MR Images Of Phantom Research Articles

Alkyl Chain Appended Fe(III) Catecholate Complex as a Dual-Modal T1 MRI-NIR Fluorescence Imaging Agent via Second Sphere Water Interactions.

The C12-alkyl chain-conjugated Fe(III) catecholate complex [Fe(C12CAT)3]3-, Fe(C12CAT)3 [C12CAT = N-(3,4-dihydroxyphenethyl)dodecanamide], was synthesized and characterized, reported as a dual-modal T1-MRI and an optical imaging probe. The DFT-optimized structure of Fe(C12CAT)3 reveals a distorted octahedral coordination geometry around the high spin Fe(III) center. The formation constant (-log K) of Fe(C12CAT)3 was calculated as 45.4. The complex exhibited r1-relaxivity values of 2.31 ± 0.12 and 1.52 ± 0.06 mM-1 s-1 at 25 and 37 °C, respectively, on 1.41 T at pH 7.3 via second-sphere water interactions. The interaction of Fe(C12CAT)3 with human serum albumin showed concomitant enhancement of r1-relaxivity to 6.44 ± 0.15 mM-1 s-1. The MR phantom images are significantly brighter and directly correlate to the concentration of Fe(C12CAT)3. Adding an external fluorescent marker IR780 dye to Fe(C12CAT)3 leads to the formation of self-assembly by C12-alkyl chains. It resulted in the fluorescence quenching of the dye, and its critical aggregation concentration was calculated as 70 μM. The aggregated matrix of Fe(C12CAT)3 and IR780 dye is spherical, with an average hydrodynamic diameter of 189.5 nm. This self-assembled supramolecular system is found to be non-fluorescent and was "turn-on" under acidic pH via dissociation of aggregates. The r1-relaxivity is found to be unchanged during the matrix aggregation and disaggregation. The probe showed MRI ON and fluorescent OFF under physiological conditions and MRI ON and fluorescent ON under acidic pH. The cell viability experiments showed that the cells are 80% viable at 1 mM probe concentration. Fluorescence experiments and MR phantom images showed that Fe(C12CAT)3 is a potential dual model imaging probe to visualize the acidic pH environment of the cells.

System-dependent image distortion related to gantry positions of a 0.35 T MRgRT: Characterization and the corresponding correction.

MR-guided radiotherapy with high accuracy treatment planning requires addressing MR imaging artifacts that originate from system imperfections. This work presents the characterization and corresponding correction of gantry-related imaging distortions including geometric distortion and isocenter shift in a 0.35 T magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT) system using distortion vector fields (DVFs). Two phantoms, the magnetic resonance imaging distortion in 3D (MRID3D ) phantom and the Fluke phantom, along with a human volunteer were imaged at different gantry angles on a 0.35 T MR-Linac. The geometric distortion and isocenter shift were characterized for both phantom images. DVFs with a field of view extended beyond the physical boundary of the MRID3D phantom were extracted from images taken at 30° gantry angle increments, with vendor-provided distortion correction turned on and off (DstOff). These extended DVFs were then applied to the relevant phantom images to correct their geometric distortions and isocenter shift at the respective gantry angles. The extended DVFs produced from the MRID3D phantom were also applied to Fluke phantom and human MR images at their respective gantry angles. The resampled images were evaluated using structural similarity index measure (SSIM) comparison with the vendor corrected images from the MRgRT system. Geometric distortion with "mean (±SD) distortion" of 3.2±0.02, 2.9±0.02, and 1.8±0.01mm and isocenter shift (±SD) of 0.49±0.3, 0.05±0.2, and 0.01±0.03mm were present in the DstOff MRID3D phantom images in right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. After resampling the originally acquired images by applying extended DVFs, the distortion was corrected to 0.18±0.02, 0.09±0.01, 0.15±0.01mm, and isocenter shift was corrected to 0.14±0.05, -0.02±0.04, and -0.07±0.05mm in RL, AP, and SI directions, respectively. The Fluke phantom average geometric distortion with "mean (±SD) distortion" of 2.7±0.1mm was corrected to 0.2±0. 1mm and the average isocenter shift (±SD) of 0.51±0.2mm, and 0.05±0.03 was corrected to -0.08±0.03mm, and -0.05±0.01 in RL and AP directions, respectively. SSIM (mean±SD) of the original images to resampled images was increased from 0.49±0.02 to 0.78±0.01, 0.45±0.02 to 0.75±0.01, and 0.86±0.25 to 0.98±0.08 for MRID3D phantom, Fluke phantom, and human MR images, respectively, for all the gantry angles compared to the vendor corrected images. The gantry-related MR imaging distortion including geometric distortion and isocenter shift was characterized and a corresponding correction was demonstrated using extended DVFs on 0.35 T MRgRT system. The characterized gantry-related isocenter shift can be combined with geometric distortion correction to provide a technique for the correction of the full system-dependent distortion in an MRgRT system.

