Adaptive stereotactic body radiation therapy planning for lung cancer.

PURPOSE: To investigate the dosimetric effects of adaptive planning on lung stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Forty of 66 consecutive lung SBRT patients were selected for a retrospective adaptive planning study. CBCT images acquired at each fraction were used for treatment planning. Adaptive plans were created using the same planning parameters as the original CT-based plan, with the goal to achieve comparable comformality index (CI). For each patient, 2 cumulative plans, nonadaptive plan (PNON) and adaptive plan (PADP), were generated and compared for the following organs-at-risks (OARs): cord, esophagus, chest wall, and the lungs. Dosimetric comparison was performed between PNON and PADP for all 40 patients. Correlations were evaluated between changes in dosimetric metrics induced by adaptive planning and potential impacting factors, including tumor-to-OAR distances (dT-OAR), initial internal target volume (ITV1), ITV change (ΔITV), and effective ITV diameter change (ΔdITV). RESULTS: 34 (85%) patients showed ITV decrease and 6 (15%) patients showed ITV increase throughout the course of lung SBRT. Percentage ITV change ranged from -59.6% to 13.0%, with a mean (±SD) of -21.0% (±21.4%). On average of all patients, PADP resulted in significantly (P=0 to .045) lower values for all dosimetric metrics. ΔdITV/dT-OAR was found to correlate with changes in dose to 5 cc (ΔD5cc) of esophagus (r=0.61) and dose to 30 cc (ΔD30cc) of chest wall (r=0.81). Stronger correlations between ΔdITV/dT-OAR and ΔD30cc of chest wall were discovered for peripheral (r=0.81) and central (r=0.84) tumors, respectively. CONCLUSIONS: Dosimetric effects of adaptive lung SBRT planning depend upon target volume changes and tumor-to-OAR distances. Adaptive lung SBRT can potentially reduce dose to adjacent OARs if patients present large tumor volume shrinkage during the treatment.

Intracardiac acoustic radiation force impulse (ARFI) and shear wave imaging in pigs with focal infarctions.

Four pigs, three with focal infarctions in the apical intraventricular septum (IVS) and/or left ventricular free wall (LVFW), were imaged with an intracardiac echocardiography (ICE) transducer. Custom beam sequences were used to excite the myocardium with focused acoustic radiation force (ARF) impulses and image the subsequent tissue response. Tissue displacement in response to the ARF excitation was calculated with a phase-based estimator, and transverse wave magnitude and velocity were each estimated at every depth. The excitation sequence was repeated rapidly, either in the same location to generate 40 Hz M-modes at a single steering angle, or with a modulated steering angle to synthesize 2-D displacement magnitude and shear wave velocity images at 17 points in the cardiac cycle. Both types of images were acquired from various views in the right and left ventricles, in and out of infarcted regions. In all animals, acoustic radiation force impulse (ARFI) and shear wave elasticity imaging (SWEI) estimates indicated diastolic relaxation and systolic contraction in noninfarcted tissues. The M-mode sequences showed high beat-to-beat spatio-temporal repeatability of the measurements for each imaging plane. In views of noninfarcted tissue in the diseased animals, no significant elastic remodeling was indicated when compared with the control. Where available, views of infarcted tissue were compared with similar views from the control animal. In views of the LVFW, the infarcted tissue presented as stiff and non-contractile compared with the control. In a view of the IVS, no significant difference was seen between infarcted and healthy tissue, whereas in another view, a heterogeneous infarction was seen to be presenting itself as non-contractile in systole.

Radiation Dose to the Lens of the Eye from Computed Tomography Scans of the Head

While it is well known that exposure to radiation can result in cataract formation, questions still remain about the presence of a dose threshold in radiation cataractogenesis. Since the exposure history from diagnostic CT exams is well documented in a patient’s medical record, the population of patients chronically exposed to radiation from head CT exams may be an interesting area to explore for further research in this area. However, there are some challenges in estimating lens dose from head CT exams. An accurate lens dosimetry model would have to account for differences in imaging protocols, differences in head size, and the use of any dose reduction methods.

The overall objective of this dissertation was to develop a comprehensive method to estimate radiation dose to the lens of the eye for patients receiving CT scans of the head. This research is comprised of a physics component, in which a lens dosimetry model was derived for head CT, and a clinical component, which involved the application of that dosimetry model to patient data.

The physics component includes experiments related to the physical measurement of the radiation dose to the lens by various types of dosimeters placed within anthropomorphic phantoms. These dosimeters include high-sensitivity MOSFETs, TLDs, and radiochromic film. The six anthropomorphic phantoms used in these experiments range in age from newborn to adult.

First, the lens dose from five clinically relevant head CT protocols was measured in the anthropomorphic phantoms with MOSFET dosimeters on two state-of-the-art CT scanners. The volume CT dose index (CTDIvol), which is a standard CT output index, was compared to the measured lens doses. Phantom age-specific CTDIvol-to-lens dose conversion factors were derived using linear regression analysis. Since head size can vary among individuals of the same age, a method was derived to estimate the CTDIvol-to-lens dose conversion factor using the effective head diameter. These conversion factors were derived for each scanner individually, but also were derived with the combined data from the two scanners as a means to investigate the feasibility of a scanner-independent method. Using the scanner-independent method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter, most of the fitted lens dose values fell within 10-15% of the measured values from the phantom study, suggesting that this is a fairly accurate method of estimating lens dose from the CTDIvol with knowledge of the patient’s head size.

