MR Contrast Agents Research Articles

Active biloma and the use of hepatobiliary specific MR contrast agent.

We present a case of a woman in her 70s, with right upper quadrant pain and jaundice, who underwent laparoscopic cholecystectomy 14 days, previously. The ultrasound and computer tomography scan revealed a fluid lesion in the gallbladder fossa with intrahepatic extension. At this point a wide differential diagnosis was possible. In order to reach a definitive diagnosis, a magnetic resonance imaging exam with a biliary excretion contrast agent - gadoxetate disodium (hepatobiliary specific paramagnetic gadolinium-based contrast) was obtained, which showed a lesion with delayed, but important contrast enhancement, 4 hours after contrast injection, demonstrating leaking of bile reaching the final diagnosis of biloma. Our patient was successfully treated with ultrasound-guided percutaneous drainage.

Monitoring Blood-Brain Barrier Opening in Rats with a Preclinical Focused Ultrasound System.

The brain has a highly selective semipermeable blood barrier, termed the blood-brain barrier (BBB), which prevents the delivery of therapeutic macromolecular agents to the brain. The integration of MR-guided low-intensity pulsed focused ultrasound (FUS) with microbubble pre-injection is a promising technique for non-invasive and non-toxic BBB modulation. MRI can offer superior soft-tissue contrast and various quantitative assessments, such as vascular permeability, perfusion, and the spatial-temporal distribution of MRI contrast agents. Notably, contrast-enhanced MRI techniques with gadolinium-based MR contrast agents have been shown to be the gold standard for detecting BBB openings. This study outlines a comprehensive methodology involving MRI protocols and animal procedures for monitoring BBB opening in a rat model. The rat model provides the added benefit of jugular vein catheter utilization, which facilitates rapid medication administration. A stereotactic-guided preclinical FUS transducer facilitates the refinement and streamlining of animal procedures and MRI protocols. The resulting methods are characterized by reproducibility and simplicity, eliminating the need for specialized surgical expertise. This research endeavors to contribute to the optimization of preclinical procedures with rat models and encourage further investigation into the modulation of the BBB to enhance therapeutic interventions in neurological disorders.

Bio-responsive polymers for dual 31P/19F-magnetic resonance to detect reactive oxygen species in vivo

Biocompatible metal-free agents are emerging as a promising alternative to commercial magnetic resonance (MR) contrast agents, but there is an additional need for novel probes with enhanced responsiveness in preclinical MR testing to effectively target diverse pathological conditions. To address this, we develop hydrophilic phospho-/fluoropolymers as dual MR probes. Incorporating thiophosphoester groups (P = S) into the polymer structure produces a distinct chemical shift (~59 ppm) in phosphorus MR (31P-MR), reducing biological signals interference. Reactive oxygen species (ROS) oxidize the P = S groups, causing a detectable shift in 31P-MR, enabling precise localization of ROS, abundant in inflammation and cancer. To enhance this capability, bioinert trifluoromethyl groups (CF3) are added, creating a “hotspot” for fluorine MR (19F-MR), aiding in vivo localization. Both in vitro and in vivo testing demonstrate the probe’s high specificity and responsiveness, underscoring its potential as a sensitive ROS sensor and dual MR-traceable tool in cancer research.

Construction of CXCR4 Receptor-Targeted CuFeSe2 Nano Theranostic Platform and Its Application in MR/CT Dual Model Imaging and Photothermal Therapy.

Targeting, imaging, and treating tumors represent major clinical challenges. Developing effective theranostic agents to address these issues is an urgent need. We introduce an "all-in-one" tumor-targeted theranostic platform using CuFeSe2-based composite nanoparticles (CuFeSe2@PA) for magnetic resonance (MR) and computed tomography (CT) dual model imaging-guided hyperthermia tumor ablation. Plerixafor (AMD3100) is bonded to the surface of CuFeSe2 as a targeting unit. Due to the robust interaction between AMD3100 and the overexpressed Chemokine CXC type receptor 4 (CXCR4) on the membrane of 4T1 cancer cells, CuFeSe2@PA specifically recognizes 4T1 cancer cells, enriching the tumor region. CuFeSe2@PA serves as a contrast agent for T2-weighted MR imaging (relaxivity value of 1.61 mM-1 s-1) and CT imaging. Moreover, it effectively suppresses tumor growth through photothermal therapy (PTT) owing to its high photothermal conversion capability and stability, with minimized side effects demonstrated both in vitro and in vivo. CuFeSe2@PA nanoparticles show potential as dual-mode imaging contrast agents for MR and CT and provide an effective means of tumor treatment through photothermal therapy. The surface modification with Plerixafor enhances the targeting ability of the nanoparticles, performing more significant efficacy and biocompatibility in the 4T1 cancer cell model. The study demonstrates that CuFeSe2@PA is a promising multifunctional theranostic platform with clinical application potential.