Synthesis, characterization and relaxivity validations of Gd(III) complex of DOTA tetrahydrazide as MRI contrast agent

We report a novel Gadolinium(III) complex of (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetra(acetohydrazide) (Gd(III)L1) as a potential contrast agent for high resolution images in MRI and its molecular structure prediction by DFT calculations. The DOTA tetrahydrazide ligand framework (L1) was synthesized by the reaction of 1,4,7,10-tetraazacyclododecane (cyclen) with bromo derivative of conjugated t-butyl carbazate and followed by the subsequent cleavage of Boc moieties. The corresponding Gd(III) complex was prepared in an aqueous medium with the adjustment of pH to 7.0. The Gd(III)L1 complex shows the longitudinal relaxivity of 4.9 mM−1s−1 and transverse relaxivity of 6.2 mM−1s−1 at 37 ⁰C. The as-prepared complex Gd(III)L1 displays the enhanced intensity of T1 weighted phantom MR images with various concentrations at 7.0 T MRI scanner, which pave the way to achieve higher resolution images in MRI.

MR Denoising Increases Radiomic Biomarker Precision and Reproducibility in Oncologic Imaging.

Several noise sources, such as the Johnson-Nyquist noise, affect MR images disturbing the visualization of structures and affecting the subsequent extraction of radiomic data. We evaluate the performance of 5 denoising filters (anisotropic diffusion filter (ADF), curvature flow filter (CFF), Gaussian filter (GF), non-local means filter (NLMF), and unbiased non-local means (UNLMF)), with 33 different settings, in T2-weighted MR images of phantoms (N = 112) and neuroblastoma patients (N = 25). Filters were discarded until the most optimal solutions were obtained according to 3 image quality metrics: peak signal-to-noise ratio (PSNR), edge-strength similarity-based image quality metric (ESSIM), and noise (standard deviation of the signal intensity of a region in the background area). The selected filters were ADFs and UNLMs. From them, 107 radiomics features preservation at 4 progressively added noise levels were studied. The ADF with a conductance of 1 and 2 iterations standardized the radiomic features, improving reproducibility and quality metrics.

Clinical impact of magnetic resonance imaging distortions on gamma knife radiosurgery.

IntroductionMagnetic resonance imaging (MRI) is the preferred imaging modality for Leksell Gamma Knife® (LGK) stereotactic radiosurgery (SRS) treatment planning (TP) due to superior soft tissue definition compared to computed tomography (CT). However, inherent distortions in MRI can affect treatment accuracy. The aim of this study was to develop a model to visualise the effect of MRI distortion on LGK SRS target coverage.MethodsA model was developed using MR images of a QUASARTM GRID3D QA phantom. One hundred and twenty‐five points were compared against known phantom geometry. Using linear interpolation, the model was applied retrospectively to 10 brain metastases patient data sets treated with LGK. The model estimated the corrected shot position accounting for distortion. A total of 44 metastases were investigated regarding the effects of MRI distortion on target coverage.ResultsThe model indicated significantly reduced mean error by 0.30 mm and variance by 0.09 mm (P = 0.008). After model application, 23 (53%) metastases showed reduced coverage. Six of the 23 metastases were deemed to be potentially clinically significant changes. Results indicated MRI distortion had a greater effect on smaller targets (mean 0.06cc) located further away from the image isocentre (mean 64.88 mm).ConclusionThis study developed a model to visualise the effect of MRI distortion on LGK SRS target coverage. Results suggest that MRI distortion can affect target coverage and the developed model may be one method to assess its impact. These results indicate that MRI distortion may have a greater effect on smaller targets located at the image periphery.

