Properties Of Contrast Agents Research Articles

Fe2+-Dominated Relaxometric Properties of Iron Oxide Nanoparticles as MRI Contrast Agents.

Iron oxide nanoparticles (IONPs) have garnered significant interest as magnetic resonance imaging (MRI) contrast agents due to their exceptional magnetic properties and biocompatibility. Toward more precise diagnosis of diseases, the relaxometric properties of IONPs have become a key research focus. Despite extensive studies on structural factors such as size, morphology, surface modification, crystalline phase, and aggregation state, the correlation between the intrinsic structure and relaxometric behavior remains unclear, particularly for ultrasmall IONPs. To address this issue, we carefully compared IONPs with identical size, shape, and surface modification and found out strong correlations among the content of Fe2+ ions, oxygen vacancies, and the relaxometric properties. By optimizing the reaction system, ultrasmall IONPs showing outstanding relaxometric performance, with longitudinal relaxivity up to 9.0 mM-1 s-1 and transverse relaxivity up to 28.5 mM-1 s-1, were successfully obtained. These results underscore the pivotal role of Fe2+ in the relaxometric properties of IONP-based MRI contrast agents.

Fluorescence and magnetic resonance imaging of ONL-93 cells in a rat model of ischemic

ObjectivesThe current methods for detecting myelin changes in ischemic stroke are indirect and cannot accurately reflect their status. This study aimed to develop a novel fluorescent-magnetic resonance dual-modal molecular imaging probe for direct imaging of myelin. MethodsCompounds 7a and 7b were synthesized by linking the MeDAS group and Gadolinium (III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate. Compound 7a was selected for characterization and further study. Cell uptake, cytotoxicity, and magnetic resonance imaging scans were performed on cells. In vitro experiments on frozen brain sections from 7-day-old, 8-week-old, and ischemic stroke rats were compared with commercially available Luxol Fast Blue staining. After HPLC and MR scanning, brain tissue was soaked in 7a and scanned using T1WI and T1maps sequences. ResultsSpectrophotometer results showed that compounds 7a and 7b had fluorescent properties. MR scans indicated that the compounds had contrast agent properties. Cells could uptake 7a and exhibited high signals in imaging scans. Compound 7a brain tissue staining showed more fluorescence in myelin-rich regions and identified injury sites in ischemic stroke rats. MR scanning of brain sections provided clear myelin contrast. ConclusionA novel fluorescent-magnetic resonance dual-modal molecular imaging probe for direct imaging of myelin was successfully developed and tested in rats with ischemic stroke. These findings provide new insights for the clinical diagnosis of demyelinating diseases.

Progress in ultrasmall ferrite nanoparticles enhanced T1 magnetic resonance angiography.

Contrast-enhanced magnetic resonance angiography (CE-MRA) plays a critical role in diagnosing and monitoring various vascular diseases. Achieving high-sensitivity detection of vascular abnormalities in CE-MRA depends on the properties of contrast agents. In contrast to clinically used gadolinium-based contrast agents (GBCAs), the new generation of ultrasmall ferrite nanoparticles-based contrast agents have high relaxivity, long blood circulation time, easy surface functionalization, and high biocompatibility, hence showing promising prospects in CE-MRA. This review aims to comprehensively summarize the advancements in ultrasmall ferrite nanoparticles-enhanced MRA for detecting vascular diseases. Additionally, this review also discusses the future clinical translational potential of ultrasmall ferrite nanoparticles-based contrast agents for vascular imaging. By investigating the current status of research and clinical applications, this review attempts to outline the progress, challenges, and future directions of using ultrasmall ferrite nanoparticles to drive the field of CE-MRA into a new frontier of accuracy and diagnostic efficacy.

Effect of gamma irradiation on the size of cellulose nanocrystals with polyethylene glycol and sodium hydroxide/Gd2O3 nanocomposite as contrast agent in magnetic resonance imaging (MRI)

