T1 Agents Research Articles

Chitosan‐Based Nanogels Containing Ln3+ Chelates (Ln=Gd, Dy) as T1 and T2 MRI Probes

AbstractNovel nanogels, characterized by high stability and incorporating macrocyclic chelates of Gd(III) and Dy(III), were synthesized and assessed for their effectiveness as T1 and T2 relaxation agents, respectively. In this specific design, we employed octacoordinated bifunctional Gd‐1,7‐DOTAGA2 chelate to cross‐link chitosan chains. The results revealed that the sample exhibited a relaxivity value at clinical magnetic field strengths (1.5 T), approximately seven times higher than that of currently available clinical contrast agents and good MRI contrast efficacy at both 7.1 and 1 T. Furthermore, the nanogel displayed excellent stability in biological fluids, with no discernible interactions with serum biomolecules and no release of metal. In addition to Gd(III)‐based probes commonly used as T1 positive contrast agents, the nanogel with the corresponding Dy‐1,7‐DOTAGA2 chelate was prepared to explore its potential as a T2 MRI probe. Dy‐based nanogel demonstrated notably elevated transverse relaxivity values compared to the free chelate at high magnetic fields (>3 T) and significant T2 MRI contrast at 7.1 T, a capability often lacking when employing an equivalent concentration of a low‐molecular‐weight Dy(III) complex. The characterization of paramagnetic complexes was completed through the measurement of 1H NMRD profiles and 17O NMR data.

Nano-technological advancements in multimodal diagnosis and treatment

<p>Nanomedicine, which is blazing new trails in modern healthcare, exploits the distinctive attributes of nanoparticles (NPs) to reimagine diagnosis and therapy. With imaging, this “magic ammunition” enhances the capability of MRI, a noninvasive, high-resolution technology that can pinpoint cancers with astonishing precision. Unlike traditional treatments, which muddle the distinction between diseased and healthy tissue, gold nanoparticles (AuNPs) directly target tumors, using increased permeability and retention (EPR) effects for crystal-clear, early-stage detection. While gadolinium (Gd (III)) T1 agents are the most widely used in clinical practice, iron oxide T2 agents have fallen out of favor due to failing to perform. Beyond imaging, NPs offer a “one-two punch” in the treatment of complicated disorders by enabling photothermal (PTT), photodynamic (PDT), and multimodal therapies (MMT), as well as nano drug delivery systems (NDDS). This nanotechnology-based technique personalizes medicines for diseases such as tuberculosis (TB) and cardiovascular disease (CVD), focusing on damaged tissues to improve therapeutic response. In tuberculosis, NPs circumvent medication resistance by delivering medicines directly to infected cells, thus avoiding biological barriers that impede standard treatments. Similarly, in CVD, NPs target arterial plaques to improve treatment accuracy while reducing systemic adverse effects. Furthermore, the genomic “blueprint” is evolving parallel to nanotechnology, with India's “Genome India” initiative mapping 10,000 genomes, lighting the path for genetic chips suited for specific disorders and moment tests. The convergence of nanotechnology and genomes is an arcade modification, bringing accuracy and personalization to the forefront of cancer and tuberculosis treatment.</p>

MRI Contrasting Agent Based on Mn-MOF-74 Nanoparticles with Coordinatively Unsaturated Sites.

The development of magnetic resonance imaging (MRI) contrasting agents (CAs) that are safer and have a higher relaxivity than Gd(III)-based agents is a significant research topic. Herein, we propose the use of a Mn-based metal organic framework (MOF), Mn-MOF-74, characterized by a safe paramagnetic center, a coordinatively unsaturated site (CUS) for aquation, and a long rotational correlation time, endowing high relaxivity. Furthermore, biocompatibility and delivery to the tumor are generally expected for MOFs that are obtainable in the nanometer size range. Drop-wise mixing of 2,5-dihydroxyterephthalic acid (DHTP) and Mn(II) acetate yielded Mn-MOF-74 with a diameter of < 150nm, which was then modified with 1-fivefold higher amounts of poly(ethylene glycol) (M.W. = 5000) to afford MOFs stably dispersed in water for at least 24h. The longitudinal and transverse relaxivity of the PEG-modified MOF was in the range of r1 = 8.08-13.5 and r2 = 32.7-46.8mM-1s-1, respectively (1.0T, 23.7-23.9°C), being larger than those of typical Gd(III)- and Mn(II)-based CAs of single-nuclear metal complexes. The in vivo imaging of a tumor-bearing mouse clearly showed that the tumor could be readily recognized due to signal enhancement (117%) in T1-weighted images, whereas other tissues showed small signal changes. These results suggest that PEG-Mn-MOF-74 can be passively delivered to tumors and can act as a high-relaxivity T1 agent.

