR) spectra of the dissolved gas were obtained. The NMR spectra were found to be correlated strongly with the emulsion droplet size distribution. The NMR line width is determined by xenon exchange between the PFOB droplets and the aqueous environment. Our findings show that, in a 1.5-Tesla field, relatively narrow 129Xe NMR spectra are obtained for droplet sizes larger than 5 microm. Preliminary results on animal models show that PFOB emulsions have potential as hyperpolarized 129Xe carriers for in vivo magnetic resonance applications.

Animals↗

Signal modulation in (1)H magnetic resonance spectroscopy using contrast agents: proton relaxivities of choline, creatine, and N-acetylaspartate.

The effect of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) on the proton relaxation properties of choline, creatine and N-acetylaspartate has been assessed quantitatively. The compounds studied, either directly or indirectly as chemical constituents of other compounds, contribute to proton MR spectroscopy observable metabolite resonances. The longitudinal and transverse Gd-DTPA proton relaxivities of the methyl groups of choline, creatine, and N-acetylaspartate have been determined at 1.5 T. The longitudinal relaxivity of lactate has also been measured. Longitudinal and transverse relaxivity values were found to vary in the order N-acetylaspartate < creatine < choline. Using choline as an example, the maximum possible signal enhancement predicted in vivo in the presence of 0.5 mM Gd-DTPA (using a T(1)-weighted sequence, TR = 888 msec, TE = 20 msec) was found to be approximately 100 %. For a T(2)-weighted sequence (TR = 3000 msec, TE = 270 msec) a maximum signal loss of 53 % was calculated. The present study indicates why the use of contrast agents in spectroscopic investigations may lead to significant changes in signal intensities. Magn Reson Med 42:1155-1158, 1999.

Aspartic Acid↗

Vascular occlusion using focused ultrasound surgery for use in fetal medicine.

OBJECTIVE: Focused ultrasound surgery (FUS) is being developed clinically for the non-invasive treatment of soft tissue tumours of the prostate, bladder, liver, kidney, muscle and breast. In the work described in this paper, the application of FUS is extended to investigate the potential to induce vascular occlusion, with the aim of applying the technique to problems in fetal medicine and oncology. METHODS: In this feasibility study the occlusion of femoral blood flow in vivo is demonstrated using an array of multiple single exposures of 1.7 MHz focused ultrasound. These were placed in two rows of four lesions at a focal depth of 5 mm. The 4660-W cm-2 (free field spatial peak intensity) 2-s exposures were placed 2 mm apart. Vascular patency was assessed using a Siemens Vision (1.5T) magnetic resonance (MR) imaging scanner with an extremity coil, and intravenous gadolinium contrast agent. FLASH and FISP MR sequences were used to obtain full 3D data sets providing information on soft tissue damage and perfusion. RESULTS AND CONCLUSION: Total vascular occlusion was achieved in four of nine cases and significant vascular disruption in five of nine cases. Refinement of the FUS technique and long-term studies are now indicated prior to initial clinical application in fetal medicine.

Animals↗

Magnetic resonance detects metabolic changes associated with chemotherapy-induced apoptosis.

Apoptosis was induced by treating L1210 leukaemia cells with mechlorethamine, and SW620 colorectal cells with doxorubicin. The onset and progression of apoptosis were monitored by assessing caspase activation, mitochondrial transmembrane potential, phosphatidylserine externalization, DNA fragmentation and cell morphology. In parallel, 31P magnetic resonance (MR) spectra of cell extracts were recorded. In L1210 cells, caspase activation was detected at 4 h. By 3 h, the MR spectra showed a steady decrease in NTP and NAD, and a significant build-up of fructose 1,6-bisphosphate (F-1,6-P) dihydroxyacetonephosphate and glycerol-3-phosphate, indicating modulation of glycolysis. Treatment with iodoacetate also induced a build-up of F-1,6-P, while preincubation with two poly(ADP-ribose) polymerase inhibitors, 3-aminobenzamide and nicotinamide, prevented the drop in NAD and the build-up of glycolytic intermediates. This suggested that our results were due to inhibition of glyceraldehyde-3-phosphate dehydrogenase, possibly as a consequence of NAD depletion following poly(ADP-ribose) polymerase activation. Doxorubicin treatment of the adherent SW620 cells caused cells committed to apoptosis to detach. F-1,6-P was observed in detached cells, but not in treated cells that remained attached. This indicated that our observations were not cell line- or treatment-specific, but were correlated with the appearance of apoptotic cells following drug treatment. The 31P MR spectrum of tumours responding to chemotherapy could be modulated by similar effects.

