Relationship between imaging parameters and distortion in magnetic resonance images for gamma knife treatment planning.

In magnetic resonance imaging (MRI), it is necessary to reduce image distortion as much as possible because it suppresses the increase in the planning target volume. This study investigated the relationship between imaging parameters and image distortion when using G-frames. The images were obtained using a 1.5-T MRI system with a 09-101 Pro-MRI phantom. Image distortion was measured by changing the RF pulse mode, gradient mode, asymmetric echo, and bandwidth (BW). The image distortion was increased in the high RF mode than in the Normal mode. The image distortion increased in the following order: Whisper â‰¦ Normal < Fast in the different gradient modes. The image distortion increased in the following order: Without â‰¦ Weak < Strong in the different asymmetric echo modes. The image distortion increased in the following order: 300 Hz/pixel > 670 Hz/pixel â‰§ REF (150 Hz/pixel) in the different Bw. The relationship between parameters and image distortion was clarified in this study when G-frames were used for gamma knife therapy. There is had relationship between the parameters causing variation in the gradient magnetic field and image distortion. Therefore, these parameters should be adjusted to minimize distortion.

Dual Therapeutic Action of a Neutralizing Anti-FGF2 Aptamer in Bone Disease and Bone Cancer Pain.

Fibroblast growth factor 2 (FGF2) plays a crucial role in bone remodeling and disease progression. However, the potential of FGF2 antagonists for treatment of patients with bone diseases has not yet been explored. Therefore, we generated a novel RNA aptamer, APT-F2, specific for human FGF2 and characterized its properties in vitro and in vivo. APT-F2 blocked binding of FGF2 to each of its four cellular receptors, inhibited FGF2-induced downstream signaling and cells proliferation, and restored osteoblast differentiation blocked by FGF2. APT-F2P, a PEGylated form of APT-F2, effectively blocked the bone disruption in mouse and rat models of arthritis and osteoporosis. Treatment with APT-F2P also exerted a strong analgesic effect, equivalent to morphine, in a mouse model of bone cancer pain. These findings demonstrated dual therapeutic action of APT-F2P in bone diseases and pain, providing a promising approach to the treatment of bone diseases.

Carotid and aortic plaque imaging using 3D gradient-echo imaging and the three-point Dixon method with improved motion-sensitized driven-equilibrium (iMSDE).

BACKGROUND: We devised a method that combines the 3D-Dixon-gradientecho (GRE) method with an improved motion-sensitized driven-equilibrium (iMSDE) to suppress blood flow signals. PURPOSE: The purpose of this study was to evaluate the effectiveness of the new method we developed plaque imaging method (3D-Dixon-GRE with the iMSDE method). STUDY TYPE: Retrospective cohort. POPULATION: Thirty-nine patients who underwent cervical plaque imaging. FIELD STRENGTH/SEQUENCE: 3.0 T/3D-GRE. ASSESSMENT: Signal intensities of the common carotid artery, aorta, plaque, muscle, and subcutaneous fat were measured through the VISTA and the 3D-Dixon-GRE with iMSDE methods, and each contrast was calculated. STATISTICAL TEST: Used the Mann Whitney U test. P-values below 0.05 were considered statistically significant. RESULTS: Plaque and muscle contrast estimated through the VISTA method and 3D-Dixon-GRE with iMSDE method was 1.60 ± 0.96 and 2.04 ± 1.06, respectively, (P < 0.05). The contrast between the flow (common carotid artery and Aorta) and muscle according to the VISTA method and 3D-Dixon-GRE with iMSDE method was 0.24 ± 0.11 and 0.40 ± 0.12, respectively (P < 0.001). Finally, the mean contrast for subcutaneous fat and muscle at six locations was 3.05 ± 1.25 and 0.81 ± 0.23 for the VISTA method and 3D-Dixon-GRE with the iMSDE method, respectively (P < 0.001). DATA CONCLUSION: Compared to the conventional method (VISTA), the 3D-Dixon-GRE with iMSDE method is preferable in relation to the fat suppression effect, but it is disadvantageous regarding blood flow signal suppression. Therefore, the 3D-Dixon-GRE with the iMSDE method could be considered useful for plaque imaging.

RNA plasticity and selectivity applicable to therapeutics and novel biosensor development.

