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Biomedical subjects

S Webb

Publications and source records attributed to S Webb.

At least 91 records · Page 5Linked to original sources
PubMed2000

A quantitative treatment planning study evaluating the potential of dose escalation in conformal radiotherapy of the oesophagus.

BACKGROUND AND PURPOSE: This study aims to evaluate the reduction in radiation dose to normal thoracic structures through the use of conformal radiotherapy techniques in the treatment of oesophageal cancer, and to quantify the resultant potential for dose escalation. MATERIALS AND METHODS: Three different CT-derived treatment plans were created and compared for each of ten patients. A two-phase treatment with conventional straight-edged fields and standard blocks (CV2), a two-phase conformal plan (CF2), and a three-phase conformal plan where the third phase was delivered to the gross tumour only (CF3), were considered for each patient. Escalated dose levels were determined for techniques CF2 and CF3, which by virtue of the conformal field shaping, did not increase the mean lung dose. The resulting increase in tumour control probability (TCP) was estimated. RESULTS: A two-phase conformal technique (CF2) reduced the volume of lung irradiated to 18 Gy from 19.7+/-11.8 (1 SD) to 17.1+/-12.3% (P=0.004), and reduced the normal tissue complication probability (NTCP) from 2.4+/-4.0 to 0.7+/-1.6% (P=0.02) for a standard prescribed dose of 55 Gy. Consequently, technique CF2 permitted a target dose of 59.1+/-3.2 Gy without increasing the mean lung dose. Technique CF3 facilitated a prescribed dose of 60.7+/-4.3 Gy to the target, the additional 5 Gy increasing the TCP from 53. 1+/-5.5 to 68.9+/-4.1%. When the spinal cord tolerance was raised from 45 to 48 Gy, technique CF3 allowed 63.6+/-4.l Gy to be delivered to the target, thereby increasing the TCP to 78.1+/-3.2%. CONCLUSIONS: Conformal radiotherapy techniques offer the potential for a 5-10 Gy escalation in dose delivered to the oesophagus, without increasing the mean lung dose. This is expected to increase local tumour control by 15-25%.

Adult↗
PubMed2000

The dosimetric consequences of inter-fractional patient movement on conventional and intensity-modulated breast radiotherapy treatments.

BACKGROUND AND PURPOSE: A method has been developed to enable a comparison to be made between the effects of movement on conventional tangential breast treatments and intensity-modulated treatments delivered using compensators. MATERIALS AND METHODS: The effects of set-up error and organ motion were studied for a set of six patients. Images were taken of these patients over the course of their treatment and conventional wedged and compensated treatment plans were designed for each. Dose-volume statistics were used to evaluate each of the treatment plans by examining the volume outside the dose range 95-105%. To assess the effects of movement alone, the volume change from day 1 was also calculated. RESULTS: Thirty-six estimated CT-sets were available for evaluation. Measurements of breast volume showed the volume to increase to a peak between fraction 4 and 8 and then decrease back below the initial volume. The standard treatment was found to yield 29/36 plans (81%) with greater than 5% volume outside the dose range 95-105%. For the compensated plans this dropped to 11/36 plans (31%). The analysis of the volume changes from day 1 showed that for both standard and compensated treatments 7/30 plans (23%) had an increase in volume outside the dose range 95-105% of greater than 5% of the total planning target volume. CONCLUSIONS: The compensated treatment is more susceptible to patient movement. However, the actual volume of tissue outside 95-105% dose is less when compared to standard treatment implying the compensated treatment is still superior.

Artifacts↗
PubMed2000

Enhancing the efficiency of introducing precise mutations into the mouse genome by hit and run gene targeting.