Analysis of magnetic resonance contrast agent entrapment following reversible electroporation in vitro.

Administering gadolinium-based contrast agent before electroporation allows the contrast agent to enter the cells and enables MRI assessment of reversibly electroporated regions. The aim of this study was evaluation of contrast agent entrapment in Chinese hamster ovary (CHO) cells and comparison of these results with those determined by standard in vitro methods for assessing cell membrane permeability, cell membrane integrity and cell survival following electroporation. Cell membrane permeabilization and cell membrane integrity experiments were performed using YO-PRO-1 dye and propidium iodide, respectively. Cell survival experiments were performed by assessing metabolic activity of cells using MTS assay. The entrapment of gadolinium-based contrast agent gadobutrol inside the cells was evaluated using T1 relaxometry of cell suspensions 25 min and 24 h after electroporation and confirmed by inductively coupled plasma mass spectrometry. Contrast agent was detected 25 min and 24 h after the delivery of electric pulses in cells that were reversibly electroporated. In addition, contrast agent was present in irreversibly electroporated cells 25 min after the delivery of electric pulses but was no longer detected in irreversibly electroporated cells after 24 h. Inductively coupled plasma mass spectrometry showed a proportional decrease in gadolinium content per cell with shortening of T1 relaxation time (R 2 = 0.88 and p = 0.0191). Our results demonstrate that the contrast agent is entrapped in cells exposed to reversible electroporation but exits from cells exposed to irreversible electroporation within 24 h, thus confirming the hypothesis on which detection experiments in vivo were based.

Erythrocyte nano-ghosts with dual optical and magnetic resonance characteristics.

Fluorescent organic dyes provide imaging capabilities at cellular and sub-cellular levels. However, a common problem associated with some of the existing dyes such as the US FDA-approved indocyanine green (ICG) is their weak fluorescence emission. Alternative dyes with greater emission characteristics would be useful in various imaging applications. Complementing optical imaging, magnetic resonance (MR) imaging enables deep tissue imaging. Nano-sized delivery systems containing dyes with greater fluorescence emission as well as MR contrast agents present a promising dual-mode platform with high optical sensitivity and deep tissue imaging for image-guided surgical applications. We have engineered a nano-sized platform, derived from erythrocyte ghosts (EGs), with dual near-infrared fluorescence and MR characteristics by co-encapsulation of a brominated carbocyanine dye and gadobenate dimeglumine (Gd-BOPTA). We have investigated the use of three brominated carbocyanine dyes (referred to as BrCy106, BrCy111, and BrCy112) with various degrees of bromination, structural symmetry, and acidic modifications for encapsulation by nano-sized EGs (nEGs) and compared their resulting optical characteristics with nEGs containing ICG. We find that asymmetric dyes (BrCy106 and BrCy112) with one dibromobenzene ring offer greater fluorescence emission characteristics. For example, the relative fluorescence quantum yield ( ) for nEGs fabricated using of BrCy112 is -fold higher than nEGs fabricated using the same concentrations of ICG. The dual-mode nEGs containing BrCy112 and Gd-BOPTA show a nearly twofold increase in their as compared with their single optical mode counterpart. Cytotoxicity is not observed upon incubation of SKOV3 cells with nEGs containing BrCy112. Erythrocyte nano-ghosts with dual optical and MR characteristics may ultimately prove useful in various biomedical imaging applications such as image-guided tumor surgery where MR imaging can be used for tumor staging and mapping, and fluorescence imaging can help visualize small tumor nodules for resection.

Real-Time Metabolic Magnetic Resonance Spectroscopy of Pancreatic and Colon Cancer Tumor-Xenografts with Parahydrogen Hyperpolarized 1-13C Pyruvate-d3.

