Positive Contrast Research Articles

Resolution and registration in dual-plane co-RASOR MR

Magnetic resonance imaging (MRI) has superior soft tissue contrast and lower interobserver variability compared to computed tomography and advances in equipment and pseudo-CT estimation have allowed for MR-only radiation therapy planning. Dedicated MR sequences have been used to localize paramagnetic structures with positive contrast, and most implanted seeds are gold fiducial markers (GFMs). We used a fast, dual-plane co-RASOR sequence to localize implanted GFMs with positive contrast in phantom and tissue to assess their resolution and registration accuracy of registration to CT. Off-resonant reconstructions of co-RASOR images were able to resolve GFMs down to 5 mm apart at 12 cm FOV. No systematic biases were observed by comparing registration of co-RASOR and bSSFP to CT images in an MR-compatible Lego phantom with a set of highly visible known points. The standard deviations of the MR to CT distance errors were <0.5 mm in all directions. We separated the component due to registration by comparing the two MR sequences, which had a maximum standard deviation of 0.36 mm in the SI-direction. Registration using the positive contrast points in a porcine sample phantom showed increased errors, but co-RASOR still performs acceptably with a target registration error of <0.75 mm. The dual-plane co-RASOR sequence could then be used for both registration and image tracking when performing MR-only radiation therapy planning.

Noninvasive label-free detection of circulating white and red blood clots in deep vessels with a focused photoacoustic probe.

Blood clotting is a serious clinical complication of many medical procedures and disorders including surgery, catheterization, transplantation, extracorporeal circuits, infections, and cancer. This complication leads to high patient morbidity and mortality due to clot-induced pulmonary embolism, stroke, and in some cases heart attack. Despite the clear medical significance, little progress has been made in developing the methods for detection of circulating blood clots (CBCs), also called emboli. We recently demonstrated the application of in vivo photoacoustic (PA) flow cytometry (PAFC) with unfocused ultrasound transducers for detection of CBCs in small vessels in a mouse model. In the current study, we extend applicability of PAFC for detection of CBCs in relatively large (1.5-2 mm) and deep (up to 5-6 mm) blood vessels in rat and rabbit models using a high pulse rate 1064 nm laser and focused ultrasound transducer with a central hole for an optic fiber. Employing phantoms and chemical activation of clotting, we demonstrated PA identification of white, red, and mixed CBCs producing negative, positive, and mixed PA contrast in blood background, respectively. We confirmed that PAFC can detect both red and white CBCs induced by microsurgical procedures, such as a needle or catheter insertion, as well as stroke modeled by injection of artificial clots. Our results show great potential for a PAFC diagnostic platform with a wearable PA fiber probe for diagnosis of thrombosis and embolism in vivo that is impossible with existing techniques.

Dual T1/ T2 Nanoscale Coordination Polymers as Novel Contrast Agents for MRI: A Preclinical Study for Brain Tumor.

In the last years, extensive attention has been paid on designing and developing functional imaging contrast agents for providing accurate noninvasive evaluation of pathology in vivo. However, the issue of false-positives or ambiguous imaging and the lack of a robust strategy for simultaneous dual-mode imaging remain to be fully addressed. One effective strategy for improving it is to rationally design magnetic resonance imaging (MRI) contrast agents (CAs) with intrinsic T1/ T2 dual-mode imaging features. In this work, the development and characterization of one-pot synthesized nanostructured coordination polymers (NCPs) which exhibit dual mode T1/ T2 MRI contrast behavior is described. The resulting material comprises the combination of different paramagnetic ions (Fe3+, Gd3+, Mn2+) with selected organic ligands able to induce the polymerization process and nanostructure stabilization. Among them, the Fe-based NCPs showed the best features in terms of colloidal stability, low toxicity, and dual T1/ T2 MRI contrast performance overcoming the main drawbacks of reported CAs. The dual-mode CA capability was evaluated by different means: in vitro phantoms, ex vivo and in vivo MRI, using a preclinical model of murine glioblastoma. Interestingly, the in vivo MRI of Fe-NCPs show T1 and T2 high contrast potential, allowing simultaneous recording of positive and negative contrast images in a very short period of time while being safer for the mouse. Moreover, the biodistribution assays reveals the persistence of the nanoparticles in the tumor and subsequent gradual clearance denoting their biodegradability. After a comparative study with commercial CAs, the results suggest these nanoplatforms as promising candidates for the development of dual-mode MRI CAs with clear advantages.