Second, the dose reduction potential of organ-based tube current modulation (OB-TCM) and its effect on the CTDIvol-to-lens dose estimation method was investigated. The lens dose was measured with MOSFET dosimeters placed within the same six anthropomorphic phantoms. The phantoms were scanned with the five clinical head CT protocols with OB-TCM enabled on the one scanner model at our institution equipped with this software. The average decrease in lens dose with OB-TCM ranged from 13.5 to 26.0%. Using the size-specific method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter for protocols with OB-TCM, the majority of the fitted lens dose values fell within 15-18% of the measured values from the phantom study.

Third, the effect of gantry angulation on lens dose was investigated by measuring the lens dose with TLDs placed within the six anthropomorphic phantoms. The 2-dimensional spatial distribution of dose within the areas of the phantoms containing the orbit was measured with radiochromic film. A method was derived to determine the CTDIvol-to-lens dose conversion factor based upon distance from the primary beam scan range to the lens. The average dose to the lens region decreased substantially for almost all the phantoms (ranging from 67 to 92%) when the orbit was exposed to scattered radiation compared to the primary beam. The effectiveness of this method to reduce lens dose is highly dependent upon the shape and size of the head, which influences whether or not the angled scan range coverage can include the entire brain volume and still avoid the orbit.

The clinical component of this dissertation involved performing retrospective patient studies in the pediatric and adult populations, and reconstructing the lens doses from head CT examinations with the methods derived in the physics component. The cumulative lens doses in the patients selected for the retrospective study ranged from 40 to 1020 mGy in the pediatric group, and 53 to 2900 mGy in the adult group.

This dissertation represents a comprehensive approach to lens of the eye dosimetry in CT imaging of the head. The collected data and derived formulas can be used in future studies on radiation-induced cataracts from repeated CT imaging of the head. Additionally, it can be used in the areas of personalized patient dose management, and protocol optimization and clinician training.

Advanced Applications of 3D Dosimetry and 3D Printing in Radiation Therapy

As complex radiotherapy techniques become more readily-practiced, comprehensive 3D dosimetry is a growing necessity for advanced quality assurance. However, clinical implementation has been impeded by a wide variety of factors, including the expense of dedicated optical dosimeter readout tools, high operational costs, and the overall difficulty of use. To address these issues, a novel dry-tank optical CT scanner was designed for PRESAGE 3D dosimeter readout, relying on 3D printed components and omitting costly parts from preceding optical scanners. This work details the design, prototyping, and basic commissioning of the Duke Integrated-lens Optical Scanner (DIOS).

The convex scanning geometry was designed in ScanSim, an in-house Monte Carlo optical ray-tracing simulation. ScanSim parameters were used to build a 3D rendering of a convex ‘solid tank’ for optical-CT, which is capable of collimating a point light source into telecentric geometry without significant quantities of refractive-index matched fluid. The model was 3D printed, processed, and converted into a negative mold via rubber casting to produce a transparent polyurethane scanning tank. The DIOS was assembled with the solid tank, a 3W red LED light source, a computer-controlled rotation stage, and a 12-bit CCD camera. Initial optical phantom studies show negligible spatial inaccuracies in 2D projection images and 3D tomographic reconstructions. A PRESAGE 3D dose measurement for a 4-field box treatment plan from Eclipse shows 95% of voxels passing gamma analysis at 3%/3mm criteria. Gamma analysis between tomographic images of the same dosimeter in the DIOS and DLOS systems show 93.1% agreement at 5%/1mm criteria. From this initial study, the DIOS has demonstrated promise as an economically-viable optical-CT scanner. However, further improvements will be necessary to fully develop this system into an accurate and reliable tool for advanced QA.

Pre-clinical animal studies are used as a conventional means of translational research, as a midpoint between in-vitro cell studies and clinical implementation. However, modern small animal radiotherapy platforms are primitive in comparison with conventional linear accelerators. This work also investigates a series of 3D printed tools to expand the treatment capabilities of the X-RAD 225Cx orthovoltage irradiator, and applies them to a feasibility study of hippocampal avoidance in rodent whole-brain radiotherapy.

As an alternative material to lead, a novel 3D-printable tungsten-composite ABS plastic, GMASS, was tested to create precisely-shaped blocks. Film studies show virtually all primary radiation at 225 kVp can be attenuated by GMASS blocks of 0.5cm thickness. A state-of-the-art software, BlockGen, was used to create custom hippocampus-shaped blocks from medical image data, for any possible axial treatment field arrangement. A custom 3D printed bite block was developed to immobilize and position a supine rat for optimal hippocampal conformity. An immobilized rat CT with digitally-inserted blocks was imported into the SmART-Plan Monte-Carlo simulation software to determine the optimal beam arrangement. Protocols with 4 and 7 equally-spaced fields were considered as viable treatment options, featuring improved hippocampal conformity and whole-brain coverage when compared to prior lateral-opposed protocols. Custom rodent-morphic PRESAGE dosimeters were developed to accurately reflect these treatment scenarios, and a 3D dosimetry study was performed to confirm the SmART-Plan simulations. Measured doses indicate significant hippocampal sparing and moderate whole-brain coverage.

