Microgel-Based Thermosensitive MRI Contrast Agent

Monitoring subtle temperature changes noninvasively remains a challenge for magnetic resonance imaging (MRI). A temperature-sensitive contrast agent based on thermosensitive microgel is proposed and synthesized using a manganese tetra­(3-vinylphenyl) porphyrin core reacting with <i>N</i>-isopropylacrylamide (NIPAM) or <i>N</i>-isopropylmethacrylamide (NIPMAM) monomers and <i>N</i>,<i>N</i>′-methylenebis­(acrylamide) (MBA) cross-linkers. The volume of the NIPAM-incorporated microgel (<b>M-1</b>) decreased sharply around its lower critical solution temperature (LCST, 29–33 °C), whereas the volume of the NIPMAM-incorporated microgel (<b>M-2</b>) decreased gradually. MR longitudinal relaxivity (<i>r</i>₁) enhancement (44%) was obtained for <b>M-1</b>, while the corresponding change for <b>M-2</b> was much smaller. <b>M-1</b> was further optimized in synthesis without an MBA cross-linker to obtain <b>M-3</b> which showed a 67% increase in <i>r</i>₁ around its LCST. Our results suggested that the longitudinal relaxivity is strongly modulated by microgel volume change around the LCST, leading to a significant increase in <i>r</i>₁. This novel thermally sensitive microgel could potentially be applied to monitor small temperature changes using MRI methods

Using Magnetic Resonance Imaging to Study Enzymatic Hydrogelation

Herein, we report, for the first time, the use of MRI methods to study enzymatic hydrogelation. Supramolecular hydrogels have been exploited as biomaterials for many applications. However, behaviors of the water molecules encapsulated in hydrogels have not been fully understood. In this work, we designed a precursor <b>1</b> which could self-assemble into nanofibers and form hydrogel <b>I</b> (gel <b>I</b>) upon the catalysis of phosphatase. The differences of mechanic property, pore size, water diffusion rate, and magnetic resonance relaxation times <i>T</i>₁ and <i>T</i>₂ of gel <b>I</b> containing different concentrations of <b>1</b> were systematically studied and analyzed. <i>T</i>₁, <i>T</i>₂, and diffusion-weighted ¹H MR images from gel <b>I</b> phantoms were obtained at 9.4 T. Analyses of the MRI data uncovered how the density of the nanofiber networks affects the relaxation behaviors of the water protons encapsulated in such hydrogels. Rheological analyses and cryo-TEM observations showed increased gel elasticities with increased concentrations of <b>1</b> while the pore sizes of gel <b>I</b> decreased. This also resulted in an increase in the proton relaxation rate (i.e., shortened <i>T</i>₁, <i>T</i>₂, and apparent diffusion coefficient (ADC)) for the water encapsulated in the hydrogel. With MRI, our study provides a new in vitro method to potentially mimic and study in vivo diseases that involve fibrous aggregates

Alkaline Phosphatase-Instructed Self-Assembly of Gadolinium Nanofibers for Enhanced T₂‑Weighted Magnetic Resonance Imaging of Tumor

Alkaline phosphatase (ALP) is an important enzyme but using ALP-instructed self-assembly of gadolinium nanofibers for enhanced T₂-weighted magnetic resonance imaging (MRI) of tumor has not been reported. In this work, we rationally designed a hydrogelator Nap-FFFYp-EDA-DOTA­(Gd) (<b>1P</b>) which, under the catalysis of ALP, was able to self-assemble into gadolinium nanofibers to form hydrogel Gel <b>I</b> for enhanced T₂-weighted MR imaging of ALP activity <i>in vitro</i> and in tumor. T₂ phantom MR imaging indicated that the transverse relaxivity (<i>r</i>₂) value of Gel <b>I</b> was 33.9% higher than that of <b>1P</b> and both of them were 1 order of magnitude higher than that of Gd-DTPA. <i>In vivo</i> T₂-weighted MR imaging showed that, at 9.4 T, ALP-overexpressing HeLa tumors of <b>1P</b>-injected mice showed obviously enhanced T₂ contrast. We anticipate that, by replacing ALP with other enzymes, our approach could be applied for MR diagnosis of other diseases in the future

Effects of the Magnetic Resonance Imaging Contrast Agent Gd-DTPA on Plant Growth and Root Imaging in Rice

<div><p>Although paramagnetic contrast agents have a wide range of applications in medical studies involving magnetic resonance imaging (MRI), these agents are seldom used to enhance MRI images of plant root systems. To extend the application of MRI contrast agents to plant research and to develop related techniques to study root systems, we examined the applicability of the MRI contrast agent Gd-DTPA to the imaging of rice roots. Specifically, we examined the biological effects of various concentrations of Gd-DTPA on rice growth and MRI images. Analysis of electrical conductivity and plant height demonstrated that 5 mmol Gd-DTPA had little impact on rice in the short-term. The results of signal intensity and spin-lattice relaxation time (T1) analysis suggested that 5 mmol Gd-DTPA was the appropriate concentration for enhancing MRI signals. In addition, examination of the long-term effects of Gd-DTPA on plant height showed that levels of this compound up to 5 mmol had little impact on rice growth and (to some extent) increased the biomass of rice.</p></div

Spin-lattice relaxation times (T1) of root samples that treated with different concentrations of Gd-DTPA at different time points.

<p>Spin-lattice relaxation times (T1) of root samples that treated with different concentrations of Gd-DTPA at different time points.</p

Treatment with 5-DTPA in different growth media.

<p>The plant height was altered at different growth periods. The growth media included sandy soil and paddy soil. A1 and B1 represent sandy soil and paddy soil treated with Gd-DTPA, and A2 and B2 represent untreated sandy soil and paddy soil, respectively.</p

Comparison of plant heights after short-term treatment with different concentrations of Gd-DTPA solution.

<p>Comparison of plant heights after short-term treatment with different concentrations of Gd-DTPA solution.</p

Differences in electrical conductivity (EC) in root samples of rice plants treated with different levels of Gd-DTPA for different periods of time.

<p>Differences in electrical conductivity (EC) in root samples of rice plants treated with different levels of Gd-DTPA for different periods of time.</p

MRI images (transverse slices) of rice root samples immersed in different concentrations of Gd-DTPA for 3 h (A), 6 h (B), 9 h (C) and 12 h (D).

<p>In each image, numbers 1 to 5 represent 0-DTPA, respectively.</p

Concentrations of Gd in rice roots treated with 5-DTPA at different time points.

<p>Concentrations of Gd in rice roots treated with 5-DTPA at different time points.</p