Vivo MR Imaging Research Articles

A Bis(Aquated) Mn(II)-Based MRI Contrast Agent with a Rigid Hydroquinazoline Unit: Synthesis, Characterization, and in Vivo MR Imaging Study.

Since the finding of nephrogenic systemic fibrosis (NFS) in patients with renal impairment and the long-term accumulation of Gd(III) ions in the central nervous system, the search for nongadolinium ion-based MRI contrast agents made of nutrient metal ions has drawn paramount attention. In this context, the development of Mn(II)-based MRI contrast agents has been a subject of interest for the last few decades. Herein, we report a pentadentate ligand (Li2[BenzPic2]) composed of two picolinate moieties and a rigid 1,2,3,4-tetrahydroquinazoline unit and the corresponding bis(aquated) Mn(II) complex (Complex 1). The complex exhibited high thermodynamic stability (log Kcond = 11.62) and kinetic inertness similar to that of the clinically approved Gd(III)-based contrast agent Magnevist. Complex 1 exerted longitudinal relaxivity (r1) of 5.32 mM-1 s-1 at 1.41 T, 37 °C, pH 7.4, and it increased by 3.6-fold in the presence of serum albumin protein, confirming a substantial rigidifying interaction (albumin association constant KA = 1.66 × 103 M-1) between the protein and the amphiphilic (log P = -0.45) contrast agent. An intravenous dose of 0.08 mmol/kg in a healthy mouse, excellent MRI signal intensity enhancement in the vasculature of the mouse liver, and brightened images of the gallbladder, kidney, and liver were realized.

Captopril-Loaded Superparamagnetic Nanoparticles as a New Dual-Mode Contrast Agent for Simultaneous In Vitro/In Vivo MR Imaging and Drug Delivery System

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely applied as magnetic resonance imaging (MRI) contrast agents and drug carriers in drug delivery systems (DDSs) for diagnostics and treatment of diseases. Observation of drug delivery, drug release, and monitoring of the treatment can be performed by MRI. Magnetic nanoparticles (MNPs) can be used as dual-mode agents for simultaneous MRI contrast and drug delivery. Application of dual-mode MRI-contrast and drug-carrier agent is especially useful in targeted DDS. In this study, we report on the preparation of captopril-coated MNPs as a new dual-mode agent for simultaneous MRI contrast and DDS. The influence of contrast agent on the longitudinal (T1) and transverse (T2, T2*) relaxation times was studied and it was found that the effect on T2 and T2* exceeds the effect on T1, which leads to darkening of the MR image. Release of captopril from γ-Fe2O3@SiO2@captopril system was studied at three pH values and it was established that the drug release at pH 1.2 was greater than that at pH 4.8 and 7.4. The obtained results show that MNPs loaded with captopril can be used as dual-mode MRI contrast agent and DDS system.

In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4 -TAT Nanoprobes.

Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T-cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T-cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T-cell immunotherapy targeting glioma. In this work, ultrasmall T1 MR-based nanoprobes, NaGdF4 -TAT, as molecular probes with high longitudinal relaxivity (8.93 mm-1 s-1 ) are designed. By means of HIV-1 transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled with the NaGdF4 -TAT nanoprobes without any measurable side effects on the labeled T-cells, which is remarkably superior to that of the control fluorescein isothiocyanate-NaGdF4 concerning labeling efficacy. Labeled adoptive T-cell clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h after intravenous infusion of 107 labeled T-cells by T1 -weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF4 -TAT nanoprobes labeling of T-cells may be a promising method to track adoptive T-cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas.

In Vivo MR Imaging of Dual MRI Reporter Genes and Deltex-1 Gene-modified Human Mesenchymal Stem Cells in the Treatment of Closed Penile Fracture.

The purpose of this study was to investigate the feasibility of dual magnetic resonance imaging (MRI) reporter genes, including ferritin heavy subunit (Fth) and transferrin receptor (TfR), which provide sufficient MRI contrast for in vivo MRI tracking, and the Deltex-1 (DTX1) gene, which promotes human mesenchymal stem cell (hMSC) differentiation to smooth muscle cells (SMCs), to treat closed penile fracture (CPF). Multi-gene co-expressing hMSCs were generated. The expression of mRNA and proteins was assessed, and the original biological properties of hMSCs were determined and compared. The intracellular uptake of iron was evaluated, and the ability to differentiate into SMCs was detected. Fifty rabbits with CPF were randomly transplanted with PBS, hMSCs, Fth-TfR-hMSCs, DTX1-hMSCs, and Fth-TfR-DTX1-hMSCs. In vivo MRI was performed to detect the distribution and migration of the grafted cells and healing progress of CPF, and the results were correlated with histology. The mRNA and proteins of the multi-gene were highly expressed. The transgenes could not influence the original biological properties of hMSCs. The dual MRI reporter genes increased the iron accumulation capacity, and the DTX1 gene promoted hMSC differentiation into SMCs. The distribution and migration of the dual MRI reporter gene-modified hMSCs, and the healing state of CPF could be obviously detected by MRI and confirmed by histology. The dual MRI reporter genes could provide sufficient MRI contrast, and the distribution and migration of MSCs could be detected in vivo. The DTX1 gene can promote MSC differentiation into SMCs for the treatment of CPF and effectively inhibit granulation tissue formation.

