Case report: high-dose carvedilol as a potential key drug for arrhythmias in histiocytoid cardiomyopathy.

Background: Histiocytoid cardiomyopathy is a rare infancy cardiac disorder manifesting as severe cardiac arrhythmias or dilated cardiomyopathy. There is no specific treatment for these arrhythmias. This is the first report of infantile histiocytoid cardiomyopathy whose refractory ventricular arrhythmias were successfully controlled by high-dose carvedilol. Case summary: A 4-month-old girl presented with asystole, and recurrent ventricular tachycardias. From the histological findings and clinical symptoms, she was diagnosed as histiocytoid cardiomyopathy. Sedatives were the most effective therapy for her arrhythmia, but the cardiac sympathetic denervation was not effective enough. Finally, her ventricular arrhythmias were controlled with high-dose carvedilol, and she was discharged on hospitalization Day 393. Discussion: Carvedilol is the only beta blocker that directly acts on the ryanodine receptor (RyR2) and inhibits store-overload-induced Ca2+ release (SOICR) in myocardium at high dosage. The arrhythmias did not disappear with bisoprolol, landiolol, or verapamil, but high-dose carvedilol was effective. This clinical course suggested that the arrhythmias in histiocytoid cardiomyopathy might be related with SOICR. High-dose carvedilol might be a key drug for patients with histiocytoid cardiomyopathy.

Modulation transfer function measurement of three-dimensional T1-weighted turbo spin echo sequence with low refocusing flip angles using single-plate method.

This study aimed to demonstrate the usefulness of modulation transfer function (MTF) measurements using the single-plate method to evaluate changes in resolution properties that are dependent on three parameters: echo train length (ETL), low refocusing flip angle (RFA), and start-up echo in three-dimensional T1-weighted turbo spin echoes (TSE) with a low RFA and to optimize these parameters. Although the MTFs were slightly degraded with an RFA of 120°, they were considerably degraded with an RFA of ≤ 90°. On the other hand, the MTF of low RFA was greatly improved by setting the start-up echo, allowing setting a long ETL. The single-plate method provided a clear and easy evaluation of the resolution properties of low RFA TSE. Furthermore, this method allows us to visualize changes in the signal intensity of each echo in k-space, depending on the sequence variation. These results suggest that the MTF measurement using the single-plate method is useful for evaluating the resolution properties of TSE sequences and optimizing the measured parameters.

Can magnetic resonance imaging after cranioplasty using titanium mesh detect brain tumors?

This study determined the dependence of the concentration and position of contrast-enhanced tumors on the radio frequency (RF)-shielding effect of titanium mesh using the contrast-to-noise ratio (CNR) in magnetic resonance imaging (MRI). A phantom was constructed by filling a plastic container with manganese chloride tetrahydrate and agar. Four cellophane cylindrical containers were arranged from the end of the plastic container, and the brain tumor model was filled with gadobutrol diluted with NaCl, with molarity values of 0.2-1.0 mmol/L. The titanium mesh board was set on the left side of the phantom. Images were acquired using a 1.5-T MRI as well as two-dimensional spin-echo (2D SE) and three-dimensional fast spoiled gradient echo (3D FSPGR) sequences. CNR was calculated using the signal intensity values of the tumor model, surrounding area of the brain model, and background noise. Furthermore, the fractional change in CNR was calculated using values of CNR with and without the mesh. Moreover, a profile of CNR was created. The fractional change in CNR decreased at the brain tumor positions present near the mesh and at a contrast medium concentration of approximately ≤ 0.5 mmol/L in 2D SE and ≤ 0.25 mmol/L in 3D FSPGR. According to the CNR profiles, directly under the mesh, almost all contrast concentrations in 2D SE was unrecognizable; however, at a concentration of ≥ 0.5 mmol/L in 3D FSPGR was recognizable.

Echo-planar imaging is superior to fast spin-echo diffusion-weighted imaging for cranioplasty using titanium mesh in brain magnetic resonance imaging: a phantom study.

This study aimed to compare the radiofrequency (RF) shielding effects of titanium mesh of echo-planar imaging (EPI) versus fast spin-echo (FSE) diffusion-weighted imaging (DWI) to establish a suitable sequence for patients who undergo cranioplasty and for whom titanium mesh was used in brain magnetic resonance imaging (MRI). A 1.5-T MRI scanner with clinical setting sequences was used. A phantom for the examination constructed using a sucrose solution in a plastic container was used to compare the signal attenuation (SA) ratio, area of RF shielding effect (Area), normalized absolute average deviation (NAAD), and apparent diffusion coefficient (ADC) between EPI and FSE-DWI. EPI provided significantly better SA ratio, Area, and NAAD (P < 0.01). When the number of slices increased, the RF shielding became more negative. There was no significant difference in the ADC. Regardless of the k-trajectory, EPI-DWI had a lower RF shielding effect than FSE-DWI in patients undergoing cranioplasty.

Three-dimensional Gradient-echo is Effective in Suppressing Radiofrequency Shielding by a Titanium Mesh.

