Development of a novel lipidic nanoparticle probe using liposomal encapsulated Gd2O3-DEG for molecular MRI.

Recently, it has been showed that gadolinium oxide nanoparticles can provide high-contrast enhancement in magnetic resonance imaging (MRI). Moreover, liposomes due to high biocompatibility have shown unique model systems, with the most successful application being the drug delivery system. As a suitable cell-tracking contrast agent (CA) in molecular MRI (mMRI), the synthesis and optimisation characteristic of a novel paramagnetic liposomes (PMLs) based on gadolinium nanoparticles, essentially composed of a new complex of gadolinium oxide-diethylene glycol (Gd2O3-DEG) loaded in liposomes have been determined in this research. Gd2O3-DEG was prepared by a new supervised polyol method and was encapsulated with liposome by the film hydration method. The paramagnetic liposome nanoparticle (PMLN) sizes ranged from 65 to 170 nm. The r1 of PMLNs and Gd2O3-DEG were much higher than that of Gd-diethylenetriamine penta-acetic acid (Gd-DTPA). In MC/9 cell lines, the experiments showed similar results as in water. PMLNs with lower T1 than Gd-DTPA are sensitive, positive MRI CA that could be attractive candidates for cellular and molecular lipid content targets such as diagnostic applications.

Lymph Node Metastases Detection Using Gd2O3@PCD as Novel Multifunctional Contrast Imaging Agent in Metabolic Magnetic Resonance Molecular Imaging.

Axillary lymph node detection is crucial to staging and prognosis of the lymph node metastatic spread in breast cancer. Currently, lymphoscintigraphy and blue dye, as the conventional methods to localize sentinel lymph nodes (SLNs), are invasive and can only be performed during surgery. This study has had a novel hybrid gadolinium oxide nanoparticle coating with Cyclodextrin-based polyester as a high-relaxivity T1 magnetic resonance molecular imaging (MRMI) contrast agent (CA). Twelve female BALB/c mice were randomly divided into three groups of four mice; each group was injected with 4T1 cells to obtain metastasis lymph nodes and diagnosed by using the 3D T1W (VIBE) MRI (Siemens 3T, Prisma). The synthesized Gd2O3@PCD nanoparticles with a suitable particle size range of 20-40 nm have had much higher longitudinal relaxivity (r 1) for Gd2O3@PCD and Gd-DOTA (Dotarem) with the values of 3.98 mM-1·s-1 ± 0.003 and 2.71 mM-1·s-1 ± 0.005, respectively. Identical MR images in coronal views were subsequently obtained to create time-intensity curves of the right axillary lymph nodes and to measure the contrast ratio (CR). The peak CR and qualitative assessment of axillary lymph nodes at five-time points were evaluated. After subcutaneous injection, the contrast ratio of axillary lymph node and tumor in mice exhibited CR peak of Gd2O3@PCD and Dotarem with the values of 2.21 ± 0.06 and 0.40 ± 0.004 for lymph node and 2.54 ± 0.04 and 1.21 ± 0.007 for the tumor, respectively. Furthermore, the lumbar-aortic lymph node is weakly visible in the original coronal image. In conclusion, the use of Gd2O3@PCD nanoparticles as novel MRMI CAs enables high resolution for the detection of lymph node metastasis in mice with the potential capability for breast cancer diagnostic imaging.

Novel FMRI-Compatible wrist robotic device for brain activation assessment during rehabilitation exercise.

Magnetic Resonance Imaging (MRI) can be applied to study the effects of rehabilitation strategies for neuroscience research. An MRI-wrist robot is designed and used as a clinical tool to examine the process of the brain plasticity changes. In this robot, the patient actuation is accomplished with two standard air cylinders, located inside the MRI chamber with two degrees of freedom (flexion-extension and ulna-radial deviation) with pneumatic air transmission, consisting of simple mechanism converting rotary motion to linear independently. A pilot study of brain image aiming at revealing more effective therapeutic strategies carried out to confirm the technical aspects of the development and validation. In a healthy subject, both wrist movement of robot and subject demonstrated brain activity in the contralateral primary somatosensory cortex. Because the robot does not move during the patient's body, a stand was designed to allow the wrist robot and patient to fit comfortably within the MRI machine. While all the parts of the robot were carefully selected with strict MRI compatibility requirements, the robot was tested by presenting some pilot imaging data with null effects on the image quality, as well. Finally, the possible further development of the robot has been introduced for a rehabilitation assessment.

Dosimetry and Radioenhancement Comparison of Gold Nanoparticles in Kilovoltage and Megavoltage Radiotherapy using MAGAT Polymer Gel Dosimeter.

BACKGROUND: Numerous unique characteristics of the nanosized gold, including high atomic number, low toxicity, and high biocompatibility make it one of the most appropriate nanostructures to boost radiotherapy efficacy. Many in-vivo and in-vitro investigations have indicated that gold nanoparticles (AuNPs) can significantly increase tumor injuries in low kilovoltage radiotherapy. While deep-lying tumors require much higher energy levels with greater penetration power, and investigations carried out in megavoltage energy range show contradictory results. OBJECTIVE: In this study, we quantitatively assess and compare dose enhancement factors (DEFs) obtained through AuNPs under radiation of Cobalt-60 source (1.25MeV) versus Iridium-192 source (380 KeV) using MAGAT gel dosimeter. MATERIAL AND METHODS: MAGAT polymer gel in both pure and combined with 0.2 mM AuNPs was synthesized. In order to quantify the effect of energy on DEF, irradiation was carried out by Co-60 external radiotherapy and Ir-192 internal radiotherapy. Finally, readings of irradiated and non-irradiated gels were performed by MR imaging. RESULTS: The radiation-induced R2 (1/T2) changes of the gel tubes doped with AuNPs compared to control samples, upon irradiation of beams released by Ir-192 source showed a significant dose enhancement (15.31% ±0.30) relative to the Co-60 external radiotherapy (5.85% ±0.14). CONCLUSION: This preliminary study suggests the feasibility of using AuNPs in radiation therapy (RT), especially in low-energy sources of brachytherapy. In addition, MAGAT polymer gel, as a powerful dosimeter, could be used for 3D visualization of radiation dose distribution of AuNPs in radiotherapy.

