Dual-contrast Imaging Research Articles

Silicon Carbide Nanoparticles as a Photoacoustic and Photoluminescent Dual-Imaging Contrast Agent for Long-Term Cell Tracking.

Silicon carbide nanoparticles (SiCNPs) are durable, physically resilient, chemically inert, and biocompatible. Silicon carbide particles smaller than 10 nm show photoluminescence due to quantum confinement effects and have been reported in imaging different cell lines. To further explore the potential of silicon carbide nanomaterials in cell imaging, we studied the photoluminescence and photoacoustic properties of three SiCNPs of approximately 30, 80, and 620 nm. All these SiCNPs show photoluminescence and photoacoustic signals, and the 620 nm silicon carbide nanoparticles (SiCNP620) show the highest photoluminescence and photoacoustic intensity. SiCNP620 is biocompatible with a good cell labeling capacity. It could image mesenchymal stem cells in vitro for more than 20 days via photoluminescence even when the cells were differentiated into adipocytes and osteocytes. The same SiCNP620 could also produce photoacoustic signals and track stem cells in vivo for over 14 days.

Clinical feasibility of optical coherence micro-elastography for imaging tumor margins in breast-conserving surgery.

It has been demonstrated that optical coherence micro-elastography (OCME) provides additional contrast of tumor compared to optical coherence tomography (OCT) alone. Previous studies, however, have predominantly been performed on mastectomy specimens. Such specimens typically differ substantially in composition and geometry from the more clinically relevant wide-local excision (WLE) specimens excised during breast-conserving surgery. As a result, it remains unclear if the mechanical contrast observed is maintained in WLE specimens. In this manuscript, we begin to address this issue by performing a feasibility study of OCME on 17 freshly excised, intact WLE specimens. In addition, we present two developments required to sustain the progression of OCME towards intraoperative deployment. First, to enable the rapid visualization of en face images required for intraoperative assessment, we describe an automated segmentation algorithm to fuse en face micro-elastograms with OCT images to provide dual contrast images. Secondly, to validate contrast in micro-elastograms, we present a method that enables co-registration of en face images with histology of WLE specimens, sectioned in the orthogonal plane, without any modification to the standard clinical workflow. We present a summary of the observations across the 17 specimens imaged in addition to representative micro-elastograms and OCT images demonstrating contrast in a number of tumor margins, including those involved by invasive ductal carcinoma, mucinous carcinoma, and solid-papillary carcinoma. The results presented here demonstrate the potential of OCME for imaging tumor margins.

Performances of a Pristine Graphene–Microbubble Hybrid Construct as Dual Imaging Contrast Agent and Assessment of Its Biodistribution by Photoacoustic Imaging

AbstractCoupling near‐infrared (NIR) nanoscale absorbing materials with microbubbles (MBs) can generate a multifunctional dual imaging contrast agent. A new approach is presented for a hybrid photoacoustic/ultrasound contrast enhancer where pristine graphene is stably tethered to poly(vinyl alcohol) (PVA)‐based MBs. The main advantages of this approach are i) the preservation of optical and mechanical properties of intact graphene for an efficient photoacoustic (PA) enhancement and ii) the echogenicity and biocompatibility due to the robust anchoring of graphene to the bioinert PVA shell. PVA MBs provide ideal platforms for drug loading and ligand tethering for specific tumor targeting. One of the crucial goals toward this direction is optimizing this system in terms of balance between favorable acoustic/photoacoustic properties, immune shielding, and cytotoxicity. Such a combination strongly depends on the bridging moieties between graphene and the microbubble surface and can be easily tuned by PEGylation. The optimized graphene PVA MBs as contrast agent provide an efficient enhancement in vivo both in ultrasound and photoacoustic modes. The spectrally separable absorbance profile allows to a first demonstration of performing real‐time in vivo multiplexed photoacoustic imaging of graphene PVA MBs, and assessment of their full body biodistribution using a Vevo LAZR‐X photoacoustic imaging system.

Tumor-penetrating Peptide Conjugated and Doxorubicin Loaded T1-T2 Dual Mode MRI Contrast Agents Nanoparticles for Tumor Theranostics.