Parahydrogen-induced polarization (PHIP) is an emerging technique to enhance the signal of stable isotope metabolic contrast agents for Magnetic Resonance (MR). The objective of this study is to continue establishing 1-13C-pyruvate-d3, signal-enhanced via PHIP, as a hyperpolarized contrast agent, obtained in seconds, to monitor metabolism in human cancer. Our focus was on human pancreatic and colon tumor xenografts. 1-13C-vinylpyruvate-d6 was hydrogenated using parahydrogen. Thereafter, the polarization of the protons was transferred to 13C. Following a workup procedure, the free hyperpolarized 1-13C-pyruvate-d3 was obtained in clean aqueous solution. After injection into animals bearing either pancreatic or colon cancer xenografts, slice-selective MR spectra were acquired and analyzed to determine rate constants of metabolic conversion into lactate and alanine. 1-13C-pyruvate-d3 proved to follow the increased metabolic rate to lactate and alanine in the tumor xenografts.

Towards medical imaging of drug photoactivation: Development of light responsive magnetic resonance imaging and chemical exchange saturation transfer contrast agents

AbstractIn recent years, the use of light to selectively and precisely activate drugs has been developed along the fundamental concepts of photopharmacology. One of the key methods in this field relies on transiently silencing the drug activity with photocleavable protecting groups (PPGs). To effectively utilize light‐activated drugs in future medical applications, physicians will require a reliable method to assess whether light penetrates deep enough into the tissues to activate the photoresponsive theragnostic agents. Here, we describe the development and evaluation of magnetic resonance (MR) imaging agents that allow for the detection of light penetration and drug activation in the tissues using non‐invasive whole‐body magnetic resonance imaging (MRI) and chemical exchange saturation transfer (CEST)‐MRI modalities. The approach relies on the use of PPG‐protected MR contrast agents, which upon irradiation with light change their imaging signal. A Gadolinium(III)‐based MRI contrast agent is presented that undergoes a significant change in relaxivity (25%) upon uncaging, providing a reliable indicator of light‐induced cargo release. Additionally, we introduce the first light‐responsive CEST‐MRI imaging agent, enabling positive signal enhancement (off‐to‐on) upon light activation, offering a novel approach to visualize the activation of photoactive agents in living tissues. This research provides a proof‐of‐principle for the non‐invasive, whole‐body imaging of light penetration and drug activation with high temporal resolution characteristic of MR methods.

Pt(II)‐Phenanthroline‐Ln(III)‐DOTA d–f Hybrids as Small‐Molecule Theranostics

Abstract1,10‐Phenanthroline d‐ or f‐metal complexes can be utilised in biomedical applications such as imaging or therapeutics. Herein, we designed bimetallic d‐block metal‐phenanthroline f‐block metal‐1,4,7,10‐tetraazacyclododecane‐1,4,7,1,0‐tetraacetic acid (DOTA) conjugates as theranostic agents to simultaneously achieve both of these applications. Luminescence studies show the 1,10‐phenanthroline‐Eu(III)‐DOTA complexes displayed an off/on/off pH‐dependent switch, demonstrating their potential as pH‐responsive lanthanide luminescence probes. Relaxometry studies showed that the 1,10‐phenanthroline‐Gd(III)‐DOTA complexes present a r1 of 5.15±0.05 mM−1 s−1 and could thus be used as magnetic resonance (MR) contrast agents. Complexation of Pt(II) by the 1,10‐phenanthroline moiety resulted in quenching of the Eu(III) luminescence, but an enhancement of the Gd(III) relaxivity (r1=7.53±0.69 mM−1 s−1). Cell viability studies of the d–f hybrids in a cancer cell line showed the potential of these complexes as anticancer agents, as the IC50 for the Pt(II)/Gd(III) complex (IC50=24.9 μM) was lower than that of cisplatin (IC50=31.6 μM). As such, Pt(II)‐1,10‐phenanthroline‐Gd(III)‐DOTA complexes are promising theranostic agents for cancer therapy.

Development of Ln(III) Derivatives as 19F Parashift Probes.

