The concept of in-air output ratio ͑S c ͒ was introduced to characterize how the incident photon ... more The concept of in-air output ratio ͑S c ͒ was introduced to characterize how the incident photon fluence per monitor unit ͑or unit time for a Co-60 unit͒ varies with collimator settings. However, there has been much confusion regarding the measurement technique to be used that has prevented the accurate and consistent determination of S c . The main thrust of the report is to devise a theoretical and measurement formalism that ensures interinstitutional consistency of S c . The in-air output ratio, S c , is defined as the ratio of primary collision water kerma in free-space, K p , per monitor unit between an arbitrary collimator setting and the reference collimator setting at the same location. Miniphantoms with sufficient lateral and longitudinal thicknesses to eliminate electron contamination and maintain transient electron equilibrium are recommended for the measurement of S c . The authors present a correction formalism to extrapolate the correct S c from the measured values using high-Z miniphantom. Miniphantoms made of high-Z material are used to measure S c for small fields ͑e.g., IMRT or stereotactic radiosurgery͒. This report presents a review of the components of S c , including headscatter, source-obscuring, and monitor-backscattering effects. A review of calculation methods ͑Monte Carlo and empirical͒ used to calculate S c for arbitrary shaped fields is presented. The authors discussed the use of S c in photon dose calculation algorithms, in particular, monitor unit calculation. Finally, a summary of S c data ͑from RPC and other institutions͒ is included for QA purposes.
Magnetic fields are known to alter radiation dose deposition. Before patients receive treatment u... more Magnetic fields are known to alter radiation dose deposition. Before patients receive treatment using an MRI-linear accelerator (MRI-Linac), preclinical studies are needed to understand the biological consequences of magnetic-field-induced dose effects. In the present study, the authors sought to identify a beam energy and magnetic field strength combination suitable for preclinical murine experiments. Magnetic field dose effects were simulated in a mouse lung phantom using various beam energies (225 kVp, 350 kVp, 662 keV [Cs-137], 2 MV, and 1.25 MeV [Co-60]) and magnetic field strengths (0.75, 1.5, and 3 T). The resulting dose distributions were compared with those in a simulated human lung phantom irradiated with a 6 or 8 MV beam and orthogonal 1.5 T magnetic field. In the human lung phantom, the authors observed a dose increase of 45% and 54% at the soft-tissue-to-lung interface and a dose decrease of 41% and 48% at the lung-to-soft-tissue interface for the 6 and 8 MV beams, respectively. In the mouse simulations, the magnetic fields had no measurable effect on the 225 or 350 kVp dose distribution. The dose increases with the Cs-137 beam for the 0.75, 1.5, and 3 T magnetic fields were 9%, 29%, and 42%, respectively. The dose decreases were 9%, 21%, and 37%. For the 2 MV beam, the dose increases were 16%, 33%, and 31% and the dose decreases were 9%, 19%, and 30%. For the Co-60 beam, the dose increases were 19%, 54%, and 44%, and the dose decreases were 19%, 42%, and 40%. The magnetic field dose effects in the mouse phantom using a Cs-137, 3 T combination or a Co-60, 1.5 or 3 T combination most closely resemble those in simulated human treatments with a 6 MV, 1.5 T MRI-Linac. The effects with a Co-60, 1.5 T combination most closely resemble those in simulated human treatments with an 8 MV, 1.5 T MRI-Linac.
Antimicrobial agents and chemotherapy, Jan 29, 2015
Antimicrobial Peripherally inserted central catheters (PICCs) might reduce the incidence of CLABS... more Antimicrobial Peripherally inserted central catheters (PICCs) might reduce the incidence of CLABSI. We tested biocompatibility of a novel gendine (combination of chlorhexidine-CHX and gentian violet-GV) PICC in a rabbit intravascular model and tested antimicrobial efficacy in comparison with commercially available minocycline/rifampin (M/R), and CHX PICCs in an in vitro biofilm colonization model.Gendine and uncoated control PICCs were inserted in the jugular veins of rabbits for 4 days. Histopathologic analysis was performed at the end of the four day period and circulating levels of CHX and GV in blood were measured at different time points using liquid chromatography/mass spectrometry. Antimicrobial efficacy of the PICCs were tested following simulated intravascular indwells of 24 hours and 1 week against clinical isolates of methicillin-resistant Staphylococcus aureus, Vancomycin-resistant enterococci Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Enterobacte...
