Early stage disease diagnosis still remains a challenge despite much efforts to develop novel imaging and diagnostic techniques. Nanoparticles used as molecular imaging contrast agents with multifunctionality and flexibility provide a platform for targeting the specific disease biomarkers and integration of imaging modalities. In this work, we developed a simplified method for synthesis of radiolabeled targeted super paramagnetic iron oxide nanoparticles (SPIOs). This method takes advantage of the chelator BAT that is conjugated to the PEG before the coating process begins. The effect of nanoparticle size and PEG density was investigated in a series of in vivo experiments. The 64Cu-VINP-SPIOs were used in the PET imaging of inflammation and 64Cu-CD105-SPIOs were used in imaging of 4T1 murine tumor model. In summary, we investigated the potential of the radiolabeled, targeted SPIOs in imaging atherosclerotic plaque and tumor in vivo using magnetic resonance imaging (MRI) and Positron emission tomography (PET). Our results show that dual modality SPIOs with active targeting mediated by affinity ligands can be a great tool in molecular imaging and diagnosis of early stage plaque and tumor.

Molecular breast imaging (MBI) is a relatively new clinical breast imaging modality, which has the potential to have a significant impact in breast cancer screening and perioperative breast imaging for women with high risk factors for developing breast cancer. Two objectives were proposed in this thesis to increase the use of MBI. First, a magnetic resonance (MR)-compatible gamma camera was developed for combined molecular/MR breast imaging. MBI is a functional imaging technique with high specificity and sensitivity but could benefit from the addition of anatomical information from breast MRI for lesion localization, cancer staging, treatment planning and monitoring. A small area (8cm x 8cm) cadmium zinc telluride (CZT) based gamma camera was developed and tested for MR compatibility in both sequential and simultaneous imaging conditions. Results indicated that the gamma camera was minimally affected during both sequential and simultaneous imaging with a gradient echo (GRE) and spoiled gradient echo (GRE) sequence. Signal to noise ratio (SNR) degradation was observed in the MR images but no geometric distortions were observed. Simultaneous imaging is feasible, but a reassessment of the RF shielding would be required to minimize the noise contribution degrading image quality. Second, backscatter photons were investigated as a potential dose reduction technique for MBI. While the effective dose from MBI is relatively low in comparison to other nuclear medicine procedures, the dose is considered high in relation to mammography and in order to increase acceptance as an alternative breast imaging method, dose reduction is an important objective. Backscatter photons have the same spatial information as primary photons but are typically discarded along with other scattered photons. A scatter compensation method called the triple energy window (TEW) was used to extract backscatter photons from the Compton scattering spectrum and added to the primary photons, increasing count sensitivity by 6%. The noise level matched the increase in contrast leading to negligible change in lesion contrast to noise ratio (CNR). Dose reduction is not justified with this particular technique because of the elevated noise level, but the use of backcsatter photons show potential with improved contrast. / Dissertation / Doctor of Philosophy (PhD)

