scholarly journals A nitroxides-based macromolecular MRI contrast agent with an extraordinary longitudinal relaxivity for tumor imaging via clinical T1WI SE sequence

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shiwei Guo ◽  
Xiaoming Wang ◽  
Zhiqian Li ◽  
Dayi Pan ◽  
Yan Dai ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Tumor Imaging ◽  
Cumulative Effect ◽  
Water Soluble ◽  
Mri Contrast Agent ◽  
Aqueous Environment ◽  
Potential Candidate ◽  
Tumor Site ◽  
Longitudinal Relaxivity

Abstract Background Macromoleculization of nitroxides has been an effective strategy to improve low relaxivities and poor in vivo stability, however, nitroxides-based metal-free magnetic resonance imaging (MRI) macromolecular contrast agents (mCAs) are still under-performed. These mCAs do not possess a high nitroxides content sufficient for a cumulative effect. Amphiphilic nanostructures in these mCAs are not stable enough for highly efficient protection of nitroxides and do not have adequate molecular flexibility for full contact of the paramagnetic center with the peripheral water molecules. In addition, these mCAs still raise the concerns over biocompatibility and biodegradability due to the presence of macromolecules in these mCAs. Results Herein, a water-soluble biodegradable nitroxides-based mCA (Linear pDHPMA-mPEG-Ppa-PROXYL) was prepared via covalent conjugation of a nitroxides (2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl, PROXYL) onto an enzyme-sensitive linear di-block poly[N-(1, 3-dihydroxypropyl) methacrylamide] (pDHPMA). A high content of PROXYL up to 0.111 mmol/g in Linear pDHPMA-mPEG-Ppa-PROXYL was achieved and a stable nano-sized self-assembled aggregate in an aqueous environment (ca. 23 nm) was formed. Its longitudinal relaxivity (r1 = 0.93 mM− 1 s− 1) was the highest compared to reported nitroxides-based mCAs. The blood retention time of PROXYL from the prepared mCA in vivo was up to ca. 8 h and great accumulation of the mCA was realized in the tumor site due to its passive targeting ability to tumors. Thus, Linear pDHPMA-mPEG-Ppa-PROXYL could provide a clearly detectable MRI enhancement at the tumor site of mice via the T1WI SE sequence conventionally used in clinical Gd3+-based contrast agents, although it cannot be compared with DTPA-Gd in the longitudinal relaxivity and the continuous enhancement time at the tumor site of mice. Additionally, it was demonstrated to have great biosafety, hemocompatibility and biocompatibility. Conclusions Therefore, Linear pDHPMA-mPEG-Ppa-PROXYL could be a potential candidate as a substitute of metal-based MRI CAs for clinical application. Graphic Abstract

scholarly journals Study on Establishing Reference Safe Concentrations of MRI Contrast Agents for Optimized Images: Paramagnetic Gd-DTPA-BMEA and Superparamagnetic Ferucarbotran

2021 ◽  
Vol 11 (3) ◽  
pp. 1165
Author(s):  
Wen-Tien Hsiao ◽  
Yi-Hong Chou ◽  
Jhong-Wei Tu ◽  
Ai-Yih Wang ◽  
Lu-Han Lai
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
In Vitro Experiments ◽  
Mri Contrast ◽  
In Vivo Experiments ◽  
Contrast Agent Injection

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

scholarly journals Dynamic, Simultaneous Concentration Mapping of Multiple MRI Contrast Agents with Dual Contrast - Magnetic Resonance Fingerprinting

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Christian E. Anderson ◽  
Mette Johansen ◽  
Bernadette O. Erokwu ◽  
He Hu ◽  
Yuning Gu ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Contrast Agents ◽  
Ex Vivo ◽  
Single Agent ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
Spatiotemporal Resolution ◽  
Mri Contrast ◽  
Contrast Magnetic Resonance

AbstractSynchronous assessment of multiple MRI contrast agents in a single scanning session would provide a new “multi-color” imaging capability similar to fluorescence imaging but with high spatiotemporal resolution and unlimited imaging depth. This multi-agent MRI technology would enable a whole new class of basic science and clinical MRI experiments that simultaneously explore multiple physiologic/molecular events in vivo. Unfortunately, conventional MRI acquisition techniques are only capable of detecting and quantifying one paramagnetic MRI contrast agent at a time. Herein, the Dual Contrast – Magnetic Resonance Fingerprinting (DC-MRF) methodology was extended for in vivo application and evaluated by simultaneously and dynamically mapping the intra-tumoral concentration of two MRI contrast agents (Gd-BOPTA and Dy-DOTA-azide) in a mouse glioma model. Co-registered gadolinium and dysprosium concentration maps were generated with sub-millimeter spatial resolution and acquired dynamically with just over 2-minute temporal resolution. Mean tumor Gd and Dy concentration measurements from both single agent and dual agent DC-MRF studies demonstrated significant correlations with ex vivo mass spectrometry elemental analyses. This initial in vivo study demonstrates the potential for DC-MRF to provide a useful dual-agent MRI platform.