The creation of precise clinical mutations by targeting is important in elucidating disease pathogenesis using mouse models. 'Hit and run' gene targeting is an elegant method to achieve this goal. This uses first a positive selection to introduce the targeting vector carrying the required mutation and then a negative selection to identify clones which have removed vector and wild-type sequences by intrachromosomal recombination. However, this approach has only been successfully used in a handful of cases. We used this procedure to introduce precise clinical mutations into the exon 10 region of the cystic fibrosis transmembrane conductance regulator (Cftr) gene. Using a CMV promoter driven hygromycin/thymidine kinase (hyg/tk) fusion gene as both our dominant and negative selectable marker, we targeted the Cftr locus very efficiently but only identified false runs after the negative selection step. This defect in thymidine kinase induced toxicity to gancyclovir correlated with methylation of the transgene. Consequently we devised a stringent screening procedure to select only true 'run' clones. Unfortunately these 'run' clones had lost the mutation so we altered the vector design to bias the run step to retain the mutation and used a different tk selection cassette with a HSVtk promoter sequence. This new vector design allowed both efficient 'hit and run' for two cystic fibrosis (CF) mutations with no false positives and successful germline transmission of the novel G480C missense mutation.

Animals↗
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

A new concept of multileaf collimator (the shuttling MLC)--an interpreter for high-efficiency IMRT.

This paper proposes a radically new concept for a multileaf collimator for a photon linear accelerator for delivering IMRT with high monitor-unit efficiency. The concept is to consider each M (rows) x N (columns) two-dimensional intensity-modulated beam (2D IMB) as a set of N/2 M (rows) x 2 (columns) areas of modulation. Each area is then delivered by a set of M shuttling attenuating elements (called here the shuttling MLC) with a very high monitor-unit efficiency. The elements shuttle between each of the two columns comprising the M x 2 area and the modulation is provided by the variation in dwell time of the elements. The principles of this shuttling multileaf collimator are discussed and examples illustrating its operation are given. The main achievement reported in this paper is the development and robust testing of an interpreter which describes the position-time course of movement of the elements as a function of monitor units. This interpreter fully accounts for leakage transmission through the elements. It completely avoids the across-the-rows tongue-and-groove underdose. A large number of ID and 2D IMBs have been subjected to this interpreter and it is shown that for random patterns of fluence the SMLC is more monitor-unit efficient than the Bortfeld-Boyer technique (the most efficient with a conventional MLC) when the modulation is highly structured.

Algorithms↗
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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Conformal intensity-modulated radiotherapy (IMRT) delivered by robotic linac--conformality versus efficiency of dose delivery.

Intensity-modulated radiotherapy (IMRT) may be delivered with a high-energy-photon linac mounted on a robotic gantry and executing a complex trajectory. In a previous paper an inverse-planning technique was developed for such an application. Here the work is extended to demonstrate the dependence of conformality on the size of the elemental pencil beam, on the complexity of the trajectory and on the sampling of azimuth and elevation of the collimated source. The improved conformality of complex trajectories is demonstrated and benchmarked relative to simpler trajectories, more representative of existing non-robotic IMRT techniques. Specifically, by choosing a very fine pencil beam, exquisitely conformal dose distributions have been obtained. Important sampling considerations have been determined. Expressions have been derived for the dosimetry and monitor-unit efficiency of robotic IMRT. Equivalent trajectories were computed for executing the complex robotic trajectories instead by using a conventional linac. The work benchmarks an ideal in IMRT against which more practical and more common techniques may be measured.

Humans↗
PubMed2000

Intensity modulated arc therapy (IMAT) with centrally blocked rotational fields.

A new technique for intensity-modulated beam (IMB) delivery that combines the features of intensity modulated arc therapy (IMAT) with the use of 'classical blocks' is proposed. The role of the blocks is to realize the high-gradient modulation of the intensity profile corresponding to the region to be protected within the body contour, while the MLC leaves or the secondary collimator defines the rest of the field and delivers intensity-modulated multiple rotational segments. The centrally blocked radiation fields are applied sequentially, in several rotations. Each rotation of the gantry is responsible for delivering one segment of the optimal intensity profile. The new IMAT technique is applied for a treatment geometry represented by an annular target volume centrally located within a circular body contour. The annulus encompasses a circular critical structure, which is to be protected. The beam opening and corresponding weight of each segment are determined in two ways. The first method applies a linear optimization algorithm to precalculated centrally blocked radial dose profiles. These radial profiles are calculated for a set of beam openings, ranging from the largest field that covers the whole planning target volume (PTV) to the smallest, which is 1 cm larger than the width of the central block. The optimization is subjected to dose homogeneity constraints imposed on a linear combination of these profiles and finally delivers the dimensions and weights of the rotational beams to be used in combination. The second method decomposes into several subfields the fluence profile of a rotational beam known to deliver a constant dose level to PTV. This fluence profile is determined by using the analytical method proposed by Brahme for the case of the annular PTV and the concentric organ at risk (OAR). The proper segmentation of this intensity profile provides the field sizes and corresponding weights of the subfields to be used in combination. Both methods show that for this particular treatment geometry, three to seven segments are sufficient to cover the PTV with the 95% dose level and to keep the dose level to the central critical structure under 30% of the maximum dose. These results were verified by experimentally delivering the calculated segments to radiotherapy verification films sandwiched between two cylindrical pieces of a pressed-wood phantom. The total beam time for a three-field irradiation was 77 s. The predicted and experimental dose profiles along the radius of the phantom agreed to within 5%. Generalization of this technique to real-patient treatment geometry and advantages over other conformal radiotherapy techniques are also discussed.