Brain temperature measurement using MR tomography images

Volumetric MRI thermometry is undergoing active development. The measurement bases on the resonance response of protons insidemolecules (i.e., water, fat, methylene, lipids) of the examined body. The difference between resonance frequencies gives information about the temperature of the tissue. Various MR thermal image construction methods exist because temperature influences the state of a living object in numerous ways. As a result of this, contrast characteristics of MR images of tissue depend on the value of the magnetic field induction, tissue characteristics itself, and temperature. This paper deals with brain temperature measurement based on digital analysis of T 2-weighted MR images. MR images of homogenous and inhomogeneous phantoms at different temperatures were analyzed. The relationship between image brightness, temperature, and phantom composition was determined. The temperature of the cerebrospinal fluid was calculated.

Removal of high density Gaussian noise in compressed sensing MRI reconstruction through modified total variation image denoising method

A modified total variation MRI image denoising method is proposed in this paper. First, the proposed method removes the noise in K-space in compressed sensing MRI reconstruction. Then, the removed K-space data is used as a partial frequency observation in compressed sensing MRI model. The proposed method shows better results than RecPF method, LDP method, TVCMRI method, and FCSA method in sparse MRI reconstruction. The proposed method is tested against Shepp-Logan phantom and real MR images corrupted by noise of different intensity level, and it gives better Signal-to-Noise Ratio (SNR), the relative error (ReErr), and the structural similarity (SSIM) than RecPF, LDP, TVCMRI, and FCSA.

Effect of Ligand Chirality and Hyperconjugation on the Thermodynamic Stability of a Tris(aquated) GdIII Complex: Synthesis, Characterization, and T1‐Weighted Phantom MR Image Study

The hexadentate chiral alanine‐based ligand, Li3cbda, in a reaction with hydrated GdCl3 at pH ~ 6.5 provided the corresponding nine‐coordinated, neutral GdIII complex (1). The hydration state (q) of complex 1 was 3.1 ± 0.1, as determined by luminescence decay time measurements of TbIII congener in H2O and D2O. Complex 1 exhibited thermodynamic stability, log KGdL = 14.64 in 0.15 m NaCl solution at 25 °C. At 1.41 T, pH ≈ 7.4, and 25 °C, the complex offered longitudinal relaxivity, r1 = 10.95 mm–1 s–1, which was in accordance with three inner‐sphere water molecules. While, the relaxivity value remained unaffected in the pH range of 4.0 to 7.4, under basic conditions (pH ≥ 10) a reduction in the relaxivity value to 6.68 mm–1 s–1 was observed. A similar phenomenon was also realized in the presence of endogenous anions (100 equivalents of F– and HCO3–), which implied the removal of coordinated‐water molecules under the conditions. Phantom MR imaging under the clinical scanner at 1.5 T showed the enhancement in the image intensity with increasing concentration of the complex. As expected, the image intensity of 1 mm complex 1 was about three times compared to 1 mm MultiHance® solution.

The Use of Strong Inductively Coupled Wireless Surface Coil and Transmit/Receive Volume Coil for 1H/19F MRI

In this paper, we considered the use of a wireless coil designed from a routine surface coil in 1H/19F magnetic resonance imaging (MRI). When it was positioned within a transmit/receive volume coil, a strong inductive coupling was appeared. A high sensitivity and undistorted B1 field distribution formed from the location of the wireless coil were observed only in a co-rotating current mode (high-frequency mode). For this matching quality, MR images of phantoms and mouse brain were acquired. The use of inductively coupled coil system has allowed to obtain 1H/19F MR images with the greater SNR directly from the location of the wireless coil in more than 6–7 times in comparison with using only transmit/receive volume coil. Compared to use only transmit/receive surface coil, the 1H NMR signal acquired directly from the wireless coil location was more than three times higher. At the same time, the use of an active decoupling between transmit and receive coils gives better results than using a strong inductively coupled coil system, but a reduction of the SNR near the wireless coil location is less no more than 20%. The results present the possibilities of using the wireless coil in conventional 1H/19F MRI studies and can be useful for implantable coil applications.

