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Biomedical subjects

S Webb

Publications and source records attributed to S Webb.

At least 19 recordsLinked to original sources
PubMed2006

Direct-aperture optimization applied to selection of beam orientations in intensity-modulated radiation therapy.

Direct-aperture optimization (DAO) was applied to iterative beam-orientation selection in intensity-modulated radiation therapy (IMRT), so as to ensure a realistic segmental treatment plan at each iteration. Nested optimization engines dealt separately with gantry angles, couch angles, collimator angles, segment shapes, segment weights and wedge angles. Each optimization engine performed a random search with successively narrowing step sizes. For optimization of segment shapes, the filtered backprojection (FBP) method was first used to determine desired fluence, the fluence map was segmented, and then constrained direct-aperture optimization was used thereafter. Segment shapes were fully optimized when a beam angle was perturbed, and minimally re-optimized otherwise. The algorithm was compared with a previously reported method using FBP alone at each orientation iteration. An example case consisting of a cylindrical phantom with a hemi-annular planning target volume (PTV) showed that for three-field plans, the method performed better than when using FBP alone, but for five or more fields, neither method provided much benefit over equally spaced beams. For a prostate case, improved bladder sparing was achieved through the use of the new algorithm. A plan for partial scalp treatment showed slightly improved PTV coverage and lower irradiated volume of brain with the new method compared to FBP alone. It is concluded that, although the method is computationally intensive and not suitable for searching large unconstrained regions of beam space, it can be used effectively in conjunction with prior class solutions to provide individually optimized IMRT treatment plans.

Algorithms↗
PubMed2006

Optimum parameters in a model for tumour control probability, including interpatient heterogeneity: evaluation of the log-normal distribution.

The heterogeneity of human tumour radiation response is well known. Researchers have used the normal distribution to describe interpatient tumour radiosensitivity. However, many natural phenomena show a log-normal distribution. Log-normal distributions are common when mean values are low, variances are large and values cannot be negative. These conditions apply to radiosensitivity. The aim of this work was to evaluate the log-normal distribution to predict clinical tumour control probability (TCP) data and to compare the results with the homogeneous (delta-function with single alpha-value) and normal distributions. The clinically derived TCP data for four tumour types-melanoma, breast, squamous cell carcinoma and nodes-were used to fit the TCP models. Three forms of interpatient tumour radiosensitivity were considered: the log-normal, normal and delta-function. The free parameters in the models were the radiosensitivity mean, standard deviation and clonogenic cell density. The evaluation metric was the deviance of the maximum likelihood estimation of the fit of the TCP calculated using the predicted parameters to the clinical data. We conclude that (1) the log-normal and normal distributions of interpatient tumour radiosensitivity heterogeneity more closely describe clinical TCP data than a single radiosensitivity value and (2) the log-normal distribution has some theoretical and practical advantages over the normal distribution. Further work is needed to test these models on higher quality clinical outcome datasets.

Breast Neoplasms↗
PubMed2006

IMRT delivery to a moving target by dynamic MLC tracking: delivery for targets moving in two dimensions in the beam's eye view.

A new modification of the dynamic multileaf collimator (dMLC) delivery technique for intensity-modulated therapy (IMRT) is outlined. This technique enables the tracking of a target moving through rigid-body translations in a 2D trajectory in the beam's eye view. The accuracy of the delivery versus that of deliveries with no tracking and of 1D tracking techniques is quantified with clinically derived intensity-modulated beams (IMBs). Leaf trajectories calculated in the target-reference frame were iteratively synchronized assuming regular target motion. This allowed the leaves defined in the lab-reference frame to simultaneously follow the target motion and to deliver the required IMB without violation of the leaf maximum-velocity constraint. The leaves are synchronized until the gradient of the leaf position at every instant is less than a calculated maximum. The delivered fluence in the target-reference frame was calculated with a simple primary-fluence model. The new 2D tracking technique was compared with the delivered fluence produced by no-tracking deliveries and by 1D tracking deliveries for 33 clinical IMBs. For the clinical IMBs normalized to a maximum fluence of 200 MUs, the rms difference between the desired and the delivered IMB was 15.6 +/- 3.3 MU for the case of a no-tracking delivery, 7.9 +/- 1.6 MU for the case where only the primary component of motion was corrected and 5.1 +/- 1.1 MU for the 2D tracking delivery. The residual error is due to interpolation and sampling effects. The 2D tracking delivery technique requires an increase in the delivery time evaluated as between 0 and 50% of the unsynchronized delivery time for each beam with a mean increase of 13% for the IMBs tested. The 2D tracking dMLC delivery technique allows an optimized IMB to be delivered to moving targets with increased accuracy and with acceptable increases in delivery time. When combined with real-time knowledge of the target motion at delivery time, this technique facilitates improved target conformality relative to no-tracking deliveries and allows PTV margin reduction.

