Nancy Ford

This study demonstrated a method that can characterize the development of FLASH and conventional radiotherapy-induced pulmonary complications with in vivo respiratory-gated micro-CT imaging methods in free-breathing mice. Thirty C57BL/6 mice were selected for this research project. Baseline respiratory-gated micro-CT images of individuals were collected a week before receiving treatments. During each imaging session, we collected two images for the end-expiration and peak-inspiration phases. Mice were equally distributed into five groups after baseline respiratory-gated micro-CT imaging sessions to receive different radiation treatments. Treatments administered included no irradiated, 10 MV photon ultra-high dose-rate radiotherapy (FLASH-RT) and conventional radiotherapy at two dose levels 15 Gy and 30 Gy targeting on lungs. Mice received repeated respiratory-gated micro-CT scans up to 24 weeks post treatment. For data analysis, regions of interest were drawn starting 2 mm above the carina and covering the entire lung. After selecting threshold numbers, we did semi-manual lung segmentation. The lung's morphological, structural, and functional information was measured to evaluate injuries in pulmonary tissues. Statistics analysis were performed using ANOVA repeated measurement. We monitored the development of lung inflammation, radiation pneumonitis, and fibrosis through respiratory-gated micro-CT images at different timelines, which were also confirmed with histogram analysis. We found significant differences between high-dose conventional and the control groups. Our study showed that the respiratory-gated imaging method can identify the development of pulmonary inflammation and radiation. The murine model suggested that conventional radiation treatment had more severe complications than the FLASH group. This experimental work is the first study using the in vivo respiratory-gated imaging method to monitor the progression of 10 MV photon FLASH-RT-induced pulmonary complications in free-breathing mice.

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Micro-computed tomography (micro-CT) imaging has been used to study anatomical features in experimental subjects, including small animals. To improve the visibility of organs and soft tissues, contrast agents (CAs) were developed. This created opportunities for studying disease progression through a noninvasive imaging technique.A time course study was performed to determine if the novel MVivo AuNH₂, will be taken up by healthy hepatocytes and behave like a liver targeting CA. Two versions of MVivo AuNH₂ with a terminal amine polyethylene glycol (PEG) but one has a negative zeta potential and the other has a positive zeta potential. The experimental results show no difference in greyscale values against the blood pool CA, MVivo Au, particularly in the liver. This indicated that the modifications were not enough to introduce a liver-targeting property to MVivo AuNH₂.A second time course study was performed on a novel CA, Fenestra HDVC, a concentrated version of the blood pool CA, Fenestra VC. Through experimental work, it was confirmed that Fenestra HDVC did have twice the amount of iodine, the iodine concentration was at 100 mg/mL, and that it also had dual-imaging properties. So, upon injection it will behave like a blood pool CA for a few hours then behave like a liver targeting CA until total elimination. The dual-imaging property of Fenestra HDVC was used in a tumor study to determine its effectiveness in monitoring liver tumor growth through in vivo micro-CT scans. The number of tumors, tumor volumes and total tumor burden were calculated from the in vivo images and compared with the calculations made from the ex vivo images of the excised tumorous liver. The results provide strong evidence that Fenestra HDVC can enhance the liver to show growth of multiple tumor nodules. The tumor volume measurements were also similar to those obtained from the ex vivo images showing that in vivo micro-CT scans using Fenestra HDVC can be used to detect and study liver cancer. This experimental work provides a foundation for future research in liver cancer studies that use Fenestra HDVC as the CA for in vivo micro-CT imaging in small animals.