IsoPhasor: a generic and precise marker visualization, localization, and quantification method based on phase saddles in 3D MR imaging.

To derive a generic approach for accurate localization and characterization of susceptibility markers in MRI, compatible with many common types of pulse sequences, sampling trajectories, and acceleration methods. A susceptibility marker's dipolar phase evolution creates 3 saddles in the phase gradient of the spatial encoding, for each sampled data point in k-space. The signal originating from these saddles can be focused at the location of the marker to create positive contrast. The required phase shift can be calculated from the scan parameters and the marker properties, providing a marker detection algorithm generic for different scan types. The method was validated numerically and experimentally for a broad range of spherical susceptibility markers (0.3 < radius < 1.6 mm, 10 < |∆χ| < 3300 ppm), under various conditions. For all numerical and experimental phantoms, the average localization error was below one third of the voxel size, whereas the average error in magnetic strength quantification was 7%. The experiments included different pulse sequences (gradient echo, spin echo [SE], and free induction decay scans), sampling strategies (Cartesian, radial), and acceleration methods (echo planar imaging EPI, turbo SE). Spherical markers can be identified from their phase saddles, enabling clear visualization, precise localization, and accurate quantification of their magnetic strength, in a wide range of clinically relevant pulse sequences and sampling strategies.

An efficient tumor-inducible nanotheranostics for magnetic resonance imaging and enhanced photodynamic therapy

Though imaging guided photodynamic therapy (PDT) has emerged as a promising cancer therapy, how to enhance the PDT efficiency is still a research hotpot due to the tumor hypoxia and insufficient dosage of photosensitizers in the tumor site. Herein, a multifunctional theranostic nanoplatform was rationally constructed by nanoscale metal organic frameworks (NMOFs), bovine serum albumin (BSA), sulfadiazines (SDs), and MnO2. Porphyrin as organic ligands involved in the formation of NMOFs, which could allow more photosensitizers in one system. BSA as ideal carrier endows the nanoplatform with low toxicity and long circulation. SDs was introduced to provide actively targeting for the over-expressed carbonic anhydrase IX (CA IX) in tumor cells. More importantly, this nanoplatform can overcome the hypoxic microenvironment via down-regulating CA IX and catalyzing H2O2 to generate O2, resulting in significantly enhanced PDT effect, which was demonstrated by the photocytotoxicity against 4T1 cells and the decreased tumor volume. In addition, in vitro/vivo T1-weighted MRI results showed that the nanoplatform could be served as positive MRI contrast agent with a higher longitudinal relaxivity value (r1) at 6.09 mM−1 s−1 than that of clinical clinical contrast agent (Gd-DTPA, r1 = 4.33 mM−1 s−1). Such theranostic nanoplatform integrates multifunctional contents into one system and thereby provides a new strategy for targeted tumor therapy.

The effect of size and aspect ratio of Fe-MIL-88B-NH2 metal-organic frameworks on their relaxivity and contrast enhancement properties in MRI: in vitro and in vivo studies