Tissue-susceptibility matched carbon nanotube electrodes for magnetic resonance imaging

Test disk electrodes were fabricated from carbon nanotubes (CNT) using the Carbon Nanotube Templated Microfabrication (CNT-M) technique. The CNT-M process uses patterned growth of carbon nanotube forests from surfaces to form complex patterns, enabling electrode sizing and shaping. The additional carbon infiltration process stabilizes these structures for further processing and handling. At a macroscopic scale, the electrochemical, electrical and magnetic properties, and magnetic resonance imaging (MRI) characteristics of the disk electrodes were investigated; their microstructure was also assessed. CNT disk electrodes showed electrical resistivity around 1 Ω·cm, charge storage capacity between 3.4 and 38.4 mC/cm2, low electrochemical impedance and magnetic susceptibility of −5.9 to −8.1 ppm, closely matched to that of tissue (∼−9 ppm). Phantom MR imaging experiments showed almost no distortion caused by these electrodes compared with Cu and Pt-Ir reference electrodes, indicating the potential for significant improvement in accurate tip visualization.

A Bishydrated, Eight–Coordinate Gd(III) Complex with Very Fast Water Exchange: Synthesis, Characterization, and Phantom MR Imaging

AbstractWe report here the physical‐chemical characterization of a highly water‐soluble Gd(III) complex (complex 1) formed with the asymmetric hexadentate ligand H4bedik (2,2′‐((2‐(bis (carboxymethyl)amino)benzyl)azanediyl)diacetic acid). The number of water molecules directly coordinated to the metal, q=2.2, was assessed by measuring luminescence lifetimes of the Tb(III) analogue (complex 2) in H2O and D2O and it further was confirmed by 17O chemical shift measurements on the Gd(III) complex. The complex has moderate thermodynamic stability and remains insensitive to physiological anions [biphosphate (HPO42−), bicarbonate (HCO3−)] and pH variation (in the range 5–10) of the medium as evidenced by negligible changes in longitudinal relaxivity (r1) at 1.41 T, 25 °C. The Gd(III) complex exhibits very fast water exchange, among the fastest reported for Gd(III) chelates, and high relaxivity at high magnetic fields (r1=7.47 mM–1s–1 at 9.4 T, pH ∼ 7 and 25 °C). Interestingly, the very high positive value of the activation entropy indicates a dissociatively activated water exchange for this eight‐coordinate complex.

Optimizing the Relaxivity of MRI Probes at High Magnetic Field Strengths With Binuclear GdIII Complexes.

The key criteria to optimize the relaxivity of a Gd(III) contrast agent at high fields (defined as the region ≥ 1.5 T) can be summarized as follows: (i) the occurrence of a rotational correlation time τR in the range of ca. 0.2–0.5 ns; (ii) the rate of water exchange is not critical, but a τM < 100 ns is preferred; (iii) a relevant contribution from water molecules in the second sphere of hydration. In addition, the use of macrocycle-based systems ensures the formation of thermodynamically and kinetically stable Gd(III) complexes. Binuclear Gd(III) complexes could potentially meet these requirements. Their efficiency depends primarily on the degree of flexibility of the linker connecting the two monomeric units, the absence of local motions and the presence of contribution from the second sphere water molecules. With the aim to maximize relaxivity (per Gd) over a wide range of magnetic field strengths, two binuclear Gd(III) chelates derived from the well-known macrocyclic systems DOTA-monopropionamide and HPDO3A (Gd2L1 and Gd2L2, respectively) were synthesized through a multistep synthesis. Chemical Exchange Saturation Transfer (CEST) experiments carried out on Eu2L2 at different pH showed the occurrence of a CEST effect at acidic pH that disappears at neutral pH, associated with the deprotonation of the hydroxyl groups. Then, a complete 1H and 17O NMR relaxometric study was carried out in order to evaluate the parameters that govern the relaxivity associated with these complexes. The relaxivities of Gd2L1 and Gd2L2 (20 MHz, 298 K) are 8.7 and 9.5 mM−1 s−1, respectively, +77% and +106% higher than the relaxivity values of the corresponding mononuclear GdDOTAMAP-En and GdHPDO3A complexes. A significant contribution of second sphere water molecules was accounted for the strong relaxivity enhancement of Gd2L2. MR phantom images of the dinuclear complexes compared to GdHPDO3A, recorded at 7 T, confirmed the superiority of Gd2L2. Finally, ab initio (DFT) calculations were performed to obtain information about the solution structure of the dinuclear complexes.

