Development of Multi-modal and Super-resolved Retinal Imaging Systems

Advancements in retinal imaging technologies have drastically improved the quality of eye care in the past couple decades. Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) are two examples of critical imaging modalities for the diagnosis of retinal pathologies. However current-generation SLO and OCT systems have limitations in diagnostic capability due to the following factors: the use of bulky tabletop systems, monochromatic imaging, and resolution degradation due to ocular aberrations and diffraction.

Bulky tabletop SLO and OCT systems are incapable of imaging patients that are supine, under anesthesia, or otherwise unable to maintain the required posture and fixation. Monochromatic SLO and OCT imaging prevents the identification of various color-specific diagnostic markers visible with color fundus photography like those of neovascular age-related macular degeneration. Resolution degradation due to ocular aberrations and diffraction has prevented the imaging of photoreceptors close to the fovea without the use of adaptive optics (AO), which require bulky and expensive components that limit the potential for widespread clinical use.

In this dissertation, techniques for extending the diagnostic capability of SLO and OCT systems are developed. These techniques include design strategies for miniaturizing and combining SLO and OCT to permit multi-modal, lightweight handheld probes to extend high quality retinal imaging to pediatric eye care. In addition, a method for extending true color retinal imaging to SLO to enable high-contrast, depth-resolved, high-fidelity color fundus imaging is demonstrated using a supercontinuum light source. Finally, the development and combination of SLO with a super-resolution confocal microscopy technique known as optical photon reassignment (OPRA) is demonstrated to enable high-resolution imaging of retinal photoreceptors without the use of adaptive optics.

Evaluation of the Does Reduction Potential Using a Breast Positioning Technique for Organ-based Tube Current Modulated CT Examinations

Purpose: The purpose of this work was to investigate the breast dose saving potential of a breast positioning technique (BP) for thoracic CT examinations with organ-based tube current modulation (OTCM).

Methods: The study included 13 female patient models (XCAT, age range: 27-65 y.o., weight range: 52 to 105.8 kg). Each model was modified to simulate three breast sizes in standard supine geometry. The modeled breasts were further deformed, emulating a BP that would constrain the breasts within 120° anterior tube current (mA) reduction zone. The tube current value of the CT examination was modeled using an attenuation-based program, which reduces the radiation dose to 20% in the anterior region with a corresponding increase to the posterior region. A validated Monte Carlo program was used to estimate organ doses with a typical clinical system (SOMATOM Definition Flash, Siemens Healthcare). The simulated organ doses and organ doses normalized by CTDIvol were compared between attenuation-based tube current modulation (ATCM), OTCM, and OTCM with BP (OTCMBP).

Results: On average, compared to ATCM, OTCM reduced the breast dose by 19.3±4.5%, whereas OTCMBP reduced breast dose by 36.6±6.9% (an additional 21.3±7.3%). The dose saving of OTCMBP was more significant for larger breasts (on average 32, 38, and 44% reduction for 0.5, 1.5, and 2.5 kg breasts, respectively). Compared to ATCM, OTCMBP also reduced thymus and heart dose by 12.1 ± 6.3% and 13.1 ± 5.4%, respectively.

Conclusions: In thoracic CT examinations, OTCM with a breast positioning technique can markedly reduce unnecessary exposure to the radiosensitive organs in the anterior chest wall, specifically breast tissue. The breast dose reduction is more notable for women with larger breasts.

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.