Aptamers are short, single-stranded nucleic acid sequences that are selected in vitro from large oligonucleotide libraries based on their high affinity to a target molecule. Hence, aptamers can be thought of as a nucleic acid analog to antibodies. However, several viewpoints hold that the potential of aptamers arises from interesting characteristics that are distinct from, or in some cases, superior to those of antibodies. This review summarizes the recent achievements in aptamer programs developed in our laboratory against basic and therapeutic protein targets. Through these studies, we became aware of the remarkable conformational plasticity and selectivity of RNA, on which the published report has not shed much light even though this is evidently a crucial feature for the strong specificity and affinity of RNA aptamers.

Influence of half Fourier and elliptical scanning (radial scan) on magnetic resonance images.

This study aimed to investigate the effect of using slice partial Fourier (SPF), phase partial Fourier (PPF), and radial scan (Elliptical scanning) methods on image quality. Changes in signal-to-noise ratio (SNR), effective slice thickness, and in-plane resolution were measured in 3D-gradient echo when SPF, PPF, and radial scan were used. Effective slice thickness increased and SNR increased when SPF was used; in-plane resolution decreased and SNR decreased when PPF was used; effective slice thickness did not change, in-plane resolution decreased, and SNR increased when the radial scan method was used. The radial scan method reduces image quality and imaging time compared to those in the SPF and PPF methods.

Conformational plasticity of RNA for target recognition as revealed by the 2.15 A crystal structure of a human IgG-aptamer complex.

Aptamers are short single-stranded nucleic acids with high affinity to target molecules and are applicable to therapeutics and diagnostics. Regardless of an increasing number of reported aptamers, the structural basis of the interaction of RNA aptamer with proteins is poorly understood. Here, we determined the 2.15 Å crystal structure of the Fc fragment of human IgG1 (hFc1) complexed with an anti-Fc RNA aptamer. The aptamer adopts a characteristic structure fit to hFc1 that is stabilized by a calcium ion, and the binding activity of the aptamer can be controlled many times by calcium chelation and addition. Importantly, the aptamer-hFc1 interaction involves mainly van der Waals contacts and hydrogen bonds rather than electrostatic forces, in contrast to other known aptamer-protein complexes. Moreover, the aptamer-hFc1 interaction involves human IgG-specific amino acids, rendering the aptamer specific to human IgGs, and not crossreactive to other species IgGs. Hence, the aptamer is a potent alternative for protein A affinity purification of Fc-fusion proteins and therapeutic antibodies. These results demonstrate, from a structural viewpoint, that conformational plasticity and selectivity of an RNA aptamer is achieved by multiple interactions other than electrostatic forces, which is applicable to many protein targets of low or no affinity to nucleic acids.

Carbon-Ion Radiotherapy Using Metal Artifact Reduction Computed Tomography in a Patient with Prostate Cancer with Bilateral Hip Prostheses: A Case Report.

Carbon-ion radiotherapy (CIRT) for prostate cancer is both safe and efficacious; beam range calculations use relative stopping power ratio, which is derived from computed tomography (CT) values. However, hip prostheses are made of high atomic number materials and show severe artifacts on CT images. Therefore, it is not possible to accurately calculate dose distribution for CIRT in patients with prostate cancer with hip prostheses. Here, we describe the management of a 77-year-old man with prostate cancer who had previously undergone bilateral hip replacement. CIRT, in combination with androgen deprivation therapy, was recommended as definitive treatment for prostate cancer. Planning CT, magnetic resonance (MRI), and CT images with metal artifact reduction (MAR) were acquired for CIRT planning. MRI and MAR images were superimposed on the planning CT to delineate target volume and organs at risk. The radiation treatment plan consisted of a total dose of 51.6 Gy (relative biological effect) to be delivered in 12 fractions over 3 weeks, and the patient was irradiated in the supine and prone positions with a vertical beam, on alternating days. CIRT was completed as scheduled. No adverse events were observed during treatment or at 3 months after treatment initiation. While we show that CIRT may be a treatment option for patients with prostate cancer with bilateral hip prostheses, further studies are needed to evaluate treatment efficacy and late toxicity and to determine how CIRT can be administered to patients with prostate cancer with bilateral hip prostheses.

