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Biomedical subjects

Mark Oldham

Publications and source records attributed to Mark Oldham.

10 recordsLinked to original sources

Digital tomosynthesis with an on-board kilovoltage imaging device.

PURPOSE: To generate on-board digital tomosynthesis (DTS) and reference DTS images for three-dimensional image-guided radiation therapy (IGRT) as an alternative to conventional portal imaging or on-board cone-beam computed tomography (CBCT). METHODS AND MATERIALS: Three clinical cases (prostate, head-and-neck, and liver) were selected to illustrate the capabilities of on-board DTS for IGRT. Corresponding reference DTS images were reconstructed from digitally reconstructed radiographs computed from planning CT image sets. The effect of scan angle on DTS slice thickness was examined by computing the mutual information between coincident CBCT and DTS images, as the DTS scan angle was varied from 0 degrees to 165 degrees . A breath-hold DTS acquisition strategy was implemented to remove respiratory motion artifacts. RESULTS: Digital tomosynthesis slices appeared similar to coincident CBCT planes and yielded substantially more anatomic information than either kilovoltage or megavoltage radiographs. Breath-hold DTS acquisition improved soft-tissue visibility by suppressing respiratory motion. CONCLUSIONS: Improved bony and soft-tissue visibility in DTS images is likely to improve target localization compared with radiographic verification techniques and might allow for daily localization of a soft-tissue target. Breath-hold DTS is a potential alternative to on-board CBCT for sites prone to respiratory motion.

Algorithms↗

Physics and imaging for targeting of oligometastases.

Oligometastases refer to metastases that are limited in number and location and are amenable to regional treatment. The majority of these metastases appear in the brain, lung, liver, and bone. Although the focus of interest in the past within radiation oncology has been on the treatment of intracranial metastases, there has been growing interest in extracranial sites such as the liver and lung. This is largely because of the rapid development of targeting techniques for oligometastases such as intensity-modulated and image-guided radiation therapy, which has made it possible to deliver single or a few fractions of high-dose radiation treatments, highly conformal to the target. The clinical decision to use radiation to treat oligometastases is based on both radiobiological and physics considerations. The radiobiological considerations involve improvement of treatment schema for time, dose, and volume. Areas of interests are hypofractionation, tumor and normal tissue tolerance, and hypoxia. The physics considerations for oligometastases treatment are focused mainly on ensuring treatment accuracy and precision. This article discusses the physics and imaging aspects involved in each step of the radiation treatment process for oligometastases, including target definition, treatment simulation, treatment planning, pretreatment target localization, radiation delivery, treatment verification, and treatment evaluation.

Dose Fractionation, Radiation↗

Three-dimensional imaging of xenograft tumors using optical computed and emission tomography.

The physical basis and preliminary applications of optical computed tomography (optical-CT) and optical emission computed tomography (optical-ECT) are introduced, as new techniques with potential to provide unique 3D information on a variety of aspects of tumor structure and function. A particular focus here is imaging tumor micro-vasculature, and the spatial distribution of viable tumor cells, although the techniques have the potential for much wider application. The principle attractiveness of optical-CT and optical-ECT are that high resolution (<20 microm) and high contrast co-registered 3D images of structure and function can be acquired for relatively large intact samples. The unique combination of high contrast and resolution offers advantages over micro-CT and micro-MRI, and the lack of requirement for sectioning offers advantages over confocal microscopy, conventional microscopy, and histological sectioning techniques. Optical-CT/ECT are implemented using in-house custom apparatus and a commercial dissecting microscope capable of both transmission and fluorescence imaging. Basic studies to characterize imaging performance are presented. Negligible geometrical distortion and accurate reconstruction of relative attenuation coefficients was observed. Optical-CT and optical-ECT are investigated here by application to high resolution imaging of HCT116 xenograft tumors, about 1 cc in dimension, which were transfected with constitutive red fluorescent protein (RFP). Tumor microvasculature was stained in vivo by tail vein injection of either passive absorbing dyes or active fluorescent markers (FITC conjugated lectin). Prior to imaging, the tumors were removed (ex vivo) and optically cleared in a key process to make the samples amenable to light transmission. The cleared tumors were imaged in three modes (i) optical-CT to image the 3D distribution of microvasculature as indicated by absorbing dye, (ii) optical-ECT using the FITC excitation and emission filter set, to determine microvasculature as indicated by lectin-endothelial binding, and (iii) optical-ECT using the DSRed2 filter set to determine the 3D distribution of viable tumor as indicated by RFP emission. A clear correlation was observed between the independent vasculature imaging modes (i) and (ii) and postimaging histological sections, providing substantial validation of the optical-CT and optical-ECT techniques. Strong correlation was also observed between the RFP imaging of mode iii, and modes i and ii, supporting the intuitive conclusion that well-perfused regions contain significant viable tumor. In summary, optical-CT and optical-ECT, when combined with new optical clearing techniques, represent powerful new imaging modalities with potential for providing unique information on the structure and function of tumors.