Nanomedicine: Nanotechnology, Biology and Medicine, 2015
We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conj... more We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conjugated gold nanorods. Progressive receptor-mediated internalization of conjugated nanorods over time increases the radiation interaction cross-section of cells and contributes to the effects observed in vitro. The low concentrations of gold required, the long interval between injection of nanoparticles and radiation, and the use of megavoltage radiation to generate radiosensitization in vivo foretell the possibility of eventual clinical translation of this approach.
Journal of immunology (Baltimore, Md. : 1950), 2014
Transcriptional mechanisms governing hematopoietic stem cell (HSC) quiescence, self-renewal, and ... more Transcriptional mechanisms governing hematopoietic stem cell (HSC) quiescence, self-renewal, and differentiation are not fully understood. Sequence-specific ssDNA-binding protein 2 (SSBP2) is a candidate acute myelogenous leukemia (AML) suppressor gene located at chromosome 5q14. SSBP2 binds the transcriptional adaptor protein Lim domain-binding protein 1 (LDB1) and enhances LDB1 stability to regulate gene expression. Notably, Ldb1 is essential for HSC specification during early development and maintenance in adults. We previously reported shortened lifespan and greater susceptibility to B cell lymphomas and carcinomas in Ssbp2(-/-) mice. However, whether Ssbp2 plays a regulatory role in normal HSC function and leukemogenesis is unknown. In this study, we provide several lines of evidence to demonstrate a requirement for Ssbp2 in the function and transcriptional program of hematopoietic stem and progenitor cells (HSPCs) in vivo. We found that hematopoietic tissues were hypoplastic i...
This study evaluated the secondary cancer risk from volumetric-modulated arc therapy (VMAT) for s... more This study evaluated the secondary cancer risk from volumetric-modulated arc therapy (VMAT) for spine radiotherapy compared with intensity-modulated radiotherapy (IMRT) and 3-dimensional conformal radiotherapy (3DCRT). Computed tomography images of an Radiological Physics Center spine anthropomorphic phantom were exported to a treatment planning system (Pinnacle 3 , version 9.4). Radiation treatment plans for spine were prepared using VMAT (dual-arc), 7-field IMRT (beam angles: 1101,1 301, 1501,1 8 0 1,2 1 0 1, 2301, and 2501), and 4-field 3DCRT technique. The mean and maximum doses, dosevolume histograms, and volumes receiving more than 2 and 4 Gy to organs at risk (OARs) were calculated and compared. The lifetime risk for secondary cancers was estimated according to the National Cancer Registry Programme Report 116. VMAT delivered the lowest maximum dose to the esophagus (4.03 Gy), bone (8.11 Gy), heart (2.11 Gy), spinal cord (6.45 Gy), and whole lung (5.66 Gy) as compared with other techniques (IMRT and 3DCRT). The volumes of OAR (esophagus) receiving more than 4 Gy were 0% for VMAT, 27.06% for IMRT, and up to 32.35% for 3DCRT. The estimated risk for secondary cancer in the respective OAR is considerably lower in VMAT compared with other techniques. The results of maximum doses and volumes of OARs suggest that the risk of secondary cancer induction for the spine in VMAT is lower than IMRT and 3DCRT, whereas VMAT has the best target coverage compared with the other techniques.
Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS).... more Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS). Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP) magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC), an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-¹³C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping.