Algorithms↗
PubMed2006

A strategy to minimize errors from differential intrafraction organ motion using a single configuration for a 'breathing' multileaf collimator.

Intensity-modulated radiation therapy (IMRT) can be delivered by the 'sliding-leaves' dynamic multileaf collimator (DMLC) technique. Intrafraction organ motion can be accommodated by arranging an identical tracking motion for 'breathing leaves'. However, this is only possible for very specific circumstances such as regular, mathematically parameterizable, rigid-body, density-conserving, one-dimensional translations. In this paper, we investigate what happens when planes of tissue in the line of sight of the MLC have differential motion with respect to the moving leaves. In this situation, there is no solution to the problem and a perfect tracking motion cannot be arranged. However, an iterative minimization-of-errors 'solution' (or strategy) can be found and the technique is presented for this. From this, under certain mathematically simple differential motions it is possible to obtain some elegant algebraic solutions which are presented. In general, however, a lengthy computational minimization is required and results of examples of these are presented.

Algorithms↗
PubMed2006

Motion effects in (intensity modulated) radiation therapy: a review.

During a course of fractionated radiation therapy and between the fractions the tissues of the human body may move relative to some reference location in which the radiation therapy was planned. This has been known for over a century and simple 'coping mechanisms' (margins) have been used to approximately compensate. Since the introduction of highly accurate conformal radiation therapy and intensity-modulated radiation therapy (IMRT) attention has focused strongly in the last few years on understanding and compensating more appropriately for these motions. Thus, unlike most of the reviews in this special 50th anniversary issue which look back over decades of development, this one looks back at most within just the past decade and reviews the current situation. There is still much more work to be done and many of the techniques reviewed are themselves not yet implemented widely in the clinic.

Artifacts↗
PubMed2006

Investigating the fundamentals of IMRT decomposition using ten simple collimator models.

The fundamentals of IMRT collimation have been studied using ten conceptual collimators. Spanning a range of complexities from the LINAC jaws alone to a full multi-leaf collimator (MLC), these collimators were designed with two abilities in mind: (1) to be able to define arbitrary field shapes, and (2) to be able to irradiate multiple, disconnected regions in a single segment. The collimators were tested by finding decompositions of random and clinical intensity-modulated beams (IMBs), and collimator performance was measured using both the number of segments required to complete the IMB and the monitor-unit efficiency of the treatment. The decompositions were run on 10 x 10 IMBs with integer bixel values randomly between 1 and 10, and clinical IMBs of varying sizes from lung, head and neck, and pelvic patients taken from a Pinnacle treatment-planning system. Results confirmed that although treatment performance improves with increased collimator complexity, it is not solely dependent on the number of segment shapes deliverable by the collimator but instead on how well these shapes lend themselves to IMRT delivery.

Computer Simulation↗
PubMed2006

Quantification of the fluence error in the motion-compensated dynamic MLC (DMLC) technique for delivering intensity-modulated radiotherapy (IMRT).

When a correction for intrafraction organ motion is to be attempted using the dynamic multileaf collimator (DMLC) 'breathing leaves' technique for intensity-modulated radiotherapy (IMRT), there is a finite response time between the measurement of organ motion and the feeding of a corresponding corrective motion to the leaves. Whilst small this is non-zero. This letter presents a computational strategy to assess the error introduced to the delivered fluence by this system latency. The error depends on the functional form of the intended fluence modulation, the variability of the breathing motion and the magnitude of the system latency.

Algorithms↗
PubMed2006

Chronic toxicity of sediment-associated linear alkylbenzene sulphonates (LAS) to freshwater benthic organisms.

The toxicity of linear alkylbenzene sulphonates (LAS), to freshwater benthic organisms was assessed during exposure to spiked sediment. Lethal and sub-lethal end-points were monitored for two organisms (oligochaete Lumbriculus variegatus and nematode Caenorhabditis elegans). Results demonstrated relatively low toxicity (LOECs>100 mg/kg dry weight). No observed effect concentrations (NOECs) of 81 mg/kg dw (Lumbriculus) and 100 mg/kg dw (Caenorhabditis) were determined. For the oligochaete, no specific endpoint was particularly sensitive to LAS. For the nematode, egg production was the most sensitive endpoint. Significant degradation was measured over the 28-day duration of the Lumbriculus study, equating to a half-life of 20 days in sediment.

Alkanesulfonic Acids↗
PubMed2006

Comparative efficiency of the multi-leaf collimator and variable-aperture collimator in intensity-modulated radiotherapy.