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Purpose: Cone beam computed tomography (CBCT) image quality is known to be affected by artifacts produced by metal restorations, causing image deterioration via bright streaks and loss of gray values in the vicinity of the metallic structure. The aim of the study is to determine the impact of progressively increasing metal artifacts on the measurement accuracy of commonly evaluated points in implant treatment planning. Methods: Holes were drilled into porcine mandibles at known distances from the alveolar crest on the buccal and lingual surfaces and filled with gutta percha. Repeated CBCT images were taken, with progressively increasing amalgam restorations and stainless-steel crowns (up to a total of 8 restorations per jaw). The imaging field of view (FOV) was of a single site (5x5cm) in 2 different locations in the mandible, as well as a full arch FOV (10x5cm). Measurement between the buccal and lingual gutta percha points on the mandible was performed using a digital caliper to establish the difference between caliper measurements compared to the same measurements taken digitally on the CBCT images. Measurements were compared under conditions with no restorations and with increasing numbers of restorations. Results: Comparison between caliper measurements and baseline CBCT with no metal artifact demonstrated differences ranging from 0-1.7 mm. This range of variation appears to be consistent even with increasing metal artifact, with no clear detectable pattern of change. When compared to baseline measurements, scans with amalgam and stainless-steel restorations showed a maximum difference of 0.54 ± 0.64 mm and 0.62 ± 0.64 mm respectively. The change in measurements was not found to be significantly different with increasing metal restorations.Conclusions: There may be a variation of up to 1.7 mm between measured anatomical points and CBCT imaging under commonly used settings. While this result may be clinically important, it does not appear to be affected by increasing metal artifact due to amalgam restorations or stainless-steel crowns. The findings of this study support current clinical practices accounting for a safety margin of up to 2 mm with any CBCT image, and not limiting CBCT scans for patients with multiple metal restorations.

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Objectives: Contrast agents are required to be able to view and differentiate tissues in 3-D computed tomography (CT) due to similarities in density. Pre-clinical contrast agents used for radiology are not visible when viewed histologically, and visa versa. Identifying a single agent that is visible in both x-ray and optical imaging, would ensure that the target tissues can be easily identified and correlated in both images, without the need of additional staining techniques. Here we present an approach for imaging the murine cardiovascular system and organs, and melanoma tumours using micro-computed tomography (micro-CT) and optical projection tomography (OPT), using fluorescently-labeled gold nanoparticles.Materials and Methods: A 1% agarose phantom was used with 2 µl of the Cy3 fluorescently-labeled gold nanoparticles deposited in the block, and imaged with micro-CT and OPT. In vivo systemic testing involved tail vein intravascular injections into mice using Cy3 fluorescently-coated gold nanorods. These mice were subjected to micro-CT scans, both before and after contrast injection. Once euthanized, the heart, liver and kidneys were excised, scanned using the higher resolution specimen micro-CT scanner, then prepared, and visualized under OPT using filtered UV light at 545-610nm. Localized in vivo testing was performed using B16F10 cells to induce tumour growth in the right hind legs of mice. Cy3 fluorescently-coated gold nanorods were injected directly into the tumours prior to imaging. The mice were scanned with in vivo micro-CT for pre- and post-contrast scans. Once euthanized, the hind leg was dissected and scanned with a specimen micro-CT at a higher resolution. The dissected hind legs were prepared and visualized under OPT using filtered UV light at 545-610 nm.Results: Using the agarose phantom, the gold nanoparticles were visible under both micro-CT and OPT, with co-localization between images. With the in vivo systemic testing, the nanoparticles were not visible. The in vivo localized tumour study showed the distribution of the gold nanoparticles within the tumours, allowing for visualization under micro-CT. OPT imaging was successful and co-localized to micro-CT.Conclusions: Cy3 fluorescently-labeled gold nanorods injected into murine melanoma tumours can be visualized under micro-CT imaging, and co-localized to OPT.

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Objectives: This study was conducted to optimize the CBCT image quality in implant dentistry using both clinical and quantitative image quality evaluation with measurement of the radiation dose. Materials and methods: A natural bone human skull phantom and an image quality phantom were used to evaluate the images produced after changing the exposure parameters (kVp and mA). A 10x5 cm² FOV was selected for average adult. Five scans were taken with varying kVp (70 kVp, 75 kVp, 80 kVp, 85 kVp, 90 kVp) first at fixed 4 mA. After assessment of the scans and selecting the best kVp, nine scans were taken with varying mA (2 mA, 2.5 mA, 3.2 mA, 4 mA, 5 mA, 6.3 mA, 10 mA, 12 mA) and the optimal kVp was fixed. A dosimetry index phantom was used to measure the absorbed dose for each scan setting. Quantitative image quality was assessed for noise, uniformity, artifact added value, contrast-to-noise ratio, spatial resolution and geometrical distortion. A clinical assessment of implant related anatomical landmarks was done in random order by two blinded examiners. Results: The absorbed dose was reduced with reduction of exposure settings. The quantitative image quality values were acceptable at variable exposure settings. The anatomical landmarks of the maxilla had good quality at all different kVp settings. To produce good image quality, the mandibular landmarks demanded higher exposure parameters than maxilla. Conclusion: Changing the exposure parameters does not necessarily produce higher image quality outcomes but does affect the radiation dose to the patient. The image quality could be optimized for implant treatment planning at lower exposure settings and dose than the default settings.