Redox-Responsive MRI Probes Based on First-Row Transition-Metal Complexes.

The presence of multiple oxidation and spin states of first-row transition-metal complexes facilitates the development of switchable MRI probes. Redox-responsive probes capitalize on a change in the magnetic properties of the different oxidation states of the paramagnetic metal ion center upon exposure to biological oxidants and reductants. Transition-metal complexes that are useful for MRI can be categorized according to whether they accelerate water proton relaxation (T1 or T2 agents), induce paramagnetic shifts of 1H or 19F resonances (paraSHIFT agents), or are chemical exchange saturation transfer (CEST) agents. The various oxidation state couples and their properties as MRI probes are summarized with a focus on Co(II)/Co(III) or Fe(II)/Fe(III) complexes as small molecules or as liposomal agents. Solution studies of these MRI probes are reviewed with an emphasis on redox changes upon treatment with oxidants or with enzymes that are physiologically important in inflammation and disease. Finally, we outline the challenges of developing these probes further for in vivo MRI applications.

One-step construction of bifunctional nanoprobes for NIR afterglow and T2-weighted MR imaging

In this study, spinel-phase Zn2Ga3-xFe3+xGe0.75O8 (x = 0, 0.002, 0.004, 0.02, 0.04, 0.08, 0.2) and Zn2Ga2.98-xFe3+xCr0.02Ge0.75O8 (x = 0, 0.0004, 0.001, 0.002 0.003, 0.004) nanoparticles were prepared by one-step hydrothermal method in combination with vacuum annealing. For ZGGO: Fe3+ nanoparticles, the near infrared (NIR) emissions (∼725 nm) originate from the 4T1(4G)→6A1(6S) transition of Fe3+ occupying octahedral and tetrahedral sites of Ga3+. Furthermore, their afterglow time is more than 15 min and Fe3+ doping will influence the generation of antisite defects pair (GaZn0−ZnGa′). For Cr3+ and Fe3+ co-doped ZGGO nanoparticles with average size of ∼46 nm, the NIR persistent luminescence around ∼700 nm, originating from the 2E→4A2 and 4T2→4A2 transitions of Cr3+, can be observed and the afterglow time exceeds 850 min. With the increase of Fe3+ concentration, the afterglow intensity decreases due to the decreased number of (GaZn0−ZnGa′) defects and deeper traps. In particular, autofluorescence-free imaging and MR imaging were successfully realized by using ZGGO: Cr3+, Fe3+0.002 nanoparticles dispersed in the simulated biological fluid environments (H2O, SLS and HSA). Their clear afterglow images can be acquired within 3 min after the stoppage of the UV irradiation and their transversal relaxivity (r2) is in the range of 227–140 mM−1s−1, which is close to the conventional Feridex T2 agent (108 mM−1s−1). Our results suggest that ZGGO: Cr3+, Fe3+ nanoprobes have potential applications in the diagnosis and therapy of disease.

GdDO3NI Enhanced Magnetic Resonance Imaging Allows Imaging of Hypoxia After Brain Injury.

