Magnetic Resonance Imaging Probes Research Articles

Activatable 19F MRI nanoparticle probes for the detection of reducing environments.

(19)F magnetic resonance imaging (MRI) probes that can detect biological phenomena such as cell dynamics, ion concentrations, and enzymatic activity have attracted significant attention. Although perfluorocarbon (PFC) encapsulated nanoparticles are of interest in molecular imaging owing to their high sensitivity, activatable PFC nanoparticles have not been developed. In this study, we showed for the first time that the paramagnetic relaxation enhancement (PRE) effect can efficiently decrease the (19)F NMR/MRI signals of PFCs in silica nanoparticles. On the basis of the PRE effect, we developed a reduction-responsive PFC-encapsulated nanoparticle probe, FLAME-SS-Gd(3+) (FSG). This is the first example of an activatable PFC-encapsulated nanoparticle that can be used for in vivo imaging. Calculations revealed that the ratio of fluorine atoms to Gd(3+) complexes per nanoparticle was more than approximately 5.0×10(2), resulting in the high signal augmentation.

NaGdF4 Nanoparticles Coated with Functionalised Ethylenediaminetetraacetic Acid as Versatile Probes for Dual Optical and Magnetic Resonance Imaging.

NaGdF4 nanoparticles (NPs) coated with organic ligands are known to provide efficient "positive" contrast in magnetic resonance imaging (MRI). Strongly chelating ligands, such as ethylenediaminetetraacetic acid (EDTA) and d,l-1,2-diaminopropionic-N,N,N',N'-tetraacetic acid (EDTACOOH), which is an EDTA derivative with a functionalisable carboxylic group, were used to coat NaGdF4 . The carboxylic group was used to insert a polyethylene glycol (PEG) functionality (to give EDTAPEG) to favour better suspension and stealth and/or a fluorescent dye to obtain dual optical/MRI probes. The relaxometric behaviour of these NPs was investigated as a function of the magnetic field strength, and a significant contribution from water molecules hydrogen bonded to the organic coating was evidenced. The chemical stability of the NPs was evaluated both in a physiological medium and in the presence of a strong chelating agent. Finally, the dye-functionalised NPs were tested in ovarian carcinoma cells as dual optical and MRI probes.

Novel 19F Activatable Probe for the Detection of Matrix Metalloprotease-2 Activity by MRI/MRS

Matrix metalloproteases (MMPs) have been found to be highly expressed in a variety of malignant tumor tissues. Noninvasive visualization of MMP activity may play an important role in the diagnosis of MMP associated diseases. Here we report the design and synthesis of a set of fluorine-19 dendron-based magnetic resonance imaging (MRI) probes for real-time imaging of MMP-2 activity. The probes have the following features: (a) symmetrical fluorine atoms; (b) the number of fluorine atoms can be increased through facile chemical modification; (c) readily accessible peptide sequence as the MMP-2 substrate; (d) activatable 19F signal (off/on mode) via paramagnetic metal ion incorporation. Following optimization for water solubility, one of the probes was selected to evaluate MMP-2 activity by 19F magnetic resonance spectroscopy (MRS). Our results showed that the fluorine signal increased by 8.5-fold in the presence of MMP-2. The specific cleavage site was verified by mass spectrometry. The selected probe was further applied to detect secreted MMP-2 activity of living SCC7 squamous cell carcinoma cells. The fluorine signal was increased by 4.8-fold by MRS analysis after 24 h incubation with SCC7 cells. This type of fluorine probe can be applied to evaluate other enzyme activities by simply tuning the substrate structures. This symmetrical fluorine dendron-based probe design extends the scope of the existing 19F MRI agents and provides a simple but robust method for real-time 19F MRI application.

Characterization of a lanthanide complex encapsulated with MRI contrast agents into liposomes for biosensor imaging of redundant deviation in shifts (BIRDS).