Metal-organic frameworks (MOFs) have shown a great potential as a novel contrast agent in magnetic resonance imaging (MRI) due to their unique properties including versatile structures, composition, and surface chemistry. Fe-MIL-88B-NH2 (MILs) was synthesized using Fe+3 ions and 2-aminoterephthalic acids (NH2-BDC) in the presence of acetic acid and Pluronic F127 under a hydrothermal process. Three MILs in different sizes were synthesized by using variant CH3COOH/Fe+3 molar ratios and denoted as MIL-S, MIL-M, and MIL-L having average sizes of 60, 350, and 730 nm, respectively. The effect of aspect ratio and particle size of MILs was investigated on proton relaxivity and contrast enhancement in aqueous, in vitro, and in vivo MR images. MRI study indicated that by increasing the MILs size, the incremental transverse relaxivity was achieved from 13.53 to 50.80 for r2 and from 38.75 to 60.25 for r2*, while the difference between r2 and r2* was decreased obviously. The r2/r1 ratios were found to be 5.80, 42.27, and 127.00 for MIL-S, MIL-M, and MIL-L, respectively. All MILs demonstrated T2-weighted MR imaging performance. Furthermore, no susceptibility artifacts were observed on T2-weighted images of MILs. By decreasing the size of MILs, r2/r1 ratio was reduced sharply and T1 contrast was also observed for MIL-S. MIL-S was used for in vitro and in vivo study due to its capability in simultaneous T1 and T2 contrast enhancements. MTT and hemolysis assays showed no significant cytotoxicity and hemolysis for MIL-S against normal human breast cell line (MCF-10A) and red blood cells, respectively, at concentrations of Fe+3 up to 300 μg/mL (p < 0.05). T1-weighted images acquired from in vitro study interestingly showed that the signal intensity of MIL-S is more than Dotarem. The in vivo experiment revealed that the signal intensity of mice liver decreased sharply after injection resulting in increase of negative contrast enhancement. The negative contrast enhancement decreased gradually by the time under T2-weighted imaging mode confirming application of MIL-S as a T2 contrast agent in biomedical applications (up to 12 h post-injection). Although a decrease of the size resulted in bright contrast in aqueous solution for MIL-S, it did not show proper efficiency for in vivo positive contrast enhancement. The advantages, including simple preparation and accessibility, acceptable potency and selectivity, blood compatibility, and suitable cytocompatibility as well as enough circulation time, make MIL-S as a dual MRI contrast agent to differentiate between low-contrast tissues for in vivo experiments.

Utility of radiopaque urinary catheter placement before computed tomographic examination in two dogs with multiple pelvic fractures

Pelvic fractures are a common sequel to traumatic injuries in dogs, often caused by vehicular collisions. Urethral injury is a recognised complication of pelvic trauma. Retrograde positive contrast urethrography is...

Reward shifts in forced-choice and free-choice autoshaping with rats.

Successive negative contrast (SNC) involves a disruption of behavior when the paired reward is unexpectedly reduced from a large to a small amount, relative to a control always receiving the small amount. Five experiments with rats explored SNC in the Pavlovian autoshaping procedure in which a retractable lever is paired with the delivery of food pellets. In Experiment 1, a 12-to-2 pellet downshift either early in training (after 3 sessions) or late in training (after 20 sessions) yielded no significant evidence of SNC either in terms of lever pressing or goal entries. Experiment 2 showed that presession feeding (another form of reward devaluation) suppressed lever pressing in nonreinforced tests early in training. However, no statistical evidence of lever pressing suppression was found late in training. Presession feeding also suppressed lever pressing late in training if the test session included reinforcements. Experiment 3, using reward downshift, showed that adding a nontarget lever produced no statistical evidence of response suppression to the target lever during the downshift. Lever pressing to the target lever increased and goal entries tended to decrease after a 12-to-2 pellet downshift. Using a within-subject design and two target levers with distinct reward values (Experiment 4), reward downshift produced evidence of lever pressing enhancement in single-lever trials, but lever pressing suppression and a switch in preference to the unshifted lever in nonreinforced free-choice trials. Experiment 5 replicated these within-subject SNC effects, but found only modest evidence for a successive positive contrast effect in free-choice behavior. These results suggest that autoshaping in rats may induce response invigoration in forced-choice situations, but response suppression in free-choice situations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A hybrid system: MnO-incorporated mesoporous silica nanoparticles for theranostic applications

