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PurposeThe purpose of this study was to improve triggering efficiency of the prospective respiratory amplitude-triggered 4-dimensional magnetic resonance imaging (4DMRI) method and to develop a 4DMRI imaging protocol that could offer T2 weighting for better tumor visualization, good spatial coverage and spatial resolution, and respiratory motion sampling within a reasonable amount of time for radiation therapy applications.Methods and materialsThe respiratory state splitting (RSS) and multi-shot acquisition (MSA) methods were analytically compared and validated in a simulation study by using the respiratory signals from 10 healthy human subjects. The RSS method was more effective in improving triggering efficiency. It was implemented in prospective respiratory amplitude-triggered 4DMRI. 4DMRI image datasets were acquired from 5 healthy human subjects. Liver motion was estimated using the acquired 4DMRI image datasets.ResultsThe simulation study showed the RSS method was more effective for improving triggering efficiency than the MSA method. The average reductions in 4DMRI acquisition times were 36% and 10% for the RSS and MSA methods, respectively. The human subject study showed that T2-weighted 4DMRI with 10 respiratory states, 60 slices at a spatial resolution of 1.5 × 1.5 × 3.0 mm(3) could be acquired in 9 to 18 minutes, depending on the individual's breath pattern. Based on the acquired 4DMRI image datasets, the ranges of peak-to-peak liver displacements among 5 human subjects were 9.0 to 12.9 mm, 2.5 to 3.9 mm, and 0.5 to 2.3 mm in superior-inferior, anterior-posterior, and left-right directions, respectively.ConclusionsWe demonstrated that with the RSS method, it was feasible to acquire high-quality T2-weighted 4DMRI within a reasonable amount of time for radiation therapy applications.

High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1w contrast nanoparticle with improved safety. We report the development, optimization, and characterization of a gadolinium–manganese hybrid nanocolloid (MnOL-Gd NC; 138 ± 10 (D av )/nm; PDI: 0.06; zeta: − 27 ± 2 mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5 nM/voxel and lower levels consistent with the level expression anticipated for sparse biomarkers, such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10 nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo while retaining minimal transmetallation risk. From the Clinical Editor The authors developed a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC) in this study. These were used as a high-relaxivity paramagnetic MR molecular imaging agent in experimental models. It was shown that MnOL-Gd NC could provide high T1w MR contrast for targeted imaging. As the level of gadolinium used was reduced, there was also reduced risk of systemic side effects from complement activation. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to use magnetic resonance (MR) molecular imaging to 1) characterize the aortic neovascular development in a rat model of atherosclerosis and 2) monitor the effects of an appetite suppressant on vascular angiogenesis progression. Background: The James C. Russell:LA corpulent rat strain (JCR:LA-cp) is a model of metabolic syndrome characterized by obesity, insulin resistance, hyperlipidemia, and vasculopathy, although plaque neovascularity has not been reported in this strain. MR molecular imaging with ανβ3-targeted nanoparticles can serially map angiogenesis in the aortic wall and monitor the progression of atherosclerosis. Methods: Six-week old JCR:LA-cp (+/?; lean, n = 5) and JCR:LA-cp (cp/cp; obese, n = 5) rats received standard chow, and 6 obese rats were fed the appetite suppressant benfluorex over 16 weeks. Body weight and food consumption were recorded at baseline and weeks 4, 8, 12, and 16. MR molecular imaging with ανβ3-targeted paramagnetic nanoparticles was performed at weeks 0, 8, and 16. Fasted plasma triglyceride, cholesterol, and glucose were measured immediately before MR scans. Plasma insulin and leptin levels were assayed at weeks 8 and 16. Results: Benfluorex reduced food consumption (p < 0.05) to the same rate as lean animals, but had no effect on serum cholesterol or triglyceride levels. MR (3-T) aortic signal enhancement with ανβ3-targeted nanoparticles was initially equivalent between groups, but increased (p < 0.05) in the untreated obese animals over 16 weeks. No signal change (p > 0.05) was observed in the benfluorex-treated or lean rat groups. MR differences paralleled adventitial microvessel counts, which increased (p < 0.05) among the obese rats and were equivalently low in the lean and benfluorex-treated animals (p > 0.05). Body weight, insulin, and leptin were decreased (p < 0.05) from the untreated obese animals by benfluorex, but not to the lean control levels (p < 0.05). Conclusions: Neovascular expansion is a prominent feature of the JCR:LA-cp model. MR imaging with ανβ3-targeted nanoparticles provided a noninvasive assessment of angiogenesis in untreated obese rats, which was suppressed by benfluorex. [Copyright &y& Elsevier]

