Electrophysiological characteristics of R47W and A298T mutations in CLC-1 of myotonia congenita patients and evaluation of clinical features

Myotonia congenita (MC) is a genetic disease that displays impaired relaxation of skeletal muscle and muscle hypertrophy. This disease is mainly caused by mutations of CLCN1 that encodes human skeletal muscle chloride channel (CLC-1). CLC-1 is a voltage gated chloride channel that activates upon depolarizing potentials and play a major role in stabilization of resting membrane potentials in skeletal muscle. In this study, we report 4 unrelated Korean patients diagnosed with myotonia congenita and their clinical features. Sequence analysis of all coding regions of the patients was performed and mutation, R47W and A298T, was commonly identified. The patients commonly displayed transient muscle weakness and only one patient was diagnosed with autosomal dominant type of myotonia congenita. To investigate the pathological role of the mutation, electrophysiological analysis was also performed in HEK 293 cells transiently expressing homo- or heterodimeric mutant channels. The mutant channels displayed reduced chloride current density and altered channel gating. However, the effect of A298T on channel gating was reduced with the presence of R47W in the same allele. This analysis suggests that impaired CLC-1 channel function can cause myotonia congenita and that R47W has a protective effect on A298T in relation to channel gating. Our results provide clinical features of Korean myotonia congenita patients who have the heterozygous mutation and reveal underlying pathophyological consequences of the mutants by taking electrophysiological approach.

Dose-Volume Analysis of Lung and Heart according to Respiration in Breast Cancer Patients Treated with Breast Conserving Surgery / 한국유방암학회지

PURPOSE: Adjuvant radiotherapy of breast cancer using a photon tangential field incurs a risk of late heart and lung toxicity. The use of free breathing (FB), expiration breath hold (EBH), and deep inspiration breath hold (DIBH) during tangential breast radiotherapy as a means of reducing irradiated lung and heart volume was evaluated. METHODS: In 10 women with left-sided breast cancer (mean age, 44 years) post-operative computed tomography (CT) scanning was done under different respiratory conditions using FB, EBH, and DIBH in 3 CT scans. For each scan, an optimized radiotherapy plan was designed with 6 MV photon tangential fields encompassing the clinical target volume after breast-conserving surgery. RESULTS: The results of dose-volume histograms were compared using three breathing pattern techniques for the irradiated volume and dose to the heart. A significant reduction dose to the irradiated heart volume for the DIBH breathing technique was compared to FB and EBH breathing techniques (p<0.05). CONCLUSION: This study demonstrated that the irradiated heart volume can be significantly reduced in patients with left-sided breast cancer using the DIBH breathing technique for tangential radiotherapy.

A Study of Characteristics of MicroLion Liquid Ionization Chamber for 6 MV Photon Beam / 의학물리

Recently PTW developed a MicroLion liquid ionization chamber which is water_equivalent and has a small sensitive volume of 0.002 cm3. The aim of this work is to investigate such dosimetric characteristics as dose linearity, dose rate dependency, spatial resolution, and output factors of the chamber for the external radiotherapy photon beam. The results were compared to those of Semiflex chamber, Pinpoint chamber and Diode chamber with the sensitive volumes of 0.125 cm3, 0.03 cm3 and 0.0025 cm3, respectively and evaluated to be suitable for small fields. This study was performed in the 6MV photon energy from a Varian 2300 C/D linac accelerator and the MP3 water phantom (PTW, Freiburg) was used. Penumbras in the varios field sizes ranged from 0.5x0.5 cm2 to 10x10 cm2 were used to evaluate the spatial resolution. Output factors were measured in the field sizes of 0.5x0.5 to 40x40 cm2. Readings of the chamber was linearly proportional to dose. Dose rate dependency was measured from 100 MU/min to 600 MU/min, showed a maximum difference of 5.0%, and outputs decreased with dose rates. The spatial resolutions determined with comparing profiles for the field sizes of 0.5x0.5 cm2 to 10x10 cm2 agreed between every detector except the Semiflex chamber to within 2%. Outputs of detectors were compared to that of Semiflex chamber and showed good agreements within 2% for every chamber. This study shows that MicroLion chamber characterized by a high signal-to-noise ratio and water equivalence could be suitable for the small field dosimetry.

Study on the Small Fields Dosimetry for High Energy Photon-based Radiation Therapy / 의학물리