Monte Carlo (MC) modeling of a 6 MV photon beam was used to study the dose perturbation from a ti... more Monte Carlo (MC) modeling of a 6 MV photon beam was used to study the dose perturbation from a titanium rod 5 mm in diameter in various small fields range from 2 × 2 to 5 × 5 cm(2). The results showed that the rod increased the dose to water by ∼6% at the water-rod interface because of electron backscattering and decreased the dose by ∼7% in the shadow of the rod because of photon attenuation. The Pinnacle(3) treatment planning system calculations matched the MC results at the depths more than 1 cm past the rod when the correct titanium density of 4.5 g cm(-3) was used, but significantly underestimated the backscattering dose at the water-rod interface. A CT-density table with a top density of 1.82 g cm(-3) (cortical bone) is a practical way to reduce the dosimetric error from the artifacts by preventing high density assignment to them, but can underestimates the attenuation by the titanium rod by 6%. However, when multi-beam with intensity modulation is used in actual patient spinal stereotactic radiosurgery treatment, the dosimetric effect of assigning 4.5 instead of 1.82 g cm(-3) to titanium implants is complicated. It ranged from minimal effect to 2% dose difference affecting 15% target volume in the study. When hardware is in the beam path, density override to the titanium hardware is recommended.
The device developed by the authors and described here enables the user to measure the depth from... more The device developed by the authors and described here enables the user to measure the depth from the water surface to the point of measurement for a cylindrical ion chamber with a waterproof plastic cap in a water phantom, free of surface-tension error with a high precision. The device seeks vertical orientation and provides the convenience of hands-free operation. The measurement process is simple and quick with a precision of 0.1 mm. (The device is currently available as a 'water phantom depth gauge' from Nuclear Associates, Division of Victoreen Inc., Clare Place, NY, USA.)
A new approach to intraoperative radiation therapy led to the development of mobile linear electr... more A new approach to intraoperative radiation therapy led to the development of mobile linear electron accelerators that provide lower electron energy beams than the usual conventional accelerators commonly encountered in radiotherapy. Such mobile electron accelerators produce electron beams that have nominal energies of 4, 6, 9 and 12 MeV. This work compares the absorbed dose output calibrations using both the AAPM TG-51 and TG-21 dose calibration protocols for two types of ion chambers: a plane-parallel (PP) ionization chamber and a cylindrical ionization chamber. Our results indicate that the use of a 'Markus' PP chamber causes 2-3% overestimation in dose-output determination if accredited dosimetry-calibration laboratory based chamber factors (N(60Co)(D,w,) Nx) are used. However, if the ionization chamber factors are derived using a cross-comparison at a high-energy electron beam, then a good agreement is obtained (within 1%) with a calibrated cylindrical chamber over the entire energy range down to 4 MeV. Furthermore, even though the TG-51 does not recommend using cylindrical chambers at the low energies, our results show that the cylindrical chamber has a good agreement with the PP chamber not only at 6 MeV but also down to 4 MeV electron beams.
The strongest of five 'early' promoters of Bacillus subtilis phage SPPl was localized in a DNA re... more The strongest of five 'early' promoters of Bacillus subtilis phage SPPl was localized in a DNA restriction fragment by analysis of RNA polymerase binding and R-loop formation. The nucleotide sequence of the promoter region was established. The signal structures identified were similar to those recognized by the oS5 RNA polymerase of B. subtilis. The promoter precedes an open reading frame with 51 codons. A protein with the M , predicted from the nucleotide sequence was identified in minicells.