The attractive properties of gadolinium-based nanoparticles as a positive contrast agent for magnetic resonance imaging (MRI) have piqued the interest of both researchers and clinicians. Nonetheless, due to the biotoxicity of gadolinium (III) ions' free radicals, there is a need to address this issue. Therefore, this research aimed to develop a biocompatible, dispersible, stable, hydrophilic, and less toxic cellulose nanocrystals/gadolinium oxide nanocomposite as contrast agent properties for MRI purposes. This study aimed to synthesize gadolinium oxide nanoparticles coated with cellulose nanocrystals with polyethylene glycol and sodium hydroxide (CNCs-PEG/NaOH)/Gd2O3 using the gamma irradiation method to reduce the particle size. The results showed that using a gamma irradiation dose of 10 kGy, quasi-spherical morphology with a size of approximately 5.5 ± 0.65 nm could be produced. Furthermore, the cytocompatibility of (CNCs-PEG/NaOH)/Gd2O3 nanocomposite synthesized was assessed through MTT assay tests on Hep G2 cells, which demonstrated good cytocompatibility without any cytotoxic effects within a concentration range of (10 μg/mL −150 μg/mL) and had sufficient cellular uptake. Moreover, the T1-weighted MRI of (CNCs-PEG/NaOH)/Gd2O3 nanocomposite revealed promising results as a positive contrast agent. It is envisaged that the gamma irradiation method is promising in synthesizing (CNCs-PEG/NaOH)/Gd2O3 nanocomposite with nanoscale for different applications, especially in the radiotherapy field.

Fluorescence-informed photoacoustic discrimination of multiple chromophores by lifetime mapping optically gated responses

Synchronously Amplified Photoacoustic Image Recovery (SAPhIRe) offers improved background suppression using non-linear properties of modulatable contrast agents. Using SAPhIRe, multiple contrast agents in the same absorption window can be detected independently based on their unique triplet-state lifetimes. Here, we have demonstrated the unmixing of rose bengal and eosin Y signals from solution based on triplet-state lifetime mapping using both fluorescence and photoacoustics. Varying the pump-probe delay enables resolution and recovery of fast-decaying rose bengal and of slowly decaying eosin Y modulated photoacoustic signals, resulting from optically gated triplet state residence. Distinct images were reconstructed within tissue-mimicking phantom using the fitting coefficients of triplet-state lifetimes. Fluorescence was used to screen for modulation prior to photoacoustic imaging. The results suggest that lifetime unmixing can be utilized to simultaneously detect multiple pathologies with overlapping spectra using photoacoustic imaging.

Physicochemical Descriptors in Biodistribution and Clearance of Contrast Agents

Hepatobiliary and renal excretions are the two major in vivo elimination pathways, of which prediction is particularly important for the optimization of systemic and/or target‐site exposure of new near‐infrared (NIR) fluorescent contrast agents. To characterize the physicochemical descriptors associated with each clearance route, a compound library containing more than 760 NIR fluorophores is analyzed and systematically reviewed in this study. Although there are a host of biochemical and physiological mechanisms that ultimately determine the in vivo fate of any given molecule, the physicochemical properties of contrast agents including molecular weight, hydrophobicity, topological polar surface area, molecular charges, and hydrogen/rotatable bonds are often indicative of each clearance route. The approach developed is anticipated to be useful in early lead identification studies when selecting NIR fluorescent contrast agents from large database screenings. It may also be applied to prioritize synthetically feasible chemical modifications during lead compound optimization.

Nonlinear acoustic properties of ultrasound contrast agents encapsulated by an anisotropic visco-elastic shell

Nonlinear acoustic properties of ultrasound contrast agents encapsulated by an anisotropic visco-elastic shell

Modeling Gd3+ Complexes for Molecular Dynamics Simulations: Toward a Rational Optimization of MRI Contrast Agents.

The correct parametrization of lanthanide complexes is of the utmost importance for their characterization using computational tools such as molecular dynamics simulations. This allows the optimization of their properties for a wide range of applications, including medical imaging. Here we present a systematic study to establish the best strategies for the correct parametrization of lanthanide complexes using [Gd(DOTA)]- as a reference, which is used as a contrast agent in MRI. We chose the bonded model to parametrize the lanthanide complexes, which is especially important when considering the study of the complex as a whole (e.g., for the study of the dynamics of its interaction with proteins or membranes). We followed two strategies: a so-called heuristic approach employing strategies already published by other authors and another based on the more recent MCPB.py tool. Adjustment of the Lennard-Jones parameters of the metal was required. The final topologies obtained with both strategies were able to reproduce the experimental ion to oxygen distance, vibrational frequencies, and other structural properties. We report a new strategy to adjust the Lennard-Jones parameters of the metal ion in order to capture dynamic properties such as the residence time of the capping water (τm). For the first time, the correct assessment of the τm value for Gd-based complexes was possible by recording the dissociative events over up to 10 μs all-atom simulations. The MCPB.py tool allowed the accurate parametrization of [Gd(DOTA)]- in a simpler procedure, and in this case, the dynamics of the water molecules in the outer hydration sphere was also characterized. This sphere was divided into the first hydration layer, an intermediate region, and an outer hydration layer, with a residence time of 18, 10 and 19 ps, respectively, independent of the nonbonded parameters chosen for Gd3+. The Lennard-Jones parameters of Gd3+ obtained here for [Gd(DOTA)]- may be used with similarly structured gadolinium MRI contrast agents. This allows the use of molecular dynamics simulations to characterize and optimize the contrast agent properties. The characterization of their interaction with membranes and proteins will permit the design of new targeted contrast agents with improved pharmacokinetics.

