Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods.
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ABSTRACT:
SUBMITTER: Bernstein AL
PROVIDER: S-EPMC4868985 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Gold nanoparticles (gold-NPs) have lately been proposed as alternative contrast agents to iodine-based contrast agents (iodine-CA) for computed tomography (CT) angiography. The aims of this study were to confirm an appropriate environment in which to evaluate such novel contrast agents, to investigate the comparative contrast of iodine-CA versus gold-NP, and to determine optimal scanning parameters for gold-NP.Three different clinical scanners were used to acquire CT images. A range of concentrations (10 mM to 1.5 M) of gold-NP and iodine-CA were scanned with varying x-ray tube voltages and currents, reconstruction kernels, protocols, and scanner models. The different environments investigated were air, water, and water with a bone simulant (Ca3(PO4)2). Regression coefficients were derived from the attenuation values plotted against concentration and compared for statistical significance using t values.As expected, contrast was linearly related to concentrations up to 500 to 1000 mM, depending on the conditions used, whereupon a plateau of 3000 Hounsfield units was reached. Attenuation was significantly different depending on the environment used (air, water, or water and bone simulant). Contrast is dependent on the x-ray tube voltage used, with the contrast produced from iodine-CA sharply declining with increasing voltage, whereas the contrast of gold-NP varied less with tube voltage but was maximal at 120 kV in water with bone simulant. Current, reconstruction kernels, protocols, and scanner model had less effect on contrast.Water with a bone simulant is a preferable environment for evaluating novel cardiac CT contrast agents. Relative iodine-CA versus gold-NP contrast is dependent on the scanning conditions used. Optimal scanning conditions for gold-NP will likely use an x-ray tube voltage of 120 kV.
| S-EPMC3582405 | biostudies-literature
Project description: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.
| S-EPMC6797746 | biostudies-literature
Project description:Computed tomography (CT) is an X-ray-based whole-body imaging technique that is widely used in medicine. Clinically approved contrast agents for CT are iodinated small molecules or barium suspensions. Over the past seven years there has been a great increase in the development of nanoparticles as CT contrast agents. Nanoparticles have several advantages over small molecule CT contrast agents, such as long blood-pool residence times and the potential for cell tracking and targeted imaging applications. Furthermore, there is a need for novel CT contrast agents, owing to the growing population of renally impaired patients and patients hypersensitive to iodinated contrast. Micelles and lipoproteins, a micelle-related class of nanoparticle, have notably been adapted as CT contrast agents. In this review we discuss the principles of CT image formation and the generation of CT contrast. We discuss the progress in developing nontargeted, targeted and cell tracking nanoparticle CT contrast agents. We feature agents based on micelles and used in conjunction with spectral CT. The large contrast agent doses needed will necessitate careful toxicology studies prior to clinical translation. However, the field has seen tremendous advances in the past decade and we expect many more advances to come in the next decade.
| S-EPMC3905628 | biostudies-other
Project description:Gold nanoparticles (AuNP) have been proposed for many applications in medicine. Although large AuNP (>5.5 nm) are desirable for their longer blood circulation and accumulation in diseased tissues, small AuNP (<5.5 nm) are required for excretion via the kidneys. We present a novel platform where small, excretable AuNP are encapsulated into biodegradable poly di(carboxylatophenoxy)phosphazene (PCPP) nanospheres. These larger nanoparticles (Au-PCPP) can perform their function as contrast agents, then subsequently break down into harmless byproducts and release the AuNP for swift excretion. Homogeneous Au-PCPP were synthesized using a microfluidic device. The size of the Au-PCPP can be controlled by the amount of polyethylene glycol-polylysine (PEG-PLL) block co-polymer in the formulation. Synthesis of Au-PCPP nanoparticles and encapsulation of AuNP in PCPP were evaluated using transmission electron microscopy and their biocompatibility and biodegradability confirmed in vitro. The Au-PCPP nanoparticles were found to produce strong computed tomography contrast. The UV-Vis absorption peak of Au-PCPP can be tuned into the near infrared region via inclusion of varying amounts of AuNP and controlling the nanoparticle size. In vitro and in vivo experiments demonstrated the potential of Au-PCPP as contrast agents for photoacoustic imaging. Therefore, Au-PCPP nanoparticles have high potency as contrast agents for two imaging modalities, as well as being biocompatible and biodegradable, and thus represent a platform with potential for translation into the clinic.