In 1999, the AAPM introduced a reference dosimetry protocol, known as TG51, based on an absorbed ... more In 1999, the AAPM introduced a reference dosimetry protocol, known as TG51, based on an absorbed dose standard. This replaced the previous protocol, known as TG21, which was based on an air kerma standard. A significant body of literature has emerged discussing the improved accuracy and robustness of the absorbed dose standard, and quantifying the changes in baseline dosimetry with the introduction of the absorbed dose protocol. A significant component playing a role in the overall accuracy of beam output determination is the variability due to the use of different dosimeters. This issue, not adequately addressed in the past, is the focus of the present study. This work provides a comparison of absorbed dose determinations using 21 different makes and models of ion chambers for low- and high-energy photon and electron beams. The study included 13 models of cylindrical ion chambers and eight models of plane-parallel chambers. A high degree of precision (<0.25%) resulted from measurements with all chambers in a single setting, a sufficient number of repeat readings, and the use of high quality ion chambers as external monitors. Cylindrical chambers in photon beams show an improvement in chamber-to-chamber consistency with TG51. For electron dosimetry with plane-parallel chambers, the parameters Ngas and the product ND,w x k(ecal) were each determined in two ways, based on (i) an ADCL calibration, and (ii) a cross comparison with an ADCL-calibrated cylindrical chamber in a high-energy electron beam. Plane-parallel chamber results, therefore, are presented for both methods of chamber calibration. Our electron results with technique (i) show that plane-parallel chambers, as a group, overestimate the beam output relative to cylindrical chambers by 1%-2% with either protocol. Technique (ii), by definition, normalizes the plane-parallel results to the cylindrical results. In all cases, the maximum spread in output from the various cylindrical chambers is <2% implying a standard deviation of less than 0.5%. For plane-parallel chambers, the maximum spread is somewhat larger, up to 3%. A few chambers have been identified as outliers.
A key component of the Radiological Physics Center's (RPC) on-site dosimetry review visit... more A key component of the Radiological Physics Center's (RPC) on-site dosimetry review visits are photon beam calibrations for which determination of the energy of the x ray is a key element. The ratio of ionizations, TPR20/TPR10, for a 10 cm x 10 cm field at depths of 20 and 10 cm for a constant SCD is used as a quantitative measure of beam quality in the Task Group 21 protocol. The RPC has measured both TPR20/TPR10 and the corresponding ratio of percent depth dose (D20/D10) at a constant SSD for 685 photon beams (4-25 MV) for most makes and models if accelerators. A strong correlation between TPR20/TPR10 and D20/D10 is presented which allows the determination of the TPR ratio from the measurement of the ratio of percent depth doses. An analysis of the uncertainty introduced in the TG-21 factors (L/rho, Pwall, Prepl) caused by the spread in the measured data and translated into the determination of the TPR ratio results in an insignificant error (< 0.3%). This empirical relationship provides an alternate technique for quantifying the beam quality defined in the TG-21 protocol without surrendering any loss of precision in output calibration. This technique may be found by those who calibrate at a fixed SSD to be an easier and quicker method.
The water equivalency of five "water-equivalent" solid phantom materials was ev... more The water equivalency of five "water-equivalent" solid phantom materials was evaluated in terms of output calibration and energy characterization over a range of energies for both photon (Co-60 to 24 MV) and electron (6-20 MeV) beams. Evaluations compared absorbed doses calculated from ionization measurements using the same dosimeter in the solid phantom materials and in natural water (H2O). Ionization measurements were taken at various calibration depths. The Radiological Physics Center's standard dosimetry system, a Farmer-type ion chamber in a water phantom, was used. Complying with the TG-21 calibration protocol, absorbed doses were calculated using eight measurement and calculational techniques for photons and five for electrons. Results of repeat measurements taken over a period of 2 1/2 years were reproducible to within a +/- 0.3% spread. Results showed that various combinations of measurement techniques and solid phantom materials caused a spread of 3%-4% in the calculation of dose relative to the dose determined from measurements in water for all beam energies on both modalities. An energy dependence of the dose ratios was observed for both photons and electrons.
ABSTRACT Dosimetry measurements of a (131)Cs brachytherapy source have been performed in liquid w... more ABSTRACT Dosimetry measurements of a (131)Cs brachytherapy source have been performed in liquid water employing thermoluminescence dosimeters. A search of the literature reveals that this is the first time a complete set of dosimetric parameters for a brachytherapy "seed" source has been measured in liquid water. This method avoids the medium correction uncertainties introduced by the use of water-equivalent plastic phantoms. To assure confidence in the results, four different sources were employed for each parameter measured, and measurements were performed multiple times. The measured dosimetric parameters presented here are based on the AAPM Task Group 43 formalism. The dose-rate constant measured in liquid water was (1.063 +/- 0.023) cGy h(-1) U(-1) and was based on the air-kerma strength standard for this source established by the National Institute of Standards and Technology. Measured values for the 2D anisotropy function and the radial dose function are presented.