In Vivo MR Imaging of the Flow of the Brain Interstitial Fluid

Objectives: To image the flow of the brain interstitial fluid (ISF) in the deep nuclei. Keywords: Brain interstitial space; magnetic resonance imaging; brain interstitial fluid, diffusion, substantia nigra.

In Vivo MR Imaging of Fibrin in a Neuroblastoma Tumor Model by Means of a Targeting Gd-Containing Peptide.

A magnetic resonance imaging contrast agent based on a tetrameric Gd-DTPA-like system linked to a fibrin-targeting peptide (Gd-F) has been designed for in vivo tumor characterization. Gd-F was synthesized following Fmoc-SPPS strategy. Binding was measured using soluble fibrin DD(E) fragment and a dried fibrin assay. Contrast efficiency was tested on human and mouse clots and in vivo on Neuro2A tumor model. An anti-thrombotic drug was used to evaluate Gd-F sensitivity for changes in fibrin availability at the tumor site. The high relaxivity of Gd-F (42mM(-1)s(-1), per molecule) yielded a strong signal enhancement in human and murine clots. High contrast was also measured in vivo in Neuro2A tumors, with a persistent enhancement in tumor rim and stroma. Upon treatment with an anti-thrombotic drug, the contrast uptake was significantly reduced in the tumor area confirming the specificity of the probe. Gd-F resulted to be an efficient probe for tumor delineation and for monitoring fibrin deposits during tumor progression and anti-thrombotic therapy.

SU‐D‐18C‐03: In Vivo MR Imaging Using a Combined Single‐Point Dixon and Phase‐Sensitive Inversion Recovery Technique

Purpose:To demonstrate combined single‐point Dixon water/fat separation and phase sensitive inversion recovery imaging in in vivo brain images acquired in a single scan.Methods:A single inversion recovery image is acquired with an inversion‐time (TI) selected to maximize the dynamic range of the longitudinal magnetization of the water signals and at an echo time (TE) to introduce an orthogonal phase‐difference (i.e. 90°) between the fat and water signals. In the image reconstruction, spatially smooth background phase errors due to static magnetic field inhomogeneity are estimated by applying a region growing based phase correction algorithm: the algorithm first determines spatial phase jumps of 180° and then the second spatial phase jumps of 90°. After the background phase‐errors are removed from the acquired image, phase sensitive inversion recovery (PSIR) water‐only image and a separate fat‐only image can be generated as the real and imaginary parts of the phase‐corrected image, respectively.Results:The pulse sequence was implemented on a 3T whole‐body clinical scanner and a single brain image of a healthy volunteer was acquired. The acquired image was confirmed to contain an orthogonal phase difference between water and fat boundaries and 180o phase difference between the boundaries of long and short T1‐water tissues. The background phase errors were successfully determined and removed by the proposed phase correction algorithm and uniformly separated fat‐only and PSIR water‐only images were reconstructed without artefacts.Conclusion:We demonstrated combined single‐point Dixon water/fat separation and PSIR imaging in in vivo brain images acquired in a single scan. Such images can be useful when fat suppression and enhanced T1‐contrast are desired. Potential areas of application may include imaging of the brain or myocardium.

In Vivo MR Imaging of Intraarterially Delivered Magnetically Labeled Mesenchymal Stem Cells in a Canine Stroke Model

BackgroundThis study aimed to evaluate the feasibility of intraarterial (IA) delivery and in vivo MR imaging of superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in a canine stroke model.MethodologyMSCs harvested from beagles’ bone marrow were labeled with home-synthesized SPIO. Adult beagle dogs (n = 12) were subjected to left proximal middle cerebral artery (MCA) occlusion by autologous thrombus, followed by two-hour left internal carotid artery (ICA) occlusion with 5 French vertebral catheter. One week later, dogs were classified as three groups before transplantation: group A: complete MCA recanalization, group B: incomplete MCA recanalization, group C: no MCA recanalization. 3×106 labeled-MSCs were delivered through left ICA. Series in vivo MRI images were obtained before cell grafting, one and 24 hours after transplantation and weekly thereafter until four weeks. MRI findings were compared with histological studies at the time point of 24 hours and four weeks.Principal FindingsHome-synthesized SPIO was useful to label MSCs without cell viability compromise. MSCs scattered widely in the left cerebral hemisphere in group A, while fewer grafted cells were observed in group B and no cell was detected in group C at one hour after transplantation. A larger infarction on the day of cell transplantation was associated with more grafted cells in the brain. Grafted MSCs could be tracked effectively by MRI within four weeks and were found in peri-infarction area by Prussian blue staining.ConclusionIt is feasible of IA MSCs transplantation in a canine stroke model. Both the ipsilateral MCA condition and infarction volume before transplantation may affect the amount of grafted cells in target brain. In vivo MR imaging is useful for tracking IA delivered MSCs after SPIO labeling.