Purposely designed magnetic resonance imaging (MRI) probes encapsulated in liposomes, which alter contrast by their paramagnetic effect on longitudinal (T₁) and transverse (T₂) relaxation times of tissue water, hold promise for molecular imaging. However, a challenge with liposomal MRI probes that are solely dependent on enhancement of water relaxation is lack of specific molecular readouts, especially in strong paramagnetic environments, thereby reducing the potential for monitoring disease treatment (e.g., cancer) beyond the generated MRI contrast. Previously, it has been shown that molecular imaging with magnetic resonance is also possible by detecting the signal of non-exchangeable protons emanating from paramagnetic lanthanide complexes themselves [e.g., TmDOTP⁵⁻, which is a Tm³⁺ -containing biosensor based on a macrocyclic chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate), DOTP⁵⁻] with a method called biosensor imaging of redundant deviation in shifts (BIRDS). Here, we show that BIRDS is useful for molecular imaging with probes like TmDOTP⁵⁻ even when they are encapsulated inside liposomes with ultrastrong T₁and T₂contrast agents (e.g., Magnevist and Molday ION, respectively). We demonstrate that molecular readouts such as pH and temperature determined from probes like TmDOTP⁵⁻ are resilient, because the sensitivity of the chemical shifts to the probe's environment is not compromised by the presence of other paramagnetic agents contained within the same nanocarrier milieu. Because high liposomal encapsulation efficiency allows for robust MRI contrast and signal amplification for BIRDS, nanoengineered liposomal probes containing both monomers, TmDOTP⁵⁻ and paramagnetic contrast agents, could allow high spatial resolution imaging of disease diagnosis (with MRI) and status monitoring (with BIRDS).

Whole-body DWI in patients with lymphoma: imaging findings, pitfalls, and limitations

Whole body (WB) imaging plays an essential role in the management of lymphoma patients, including defining the full extent of the disease at baseline, allowing for an accurate staging and therefore an adapted treatment strategy, assessing treatment response and detecting relapse. Contrast-enhanced computed tomography (CT) has long been the imaging technique most commonly used for staging and follow up of malignant lymphoma, using International Working Group (IWG) criteria [1]. However, CT lacks functional and metabolic information, compromising identification of disease in non-enlarged lymph nodes or other organs, as well as sufficient contrast in certain organs as for example the spleen or bone marrow. In 2007, IWG response criteria were revised, incorporating Positron Emission Tomography (PET) with 18-fluorodeoxyglucose (FDG) information [2], thus combining metabolic information and anatomical data of the CT resulting in a higher accuracy than the both imaging modalities taken separately [3]. Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) probes noninvasively the random microscopic motion of water molecules in the body, reflecting cellularity and cell membrane integrity. Because of their high cellularity and high nuclear-to-cytoplasm ratio, lymphomas have a lower apparent diffusion coefficient (ADC) than other tumors [4]. WB-DW-MRI allows both anatomical information, as well as functional and quantitative evaluation of tumor sites, thanks to the extraction of the apparent diffusion coefficient (ADC). At staging, lymphoma lesions have low ADC value except necrotic areas. Recent studies comparing whole-body DWI to PET-CT have demonstrated the potential role of whole-body DWI in routine lymphoma patient care but included only a small number of patients. Using the DWIBS technique (diffusion weighted imaging with background body signal suppression), Abdulqadhr et al. compared whole-body DWI and PET/CT at staging with an agreement in the Ann Arbor stage for 90.3% of patients [5]. Based on ADC analysis, Lin et al showed an agreement at baseline in 93% of patients [4]. Response assessment is necessary during therapy to readapt treatment strategy if necessary, and to document a complete remission at the end of treatment. After treatment, an increase in ADC value of residual masses has been demonstrated [6]. Recent technical breakthroughs in MRI technology such as echo-planar imaging (EPI), high gradient amplitudes, combined phased-array surface coils covering the patient, and parallel imaging, have drastically improved patient comfort and acceptance for whole body MRI [7,8], making this technique feasible in clinical routine, illustrating the need for radiologists to get familiar with this technique. As a result, WB-DW-MRI with ADC mapping has become a promising tool for lymphoma staging and re-staging, and response assessment. Based on our 4-years experience with WB-DW-MRI applied in Hodgkin and diffuse large B-cell lymphoma patients together with 18FDG-PET/CT, our objective is to offer radiologists the information required to optimize acquisition whole body DWI parameters on both 1.5 and 3T MR systems. We will expose the spectrum of imaging findings and discuss the pitfalls, limitations, and potential challenges of WB-DW-MRI in caring for lymphoma patients.