Brain tissue hypoxia is a common consequence of traumatic brain injury (TBI) due to the rupture of blood vessels during impact and it correlates with poor outcome. The current magnetic resonance imaging (MRI) techniques are unable to provide a direct map of tissue hypoxia. To investigate whether GdDO3NI, a nitroimidazole-based T1 MRI contrast agent allows imaging hypoxia in the injured brain after experimental TBI. Prospective. TBI-induced mice (controlled cortical impact model) were intravenously injected with either conventional T1 agent (gadoteridol) or GdDO3NI at 0.3 mmol/kg dose (n=5 for each cohort) along with pimonidazole (60 mg/kg) at 1 hour postinjury and imaged for 3 hours following which they were euthanized. 7 T/T2 -weighted spin echo and T1 -weighted gradient echo. Injured animals were imaged with T2 -weighted spin-echo sequence to estimate the extent of the injury. The mice were then imaged precontrast and postcontrast using a T1 -weighted gradient-echo sequence for 3 hours postcontrast. Regions of interests were drawn on the brain injury region, the contralateral brain as well as on the cheek muscle region for comparison of contrast kinetics. Brains were harvested immediately post-imaging for immunohistochemical analysis. One-way analysis of variance and two-sample t-tests were performed with a P< 0.05 was considered statistically significant. GdDO3NI retention in the injury region at 2.5-3 hours post-injection was significantly higher compared to gadoteridol (mean retention fraction 63.95% ± 27.43% vs. 20.68% ± 7.43% for gadoteridol at 3 hours) while it rapidly cleared out of the muscle region. Pimonidazole staining confirmed the presence of hypoxia in both gadoteridol and GdDO3NI cohorts, and the later cohort showed good agreement with MRI contrast enhancement. GdDO3NI was successfully shown to visualize hypoxia in the brain post-TBI using T1 -weighted MRI at 2.5-3 hours postcontrast. 1 TECHNICAL EFFICACY: Stage 1.

Ultracompact Iron Oxide Nanoparticles with a Monolayer Coating of Succinylated Heparin: A New Class of Renal-Clearable and Nontoxic T1 Agents for High-Field MRI.

Herein, we present a new magnetic iron oxide nanoparticle (MION) with a succinylated heparin monolayer coating, which exhibits the highest T1 relaxivity at 7 T and the lowest r2/r1 reported for any MION at these high-field conditions. While the recent proliferation of 7 T MRI instruments in hospitals worldwide has enabled widespread access to higher quality, more finely detailed, diagnostic imaging, clinically available contrast agents have not kept pace due to the general phenomenon of reduced efficacy of T1 relaxation as magnetic field strength is increased. Development of new MION agents is one strategy to address this need, and to this end, we demonstrate the in vitro magnetic properties of the MIONs reported here to extend to in vivo applications, providing greatly increased contrast in tumor imaging in a murine xenograft subject at 7 T. While MION-based contrast agents can have side effects in clinical application, these are generally thought to be less than those of gadolinium-based agents and here are further reduced by the small size allowing direct glomerular filtration from the blood followed by renal-excretion. Finally, we show the succinylated heparin monolayer coating to provide class leading magnetic properties over a homologous series of particles with core size ranging from 2 to 18 nm and show the properties to be strongly related to the surface area. We suggest the increased porosity and hydrophilicity of the coating to increase water accessibility to the surface resulting in the increased magnetic properties.

Dysprosium-Modified Gold Nanoparticles as T2ex Contrast Agents for Magnetic Resonance Imaging

With the development of high magnetic field strength in magnetic resonance imaging (MRI), there is a demand to develop MRI contrast agents to attain high relaxation effects. Compared to typical T1 agents, the transverse relaxation rate of T2-based contrast agents increases with increasing magnetic field strength. However, better contrast agents are needed to improve the signal-to-noise issue. Here, a series of T2ex contrast agents composed of an Au nanoparticle (NP) and a dysprosium complex (AuNP-DyDOTA(amide)x) were designed. The transverse relaxivity of three molecules bearing different side arm chains were investigated. After screening by NMR signals, the transverse relaxivity of AuNP-DyDOTA(amide)2 achieved 22.9 mM–1 s–1 at 9.4 T, which is higher than dysprosium-based small molecules. The in vivo results demonstrate that the AuNP-DyDOTA(amide)2 is very efficient for specific accumulation in tumor regions and rapid metabolization was realized, making them promising for ultrahigh field strength imaging and clinical diagnosis in the future.

Nanoparticle-Based Paramagnetic Contrast Agents for Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is a noninvasive medical imaging modality that is routinely used in clinics, providing anatomical information with micron resolution, soft tissue contrast, and deep penetration. Exogenous contrast agents increase image contrast by shortening longitudinal (T1) and transversal (T2) relaxation times. Most of the T1 agents used in clinical MRI are based on paramagnetic lanthanide complexes (largely Gd-based). In moving to translatable formats of reduced toxicity, greater chemical stability, longer circulation times, higher contrast, more controlled functionalisation and additional imaging modalities, considerable effort has been applied to the development of nanoparticles bearing paramagnetic ions. This review summarises the most relevant examples in the synthesis and biomedical applications of paramagnetic nanoparticles as contrast agents for MRI and multimodal imaging. It includes the most recent developments in the field of production of agents with high relaxivities, which are key for effective contrast enhancement, exemplified through clinically relevant examples.