| S-EPMC4941627 | biostudies-literature
Project description:Nanostructures have potential for use in biomedical applications such as sensing, imaging, therapeutics, and drug delivery. Among nanomaterials, gold nanostructures are of considerable interest for biomedical research, owing to their bio-inertness, controllable surface chemistry, X-ray opacity, and optical properties. Gold nanocages are particularly attractive for imaging and therapeutic applications, because they strongly absorb light in the near infra-red region which has high light transmission in tissue. However, the X-ray attenuation of nanocages is relatively low due to their hollow structure. In this study, for the first time, we sought to combine the attractive optical properties of nanoshells with the high payloads of solid nanoparticles and investigated their biomedical applications. Here, we report the engineering of Wulff in a cage nanoparticles via converting gold Wulff-shaped seeds into gold-silver core-shell structures and then performing a galvanic replacement reaction. The structure of these nanoparticles was determined using transition electron microscopy. This morphological transformation of gold nanoparticles shaped as truncated octahedrons into a complex Wulff in a cage nanoparticles during the reaction resulted in extensive changes in their optical properties that made these unique structures a potential contrast agent for photoacoustic imaging. We found that the Wulff in a cage nanoparticles had no adverse effects on the viabilities of J774A.1, Renca, and HepG2 cells at any of the concentrations tested. In vitro and in vivo experiments showed robust signals in both photoacoustic imaging and computed tomography. To the best of our knowledge, this is the first report of Wulff in a cage nanoparticles serving as a platform for multiple imaging modalities. This unique multifunctional nanostructure, which integrates the competencies of both core and shell structures, allows their use as contrast agents for photoacoustic imaging, computed tomography and as a potential agent for photothermal therapy.
| S-EPMC6190607 | biostudies-literature
Project description:BackgroundThe accumulation of macrophages in inflamed atherosclerotic plaques has long been recognized. In an attempt to develop an imaging agent for detection of vulnerable plaques, we evaluated the feasibility of a liposomal-iodine nanoparticle contrast agent for computed tomography imaging of macrophage-rich atherosclerotic plaques in a mouse model.Methods and resultsLiposomal-iodine formulations varying in particle size and polyethylene glycol coating were fabricated and shown to stably encapsulate the iodine compound. In vitro uptake studies using optical and computed tomography imaging in the RAW 264.7 macrophage cell line identified the formulation that promoted maximal uptake. Dual-energy computed tomography imaging using this formulation in apolipoprotein E-deficient (ApoE(-/-)) mice (n=8) and control C57BL/6 mice (n=6) followed by spectral decomposition of the dual-energy images enabled imaging of the liposomes localized in the plaque. Imaging cytometry confirmed the presence of liposomes in the plaque and their colocalization with a small fraction (≈2%) of the macrophages in the plaque.ConclusionsThe results demonstrate the feasibility of imaging macrophage-rich atherosclerotic plaques using a liposomal-iodine nanoparticle contrast agent and dual-energy computed tomography.
| S-EPMC3760185 | biostudies-literature
Project description:There is an increasing interest in iterative reconstruction (IR) as a key tool to improve quality and increase applicability of x-ray CT imaging. IR has the ability to significantly reduce patient dose; it provides the flexibility to reconstruct images from arbitrary x-ray system geometries and allows one to include detailed models of photon transport and detection physics to accurately correct for a wide variety of image degrading effects. This paper reviews discretization issues and modelling of finite spatial resolution, Compton scatter in the scanned object, data noise and the energy spectrum. The widespread implementation of IR with a highly accurate model-based correction, however, still requires significant effort. In addition, new hardware will provide new opportunities and challenges to improve CT with new modelling.