Gadolinium-based contrast agents targeted to amyloid aggregates for the early diagnosis of Alzheimer's disease by MRI.

While important efforts were made in the development of positron emission tomography (PET) tracers for the in vivo molecular diagnosis of Alzheimer's disease, very few investigations to develop magnetic resonance imaging (MRI) probes were performed. Here, a new generation of Gd(III)-based contrast agents (CAs) is proposed to detect the amyloid β-protein (Aβ) aggregates by MRI, one of the earliest biological hallmarks of the pathology. A building block strategy was used to synthesize a library of 16 CAs to investigate structure-activity relationships (SARs) on physicochemical properties and binding affinity for the Aβ aggregates. Three types of blocks were used to modulate the CA structures: (i) the Gd(III) chelates (Gd(III)-DOTA and Gd(III)-PCTA), (ii) the biovectors (2-arylbenzothiazole, 2-arylbenzoxazole and stilbene derivatives) and (iii) the linkers (neutrals, positives and negatives with several lengths). These investigations revealed unexpected SARs and a difficulty of these probes to cross the blood-brain barrier (BBB). General insights for the development of Gd(III)-based CAs to detect the Aβ aggregates are described.

ICAM-1 as a molecular target for triple negative breast cancer.

Triple negative breast cancers (TNBCs) have a high mortality rate owing to aggressive proliferation and metastasis and a lack of effective therapeutic options. Herein, we describe the overexpression of intercellular adhesion molecule-1 (ICAM-1) in human TNBC cell lines and tissues, and demonstrate that ICAM-1 is a potential molecular target and biomarker for TNBC therapy and diagnosis. We synthesized ICAM-1 antibody-conjugated iron oxide nanoparticles (ICAM-IONPs) as a magnetic resonance imaging (MRI) probe to evaluate tumor targeting. Quantitative analysis of ICAM-1 surface expression predicted the targeting capability of ICAM-IONPs to TNBC cells. MRI of the TNBC xenograft tumor after systemic administration of ICAM-IONPs, coupled with iron quantification and histology, demonstrated a significant and sustained MRI contrast enhancement and probe accumulation in tumors with ICAM-1 overexpression relative to control. Identification of ICAM-1 as a TNBC target and biomarker may lead to the development of a new strategy and platform for addressing a critical gap in TNBC patient care.

Structure-redox-relaxivity relationships for redox responsive manganese-based magnetic resonance imaging probes.

