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Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed in aggressive prostate cancer (PCa) and has been extensively studied as a PCa diagnostic imaging biomarker. Multiple imaging modalities have exploited PSMA as a biomarker including magnetic resonance (MR), Optical, and PET imaging. Of all the imaging MR imaging provides the most detailed information, concurrently providing anatomical, functional, and potentially molecular information. However, the lower sensitivity of MR requires development of molecular MR contrast agents that provides high signal-to-noise ratios. Herein, we report the first targeted and activatable Gd(III)-based MR contrast agents prostate cancer probe 1 and 2 (PCP-1 and -2). We successfully used PCP-2 to differentiate between PSMA+ and PSMA- prostate cancer cells with both in vitro fluorescence imaging and in vivo MR imaging. The in vivo MR imaging results were further supported by ex vivo fluorescence imaging studies, showcasing the unique bimodal feature of PCP-2. Furthermore, PCP-2 highlights a unique molecular MR probe design strategy that improved the sensitivity of traditional biomarker-targeted MR imaging, addressing a critical unmet need in molecular MR imaging field. This work represents the first example of a targeted and activatable MR contrast agent that can be systemically administered in vivo to highlight PSMA+ prostate tumors, paving the way for the clinical translation of MR PSMA imaging.

Purpose: To identify the MRI-hallmarks of liver metastatic neuroendocrine tumors (mNETs) with different localization of primary tumor.Material and methods: 75 liver mNET patients were enrolled in the study. The hepatic metastasis patients were divided into two groups: with pancreatic mNETs (n = 37) and with gastrointestinal tract (gut) mNETs (n = 38), including those of a stomach, small and large bowel, and appendicular primary. All patients underwent abdominal contrast-enhanced MRI with the measurement: the number and the maximum size of the lesions, the presence and size of avascular zones in the lesions, the presence of MRI signs of hemoglobin deg-radation products. In the region of interest, which corresponded to a rounded section in the solid portions of metastases, were measured quantitative indicators of signal intensity on T2-weighted images (WI), native and post-contrast T1-WI, the degree of accumulation of MR contrast agent (MRCA) and its washout, the value of apparent diffusion coefficient (ADC). A total of 171 lesions were assessed. The data were compared in the varying localization of the primary NET groups of patients.Results: The study demonstrated that the solid portion of the gut mNETs compared with that of the pancreatic mNETs are characterized by lower ADC-value (p = 0.0102, medians: pancreatic mNETs — 1036 × 10–3 mm2/s, gut mNETs — 846 × 10–3 mm2/s), less active accumulation of MRCA on the arterial (p = 0.0002, medians: pan-creatic mNETs — 1.48, gut mNETs — 1.24) and venous (p = 0.0026, median: pancreatic mNETs — 2.22, gut mNETs — 1.9) phases of contrast enhancement, longer washout of MRCA (p = 0.0057, median: pan-creas mNETs — 0.92, gut mNETs — 0.98). Based on regression-factor analysis, a model for determining the localization of primary tumors based on MRI signs of liver mNETs was created with an accuracy of 93.8 %.Conclusion: Gut mNETs compared with that of the pancreatic mNETs are characterized by lower ADC-value, less active accumulation and longer washout of MRCA. The data can be used to draw up a personalized examination plan of patient with liver mNETs from the unknown primary.

To assess the value of hepatospecific MR contrast agent uptake on hepatobiliary phase (HBP) images to detect marked activation of the β-catenin pathway in hepatocellular adenomas (HCAs). This multicentric retrospective IRB-approved study included all patients with a pathologically proven HCA who underwent gadobenate dimeglumine–enhanced liver MRI with HBP. Tumor signal intensity on HBP was first assessed visually, and lesions were classified into three distinct groups—hypointense, isointense, or hyperintense—according to the relative signal intensity to liver. Uptake was then quantified using the lesion-to-liver contrast enhancement ratio (LLCER). Finally, the accuracy of HBP analysis in depicting marked β-catenin activation in HCA was evaluated. A total of 124 HCAs were analyzed including 12 with marked β-catenin activation (HCA B+). Visual analysis classified 94/124 (76%), 12/124 (10%), and 18/124 (14%) HCAs as being hypointense, isointense, and hyperintense on HBP, respectively. Of these, 1/94 (1%), 3/12 (25%), and 8/18 (44%) were HCA B+, respectively (p