Potential fluorescence and magnetic resonance imaging modality using mixed lanthanide oxide nanoparticles.

Imaging is a very important technique in the diagnosis and treatment of cancer diseases. This study developed a dual modality (fluorescence/MR) imaging technique for cancer cell lines (HeLa) and T2-weighted phantom imaging by using a mixed lanthanide (Dy/Er/Tb) oxide nanoparticles. To further enhance the solubility, stability and biocompatibility of mixed lanthanide oxide, the nanoparticles were coated with folic acid as well as G4.5 PAMAM dendrimer. The coated nanoparticles were then compared, the later with results demonstrating pronounced effects in both T2 weighted phantom MR and fluorescence imaging of the cancer cell lines. Imaging enhancement was attributed to a synergistic effect of the fluorescent properties and higher water solubility of the PAMAM dendrimer when compared to the folic acid. Besides, mixed lanthanides of Dy and Tb were used for T2 weighted MR imaging, while mixed lanthanides of Er and Tb were used for fluorescence imaging in the near infrared and visible regions, and were synthesized in the facile composition control. Hence, the mixed lanthanide oxides are packed together, and stable, which is used to facilitate biomedical imaging in vitro. To conclude, the G4.5 PAMAM dendrimer coated mixed lanthanide oxide nanoparticles will be used for dual-modality (fluorescence/MR imaging) cancer cell line detection in both in vitro and in vivo study.

Synthesis of Iron Oxide Nanoclusters by Thermal Decomposition.

Herein, we report a novel one-step solvothermal synthesis of magnetite nanoclusters (MNCs). In this report, we discuss the synthesis, structure, and properties of MNCs and contrast enhancement in T2-weighted MR images using magnetite nanoclusters. The effect of different organic acids, used as surfactants, on the size and shape of MNCs was investigated. The structure and properties of samples were determined by magnetic measurements, TGA, TEM, HRTEM, XRD, FTIR, and MRI. Magnetic measurements show that obtained MNCs have relatively high saturation magnetization values (65.1-81.5 emu/g) and dependence of the coercive force on the average size of MNCs was established. MNCs were transferred into an aqueous medium by Pluronic F-127, and T2-relaxivity values were determined. T2-Weighted MR phantom images clearly demonstrated that such magnetite nanoclusters can be used as contrast agents for MRI.

A New Bis(aquated) High Relaxivity Mn(II) Complex as an Alternative to Gd(III)-Based MRI Contrast Agent.

Disclosed here are a piperazine, a pyridine, and two carboxylate groups containing pentadentate ligand H2pmpa and its corresponding water-soluble Mn(II) complex (1). DFT-based structural optimization implied that the complex had pentagonal bipyramidal geometry where the axial positions were occupied by two water molecules, and the equatorial plane was constituted by the ligand ON3O donor set. Thus, a bis(aquated) disc-like Mn(II) complex has been synthesized. The complex showed higher stability compared with Mn(II)-EDTA complex [log KMnL = 14.29(3)] and showed a very high r1 relaxivity value of 5.88 mM-1 s-1 at 1.41 T, 25 °C, and pH = 7.4. The relaxivity value remained almost unaffected by the pH of the medium in the range of 6-10. Although the presence of 200 equiv of fluoride and bicarbonate anions did not affect the relaxivity value appreciably, an increase in the value was noticed in the presence of phosphate anion due to slow tumbling of the complex. Cell viability measurements, as well as phantom MR images using clinical MRI imager, consolidated the possible candidature of complex 1 as a positive contrast agent.

A singular K-space model for fast reconstruction of magnetic resonance images from undersampled data.