19F parashift probes with paramagnetically shifted reporter nuclei provide attractive platforms to develop molecular imaging probes. These probes enable ratiometric detection of molecular disease markers using a direct detection technique. Here, we describe a series of trivalent lanthanide (Ln(III)) complexes that are structural analogues of the clinically approved MR contrast agent (CA) ProHance to obtain LnL 19F parashift probes. We evaluated trans-gadolinium paramagnetic lanthanides compared to diamagnetic YL for 19F chemical shift and relaxation rate enhancement. The paramagnetic contribution to chemical shift (δPCS) for paramagnetic LnL exhibited either shifts to lower frequency (δPCS < 0 for TbL, DyL, and HoL) or shifts to higher frequency (δPCS > 0 for ErL, TmL, and YbL) compared to YL 19F spectroscopic signal. Zero-echo time pulse sequences achieved 56-fold sensitivity enhancement for DyL over YL, while developing probe-specific pulse sequences with fast delay times and acquisition times achieved 0.6-fold enhancement in limit of detection for DyL. DyL provides an attractive platform to develop 19F parashift probes for ratiometric detection of enzymatic activity.

Super High Contrast USPIO-Enhanced Cerebrovascular Angiography Using Ultrashort Time-to-Echo MRI.

Ferumoxytol (Ferahame, AMAG Pharmaceuticals, Waltham, MA) is increasingly used off-label as an MR contrast agent due to its relaxivity and safety profiles. However, its potent T2∗ relaxivity limits achievable T1-weighted positive contrast and leads to artifacts in standard MRI protocols. Optimization of protocols for ferumoxytol deployment is necessary to realize its potential. We present first-in-human clinical results of the Quantitative Ultrashort Time-to-Echo Contrast Enhanced (QUTE-CE) MRA technique using the superparamagnetic iron oxide nanoparticle agent ferumoxytol for vascular imaging of the head/brain in 15 subjects at 3.0T. The QUTE-CE MRA method was implemented on a 3T scanner using a stack-of-spirals 3D Ultrashort Time-to-Echo sequence. Time-of-flight MRA and standard TE T1-weighted (T1w) images were also collected. For comparison, gadolinium-enhanced blood pool phase images were obtained retrospectively from clinical practice. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and intraluminal signal heterogeneity (ISH) were assessed and compared across approaches with Welch's two-sided t-test. Fifteen volunteers (54 ± 17 years old, 9 women) participated. QUTE-CE MRA provided high-contrast snapshots of the arterial and venous networks with lower intraluminal heterogeneity. QUTE-CE demonstrated significantly higher SNR (1707 ± 226), blood-tissue CNR (1447 ± 189), and lower ISH (0.091 ± 0.031) compared to ferumoxytol T1-weighted (551 ± 171; 319 ± 144; 0.186 ± 0.066, respectively) and time-of-flight (343 ± 104; 269 ± 82; 0.190 ± 0.016, respectively), with p < 0.001 in each comparison. The high CNR increased the depth of vessel visualization. Vessel lumina were captured with lower heterogeneity. Quantitative Ultrashort Time-to-Echo Contrast-Enhanced MR angiography provides approximately 5-fold superior contrast with fewer artifacts compared to other contrast-enhanced vascular imaging techniques using ferumoxytol or gadolinium, and to noncontrast time-of-flight MR angiography, for clinical vascular imaging. This trial is registered with NCT03266848.

Gadolinium-Based Magnetic Resonance Theranostic Agent with Gallic Acid as an Anti-Neuroinflammatory and Antioxidant Agent.

Studies in the field have actively pursued the incorporation of diverse biological functionalities into gadolinium-based contrast agents, aiming at the amalgamation of MRI imaging and therapeutic capabilities. In this research, we present the development of Gd-Ga, an anti-neuroinflammatory MR contrast agent strategically designed to target inflammatory mediators for comprehensive imaging diagnosis and targeted lesion treatment. Gd-Ga is a gadolinium complex composed of 1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetylamide (DO3A) conjugated with gallic acid (3,4,5-trihydroxybenzoic acid). Upon intravenous administration in LPS-induced mouse models, Gd-Ga demonstrated a remarkable three-fold increase in signal-to-noise (SNR) variation compared to Gd-DOTA, particularly evident in both the cortex and hippocampus 30 min post-MR monitoring. In-depth investigations, both in vitro and in vivo, into the anti-neuroinflammatory properties of Gd-Ga revealed significantly reduced protein expression levels of pro-inflammatory mediators compared to the LPS group. The alignment between in silico predictions and phantom studies indicates that Gd-Ga acts as an anti-neuroinflammatory agent by directly binding to MD2. Additionally, the robust antioxidant activity of Gd-Ga was confirmed by its effective scavenging of NO and ROS. Our collective findings emphasize the immense potential of this theranostic complex, where a polyphenol serves as an anti-inflammatory drug, presenting an exceptionally efficient platform for the diagnosis and treatment of neuroinflammation.