Ca(II) ions are critical for the proper function of neurons by contributing to synaptic signaling and regulating neuronal plasticity. Dysregulation of Ca(II) is associated with a number of pathologies that cause neurodegeneration; therefore the ability to monitor Ca(II) intracellularly is an important target for molecular imaging. Contrast-enhanced MR imaging is a promising modality for imaging changes in Ca(II) concentrations. However, the majority of Ca(II) responsive MR agents are limited to the extracellular space or hindered by poor cellular uptake. Here, we describe a new class of multimodal, bioresponsive Ca(II) magnetic resonance agents that are coupled to the NIR probe IR-783. This new design is based on previous generations of our Ca(II) MR agents but overcomes two significant challenges: (1) the presence of the NIR probe dramatically increases cellular uptake of the agent and (2) provides histological validation of the MR signal using NIR fluorescence imaging. IR-783 targets organic anion transporter polypeptides, and we demonstrate that the agents are not toxic in HT-22 or U-87 MG cells up to 20 μM. The cellular uptake of complex

Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA)4 based on the integrin α6-targeted RWY peptide that we previously identified to detect HCC. Contrast-enhanced MRI was carried out to evaluate the use of RWY-dL-(Gd-DOTA)4 to detect HCC lesions in subcutaneous and diethylnitrosamine (DEN)-induced HCC mouse models. Enhancement MR signals were observed in HCC-LM3 subcutaneous liver tumors in the first 5 min post-injection of RWY-dL-(Gd-DOTA)4 at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA)4 generated superior contrast enhancement for liver tumors in chemical-induced HCC mice. Importantly, RWY-dL-(Gd-DOTA)4 provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA)4 showed minimal gadolinium retention in normal tissues and organs at 48 h post-injection. These findings potentiate the use of RWY-dL-(Gd-DOTA)4 for the MRI of HCC to improve the diagnosis of HCC.

Contrast agents themselves and their use in medical imaging evolve very rapidly. Applications such as perfusion imaging make contrast agents critical elements of medical imaging. Tissue-specific contrast agents such as hepatocyte-specific MR contrast agent Gd-EOB-DTPA are smart molecules and will become commonplace in the near future. Artificial intelligence will make it possible to collect more detailed and sophisticated data using reduced amounts of contrast agents.

The emergence of activatable magnetic resonance (MR) contrast agents has prompted significant interest in the detection of functional markers of diseases, resulting in the creation of a plethora of nanoprobes capable of detecting these biomarkers. These markers are commonly dysregulated in several chronic diseases, specifically select cancers and inflammatory diseases. Recently, the development of redox-sensitive nanoparticle-based contrast agents has gained momentum given advances in medicine linking several inflammatory diseases to redox imbalance. Researchers have pinpointed redox dysregulation as an opportunity to use activatable MR contrast agents to detect and stage several diseases as well as monitor the treatment of inflammatory diseases or conditions. These new classes of agents represent an advancement in the field of MR imaging as they elicit a response to stimuli, creating contrast while providing evidence of biomarker changes and commensurate disease state. Most redox-sensitive nanoparticle-based contrast agents are sensitive to reductive glutathione or oxidative reactive oxygen species. In this review, we will explore recent investigations into redox-activatable, nanoparticle-based MR contrast agent candidates.

Molecular magnetic resonance (MR) imaging utilizes molecular probes to provide added biochemical or cellular information to what can already be achieved with anatomical and functional MR imaging. This review provides an overview of molecular MR and focuses specifically on molecular MR contrast agents that provide contrast by shortening the T(1) time. We describe the requirements for a successful molecular MR contrast agent and the challenges for clinical translation. The review highlights work from the last five years and places an emphasis on new contrast agents that have been validated in multiple preclinical models. Applications of molecular MR include imaging of inflammation, fibrosis, fibrogenesis, thromboembolic disease, and cancers. Molecular MR is positioned to move beyond detection of disease to the quantitative staging of disease and measurement of treatment response.