The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs.Methods: In this study, a tumor-penetrating peptide RGERPPR (RGE) modified, Gd-DTPA conjugated, and doxorubicin (DOX) loaded Fe3O4@SiO2@mSiO2 nanoparticle drug delivery system (Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs) was prepared for tumor theranostics.Results: The Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs showed a z-average hydrodynamic diameter of about 90 nm, and a pH-sensitive DOX release profile. The 3 T MRI results confirmed the relaxivity of the NPs (r1 = 6.13 mM-1S-1, r2 = 36.89 mM-1S-1). The in vitro cellular uptake and cytotoxicity assays on U87MG cells confirmed that the conjugation of RGERPPR played a significant role in increasing the cellular uptake and cytotoxicity of the NPs. The near-infrared fluorescence in vivo imaging results showed that the NPs could be significantly accumulated in the U87MG tumor tissue, which should result from the mediation of the tumor-penetrating peptide RGERPPR. The MRI results showed that the NPs offered a T1-T2 dual mode contrast imaging effect which would lead to a more precise diagnosis. Compared with unmodified NPs, the RGE-modified NPs showed significantly enhanced MR imaging signal in tumor tissue and antitumor effect, which should also be attributed to the tumor penetrating ability of RGERPPR peptide. Furthermore, the Hematoxylin and Eosin (H&E) staining and TUNEL assay proved that the NPs produced obvious cell apoptosis in tumor tissue.Conclusions: These results indicated that Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs are an effective targeted delivery system for tumor theranostics, and should have a potential value in the personalized treatment of tumor.

Multicolor spectral photon-counting computed tomography: in vivo dual contrast imaging with a high count rate scanner

A new prototype spectral photon-counting computed tomography (SPCCT) based on a modified clinical CT system has been developed. SPCCT analysis of the energy composition of the transmitted x-ray spectrum potentially allows simultaneous dual contrast agent imaging, however, this has not yet been demonstrated with such a system. We investigated the feasibility of using this system to distinguish gold nanoparticles (AuNP) and an iodinated contrast agent. The contrast agents and calcium phosphate were imaged in phantoms. Conventional CT, gold K-edge, iodine and water images were produced and demonstrated accurate discrimination and quantification of gold and iodine concentrations in a phantom containing mixtures of the contrast agents. In vivo experiments were performed using New Zealand White rabbits at several times points after injections of AuNP and iodinated contrast agents. We found that the contrast material maps clearly differentiated the distributions of gold and iodine in the tissues allowing quantification of the contrast agents’ concentrations, which matched their expected pharmacokinetics. Furthermore, rapid, repetitive scanning was done, which allowed measurement of contrast agent kinetics with high temporal resolution. In conclusion, a clinical scale, high count rate SPCCT system is able to discriminate gold and iodine contrast media in different organs in vivo.

Compressed sensing based simultaneous black- and gray-blood carotid vessel wall MR imaging

ObjectiveIn this study, we sought to demonstrate the blood suppression performance, image quality and morphological measurements for compressed sensing (CS) based simultaneous 3D black- and gray-blood imaging sequence (CS-siBLAG) in carotid vessel wall MR imaging. Materials and methodsSeven healthy volunteers and five patients were recruited. Healthy subjects underwent five CS-siBLAG scans with 1, 2, 3, 4 and 5-fold accelerations. Signal-to-tissue ratio (STR) and contrast-to-tissue ratio (CTR) were computed as the measures of flowing signal suppression performance and the image quality for black-blood imaging of the technique. Vessel lumen area (LA) and wall area (WA) were compared between fully sampled acquisition and each accelerated acquisition. Patients underwent three CS-siBLAG scans with 1, 3 and 5-fold accelerations as well as a 3D time of flight (3D TOF) scan. Two radiologists reviewed the under-sampled black- and gray-blood image quality. ResultsSTR and CTR values obtained with 2 to 5-fold accelerations were not significantly different from those with full acquisition. LA and WA measured at 2×, 3×, 4× and 5× were all highly correlated to the corresponding values at 1×. For patients imaging, two radiologists both found that the dual-contrast images at 3× acceleration exhibited comparable image quality to that of the fully sampled acquisition, and that the images at 5× exhibited slightly blurred vessel wall and outer vessel wall boundaries. ConclusionBy combining the CS under-sampling pattern and reconstruction, pseudo-centric phase encoding order and dual blood contrast sequences, this technique provides spatially registered black- and gray-blood images and excellent visualization for vessel wall imaging and gray-blood imaging in a short scan time.