The need for an alternative $${ T}_{1}$$ contrast enhancer for magnetic resonance imaging (MRI) has been escalating owing to the toxicity profiles observed with the use of commercial contrast agents. Manganese oxide nanoparticles provide an optimal solution for the problem, as it is an endogenous co-factor for many enzymes in the biological system. In the present work, we have synthesized mesoporous silica nanoparticles encapsulated with manganese oxide nanoparticles as a positive contrast enhancer for MRI applications. Spherical magnetic MnO nanoparticles with divalent oxidation state were also synthesized and utilized as control to compare the efficiency of the nano-hybrid system. MRI showed higher contrast enhancement with the use of nano-hybrid and the relaxivity value for $${ T}_{1}$$ -weighted imaging was calculated to be $$2.6~\hbox {mg ml}^{-1}~\hbox {s}^{-1}$$ . Also, the developed system was validated for its usefulness as a therapeutic system through adsorption studies. Therefore, the nano-hybrid has the potential to be a competent MRI contrast enhancer that could be used for theranostic applications.

Imaging of a high concentration of iron labeled cells with positive contrast in a rat knee.

The sweep imaging with Fourier transformation (SWIFT) imaging technique has been shown to provide positive contrast from diluted cell suspensions labeled with super-paramagnetic iron oxide (SPIO) in a tissue, as an alternative to T2*-weighted imaging. Here we demonstrate a variation of the SWIFT technique that yields a hyperintense signal from a concentrated cell suspension. The proposed technique provides minimal background signal from host tissue and facilitates visualization of injected cells. The proton resonance frequency and linewidth were determined for SPIO solutions of different concentrations. The original SWIFT sequence was modified and a dual saturation Gaussian shape RF pulse with ~200 Hz bandwidth was incorporated into the acquisition protocol to suppress host tissue and fat signals. This modification of the original acquisition protocol permits the detection of a hyperintense signal from grafted cells with minimal background signal from the host tissue. SPIO particles not only induce broadening of NMR line-width but also an initiate proton resonance frequency shift. This shift is linearly proportional to the concentration of the iron oxide particles and induced by the bulk magnetic susceptibility of SPIOs. The shift of the resonance frequency of iron labeled cells allowed us effectively suppress the host tissues with saturation RF pulse to improve MRI detection of grafted cells. Iron oxide particles increase the resonance frequency of water proton signal. This shift permitted us to add the tissue/fat saturation RF pulse into the original SWIFT acquisition protocol and detect distinct hyperintense signals from grafted cells with minimal background signal from the host tissue.

MRI-based automated detection of implanted low dose rate (LDR) brachytherapy seeds using quantitative susceptibility mapping (QSM) and unsupervised machine learning (ML)

Background and purposePermanent seed brachytherapy is an established treatment option for localized prostate cancer. Currently, post-implant dosimetry is performed on CT images despite challenging target delineation due to limited soft tissue contrast. This work aims to develop an MRI-only workflow for post-implant dosimetry of prostate brachytherapy seeds. Material and methodsA prostate mimicking phantom containing twenty stranded I-125 dummy seeds and calcifications was constructed. A three-dimensional gradient-echo MR sequence was employed on 3T and 1.5T MR scanners. An optimized quantitative susceptibility mapping (QSM) technique was applied to generate positive contrast for the seeds and calcifications. Seed numbers, centroids, and orientations were determined using unsupervised machine learning algorithms (K-means and K-medoids clustering). The geometrical seed positions and the resulting dose distribution were compared to the clinical CT-based approach. ResultsThe optimized QSM-based method generated high quality positive contrast for the seeds that were significantly different from that for calcifications and could be easily differentiated by thresholding. The estimated seed centroids from both 3T and 1.5T MR data were in perfect agreement with the standard CT-based seed detection algorithm (maximum difference of 0.7 mm). The estimated seed orientations were highly correlated with the actual orientations (R > 0.98). ConclusionsThe proposed MRI-based workflow enabling an accurate and robust means to localize the seeds (position and orientation) upon validation on complex seed configurations, has the potential to replace the current widely practiced CT-based workflow.

Dynamic blood flow phantom with negative and positive photoacoustic contrasts.