International audience; Early detection of thrombotic events remains a big medical challenge. Dextran-based submicronic particles bearing Gd(DOTA) groups and functionalized with fucoidan have been produced via a simple and green water-in-oil emulsification/co-crosslinking process. Their capacity to bind to human activated platelets was evidenced in vitro as well as their cytocompatibility with human endothelial cells. The presence of Gd(DOTA) moieties was confirmed by elemental analysis and total reflection X-ray fluorescence (TRXF) spectrometry. Detailed characterization of particles was performed in terms of size distribution, morphology, and relaxation rates. In particular, longitudinal and transversal proton relaxivities were respectively 1.7 and 5.0 times higher than those of DOTAREM. This study highlights their potential as an MRI diagnostic platform for atherothrombosis.

This chapter reviews the main features of the radiopharmaceuticals used for lymphoscintigraphy and the factors that affect their performances. Since radiopharmaceuticals for lymphoscintigraphy are injected interstitially, extracellular matrix composition and solute proprieties have significant influence on the capability of radiopharmaceuticals to move through the interstitium into the lymphatic vessels and until the lymph nodes. Weight, size, shape, and charges are the main factors affecting the final results of lymphoscintigraphy. The chapter also reviews alternative techniques for lymphatic mapping using nonradioactive agents, including iodinated contrast medium for CT lymphography, gadolinium-based agents for MR lymphography, and fluorescent agents for optical lymphatic mapping. Perspectives for the use of multimodal lymphatic mapping agents are also summarized. The chapter also describes instrumentations available for sentinel lymph node localization, summarizing the main features of handheld intraoperative gamma probe as well as of portable imaging devices.

Purpose To evaluate whether gadolinium penetrates human cerebrospinal fluid (CSF) after MR imaging (MRI) with a gadolinium-based contrast agent (GBCA). Materials and Methods For this retrospective study, the authors analyzed 60 CSF samples from 57 patients (median age, 50 years; range, 3-92 years) who underwent one contrast material-enhanced MRI examination with gadoterate meglumine within 60 days of CSF extraction between January and December 2016. CSF samples from patients who underwent MRI without contrast material administration (n = 22) or those who underwent contrast-enhanced MRI at least 1 year before extraction (n = 2) were analyzed and used as control samples. CSF measurements were performed with inductively coupled plasma mass spectrometry by monitoring the gadolinium 158 isotope. Statistical analyses were performed by using a preliminary Kruskal-Wallis test. Results Higher CSF gadolinium concentrations were detected within the first 8 hours after GBCA administration (mean concentration, 1152 ng/mL ± 734.6). Concentrations were lower between 8 and 48 hours (872 ng/mL ± 586). After 48 hours, gadolinium was almost completely cleared from CSF (121 ng/mL ± 296.3). All but two samples from the 24 control patients (median age, 60.5 years; range, 19-79 years) were negative for the presence of gadolinium. Those samples were from patients who had undergone GBCA-enhanced MRI examination more than a year before CSF extraction (0.1 and 0.2 ng/mL after 1 and 3 years, respectively). The concentrations in patients with chronic renal insufficiency (n = 3), cerebral toxoplasmosis (n = 1), and liver cirrhosis (n = 1) were higher than the mean concentrations. Conclusion Gadoterate meglumine can be detected in human CSF after intravenous administration.

Metal–organic framework (MOF) chemistry offers the unique possibility of bridging organic and inorganic chemistry to develop hybrid crystalline porous materials and opens the door to the synthesis of highly functional bulk- or nano-materials. A potential future field of application is their biomedical application as a theranostic agent or simply as a new contrast agent for magnetic resonance imaging (MRI). MRI is one of the most versatile imaging modalities in routine clinical examinations due to a wide range of usable contrast mechanisms. This in turn leads to a variety of conceivable nanoparticle designs as an MR contrast agent or theranostic. This review aims to integrate the state-of-the-art of MOF nanoparticles and their use in MRI. It gives an overview of the work done so far, focusing especially on the clinical applicability. Furthermore, it summarises the different factors for MR signal formation mechanisms important for the development of MR active nanoparticles and provides suggestions for a better comparison between different studies.