Effects of shell-integrated Sudan Black dye on the acoustic activity and ultrasound imaging properties of lipid-shelled nanoscale ultrasound contrast agents.

.Significance: An effective contrast agent for concurrent multimodal photoacoustic (PA) and ultrasound (US) imaging must have both high optical absorption and high echogenicity. Integrating a highly absorbing dye into the lipid shell of gas core nanobubbles (NBs) adds PA contrast to existing US contrast agents but may impact agent ultrasonic response.Aim: We report on the development and ultrasonic characterization of lipid-shell stabilized NBs with integrated Sudan Black (SB) B dye in the shell as dual-modal PA-US contrast agents.Approach: Perfluoropropane NBs stabilized with a lipid shell including increasing concentrations of SB B dye were formulated by amalgamation (SBNBs). Physical properties of SBNBs were characterized using resonant mass measurement, transmission electron microscopy and pendant drop tensiometry. Concentrated bubble solutions were imaged for 8 min to assess signal decay. Diluted bubble solutions were stimulated by a focused transducer to determine the response of individual NBs to long cycle (30 cycle) US. For assessment of simultaneous multimodal contrast, bulk populations of SBNBs were imaged using a PA and US imaging platform.Results: We produced high agent yield () with a mean diameter of to 300 nm depending on SB loading. A 40% decrease in bubble yield was measured for solutions with 0.3 and SB. The addition of SB to the shell did not substantially affect NB size despite an increase in surface tension by up to . The bubble decay rate increased after prolonged exposure (8 min) by dyed bubbles in comparison to their undyed counterparts (2.5-fold). SB in bubble shells increased gas exchange across the shell for long cycle US. PA imaging of these agents showed an increase in power (up to 10 dB) with increasing dye.Conclusions: We added PA contrast function to NBs. The addition of SB increased gas exchange across the NB shell. This has important implications in their use as multimodal agents.

An In Vitro Comparative Study of Three Drug-Eluting Beads Loaded with Raltitrexed.

Background: This study investigated the raltitrexed loading method, compatible stability with contrast agent, release profiles, and morphological properties of CalliSpheres, DC Bead, and HepaSphere. Materials and Methods: The amounts of raltitrexed added, loading medium, loading condition, and drug concentrations were investigated as factors influencing drug loading efficiency. Compatible stability with iopamidol was tested. Release profiles were accessed by a flowthrough apparatus system. Morphological properties were evaluated by a scanning electron microscope (SEM). Diameters were measured by a laser diffraction particle size analyzer. Results: With the optimized method, the amount of raltitrexed loading to a marketed drug-eluting beads (DEBs) package was 2.67 mg for CalliSpheres, 2.34 mg for DC Bead, and 3.19 mg for HepaSphere. For all three DEBs, the drug leak rate was >50% within 2 h after mixing with iopamidol, and the time to reach 75% of the release plateau was within 10 min. Diameters increased after drug loading. Drug crystals were observed on the surface of DEBs in SEM. Conclusions: The amount of drug loading could meet clinical requirements by the optimized method. All three raltitrexed-loaded DEBs showed poor compatible stability with iopamidol, as well as rapid drug release performance, which should be noticed in clinical practice.

