Imaging technologies are being increasingly employed to guide the delivery of cancer therapies with the intent to increase their performance and efficacy. To date, many patients have benefited from image-guided treatments through prolonged survival and improvements in quality of life. Advances in nanomedicine have enabled the development of multifunctional imaging agents that can further increase the performance of image-guided cancer therapy. Specifically, this talk will focus on examples that demonstrate the benefits and application of nanomedicine in the context of image-guide surgery, personalized drug delivery, tracking of cell therapies and high precision radiotherapy delivery.
The ability of computed tomography (CT) and magnetic resonance (MR) imaging to visualize and discriminate between normal and diseased tissues is improved with contrast agents, which are designed to differentially accumulate in tissues and modify their inherent imaging signal. Conventional contrast agents are limited to a single modality and require fast acquisitions due to rapid clearance following injection. Encapsulation of iohexol and gadoteridol within a nano-engineered liposome has been achieved and can increase their in vivo half-life to several days. We hypothesize that the persistence of this contrast agent in vivo, and the simultaneous co-localized contrast enhancement across modalities will improve longitudinal image registration. This work investigates the in vivo registration performance of the dual-modality contrast agent under realistic conditions. Previous characterizations of single-modality contrast agents were limited to qualitative inspections of signal intensity enhancement. We present quantitative, information theoretic methods for assessing image registration performance. The effect of increased localized contrast upon the mutual information of the MR and CT image sets was shown to increase post-injection. Images registered post- injection had a decreased registration error compared with pre-contrast images. Performance was maintained over extended time frames, contrast agent concentrations, and with decreased field-of-view. This characterization allows optimization of the contrast agent against desired performance for a given imaging task. The ability to perform robust longitudinal image registration is essential for pre-clinical investigations of tumor development, monitoring of therapy response, and therapy guidance over multiple fractions where registration of online cone-beam CT to planning CT and MR is necessary.
Contrast agents are widely employed in medical imaging for improved visualization of anatomy and disease
characterization. In recent years, there is increasing interest in developing novel contrast agents and using their tissue
accumulation and clearance patterns to obtain physiological information. The goal of this investigation is to assess the
utility of a long circulating dual modality liposomal contrast agent for longitudinal imaging applications in computed
tomography (CT) and magnetic resonance (MR) imaging. It was demonstrated that this high molecular weight contrast
agent is retained in healthy vasculature (circulation half-life of ~20 hours in mice and ~100 hours in rabbits), but it is
able to leak through abnormal tumor vasculature into the tumor interstitium. The rate of its differential tumor uptake was
monitored in CT and MR longitudinally over a 48-hour period and a map of the rate of change of contrast enhancement
was produced. This contrast agent has shown potential for anatomic and physiological imaging of healthy and abnormal
blood vessels in CT and MR. It may become a useful tool for tumor vasculature assessment before, during and after antitumor
Multimodality imaging has gained momentum in radiation therapy planning and image-guided treatment delivery. Specifically, computed tomography (CT) and magnetic resonance (MR) imaging are two complementary imaging modalities often utilized in radiation therapy for visualization of anatomical structures for tumour delineation and accurate registration of image data sets for volumetric dose calculation. The development of a multimodal contrast agent for CT and MR with prolonged in vivo residence time would provide long-lasting spatial and temporal correspondence of the anatomical features of interest, and therefore facilitate multimodal image registration, treatment planning and delivery. The multimodal contrast agent investigated consists of nano-sized stealth liposomes encapsulating conventional iodine and gadolinium-based contrast agents. The average loading achieved was 33.5 ± 7.1 mg/mL of iodine for iohexol and 9.8 ± 2.0 mg/mL of gadolinium for gadoteridol. The average liposome diameter was 46.2 ± 13.5 nm. The system was found to be stable in physiological buffer over a 15-day period, releasing 11.9 ± 1.1% and 11.2 ± 0.9% of the total amounts of iohexol and gadoteridol loaded, respectively. 200 minutes following in vivo administration, the contrast agent maintained a relative contrast enhancement of 81.4 ± 13.05 differential Hounsfield units (ΔHU) in CT (40% decrease from the peak signal value achieved 3 minutes post-injection) and 731.9 ± 144.2 differential signal intensity (ΔSI) in MR (46% decrease from the peak signal value achieved 3 minutes post-injection) in the blood (aorta), a relative contrast enhancement of 38.0 ± 5.1 ΔHU (42% decrease from the peak signal value achieved 3 minutes post-injection) and 178.6 ± 41.4 ΔSI (62% decrease from the peak signal value achieved 3 minutes post-injection) in the liver (parenchyma), a relative contrast enhancement of 9.1 ± 1.7 ΔHU (94% decrease from the peak signal value achieved 3 minutes post-injection) and 461.7 ± 78.1 ΔSI (60% decrease from the peak signal value achieved 5 minutes post-injection) in the kidney (cortex) of a New Zealand white rabbit. This multimodal contrast agent, with prolonged in vivo residence time and imaging efficacy, has the potential to bring about improvements in the fields of medical imaging and radiation therapy, particularly for image registration and guidance.