A library of 10 Mn-containing complexes capable of switching reversibly between the Mn(II) and Mn(III) oxidation states was prepared and evaluated for potential usage as MRI reporters of tissue redox activity. We synthesized N-(2-hydroxybenzyl)-N,N′,N′-ethylenediaminetriacetic acid (HBET) and N-(2-hydroxybenzyl-N,N′,N′-trans-1,2-cyclohexylenediaminetriacetic acid (CyHBET) ligands functionalized (−H, −OMe, −NO2) at the 5-position of the aromatic ring. The Mn(II) complexes of all ligands and the Mn(III) complexes of the 5-H and 5-NO2 functionalized ligands were synthesized and isolated, but the Mn(III) complexes with the 5-OMe functionalized ligands were unstable. 1H relaxivity of the 10 isolable complexes was measured at pH 7.4 and 37 °C, 1.4 T. Thermodynamic stability, pH-dependent complex speciation, hydration state, water exchange kinetics of the Mn(II) complexes, and pseudo-first order reduction kinetics of the Mn(III) complexes were studied using a combination of pH-potentiometry, UV–vis spectroscopy, and 1H and 17O NMR measurements. The effects of ligand structural and electronic modifications on the Mn(II/III) redox couple were studied by cyclic voltammetry. The Mn(II) complexes are potent relaxation agents as compared to the corresponding Mn(III) species with [MnII(CyHBET)(H2O)]2– exhibiting a 7.5-fold higher relaxivity (3.3 mM–1 s–1) than the oxidized form (0.4 mM–1 s–1). At pH 7.4, Mn(II) exists as a mixture of fully deprotonated (ML) and monoprotonated (HML) complexes and Mn(II) complex stability decreases as the ligands become more electron-releasing (pMn for 10 μM [MnII(CyHBET–R′)(H2O)]2– decreases from 7.6 to 6.2 as R′ goes from −NO2 to −OMe, respectively). HML speciation increases as the electron-releasing nature of the phenolato-O donor increases. The presence of a water coligand is maintained upon conversion from HML to ML, but the water exchange rate of ML is faster by up to 2 orders of magnitude (kex310 for H[MnII(CyHBET)(H2O)]− and [MnII(CyHBET)(H2O)]2– are 1.2 × 108 and 1.0 × 1010 s–1, respectively). The Mn(II/III) redox potential can be tuned over a range of 0.30 V (E1/2 = 0.27–0.57 V) through electronic modifications to the 5-substituent of the aromatic ligand component. However, care must be taken in tuning the ligand electronics to avoid Mn(III)–ligand autoredox. Taken together, these results serve to establish criteria for optimizing Mn(III) versus Mn(II) relaxivity differentials, complex stability, and Mn(II/III) redox potential.

In vivo targeted peripheral nerve imaging with a nerve-specific nanoscale magnetic resonance probe

Neuroimaging plays a pivotal role in clinical practice. Currently, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography (PET) are applied in the clinical setting as neuroimaging modalities. There is no optimal imaging modality for clinical peripheral nerve imaging even though fluorescence/bioluminescence imaging has been used for preclinical studies on the nervous system. Some studies have shown that molecular and cellular MRI (MCMRI) can be used to visualize and image the cellular and molecular level of the nervous system. Other studies revealed that there are different pathological/molecular changes in the proximal and distal sites after peripheral nerve injury (PNI). Therefore, we hypothesized that in vivo peripheral nerve targets can be imaged using MCMRI with specific MRI probes. Specific probes should have higher penetrability for the blood-nerve barrier (BNB) in vivo. Here, a functional nanometre MRI probe that is based on nerve-specific proteins as targets, specifically, using a molecular antibody (mAb) fragment conjugated to iron nanoparticles as an MRI probe, was constructed for further study. The MRI probe allows for imaging the peripheral nerve targets in vivo.

In vivo magnetic resonance imaging of tumor protease activity.

Increased expression of cathepsins has diagnostic as well as prognostic value in several types of cancer. Here, we demonstrate a novel magnetic resonance imaging (MRI) method, which uses poly-L-glutamate (PLG) as an MRI probe to map cathepsin expression in vivo, in a rat brain tumor model. This noninvasive, high-resolution and non-radioactive method exploits the differences in the CEST signals of PLG in the native form and cathepsin mediated cleaved form. The method was validated in phantoms with known physiological concentrations, in tumor cells and in an animal model of brain tumor along with immunohistochemical analysis. Potential applications in tumor diagnosis and evaluation of therapeutic response are outlined.

Progesterone-targeted magnetic resonance imaging probes.

