Contrast Agents In Water Research Articles

Development of a contrast-enhanced micro computed tomography protocol for the oval squid (Sepioteuthis lessoniana) brain.

Coleoid cephalopods (squid, cuttlefish, and octopus) have a well-developed and complex central nervous system. Its absolute size is the largest among invertebrates, and the brain-to-body mass ratio is larger than that of fish and reptiles and equivalent to that of birds and mammals. Although a number of histological studies have been conducted on the brains of cephalopods, most of them used a light microscope or an electron microscope, which show the microstructure of the brain, but often cannot image the whole brain instantaneously. Of late, micro computed tomography (CT) has gained popularity for imaging animal brains because it allows for noninvasive three-dimensional (3D) reconstruction and preprocessing that are not cumbersome. To perform micro-CT on cephalopod brains, we first tested conditions suitable for preprocessing, paying special attention to staining conditions that would provide high contrast images. Four agents, iodine in 99.5% ethanol, iodine potassium iodide in water (IKI), phosphotungstic acid in 70% ethanol, and nonionic iodinated contrast agent in water, were tested at various concentrations and durations on brain of juvenile oval squid. To evaluate the quality of staining, we calculated the contrast ratio of the two-dimensional (2D) images and compared 3D segmentation of the best and worst 2D images. We concluded that 3% IKI staining for 7 days was the best combination to enhance the images contrast of the oval squid brain, in which each brain lobe was clearly detected and 3D segmentation of the whole brain was possible. The wider applicability of this preprocessing method for micro-CT of the brains of other cephalopods is discussed.

Insights into Preformed Human Serum Albumin Corona on Iron Oxide Nanoparticles: Structure, Effect of Particle Size, Impact on MRI Efficiency, and Metabolization.

In the past decade, profuse research efforts explored the uses of iron oxide particles in nanomedicine. To a great extent, the efficiency and fate of those magnetic nanoparticles depend on how their surfaces interface with the proteins in a physiological environment. It is well reported how an ungoverned protein corona can be detrimental to cellular uptake and targeting efficiency and how it can modify the nanoparticles biodistribution. Novel strategies are emerging to achieve enhanced and more reproducible performances of engineered nanoparticles with a custom-built protein corona. Here we report on a generalized protocol to preform a monolayer of human serum albumin (HSA) on superparamagnetic iron oxide nanoparticles (SPIONs) of different sizes. The resulting molecular structures are described by molecular dynamics simulations of the hybrid nanoconjugates. The simulations outcomes regarding the number of proteins in the corona and their monolayer arrangement on the particle surface are in agreement with the results obtained from dynamic light scattering and electronic microscopy analysis. Using tryptophan fluorescence quenching, we revealed the existence of a strong interaction between the SPIONs and the HSA which endorses the robustness of the protein-nanoparticle conjugates in this system. Moreover, we evaluated the effect of the HSA corona on the SPIONs efficiency as magnetic resonance imaging (MRI) contrast agents in water, human serum, and saline media. The protein corona did not affect the efficiency of the SPIONs as T2 contrast agents but reduce their T1 efficiency. In addition, we observed a greater stability for HSA-SPIONs nanoconjugates in saline and in acid media, preventing nanoparticle dissolution in extreme gastric conditions.

Mesoporous 3D carbon framework encapsulated manganese oxide nanoparticles as biocompatible T1 MR imaging probe

Magnetic resonance imaging (MRI) is one of the widely used medical diagnostic techniques due to its non-invasive nature, higher resolution and efficiency in soft tissue imaging. MRI contrast agents with high relaxivity and biocompatibility are of great importance for successful clinical diagnosis. Manganese based substances have emerged as new class of MR imaging agents due to their impressive contrast ability. In this study, we have reported development of manganese oxide (Mn3O4) nanoparticles encapsulated in mesoporous 3D carbon framework (CF) functionalized by polyethylene glycol (PEG) as T1 based MRI contrast agent. PEG functionalization endowed solubility and stability of the contrast agent in water which are highly essential traits of MRI contrast agents. The carbon framework provided excellent biocompatibility by ruling out possibility of metal ion exposure (offering suitability for in vivo application) and simultaneously enabled water exchange through its pores which led to T1 contrast improvement. The as-prepared PEG modified manganese oxide@CF nanosystem exhibited paramagnetic behaviour at room temperature, enhanced water proton relaxation and facilitated contrast of T1-weighted MR images.

Carboxymethyl cellulose (CMC)-loaded Co-Cu doped manganese ferrite nanorods as a new dual-modal simultaneous contrast agent for magnetic resonance imaging and nanocarrier for drug delivery system

We synthesized Co0.25Cu0.25Mn0.5Fe2O4@CMC (CCMFe2O4@CMC) nanorods as a new dual-modal simultaneous for magnetic resonance imaging contrast agent and nanocarrier for drug delivery system. Impact of CCMFe2O4@CMC nanorods were investigated on the longitudinal (T1), transverse (T2) and transverse (T2∗) relaxation times for in vitro MRI contrast agent in water and also for drug delivery system, l-dopa was coated on CCMFe2O4@CMC nanorods and then in vitro drug release test was carried out at three PHs values and different temperatures. In vitro MR imaging demonstrated that r2 value of CCMFe2O4@CMC nanorods is 138.33mM−1s−1, CCMFe2O4@CMC is useful as T2 contrast agent relative to other T2 contrast agants. In vitro drug release test shows the amount of released l-dopa from CCMFe2O4@CMC nanorods at medium with pH = 1.2 is more than pH = 5.3 and 7.4.