PD27-05 BENCHTOP BLADDER PHANTOM PRESSURE ESTIMATION USING ULTRASOUND CONTRAST AGENTS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-05 BENCHTOP BLADDER PHANTOM PRESSURE ESTIMATION USING ULTRASOUND CONTRAST AGENTS Kourosh Kalayeh, J. Brian Fowlkes, Jake Claflin, Mario L. Fabiilli, William W. Schultz, and Bryan S. Sack Kourosh KalayehKourosh Kalayeh More articles by this author , J. Brian FowlkesJ. Brian Fowlkes More articles by this author , Jake ClaflinJake Claflin More articles by this author , Mario L. FabiilliMario L. Fabiilli More articles by this author , William W. SchultzWilliam W. Schultz More articles by this author , and Bryan S. SackBryan S. Sack More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lack of a catheter-free, physiological method for evaluating bladder pressure is considered to be a major challenge in urodynamic testing. We hypothesize that pressure sensitive acoustic properties of ultrasound contrast agents (UCAs)–a method known as SubHarmonic Aided Pressure Estimation (SHAPE)–adequately estimates benchtop bladder phantom pressures. METHODS: The designed bladder phantom simulates non-voiding contractions (NVCs) and variable compliance. Laboratory made equivalent of a commercial UCA is diluted in 0.9 % normal saline (0.08 % v/v) and infused using urodynamic equipment (30 ml/min). Simultaneous subharmonic signal scattered by UCAs is acquired with ultrasound scanner (GE LOGIQ E10 and C2-9 probe using SHAPE mode) and calibrated with a linear fit to yield bladder pressure values. For the variable compliance bladder model, measurements are obtained at 10 cmH2O pressure increments while for the NVC model measurements are acquired continuously. RESULTS: Examples of pressure tracings and SHAPE estimations for the two models are shown. The maximum absolute errors for variable compliance and NVCs are less than 8 cmH2O (8 %) and 16 cmH2O (16 %), respectively. The mean R−squared values for both models (n=4) is R2=0.89±0.09. CONCLUSIONS: Subharmonic signal scattered by UCAs can be strongly correlated with phantom bladder pressures. This is the first step towards creating a catheter-free voiding bladder pressure measurement using SHAPE. Source of Funding: Societies for Pediatric Urology and UofM Mcubed © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e444-e445 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kourosh Kalayeh More articles by this author J. Brian Fowlkes More articles by this author Jake Claflin More articles by this author Mario L. Fabiilli More articles by this author William W. Schultz More articles by this author Bryan S. Sack More articles by this author Expand All Advertisement Loading ...

Optimized Loading of Idarubicin in CalliSpheres® Drug-Eluting Beads and Characterization of Release Profiles and Morphological Properties.

This study aimed to investigate the idarubicin loading method, compatible stability with contrast agent, release profiles, and morphological properties of 50–150, 100–300, and 300–500 μm CalliSpheres®. The amounts of idarubicin added, loading medium, loading condition, and drug concentration were investigated as factors influencing drug loading efficiency. The drug loading rate was negatively correlated with the amount drug added and diameter of CalliSpheres® and positively correlated with the drug concentration. Compared to loading in purified water and incubation at room temperature, 5% glucose, heating, and ultrasound could accelerate drug loading. The idarubicin loading efficiency was above 95% after 10 min for all three CalliSpheres® with the optimized method of adding 20 mg of idarubicin at a concentration of 2 mg/mL and incubating at room temperature. The drug leak rate was under 1% within 8 h after mixing with iopamidol. Drug release tests indicated the sustained-release performance of CalliSpheres®, and the time to reach 75% of the release plateau level was 8, 26, and 51 min for 50–150, 100–300, and 300–500 μm CalliSpheres®, respectively. After idarubicin loading, the diameters increased by 12%, 36%, and 38% for 50–150, 100–300, and 300–500 μm CalliSpheres®, respectively, and the surface of CalliSpheres® was observed to become smoother than that before drug loading. All three CalliSpheres® presented satisfactory loading efficiency with the optimized method, as well as proper compatible stability and sustained release performance. Among them, 100–300 μm CalliSpheres® are recommended.

Characterization and biodistribution of Au nanoparticles loaded in PLGA nanocarriers using an original encapsulation process