Paramagnetic and Superparamagnetic Inorganic Nanoparticles for T1-Weighted Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) has become a promising technique in the early diagnosis of cancers, especially the application of contrast agents can further enhance the detection limit. Compared with the dark signal in "negative" contrast agents (T2), "positive" contrast agents (T1) with bright signal are more desirable for high-resolution imaging. However, the clinically used gadolinium complexes have short circulation time and the risk of nephrogenic system fibrosis. Therefore, to overcome the disadvantage of T2 agents and traditional T1 agents, it is very interesting to develop nano-scaled T1-weighted MRI contrast agents with safer and more precise imaging performance. The present review systematically summarized the recent progress of paramagnetic and superparamagnetic inorganic nanoparticles as T1-weighted MRI contrast agents, including gadolinium oxide nanoparticles, gadoliniumbased upconversion nanoparticles, manganese oxide nanoparticles, and ultra-small iron oxide nanoparticles. Moreover, we also described their applications in multi-modal imaging and visualized theranostics.

Graphene oxide / MnWO4 nanocomposite for magnetic resonance / photoacoustic dual-model imaging and tumor photothermo-chemotherapy

A multifunctional theranostic nanoplatform based on nanosized graphene oxide (GO) and MnWO4 has been developed by in situ growth of MnWO4 nanoparticles onto GO surfaces in a hyperthermia polyol medium containing polyethylene glycol (PEG). In comparison with GO and MnWO4/PEG, the near infrared (NIR) absorbance of the produced GO/MnWO4/PEG nanocomposite is significantly improved, resulting in an enhanced photothermal conversion capability and a good photoacoustic (PA) imaging performance. It is worth to note that the longitudinal relaxivity r1 of GO/MnWO4/PEG reaches impressively 11.34 mM−1 s−1 in a 0.5 T magnetic field, which is significantly higher than ordinary Mn(II)-based T1 agents. In vivo magnetic resonance and PA imaging demonstrate that GO/MnWO4/PEG could serve as an efficient bimodal contrast agent to guide the cancer treatment. GO/MnWO4/PEG shows a high loading capacity for anticancer drug doxorubicin hydrochloride (DOX) by noncovalent forces, and the drug release could be triggered by lower pH value and external NIR light. Effective synergistic photothermo-chemotherapy has been performed in xenograft 4T1 tumor models after intravenous administration of GO/MnWO4/PEG/DOX. No obvious toxicity and side effect have been observed during in vivo treatment. These positive results suggest the promising application of GO/MnWO4/PEG as a versatile nanoplatform for multimodal imaging-guided cancer synergistic therapy.

Spatiotemporal heterogeneity of tumor vasculature during tumor growth and antiangiogenic treatment: MRI assessment using permeability and blood volume parameters.

Tumor heterogeneity is an important concept when assessing intratumoral variety in vascular phenotypes and responses to antiangiogenic treatment. This study explored spatiotemporal heterogeneity of vascular alterations in C6 glioma mice during tumor growth and antiangiogenic treatment on serial MR examinations (days 0, 4, and 7 from initiation of vehicle or multireceptor tyrosine kinase inhibitor administration). Transvascular permeability (TP) was quantified on dynamic‐contrast‐enhanced MRI (DCE‐MRI) using extravascular extracellular agent (Gd‐DOTA); blood volume (BV) was estimated using intravascular T2 agent (SPION). With regard to region‐dependent variability in vascular phenotypes, the control group demonstrated higher TP in the tumor center than in the periphery, and greater BV in the tumor periphery than in the center. This distribution pattern became more apparent with tumor growth. Antiangiogenic treatment effect was regionally heterogeneous: in the tumor center, treatment significantly suppressed the increase in TP and decrease in BV (ie, typical temporal change in the control group); in the tumor periphery, treatment‐induced vascular alterations were insignificant and BV remained high. On histopathological examination, the control group showed greater CD31, VEGFR2, Ki67, and NG2 expression in the tumor periphery than in the center. After treatment, CD31 and Ki67 expression was significantly suppressed only in the tumor center, whereas VEGFR2 and α‐caspase 3 expression was decreased and NG2 expression was increased in the entire tumor. These results demonstrate that MRI can reliably depict spatial heterogeneity in tumor vascular phenotypes and antiangiogenic treatment effects. Preserved angiogenic activity (high BV on MRI and high CD31) and proliferation (high Ki67) in the tumor periphery after treatment may provide insights into the mechanism of tumor resistance to antiangiogenic treatment.