Safety of Administering Intravenous CT Contrast Agents Repeatedly or Using Both CT and MRI Contrast Agents on the Same Day: An Animal Study.

To investigate molecular and functional consequences of additional exposures to iodine- or gadolinium-based contrast agents within 24 hours from the initial intravenous administration of iodine-based contrast agents through an animal study. Fifty-six Sprague-Dawley male rats were equally divided into eight groups: negative control, positive control (PC) with single-dose administration of CT contrast agent, and additional administration of either CT or MR contrast agents 2, 4, or 24 hours from initial CT contrast agent injection. A 12 µL/g of iodinated contrast agent or a 0.47 µL/g of gadolinium-based contrast agent were injected into the tail vein. Serum levels of blood urea nitrogen, creatinine, cystatin C (Cys C), and malondialdehyde (MDA) were measured. mRNA and protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Levels of serum creatinine (SCr) were significantly higher in repeated CT contrast agent injection groups than in PC (0.21 ± 0.02 mg/dL for PC; 0.40 ± 0.02, 0.34 ± 0.03, and 0.41 ± 0.10 mg/dL for 2-, 4-, and 24-hour interval groups, respectively; P < 0.001). There was no significant difference in the average Cys C and MDA levels between PC and repeated CT contrast agent injection groups (Cys C, P = 0.256-0.362; MDA, P > 0.99). Additional doses of MR contrast agent did not make significant changes compared to PC in SCr (P > 0.99), Cys C (P = 0.262), and MDA (P = 0.139-0.771) levels. mRNA and protein levels of KIM-1 and NGAL were not significantly different among additional CT or MR contrast agent groups (P > 0.05). A sufficient time interval, probably more than 24 hours, between repeated contrast-enhanced CT examinations may be necessary to avoid deterioration in renal function. However, conducting contrast-enhanced MRI on the same day as contrast-enhanced CT may not induce clinically significant kidney injury.

Evaluation and Prediction of Post-Hepatectomy Liver Failure Using Imaging Techniques: Value of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging.

Despite improvements in operative techniques and perioperative care, post-hepatectomy liver failure (PHLF) remains the most serious cause of morbidity and mortality after surgery, and several risk factors have been identified to predict PHLF. Although volumetric assessment using imaging contributes to surgical simulation by estimating the function of future liver remnants in predicting PHLF, liver function is assumed to be homogeneous throughout the liver. The combination of volumetric and functional analyses may be more useful for an accurate evaluation of liver function and prediction of PHLF than only volumetric analysis. Gadoxetic acid is a hepatocyte-specific magnetic resonance (MR) contrast agent that is taken up by hepatocytes via the OATP1 transporter after intravenous administration. Gadoxetic acid-enhanced MR imaging (MRI) offers information regarding both global and regional functions, leading to a more precise evaluation even in cases with heterogeneous liver function. Various indices, including signal intensity-based methods and MR relaxometry, have been proposed for the estimation of liver function and prediction of PHLF using gadoxetic acid-enhanced MRI. Recent developments in MR techniques, including high-resolution hepatobiliary phase images using deep learning image reconstruction and whole-liver T1 map acquisition, have enabled a more detailed and accurate estimation of liver function in gadoxetic acid-enhanced MRI.

Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation.