Determination of progesterone receptor (PR) status in hormone-dependent diseases is essential in ascertaining disease prognosis and monitoring treatment response. The development of a noninvasive means of monitoring these processes would have significant impact on early detection, cost, repeated measurements, and personalized treatment options. Magnetic resonance imaging (MRI) is widely recognized as a technique that can produce longitudinal studies, and PR-targeted MR probes may address a clinical problem by providing contrast enhancement that reports on PR status without biopsy. Commercially available MR contrast agents are typically delivered via intravenous injection, whereas steroids are administered subcutaneously. Whether the route of delivery is important for tissue accumulation of steroid-modified MRI contrast agents to PR-rich tissues is not known. To address this question, modification of the chemistry linking progesterone with the gadolinium chelate led to MR probes with increased water solubility and lower cellular toxicity and enabled administration through the blood. This attribute came at a cost through lower affinity for PR and decreased ability to cross the cell membrane, and ultimately it did not improve delivery of the PR-targeted MR probe to PR-rich tissues or tumors in vivo. Overall, these studies are important, as they demonstrate that targeted contrast agents require optimization of delivery and receptor binding of the steroid and the gadolinium chelate for optimal translation in vivo.

Redox-triggered self-assembly of gadolinium-based MRI probes for sensing reducing environment.

Controlled self-assembly of small molecule gadolinium (Gd) complexes into nanoparticles (GdNPs) is emerging as an effective approach to design activatable magnetic resonance imaging (MRI) probes and amplify the r1 relaxivity. Herein, we employ a reduction-controlled macrocyclization reaction and self-assembly to develop a redox activated Gd-based MRI probe for sensing a reducing environment. Upon disulfide reduction at physiological conditions, an acyclic contrast agent 1 containing dual Gd-chelates undergoes intramolecular macrocyclization to form rigid and hydrophobic macrocycles, which subsequently self-assemble into GdNPs, resulting in a ∼60% increase in r1 relaxivity at 0.5 T. Probe 1 has high r1 relaxivity (up to 34.2 mM–1 s–1 per molecule at 0.5 T) upon activation, and also shows a high sensitivity and specificity for MR detection of thiol-containing biomolecules.

Gd-Al co-doped mesoporous silica nanoparticles loaded with Ru(bpy)₃²⁺ as a dual-modality probe for fluorescence and magnetic resonance imaging.

Mesoporous silica nanoparticles (MSNs) were co-doped with Gd(3+) and Al(3+) and then loaded with Ru(bpy)3(2+) by ion-exchange to prepare Ru/Gd-Al@MSNs. The as-prepared Ru/Gd-Al@MSNs were applied as contrast agents for in vivo fluorescence and magnetic resonance (MR) dual-modality imaging with a mouse as a model. The effects of Al(3+) and MSNs on longitudinal relaxivity (r1) and fluorescence were investigated using a series of Gd-containing silica nanoparticles, including Gd@MSNs, Gd-Al@MSNs, and Ru/Gd-Al@nonporous silica nanoparticles. Co-doping with Al(3+) improved the loading of Gd(3+); the mesoporous structure improved the water exchange rate. The improvement enhanced the MR imaging efficiency of the Ru/Gd-Al@MSN probe. A higher relaxivity (19.2 mM(-1) s(-1)) was observed compared to that from a commercial contrast agent, Gd-diethylene triamine pentaacetic acid (Gd-DTPA). Importantly, the mesoporous structure provided a large specific surface area for the loading of Ru(bpy)3(2+) by a simple ion-exchange procedure. Intense red fluorescence was observed from Ru/Gd-Al@MSN probes. The versatility of Ru/Gd-Al@MSNs for dual-modality imaging was demonstrated using in vivo fluorescence imaging and T1-weighted MR imaging with a mouse model. The nanoparticles are biocompatible and may be attractive for clinical applications.