PURPOSE: To evaluate the feasibility and accuracy of simulated postcontrast T1-weighted brain MR images generated by using precontrast MR images in patients with brain glioma. MATERIALS AND METHODS: In this retrospective study, a three-dimensional deep convolutional neural network was developed to simulate T1-weighted postcontrast images from eight precontrast sequences in 400 patients (mean age, 57 years; 239 men; from 2015 to 2020), including 332 with glioblastoma and 68 with lower-grade gliomas. Performance was evaluated by using quantitative image similarity and error metrics and enhancing tumor overlap analysis. Performance was also assessed on a multicenter external dataset (n = 286 from the 2019 Multimodal Brain Tumor Segmentation Challenge; mean age, 60 years; ratio of men to women unknown) by using transfer learning. A subset of cases was reviewed by neuroradiologist readers to assess whether simulated images affected the ability to determine the tumor grade. RESULTS: Simulated whole-brain postcontrast images were both qualitatively and quantitatively similar to the real postcontrast images in terms of quantitative image similarity (structural similarity index of 0.84 ± 0.05), pixelwise error (symmetric mean absolute percent error of 3.65%), and enhancing tumor compartment overlap (Dice coefficient, 0.65 ± 0.25). Similar results were achieved with the external dataset (Dice coefficient, 0.62 ± 0.27). There was no difference in the ability of the neuroradiologist readers to determine the tumor grade in real versus simulated images (accuracy, 87.7% vs 90.6%; P = .87). CONCLUSION: The developed model was capable of producing simulated postcontrast T1-weighted MR images that were similar to real acquired images as determined by both quantitative analysis and radiologist assessment. Keywords: MR-Contrast Agent, MR-Imaging, CNS, Brain/Brain Stem, Contrast Agents-Intravenous, Neoplasms-Primary, Experimental Investigations, Technology Assessment, Supervised Learning, Transfer Learning, Convolutional Neural Network, Deep Learning Algorithms, Machine Learning Algorithms Supplemental material is available for this article. © RSNA, 2021

Benign biliary diseases include a large spectrum of congenital and acquired disorders, which have different prognosis and require different treatment management. The diagnosis may be challenging since some benign disorders may mimic malignancy. Imaging has an important role in the diagnostic process, for treatment decision and planning and in patient follow up. Magnetic resonance (MR) with magnetic resonance cholangiopancreatography (MRCP) sequences is the imaging modality of choice for biliary diseases and has demonstrated high diagnostic accuracy. Moreover, the use of a hepato-specific MR contrast agent allows morphological and functional assessment of the liver and the biliary tree improving the diagnostic performance.

Engineering multiple theranostic modalities into a single nanoscale entity holds great potential to rejuvenate cancer treatments; however, enabling the sophisticated spatiotemporal control of each component for maximizing theranostic improvement and minimizing side effects concurrently remains a challenge. Herein, an intelligent detachable "nanorocket" is developed to sequentially manipulate and optimize multitheranostic processes for magnetic resonance-assisted ultrasound-drug combined therapy (MR-HIFU-Drug). The "nanorocket" is constructed by integrating multicomponent (MnCO3, doxorubicin, silica) on the pH-sensitive CaCO3 nanoparticles step by step via cation exchange and controlled heterogeneous nucleation, in which doxorubicin is encapsulated in both carbonates and silica component. The "nanorocket" can initiate sequential detachment in the acidic tumor microenvironment. Specifically, carbonates decompose instantly, releasing Mn2+ as the MR contrast agent and leaving hollow silica nanostructure behind as the HIFU synergistic agent. Consequently, burst release of drug is also triggered, further triggering the degradation of silica, which in turn regulates the slow release of drug from the silica matrix. Thus, efficient tumor inhibition is achieved by enhanced HIFU ablation and biphase release of doxorubicin with a stepwise clearance of Mn and Si. This work establishes a system for the systematic spatiotemporal dispatch of diverse theranostic components for the balance of efficacy and safety in cancer theranostics.