<p>X-ray mammography has been the gold standard for breast imaging for decades, despite the significant limitations posed by the two dimensional (2D) image acquisitions. Difficulty in diagnosing lesions close to the chest wall and axilla, high amount of structural overlap and patient discomfort due to compression are only some of these limitations. To overcome these drawbacks, three dimensional (3D) breast imaging modalities have been developed including dual modality single photon emission computed tomography (SPECT) and computed tomography (CT) systems. This thesis focuses on the development and integration of the next generation of such a device for dedicated breast imaging. The goals of this dissertation work are to: [1] understand and characterize any effects of fully 3-D trajectories on reconstructed image scatter correction, absorbed dose and Hounsifeld Unit accuracy, and [2] design, develop and implement the fully flexible, third generation hybrid SPECT-CT system capable of traversing complex 3D orbits about a pendant breast volume, without interference from the other. Such a system would overcome artifacts resulting from incompletely sampled divergent cone beam imaging schemes and allow imaging closer to the chest wall, which other systems currently under research and development elsewhere cannot achieve. </p><p>The dependence of x-ray scatter radiation on object shape, size, material composition and the CT acquisition trajectory, was investigated with a well-established beam stop array (BSA) scatter correction method. While the 2D scatter to primary ratio (SPR) was the main metric used to characterize total system scatter, a new metric called ‘normalized scatter contribution’ was developed to compare the results of scatter correction on 3D reconstructed volumes. Scatter estimation studies were undertaken with a sinusoidal saddle (±15° polar tilt) orbit and a traditional circular (AZOR) orbit. Clinical studies to acquire data for scatter correction were used to evaluate the 2D SPR on a small set of patients scanned with the AZOR orbit. Clinical SPR results showed clear dependence of scatter on breast composition and glandular tissue distribution, otherwise consistent with the overall phantom-based size and density measurements. Additionally, SPR dependence was also observed on the acquisition trajectory where 2D scatter increased with an increase in the polar tilt angle of the system. </p><p>The dose delivered by any imaging system is of primary importance from the patient’s point of view, and therefore trajectory related differences in the dose distribution in a target volume were evaluated. Monte Carlo simulations as well as physical measurements using radiochromic film were undertaken using saddle and AZOR orbits. Results illustrated that both orbits deliver comparable dose to the target volume, and only slightly differ in distribution within the volume. Simulations and measurements showed similar results, and all measured dose values were within the standard screening mammography-specific, 6 mGy dose limit, which is used as a benchmark for dose comparisons.</p><p>Hounsfield Units (HU) are used clinically in differentiating tissue types in a reconstructed CT image, and therefore the HU accuracy of a system is very important, especially when using non-traditional trajectories. Uniform phantoms filled with various uniform density fluids were used to investigate differences in HU accuracy between saddle and AZOR orbits. Results illustrate the considerably better performance of the saddle orbit, especially close to the chest and nipple region of what would clinically be a pedant breast volume. The AZOR orbit causes shading artifacts near the nipple, due to insufficient sampling, rendering a major portion of the scanned phantom unusable, whereas the saddle orbit performs exceptionally well and provides a tighter distribution of HU values in reconstructed volumes. </p><p>Finally, the third generation, fully-suspended SPECT-CT system was designed in and developed in our lab. A novel mechanical method using a linear motor was developed for tilting the CT system. A new x-ray source and a custom made 40 x 30 cm2 detector were integrated on to this system. The SPECT system was nested, in the center of the gantry, orthogonal to the CT source-detector pair. The SPECT system tilts on a goniometer, and the newly developed CT tilting mechanism allows ±15° maximum polar tilting of the CT system. The entire gantry is mounted on a rotation stage, allowing complex arbitrary trajectories for each system, without interference from the other, while having a common field of view. This hybrid system shows potential to be used clinically as a diagnostic tool for dedicated breast imaging.</p> / Dissertation

The recent increase in survival rates of most cancers is due to early detection greatly aided by medical imaging modalities. Combined ultrasound and photoacoustic imaging provide both morphological and functional/molecular information which can help to detect and diagnose cancer in its earliest stages. However, both modalities can benefit from the use of contrast agents. The objective of this thesis was to design, synthesize, and test a nano-sized, dual contrast agent for combined ultrasound and photoacoustic imaging named Photoacoustic nanoDroplets. This agent consists of liquid perfluorocarbon nanodroplets with encapsulated plasmonic nanoparticles. These dual contrast agents utilize optically triggered vaporization for photoacoustic signal generation, providing significantly higher signal amplitude than that from the traditionally used mechanism, thermal expansion. Upon pulsed laser irradiation, liquid perfluorocarbon undergoes a liquid-to-gas phase transition generating giant photoacoustic transients from these dwarf nanoparticles. Once triggered, the gaseous phase provides ultrasound contrast enhancement. Demonstrated in this work are the design, synthesis, characterization, and testing of Photoacoustic nanoDroplets in phantom and animal studies, and preliminary work into adapting these agents into targeted, drug delivery vehicles for simultaneous detection, diagnosis, and treatment of diseases. / text

No description available.

<p>Dual modality imaging systems such as SPECT/CT have become commonplace in medical imaging as it aids in diagnosing diseases by combining anatomical images with functional images. We are interested in developing a dual modality imaging system combining SPECT and MR imaging because MR does not require any ionizing radiation to image anatomical structures and it is known to have superior soft tissue contrast to CT. However, one of the fundamental challenges in developing a SPECT/MR system is that traditional gamma cameras with photomultiplier tubes are not compatible within magnetic fields. New development in solid state detectors has led to the silicon photomultiplier (SiPM), which is insensitive to magnetic fields.</p> <p>We have developed a small area gamma camera with a tileable 4x4 array of SiPM pixels coupled with a CsI(Tl) scintillation crystal. A number of simulated gamma camera geometries were performed using both pixelated and monolithic scintillation crystals. Several event positioning algorithms were also investigated as an alternative to conventional Anger logic positioning. Simulations have shown that we can adequately resolve intrinsic spatial resolution down to 1mm, even in the presence of noise. Based on the results of these simulations, we have built a prototype SiPM system comprised of 16 detection channels coupled to discrete crystals. A charge sensitive preamplifier, pulse height detection circuit and a digital acquisition system make up our pulse processing components in our gamma camera system. With this system, we can adequately distinguish each crystal element in the array and have obtained an energy resolution of 30±1 (FWHM) with Tc-99m (140keV). In the presence of a magnetic field, we have seen no spatial distortion of the resultant image and have obtained an energy resolution of 31±3.</p> / Master of Science (MSc)