The potential of the variable-aperture collimator (VAC) in intensity-modulated radiation therapy (IMRT) has been evaluated by comparing its performance with that of the multi-leaf collimator (MLC). This comparison used a decomposition algorithm to find the series of collimator segments that would treat a given intensity-modulated beam (IMB). Collimator performance was measured using both the number of segments required to complete the IMB and the monitor-unit efficiency of the treatment. The VAC was modelled with aperture sizes from 4 x 4 cm to 20 x 20 cm, and these apertures were allowed to be located anywhere within the IMB. To enable a direct comparison, a similar scanning MLC was modelled at the same range of aperture sizes. Using both collimators, decompositions were run on 10 x 10 and 20 x 20 random IMBs with integer bixel values ranging from 1 to 10. Clinical IMBs from lung, head and neck, and pelvic patients were taken from a Pinnacle treatment-planning system and tested in the same manner. It was found that for all treatment sites, a small, scanning MLC performs as well or better than an equivalent sized VAC in both number of segments and monitor-unit efficiency, and would be an efficient choice for centres looking for a simple collimator for IMRT.

Algorithms↗
PubMed2006

Does elastic tissue intrafraction motion with density changes forbid motion-compensated radiotherapy?

Intrafraction organ motion disturbs the otherwise highly conformal dose distributions planned for conformal radiotherapy and intensity-modulated radiotherapy. If the organ motions are rigid-body translations and preserve voxel density, techniques to make the beam follow the target by synchronous breathing can be arranged. Several potential difficulties disturb this oversimple statement and one of these is addressed in this paper. The effects of general elastic motion without preserving density are investigated. The effects are complex. Dose-space voxels disconnect from the planned irradiation bixel; voxels in a set aligned with a particular bixel cease to be so aligned even with a different bixel on elastic motion. Furthermore the density changes to conserve mass and this further perturbs the dose distribution. These effects are demonstrated here via simple examples but it may be impossible to make 'beam-breathing' strategies to compensate for them. Consequently understanding (and possibly ignoring) these second-order effects may be all that is possible.

Algorithms↗
PubMed2006

The p53-inducible apoptotic protein AMID is not required for normal development and tumor suppression.

AMID is an apoptosis-inducing factor (AIF)-homologous and mitochondria-associated protein that has been implicated in caspase-independent apoptosis. Transcription of human AMID gene is upregulated by p53 and downregulated in tumors in comparison to their matched normal tissues, suggesting the possibility that AMID is involved in the downstream effects of p53. To investigate the physiological functions of AMID, we generated AMID-deficient mice by gene targeting. AMID-deficient mice are viable and fertile, develop normally and lack obvious phenotypic changes compared to wild-type mice up to 1 year old. AMID(-/-) mice up to 1 year old have no spontaneous tumors and show similar fibrosarcoma incidence after MCA inoculation compared to wild-type mice. AMID(-/-) embryonic fibroblasts exhibit normal proliferation but slightly increased resistance to genotoxin-induced growth arrest. These findings suggest that AMID is not required for normal development and p53-mediated tumor suppression.

Amino Acid Sequence↗
PubMed2006

Do migraineurs have difficulty judging direction of simulated heading?

Some migraineurs have increased thresholds for the detection of global dot motion. We investigated whether migraineurs show consequential abnormalities in the determination of direction of self-motion (heading) from simulated optic flow. The ability to determine heading from optic flow is likely to be necessary for optimal determination of self-motion through the environment. Twenty-five migraineurs and 25 controls participated. Global dot motion coherence thresholds were assessed, in addition to performance on two simulated heading tasks: one with a symmetrical flow field, and the second with differing velocity of optic flow on the left and right sides of the participant. While some migraineurs demonstrated abnormal global motion coherence thresholds, there was no difference in performance on the heading tasks at either simulated walking (5 km/h) or driving (50 km/h) speeds. Increased global motion coherence thresholds in migraineurs do not result in abnormal judgements of heading from 100% coherent optic flow.

Adolescent↗
PubMed2006

Relative adrenal insufficiency in etomidate-naïve patients with septic shock.

A recent study reported that 77% of patients with septic shock had relative adrenal insufficiency. However, all patients were mechanically ventilated and received high-dose inotropes. In addition, at least 24% had prior exposure to etomidate, a drug known to suppress adrenal function. We studied the incidence of relative adrenal insufficiency in etomidate-naïve patients with septic shock by analysing the adrenal response to high-dose short synacthen test in 113 consecutive patients from three university-affiliated intensive care units in Australia. Patients were allocated to three groups according to severity of illness and inclusion criteria of the trial of low dose hydrocortisone supplementation using information from patient records. Of the 113 patients, 98 had septic shock (Group A). The incidence of relative adrenal insufficiency in this subpopulation was 24.5%. Eighty-one per cent of patients with septic shock were mechanically ventilated (Group B). In this group, the incidence of relative adrenal insufficiency was 27.8%. Only 38 of the 98 patients with septic shock (39%) fulfilled inclusion criteria for the steroid supplementation trial (Group C). In this group, the incidence of relative adrenal insufficiency was only 34.2%. In all groups its presence was associated with a higher mortality. We conclude that the incidence of relative adrenal insufficiency in etomidate-naive septic shock patients was lower than observed in the steroid supplementation trial. Further, in those who fulfilled inclusion criteria for the trial, the incidence of relative adrenal insufficiency was half that reported by the trial. Our observations raise concerns about the generalizability of the findings of the above trial to etomidate-naïve patients.