In vivo photoacoustic (PA) flow cytometry (PAFC) has great clinical potential for early, noninvasive diagnosis of cancer, infections (e.g., malaria and bacteremia), sickle anemia, and cardiovascular disorders, including stroke prevention through detection of circulating white clots with negative PA contrast. For clinical applications, this diagnostic platform still requires optimization and calibration. We have already demonstrated that this need can be partially addressed by in vivo examination of large mouse blood vessels, which are similar to human vessels used. Here, we present an alternative method for PAFC optimization that utilizes novel, clinically relevant phantoms resembling pigmented skin, tissue, vessels, and flowing blood. This phantom consists of a scattering-absorbing medium with a melanin layer and plastic tube with flowing beads to model light-absorbing red blood cells (RBCs) and circulating tumor cells (CTCs), as well as transparent beads to model white blood cells and clots. Using a laser diode, we demonstrated the extraordinary ability of PAFC to dynamically detect fast-moving mimic CTCs with positive PA contrast and white clots with negative PA contrast in an RBC background. Time-resolved detection of the delayed PA signals from blood vessels demonstrated complete suppression of the PA background from the modeled pigmented skin. This novel, medically relevant, dynamic blood flow phantom can be used to calibrate and maintain PAFC parameters for routine clinical applications.

Multifunctional Rare-Earth Element Nanocrystals for Cell Labeling and Multimodal Imaging.

In this work, we describe a simple solvothermal route for the synthesis of Eu3+-doped gadolinium orthovanadate nanocrystals (Eu:GdVO4-PAA) functionalized with poly(acrylic)acid (PAA), that are applicable as cell labeling probes for multimodal cellular imaging. The Eu3+ doping of the vanadate matrix provides optical functionality, due to red photoluminescence after illumination with UV light. The Gd3+ ions of the nanocrystals reduce the T1 relaxation time of surrounding water protons, allowing these nanocrystals to act as a positive MRI contrast agent with a r1 relaxivity of 1.97 mM-1 s-1. Low background levels of Eu3+, Gd3+, and V5+ in biological systems make them an excellent label for elemental microscopy by Laser Ablation (LA)-ICP-MS. Synthesis resulted in polycrystalline nanocrystals with a hydrodynamic diameter of 55 nm and a crystal size of 36.7 nm, which were further characterized by X-ray diffraction (XRD), photoluminescence spectroscopy (PL) and transmission electron microscopy (TEM). The multifunctional nanocrystals were subsequently used for intracellular labeling of both human adipose-derived stem cells (MSCs) and A549 (adenocarcinomic human alveolar basal epithelial) cells.

Impact of ligands structure on formation of hydrophilic colloids from their Gd(III) complexes with high magnetic relaxivity

The present paper introduces specific structure of thiacalix[4]arenes derivatives adopting 1,3-alternate conformation with alkyl-carboxyl substituents as ligands for conversion of their complexes with Gd(III) ions into hydrophilic colloids with longitudinal (r1) and transverse relaxivities (r2) higher than that of Gd(III)-based commercial contrast agents (r1 = 20.53 and r2 = 23.46 mM−1 s−1 at 0.47 T). pH-dependent coordination of Gd(III) ions via carboxyl substituents of the thiacalix[4]arenes is the driving force for the complex formation, while the precipitation of the complexes is the basis for the colloids formation. Tert-butyl and butyl substituents of thiacalix[4]arenes were found to be of crucial impact on the complex precipitation. The specific inner- and outer-sphere ligand environment provided by the thiacalix[4]arene ligands was revealed as the optimal for high r1 and r2 values of the colloids. High relaxivities along with negligible cytotoxicity open up the possibility of their further use as positive contrast agents in magnetic resonance imaging (MRI).

Typology and Circuitry of Suppressed-by-Contrast Retinal Ganglion Cells.