Hyperpolarized 129Xe MRI comprises a unique array of structural and functional lung imaging techniques. Technique standardization across sites is increasingly important given the recent FDA approval of 129Xe as an MR contrast agent and as interest in 129Xe MRI increases among research and clinical institutions. Members of the 129Xe MRI Clinical Trials Consortium (Xe MRI CTC) have agreed upon best practices for each of the key aspects of the 129Xe MRI workflow, and these recommendations are summarized in a recent publication. This work provides practical information to develop an end-to-end workflow for collecting 129Xe MR images of lung ventilation according to the Xe MRI CTC recommendations. Preparation and administration of 129Xe for MR studies will be discussed and demonstrated, with specific topics including choice of appropriate gas volumes for entire studies and for individual MR scans, preparationand delivery of individual 129Xe doses, and best practices for monitoring subject safety and 129Xe tolerability during studies. Key MR technical considerations will also be covered, including pulse sequence types and optimized parameters, calibration of 129Xe flip angle and center frequency, and 129Xe MRI ventilation image analysis.

NIMG-19. TUMOR PARAMETERS AFFECTED BY NANOCOMBRESTATIN THERAPY IN AN EXPERIMENTAL RAT MODEL OF GLIOMA

Abstract INTRODUCTION: of polymeric nanoparticles in cancer therapeutics is widely investigated since nanomedicine often enables the intratumoral delivery of drugs with increased efficacy with minimal side effects. In this study magnetic resonance imaging (MRI) monitoring was employed to study the therapeutic effect of nanocombretastatin (G3-CA4) in an orthotopic glioma model. Water insoluble combretastatin (CA4) was conjugated to a small-sized water soluble G3-succinimic acid PAMAM dendrimer. Tumor growth and vascular parameters were assessed non-invasively using MRI. In the brain, intravenously (iv) administered magnetic resonance (MR) contrast agents (CAs) can be used to measure the biomarkers of tumor perfusion - the blood-to-brain transvascular transfer constant (K-trans), tumor plasma volume (Vp), the extravascular extracellular space (Ve) and the blood volume (VD) in cerebral tumors. K-trans, Vp, Ve and VD showed the discrimination of tumorous vasculature responding to CA4 and G3-CA4 therapies from tumorous tissues. The average K-trans, Vp, Ve and VD decreased significantly 24 hours after G3-CA4 treatment. The results showed that G3-CA4 caused a change in tumor vasculature as measured with DCE-MRI. These effects were homogenous throughout the U-251 tumor. However, CA4 did not show any change in tumor vasculature. Imaging, histological and molecular signatures of the primary glioblastoma were compared. Large necrotic area was found together with destroyed blood vessels at the core of the tumor leaving viable tissue at the rim of the tumor. In vivo studies proved that the cytotoxicity of G3-CA4 conjugate was more effective against human U-251 tumor while CA4 alone was ineffective. Therefore, we have accomplished the effective transvascular delivery of G3-CA4 into human U251 glioma tumor with a compromised blood brain tumor barrier. In vivo studies proved that the cytotoxicity of G3-CA4 conjugate is more effective against human U-251 tumor than that of free CA4.

High-quality Agar and Polyacrylamide Tumor-mimicking Phantom Models for Magnetic Resonance-guided Focused Ultrasound Applications.

Tissue-mimicking phantoms (TMPs) have been used extensively in clinical and nonclinical settings to simulate the thermal effects of focus ultrasound (FUS) technology in real tissue or organs. With recent technological developments in the FUS technology and its monitoring/guided techniques such as ultrasound-guided FUS and magnetic resonance-guided FUS (MRgFUS) the need for TMPs are more important than ever to ensure the safety of the patients before being treated with FUS for a variety of diseases (e.g., cancer or neurological). The purpose of this study was to prepare a tumor-mimicking phantom (TUMP) model that can simulate competently a tumor that is surrounded by healthy tissue. The TUMP models were prepared using polyacrylamide (PAA) and agar solutions enriched with MR contrast agents (silicon dioxide and glycerol), and the thermosensitive component bovine serum albumin (BSA) that can alter its physical properties once thermal change is detected, therefore offering real-time visualization of the applied FUS ablation in the TUMPs models. To establish if these TUMPs are good candidates to be used in thermoablation, their thermal properties were characterized with a custom-made FUS system in the laboratory and a magnetic resonance imaging (MRI) setup with MR-thermometry. The BSA protein's coagulation temperature was adjusted at 55°C by setting the pH of the PAA solution to 4.5, therefore simulating the necrosis temperature of the tissue. The experiments carried out showed that the TUMP models prepared by PAA can change color from transparent to cream-white due to the BSA protein coagulation caused by the thermal stress applied. The TUMP models offered a good MRI contrast between the TMPs and the TUMPs including real-time visualization of the ablation area due to the BSA protein coagulation. Furthermore, the T2-weighted MR images obtained showed a significant change in T2 when the BSA protein is thermally coagulated. MR thermometry maps demonstrated that the suggested TUMP models may successfully imitate a tumor that is present in soft tissue. The TUMP models developed in this study have numerous uses in the testing and calibration of FUS equipment including the simulation and validation of thermal therapy treatment plans with FUS or MRgFUS in oncology applications.

