Optimizing the response, precision, and cost of a DNA double-strand break dosimeter.

We developed a dosimeter that measures biological damage following delivery of therapeutic beams in the form of double-strand breaks (DSBs) to DNA. The dosimeter contains DNA strands that are labeled on one end with biotin and on the other with fluorescein and attached to magnetic microbeads. Following irradiation, a magnet is used to separate broken from unbroken DNA strands. Then, fluorescence is utilized to measure the relative amount of broken DNA and determine the probability for DSB. The long-term goal for this research is to evaluate whether this type of biologically based dosimeter holds any advantages over the conventional techniques. The purpose of this work was to optimize the dosimeter fabrication and usage to enable higher precision for the long-term research goal. More specifically, the goal was to optimize the DNA dosimeter using three metrics: the response, precision, and cost per dosimeter. Six aspects of the dosimeter fabrication and usage were varied and evaluated for their effect on the metrics: (1) the type of magnetic microbeads, (2) the microbead to DNA mass ratio at attachment, (3) the type of suspension buffer used during irradiation, (4) the concentration of the DNA dosimeter during irradiation, (5) the time waited between fabrication and irradiation of the dosimeter, and (6) the time waited between irradiation and read out of the response. In brief, the best results were achieved with the dosimeter when attaching 4.2 µg of DNA with 1 mg of MyOne T1 microbeads and by suspending the microbead-connected DNA strands with 200 µl of phosphate-buffered saline for irradiation. Also, better results were achieved when waiting a day after fabrication before irradiating the dosimeter and also waiting an hour after irradiation to measure the response. This manuscript is meant to serve as guide for others who would like to replicate this DNA dose measurement technique.

Monte Carlo Modeling and Commissioning of a Dual-layer Micro Multileaf Collimator.

The purpose of this study was to commission a first-of-its-kind dual-layer micro multileaf collimator (mMLC) system by using Monte Carlo dose calculations. The mMLC is attached on a Varian 600C linac. Having a lower and an upper layer of MLC leaves, this mMLC allows for field shaping in two orthogonal directions. The commissioning of the system was performed in two steps: without and with the mMLC attached on the linac. The treatment head without and with the mMLC was modeled in the BEAMnrc Monte Carlo (MC) code. The scoring planes for the phase space files were specified below the linac's secondary collimators (jaws) and above and below the mMLC. With the mMLC attached to the linac the field size was defined by the jaws as 10 x 10 cm(2), which is also the maximum possible field size that can be shaped by the mMLC. For the commissioning of the linac, several fields of various sizes were simulated and compared against ionization chamber measurements in a water phantom. Output factors for several field sizes, as well as percent depth dose curves and dose profiles for rectangular and irregular shape fields, were calculated and compared against measurements in water. Agreement between measured and calculated data was better than 1% and less than 1.0 mm in the penumbra region for open fields. With the mMLC attached, the agreement between measurements and MC calculations is within 1.0% or 1.0 mm in the penumbra region.

Dosimetric evaluation of a Monte Carlo IMRT treatment planning system incorporating the MIMiC.

The high dose per fraction delivered to lung lesions in stereotactic body radiation therapy (SBRT) demands high dose calculation and delivery accuracy. The inhomogeneous density in the thoracic region along with the small fields used typically in intensity-modulated radiation therapy (IMRT) treatments poses a challenge in the accuracy of dose calculation. In this study we dosimetrically evaluated a pre-release version of a Monte Carlo planning system (PEREGRINE 1.6b, NOMOS Corp., Cranberry Township, PA), which incorporates the modeling of serial tomotherapy IMRT treatments with the binary multileaf intensity modulating collimator (MIMiC). The aim of this study is to show the validation process of PEREGRINE 1.6b since it was used as a benchmark to investigate the accuracy of doses calculated by a finite size pencil beam (FSPB) algorithm for lung lesions treated on the SBRT dose regime via serial tomotherapy in our previous study. Doses calculated by PEREGRINE were compared against measurements in homogeneous and inhomogeneous materials carried out on a Varian 600C with a 6 MV photon beam. Phantom studies simulating various sized lesions were also carried out to explain some of the large dose discrepancies seen in the dose calculations with small lesions. Doses calculated by PEREGRINE agreed to within 2% in water and up to 3% for measurements in an inhomogeneous phantom containing lung, bone and unit density tissue.