Concentration-independent MRI of pH with a dendrimer-based pH-responsive nanoprobe.

The measurement of extracellular pH (pHe ) has significant clinical value for pathological diagnoses and for monitoring the effects of pH-altering therapies. One of the major problems of measuring pHe with a relaxation-based MRI contrast agent is that the longitudinal relaxivity depends on both pH and the concentration of the agent, requiring the use of a second pH-unresponsive agent to measure the concentration. Here we tested the feasibility of measuring pH with a relaxation-based dendritic MRI contrast agent in a concentration-independent manner at clinically relevant field strengths. The transverse and longitudinal relaxation times in solutions of the contrast agent (GdDOTA-4AmP)44 -G5, a G5-PAMAM dendrimer-based MRI contrast agent in water, were measured at 3 T and 7 T magnetic field strengths as a function of pH. At 3 T, longitudinal relaxivity (r1 ) increased from 7.91 to 9.65 mM(-1) s(-1) (on a per Gd(3+) basis) on changing pH from 8.84 to 6.35. At 7 T, r1 relaxivity showed pH response, albeit at lower mean values; transverse relaxivity (r2 ) remained independent of pH and magnetic field strengths. The longitudinal relaxivity of (GdDOTA-4AmP)44 -G5 exhibited a strong and reversible pH dependence. The ratio of relaxation rates R2 /R1 also showed a linear relationship in a pH-responsive manner, and this pH response was independent of the absolute concentration of (GdDOTA-4AmP)44 -G5 agent. Importantly, the nanoprobe (GdDOTA-4AmP)44 -G5 shows pH response in the range commonly found in the microenvironment of solid tumors.

Ultrasound-modulated fluorescence based on fluorescent microbubbles.

Ultrasound-modulated fluorescence (UMF) imaging has been proposed to provide fluorescent contrast while maintaining ultrasound resolution in an optical-scattering medium (such as biological tissue). The major challenge is to extract the weakly modulated fluorescent signal from a bright and unmodulated background. UMF was experimentally demonstrated based on fluorophore-labeled microbubble contrast agents. These contrast agents were produced by conjugating N-hydroxysuccinimide (NHS)-ester-attached fluorophores on the surface of amine-functionalized microbubbles. The fluorophore surface concentration was controlled so that a significant self-quenching effect occurred when no ultrasound was applied. The intensity of the fluorescent emission was modulated when microbubbles were oscillated by ultrasound pulses, presented as UMF signal. Our results demonstrated that the UMF signals were highly dependent on the microbubbles' oscillation amplitude and the initial surface fluorophore-quenching status. A maximum of ∼42% UMF modulation depth was achieved with a single microbubble under an ultrasound peak-to-peak pressure of 675 kPa. Further, UMF was detected from a 500-μm tube filled with contrast agents in water and scattering media with ultrasound resolution. These results indicate that ultrasound-modulated fluorescent microbubble contrast agents can potentially be used for fluorescence-based molecular imaging with ultrasound resolution in the future.

Sub‐second proton imaging of 13C hyperpolarized contrast agents in water

Indirect proton detection of (13)C hyperpolarized contrast agents potentially enables greater sensitivity. Presented here is a study of sub-second projection imaging of hyperpolarized (13)C contrast agent addressing the obstacle posed by water suppression for indirect detection in vivo. Sodium acetate phantoms were used to develop and test water suppression and sub-second imaging with frequency-selective RF pulses using spectroscopic and imaging indirect proton detection. A 9.8 mm aqueous solution of (13)C PHIP hyperpolarized 2-hydroxyethyl-(13)C-propionate-d2,3,3 (HEP), <P> ~25% was used for demonstration of indirect proton sub-second imaging detection. Balanced 2D FSSFP (fast steady-state free precession) allowed the recording of proton images with a field of view of 64 × 64 mm(2) and spatial resolution 2 × 2 mm(2) with total acquisition time of less than 0.2 s. In thermally polarized sodium 1-(13)C-acetate, (13) C to (1)H polarization transfer efficiency of 45.1% of the theoretically predicted values was observed in imaging detection corresponding to an 11-fold overall sensitivity improvement compared with direct (13)C FSSFP imaging. (13)C to (1)H polarization transfer efficiency of 27% was observed in imaging detection, corresponding to a 3.25-fold sensitivity improvement compared with direct (13)C FSSFP imaging with hyperpolarized HEP. The range of potential applications and limitations of this sub-second and ultra-sensitive imaging approach are discussed.