Super paramagnetic iron oxide and gadolinium (FeGdO3) nanopowder synthesized by hydrolytic approach passes high level of biocompatibility and MRI-based dual contrast property for competent molecular imaging and therapeutic interventions

The synthesis of monodispersable FeGdO3 nanopowder with well-defined architectural framework was carried out by using metal chloride as a single source molecular precursor by modifying reaction conditions to obtain an ultra-pure surface area for better understanding the chemistry involved in micro to nanoscale. By controlling the reaction parameters at the molecular level helps to synthesize a technology oriented nanomaterials with high crystalline particle size and shape with required surface morphologies at the nanoscale. The FeGdO3 nanomaterial was characterized by XRD, SEM, TEM, thermal analysis and FT-IR. The x-ray diffraction patterns indicate the formation of square planar crystallite size of 41.65 nm after annealing. The integral properties of nanomaterial depend upon the synthetic approach through self-assembly which helps in the formation of primary nuclei from metal chloride as smart molecular precursor. This opens a new exciting vista for a better understanding of the reaction conditions and growth mechanisms. We used two cell types; human mesenchymal stem cells (MSCs) derived from umbilical cord blood and human neuronal cells to evaluate the toxicity and dual contrast properties of FeGdO3 nanoparticles further their application in high contrast imaging and stem cell labeling and tracking. We found that various concentrations of FeGdO3 nanoparticles do not influence the cellular mechanisms involved in cell survival and proliferation which proves high biocompatibility nature of FeGdO3 nanoparticles with cells. Enhanced signal intensity during low-field MRI (1.5T) with iron oxide and gadolinium provides its further clinical implications as dual contrast imaging agent with more advancements.

Flow artifact removal in carotid wall imaging based on black and gray-blood dual-contrast images subtraction

To develop and validate a dual-contrast image subtraction (DCIS) strategy for eliminating the flow artifacts in black-blood carotid MRI. Twelve patients with carotid stenosis and eight healthy volunteers were imaged using the black and gray-blood dual-contrast imaging based on the relaxation-enhanced compressed sensing three-dimensional motion-sensitizing driven equilibrium prepared rapid-gradient-echo (RECS-3D MERGE) sequence. Subtraction of black-blood images (BBIs) and gray-blood images (GBIs), together with a preweighting procedure, was performed to eliminate the residual blood signal in BBIs. A wavelet denoising procedure was applied to offset the noise amplification. In addition to the lumen signal-to-noise ratio (SNR) and wall-lumen contrast-to-noise ratio (CNR), the signal variance ratio (SVR) and contrast variance ratio (CVR) were also used to evaluate the blood suppression efficiency. By choosing the weighting factor of one, the lumen SNR of DCIS images was approximately 1% of that of the original BBIs, and the CNR showed a 91.4% improvement as compared with the BBIs. The median of the lumen SVR decreased to zero, and the CVR increased to 123% of that of the BBIs. DCIS is demonstrated to be an effective strategy for sufficiently removing the residual flow signal from black-blood carotid MRI. Magn Reson Med 77:1612-1618, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

In vivo magnetic resonance and fluorescence dual imaging of tumor sites by using dye-doped silica-coated iron oxide nanoparticles