Reconstructing magnetic resonance images from undersampled k-space data is a challenging problem. This paper introduces a novel method of image reconstruction from undersampled k-space data based on the concept of singularizing operators and a novel singular k-space model. Exploring the sparsity of an image in the k-space, the singular k-space model (SKM) is proposed in terms of the k-space functions of a singularizing operator. The singularizing operator is constructed by combining basic difference operators. An algorithm is developed to reliably estimate the model parameters from undersampled k-space data. The estimated parameters are then used to recover the missing k-space data through the model, subsequently achieving high-quality reconstruction of the image using inverse Fourier transform. Experiments on physical phantom and real brain MR images have shown that the proposed SKM method constantly outperforms the popular total variation (TV) and the classical zero-filling (ZF) methods regardless of the undersampling rates, the noise levels, and the image structures. For the same objective quality of the reconstructed images, the proposed method requires much less k-space data than the TV method. The SKM method is an effective method for fast MRI reconstruction from the undersampled k-space data. Graphical abstract Two Real Images and their sparsified images by singularizing operator.

Virtual phantom magnetic resonance imaging (ViP MRI) on a clinical MRI platform.

The purpose of this study was to implement Virtual Phantom Magnetic Resonance Imaging (ViP MRI), a technique that allows for generating reference signals in MR images using radiofrequency (RF) signals, on a clinical MR system and to test newly designed virtual phantoms. MRI experiments were conducted on a 1.5 T MRI scanner. Electromagnetic modelling of the ViP system was done using the principle of reciprocity. The ViP RF signals were generated using a compact waveform generator (dimensions of 26 cm × 18 cm × 16 cm), connected to a homebuilt 25 mm-diameter RF coil. The ViP RF signals were transmitted to the MRI scanner bore, simultaneously with the acquisition of the signal from the object of interest. Different types of MRI data acquisition (2D and 3D gradient-echo) as well as different phantoms, including the Shepp-Logan phantom, were tested. Furthermore, a uniquely designed virtual phantom - in the shape of a grid - was generated; this newly proposed phantom allows for the investigations of the vendor distortion correction field. High quality MR images of virtual phantoms were obtained. An excellent agreement was found between the experimental data and the inverse cube law, which was the expected functional dependence obtained from the electromagnetic modelling of the ViP system. Short-term time stability measurements yielded a coefficient of variation in the signal intensity over time equal to 0.23% and 0.13% for virtual and physical phantom, respectively. MR images of the virtual grid-shaped phantom were reconstructed with the vendor distortion correction; this allowed for a direct visualization of the vendor distortion correction field. Furthermore, as expected from the electromagnetic modelling of the ViP system, a very compact coil (diameter ~ cm) and very small currents (intensity ~ mA) were sufficient to generate a signal comparable to that of physical phantoms in MRI experiments. The ViP MRI technique was successfully implemented on a clinical MR system. One of the major advantages of ViP MRI over previous approaches is that the generation and transmission of RF signals can be achieved with a self-contained apparatus. As such, the ViP MRI technique is transposable to different platforms (preclinical and clinical) of different vendors. It is also shown here that ViP MRI could be used to generate signals whose characteristics cannot be reproduced by physical objects. This could be exploited to assess MRI system properties, such as the vendor distortion correction field.

Accuracy of deformable image registration on magnetic resonance images in digital and physical phantoms.