Prospective Estimation of Radiation Dose and Image Quality for Optimized CT Performance

X-ray computed tomography (CT) is a non-invasive medical imaging technique that generates cross-sectional images by acquiring attenuation-based projection measurements at multiple angles. Since its first introduction in the 1970s, substantial technical improvements have led to the expanding use of CT in clinical examinations. CT has become an indispensable imaging modality for the diagnosis of a wide array of diseases in both pediatric and adult populations [1, 2]. Currently, approximately 272 million CT examinations are performed annually worldwide, with nearly 85 million of these in the United States alone [3]. Although this trend has decelerated in recent years, CT usage is still expected to increase mainly due to advanced technologies such as multi-energy [4], photon counting [5], and cone-beam CT [6].

Despite the significant clinical benefits, concerns have been raised regarding the population-based radiation dose associated with CT examinations [7]. From 1980 to 2006, the effective dose from medical diagnostic procedures rose six-fold, with CT contributing to almost half of the total dose from medical exposure [8]. For each patient, the risk associated with a single CT examination is likely to be minimal. However, the relatively large population-based radiation level has led to enormous efforts among the community to manage and optimize the CT dose.

As promoted by the international campaigns Image Gently and Image Wisely, exposure to CT radiation should be appropriate and safe [9, 10]. It is thus a responsibility to optimize the amount of radiation dose for CT examinations. The key for dose optimization is to determine the minimum amount of radiation dose that achieves the targeted image quality [11]. Based on such principle, dose optimization would significantly benefit from effective metrics to characterize radiation dose and image quality for a CT exam. Moreover, if accurate predictions of the radiation dose and image quality were possible before the initiation of the exam, it would be feasible to personalize it by adjusting the scanning parameters to achieve a desired level of image quality. The purpose of this thesis is to design and validate models to quantify patient-specific radiation dose prospectively and task-based image quality. The dual aim of the study is to implement the theoretical models into clinical practice by developing an organ-based dose monitoring system and an image-based noise addition software for protocol optimization.

More specifically, Chapter 3 aims to develop an organ dose-prediction method for CT examinations of the body under constant tube current condition. The study effectively modeled the anatomical diversity and complexity using a large number of patient models with representative age, size, and gender distribution. The dependence of organ dose coefficients on patient size and scanner models was further evaluated. Distinct from prior work, these studies use the largest number of patient models to date with representative age, weight percentile, and body mass index (BMI) range.

With effective quantification of organ dose under constant tube current condition, Chapter 4 aims to extend the organ dose prediction system to tube current modulated (TCM) CT examinations. The prediction, applied to chest and abdominopelvic exams, was achieved by combining a convolution-based estimation technique that quantifies the radiation field, a TCM scheme that emulates modulation profiles from major CT vendors, and a library of computational phantoms with representative sizes, ages, and genders. The prospective quantification model is validated by comparing the predicted organ dose with the dose estimated based on Monte Carlo simulations with TCM function explicitly modeled.

Chapter 5 aims to implement the organ dose-estimation framework in clinical practice to develop an organ dose-monitoring program based on a commercial software (Dose Watch, GE Healthcare, Waukesha, WI). In the first phase of the study we focused on body CT examinations, and so the patient’s major body landmark information was extracted from the patient scout image in order to match clinical patients against a computational phantom in the library. The organ dose coefficients were estimated based on CT protocol and patient size as reported in Chapter 3. The exam CTDIvol, DLP, and TCM profiles were extracted and used to quantify the radiation field using the convolution technique proposed in Chapter 4.

With effective methods to predict and monitor organ dose, Chapters 6 aims to develop and validate improved measurement techniques for image quality assessment. Chapter 6 outlines the method that was developed to assess and predict quantum noise in clinical body CT images. Compared with previous phantom-based studies, this study accurately assessed the quantum noise in clinical images and further validated the correspondence between phantom-based measurements and the expected clinical image quality as a function of patient size and scanner attributes.

Chapter 7 aims to develop a practical strategy to generate hybrid CT images and assess the impact of dose reduction on diagnostic confidence for the diagnosis of acute pancreatitis. The general strategy is (1) to simulate synthetic CT images at multiple reduced-dose levels from clinical datasets using an image-based noise addition technique; (2) to develop quantitative and observer-based methods to validate the realism of simulated low-dose images; (3) to perform multi-reader observer studies on the low-dose image series to assess the impact of dose reduction on the diagnostic confidence for multiple diagnostic tasks; and (4) to determine the dose operating point for clinical CT examinations based on the minimum diagnostic performance to achieve protocol optimization.

Chapter 8 concludes the thesis with a summary of accomplished work and a discussion about future research.