APACHE↗
PubMed2006

A quantitative study of IMRT delivery effects in commercial planning systems for the case of oesophagus and prostate tumours.

This study focuses on understanding the impact of intensity-modulated radiotherapy (IMRT) delivery effects when applied to plans generated by commercial treatment-planning systems such as Pinnacle (ADAC Laboratories Inc.) and CadPlan/Helios (Varian Medical Systems). These commercial planning systems have had several version upgrades (with improvements in the optimization algorithm), but the IMRT delivery effects have not been incorporated into the optimization process. IMRT delivery effects include head-scatter fluence from IMRT fields, transmission through leaves and the effect of the rounded shape of the leaf ends. They are usually accounted for after optimization when leaf sequencing the "optimal" fluence profiles, to derive the delivered fluence profile. The study was divided into two main parts: (a) analysing the dose distribution within the planning-target volume (PTV), produced by each of the commercial treatment-planning systems, after the delivered fluence had been renormalized to deliver the correct dose to the PTV; and (b) studying the impact of the IMRT delivery technique on the surrounding critical organs such as the spinal cord, lungs, rectum, bladder etc. The study was performed for tumours of (i) the oesophagus and (ii) the prostate and pelvic nodes. An oesophagus case was planned with the Pinnacle planning system for IMRT delivery, via multiple-static fields (MSF) and compensators, using the Elekta SL25 with a multileaf collimator (MLC) component. A prostate and pelvic nodes IMRT plan was performed with the Cadplan/Helios system for a dynamic delivery (DMLC) using the Varian 120-leaf Millennium MLC. In these commercial planning systems, since IMRT delivery effects are not included into the optimization process, fluence renormalization is required such that the median delivered PTV dose equals the initial prescribed PTV dose. In preparing the optimum fluence profile for delivery, the PTV dose has been "smeared" by the IMRT delivery techniques. In the case of the oesophagus, the critical organ, spinal cord, received a greater dose than initially planned, due to the delivery effects. The increase in the spinal cord dose is of the order of 2-3 Gy. In the case of the prostate and pelvic nodes, the IMRT delivery effects led to an increase of approximately 2 Gy in the dose delivered to the secondary PTV, the pelvic nodes. In addition to this, the small bowel, rectum and bladder received an increased dose of the order of 2-3 Gy to 50% of their total volume. IMRT delivery techniques strongly influence the delivered dose distributions for the oesophagus and prostate/pelvic nodes tumour sites and these effects are not yet accounted for in the Pinnacle and the CadPlan/Helios planning systems. Currently, they must be taken into account during the optimization stage by altering the dose limits accepted during optimization so that the final (sequenced) dose is within the constraints.

Algorithms↗
PubMed2005

Limitations of a simple technique for movement compensation via movement-modified fluence profiles.

The delivery of intensity-modulated radiation therapy (IMRT) through the dynamic multileaf collimator (dMLC) technique is well known and recently it has been shown how this can be modified to deliver fluence to a body which is moving in a regular and totally predictable manner. This involves making the leaves 'breath' in tandem with the body motion. This note presents an entirely alternative suggestion in which the leaves do not 'breath' at all but the fluence profile to be mapped to the unbreathing leaf motions is modified so that, when sampled by the specified motion, the actual fluence delivered is close to the desired fluence. Limitations of the concept are discussed.

Algorithms↗
PubMed2005

The effect on IMRT conformality of elastic tissue movement and a practical suggestion for movement compensation via the modified dynamic multileaf collimator (dMLC) technique.

A major remaining problem in delivering radiotherapy, specifically intensity-modulated radiation therapy (IMRT), is the need to accommodate and correct for intrafraction movement. The developing availability of 4D computed tomographic images can potentially form the basis of the new field of image-guided IMRT. It is important to understand the effects on delivered dose of the patient breathing during IMRT and this paper models the effect which applies whether there is or is not a time component to the IMRT delivery method. It then goes on to suggest a practical correction strategy. The 'stretch-and-shift-the-planned-modulations' strategy is proposed and a practical method to deliver this is explained. This practical strategy is based on a modification of the dynamic multileaf collimator IMRT method whereby the leaves are arranged to 'breath' in tandem with the breathing of the patient. Some examples are also given from a study of mismatching the patient and leaf-correction motions.

Algorithms↗
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↗