In case of radiation treatment using small field high-energy photon beams, an accurate dosimetry is a challenging task because of dosimetrically unfavorable phenomena such as dramatic changes of the dose at the field boundaries, dis-equilibrium of the electrons, and non-uniformity between the detector and the phantom materials. In this study, the absorbed dose in the phantom was measured by using an ion chamber and a diode detector widely used in clinics. GAFCHROMIC(R) EBT films composed of water equivalent materials was also evaluated as a small field detector and compared with ionchamber and diode detectors. The output factors at 10 cm depth of a solid phantom located 100 cm from the 6 MV linear accelerator (Varian, 6 EX) source were measured for 6 field sizes (5x5 cm2, 2x2 cm2, 1.5x1.5 cm2, 1x1 cm2, 0.7x0.7 cm2 and 0.5x0.5 cm2). As a result, from 5x5 cm2 to 1.5x1.5 cm2 field sizes, absorbed doses from three detectors were accurately identified within 1%. Wheres, the ion chamber underestimated dose compared to other detectors in the field sizes less than 1x1 cm2. In order to correct the observed underestimation, a convolution method was employed to eliminate the volume averaging effect of an ion chamber. Finally, in 1x1 cm2 field the absorbed dose with a diode detector was about 3% higher than that with the EBT film while the dose with the ion chamber after volume correction was 1% lower. For 0.5x0.5 cm2 field, the dose with the diode detector was 1% larger than that with the EBT film while dose with volume corrected ionization chamber was 7% lower. In conclusion, the possiblity of GAFCHROMIC(R) EBT film as an small field dosimeter was tested and further investigation will be proceed using Monte Calro simulation.

Preliminary Study on Performance Evaluation of a Stacking-structure Compton Camera by Using Compton Imaging Simulator / 의학물리

A Compton camera, which is based on the geometrical interpretation of Compton scattering, is a very promising gamma-ray imaging device considering its several advantages over the conventional gamma-ray imaging devices: high imaging sensitivity, 3-D imaging capability from a fixed position, multi-tracing functionality, and almost no limitation in photon energy. In the present study, a Monte Carlo-based, user-friendly Compton imaging simulator was developed in the form of a graphical user interface (GUI) based on Geant4 and MATLAB (TM). The simulator was tested against the experimental result of the double-scattering Compton camera, which is under development at Hanyang University in Korea. The imaging resolution of the simulated Compton image well agreed with that of the measured image. The imaging sensitivity of the measured data was 2~3 times higher than that of the simulated data, which is due to the fact that the measured data contains the random coincidence events. The performance of a stacking-structure type Compton camera was evaluated by using the simulator. The result shows that the Compton camera shows its highest performance when it uses 4 layers of scatterer detectors.

Chamber to Chamber Variations of a Cylindrical Ionization Chamber for the Calibration of an (192)Ir Brachytherapy Source Based on an Absorbed Dose to Water Standards / 의학물리

This work is for the preliminary study for the calibration of an (192)Ir brachytherapy source based on an absorbed dose to water standards. In order to calibrate brachytherapy sources based on absorbed dose to water standards using a clyndirical ionization chamber, the beam quality correction factor kappa(Q,Q0) is needed. In this study kappa(Q,Q0)s were determined by both Monte carlo simulation and semiexperimental methods because of the realistic difficulties to use primary standards to measure an absolute dose at a specified distance. The 5 different serial numbers of the PTW30013 chamber type were selected for this study. While chamber to chamber variations ran up to maximum 4.0% with the generic kappa gen(Q,Q0), the chamber to chamber variations were within a maximum deviation of 0.5% with the individual kappa ind(Q,Q0). The results show why and how important ionization chambers must be calibrated individually for the calibration of (192)Ir brachytherapy sources based on absorbed dose to water standards. We hope that in the near future users will be able to calibrate the brachytherapy sources in terms of an absorbed dose to water, the quantity of interest in the treatment, instead of an air kerma strength just as the calibration in the high energy photon and electron beam.

A Comparative Study of Subset Construction Methods in OSEM Algorithms using Simulated Projection Data of Compton Camera / 핵의학분자영상

PURPOSE: In this study we propose a block-iterative method for reconstructing Compton scattered data. This study shows that the well-known expectation maximization (EM) approach along with its accelerated version based on the ordered subsets principle can be applied to the problem of image reconstruction for Compton camera. This study also compares several methods of constructing subsets for optimal performance of our algorithms. MATERIALS AND METHODS: Three reconstruction algorithms were implemented; simple backprojection (SBP), EM, and ordered subset EM (OSEM). For OSEM, the projection data were grouped into subsets in a predefined order. Three different schemes for choosing nonoverlapping subsets were considered; scatter angle-based subsets, detector position-based subsets, and both scatter angle- and detector position-based subsets. EM and OSEM with 16 subsets were performed with 64 and 4 iterations, respectively. The performance of each algorithm was evaluated in terms of computation time and normalized mean-squared error. RESULTS: Both EM and OSEM clearly outperformed SBP in all aspects of accuracy. The OSEM with 16 subsets and 4 iterations, which is equivalent to the standard EM with 64 iterations, was approximately 14 times faster in computation time than the standard EM. In OSEM, all of the three schemes for choosing subsets yielded similar results in computation time as well as normalized mean-squared error. CONCLUSION: Our results show that the OSEM algorithm, which have proven useful in emission tomography, can also be applied to the problem of image reconstruction for Compton camera. With properly chosen subset construction methods and moderate numbers of subsets, our OSEM algorithm significantly improves the computational efficiency while keeping the original quality of the standard EM reconstruction. The OSEM algorithm with scatter angle- and detector position-based subsets is most available.