Ultrasmallsuperparamagnetic iron oxide (USPIO) has been suggested to be a negative MR contrast agent to detect metastatic lymph nodes. Previously reported studies have evaluated the diagnostic performance of USPIO-enhanced MR lymph node imaging based on signal intensity. In this study, we investigate the specific performance of three different parametric approaches (normalized signal intensity, R2* and susceptibility) using 3D multi-echo gradient echo to quantify the USPIO particles in lymph nodes. Nine rabbits with VX2 tumor implants were scanned before and after USPIO injection. From 3D multi-echo GRE magnitude and phase data, we generated multi-echo combined T2*-weighted images, an R2* map, and a quantitative susceptibility map. Eighteen lymph nodes (nine reactive and nine metastatic) were evaluated and showed remarkable signal drops in the area of USPIO accumulation. On parametric analysis, the R2* difference before and after USPIO injection was significantly different (p

The practice of contrast-enhanced magnetic resonance angiography (CEMRA) has changed significantly in the span of a decade. Concerns regarding gadolinium (Gd)-associated nephrogenic systemic fibrosis in those with severely impaired renal function spurred developments in low-dose CEMRA and non-contrast MRA as well as efforts to seek alternative MR contrast agents. Originally developed for MR imaging use, ferumoxytol (an ultra-small superparamagnetic iron oxide nanoparticle), is currently approved by the US Food and Drug Administration for the treatment of iron deficiency anaemia in adults with renal disease. Since its clinical availability in 2009, there has been rising interest in the scientific and clinical use of ferumoxytol as an MR contrast agent. The unique physicochemical and pharmacokinetic properties of ferumoxytol, including its long intravascular half-life and high r1 relaxivity, support a spectrum of MRI applications beyond the scope of Gd-based contrast agents. Moreover, whereas Gd is not found in biological systems, iron is essential for normal metabolism, and nutritional iron deficiency poses major public health challenges worldwide. Once the carbohydrate shell of ferumoxytol is degraded, the elemental iron at its core is incorporated into the reticuloendothelial system. These considerations position ferumoxytol as a potential game changer in the field of CEMRA and MRI. In this paper, we aim to summarise our experience with the cardiovascular applications of ferumoxytol and provide a brief synopsis of ongoing investigations on ferumoxytol-enhanced MR applications.

Background A variety of magnetic resonance (MR) lymphographic agents have been proposed for mapping the lymph nodes draining the prostate. Purpose To investigate the feasibility of using ferumoxytol (an FDA-approved iron oxide agent) for lymph node mapping of the prostate on imaging (MRI) in a non-human primate (NHP) Macaque model. Material and Methods Four NHPs weighing 5–13 kg underwent injection of ferumoxytol after a needle was introduced transrectally under MRI guidance into the prostate using a commercially available intrarectal MRI biopsy guide. Ferumoxytol was administered at dosage in the range of 0.15–0.75 mg Fe/kg in a fixed injection volume of 0.2 mL. T1-weighted MRI was performed at 3 T starting immediately and extending at least 45 min post-injection. Two readers evaluated the images in consensus. The NHPs tolerated the ferumoxytol injections at all doses with no evident side effects. Results It was determined that the lowest dose of 0.15 mg Fe/kg produced the best outcome in terms of lymph node visualization and draining nodes were reliably visualized at this dose and volume. Conclusion Thus, MRI with intraprostatic injection of ferumoxytol may be considered an effective T1 contrast agent for prospective mapping of lymph nodes draining the prostate and, thus, for attempted sentinel lymph node identification in prostate cancer. Large clinical trials to determine safety and efficacy are needed.

In recent decades, extensive attention has been paid to developing anatomic and functional imaging contrast agents that could provide a wealth of complementary bioimaging information. Among them, dual-mode nanoprobes that combine anatomic magnetic resonance imaging (MRI) with functional fluorescent imaging have been mostly used for separated imaging. However, the lack of a machine for simultaneous dual-mode imaging greatly limits further clinical application. One effective strategy is to rationally design MRI contrast agents that own both anatomic and functional MR imaging capability on a single MRI machine, which is highly attractive but remains a great challenge. Herein, ultrasmall NaGdF4@PLL nanodots (NDs) were developed as a novel class of MR contrast agent, which offers a high longitude relaxivity (6.42 mM(-1) s(-1)) for T1-weighted MRI and an excellent sensitive chemical exchange saturation transfer (CEST) effect for pH mapping (at +3.7 ppm). Further in vivo animal experiments show the feasibility of NaGdF4@PLL NDs as contrast agents for efficient kidney and brain tumor diagnosis and pH mapping, which will undoubtedly enhance the diagnosis accuracy and is beneficial for disease precaution and prognosis. Different from other complex dual-mode nanoprobes, the as-constructed NaGdF4@PLL NDs enable both anatomic and functional imaging on a single MR machine, which is a simple and cost-effective new approach to realize dual-mode MR imaging and holds great potential for future clinical application.