Spatial frequency modulates the human visual cortical response to temporal frequency variation: an fMRI study.

The brain response to temporal frequencies (TF) has been already reported, but with no study for different TFs with respect to various spatial frequencies (SF). Functional Magnetic Resonance Imaging (fMRI) experiments were performed by 1.5 Tesla General Electric-system in 14 volunteers (9 males and 5 females, range 19-26 years) during square-wave reversal checkerboard visual stimulation with different temporal frequencies of 4, 6, 8 and 10 Hz in two states of low SF of 0.5 and high SF of 8 cpd (cycles/degree). The activation map was created using the data obtained from the block designed fMRI study. Pixels whose correlation coefficient value was above a threshold of 0.33, in significant level P<0.01 were considered activated. The average percentage BOLD (blood oxygenation level dependent) signal change for all activated pixels within the occipital lobe, multiplied by the total number of activated pixels within the occipital lobe, was used as the criterion for the strength of the fMRI signal at each state of TF&SF. The results demonstrated that the strength of the fMRI signal in response to different TFs was maximum in 6Hz for high SF of 8 cpd, while it was maximum at TF of 8Hz for low SF of 0.5 cpd. The results of this study agree with the results of animal invasive neurophysiological studies showing spatial and temporal frequency selectivity of neurons in visual cortical areas. These results can be useful for vision therapy (such as the treatment of Amblyopia) and selecting visual task in fMRI studies.

Platelet-based MPLE denoising of SPECT images: phantom and patient study.

In this study the evaluation of a Platelet-based Maximum Penalized Likelihood Estimation (MPLE) for denoising SPECT images was performed and compared with other denoising methods such as Wavelets or Butterworth filteration. Platelet-based MPLE factorization as a multiscale decomposition approach has been already proposed for better edges and surfaces representation due to Poisson noise and inherent smoothness of this kind of images. We applied this approach on both simulated and real SPECT images. For NEMA phantom images, the measured noise levels before (M(b)) and after (M(a)) denoising with Platelet-based MPLE approach were M(b)=2.1732, M(a)=0.1399. In patient study for 32 cardiac SPECT images, the difference between noise level and SNR before and after the approach were (M(b)=3.7607, SNR(b)=9.7762, M(a)=0.7374, SNR(a)=41.0848) respectively. Thus the Coefficient Variance (C.V) of SNR values for denoised images with this algorithm as compared with Butterworth filter, (145/33%) was found. For 32 brain SPECT images the Coefficient Variance of SNR values, (196/17%) was obtained. Our results shows that Platelet-based MPLE is a useful method for denoising SPECT images considering better homogenous image, improvements in SNR, better radioactive uptake in target organ and reduction of interfering activity from background radiation to compare to that of other conventional denoising methods.

Spatial frequency dependence of the human visual cortical response to temporal frequency modulation studied by fMRI.

The brain response to temporal frequencies (TF) has been already reported, but with no study for different TF in respect to various spatial frequencies (SF). fMRI was performed by 1.5T GE-system in 14 volunteers during checkerboard visual stimulation, with TFs of 4, 6, 8 and 10Hz in low and high SFs of 0.5 and 8cpd. The averaged percentage BOLD signal changes demonstrated the amplitude of the fMRI response to different TFs which was maximally at 6Hz for high SF of 8cpd, and at 8Hz for low SF of 0.5cpd. The results are useful for vision therapy (such as the treatment of Amblyopia) and for fMRI applications incorporating visual tasks.

Optimization of MR-Relaxometry for BMD-measurements and its Correlation with DEXA.

The aim of this study was to optimize MRI conventional protocols for BMD measurements using MR-Relaxometry in systems not facilitated with special multi echo protocols. Since, cortical and trabecular bone separation can not be performed in DEXA, so the results might lead to erroneous interpretation of BMD values. One method for bone quality determination is MR relaxometry that derives R2(=1/T2), R2*(=1/T2*) and R2'(=R2*-R2). This study was performed by 1.5T MRI system(Picker Vista-Q800), an uniformity phantom(1.25gr/l CuSO4, with T2=200ms for calibration), a body RF-Coil, 7 normal, 7 osteopenia, 7 osteoporosis volunteers and Lunar DEXA system(DPX-MD). To determine R2*and R2, multi GE and SE protocols with different TE/TR were used. Then in phantom and in coronal section of femoral-neck, relaxation rates were compared with BMD. The slope of neperian-logarithm of signal vs. TE in GE as -R2*used for protocol optimization. Therefore, for phantom calibration, optimized GE parameters of TE=13.42/18/26.8 ms, TR=800ms and ST=8mm used for the measurement of R2*, while, the measurement of R2 required the optimized SE parameters of TE=30/60/90/120ms, TR=800ms and ST=8mm, with CV(R2*)=2.96%, CV(R2)=3%, respectively. In volunteers for SE, TE of 36/54/63/72ms and TR=800ms were used, while, for GE the TEs/TR were the same as those of phantom study. R2*and R2' showed a significant positive correlation with BMD, r=0.62(p<0.05) & r=0.62(p<0.05) respectively. Finally, in accordance with DEXA values, the results showed that MR-Relaxometry is a proper tool for BMD-measurements in femoral-neck. Also it may be used as a complement method for DEXA failure in BMD-assessments.