PURPOSE: To determine which sequence for frequently used general contrast-enhanced brain MRI shows the least radiofrequency shielding effect of a titanium mesh in cranioplasty using a phantom. METHODS: A 1.5T MRI scanner was used. Frequently used general 2D and 3D spin-echo sequences (SE) and T1 spoiled gradient echo sequences (GRE) used for MRI in clinical settings were adopted in this study. A titanium mesh was placed above a cubic phantom containing manganese chloride tetrahydrate and sodium chloride. The signal attenuation ratio and normalized absolute average deviation (NAAD) were calculated. Moreover, the flip angle (FA) dependency in SE and area of excitation dependency in 3D sequences were analyzed using NAAD. RESULTS: The signal attenuation ratio at the position nearest to the titanium mesh for 2D SE was 71.8% larger than that at the position nearest to the titanium mesh for 3D GRE. With regard to NAAD, 3D GRE showed the highest values among the sequences. When FA was increased, radiofrequency shielding effect was improved. There were no significant differences between the narrow and wide area of excitation. 3D GRE showed the least radiofrequency shielding effect, and it was considered as the optimal sequence for MRI in the presence of a titanium mesh. CONCLUSION: 3D GRE shows the least radiofrequency shielding effect of a titanium mesh after cranioplasty among frequently used general sequences for contrast-enhanced brain MRI.

Single-plate method for practical modulation transfer function measurement in magnetic resonance imaging.

A new "single-plate method" is presented for measuring the modulation transfer function (MTF) in magnetic resonance imaging (MRI). This method sets a slice plane perpendicular to a single-plate phantom to eliminate contamination effects from the direction perpendicular to the measurement direction in the image plane, which occur with a conventional ramp method. As no practical method for measuring the MTF has been established for MRI, we examined whether the MTF can be measured practically using the single-plate method for various fast imaging sequences. Furthermore, the MTFs of T1-weighted (T1W) fast spin echo (FSE) and conventional spin echo (CSE) images obtained using the single-plate method and ramp method were compared. The measured MTFs of T1W CSE images revealed rectangular shapes with a sharp decrease near the Nyquist cutoff frequency in both phase-encoding (PE) and frequency-encoding (readout, RO) directions. The measured MTFs of T1W FSE images obtained with centric-order acquisition showed symmetric step-function shapes reflecting k-space segmentation determined by the echo train length (ETL). The measured MTFs of T2-weighted (T2W) FSE images showed asymmetric step-function shapes reflecting differences in T2 decay of signals from samples. The MTFs obtained using the single-plate method significantly reduced the collapse caused by the contamination effect, which is observed in all the MTF measurements of the ramp method. The proposed "single-plate method" simplified the complicated MTF measurement procedure and eliminated the contamination effect. This method is expected to be useful for evaluating the resolution properties of MR fast imaging techniques with a complicated k-space trajectory.

[Evaluation of Resolution Characteristics in Three-dimensional MR Imaging Using Single Plate Thin-Ramp Method].

Recent remarkable progress of fast imaging techniques in 3D MRI has emphasized the importance of evaluation of its resolution characteristics. A trial point spread function (PSF) measurement was conducted using the ramp method, a conventional measurement method for the slice profile of 2D imaging, as an approach to evaluate the resolution characteristics of 3D imaging. However, problems peculiar to 3D imaging have arisen, such as artifacts and offsets in the slice selective direction. Therefore, we attempted PSF measurement using a phantom having a single-plate construction with only a simple ramp part (Single Plate Thin-Ramp Method) to respond to these shortcomings. By employing appropriate positioning and simple post processing, we obtained a PSF easily in both phase encoding and slice selective directions without the artifacts and offsets described above. Furthermore, it was possible to evaluate the change of resolution characteristics depending on the scan condition in three-dimensional MR image.

Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: oncogenic transformation with epithelial-mesenchymal transition.

Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days) revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin(+) undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells.

Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis.

Regulatory T cells (T(reg) cells) develop from progenitor thymocytes after the engagement of T cell antigen receptors (TCRs) with high-affinity ligands, but the underlying molecular mechanisms are still unclear. Here we show that the Nr4a nuclear receptors, which are encoded by immediate-early genes upregulated by TCR stimulation in thymocytes, have essential roles in T(reg) cell development. Mice that lacked all Nr4a factors could not produce T(reg) cells and died early owing to systemic autoimmunity. Nr4a receptors directly activated the promoter of the gene encoding the transcription factor Foxp3, and forced activation of Nr4a receptors bypassed low-strength TCR signaling to drive the T(reg) cell developmental program. Our results suggest that Nr4a receptors have key roles in determining CD4(+) T cell fates in the thymus and thus contribute to immune homeostasis.

[Slice profile measurement using a crossed thin-ramps method in three-dimensional magnetic resonance imaging].

Recent progress in variable-flip-angle fast spin-echo technology has further extended the utility of three-dimensional (3D) magnetic resonance imaging (MRI) for clinical application. The slice profile in 3D MRI is the point spread function that has a sync form in principle, whereas a slice profile in 2D imaging provides information on characteristics of selective radio frequency excitation. We investigated the optimal condition to measure 3D slice profiles using a crossed thin-ramps phantom. We found that the profile data should cover a large area in order to evaluate both the main lobe and side lobes in the slice profile, and that the appropriate slice thickness was 2 mm. We also found that artifacts in the direction perpendicular to the slice create an offset error in the measured slice profile when 3D imaging. In this paper, we describe the optimal condition and some remarks on the slice profile evaluation for 3D MRI.