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Objectives: To obtain head dimensions from patients who received dental CBCT at BC Children’s Hospital (BCCH), to apply this information to design and construct small child and adolescent head phantoms, and to measure and compare the absorbed radiation doses from CBCT and panoramic radiographs using small child, adolescent and adult head phantoms.Materials and Methods: Patients who received dental CBCT at BCCH were surveyed. Head dimensions from each subject’s image were measured to develop adolescent and small child head phantoms. The most commonly used dental CBCT imaging protocols were examined. Absorbed doses were measured for small child, adolescent and adult head phantoms with i-CAT CBCT and Planmeca panoramic radiograph machines. Results: In the patient survey, 32 patients met the inclusion criteria. The most common indications for CBCT referral were for orthodontic treatment, followed by craniofacial abnormality and cleft lip and palate. A small child phantom was developed to represent the child patients with craniofacial abnormality and an adolescent phantom was developed to represent healthy orthodontic patients. Absorbed radiation doses varied depending on machine, imaging protocol, size of phantom and location of the ion chamber in the phantoms. For CBCT images, the highest radiation was measured in the small child phantom while the lowest radiation was measured in the adult phantom. For panoramic radiographs, the i-CAT CBCT panoramic option was compared to the Planmeca panoramic radiograph machine. For both machines, the small child phantom measured the highest while the adult phantom measured the lowest radiation. For the adolescent phantom, lower values were measured with the Planmeca machine while lower values were measured with i-CAT CBCT panoramic option for the small child phantom.Conclusion: Two groups of pediatric patients were referred for dental CBCT at BCCH: young patients with craniofacial abnormality and healthy adolescent patients for orthodontic assessment. A consistent trend was observed for both CBCT and panoramic radiographs: the highest dose was measured in the smallest phantom while the lowest dose was measured in the largest phantom. Radiation in pediatric population is more detrimental than in adult population and it is important to child size the dose and protocol.

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Purpose: To characterize the performance of cone beam CT (CBCT) used in dentistry, investigating quantitatively the image quality and radiation dose during dental CBCT over different settings for partial rotation of the x-ray tube. Methods: Image quality and dose measurements were done on a variable field of view (FOV) dental CBCT (Carestream 9300). X-ray parameters for clinical settings were adjustable for 2-10 mA, 60-90 kVp, and two optional voxel size values, with fixed time for each protocol and FOV. The phantoms were positioned in the FOV to imitate clinical positioning. Image quality was assessed by scanning a cylindrical poly-methyl methacrylate (PMMA) image quality phantom (SEDENTEXCT IQ), and the images were analyzed using ImageJ to calculate image quality parameters such as noise, uniformity, contrast to noise ratio (CNR), and spatial resolution. A protocol proposed by SEDENTEXCT, dose index 1 (DI1), was applied to dose measurements obtained using a thimble ionization chamber and cylindrical PMMA dose index phantom (SEDENTEXCT DI). Dose distributions were obtained using Gafchromic film. Results: The image noise was 6-12.5% which, when normalized to the difference of mean voxel value of PMMA and air, was comparable between different FOVs. Uniformity was 93.5-99.7% across the images. CNR was 0.5-4.2, 0.2-4.6, 3.7-11.7, 4.3-17.8, and 6.3-14.3 for LDPE, POM, PTFE, air, and aluminum, respectively. The measured FWHM and spatial resolution were larger than the voxel size. FWHM were 0.49-0.65 mm; spatial resolution was 194.81-467.68. Dose distributions were symmetric about the rotation angle’s bisector. For large and medium FOVs at 4 mA, 80-90 kVp, and 180-250 μm, DI1 values were in the range of 1.26-3.23 mGy. DI1 values were between 1.01-1.93 mGy for small FOV (5x5 cm²) at 4-5 mA,75-84 kVp, and 200 μm. Conclusion: Noise and spatial resolution decreased and the CNR increased by increasing kVp; the geometric distortion, AAV, FWHM were very similar or the same when increasing the kVp. When FOV size increased, image noise increased and CNR decreased. FWHM and spatial resolution have no correlation with the voxel size. DI1 values were increased by increasing tube current (mA), tube voltage (kVp), and/or FOV.

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