Monte Carlo simulations of ferromagnetism in p-Cd1-xMnxTe quantum wells.

Monte Carlo simulations, in which the Schrödinger equation is solved at each Monte Carlo sweep, are employed to assess the influence of magnetization fluctuations, short-range antiferromagnetic interactions, disorder, magnetic polaron formation, and spin-Peierls instability on the carrier-mediated Ising ferromagnetism in two-dimensional electronic systems. The determined critical temperature and hysteresis are affected in a nontrivial way by the antiferromagnetic interactions. The findings explain striking experimental results for modulation-doped p-Cd1-xMnxTe quantum wells.

Real time high resolution magnetic resonance imaging for the assessment of gastric motility disorders.

BACKGROUND: The aim of this study was to evaluate whether patients with increased or decreased gastric motility can be differentiated from healthy volunteers by means of real time magnetic resonance imaging (MRI). PATIENTS AND METHODS: Ten healthy volunteers, 10 patients with gastroparesis, and 10 patients with functional pylorospasm/peptic pyloric stenosis underwent real time MRI. All patients were examined on two separate days; once prior to therapy and once after adequate therapy. Antral motility was quantified by calculating the gastric motility index. RESULTS: Patients with gastroparesis showed a lower motility index compared with the reference volunteer group while the mean motility index of the patient group with pylorospasm was more than three times higher than that of the reference value of the volunteer group. However, the gastric motility index in the patient group with gastroparesis increased, and in the group with functional pylorospasm/peptic pyloric stenosis it decreased significantly after therapy. CONCLUSION: Real time MRI is a reliable tool for assessment of gastric motion. Furthermore, differences in gastric motility index in patients with increased or decreased gastric motility could be evaluated and quantified. Due to the non-invasive character of MRI, this imaging modality may be an attractive alternative to conventional invasive diagnostic tools for gastric motility disorders and therapeutic monitoring.

Non-invasive myocardial iron assessment in thalassaemic patients. T2 relaxometry and magnetization transfer ratio measurements.

PURPOSE: To compare T2 relaxometry and magnetization transfer ratio (MTR) measurements of myocardial tissue in normal volunteers and thalassaemic patients for assessment of the myocardial iron levels. MATERIAL AND METHODS: All examinations were done on a 1 T MR system using a multi-echo spin-echo sequence with 8 echoes for T2 measurements and a gradient echo sequence for MTR measurements. Diastolic cardiac triggering was used in both sequences. Ten patients and 10 normal subjects were included in the study. T2 and MTR measurements were correlated with serum ferritin levels. RESULTS: Regression analysis between T2 and MTR measurements and ferritin demonstrated a reversed linear relationship, (r=-0.932, p<0.05) and (r= -0.824, p<0.05), respectively. Mean T2 relaxation time and mean MTR of the normal subjects (57.95+/-4.9 ms and 43.70+/-3.3%) was significantly higher than that of the thalassaemic patients (38.8+/-6.2 ms and 26.40+/-6.1%) (p<0.01), respectively. CONCLUSION: MTR measurements can be used to complement T2 measurements for non-invasive myocardial iron assessment.

Calculation of portal dose using the convolution/superposition method.

The convolution/superposition method was used to predict the dose throughout an extended volume, which includes a phantom and a portal imaging device. From the calculated dose volume, the dose delivered in the portal image plane was extracted and compared to a portal dose image. This comparison aids in verifying the beam configuration or patient setup after delivery of the radiation. The phantoms used to test the accuracy of this method include a solid water cube, a Nuclear Associates CT phantom, and an Alderson Rando thorax phantom. The dose distribution in the image plane was measured with film and an electronic portal imaging device in each case. The calculated portal dose images were within 4% of the measured images for most voxels in the central portion of the field for all of the extended volumes. The convolution/superposition method also enables the determination of the scatter and primary dose contributions using the particular dose deposition kernels for each contribution. The ratio of primary dose to total dose was used to extract the primary dose from the detected portal image, which enhances the megavoltage portal images by removing scatter blurring. By also predicting the primary energy fluence, we can find the ratio of computed primary energy fluence to total dose. Multiplying this ratio by the measured dose image estimates the relative primary energy fluence at the portal imager. The image of primary energy fluence possesses higher contrast and may be used for further quantitative image processing and dose modeling.