The difficulty in delineating tumor is a major obstacle for better outcomes in cancer treatment of patients. The use of single-imaging modality is often limited by inadequate sensitivity and resolution. Here, we present the synthesis and the use of monodisperse iron oxide nanoparticles coated with fluorescent silica nano-shells for fluorescence and magnetic resonance dual imaging of tumor. The as-synthesized core–shell nanoparticles were designed to improve the accuracy of diagnosis via simultaneous tumor imaging with dual imaging modalities by a single injection of contrast agent. The iron oxide nanocrystals (~11 nm) were coated with Rhodamine B isothiocyanate-doped silica shells via reverse microemulsion method. Then, the core–shell nanoparticles (~54 nm) were analyzed to confirm their size distribution by transmission electron microscopy and dynamic laser scattering. Photoluminescence spectroscopy was used to characterize the fluorescent property of the dye-doped silica shell-coated nanoparticles. The cellular compatibility of the as-prepared nanoparticles was confirmed by a trypan blue dye exclusion assay and the potential as a dual-imaging contrast agent was verified by in vivo fluorescence and magnetic resonance imaging. The experimental results show that the uniform-sized core–shell nanoparticles are highly water dispersible and the cellular toxicity of the nanoparticles is negligible. In vivo fluorescence imaging demonstrates the capability of the developed nanoparticles to selectively target tumors by the enhanced permeability and retention effects and ex vivo tissue analysis was corroborated this. Through in vitro phantom test, the core/shell nanoparticles showed a T2 relaxation time comparable to Feridex® with smaller size, indicating that the as-made nanoparticles are suitable for imaging tumor. This new dual-modality-nanoparticle approach has promised for enabling more accurate tumor imaging.

Evaluation of the Accuracy of Liver Lesion DCEUS Quantification With Respiratory Gating.

Confidence in the accuracy of dynamic contrast enhanced ultrasound (DCEUS) quantification parameters is imperative for the correct diagnosis of liver lesion perfusion characteristics. An important source of uncertainty in liver DCEUS acquisitions is artifacts introduced by respiratory motion. The objective of this study is to construct a respiratory motion simulation model (RMSM) of dual contrast imaging mode acquisitions of liver lesions in order to evaluate an algorithm for automatic respiratory gating (ARG). The respiratory kinetics as well as the perfusion models of the liver lesion and parenchyma used by the RMSM were solely derived from clinical data. The quality of fit (of the DCEUS data onto the bolus kinetics model) depends on the respiration amplitude. Similar trends in terms of quality of fit as a function of respiration amplitude were observed from RMSM and clinical data. The errors introduced on the DCEUS quantification under the influence of respiration were evaluated. The RMSM revealed that the error in the liver lesion DCEUS quantification parameters significantly decreased (p < 0.001) from a maximum of 32.3% to 6.2% when ARG was used. The use of RMSM clearly demonstrates the capability of the ARG algorithm in significantly reducing errors introduced from both in-plane and out-of-plane respiratory motion.

Copper oxide nanoparticles as contrast agents for MRI and ultrasound dual-modality imaging

Multimodal medical imaging is gaining increased popularity in the clinic. This stems from the fact that data acquired from different physical phenomena may provide complementary information resulting in a more comprehensive picture of the pathological state. In this context, nano-sized contrast agents may augment the potential sensitivity of each imaging modality and allow targeted visualization of physiological points of interest (e.g. tumours). In this study, 7 nm copper oxide nanoparticles (CuO NPs) were synthesized and characterized. Then, in vitro and phantom specimens containing CuO NPs ranging from 2.4 to 320 μg · mL−1 were scanned, using both 9.4 T MRI and through-transmission ultrasonic imaging. The results show that the CuO NPs induce shortening of the magnetic T1 relaxation time on the one hand, and increase the speed of sound and ultrasonic attenuation coefficient on the other. Moreover, these visible changes are NP concentration-dependent. The change in the physical properties resulted in a substantial increase in the contrast-to-noise ratio (3.4–6.8 in ultrasound and 1.2–19.3 in MRI). In conclusion, CuO NPs are excellent candidates for MRI-ultrasound dual imaging contrast agents. They offer radiation-free high spatial resolution scans by MRI, and cost-effective high temporal resolution scans by ultrasound.

Coexisting and mixing phenomena of thermoacoustic and magnetoacoustic waves in water.

Concurrent generation and mixing phenomenon of thermoacoustic (TA) and magnetoacoustic (MA) waves in water are predicted and observed. A theory unifying TA and MA is further put forward to analyze it. By scaling down the radio frequency in thermoacoustics to the low mega Hertz range and by incorporating appropriately a static magnetic field, TA and MA waves are simultaneously generated in the conductive matter. The two waves propagate concurrently in water and produce dynamic acoustic radiation force due to water absorption. Such dynamic radiation force vibrates the absorbing water and consequently yields acoustic emissions at the inter-modulation frequencies of TA and MA waves, creating mixing effect similar to that of vibro-acoustography. The mixing effect can be potentially utilized to mimic vibro-acoustography imaging without firing external ultrasound towards intrinsic dual-contrast (elasticity and conductivity) imaging.

