Nanoparticle-based Contrast Agents Research Articles

A Facile Synthesis of Novel Self-Assembled Gold Nanorods Designed for Near-Infrared Imaging

Molecular imaging techniques now allow recognition of early biochemical, physiological, and anatomical changes before manifestation of gross pathological changes. Photoacoustic imaging represents a novel non-ionizing detection technique that combines the advantages of optical and ultrasound imaging. Noninvasive photoacoustic tomography (PAT) imaging in combination with nanoparticle-based contrast agents show promise in improved detection and diagnosis of cardiovascular and cancer related diseases. In this report, a novel strategy is introduced to achieve self-assembled colloidal gold nanorods, which are constrained to the vasculature. Gold nanorods (2-4 nm) were incorporated into the core of self-assembled lipid-encapsulated nanoparticles (sGNR) (approximately 130 nm), providing more than hundreds of gold atoms per nanoparticle of 20% colloid suspension. The physico-chemical characterization in solution and anhydrous state with analytical techniques demonstrated that the particles were spherical and highly mono dispersed. In addition to the synthesis and characterization, sensitive near-infrared photoacoustic detection was impressively demonstrated in vitro.

Quantification of SPIO nanoparticles in vivo using the finite perturber method

The susceptibility gradients generated by super-paramagnetic iron oxide (SPIO) nanoparticles make them an ideal contrast agent in magnetic resonance imaging. Traditional quantification methods for SPIO nanoparticle-based contrast agents rely on either mapping T₂* values within a region or by modeling the magnetic field inhomogeneities generated by the contrast agent. In this study, a new model-based SPIO quantification method is introduced. The proposed method models magnetic field inhomogeneities by approximating regions containing SPIOs as ensembles of magnetic dipoles, referred to as the finite perturber method. The proposed method was verified using data acquired from a phantom and in vivo mouse models. The phantom consisted of an agar solution with four embedded vials, each vial containing known but different concentrations of SPIO nanoparticles. Gaussian noise was also added to the phantom data to test performance of the proposed method. The in vivo dataset was acquired using five mice, each of which was subcutaneously implanted in the flanks with 1 × 10(5) labeled and 1 × 10(6) unlabeled C6 glioma cells. For the phantom data set, the proposed algorithm was generate accurate estimations of the concentration of SPIOs. For the in vivo dataset, the method was able to give estimations of the concentration within SPIO-labeled tumors that are reasonably close to the known concentration.

Inorganic nanoparticle-based contrast agents for molecular imaging

Inorganic nanoparticles (NPs) including semiconductor quantum dots (QDs), iron oxide NPs and gold NPs have been developed as contrast agents for diagnostics by molecular imaging. Compared with traditional contrast agents, NPs offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multimodal imaging. Here, we review recent advances in the development of contrast agents based on inorganic NPs for molecular imaging, and also touch on contrast enhancement, surface modification, tissue targeting, clearance and toxicity. As research efforts intensify, contrast agents based on inorganic NPs that are highly sensitive, target-specific and safe to use are expected to enter clinical applications in the near future.

Nanoparticles as contrast agents for in-vivo bioimaging: current status and future perspectives

Nanoparticle-based contrast agents are quickly becoming valuable and potentially transformative tools for enhancing medical diagnostics for a wide range of in-vivo imaging modalities. Compared with conventional molecular-scale contrast agents, nanoparticles (NPs) promise improved abilities for in-vivo detection and potentially enhanced targeting efficiencies through longer engineered circulation times, designed clearance pathways, and multimeric binding capacities. However, NP contrast agents are not without issues. Difficulties in minimizing batch-to-batch variations and problems with identifying and characterizing key physicochemical properties that define the in-vivo fate and transport of NPs are significant barriers to the introduction of new NP materials as clinical contrast agents. This manuscript reviews the development and application of nanoparticles and their future potential to advance current and emerging clinical bioimaging techniques. A focus is placed on the application of solid, phase-separated materials, for example metals and metal oxides, and their specific application as contrast agents for in-vivo near-infrared fluorescence (NIRF) imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound (US), and photoacoustic imaging (PAI). Clinical and preclinical applications of NPs are identified for a broad spectrum of imaging applications, with commentaries on the future promise of these materials. Emerging technologies, for example multifunctional and theranostic NPs, and their potential for clinical advances are also discussed.

Potential Use of Nanoparticle Based Contrast Agents in MRI: A Molecular Imaging Perspective

The development of molecular imaging technologies represents the opportunity to differentiate tissues based upon their metabolic and functional activity rather than structural and anatomic characteristics. The goal of molecular imaging is to reveal the pathophysiology underlying the observed anatomy and to diagnose disease based upon early biochemical processes. Detection of pathologic biomarkers can lead to early recognition of diseases, better therapeutic management, and improved monitoring for recurrence. Among the current clinical imaging modalities, MRI is uniquely suited for molecular imaging applications, offering a non-invasive means to obtain both anatomic and metabolic/functional information with high spatial and temporal resolution. Site-specific MRI contrast agents have been developed to target biologic processes that occur early in the development of diseases such as atherosclerotic plaques, tumor angiogenesis, and disease specific biosignatures. Furthermore, early disease recognition, prompting therapeutic intervention and drug delivery evaluation are possible using targeted contrast agents.

Combined photoacoustic and magneto-acoustic imaging.

Ultrasound is a widely used modality with excellent spatial resolution, low cost, portability, reliability and safety. In clinical practice and in the biomedical field, molecular ultrasound-based imaging techniques are desired to visualize tissue pathologies, such as cancer. In this paper, we present an advanced imaging technique - combined photoacoustic and magneto-acoustic imaging - capable of visualizing the anatomical, functional and biomechanical properties of tissues or organs. The experiments to test the combined imaging technique were performed using dual, nanoparticle-based contrast agents that exhibit the desired optical and magnetic properties. The results of our study demonstrate the feasibility of the combined photoacoustic and magneto-acoustic imaging that takes the advantages of each imaging techniques and provides high sensitivity, reliable contrast and good penetrating depth. Therefore, the developed imaging technique can be used in wide range of biomedical and clinical application.

Nanoparticles for photoacoustic imaging

Nanoparticles have been designed and applied as contrast enhancers in various optical imaging techniques, such as optical coherence tomography, fluorescence imaging, and optical reflectance microscopy. As an emerging hybrid imaging modality, photoacoustic imaging (PAI) has also benefited from the application of these nanoparticle-based contrast agents. We review this rapidly growing field and describe the applications of nanoparticles in PAI. Particular focus is given to nanoparticles whose absorption mechanism is based on surface plasmon resonance, including gold nanoshells, nanorods, and nanocages. Dye-embedded nanoparticles are also reviewed. Specifically, the design and application of each nanoparticle-based contrast agent in relation to the field of PAI are detailed.

Nanotechnologists Seek Biological Niches

Biologists are embracing nanotechnology—the engineering and manipulating of entities in the 1 to 100 nm range—and are exploiting its potential to develop new therapeutics and diagnostics.