A study of the effect of cone shielding in intraoperative radiotherapy.

The primary goal of intraoperative radiation therapy is to irradiate the intraoperatively determined tumor target volume with a single fraction of tumoroidal dose while minimizing the dose to all adjacent healthy tissues. To reduce dose outside the treatment volume, lead sheets are often used to cover the external surface of the cone tip thus providing a shielding for the tissues outside the field. In this paper, the effect of the shielding on the depth dose distributions and dose profiles at different depths is studied based on experimental data. The results were also compared against an EGS4 Monte Carlo code for the same geometry as the measurements. The cones varied in size having diameters of 5 cm, 7 cm, and 9 cm, and the electron energies ranged from 6 MeV to 22 MeV. The depth dose curves and dose profiles (at two different depths in the phantom) were measured and computed with and without the lead shielding for the various combinations of cone sizes and electron energies using a water phantom to simulate the patient. It was found that the presence of lead increases on average across the treatment area the dose to the tumor from 2% up to 5%, while the dose outside the cone was reduced by as much as 75%. Both measurements and calculations were found to be in agreement.

Measurements of the electron dose distribution near inhomogeneities using a plastic scintillation detector.

PURPOSE: Accurate measurement of the electron dose distribution near an inhomogeneity is difficult with traditional dosimeters which themselves perturb the electron field. We tested the performance of a new high resolution, water-equivalent plastic scintillation detector which has ideal properties for this application. METHODS AND MATERIALS: A plastic scintillation detector with a 1 mm diameter, 3 mm long cylindrical sensitive volume was used to measure the dose distributions behind standard benchmark inhomogeneities in water phantoms. The plastic scintillator material is more water equivalent than polystyrene in terms of its mass collision stopping power and mass scattering power. Measurements were performed for beams of electrons having initial energies of 6 and 18 MeV at depths from 0.2-4.2 cm behind the inhomogeneities. RESULTS: The detector reveals hot and cold spots behind heterogeneities at resolutions equivalent to typical film digitizer spot sizes. Plots of the dose distributions behind air, aluminum, lead, and formulations for cortical and inner bone-equivalent materials are presented. CONCLUSION: The plastic scintillation detector is suited for measuring the electron dose distribution near an inhomogeneity.

Investigation of the convolution method for polyenergetic spectra.

The distribution of absolute dose per unit fluence from polyenergetic photon beams impinging upon a water phantom was calculated using two convolution approaches that properly account for beam hardening effects. Dose deposition kernels calculated previously using the EGS4 Monte Carlo code are convolved with the primary terma to give the dose for monoenergetic photon beams of energies ranging from 100 kev to 50 MeV. A polyenergetic dose distribution is composed of separately calculated monoenergetic components, which are appropriately weighted with the fluence spectrum to yield the polyenergetic dose distribution. Alternatively, a single convolution for the polyenergetic beam is considered, where a composite polyenergetic kernel is convolved with the respective polyenergetic terma. The effects of the polyenergetic kernel variance due to beam hardening as well as the effect of tilting the kernels for a diverging beam geometry were also examined. The depth dose data produced using the two proposed methods were compared with measured data and Monte Carlo simulations and showed good agreement.

Menarche in Greece (compared study of the population of Crete and Thrace).

We studied the factors that influence the menarcheal age in the population of Crete and Thrace, and we compared the results of the study of these two frontier districts. A) The average menarcheal age for the female students from Crete was 12 years and 5 1/2 months while for the female students from Thrace it was 12 years and 5 months. B) The average menarcheal age is higher for the students whose birth weight was less than 2.500 gr. C) The higher the father's educational level results in lower average menarcheal age and higher I.Q. level for the student. D) Comparing the average menarcheal ages of mothers and their daughters we conclude that the daughters had their menstruation 11.5 months earlier than their mothers, while that difference was 11 months in Thrace. E) In the last 60 years (1925-1985) the average menarcheal age of the Greek girls decreased by approximately 18 months. F) The body weight and the height during menarche is within the international limits of the "critical weight" and the "critical height".