Quantum dots incorporated magnetic nanoparticles for imaging colon carcinoma cells

BackgroundEngineered multifunctional nanoparticles (NPs) have made a tremendous impact on the biomedical sciences, with advances in imaging, sensing and bioseparation. In particular, the combination of optical and magnetic responses through a single particle system allows us to serve as novel multimodal molecular imaging contrast agents in clinical settings. Despite of essential medical imaging modalities and of significant clinical application, only few nanocomposites have been developed with dual imaging contrast. A new method for preparing quantum dots (QDs) incorporated magnetic nanoparticles (MNPs) based on layer-by-layer (LbL) self-assembly techniques have developed and used for cancer cells imaging.MethodsHere, citrate - capped negatively charged Fe3O4 NPs were prepared and coated with positively - charged hexadecyltrimethyl ammonium bromide (CTAB). Then, thiol - capped negatively charged CdTe QDs were electrostatically bound with CTAB. Morphological, optical and magnetic properties of the fluorescent magnetic nanoparticles (FMNPs) were characterized. Prepared FMNPs were additionally conjugated with hCC49 antibodies fragment antigen binding (Fab) having binding affinity to sialylated sugar chain of TAG-72 region of LS174T cancer cells, which was prepared silkworm expression system, and then were used for imaging colon carcinoma cells.ResultsThe prepared nanocomposites were magnetically responsive and fluorescent, simultaneously that are useful for efficient cellular imaging, optical sensing and magnetic separation. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed that the particle size is around 50 nm in diameter with inner magnetic core and outer CdTe QDs core-shell structure. Cytotoxicity test of prepared FMNPs indicates high viability in Vero cells. NPs conjugated with anti cancer antibodies were successfully labeled on colon carcinoma cells (LS174) in vitro and showed significant specificity to target cells.ConclusionThe present report demonstrates a simple synthesis of CdTe QDs-Fe3O4 NPs. The surface of the prepared FMNPs was enabled simple conjugation to monoclonal antibodies by electrostatic interaction. This property further extended their in vitro applications as cellular imaging contrast agents. Such labeling of cells with new fluorescent-magneto nanoprobes for living detection is of interest to various biomedical applications and has demonstrated the potential for future medical use.

Zirconia-doped nanoparticles: organic coating, polymeric entrapment and application as dual-imaging agents.

Zirconia nanoparticles doped with Eu3+, Tb3+ and Gd3+ ions have been synthesized following the benzyl alcohol route. The nanoparticles were coated with N-hydroxydodecanamide and encapsulated in PLGA-b-PEG-COOH nanomicelles. The magnetic and fluorescent properties of these hybrid nanocarriers were investigated, proving them to be potential dual-imaging contrast agents.

Photoacoustic emission from fluorescent nanodiamonds enhanced with gold nanoparticles

Fluorescent nanodiamonds (FNDs) have drawn much attention in recent years for biomedical imaging applications due to their desired physical properties including excellent photostability, high biocompatibility, extended far-red fluorescence emission, and ease of surface functionalization. Here we explore a new feature of FNDs, i.e. their photoacoustic emission capability, which may lead to potential applications of using FNDs as a dual imaging contrast agent for combined fluorescence and photoacoustic imaging modalities. We observed significant enhancement of photoacoustic emission from FNDs when they were conjugated with gold nanoparticles (GNPs).