Metal–organic frameworks (MOFs) have shown great potential in designing theranostic probes for cancer diagnosis and therapy due to their unique properties, including versatile structures and composition, tunable particle and pore size, enormous porosity, high surface area, and intrinsic biodegradability. In this study, we demonstrate novel MOF-based theranostic Fe3O4@UiO-66 core–shell composites constructed by in situ growth of a UiO-66 MOF shell on a Fe3O4 core for simultaneous drug delivery and magnetic resonance (MR) imaging. In the composites, the UiO-66 shell is devoted for encapsulating the drug, whereas the Fe3O4 core serves as a MR contrast agent. The Fe3O4@UiO-66 core–shell composites show good biocompatibility, high drug loading capacity, sustained drug release, and outstanding MR imaging capability, as well as effective chemotherapeutic efficacy, demonstrating the feasibility of designing theranostic Fe3O4@UiO-66 core–shell composites for cancer diagnosis and therapy.

Gadoxetate disodium is a widely used magnetic resonance (MR) contrast agent for liver MR imaging, and it provides both dynamic and hepatobiliary phase images. However, acquiring optimal arterial phase images at liver MR using gadoxetate disodium is more challenging than using conventional extracellular MR contrast agent because of the small volume administered, the gadolinium content of the agent, and the common occurrence of transient severe motion. In this article, we identify the challenges in obtaining high-quality arterial-phase images of gadoxetate disodium-enhanced liver MR imaging and present strategies for optimizing arterial-phase imaging based on the thorough review of recent research in this field.

The aim of this review is focusing on the most important safety issues in cardiovascular MRI (magnetic resonance imaging) which are categorized as: 1-safety items in patients who referred for stress cardiac MR studies. 2-Safety consideration that we must know when a patient with cardiovascular devices referred for any (cardiovascular or non-cardiovascular) MRI with focus on new protocols according to update or old devices. 3-Review safety issues in the use of MR contrast agent.

Purpose To determine whether multiple repeated administrations of gadolinium-based macrocyclic ionic MR contrast agent (MICA) are associated with intracranial gadolinium deposition and identify the predisposing factors for deposition in various clinical situations. Materials and methods In this institutional review board-approved retrospective study, 385 consecutive patients who underwent MICA-enhanced MR imaging were enrolled. The dentate nucleus-to-pons (DN/P) and globus pallidus-to-thalamus (GP/Th) signal intensity (SI) ratios on unenhanced T1-weighted images were recorded by 2 independent readers and averaged. The mean DN/P and GP/Th SI ratio difference between the last and the first examinations were tested using the one-sample t-test. Student’s t-test and stepwise regression analysis were used to identify the predisposing factors for deposition based on the number of administrations, time interval, hepatic and renal function, magnetic field strength, and chemo- or radiation therapy. Results The mean DN/P SI ratio difference was not different from zero (P = .697), even in patients with ≥20 administrations (n = 33). Only patients with abnormal renal function showed an increase in the mean DN/P SI ratio difference (P = .019). The mean DN/P SI ratio difference was not associated with any predisposing factors. However, the mean GP/Th SI ratio difference showed decrease (P < .001), which was associated with age (P = .007), number of administrations (P = .01) and number of radiation therapy sessions (P = .022) on multivariate analysis. Conclusion Multiple repeated administrations of MICA were not associated with increased T1 signal intensity in deep brain nuclei suggestive of Gd deposition in patients with normal renal function.