It has been well documented that dual-task performance is more accurate when each task is based on a different sensory modality. It is also well documented that the memory for each sense has unequal durations, particularly visual (iconic) and auditory (echoic) sensory memory. In this dissertation I address whether differences in sensory memory (e.g. iconic vs. echoic) duration have implications for the design of a multimodal display. Since echoic memory persists for seconds in contrast to iconic memory which persists only for milliseconds, one of my hypotheses was that in a visual-auditory dual task condition, performance will be better if the visual task is completed before the auditory task than vice versa. In Experiment 1 I investigated whether the ability to recall multi-modal stimuli is affected by recall order, with each mode being responded to separately. In Experiment 2, I investigated the effects of stimulus order and recall order on the ability to recall information from a multi-modal presentation. In Experiment 3 I investigated the effect of presentation order using a more realistic task. In Experiment 4 I investigated whether manipulating the presentation order of stimuli of different modalities improves humans' ability to combine the information from the two modalities in order to make decision based on pre-learned rules. As hypothesized, accuracy was greater when visual stimuli were responded to first and auditory stimuli second. Also as hypothesized, performance was improved by not presenting both sequences at the same time, limiting the perceptual load. Contrary to my expectations, overall performance was better when a visual sequence was presented before the audio sequence. Though presenting a visual sequence prior to an auditory sequence lengthens the visual retention interval, it also provides time for visual information to be recoded to a more robust form without disruption. Experiment 4 demonstrated that decision making requiring the integration of visual and auditory information is enhanced by reducing workload and promoting a strategic use of echoic memory. A framework for predicting Experiment 1-4 results is proposed and evaluated.

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Many learners find the transition from block-based programming to text-based programming difficult. Consequently, research has investigated how block-based languages support learners when making the transition to text-based programming. It categorized the way in which block-based languages support the transition into one-way transition, dual-modality and hybrid environments. This research investigates how one-way transition environments compare to dual-modality environments with regards to learning a text-based language, and how the two modalities differ with regards to the motivational factors satisfaction, enjoyment and easiness. The results show that dual-modality environments could be a better alternative than one-way transition environment when learners make the transition from block-based to text-based programming. The results also show that solving a problem in dual-modality environments could be easier than solving them in one-way transition environments, which could potentially mean that learners experience more motivation when making the transition in a dual-modality environment. This study also investigated if there is an alternative to one-way transition, dual-modality and hybrid environments when helping learners transition from block-based to text-based programming, and what a learning activity in this alternative solution could look like. It found that Blockly Games is an alternative, and describes a learning activity built in Blockly Games. Future research should aim at gaining a deeper understanding of the differences between one-way transition, dual-modality and hybrid environments, and investigate if the approach taken by Blockly Games is a better alternative. / Många elever tycker att övergången från blockbaserad programmering till textbaserad programmering är svår. Följaktligen har forskning undersökt hur blockbaserade språk stödjer elever när de gör övergången till textbaserad programmering. En studie fann att blockbaserade språk stöder denna övergång med hjälp av one-way transition miljöer, dual-modality miljöer och hybrid miljöer. Denna forskning undersöker hur one-way transition miljöer jämför sig med dual-modality miljöer när det kommer till att lära sig ett textbaserat språk, och hur de två modaliteterna skiljer sig åt med avseende på motivationsfaktorerna tillfredsställelse, njutning och lätthet. Resultaten visar att dual-modality miljöer kan vara ett bättre alternativ än one-way transition miljöer när eleverna gör övergången från blockbaserad till textbaserad programmering. Resultaten visar också att det kan vara lättare att lösa ett problem i dual-modality miljöer än att lösa dem i one-way transition miljöer, vilket potentiellt kan innebära att eleverna upplever mer motivation när de gör övergången i en dual-modality miljö. Denna studie undersökte också om det finns ett alternativ till one-way transition miljöer, dual-modality miljöer och hybrid miljöer när elever ska övergå från blockbaserad till textbaserad programmering, och hur en inlärningsaktivitet i denna alternativa lösning skulle kunna se ut. Den fann att Blockly Games är ett alternativ och beskriver en inlärningsaktivitet byggd i Blockly Games. Framtida forskning borde försöka få en djupare förståelse för skillnaderna mellan one-way transition miljöer, dual-modality miljöer och hybrid miljöer, och undersöka om det tillvägagångssätt som Blockly Games använder är ett bättre alternativ.