| S-EPMC3725149 | biostudies-literature
Project description:ObjectiveTo compare image qualities between vendor-neutral and vendor-specific hybrid iterative reconstruction (IR) techniques for abdominopelvic computed tomography (CT) in young patients.Materials and methodsIn phantom study, we used an anthropomorphic pediatric phantom, age-equivalent to 5-year-old, and reconstructed CT data using traditional filtered back projection (FBP), vendor-specific and vendor-neutral IR techniques (ClariCT; ClariPI) in various radiation doses. Noise, low-contrast detectability and subjective spatial resolution were compared between FBP, vendor-specific (i.e., iDose1 to 5; Philips Healthcare), and vendor-neutral (i.e., ClariCT1 to 5) IR techniques in phantom. In 43 patients (median, 14 years; age range 1-19 years), noise, contrast-to-noise ratio (CNR), and qualitative image quality scores of abdominopelvic CT were compared between FBP, iDose level 4 (iDose4), and ClariCT level 2 (ClariCT2), which showed most similar image quality to clinically used vendor-specific IR images (i.e., iDose4) in phantom study. Noise, CNR, and qualitative imaging scores were compared using one-way repeated measure analysis of variance.ResultsIn phantom study, ClariCT2 showed noise level similar to iDose4 (14.68-7.66 Hounsfield unit [HU] vs. 14.78-6.99 HU at CT dose index volume range of 0.8-3.8 mGy). Subjective low-contrast detectability and spatial resolution were similar between ClariCT2 and iDose4. In clinical study, ClariCT2 was equivalent to iDose4 for noise (14.26-17.33 vs. 16.01-18.90) and CNR (3.55-5.24 vs. 3.20-4.60) (p > 0.05). For qualitative imaging scores, the overall image quality ([reader 1, reader 2]; 2.74 vs. 2.07, 3.02 vs. 2.28) and noise (2.88 vs. 2.23, 2.93 vs. 2.33) of ClariCT2 were superior to those of FBP (p < 0.05), and not different from those of iDose4 (2.74 vs. 2.72, 3.02 vs. 2.98; 2.88 vs. 2.77, 2.93 vs. 2.86) (p > 0.05).ConclusionVendor-neutral IR technique shows image quality similar to that of clinically used vendor-specific hybrid IR technique for abdominopelvic CT in young patients.
| S-EPMC6715563 | biostudies-literature
Project description:PurposeTo provide additional functional information for tumor characterization, we investigated the use of dual-energy computed tomography for imaging murine lung tumors. Tumor blood volume and vascular permeability were quantified using gold and iodine nanoparticles. This approach was compared with a single contrast agent/single-energy CT method. Ex vivo validation studies were performed to demonstrate the accuracy of in vivo contrast agent quantification by CT.MethodsPrimary lung tumors were generated in LSL-Kras(G12D); p53(FL/FL) mice. Gold nanoparticles were injected, followed by iodine nanoparticles two days later. The gold accumulated in tumors, while the iodine provided intravascular contrast. Three dual-energy CT scans were performed-two for the single contrast agent method and one for the dual contrast agent method. Gold and iodine concentrations in each scan were calculated using a dual-energy decomposition. For each method, the tumor fractional blood volume was calculated based on iodine concentration, and tumor vascular permeability was estimated based on accumulated gold concentration. For validation, the CT-derived measurements were compared with histology and inductively-coupled plasma optical emission spectroscopy measurements of gold concentrations in tissues.ResultsDual-energy CT enabled in vivo separation of gold and iodine contrast agents and showed uptake of gold nanoparticles in the spleen, liver, and tumors. The tumor fractional blood volume measurements determined from the two imaging methods were in agreement, and a high correlation (R(2)?= 0.81) was found between measured fractional blood volume and histology-derived microvascular density. Vascular permeability measurements obtained from the two imaging methods agreed well with ex vivo measurements.ConclusionsDual-energy CT using two types of nanoparticles is equivalent to the single nanoparticle method, but allows for measurement of fractional blood volume and permeability with a single scan. As confirmed by ex vivo methods, CT-derived nanoparticle concentrations are accurate. This method could play an important role in lung tumor characterization by CT.
| S-EPMC3919743 | biostudies-literature
Project description:The use of nanotechnologies for biomedical applications took a real development during these last years. To allow an effective targeting for biomedical imaging applications, the adsorption of plasmatic proteins on the surface of nanoparticles must be prevented to reduce the hepatic capture and increase the plasmatic time life. In biologic media, metal oxide nanoparticles are not stable and must be coated by biocompatible organic ligands. The use of phosphonate ligands to modify the nanoparticle surface drew a lot of attention in the last years for the design of highly functional hybrid materials. Here, we report a methodology to synthesize bisphosphonates having functionalized PEG side chains with different lengths. The key step is a procedure developed in our laboratory to introduce the bisphosphonate from acyl chloride and tris(trimethylsilyl)phosphite in one step.
| S-EPMC4979661 | biostudies-literature