Due to their imaging and radiosensitizing properties, ultrasmall gadolinium chelate-coated gold nanoparticles (AuNP) represent a promising approach in the diagnosis and the treatment of tumors. However, their poor pharmacokinetic profile, especially their rapid renal clearance prevents from an efficient exploitation of their potential for medical applications. The present study focuses on a strategy which resides in the encapsulation of AuNP in large polymeric NP to avoid the glomerular filtration and then to prolong the vascular residence time. An original encapsulation procedure using the polyethyleneimine (PEI) was set up to electrostatically entrap AuNP in biodegradable poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol -PLGA (PLGA-PEG) NP. Hydrodynamic diameters of NP were dependent of the PEI/Au ratio and comprised between 115 and 196 nm for ratios equal or superior to 4. Encapsulation yield was close to 90 % whereas no loading was observed without PEI. No toxicity was observed after 24 h exposure in hepatocyte cell-lines. Entrapement of AuNP in polymeric nanocarriers facilitated the passive uptake in cancer cells after only 2 h incubation. In healthy rat, the encapsulation allowed increasing the gold concentration in the blood within the first hour after intravenous administration. Polymeric nanoparticles were sequestered in the liver and the spleen rather than the kidneys. T1-weighted magnetic resonance demonstrated that encapsulation process did not alter the contrast agent properties of gadolinium. The encapsulation of the gold nanoparticles in PLGA particles paves the way to innovative imaging-guided anticancer therapies in personalized medicine.

Nanoparticles: Untying the Gordian Knot in Conventional Computed Tomography Imaging

X-ray computed tomography (CT) imaging plays an essential role in disease diagnosis due to its noninvasive, painless mode and superior penetration depth. However, the resolution of the soft tissue ...

Targeting Nanostrategies for Imaging of Atherosclerosis

Despite the progress in cardiovascular research, atherosclerosis still represents the main cause of death worldwide. Clinically, the diagnosis of Atherosclerotic Cardiovascular Disease (ASCVD) relies on imaging methodologies including X-ray angiography and computed tomography (CT), which however still fails in the identification of patients at high risk of plaque rupture, the main cause of severe clinical events as stroke and heart attack. Magnetic resonance imaging, which is characterized by very high spatial resolution, could provide a better characterization of atherosclerotic plaque (AP) anatomy and composition, aiding in the identification of “vulnerable” plaques. In this context, hydrogel matrices, which have been demonstrated able to boost relaxometric properties of Gd-based contrast agents (CAs) by the effect of Hydrodenticity, represent a valuable tool towards the precision imaging of ASCVD improving the performance of this class of CAs while reducing systemic toxicity. In particular, hydrogel nanoparticles encapsulating Gd-DTPA can further contribute to providing CA-specific accumulation in the AP by nanoparticle surface decoration triggering an active targeting of the AP with the overall effect of allowing an earlier and more accurate diagnosis. In this work, we tested crosslinked Hyaluronic Acid Nanoparticles (cHANPs) in the complex environment of human atherosclerotic plaque. In addition, the surface of cHANPs was decorated with the antibody anti-CD36 (Ab36-cHANPs) for the active targeting of AP-associated macrophages. Results demonstrate that the Hydrodenticity of cHANPs and Ab36-cHANPs is preserved in this complex system and, preliminarily, that interaction of these probes with the AP is present.

Gd3+ Complexes Conjugated to Cyclodextrins: Hydroxyl Functions Influence the Relaxation Properties

In the search for improvement in the properties of gadolinium-based contrast agents, cyclodextrins (CDs) are interesting hydrophilic scaffolds with high molecular weight. The impact of the hydrophilicity of these systems on the MRI efficacy has been studied using five β-CDs substituted with DOTA or TTHA ligands which, respectively, allow for one (q = 1) or no water molecule (q = 0) in the inner coordination sphere of the Gd3+ ion. Original synthetic pathways were developed to immobilize the ligands at C-6 position of various hydroxylated and permethylated β-CDs via an amide bond. To describe the influence of alcohol and ether oxide functions of the CD macrocycle on the relaxation properties of the Gd3+ complexes, 1H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles, and 17O transverse relaxation rates have been measured at various temperatures. The differences observed between the hydroxylated and permethylated β-CDs bearing non-hydrated GdTTHA complexes can be rationalized by a second sphere contribution to the relaxivity in the case of the hydroxylated derivatives, induced by hydrogen-bound water molecules around the hydroxyl groups. In contrast, for the DOTA analogs the exchange rate of the water molecule directly coordinated to the Gd3+ is clearly influenced by the number of hydroxyl groups present on the CD, which in turn influences the relaxivity and gives rise to a very complex behavior of these hydrophilic systems.

Contrast agent shell properties effects on heat deposition in bubble enhanced high intensity focused ultrasound.