Quantitative evaluation of contrast agent uptake in standard fat-suppressed dynamic contrast-enhanced MRI examinations of the breast.

PurposeTo propose a method to quantify T1 and contrast agent uptake in breast dynamic contrast‐enhanced (DCE) examinations undertaken with standard clinical fat‐suppressed MRI sequences and to demonstrate the proposed approach by comparing the enhancement characteristics of lobular and ductal carcinomas.MethodsA standard fat‐suppressed DCE of the breast was performed at 1.5 T (Siemens Aera), followed by the acquisition of a proton density (PD)‐weighted sequence, also fat suppressed. Both sequences were characterized with test objects (T1 ranging from 30 ms to 2,400 ms) and calibration curves were obtained to enable T1 calculation. The reproducibility and accuracy of the calibration curves were also investigated. Healthy volunteers and patients were scanned with Ethics Committee approval. The effect of B0 field inhomogeneity was assessed in test objects and healthy volunteers. The T1 of breast tumors was calculated at different time points (pre‐, peak‐, and post‐contrast agent administration) for 20 patients, pre‐treatment (10 lobular and 10 ductal carcinomas) and the two cancer types were compared (Wilcoxon rank‐sum test).ResultsThe calibration curves proved to be highly reproducible (coefficient of variation under 10%). T1 measurements were affected by B0 field inhomogeneity, but frequency shifts below 50 Hz introduced only 3% change to fat‐suppressed T1 measurements of breast parenchyma in volunteers. The values of T1 measured pre‐, peak‐, and post‐contrast agent administration demonstrated that the dynamic range of the DCE sequence was correct, that is, image intensity is approximately directly proportional to 1/T1 for that range. Significant differences were identified in the width of the distributions of the post‐contrast T1 values between lobular and ductal carcinomas (P < 0.05); lobular carcinomas demonstrated a wider range of post‐contrast T1 values, potentially related to their infiltrative growth pattern.ConclusionsThis work has demonstrated the feasibility of fat‐suppressed T1 measurements as a tool for clinical studies. The proposed quantitative approach is practical, enabled the detection of differences between lobular and invasive ductal carcinomas, and further enables the optimization of DCE protocols by tailoring the dynamic range of the sequence to the values of T1 measured.

Two decades of dendrimers as versatile MRI agents: a tale with and without metals.

Dendrimers or dendritic polymers are a class of compounds with great potential for nanomedical use. Some of their properties, including their rigidity, low polydispersity and the ease with which their surfaces can be modified make them particularly well suited for use as MRI diagnostic or theranostic agents. For the past 20 years, researchers have recognized this potential and refined dendrimer formulations to optimize these nanocarriers for a host of MRI applications, including blood pool imaging agents, lymph node imaging agents, tumor-targeted theranostic agents and cell tracking agents. This review summarizes the various types of dendrimers according to the type of MR contrast they can provide. This includes the metallic T1 , T2 and paraCEST imaging agents, and the non-metallic diaCEST and fluorinated (19 F) heteronuclear imaging agents. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

Contrast-Enhanced Magnetic Resonance Imaging at Earth’s Magnetic Field Using Trace Gd3+ and Ho3+ Salts

Here, we report a study of contrast-enhanced magnetic resonance imaging at Earth’s field. In this study, we performed magnetic relaxation measurements of protons in water in the presence of the lanthanide ions Gd3+ and Ho3+ using the nuclear magnetic resonance technique. The results suggest that Gd3+ is a more effective T1 and T2 relaxation agent than Ho3+ and is therefore a better contrast agent. We then confirmed the relaxation phenomenon by performing a T1-weighted-contrast magnetic resonance imaging (MRI) of samples containing water doped with Gd3+ at the Earth’s magnetic field. The T1-weighted imaging experimental result indicates that the intensity is the highest for the sample doped with the highest concentration of Gd3+ and lowest for the undoped sample. This work shows the feasibility of performing contrast-enhanced MRI in Earth’s magnetic field using relaxation agents such as lanthanide ions. In addition, this work also demonstrates that, although the Earth’s field MRI does not provide the strength and capability of a clinical MRI, it is still useful as a powerful demonstration tool, especially considering its low operating costs and portability.

