The effect of the size of gold nanoparticle contrast agents on CT imaging of the gastrointestinal tract and inflammatory bowel disease.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). CT imaging with contrast agents is commonly used for visualizing the gastrointestinal (GI) tract in UC patients. CT is a common imaging modality for evaluating IBD, especially in patients with acute abdominal pain presenting to emergency departments. CT's major limitation lies in its lack of specificity for imaging UC, as the commonly used agents are not well-suited for inflamed areas. Recent studies gastrointestinal tract (GIT) in UC. Further systemic research is needed to explore novel contrast agents that can specifically image disease processes in this disease setting.

Towards the Clinical Translation of a Silver Sulfide Nanoparticle Contrast Agent: Large Scale Production with a Highly Parallelized Microfluidic Chip.

Ultrasmall silver sulfide nanoparticles (Ag 2 S-NP) have been identified as promising contrast agents for a number of modalities and in particular for dual-energy mammography. These Ag 2 S-NP have demonstrated marked advantages over clinically available agents with the ability to generate higher contrast with high biocompatibility. However, current synthesis methods are low-throughput and highly time-intensive, limiting the possibility of large animal studies or eventual clinical use of this potential imaging agent. We herein report the use of a scalable silicon microfluidic system (SSMS) for the large-scale synthesis of Ag 2 S-NP. Using SSMS chips with 1 channel, 10 parallelized channels, and 256 parallelized channels, we determined that the Ag 2 S-NP produced were of similar quality as measured by core size, concentration, UV-visible spectrometry, and in vitro contrast generation. Moreover, by combining parallelized chips with increasing reagent concentration, we were able to increase output by an overall factor of 3,400. We also found that in vivo imaging contrast generation was consistent across synthesis methods and confirmed renal clearance of the ultrasmall nanoparticles. Finally, we found best-in-class clearance of the Ag 2 S-NP occurred within 24 hours. These studies have identified a promising method for the large-scale production of Ag 2 S-NP, paving the way for eventual clinical translation.

Radioprotective garment-inspired biodegradable polymetal nanoparticles for enhanced CT contrast production.

Numerous formulations of nanoparticle-based X-ray computed tomography (CT) contrast agents made of heavy metal elements are under investigation for their ability to provide improved CT imaging. Thus far, most experimental nanoparticle-based CT contrast agents have been developed with atoms of a single element. However, inspired by the composites formed from multiple elements used in radioprotective garments, we hypothesized that contrast agents made of several elements whose K-edge energies are spaced out in the high photon flux region could achieve high, broadband X-ray attenuation across the energies used in X-ray source spectra. Herein, we synthesized sub-5 nm core inorganic nanoparticles containing gold, tantalum, and cerium, and encapsulated them in polymeric nanoparticles to form polymetal nanoparticles (PMNP). We found that PMNP with multiple payload elements generate higher and more stable CT contrast than contrast agents made from a single contrast generating material, demonstrating the potential benefits of incorporating multiple suitable elements as CT contrast payloads.

Effect of Gold Nanoparticle Size on Their Properties as Contrast Agents for Computed Tomography.

Computed tomography (CT) is one of the most commonly used clinical imaging modalities. There have recently been many reports of novel contrast agents for CT imaging. In particular, the development of gold nanoparticles (AuNP) as CT contrast agents is a topic of intense interest. AuNP have favorable characteristics for this application such as high payloads of contrast generating material, strong X-ray attenuation, excellent biocompatibility, tailorable surface chemistry, and tunable sizes and shapes. However, there have been conflicting reports on the role of AuNP size on their contrast generation for CT. We therefore sought to extensively investigate the AuNP size-CT contrast relationship. In order to do this, we synthesized AuNP with sizes ranging from 4 to 152 nm and capped them with 5 kDa m-PEG. The contrast generation of AuNP of different sizes was investigated with three clinical CT, a spectral photon counting CT (SPCCT) and two micro CT systems. X-ray attenuation was quantified as attenuation rate in Hounsfield units per unit concentration (HU/mM). No statistically significant difference in CT contrast generation was found among different AuNP sizes via phantom imaging with any of the systems tested. Furthermore, in vivo imaging was performed in mice to provide insight into the effect of AuNP size on animal biodistribution at CT dose levels, which has not previously been explored. Both in vivo imaging and ex vivo analysis with inductively coupled plasma optical emission spectroscopy (ICP-OES) indicated that AuNP that are 15 nm or smaller have long blood circulation times, while larger AuNP accumulated in the liver and spleen more rapidly. Therefore, while we observed no AuNP size effect on CT contrast generation, there is a significant effect of size on AuNP diagnostic utility.