Algorithms↗
PubMed2000

Fibroproliferation occurs early in the acute respiratory distress syndrome and impacts on outcome.

The fibroproliferative phase of acute respiratory distress syndrome (ARDS) has traditionally been regarded as a late event but recent studies that suggest increased lung collagen turnover within 24 h of diagnosis challenge this view. We hypothesized that fibroproliferation is initiated early in ARDS, characterized by the presence of fibroblast growth factor activity in the lung and would relate to clinical outcome. Patients fulfilling American/European Consensus Committee criteria for ARDS and control patients ventilated for non-ARDS respiratory failure underwent bronchoalveolar lavage (BAL) and serum sampling within 24 h of diagnosis and again at 7 d. The ability of BAL fluid (BALF) to stimulate human lung fibroblast proliferation in vitro was examined in relation to concentrations of N-terminal peptide for type III procollagen (N-PCP-III) in BALF/serum and clinical indices. At 24 h, ARDS lavage fluid demonstrated potent mitogenic activity with a median value equivalent to 70% (range 31-164) of the response to serum, and was significantly higher than control lavage (32% of serum response, range 11-42; p < 0.05). At 24 h, serum N-PCP-III concentrations were elevated in the ARDS group compared with control patients (2.8 U/ml; range 0.6-14.8 versus 1.1 U/ml; range 0.4-3.7, p < 0.0001) as were BALF N-PCP-III concentrations (2.9 U/ml; range 0. 6-11.4 versus 0.46 U/ ml; range 0.00-1.63, p < 0.01). In addition, BALF N-PCP-III concentrations at 24 h were significantly elevated in nonsurvivors of ARDS compared with survivors (p < 0.05). At 7 d, the mitogenic activity remained elevated in the ARDS group compared with control (p < 0.05) and was also significantly higher in ARDS nonsurvivors compared with survivors (67%; range 45-120 versus 31%; range 16-64, p < 0.05). These data are consistent with the hypothesis that fibroproliferation is an early response to lung injury and an important therapeutic target.

Adolescent↗
PubMed2000

Intensity modulated radiation therapy: a clinical review.

Intensity modulated radiotherapy represents a significant advance in conformal radiotherapy. In particular, it allows the delivery of dose distributions with concave isodose profiles such that radiosensitive normal tissue close to, or even within a concavity of, a tumour may be spared from radiation injury. This article reviews the clinical application of this technique to date, and discusses the practical issues of treatment planning and delivery from the clinician's perspective.

Algorithms↗
PubMed2000

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↗
PubMed2000

Self-reported musculoskeletal disorders among visiting and office home care workers.

This paper examines the associations between self-reported musculoskeletal disorders (MSDs) and work factors and injuries among home care workers. Based on 99 focus group participants and 892 survey respondents, results show a high level of MSDs among both visiting and office home care workers. While visiting home care workers tend to feel pain in the back, office workers tend to report pain in the neck and shoulder. Hazards in clients' homes, injuries moving clients and stress are associated with self-reported MSDs for visiting home care workers. Repetitive tasks and stress are associated with self-reported MSDs for office home care workers. Age and months in the profession have no affect on self-reported MSDs.

Canada↗