Animals↗

A practical three-dimensional dosimetry system for radiation therapy.

There is a pressing need for a practical three-dimensional (3D) dosimetry system, convenient for clinical use, and with the accuracy and resolution to enable comprehensive verification of the complex dose distributions typical of modern radiation therapy. Here we introduce a dosimetry system that can achieve this challenge, consisting of a radiochromic dosimeter (PRESAGE) and a commercial optical computed tomography (CT) scanning system (OCTOPUS). PRESAGE is a transparent material with compelling properties for dosimetry, including insensitivity of the dose response to atmospheric exposure, a solid texture negating the need for an external container (reducing edge effects), and amenability to accurate optical CT scanning due to radiochromic optical contrast as opposed to light-scattering contrast. An evaluation of the performance and viability of the PRESAGE/OCTOPUS, combination for routine clinical 3D dosimetry is presented. The performance of the two components (scanner and dosimeter) was investigated separately prior to full system test. The optical CT scanner has a spatial resolution of < or = 1 mm, geometric accuracy within 1 mm, and high reconstruction linearity (with a R2 value of 0.9979 and a standard error of estimation of approximately 1%) relative to independent measurement. The overall performance of the PRESAGE/OCTOPUS system was evaluated with respect to a simple known 3D dose distribution, by comparison with GAFCHROMIC EBT film and the calculated dose from a commissioned planning system. The "measured" dose distribution in a cylindrical PRESAGE dosimeter (16 cm diameter and 11 cm height) was determined by optical-CT, using a filtered backprojection reconstruction algorithm. A three-way Gamma map comparison (4% dose difference and 4 mm distance to agreement), between the PRESAGE, EBT and calculated dose distributions, showed full agreement in measurable region of PRESAGE dosimeter (approximately 90% of radius). The EBT and PRESAGE distributions agreed more closely with each other than with the calculated plan, consistent with penumbral blurring in the planning data which was acquired with an ion chamber. In summary, our results support the conclusion that the PRESAGE optical-CT combination represents a significant step forward in 3D dosimetry, and provides a robust, clinically effective and viable high-resolution relative 3D dosimetry system for radiation therapy.

Algorithms↗

Cone-beam-CT guided radiation therapy: technical implementation.

BACKGROUND AND PURPOSE: X-ray volumetric imaging system (XVI) mounted on a linear accelerator is available for image guidance applications. In preparation for clinical implementation, phantom and patient imaging studies were conducted to determine the irradiation parameters that would trade-off image quality, patient dose and scanning time. PATIENTS AND METHODS: The XVI image quality and imaging dose were benchmarked against those obtained with a helical CT scanner for a head and body phantom. The irradiation parameters were varied including the total imaging dose, number of projections, field of view, reconstruction resolution and use of a scatter rejection grid. We characterized the image quality based on relative contrast, noise, contrast to noise ratio (CNR) and point spread function (PSF). XVI scans of pelvis, head and neck and lung patients were acquired and submitted to a range of observers to identify the favorable reconstruction parameters. RESULTS: Phantom studies have demonstrated that a scatter rejection grid reduces photon scattering and improves the image uniformity. For the body phantom, the helical CT and the wide field XVI technique produce similar image quality, with surface doses of 0.025 and 0.044 Gy respectively. We have demonstrated that the local tomography technique improves the image contrast and the CNR while reducing the skin dose by 40-50% compared to the wide field technique. Clinical scans of head and neck, lung and prostate patients present good soft tissue contrast and excellent bone definition. CONCLUSIONS: With adjustment of irradiation parameters and an imaging surface dose of less than 0.05 Gy, high quality XVI images can be obtained for a phantom simulating the body thickness. XVI is currently feasible for image-guided treatments of head and neck, torso and pelvic areas using soft tissue and bony structures.

Humans↗

Cone-beam-CT guided radiation therapy: A model for on-line application.