Allogeneic Renal Graft Rejection in a Rat Model: In Vivo MR Imaging of the Homing Trait of Macrophages

To evaluate the feasibility of MR imaging to depict the in vivo recruitment of superparamagnetic iron oxide (SPIO)-labeled macrophages and to aid diagnosis of graft rejection in kidney transplantation. This study was approved by the institution's committee on animal research. Eighteen male Lewis rats received a kidney transplant; 12 had an F344 rat donor and six had a Lewis rat donor. Peritoneal macrophages were harvested from thioglycollate-treated Lewis rats, cultured, and labeled with SPIO. After resuspension of macrophages in a concentration of 1 x 10(7) cells per milliliter of Hanks balanced salt solution, 5 x 10(6) of SPIO-labeled macrophages was administered through the tail vein 2 or 5 days after transplantation in each group. The transplanted kidneys were imaged on a 4.7-T MR imager 24 hours after macrophage administration. The Wilcoxon signed rank test was performed for evaluating the differences between the relative signal intensity (SI) before and after SPIO-labeled macrophage administration. A low-SI zone was predominantly noted in the medulla of the transplanted kidneys, and the relative SI decreased significantly from 1.40 to 0.53 (P < .001) in the allogeneic transplants following SPIO-labeled macrophage administration 5 days after the allogeneic transplantation. In the syngeneic group, the lower-SI zone was not noted in the grafts. At histopathologic examination, the lower-SI zone corresponded to the distribution of the SPIO-labeled macrophages. This study demonstrates that the homing of intravenously administered SPIO-labeled macrophages can be monitored in the allograft rejection model on in vivo MR images.

In Vivo MR Imaging of Magnetically Labeled Mesenchymal Stem Cells in a Rat Model of Renal Ischemia

ObjectiveThis study was designed to evaluate in vivo MR imaging for the depiction of intraarterially injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in an experimental rat model of renal ischemia.Materials and MethodsLeft renal ischemia was induced in 12 male Sprague-Dawley rats by use of the catheter lodging method. In vivo MR signal intensity variations depicted on T2*-weighted sequences were evaluated in both the left and right kidneys prior to injection (n = 2), two hours (n = 4), 15 hours (n = 2), 30 hours (n = 2) and 72 hours (n = 2) after injection of SPIO-labeled MSCs in both kidneys. Signal intensity variations were correlated with the number of Prussian blue stain-positive cells as visualized in histological specimens.ResultsIn an in vivo study, it was determined that there was a significant difference in signal intensity variation for both the left and right cortex (40.8 ± 4.12 and 26.4 ± 7.92, respectively) and for both the left and right medulla (23.2 ± 3.32 and 15.2 ± 3.31, respectively) until two hours after injection (p < 0.05). In addition, signal intensity variation in the left renal cortex was well correlated with the number of Prussian blue stain-positive cells per high power field (r = 0.98, p < 0.05).ConclusionIntraarterial injected SPIO-labeled MSCs in an experimental rat model of renal ischemia can be detected with the use of in vivo MR imaging immediately after injection.

Comparison of Symptomatic and Asymptomatic Atherosclerotic Carotid Plaque Features with in Vivo MR Imaging

Comparison of Symptomatic and Asymptomatic Atherosclerotic Carotid Plaque Features with in Vivo MR Imaging

Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers.

To quantitate neuroanatomic parameters in healthy volunteers and to compare the values with normative values from postmortem studies. Magnetic resonance (MR) images of 116 volunteers aged 19 months to 80 years were analyzed with semiautomated procedures validated by means of comparison with manual tracings. Volumes measured included intracranial space, whole brain, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). Results were compared with values from previous postmortem studies. Whole brain and intracranial space grew by 25%-27% between early childhood (mean age, 26 months; age range, 19-33 months) and adolescence (mean age, 14 years; age range, 12-15 years); thereafter, whole-brain volume decreased such that volunteers (age range, 71-80 years) had volumes similar to those of young children. GM increased 13% from early to later (6-9 years) childhood. Thereafter, GM increased more slowly and reached a plateau in the 4th decade; it decreased by 13% in the oldest volunteers. The GM-WM ratio decreased exponentially from early childhood through the 4th decade; thereafter, it gradually declined. In vivo patterns of change in the intracranial space, whole brain, and GM-WM ratio agreed with published postmortem data. MR images accurately depict normal patterns of age-related change in intracranial space, whole brain, GM, WM, and CSF. These quantitative MR imaging data can be used in research studies and clinical settings for the detection of abnormalities in fundamental neuroanatomic parameters.