Animals↗

Experimental 3D dosimetry around a high-dose-rate clinical 192Ir source using a polyacrylamide gel (PAG) dosimeter.

It is well known that the experimental dosimetry of brachytherapy sources presents a challenge. Depending on the particular-dosimeter used, measurements can suffer from poor spatial resolution (ion chambers), lack of 3D information (film) or errors due to the presence of the dosimeter itself distorting the radiation flux. To avoid these problems, we have investigated the dosimetry of a clinical 192Ir source using a polyacrylamide gel (PAG) dosimeter. Experimental measurements of dose versus radial distance from the centre of the source (cross-line plots) were compared with calculations produced with a Nucletron NPS planning system. Good agreement was found between the planning system and gel measurements in planes selected for analysis. Gel dosimeter measurements in a coronal plane through the phantom showed a mean difference between measured absorbed dose and calculated dose of 0.17 Gy with SD = 0.13 Gy. Spatially, the errors at the reference point remain within one image pixel (1.0 mm). The use of polymer gel dosimetry shows promise for brachytherapy applications, offering complete, three-dimensional dose information, good spatial resolution and small measurement errors. Measurements close to the source, however, are difficult, due to some of the limiting properties of the polyacrylamide gel.

Acrylic Resins↗

Dynamics of polymerization in polyacrylamide gel (PAG) dosimeters: (I) ageing and long-term stability.

Few quantitative data are available on the kinetics of polymerization reactions in polymer gel (PAG) dosimeters and their long-term stability. Post-irradiation polymerization reactions have been found to continue for several weeks, posing questions regarding dosimeter stability and its achievement. In this paper we report an investigation of polymerization kinetics in PAG dosimeters and the effect of diffusing oxygen into the dosimeter, post irradiation, as a potential method of inhibiting further polymerization and stabilizing the dose distribution. Results show continuous post-irradiation changes in transverse relaxation rate R2 with time over the five week study period and that a steady-state may not be reached for a period of months. An assessment is made of the appropriate time to image the dosimeter which shows that after three to four days the polymerization change is slow compared with imaging time. The implications of the time delay between irradiation and imaging are discussed in terms of the resultant sensitivity of the dosimeter and accuracy of the dose measured. In pairs of dosimeters, one sealed the other open to air, oxygen diffusing into the dosimeter arrests polymerization. However, the diffusion rate is too slow to make this method practicable. The slow diffusion means that while in regions near the air/gel interface polymerization is quickly arrested, in deeper regions it may continue for many hours, causing artefacts in the dose distribution. In the companion paper to this from a collaborating team, a study focusing on modelling oxygen diffusion in dosimeter gel will be presented.

Acrylic Resins↗

Dynamics of polymerization in polyacrylamide gel (PAG) dosimeters: (II) modeling oxygen diffusion.

Oxygen contamination of a polyacrylamide gel (PAG) dosimeter can have a significant detrimental effect upon the performance characteristics of the gel as a dosimeter. Oxygen contamination can occur during preparation, but can also arise from the diffusion of atmospheric oxygen through vessel walls. Even 'trace' amounts of oxygen present in any gaseous space (usually nitrogen filled) between the surface of the PAG and the vessel seal can have a detectable effect. This paper describes a method used to quantify the detrimental effects of a range of oxygen concentrations upon the performance of the PAG. The results of diffusion studies for air and pure oxygen diffusing into the PAG over time are presented and coupled with a novel method of calculating oxygen concentrations in the PAG. Results obtained suggest that the diffusion is Fickian. The coefficient of diffusion D has been calculated to be (8+/-2) x 10(-6) cm2 s(-1) for oxygen diffusing into PAG stored at 4 degrees C, under the assumption that the diffusion mechanism is independent of the concentration of the diffusing species. In addition, a quantitative relation has been established between the transverse relaxation rate R2 of the PAG and the concentration of oxygen present. The implications of these findings for polymer gel dosimetry are discussed.

Acrylic Resins↗