BACKGROUND AND PURPOSE: This paper presents efficient and generalized processes for the clinical application of on-line X-ray volumetric cone-beam CT imaging (XVI) to improve the accuracy of patient set-up in radiation therapy. XVI image-guided therapy is illustrated by application to two contrasting sites, intra-cranial radiosurgery and prostate radiation therapy, with very different characteristics regarding organ motion, treatment precision, and imaging conditions. PATIENTS AND METHODS: On-line set-up errors are determined in a two-step process. First the XVI data is registered to the planning data by matching the machine-isocenter with the planning-isocenter, respectively. The machine isocenter is defined in the XVI data during the reconstruction. The planning-isocenter is defined during the planning process in the planning CT data. Set-up errors are then determined from a second registration to remove residual displacements. The accuracy of the entire procedure for on-line set-up error correction was investigated in precision radiosurgery phantom studies. RESULTS: The phantom studies showed that sub-pixel size set-up errors (down to 0.5mm) can be correctly determined and implemented in the radiosurgery environment. XVI is demonstrated to provide quality skull detail enabling precise skull based on-line alignment in radiosurgery. A 'local XVI' technique was found to give encouraging soft-tissue detail in the high-scatter pelvic environment, enabling on-line soft-tissue based set-up for prostate treatment. The two-step process for determination of set-up errors was found to be efficient and effective when implemented with a dedicated six panel interface enabling simultaneous visualization on the XVI and planning CT data sets. CONCLUSIONS: XVI has potential to significantly improve the accuracy of radiation treatments. Present image quality is highly encouraging and can enable bony and soft-tissue patient set-up error determination and correction. As with all image guided treatment techniques the development of efficient procedures to utilize on-line data are of paramount importance.

Brain Neoplasms↗

Predicting radiotherapy-induced cardiac perfusion defects.

The purpose of this work is to compare the efficacy of mathematical models in predicting the occurrence of radiotherapy-induced left ventricular perfusion defects assessed using single-photon emission computed tomography (SPECT). The basis of this study is data from 73 left-sided breast/ chestwall patients treated with tangential photon fields. The mathematical models compared were three commonly used parametric models [Lyman normal tissue complication probability (LNTCP), relative serialty (RS), generalized equivalent uniform dose (gEUD)] and a nonparametric model (Linear discriminant analysis--LDA). Data used by the models were the left ventricular dose--volume histograms, or SPECT-based dose-function histograms, and the presence/absence of SPECT perfusion defects 6 months postradiation therapy (21 patients developed defects). For the parametric models, maximum likelihood estimation and F-tests were used to fit the model parameters. The nonparametric LDA model step-wise selected features (volumes/function above dose levels) using a method based on receiver operating characteristics (ROC) analysis to best separate the groups with and without defects. Optimistic (upper bound) and pessimistic (lower bound) estimates of each model's predictive capability were generated using ROC curves. A higher area under the ROC curve indicates a more accurate model (a model that is always accurate has area = 1). The areas under these curves for different models were used to statistically test for differences between them. Pessimistic estimates of areas under the ROC curve using dose-volume histogram/ dose-function histogram inputs, in order of increasing prediction accuracy, were LNTCP (0.79/0.75), RS (0.80/0.77), gEUD (0.81/0.78), and LDA (0.84/0.86). Only the LDA model benefited from SPECT-based regional functional information. In general, the LDA model was statistically superior to the parametric models. The LDA model selected as features the left ventricular volumes above approximately 23 Gy (V23), essentially volume in field, and 33 Gy (V33), as best separating the groups with and without defects. In conclusion, the nonparametric LDA model appears to be a more accurate predictor of radiotherapy-induced left ventricular perfusion defects than commonly used parametric models.

Dose-Response Relationship, Radiation↗

Evaluation of a 2D diode array for IMRT quality assurance.