Objectives: Studies were performed to develop a prolonged antiangiogenesis therapy regimen based on theranostic ανβ3-targeted nanoparticles. Background: Antiangiogenesis therapy may normalize atherosclerotic plaque vasculature and promote plaque stabilization. ανβ3-targeted paramagnetic nanoparticles can quantify atherosclerotic angiogenesis and incorporate fumagillin to elicit acute antiangiogenic effects. Methods: In the first experiment, hyperlipidemic rabbits received ανβ3-targeted fumagillin nanoparticles (0, 30, or 90 μg/kg) with either a continued high fat diet or conversion to standard chow. The antiangiogenic response was followed for 4 weeks by cardiac magnetic resonance (CMR) molecular imaging with ανβ3-targeted paramagnetic nanoparticles. In a second 8-week study, atherosclerotic rabbits received atorvastatin (0 or 44 mg/kg diet) alone or with ανβ3-targeted fumagillin nanoparticles (only week 0 vs. weeks 0 and 4), and angiogenesis was monitored with CMR molecular imaging. Histology was performed to determine the location of bound nanoparticles and to correlate the level of CMR enhancement with the density of angiogenic vessels. Results: The ανβ3-targeted fumagillin nanoparticles reduced the neovascular signal by 50% to 75% at 1 week and maintained this effect for 3 weeks regardless of diet and drug dose. In the second study, atherosclerotic rabbits receiving statin alone had no antineovascular benefit over 8 weeks. The ανβ3-targeted fumagillin nanoparticles decreased aortic angiogenesis for 3 weeks as in study 1, and readministration on week 4 reproduced the 3-week antineovascular response with no carry-over benefit. However, atorvastatin and 2 doses of ανβ3-targeted fumagillin nanoparticles (0 and 4 weeks) achieved marked and sustainable antiangiogenesis. Microscopic studies corroborated the high correlation between CMR signal and neovessel counts and confirmed that the ανβ3-targeted nanoparticles were constrained to the vasculature of the aortic adventia. Conclusions: The CMR molecular imaging with ανβ3-targeted paramagnetic nanoparticles demonstrated that the acute antiangiogenic effects of ανβ3-targeted fumagillin nanoparticles could be prolonged when combined with atorvastatin, representing a potential strategy to evaluate antiangiogenic treatment and plaque stability. [Copyright &y& Elsevier]

Rationale and Objectives: We studied preparatory strategies for high-resolution human eye in vivo imaging with commercially available magnets and coils. Materials and Methods: We imaged normal volunteers on 1.5T systems by Philips, GE, and Siemens, using commercial ∼9 cm temporomandibular joint receive coils. Subjects fixated the nonimaged eye on a target. We compared signal (S) to tissue noise (Nt) and system noise (Ns) between images acquired with the imaged eye: 1) open, 2) held closed, 3) taped closed, and 4) taped closed with overlying water-soaked gauze. We standardized technique 4 to compare studies between manufacturers using T1-weighted parameters (repetition time/echo time/flip angle/number of signal averages = 400 ms/10–17ms/90°/4–6, in-plane resolution ∼250 × 250 μm2; 2–3 mm slices, image time = 4.3–5.2 min). We obtained similar images of an enucleated human eye to estimate in vivo effects of microsaccades and ocular pulsations. Results: Measurements of S/Nt and S/Ns gave surprising results of Nt < Ns in some instances. Ns/Nt was ≅ 1, varying ∼20%, when the eye was taped shut and covered with water-soaked gauze. T1-weighted spin echo sequences, using technique 4, produced high-quality images with good S/Nt on all systems. Images from the three manufacturers were comparable when parameters were normalized for pulse repetition time, echo time, number of signal averages, bandwidth in Hz/pixel, and reconstruction matrix. Images of the enucleated eye produced S/Nt ratios that were comparable to in vivo images in some structures. Conclusions: Our best preparatory technique produced images with in-plane resolution of ∼250 μm in 4–5 minutes with three commercial 1.5T systems. The in vivo S/Nt was comparable to in vitro values in most solid tissues but decreased in most fluid compartments. [Copyright &y& Elsevier]

An abstract of the article "F Magnetic Resonance Molecular Imaging With Perfluorocarbon Nanoparticles," by Gregory M. Lanza and colleagues is presented.