The hemodynamics of a hepatocellular nodule is the most important imaging para meter used to characterize various hepatocellular nodules in liver cirrhosis, because sequen- tial changes occur in the feeding vessels and hemodynamic status during hepatocarcinogenesis. Therefore, the imaging criteria for hepatocellular carcinoma (HCC) are also usually based on vas- cular findings, eg, early arterial uptake followed by washout in the portal venous and equilibrium phases. Contrast-enhanced ultrasonography, dynamic multidetector-row computed tomography (MDCT), and dynamic magnetic resonance (MR) imaging with gadopentetate dimeglumine (Gd- DTPA) are useful for detecting hypervascular HCC on the basis of vascular criteria but are not as useful for hypovascular HCC. Contrast-enhanced MR imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), a hepatocyte-specific MR contrast agent, is superior to dynamic MDCT and dynamic MR imaging with Gd-DTPA in detecting both hypervascular and hypovascular HCC. Moreover, Gd-EOB-DTPA-enhanced MR imaging can display each histologically differentiated HCC as hypointense relative to the liver parenchyma. 18 F-fluorodeoxyglucose positron emission tomography imaging might not be sui table for the screening and detection of HCC, given its lower diagnostic performance. However, this technique plays an important role in determining whether HCC has spread beyond the liver.

Red blood cells (RBCs) loaded with iron oxide nanoparticles have been proposed as biomimetic constructs with long half-life (ca. 20 days) in the blood compartment and potentially interesting properties (such as relaxivity) as intravascular contrast agents for magnetic resonance imaging. However, the encapsulation of nanoparticles into RBCs might affect their magnetic properties and relaxivity, which may be significantly different from the native suspension. Here, we present a relaxometric study of P904, a novel ultra small iron oxide nanoparticle developed by Guerbet, enclosed in human RBCs. We measured longitudinal (r1) and transverse (r2) relaxivity over a wide range of Larmor frequencies (0.01–300 MHz) in samples of P904-loaded RBCs, and in control samples with P904 nanoparticles dispersed in blood. Internalization of P904 into RBCs resulted in smaller r1, and in a very high r2/r1 ratio (232) at the highest field. Moreover, a shift of the Curie peak to high fields was observed in P904-loaded RBCs, possibly the result of nanoparticle size selection caused by the internalization process. High r2 relaxivity together with a high r2/r1 ratio and a very long blood half-life make P904-loaded RBCs a promising blood-pool negative contrast agent for MR diagnostic applications. Copyright © 2014 John Wiley & Sons, Ltd.

Purpose To evaluate a new formulation of manganese porphyrin as a potential gadolinium (Gd)-free extracellular magnetic resonance imaging (MRI) contrast agent for dynamic contrast-enhanced (DCE) MRI of tumors. Materials and Methods A previously reported new contrast agent, MnTCP, was evaluated in six female tumor-bearing nude rats. MRI was performed on a 3 T clinical scanner 3 to 4 weeks after inoculation of breast tumor cells in the mammary fat pads. Gd-DTPA was injected intravenously, followed by injection of MnTCP at least 2 hours later (both at 0.05 mmol/kg). T1 relaxation time measurements and DCE-MRI were performed. Results Enhancement and clearance patterns were visually similar between MnTCP and Gd-DTPA. However, relative R1 increases in all 11 tumors were larger for MnTCP over 60 minutes postcontrast, the difference being significant as late as 20 minutes (R1post/R1pre = 1.42 ± 0.15 for MnTCP vs. 1.20 ± 0.08 for Gd-DTPA, P

Here we report a simple Mn coordination complex with utility as a redox-sensitive MR probe. The HBET ligand stabilizes both the Mn(2+) and Mn(3+) oxidation states. In the presence of glutathione (GSH), low relaxivity Mn(III)-HBET is converted to high relaxivity Mn(II)-HBET with a 3-fold increase in relaxivity, and concomitant increase in MR signal. Alternately, hydrogen peroxide can convert Mn(II)-HBET to Mn(III)-HBET with a reduction in MR signal.

Peripheral lymphedema is a chronic progressive and debilitating disorder that results from abnormal lymphatic drainage. Advances in microsurgical techniques have led to the development of new treatment options for lymphedema that benefit from preoperative imaging to select the most appropriate surgical repair. Magnetic resonance (MR) lymphangiography is a noninvasive imaging modality capable of providing high-resolution 3D images of the lower extremities to define the severity and extent of lymphedema and depict individual lymphatic channels. The MR examination consists of 2 primary sequences. The first is a 3D heavily T2-weighted sequence to depict the severity and extent of the lymphedema. The second is a fat-suppressed 3D spoiled gradient-echo sequence performed after the intracutaneous injection of an extracellular gadolinium-based MR contrast agent. As venous enhancement almost always occurs, one of the interpretative challenges is differentiating enhancing lymphatic channels from superficial veins. MR techniques that can help with venous contamination include the addition of a contrast-enhanced MR venogram to the examination protocol, or the use of an iron-based blood-pool contrast agent to selectively suppress venous enhancement.