BACKGROUND AND PURPOSE: The QA of intensity modulated radiotherapy (IMRT) dosimetry is a laborious task. The goal of this work is to evaluate the dosimetric characteristics of a new 2D diode array (MapCheck from Sun Nuclear Corporation, Melbourne, Florida) and assess the role it can play in routine IMRT QA. MATERIAL AND METHODS: Fundamental properties of the MapCheck such as reproducibility, linearity and temperature dependence are studied for high-energy photon beams. The accuracy of the correction for difference of diode sensitivity is also assessed. The diode array is benchmarked against film and ion chambers for conventional and IMRT treatments. The MapCheck sensitivity to multileaf collimator position errors is determined. RESULTS: The diode array response is linear with dose up to 295 cGy. All diodes are calibrated to within +/-1% of each other, and mostly within +/-0.5%. The MapCheck readings are reproducible to within a maximum SD of +/-0.15%. A temperature dependence of 0.57%/ degrees C was noted and should be taken into account for absolute dosimetric measurement. Clinical performance of the MapCheck for relative and absolute dosimetry is demonstrated with seven beam (6 MV) head and neck IMRT plans, and compares well with film and ion chamber measurements. Comparison to calculated dose maps demonstrates that the planning system model underestimates the dose gradients in the penumbra region. CONCLUSIONS: The MapCheck offers the dosimetric characteristics required for performing both relative and absolute dose measurements. Its use in the clinic can simplify and reduce the IMRT QA workload.

Dose-Response Relationship, Radiation↗

Optical-CT gel-dosimetry. II: Optical artifacts and geometrical distortion.

There is a clear need for technology that enables accurate, high-resolution, three-dimensional (3D) measurement of intricate dose distributions associated with modern radiation treatments. A potential candidate has emerged in the form of water-equivalent "3D gel dosimetry" utilizing optical-computed-tomography (optical-CT). In a previous paper we presented basic physical characterization of an in-house prototype optical-CT scanning system. The present paper builds on that work by investigating sources of optical artifacts and geometric distortion in optical-CT scanning. Improvements in scanner design are described. Correction strategies were developed to compensate for reflection and refraction, imperfections in the water-bath, signal drift, and other effects. Refraction and reflection were identified as the principal factors causing inaccurate reconstruction of absolute attenuation coefficients. A correction specific to a given flask was developed utilizing prescans of the flask when filled with water-bath fluid, thereby isolating the refractive and reflective components for that flask. Residual artifacts were corrected by fitting a theoretical model to the well-behaved portion of these prescans and extrapolating to regions of lost data, enabling reconstruction of absolute optical-CT attenuation coefficients to within 4% of corresponding spectrophotometer values. Needle phantoms are introduced to quantify geometric distortion under a range of conditions. Radial distortion of reconstructed needle positions was reduced to < 0.3 mm (0.27% of the field of view) through adjustment of the water-bath refractive index. Geometric distortion in polymer gel due to radiation-induced refractive index changes was found to be negligible under the conditions examined. The influence of scattered light on reconstructed attenuation coefficients was investigated by repeat optical-CT scans while varying the aperture of a scatter-rejecting collimator. Significant depression of reconstructed attenuation coefficients was observed, particularly under conditions of poor scatter rejection collimation. The general conclusion is that the first-generation optical-CT technique can be made insensitive to geometrical distortion, but can be susceptible to scatter effects. For accurate reconstruction of absolute attenuation coefficients, correction strategies are essential.

Artifacts↗

Optical-CT gel-dosimetry I: basic investigations.

Comprehensive verification of the intricate dose distributions associated with advanced radiation treatments is now an immediate and substantial problem. The task is challenging using traditional dosimeters because of restrictions to point measurements (ion chambers, diodes, TLD, etc.) or planar measurements (film). In essence, rapid advances in the technology to deliver radiation treatments have not been paralleled by corresponding advances in the ability to verify these treatments. A potential solution has emerged in the form of water equivalent three dimensional (3D) gel-dosimetry. In this paper we present basic characterization and performance studies of a prototype optical-CT scanning system developed in our laboratory. An analysis of the potential role or scope of gel dosimetry, in relation to other dosimeters, and to verification across the spectrum of therapeutic techniques is also given. The characterization studies enabled the determination of nominal operating conditions for optical-CT scanning. "Finger" phantoms are introduced as a powerful and flexible tool for the investigation of optical-CT performance. The modulation-transfer function (MTF) of the system is determined to be better than 10% out to 1 mm(-1), confirming sub-mm imaging ability. System performance is demonstrated by the acquisition of a 1 x 1 x 1 mm3 dataset through the dose distribution delivered by an x-ray lens that focuses x rays in the energy range 40-80 KeV. This 3D measurement would be extremely difficult to achieve with other dosimetry techniques and highlights some of the strengths of gel dosimetry. Finally, an optical Monte Carlo model is introduced and shown to have potential to model light transport through gel-dosimetry systems, and to provide a tool for the study and optimization of optical-CT gel dosimetry. The model utilizes Mie scattering theory and requires knowledge of the variation of the particle size distribution with dose. The latter was determined here using the technique of dynamic-light-scattering.

Algorithms↗