Zn2+‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

AbstractThe gadolinium(III) complexes GdL1 and GdL2 were designed as Zn2+‐responsive bimodal magnetic resonance imaging (MRI) and fluorescence imaging probes. Upon binding to Zn2+ ions, GdL1 exhibits a bidentate or tridentate mode to form heterodinuclear GdL1Zn or heterotrinuclear (GdL1)2Zn, whereas GdL2 binds to the Zn2+ ion only in a bidentate mode to form (GdL2)2Zn. The gadolinium(III) complexes derived from both H3L1 and H3L2 exhibit remarkable interactions with human serum albumin (HSA) at both site I and site II, which result in significant enhancements of the relaxivity and remarkable improvements of T1‐weighted imaging contrast. In the presence of HSA, both the relaxivity (r1) and fluorescence exhibit 300 % enhancement with a clear blueshift of the fluorescence for GdL1Zn, which is ascribed to direct binding to HSA through the formation of a Zn–HSA coordination bond. In contrast, the presence of HSA induces smaller relaxivity increases for GdL1 (155 %), (GdL1)2Zn (183 %), GdL2 (192 %), and (GdL2)2Zn (181 %); these increases are ascribed to weaker hydrophobic interactions or stereospecificity with HSA. The contrast of T1‐weighted phantom MR images of these gadolinium(III) complexes in human serum (HS) is much improved relative to that in 4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid (HEPES) buffer solutions.

Molecular magnetic resonance probe targeting VEGF165: preparation and in vitro and in vivo evaluation.

A new method for imaging the tumor human vascular endothelial growth factor 165 (VEGF 165) is presented. A magnetic resonance imaging (MRI) probe was prepared by crosslinking ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to the aptamer for tumor vascular endothelial growth factor 165 (VEGF165-aptamer). The molecular probe was evaluated for its in vitro and in vivo activities toward VEGF165. Enzyme-linked immunosorbent assay showed that the VEGF165-aptamer-USPIO nanoparticles conjugate specifically binds to VEGF165 in vitro. A cell proliferation test showed that VEGF165-aptamer-USPIO seems to block the proliferation of human umbilical vein endothelial cells induced by free VEGF165, suggesting that VEGF165 is an effective target of this molecular probe. In xenograft mice carrying liver cancer that expresses VEGF165, T2-weighted imaging of the tumor displayed marked negative enhancement 3 h after the intravenous administration of VEGF165-aptamer-USPIO. The enhancement disappeared 6 h after administration of the probe. These results suggest the targeted imaging effect of VEGF165-aptamer-USPIO probe in vivo for VEGF165-expressing tumors. This is the first report of a targeted MRI molecular probe based on USPIO and VEGF165-aptamer.

Gadolinium Complexes Functionalized Persistent Luminescent Nanoparticles as a Multimodal Probe for Near-Infrared Luminescence and Magnetic Resonance Imaging in Vivo

The development of multimodal nanoprobes that combined properties of near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) within a single probe is very important for medical diagnosis. The NIR-emitting persistent luminescent nanoparticles (PLNPs) are ideal for optical imaging owing to no need for in situ excitation, the absence of background noise, and deep tissue penetration. However, no PLNP based multimodal nanoprobes have been reported so far. Here, we report a novel multimodal nanoprobe based on the gadolinium complexes functionalized PLNPs (Gd(III)-PLNPs) for in vivo MRI and NIR luminescence imaging. The Gd(III)-PLNPs not only exhibit a relatively higher longitudinal relaxivity over the commercial Gd(III)-diethylenetriamine pentaacetic acid complexes but also keep the superlong persistent luminescence. The prepared Gd(III)-PLNPs multimodal nanoprobe offers great potential for MRI/optical imaging in vivo.