Retinal ganglion cells (RGCs) relay ~40 parallel and independent streams of visual information, each encoding a specific feature of a visual scene, to the brain for further processing. The polarity of a visual neuron’s response to a change in contrast is generally the first characteristic used for functional classification: ON cells increase their spike rate to positive contrast; OFF cells increase their spike rate for negative contrast; ON-OFF cells increase their spike rate for both contrast polarities. Suppressed-by-Contrast (SbC) neurons represent a less well-known fourth category; they decrease firing below a baseline rate for both positive and negative contrasts. SbC RGCs were discovered over 50 years ago, and SbC visual neurons have now been found in the thalamus and primary visual cortex of several mammalian species, including primates. Recent discoveries of SbC RGCs in mice have provided new opportunities for tracing upstream circuits in the retina responsible for the SbC computation and downstream targets in the brain where this information is used. We review and clarify recent work on the circuit mechanism of the SbC computation in these RGCs. Studies of mechanism rely on precisely defined cell types, and we argue that, like ON, OFF, and ON-OFF RGCs, SbC RGCs consist of more than one type. A new appreciation of the diversity of SbC RGCs will help guide future work on their targets in the brain and their roles in visual perception and behavior.

When the weaker conquer: A contrast-dependent illusion of visual numerosity.

Humans and many nonhuman species have the capacity to perceive the approximate numerosity of a large set of elements. In the visual domain, various factors have been found to affect perceived numerosity, including, as studied here, the effect of luminance contrast. We report a new numerosity illusion in which low-contrast elements appear to be more numerous than high-contrast ones when intermixed in the same display, an effect we have called "the weak conquer the strong." The illusion occurred for both positive and negative contrast disks of the same sign; for example, white disks appeared less numerous than light gray disks when presented on a dark gray field (all positive contrasts). The illusion grew in size as the contrast difference between the two sets of disks became smaller but did not hold for disks with opposite signs, such as white and dark gray disks on a light gray field. The illusion was also eliminated when the disks were segregated spatially, in which case the high-contrast (white) disks and low-contrast (gray) disks appeared equally numerous. The illusion is due to the loss of some high-contrast elements; e.g., the perceived numerosity of the white disks was decreased whereas that of gray ones was preserved as shown by matching to isolated sets of white or gray disks. We speculate that failure in segregation coupled with error in contrast normalization may account for the numerosity illusion.

Reconceptualization innovative moments as a predictor of symptomatology improvement in treatment for depression

In previous studies, reconceptualization innovative moments were associated with successful psychotherapy. Reconceptualization has two components-(a) a positive temporal contrast between the past self and the present self (contrasting self [CS]) and (b) a description of how and/or why this change has occurred (change process [CP])-from the perspective of the client. The aim of this study is to analyse if CS and CP have the same association with outcomes as reconceptualization. Sixteen cases of clients with major depression (305 sessions) were analysed. Longitudinal regression models were used to explore if proportions of CS, CP, and reconceptualization predicted outcome measures and if outcome measures predicted CS, CP, and reconceptualization. Reconceptualization is less frequent than CS and CP taken separately, but reconceptualization was a better predictor of treatment outcomes than were its separate components. Moreover, symptom improvement did not predict reconceptualization. The construction of new meanings is important in improving depressive symptomatology. Psychotherapists can elicit these new meanings in their regular practice by posing questions that may help clients to conceptualize what is changing in themselves (CS) and questions of how this change is occurring (CP). The construction of an integrative account of these new meanings is associated with psychotherapeutic gains, and thus, reconceptualizing change could improve symptoms of depression.

Low-voltage SEM contrasts of steel surface studied by observations and electron trajectory simulations for GEMINI lens system.

Scanning electron microscopy (SEM) is a powerful tool for observing the surface of materials. Modern SEM systems have multiple detectors with different geometries. Consequently, the SEM image contrast depends on the instrument and experimental conditions even for the same sample. Understanding the SEM imaging mechanism is necessary to clarify SEM contrast. In this paper, low-voltage (LV)-SEM image contrast is investigated by comparing LV-SEM images and electron trajectory simulation results. Surface observations of oxides on a steel surface, positive charging contrast and topographic contrast in the image systematically changed with the working distance (WD). The electron trajectory simulation revealed the sharing of emitted electrons by the in-lens and Everhart-Thornley detectors, and systematic changes in the electron sharing caused by changes in WD. The image contrast was reasonably explained by the kinetic energy and take-off angle (acceptance plots) of the detected electrons derived by the electron trajectory simulations. This approach is essential to understanding the SEM image contrast obtained by SEM systems with multiple detectors. Thorough image simulations based on acceptance plots are required in future work.