Robust treatment planning in scanned carbon-ion radiotherapy for pancreatic cancer: Clinical verification using in-room computed tomography images.

Purpose: Carbon-ion beam (C-beam) has a sharp dose distribution called the Bragg peak. Carbon-ion radiation therapy, such as stereotactic body radiotherapy in photon radiotherapy, can be completed in a short period by concentrating the radiation dose on the tumor while minimizing the dose to organs at-risk. However, the stopping position of C-beam is sensitive to density variations along the beam path and such variations can lower the tumor dose as well as cause the delivery of an unexpectedly high dose to the organs at risk. We evaluated the clinical efficacy of a robust planning technique considering gastrointestinal gas (G-gas) to deliver accurate radiation doses in carbon-ion radiotherapy for pancreatic cancer. Materials and methods: We focused on the computed tomography (CT) value replacement method. Replacement signifies the overwriting of CT values in the CT images. The most effective replacement method for robust treatment planning was determined by verifying the effects of the three replacement patterns. We selected 10 consecutive patients. Pattern 1 replaces the CT value of the G-gas contours with the value of the region without G-gas (P1). This condition indicates a no-gas state. Pattern 2 replaces each gastrointestinal contour using the mean CT value of each contour (P2). The effect of G-gas was included in the replacement value. Pattern 3 indicates no replacement (P3). We analyzed variations in the target coverage (TC) and homogeneity index (HI) from the initial plan using in-room CT images. We then performed correlation analysis on the variations in G-gas, TC, and HI to evaluate the robustness against G-gas. Results: Analysis of variations in TC and HI revealed a significant difference between P1 and P3 and between P2 and P3. Although no statistically significant difference was observed between P1 and P2, variations, including the median, tended to be fewer in P2. The correlation analyses for G-gas, TC, and HI showed that P2 was less likely to be affected by G-gas. Conclusion: For a treatment plan that is robust to G-gas, P2 mean replacement method should be used. This method does not necessitate any particular software or equipment, and is convenient to implement in clinical practice.

Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population.

CD4(+)CD25(+) regulatory T (Treg) cells are crucial mediators of autoimmune tolerance. The factors that regulate Treg cells, however, are largely unknown. Here, we show that deficiency in midkine (MK), a heparin-binding growth factor involved in oncogenesis, inflammation, and tissue repair, attenuated experimental autoimmune encephalomyelitis (EAE) because of an expansion of the Treg cell population in peripheral lymph nodes and decreased numbers of autoreactive T-helper type 1 (T(H)1) and T(H)17 cells. MK decreased the Treg cell population ex vivo in a dose-dependent manner by suppression of STAT5 phosphorylation that is essential for Foxp3 expression. Moreover, administration of anti-MK RNA aptamers significantly expanded the Treg cell population and alleviated EAE symptoms. These observations indicate that MK serves as a critical suppressor of Treg cell expansion, and inhibition of MK using RNA aptamers may provide an effective therapeutic strategy against autoimmune diseases, including multiple sclerosis.

Structural and molecular basis for hyperspecificity of RNA aptamer to human immunoglobulin G.

Potential applications for functional RNAs are rapidly expanding, not only to address functions based on primary nucleotide sequences, but also by RNA aptamer, which can suppress the activity of any target molecule. Aptamers are short DNA or RNA folded molecules that can be selected in vitro on the basis of their high affinity for a target molecule. Here, we demonstrate the ability of RNA aptamers to recognize--and bind to--human IgG with high specificity and affinity. An optimized 23-nucleotide aptamer, Apt8-2, was prepared, and was shown to bind to the Fc domain of human IgG, but not to other IgG's, with high affinity. Apt8-2 was observed to compete with protein A, but not with the Fcgamma receptor, for IgG binding. NMR chemical-shift analyses localized the aptamer-binding sites on the Fc subdomain, which partially overlaps the protein A binding site but not the Fcgamma receptor binding site. The tertiary structures of the predicted recognition sites on the Fc domain differ significantly between human IgG and other species of IgGs; this, in part, accounts for the high specificity of the selected aptamer. Apt8-2 can therefore be used as a protein A alternative for affinity purification of human IgG and therapeutic antibodies. Using Apt8-2 would have several potential advantages, raising the possibility of developing new applications based on aptamer design.