In vivo MR imaging for tumor-associated initial neovascularization by supramolecular contrast agents.

Microvascular imaging is required to understand tumor angiogenesis development; however, an appropriate whole-body imaging method has not yet been established. Here, we successfully developed a supramolecular magnetic resonance (MR) contrast agent for long-term whole-tissue observation in a single individual. Fluorescein- and Gd-chelate-conjugated polyethylene glycols (PEGs) were synthesized, and their structures were optimized. Spectroscopic and pharmacokinetic analyses suggested that the fluorescein-conjugated linear and 8-arm PEGs with a molecular weight of approximately 10kDa were suitable to form a supramolecular structure to visualize the microvessel structure and blood circulation. Microvascular formation was evaluated in a glioma cell transplantation model, and neovascularization around the glioma tissue at 5 days was observed, with the contrast agent leaking out into the cancer tissue. In contrast, after 12 days, microvessel structures were formed inside the glioma tissue, but the agents did not leak out. These imaging data for the first time proved that the microvessels formed inside cancer tissues at the early stage are very leaky, but that they form continuous microvessels after 12 days.

Hepatobiliary-specific magnetic resonance contrast agents: role in biliary trauma.

Non-iatrogenic traumatic bile duct injuries (NI-TBIs) are a rare complication after abdominal trauma, with an estimated prevalence of 2.8-7.4% in patients underwent blunt liver injuries. They may be overlooked in patients with extensive multi-organ trauma, particularly hepatic, splenic and duodenal injuries, which have a prevalence of 91%, 54% and 54%, respectively. Whole body contrast-enhanced computed tomography (CE-CT) represents the examination of choice in polytraumatized hemodynamically stable patients, as it allows a comprehensive evaluation of vascular, parenchymal, bone and soft tissues injuries, but the diagnosis of any biliary leaks is limited to the evaluation of nonspecific imaging findings and on findings evolution in the follow-up, such as the progressive growth of fluid collections. Furthermore, biliary complications, such as the occurrence of biloma or biliary peritonitis, may become manifest several days after the initial trauma, often with unspecific progressive signs and symptoms. Although CT and ultrasonography can suggest bile leaks based on several nonspecific imaging findings (e.g., fluid collections), magnetic resonance imaging (MRI) using hepatobiliary contrast agents helps to identify the site and entity of post-traumatic biliary disruption. Indeed, MRI allows to obtain cholangiographic sequences that may show post-traumatic active bile leakage and cysto-biliary communications by direct visualisation of contrast material extravasation into fluid collections, increasing the preoperative accuracy of NI-TBIs. Few data are available about MRI use in the follow-up of trauma with NI-TBI management. So, in the present mini review, its role is reviewed and our preliminary experience in this field is reported.

Molecular Imaging of ACE2 Expression in Infectious Disease and Cancer.

Angiotensin-converting enzyme 2 (ACE2) is a cell-surface receptor that plays a critical role in the pathogenesis of SARS-CoV-2 infection. Through the use of ligands engineered for the receptor, ACE2 imaging has emerged as a valuable tool for preclinical and clinical research. These can be used to visualize the expression and distribution of ACE2 in tissues and cells. A variety of techniques including optical, magnetic resonance, and nuclear medicine contrast agents have been developed and employed in the preclinical setting. Positron-emitting radiotracers for highly sensitive and quantitative tomography have also been translated in the context of SARS-CoV-2-infected and control patients. Together this information can be used to better understand the mechanisms of SARS-CoV-2 infection, the potential roles of ACE2 in homeostasis and disease, and to identify potential therapeutic modulators in infectious disease and cancer. This review summarizes the tools and techniques to detect and delineate ACE2 in this rapidly expanding field.