Parameters estimation from the diffusion MRI signal using a macroscopic model

Diffusion magnetic resonance imaging (dMRI) probes the diffusion characteristics of a sample via the application of magnetic field gradient pulses. The dMRI signal from a heterogeneous sample includes the water proton magnetization from all spatial positions in a voxel. If the voxel consists of different diffusion compartments with weak exchange, while the duration of the diffusion-encoding gradient pulses is short compared to the diffusion time (the narrow pulse approximation), the dMRI signal can be approximated by the Karger model. A new macroscopic ODE model for the dMRI signal was recently derived mathematically from the microscopic multiple compartments Bloch-Torrey partial differential equation (PDE) without the narrow pulse restriction. We illustrate by numerical simulations that this ODE model accurately approximates the dMRI signal in a domain containing spherical cells of various sizes, and show preliminary results on solving the inverse problem to estimate the cellular volume fraction and surface area.

Imaging of the Vulnerable Carotid Plaque: Biological Targeting of Inflammation in Atherosclerosis using Iron Oxide Particles and MRI

Identification of those patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and the propensity of atherosclerotic lesions to cause clinical sequelae. There is currently no clinical imaging technique available to assess the degree of inflammation associated with plaques. This study aims at visualizing and characterizing atherosclerosis using antibody-conjugated superparamagnetic iron oxide (SPIO) particles as an MRI probe to assess inflammation in human atherosclerotic plaques. Atherosclerotic plaques were collected from 20 consecutive patients (n=10 from symptomatic patients, n=10 from asymptomatic patients) undergoing carotid endarterectomy (CEA) for extracranial high-grade internal carotid artery (ICA) stenosis (>70% luminal narrowing). Inflammatory markers on human atherosclerotic plaques were detected and characterized by ex vivo magnetic resonance imaging (MRI) using anti-VCAM-1 antibody and anti-E-selectin antibody-conjugated SPIO with confirmatory immunohistochemistry. Inflammation associated with human ex vivo atherosclerotic plaques could be imaged using dual antibody-conjugated SPIO by MRI. Symptomatic plaques could be distinguished from asymptomatic ones by the degree of inflammation, and the MR contrast effect was significantly correlated with the degree of plaque inflammation (r=.64, p<.001). The asymptomatic plaque population exhibited heterogeneity in terms of inflammation. The dual-targeted SPIO-induced MR signal not only tracked closely with endothelial activation (i.e. endothelial expression of VCAM-1 and E-selectin), but also reflected the macrophage burden within plaque lesions, offering a potential imaging tool for quantitative MRI of inflammatory activity in atherosclerosis. These functional molecular MRI probes constitute a novel imaging tool for ex vivo characterization of atherosclerosis at a molecular level. Further development and translation into the clinical arena will facilitate more accurate risk stratification in carotid artery disease in the future.

Targeted In Vivo Imaging of Microscopic Tumors with Ferritin‐based Nanoprobes Across Biological Barriers

The avascular microscopic breast and brain tumors (<1-2 mm diameter) can be noninvasively detected by designing human heavy-chain ferritin (HFn)-based nanoparticles as molecular probes for near-infrared fluorescence and magnetic resonance imaging. The intravenously injected HFn-based nano-particles (Cy5.5-HFn and M-HFn) can cross the endothelium, epithelium, and blood-brain barriers and be internalized into tumor cells.

Cancer Diagnosis and Treatment Guidance: Role of MRI and MRI Probes in the Era of Molecular Imaging

MRI plays a unique role in cancer treatment from three perspectives: Firstly, MRI has superior soft tissue resolution, which makes it indispensible in delineating, staging and monitoring treatment efficacy for certain tumors; Secondly, several techniques which use real-time MRI to map such physiological parameters as temperature, water content or pH have been developed to guide course of anticancer therapies; Thirdly, different targeted probes or hybrid nanoparticles are being developed to facilitate the diagnosis and treatment of tumor under guidance of MRI. In this review article, we will briefly review the first two aspects of MRI guided cancer therapy, followed by a more comprehensive review on the third part focusing on targeted MR imaging probes for personalized medicine.