Radiation therapy dose measurements are customarily performed in liquid water. The characterizati... more Radiation therapy dose measurements are customarily performed in liquid water. The characterization of brachytherapy sources is, however, generally based on measurements made with thermoluminescence dosimeters (TLDs), for which contact with water may lead to erroneous readings. Consequently, most dosimetry parameters reported in the literature have been based on measurements in water-equivalent plastics, such as Solid Water. These previous reports employed a correction factor to transfer the dose measurements from a plastic phantom to liquid water. The correction factor most often was based on Monte Carlo calculations. The process of measuring in a water-equivalent plastic phantom whose exact composition may be different from published specifications, then correcting the results to a water medium leads to increased uncertainty in the results. A system has been designed to enable measurements with TLDs in liquid water. This system, which includes jigs to support water-tight capsules of lithium fluoride in configurations suitable for measuring several dosimetric parameters, was used to determine the correction factor from water-equivalent plastic to water. Measurements of several 125I and 131Cs prostate brachytherapy sources in liquid water and in a Solid Water phantom demonstrated a correction factor of 1.039 +/- 0.005 at 1 cm distance. These measurements are in good agreement with a published value of this correction factor for an 125I source.
Since the Gafchromic film EBT has been recently replaced by the newer model EBT2, its characteriz... more Since the Gafchromic film EBT has been recently replaced by the newer model EBT2, its characterization, especially energy dependence, has become critically important. The energy dependence of the dose response of Gafchromic EBT2 film is evaluated for a broad range of energies from different radiation sources used in radiation therapy. The beams used for this study comprised of kilovoltage x rays (75, 125, and 250 kVp), 137Cs gamma (662 KeV), 60Co gamma (1.17-1.33 MeV), megavoltage x rays (6 and 18 MV), electron beams (6 and 20 MeV), and proton beams (100 and 250 MeV). The film's response to each of the above energies was measured over the dose range of 0.4-10 Gy, which corresponds to optical densities ranging from 0.05 to 0.74 for the film reader used. The energy dependence of EBT2 was found to be relatively small within measurement uncertainties (1 sigma = +/- 4.5%) for all energies and modalities. For relative and absolute dosimetry of radiation therapy beams, the weak energy dependence of the EBT2 makes it most suitable for clinical use compared to other films.
The concept of in-air output ratio ͑S c ͒ was introduced to characterize how the incident photon ... more The concept of in-air output ratio ͑S c ͒ was introduced to characterize how the incident photon fluence per monitor unit ͑or unit time for a Co-60 unit͒ varies with collimator settings. However, there has been much confusion regarding the measurement technique to be used that has prevented the accurate and consistent determination of S c . The main thrust of the report is to devise a theoretical and measurement formalism that ensures interinstitutional consistency of S c . The in-air output ratio, S c , is defined as the ratio of primary collision water kerma in free-space, K p , per monitor unit between an arbitrary collimator setting and the reference collimator setting at the same location. Miniphantoms with sufficient lateral and longitudinal thicknesses to eliminate electron contamination and maintain transient electron equilibrium are recommended for the measurement of S c . The authors present a correction formalism to extrapolate the correct S c from the measured values using high-Z miniphantom. Miniphantoms made of high-Z material are used to measure S c for small fields ͑e.g., IMRT or stereotactic radiosurgery͒. This report presents a review of the components of S c , including headscatter, source-obscuring, and monitor-backscattering effects. A review of calculation methods ͑Monte Carlo and empirical͒ used to calculate S c for arbitrary shaped fields is presented. The authors discussed the use of S c in photon dose calculation algorithms, in particular, monitor unit calculation. Finally, a summary of S c data ͑from RPC and other institutions͒ is included for QA purposes.