The rabbit lingual sentinel lymph node (SLN) could be long-term visualized by indirect lymphography using gadolinium-loaded polyethylenimine-entrapped gold nanoparticles (Gd-Au PENPs) as CT/MR dual-modal contrast agent.To investigate duration and intensity of rabbit lingual SLN enhancement using Gd-Au PENPs as a CT/MR dual-modal contrast agent.Twelve rabbits were randomly divided into indirect CT lymphography (CT-LG) and MR lymphography (MR-LG) groups. In each group, two rabbits received unilateral injection and four received bilateral injection of Gd-Au PENPs in the sub-mucosa of the tongue. Then the enhancement characteristics of SLN were investigated.The enhanced SLNs were observed in 100% in all rabbits by indirect CT-LG and MR-LG simultaneously at 1 min after injection. Then SLN enhancement was improved rapidly and the first peaks were observed at 25 min for CT-LG and 1 h for MR-LG, respectively, then SLN enhancement decreased gradually to a minimum at 2 h for CT-LG and 3 h for MR-LG. Afterwards, the enhancement intensity increased again and second peaks were observed at 24 h for both CT-LG and MR-LG. Hereafter, the intensity dropped slowly and weak enhancement was also observed at the 40th week for CT-LG and 31st day for MR-LG. Black-stained SLNs were visualized in 100% at autopsy in all rabbits.

Numerous recent articles have reported brain gadolinium deposition when using linear but not macrocyclic gadolinium-based contrast agents (GBCAs). To determine the current landscape of gadolinium use among pediatric institutions and the knowledge base of radiologists and referring providers with regard to GBCAs and brain gadolinium deposition. We e-mailed voluntary closed surveys to 5,390 physicians in various pediatric professional societies between January 2016 and March 2016. We used chi-square and Fisher exact tests to compare response distributions among specialties. We found that 80% of surveyed pediatric hospitals use macrocyclic contrast agents. In the last year, 58% switched their agent, most commonly to gadoterate meglumine, with the most common reason being brain gadolinium deposition. Furthermore, surveys indicated that 23% of hospitals are considering switching, and, of these, 83% would switch to gadoterate meglumine; the most common reasons were brain gadolinium deposition and safety. Radiologists were more aware of brain gadolinium deposition than non-radiologist physicians (87% vs. 26%; P

Magnetic resonance (MR) contrast agents have been widely used over the last 3 decades in routine clinical practice. Paul Lauterbur recognized the presence of these contrast agents, which act as paramagnetic catalysts that accelerate the T1 relaxation process. The first MR contrast agent to be approved for clinical use was in 1988, and since then, it is estimated that 200 million doses have been administered worldwide. These contrast agents have diverse clinical as well as research applications, involving almost all the body organs. This review will cover some existing as well as many new applications that have emerged over the last few decades. MR imaging now has the potential of being used to monitor enzymatic activity, gene expression, metal ion homeostasis, and cell death in vivo. In future, newer contrast agents will develop and become commercially available, expanding the current clinical applications of MR contrast media.

Gadoxetate disodium (Gd-EOB-DTPA) is a linear, non-ionic paramagnetic MR contrast agent with combined extracellular and hepatobiliary properties commonly used for several liver indications. Although gadoxetate disodium is commonly used for detection and characterization of focal lesions, a spectrum of diffuse disease processes can affect the hepatobiliary phase of imaging (i.e., when contrast accumulates within the hepatocytes). Non-focal signal abnormalities during the hepatobiliary phase can be seen with multiple disease processes such as deposition disorders, infiltrating tumors, vascular diseases, and post-treatment changes. The purpose of this paper is to review the different processes which result in non-focal signal alteration during the hepatobiliary phase and to describe imaging patterns that may order a differential diagnosis and facilitate patient management.