scholarly journals Conducting Cytocompatible Scaffolds: Composite of Sodium Hyaluronate and Colloidal Particles of Conducting Polymers

2021 ◽  
Author(s):  
Thanh Huong Truong ◽  
Lenka Musilová ◽  
Věra Kašpárková ◽  
Daniela Jasenská ◽  
Petr Ponížil ◽  
...  
Keyword(s):  
Conducting Polymers ◽  
Colloidal Particles ◽  
Sodium Hyaluronate ◽  
Water Soluble ◽  
Aqueous Environment ◽  
Ethylcarbodiimide Hydrochloride ◽  
Swelling Capacity ◽  
Thawing Process ◽  
Interconnected Pores

Abstract Novel bio-inspired conductive scaffolds composed of sodium hyaluronate containing water soluble polyaniline or polypyrrole colloidal particles (concentrations 0.108, 0.054 and 0.036 % w/w) were manufactured. For this purpose, either crosslinking with N-(3-dimethylaminopropyl-N-ethylcarbodiimide hydrochloride and N-hydroxysuccinimid or a freeze-thawing process in the presence of poly(vinylalcohol) were used. The scaffolds comprised interconnected pores with prevailing porosity values of ~30 % and pore sizes enabling the accommodation of cells. Good swelling capacity (92 – 97 %) without any sign of disintegration was typical for all samples. The elasticity modulus depended on the composition of the scaffolds, with the highest value of ~50 000 Pa obtained for the sample containing the highest content of polypyrrole particles. The scaffolds did not possess cytotoxicity and allowed cell adhesion and growth on the surface. Using the in vivo-mimicking conditions in a bioreactor, cells were also able to grow into the structure of the scaffolds. The technique of scaffold preparation used here thus overcomes the limitations of conducting polymers (e.g. poor solubility in an aqueous environment, and limited miscibility with other hydrophilic polymer matrices) and moreover leads to the preparation of cytocompatible scaffolds with potentially cell-instructive properties, which may be of advantage in the healing of damaged electro-sensitive tissues.

scholarly journals Recent Experiences and Advances in Contrast-Enhanced Subharmonic Ultrasound

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
John R. Eisenbrey ◽  
Anush Sridharan ◽  
Ji-Bin Liu ◽  
Flemming Forsberg
Keyword(s):  
Contrast Agents ◽  
Tumor Imaging ◽  
Three Dimensional ◽  
Ultrasound Contrast Agents ◽  
Surrounding Tissue ◽  
Contrast Enhanced Ultrasound ◽  
Ultrasound Contrast ◽  
Contrast Enhanced ◽  
Subharmonic Response

Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imagingin vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging.

scholarly journals Influence of Molecular Mobility on Contrast Efficiency of Branched Polyethylene Glycol Contrast Agent

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Yu-I Hsu ◽  
Atsushi Mahara ◽  
Tetsuji Yamaoka
Keyword(s):  
Polyethylene Glycol ◽  
Magnetic Resonance ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Water Soluble ◽  
Mri Contrast Agent ◽  
Proton Nuclear Magnetic Resonance ◽  
Terminal Mobility ◽  
Half Height ◽  
Branched Structure

For a water-soluble polyethylene glycol (PEG) magnetic resonance imaging (MRI) contrast agent, it has been demonstrated that the contrast efficiency was increased with increased branched structure of the contrast agent. However, the cause of enhanced contrast efficiency by the branched structure has not been clarified. Hence, we investigate the cause of the contrast agent enhancement by changing the Gd introduction ratio of the eight-arm PEG from 1.97 to 4.07; furthermore, the terminal mobility of the contrast agents with different structures was evaluated using proton nuclear magnetic resonance (1H-NMR) spectroscopy. It was shown that the relaxivity and contrast luminance of the synthesized branched PEG-Gd contrast agents are larger than those of linear PEG-Gd and commercially available contrast agents. Additionally, the change in the Gd introduction ratio did not affect the contrast efficiency. The terminal mobility results measured by NMR show that the linewidth at half height became broader with an increased number of branches, implying that the mobility of branched PEG-Gd is slower than that of linear PEG-Gd. Interestingly, the linewidth at half height of different structures did not change in an organic solvent; this phenomenon appeared specifically in water. It is suggested that the stable branched structure enabled the improvement in the relaxivity and contrast luminance.