Exploring the structure–property relationships of ultrasonic/MRI dual imaging magnetite/PLA microbubbles: magnetite@Cavity versus magnetite@Shell systems

Two types of magnetite/PLA composite microbubbles with different magnetite loading sites (magnetite nanoparticles [MNPs] were loaded in shell or core part), named as Fe3O4@Shell and Fe3O4@Cavity microbubbles, were respectively fabricated by an improved W1/O/W2 double emulsification approach and by an interfacial coprecipitation joint double emulsification approach. The preparation parameters were crucial factors for controlling the morphologies and structures of the microbubbles. To clarify the relationship between their structural characteristics and their properties, the T 2-weighted magnetic resonance imaging (MRI) capabilities as well as the sound attenuation behavior of the microbubbles were investigated. The results demonstrate that the encapsulation of MNPs in either the inner cavity or the shell provides improved sound attenuation, the two types of microbubbles provide comparable sound attenuation enhancement properties, whereas Fe3O4@Shell microbubbles exhibit better T 2-weighted MRI capabilities. The T 2 relaxation time decreased from 219.5 to 62.1 ms for the Fe3O4@Cavity microbubbles and from 163.8 to 45.7 ms for the Fe3O4@Shell microbubbles, as the iron concentration increased from 0.05 to 1 mM. In addition, both types of microbubbles exhibit no cytotoxicity to either NRK or BRL-3A metabolic cell cultures. These results suggest that these magnetite-containing microbubbles have great potential as ultrasonic/MR dual contrast imaging agents.

Amphiphilic hyaluronic acid-based nanoparticles for tumor-specific optical/MR dual imaging

The amphiphilic hyaluronic acid–5β-cholanic acid (HA–CA) conjugates were synthesized to fabricate near-infrared fluorescence (NIRF) dye conjugated and water-dispersible SPION-encapsulated hyaluronic acid nanoparticles (HNPs) for a tumor-targeted optical and magnetic resonance (MR) dual imaging contrast agent. Notably, HNPs were preferentially accumulated in the tumor region, implying that the hydrophilic HA shells of nanoparticles allow prolonged circulation and excellent active targeting of the SPION encapsulated nanoparticles in tumor-bearing mice.

In Vitro and in Vivo Studies of FePt Nanoparticles for Dual Modal CT/MRI Molecular Imaging

The water-solvable FePt nanoparticles of 3, 6, and 12 nm in diameter (3 nm-, 6 nm-, and 12 nm-FePt) were synthesized and applied as a dual modality contrast agent for CT/MRI molecular imaging. These nanoparticles present excellent biocompatibility and hemocompatibility in all test concentrations for the imaging contrast. The biodistribution analysis revealed the highest serum concentration and circulation half-life for 12 nm-FePt, followed by 6 nm-FePt then 3 nm-FePt. Thus, the 3 nm-FePt showed higher brain concentrations. Anti-Her2 antibody conjugated FePt nanoparticles demonstrated molecular expression dependent CT/MRI dual imaging contrast effect in MBT2 cell line and its Her2/neu gene knock out counterpart. Selective contrast enhancement of Her2/neu overexpression cancer lesions in both CT and MRI was found in tumor bearing animal after tail vein injection of the nanoparticles. The 12 nm-FePt outperformed 3 nm-FePt in both imaging modalities. These results indicate the potential of FePt nanoparticles to serve as novel multimodal molecular imaging contrast agents in clinical settings.

Motion artifact reduction technique for dual-contrast FSE imaging

There is considerable similarity between proton density-weighted (PDw) and T2-weighted (T2w) images acquired by dual-contrast fast spin-echo (FSE) sequences. The similarity manifests itself in image space as consistency between the phases of PDw and T2w images and in k-space as correspondence between PDw and T2w k-space data. A method for motion artifact reduction for dual-contrast FSE imaging has been developed. The method uses projection onto convex sets (POCS) formalism and is based on image space phase consistency and the k-space similarity between PDw and T2w images. When coupled with a modified dual-contrast FSE phase encoding scheme the method can yield considerable artifact reduction, as long as less than half of the acquired data is corrupted by motion. The feasibility and efficiency of the developed method were demonstrated using phantom and human MRI data.

Dual contrast GRASE (gradient-spin echo) imaging using mixed bandwidth.

Equal time spacing of RF pulses in the CPMG sequence imposes a constraint of equal signal read periods in spin-echo train imaging. GRASE imaging differs by using multiple read gradients in each pi-pi time interval, which are not constrained to be equal in number or duration. This additional degree of freedom is developed in dual contrast imaging. Closely spaced read periods are used for the PDW image to reduce T2 decay effects, while fewer low-bandwidth read periods in each of several pi-pi intervals are used to raise the signal-to-noise ratio and avoid signal averaging in the T2-weighted image.