Diagnostic Accuracy of Zero-Echo Time MRI for the Evaluation of Cervical Neural Foraminal Stenosis.

A cohort study. The aim of this study was to evaluate the clinical utility of Zero-Echo-Time (ZTE) magnetic resonance imaging (MRI) for the assessment of cervical neural foraminal stenosis (CNFS) through the comparison of inter-modality [computed tomography (CT) and ZTE-MRI] CNFS grade severity agreements. Conventional MRI limited in its ability to provide direct visualization of cortical bone. The highly organized tissue structure of cortical bone results in very short T2 values that preclude acquisition of sufficient signal intensity and positive image contrast. ZTE imaging permits visualization of tissues with very short transverse relaxation times, and is capable of displaying images with CT-like contrast. Thirty-four subjects were recruited from a clinical cohort of patients undergoing standard of care MRI and CT imaging for evaluation of CNFS. Standard of care CT imaging studies were obtained on all subjects within 6 months of their ZTE-MRI acquisition (mean time interval: 25.3 ± 54.1 days; median: 0 days). ZTE-MRI and CT imaging studies were evaluated and severity of CNFS was graded on a scale from 0 to 5 (0 = none; 5 = severe). Weighted-kappa statistics were used to assess agreement between ZTE and CT grades of CNFS on both sides (right and left) of each motion segment. Ordinal logistic mixed-effects regression analyses evaluated the effects of inter-modality position differences (flexion-extension curvature) on inter-modality differences in CNFS grade. Substantial agreement (κ = 0.72) was found between ZTE- and CT-based grades of CNFS. Significant inter-modality differences in cervical spine curvature were found for all motion segments, except C2-3 and C3-4 (P < 0.05). However, no significant relationship was found between inter-modality differences in curvature, and inter-modality differences in CNFS grade for any motion segment (P = 0.28). Results of the current study suggest that ZTE-MRI is well-suited for the evaluation of CNFS and may have the potential to obviate the need for concurrent CT scans in some cases. 2.

Cyclic RGD‐Coated Ultrasmall Gd2O3 Nanoparticles as Tumor‐Targeting Positive Magnetic Resonance Imaging Contrast Agents

The excellent theranostic properties of gadolinium oxide (Gd2O3) nanoparticles (GNPs) make them very useful as high‐performance positive magnetic resonance imaging (T1 MRI) contrast agents, X‐ray computed tomography (CT) contrast agents, and gadolinium neutron capture therapy (GdNCT) agents in tumor targeting. Among these applications, tumor‐targeting T1 MRI is investigated in this study. To this end, we employ cyclic RGDs (cRGDs; cyclic Arg–Gly–Asp peptides) as tumor‐targeting ligands to coat ultrasmall GNPs (particle diameter = 1.0–2.5 nm). Five types of commercial cRGDs are used in the coating. The cRGD‐coated GNPs (cRGD‐GNPs) are prepared through one‐pot syntheses. They exhibit longitudinal water‐proton relaxivity (r1) values of 10.0–18.7 s–1 mm–1, with r2/r1 ratios of 1.4–1.7 (r2 = transverse water‐proton relaxivity), which are 3–5 times higher than those of commercial Gd chelates. The in vivo tumor targeting of the cRGD‐GNPs is demonstrated by taking T1 MR images in a model mouse with a liver tumor using one of the five cRGD‐GNP sample solutions prepared. Approximately threefold contrast enhancements are observed in the T1 MR images in the tumor region of the liver than in the normal part of the liver, following intravenous administration of the solution. These results demonstrate that cRGD‐GNPs are potential tumor‐targeting T1 MRI contrast agents.