Oxidative Conversion of a Europium(II)-Based T1 Agent into a Europium(III)-Based paraCEST Agent that can be Detected In Vivo by Magnetic Resonance Imaging.

The Eu(II) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tetra(glycinate) has a higher reduction potential than most Eu(II) chelates reported to date. The reduced Eu(II) form acts as an efficient water proton T1 relaxation reagent, while the Eu(III) form acts as a water-based chemical exchange saturation transfer (CEST) agent. The complex has extremely fast water exchange rate. Oxidation to the corresponding Eu(III) complex yields a well-defined signal from the paraCEST agent. The time course of oxidation was studied in vitro and in vivo by T1-weighted and CEST imaging.

Smart Contrast Agents for Magnetic Resonance Imaging.

By visualizing bioactive molecules or biological parameters in vivo, molecular imaging is searching for information at the molecular level in living organisms. In addition to contributing to earlier and more personalized diagnosis in medicine, it also helps understand and rationalize the molecular factors underlying physiological and pathological processes. In magnetic resonance imaging (MRI), complexes of paramagnetic metal ions, mostly lanthanides, are commonly used to enhance the intrinsic image contrast. They rely either on the relaxation effect of these metal chelates (T(1) agents), or on the phenomenon of paramagnetic chemical exchange saturation transfer (PARACEST agents). In both cases, responsive molecular magnetic resonance imaging probes can be designed to report on various biomarkers of biological interest. In this context, we review recent work in the literature and from our group on responsive T(1) and PARACEST MRI agents for the detection of biogenic metal ions (such as calcium or zinc), enzymatic activities, or neurotransmitter release. These examples illustrate the general strategies that can be applied to create molecular imaging agents with an MRI detectable response to biologically relevant parameters.

Chemical Spacer Design for Engineering the Relaxometric Properties of Core–Shell Structured Rare Earth Nanoparticles

The development of T1/T2 dual-modality contrast agents for magnetic resonance imaging (MRI) is beneficial for eliminating artifacts. However, T1 and T2 agents in the case of direct contact will interfere with each other, and the intrinsic mechanism remains unclear yet. Gadolinium(III) is widely used as T1 contrast agents, while dysprosium(III) exhibits the strongest magnetic moment among rare earth (RE) elements due to the spin–orbital coupling and can potentially be used as T2 contrast agents. The very similar chemical properties of RE elements allow integration of Gd(III) and Dy(III) within single nanocrystals for investigating the interactions between T1 and T2 components so as to achieve T1/T2 dual-modality contrast agents with optimized performance. Therefore, core–shell–shell structured NaDyF4@NaREF4@NaGdF4:Yb,Er nanocrystals were prepared via a seed-mediated growth approach and Gd(III), Er(III), and Y(III) were chosen to construct NaREF4 spacer layer for mediating the interactions between Dy(III) a...

Temperature-dependent structure of Tb-doped magnetite nanoparticles

High quality 5 nm cubic Tb-doped magnetite nanoparticles have been synthesized by a wet-chemical method to investigate tailoring of magnetic properties for imaging and biomedical applications. We show that the Tb is incorporated into the octahedral 3+ sites. High-angle annular dark-field microscopy shows that the dopant is well-distributed throughout the particle, and x-ray diffraction measurements show a small lattice parameter shift with the inclusion of a rare-earth dopant. Magnetization and x-ray magnetic circular dichroism data indicate that the Tb spins are unpolarized and weakly coupled to the iron spin lattice at room temperature, and begin to polarize and couple to the iron oxide lattice at temperatures below 50 K. Broadband ferromagnetic resonance measurements show no increase in magnetic damping at room temperature for Tb-doped nanoparticles relative to undoped nanoparticles, further confirming weak coupling between Fe and Tb spins at room temperature. The Gilbert damping constant, α, is remarkably low for the Tb-doped nanoparticles, with α = 0.024 ± 0.003. These nanoparticles, which have a large fixed moment, a large fluctuating moment and optically active rare-earth elements, are potential high-relaxivity T1 and T2 MRI agents with integrated optical signatures.

Tuning the relaxation rates of dual-mode T(1)/T(2) nanoparticle contrast agents: a study into the ideal system.

Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date.