Quantum dots as contrast agents for in vivo tumor imaging: progress and issues

2010 ◽  
Vol 399 (7) ◽  
pp. 2331-2342 ◽  
Author(s):  
Anthony J. Tavares ◽  
Lori Chong ◽  
Eleonora Petryayeva ◽  
W. Russ Algar ◽  
Ulrich J. Krull
Keyword(s):  
Quantum Dots ◽  
Contrast Agents ◽  
Tumor Imaging

Nanostructured magnetic nanocomposites as MRI contrast agents

2015 ◽  
Vol 3 (11) ◽  
pp. 2241-2276 ◽  
Author(s):  
Erwin Peng ◽  
Fenghe Wang ◽  
Jun Min Xue
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Magnetic Nanoparticle ◽  
Mri Contrast Agents ◽  
Water Soluble ◽  
Mri Contrast Agent ◽  
Magnetic Nanocomposites ◽  
Functional Coating ◽  
Mri Contrast ◽  
Nanoparticle Assemblies

The development of water-soluble nanostructured magnetic nanocomposites based on hydrophobic magnetic nanoparticle assemblies using an organic functional coating for MRI contrast agent applications was discussed.

Gadolinium-based nanoscale MRI contrast agents for tumor imaging

2017 ◽  
Vol 5 (19) ◽  
pp. 3431-3461 ◽  
Author(s):  
Yi Cao ◽  
Lijun Xu ◽  
Ye Kuang ◽  
Dangsheng Xiong ◽  
Renjun Pei
Keyword(s):  
Contrast Agents ◽  
Tumor Imaging ◽  
Region Of Interest ◽  
Mri Contrast Agents ◽  
Tumor Diagnosis ◽  
Mri Contrast ◽  
Longitudinal Relaxivity

Gadolinium-based nanoscale MRI CAs have been considered as a promising nanoplatform for tumor diagnosis, due to their favorable capability of enhancing the longitudinal relaxivity (r1) of individual gadolinium ions, delivering to the region of interest a large number of gadolinium ions, and incorporating different functionalities.

scholarly journals Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

2015 ◽  
Vol 112 (21) ◽  
pp. 6607-6612 ◽  
Author(s):  
Shenghui Xue ◽  
Hua Yang ◽  
Jingjuan Qiao ◽  
Fan Pu ◽  
Jie Jiang ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agent ◽  
Therapeutic Interventions ◽  
Mri Contrast ◽  
Liver Cancers ◽  
Poor Treatment ◽  
Ratio Imaging ◽  
Metastatic Liver

With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd3+ and a 1011-fold greater selectivity for Gd3+ over Zn2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol−1⋅s−1/89.2 mmol−1⋅s−1 per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10–20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.

scholarly journals Identification of New Compounds with Anticonvulsant and Antinociceptive Properties in a Group of 3-substituted (2,5-dioxo-pyrrolidin-1-yl)(phenyl)-Acetamides

2021 ◽  
Vol 22 (23) ◽  
pp. 13092
Author(s):  
Michał Abram ◽  
Marcin Jakubiec ◽  
Anna Rapacz ◽  
Szczepan Mogilski ◽  
Gniewomir Latacz ◽  
...  
Keyword(s):  
Water Soluble ◽  
Calcium Currents ◽  
In Vitro Studies ◽  
Maximal Electroshock ◽  
Induction Effect ◽  
Potential Candidate ◽  
Seizure Models ◽  
Seizure Model

We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure models, including the maximal electroshock (MES) test, the pentylenetetrazole-induced seizure model (scPTZ), and the psychomotor 6 Hz (32 mA) seizure model in mice. Compound 14 showed the most robust anticonvulsant activity (ED50 MES = 49.6 mg/kg, ED50 6 Hz (32 mA) = 31.3 mg/kg, ED50scPTZ = 67.4 mg/kg). Notably, it was also effective in the 6 Hz (44 mA) model of drug-resistant epilepsy (ED50 = 63.2 mg/kg). Apart from favorable anticonvulsant properties, compound 14 revealed a high efficacy against pain responses in the formalin-induced tonic pain, the capsaicin-induced neurogenic pain, as well as in the oxaliplatin-induced neuropathic pain in mice. Moreover, compound 14 showed distinct anti-inflammatory activity in the model of carrageenan-induced aseptic inflammation. The mechanism of action of compound 14 is likely complex and may result from the inhibition of peripheral and central sodium and calcium currents, as well as the TRPV1 receptor antagonism as observed in the in vitro studies. This lead compound also revealed beneficial in vitro ADME-Tox properties and an in vivo pharmacokinetic profile, making it a potential candidate for future preclinical development. Interestingly, the in vitro studies also showed a favorable induction effect of compound 14 on the viability of neuroblastoma SH-SY5Y cells.

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