The effects of the viscoelastic shell properties of ultrasound contrast agents on heat deposition in bubble enhanced high intensity focused ultrasound (HIFU) are studied numerically using a model that solves the ultrasound acoustic field and the multi-bubble dynamics. The propagation of the nonlinear acoustic waves in the test medium is modeled using the compressible Navier-Stokes equations in a fixed Eulerian grid, while the microbubbles are modeled as discrete flow singularities, which are tracked in a Lagrangian fashion. These two models are intimately coupled such that both the acoustic field and the bubbles influence each other at each time step. The resulting temperature rise in the field is then calculated by solving a heat transfer equation applied over a much longer time scale than the computed high frequency dynamics. Three shell models for the contrast agent are considered, and the effect of each of these models on the heat deposition at the focus is studied. The differences obtained in the bubble dynamics results between the shell models are discussed. The importance of modeling the elasticity of the shell is addressed by comparing the results between Newtonian and non-Newtonian shell models. Next, a parametric study varying the shell properties is carried out, and the relative roles of the shell viscosity and elasticity in affecting the heat deposition are discussed. These observations are then used to give recommendations for the design of innovative contrast agents, specifically for the purpose of obtaining higher heat deposition in bubble enhanced HIFU.

Window-Modulated Compounding Nakagami Parameter Ratio Approach for Assessing Muscle Perfusion with Contrast-Enhanced Ultrasound Imaging

The assessment of microvascular perfusion is essential for the diagnosis of a specific muscle disease. In comparison with the current available medical modalities, the contrast-enhanced ultrasound imaging is the simplest and fastest means for probing the tissue perfusion. Specifically, the perfusion parameters estimated from the ultrasound time-intensity curve (TIC) and statistics-based time–Nakagami parameter curve (TNC) approaches were found able to quantify the perfusion. However, due to insufficient tolerance on tissue clutters and subresolvable effects, these approaches remain short of reproducibility and robustness. Consequently, the window-modulated compounding (WMC) Nakagami parameter ratio imaging was proposed to alleviate these effects, by taking the ratio of WMC Nakagami parameters corresponding to the incidence of two different acoustic pressures from an employed transducer. The time–Nakagami parameter ratio curve (TNRC) approach was also developed to estimate perfusion parameters. Measurements for the assessment of muscle perfusion were performed from the flow phantom and animal subjects administrated with a bolus of ultrasound contrast agents. The TNRC approach demonstrated better sensitivity and tolerance of tissue clutters than those of TIC and TNC. The fusion image with the WMC Nakagami parameter ratio and B-mode images indicated that both the tissue structures and perfusion properties of ultrasound contrast agents may be better discerned.

Synthesis and Comparative Evaluation of Photoswitchable Magnetic Resonance Imaging Contrast Agents.

A series of spiropyran (SP)-based magnetic resonance imaging (MRI) contrast agents have been synthesized and evaluated for changes in relaxivity resulting from irradiation with visible light. Both electron-donating and electron-withdrawing substituents were appended to the SP ring in order to study the electronic effects on the photochromic and relaxivity properties of these photoswitchable MRI contrast agents. Photoswitches lacking an electron-withdrawing substituent isomerize readily between the merocyanine and SP forms, while the addition of a nitro group prevents this process. Complexes capable of isomerizing were demonstrated to effect a change in the relaxivity of the appended gadolinium complex.

Effect of Structure and Intramolecular Distances on Photoswitchable Magnetic Resonance Imaging Contrast Agents.

Light-activated sensors are of great interest for biological applications but are limited by the depth of penetration of light. We have been interested in transducing light activation to a magnetic signal that can be detected through noninvasive imaging by magnetic resonance imaging (MRI). We have previously developed agents incorporating spiropyran derivatives as the sensing moiety and characterized features that influence photoswitching; however, we found the MRI response to be unpredictable. In this work, we delve deeper into the potential mechanisms for the observed MRI responses in an effort to better understand the structural effects on controlling magnetic properties. A series of light-activatable MRI contrast agents were synthesized and characterized to assess the effect of spiropyran positioning on contrast agent functions and properties. These compounds are based on the same spiropyran skeleton, also named 1',3',3'-trimethyl-6-nitrospiro[chromene-2,2-indoline], which is linked with an MRI contrast agent, gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (DO3A). We investigated the photo-to-magnetic conversion properties of these novel compounds by adjusting linker lengths over a range from three to seven methylene groups. The primary results indicated that the contrast agent with a five-carbon linker (25) showed the highest light-sensing ability after irradiation with visible light. The results will aid in the design of future spiropyran-based MRI sensors.