Accurate deformable image registration is necessary for longitudinal studies. The error associated with commercial systems has been evaluated using computed tomography (CT). Several in-house algorithms have been evaluated for use with magnetic resonance imaging (MRI), but there is still relatively little information about MRI deformable image registration. This work presents an evaluation of two deformable image registration systems, one commercial (Velocity) and one in-house (demons-based algorithm), with MRI using two different metrics to quantify the registration error. The registration error was analyzed with synthetic MR images. These images were generated from interpatient and intrapatient variation models trained on 28 patients. Four synthetic post-treatment images were generated for each of four synthetic pretreatment images, resulting in 16 image registrations for both the T1- and T2-weighted images. The synthetic post-treatment images were registered to their corresponding synthetic pretreatment image. The registration error was calculated between the known deformation vector field and the generated deformation vector field from the image registration system. The registration error was also analyzed using a porcine phantom with ten implanted 0.35-mm diameter gold markers. The markers were visible on CT but not MRI. CT, T1-weighted MR, and T2-weighted MR images were taken in four different positions. The markers were contoured on the CT images and rigidly registered to their corresponding MR images. The MR images were deformably registered and the distance between the projected marker location and true marker location was measured as the registration error. The synthetic images were evaluated only on Velocity. Root mean square errors (RMSEs) of 0.76 mm in the left-right (LR) direction, 0.76 mm in the anteroposterior (AP) direction, and 0.69 mm in the superior-inferior (SI) direction were observed for the T1-weighted MR images. RMSEs of 1.1 mm in the LR direction, 0.75 mm in the AP direction, and 0.81 mm in the SI direction were observed for the T2-weighted MR images. The porcine phantom MR images, when evaluated with Velocity, had RMSEs of 1.8, 1.5, and 2.7 mm in the LR, AP, and SI directions for the T1-weighted images and 1.3, 1.2, and 1.6 mm in the LR, AP, and SI directions for the T2-weighted images. When the porcine phantom images were evaluated with the in-house demons-based algorithm, RMSEs were 1.2, 1.5, and 2.1 mm in the LR, AP, and SI directions for the T1-weighted images and 0.81, 1.1, and 1.1 mm in the LR, AP, and SI directions for the T2-weighted images. The MRI registration error was low for both Velocity and the in-house demons-based algorithm according to both image evaluation methods, with all RMSEs below 3 mm. This implies that both image registration systems can be used for longitudinal studies using MRI.

Alkaline Phosphatase-Instructed Self-Assembly of Gadolinium Nanofibers for Enhanced T2-Weighted Magnetic Resonance Imaging of Tumor.

Alkaline phosphatase (ALP) is an important enzyme but using ALP-instructed self-assembly of gadolinium nanofibers for enhanced T2-weighted magnetic resonance imaging (MRI) of tumor has not been reported. In this work, we rationally designed a hydrogelator Nap-FFFYp-EDA-DOTA(Gd) (1P) which, under the catalysis of ALP, was able to self-assemble into gadolinium nanofibers to form hydrogel Gel I for enhanced T2-weighted MR imaging of ALP activity in vitro and in tumor. T2 phantom MR imaging indicated that the transverse relaxivity (r2) value of Gel I was 33.9% higher than that of 1P and both of them were 1 order of magnitude higher than that of Gd-DTPA. In vivo T2-weighted MR imaging showed that, at 9.4 T, ALP-overexpressing HeLa tumors of 1P-injected mice showed obviously enhanced T2 contrast. We anticipate that, by replacing ALP with other enzymes, our approach could be applied for MR diagnosis of other diseases in the future.

Casp3/7-Instructed Intracellular Aggregation of Fe3O4 Nanoparticles Enhances T2 MR Imaging of Tumor Apoptosis.

Large magnetic nanoparticles or aggregates are advantageous in their magnetic resonance properties over ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs), but the former are cleared faster from the blood pool. Therefore, the "smart" strategy of intracellular aggregation of USPIO NPs is required for enhanced T2-weighted MR imaging. Herein, employing an enzyme-instructed condensation reaction, we rationally designed a small molecule Ac-Asp-Glu-Val-Asp-Cys(StBu)-Lys-CBT (1) to covalently modify USPIO NPs to prepare monodispersive Fe3O4@1 NPs. In vitro results showed that Fe3O4@1 NPs could be subjected to caspase 3 (Casp3)-instructed aggregation. T2 phantom MR imaging showed that the transverse molar relaxivity (r2) of Fe3O4@1 NPs with Casp3 or apoptotic HepG2 cells was significantly larger than those of control groups. In vivo tumor MR imaging results indicated that Fe3O4@1 NPs could be specifically applied for enhanced T2 MR imaging of tumor apoptosis. We propose that the enzyme-instructed intracellular aggregation of Fe3O4 NPs could be a novel strategy for the design of "smart" probes for efficient T2 MR imaging of in vivo biomarkers.