Contrast Enhancement of Optical Coherence Tomography Images Using Branched Gold Nanoparticles

We propose the use of branched gold nanoparticles (B‐GNPs) as a contrast agent for optical coherence tomography (OCT) imaging. Our results show that even when the central source of our OCT (1325 nm) is too far from the maximum peak of the plasmon resonance, branched nanoparticles scatter light very efficiently at this wavelength. B‐GNPs were tested as a contrast agent in water and agarose‐TiO2 tissue phantoms; the estimated increments in contrast were 9.19 dB and 15.07 dB for branched nanoparticles in water with concentrations of 2.2 × 109 NPs/mL and 6.6 × 109 NPs/mL, respectively, while for agarose‐TiO2 tissue phantoms the estimated value was 3.17 dB. These results show the promising application of B‐GNPs as a contrast agent for tissue imaging using OCT, not only for sources at 1325 nm but also at other central wavelengths located between 800 and 1000 nm.

In Situ Detection of PHIP at 48 mT: Demonstration Using a Centrally Controlled Polarizer

Presented here is a centrally controlled, automated parahydrogen-based polarizer with in situ detection capability. A 20% polarization, corresponding to a 5,000,000-fold signal enhancement at 48 mT, is demonstrated on 2-hydroxyethyl-1-(13)C-propionate-d(2,3,3) using a double-tuned antenna and pulsed polarization transfer. In situ detection is a refinement of first-generation devices enabling fast calibration of rf pulses and B(0), quality assurance of hyperpolarized contrast agents, and stand-alone operation without the necessity of high-field MR spectrometers. These features are essential for biomedical applications of parahydrogen-based hyperpolarization and for clinical translation. We demonstrate the flexibility of the device by recording (13)C signal decay due to longitudinal relaxation of a hyperpolarized contrast agent at 48 mT corresponding to 2 MHz proton frequency. This appears to be the longest recorded T(1) (101 ± 7 s) for a (13)C hyperpolarized contrast agent in water.

Dual-high-frequency ultrasound excitation on microbubble destruction volume

Objective and motivation The goal of this work was to test experimentally that exposing air bubbles or ultrasound contrast agents in water to amplitude modulated wave allows control of inertial cavitation affected volume and hence could limit the undesirable bioeffects. Methods Focused transducer operating at the center frequency of 10 MHz and having about 65% fractional bandwidth was excited by 3 μs 8.5 and 11.5 MHz tone-bursts to produce 3 MHz envelope signal. The 3 MHz frequency was selected because it corresponds to the resonance frequency of the microbubbles used in the experiment. Another 5 MHz transducer was used as a receiver to produce B-mode image. Peak negative acoustic pressure was adjusted in the range from 0.5 to 3.5 MPa. The spectrum amplitudes obtained from the imaging of SonoVue TM contrast agent when using the envelope and a separate 3 MHz transducer were compared to determine their cross-section at the – 6 dB level. Results The conventional 3 MHz tone-burst excitation resulted in the region of interest (ROI) cross-section of 2.47 mm while amplitude modulated, dual-frequency excitation with difference frequency of 3 MHz produced cross-section equal to 1.2 mm. Conclusion These results corroborate our hypothesis that, in addition to the considerably higher penetration depth of dual-frequency excitation due to the lower attenuation at 3 MHz than that at 8.5 and 11.5 MHz, the sample volume of dual-frequency excitation is also smaller than that of linear 3-MHz method for more spatially confined destruction of microbubbles.

Noninvasive estimation of the pressure gradient across stenoses using sonographic contrast: in vitro validation.

Because velocity measurements to estimate the degree of arterial stenosis are susceptible to local and systemic factors, we aimed to investigate the feasibility of estimating the pressure gradient across a stenosis noninvasively by using sonographic contrast. Using a gravity-fed flow system, a 1:4000 dilution of a contrast agent in water was circulated through silicone tubes that had either focal or long-segment stenoses of varying severity in a water bath. We measured the cross-sectional areas of the normal and stenotic regions with B-mode sonography and the flow velocity with spectral Doppler sonography and calculated the pressure gradients across the stenoses using the empirically derived Young mathematical model and the simplified Bernoulli equation. Estimated gradients were compared with those measured manometerically. Both methods yielded estimates of pressure gradients that correlated with measured gradients (r > 0.988). In focal and long-segment stenoses, the Young model yielded gradients that agreed more closely with manometerically measured values than the Bernoulli equation (+/- 8% versus -24%-57%). Both methods were highly dependent on the ability to measure the luminal cross-sectional area. The presence of sonographic contrast in the vascular lumen highlighted the inner wall, allowing the accurate measurement of the luminal area to +/- 3.0%. The pressure gradient can be estimated across stenoses noninvasively. The Young model was more accurate than the simplified Bernoulli equation in this model using steady flow. Estimated gradients are highly dependent on the definition of the vascular lumen, a process aided by the use of sonographic contrast.