Magnetic fields are known to alter radiation dose deposition. Before patients receive treatment u... more Magnetic fields are known to alter radiation dose deposition. Before patients receive treatment using an MRI-linear accelerator (MRI-Linac), preclinical studies are needed to understand the biological consequences of magnetic-field-induced dose effects. In the present study, the authors sought to identify a beam energy and magnetic field strength combination suitable for preclinical murine experiments. Magnetic field dose effects were simulated in a mouse lung phantom using various beam energies (225 kVp, 350 kVp, 662 keV [Cs-137], 2 MV, and 1.25 MeV [Co-60]) and magnetic field strengths (0.75, 1.5, and 3 T). The resulting dose distributions were compared with those in a simulated human lung phantom irradiated with a 6 or 8 MV beam and orthogonal 1.5 T magnetic field. In the human lung phantom, the authors observed a dose increase of 45% and 54% at the soft-tissue-to-lung interface and a dose decrease of 41% and 48% at the lung-to-soft-tissue interface for the 6 and 8 MV beams, respectively. In the mouse simulations, the magnetic fields had no measurable effect on the 225 or 350 kVp dose distribution. The dose increases with the Cs-137 beam for the 0.75, 1.5, and 3 T magnetic fields were 9%, 29%, and 42%, respectively. The dose decreases were 9%, 21%, and 37%. For the 2 MV beam, the dose increases were 16%, 33%, and 31% and the dose decreases were 9%, 19%, and 30%. For the Co-60 beam, the dose increases were 19%, 54%, and 44%, and the dose decreases were 19%, 42%, and 40%. The magnetic field dose effects in the mouse phantom using a Cs-137, 3 T combination or a Co-60, 1.5 or 3 T combination most closely resemble those in simulated human treatments with a 6 MV, 1.5 T MRI-Linac. The effects with a Co-60, 1.5 T combination most closely resemble those in simulated human treatments with an 8 MV, 1.5 T MRI-Linac.
Antimicrobial agents and chemotherapy, Jan 29, 2015
Antimicrobial Peripherally inserted central catheters (PICCs) might reduce the incidence of CLABS... more Antimicrobial Peripherally inserted central catheters (PICCs) might reduce the incidence of CLABSI. We tested biocompatibility of a novel gendine (combination of chlorhexidine-CHX and gentian violet-GV) PICC in a rabbit intravascular model and tested antimicrobial efficacy in comparison with commercially available minocycline/rifampin (M/R), and CHX PICCs in an in vitro biofilm colonization model.Gendine and uncoated control PICCs were inserted in the jugular veins of rabbits for 4 days. Histopathologic analysis was performed at the end of the four day period and circulating levels of CHX and GV in blood were measured at different time points using liquid chromatography/mass spectrometry. Antimicrobial efficacy of the PICCs were tested following simulated intravascular indwells of 24 hours and 1 week against clinical isolates of methicillin-resistant Staphylococcus aureus, Vancomycin-resistant enterococci Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Enterobacte...
Nanomedicine: Nanotechnology, Biology and Medicine, 2015
We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conj... more We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conjugated gold nanorods. Progressive receptor-mediated internalization of conjugated nanorods over time increases the radiation interaction cross-section of cells and contributes to the effects observed in vitro. The low concentrations of gold required, the long interval between injection of nanoparticles and radiation, and the use of megavoltage radiation to generate radiosensitization in vivo foretell the possibility of eventual clinical translation of this approach.
Journal of immunology (Baltimore, Md. : 1950), 2014
Transcriptional mechanisms governing hematopoietic stem cell (HSC) quiescence, self-renewal, and ... more Transcriptional mechanisms governing hematopoietic stem cell (HSC) quiescence, self-renewal, and differentiation are not fully understood. Sequence-specific ssDNA-binding protein 2 (SSBP2) is a candidate acute myelogenous leukemia (AML) suppressor gene located at chromosome 5q14. SSBP2 binds the transcriptional adaptor protein Lim domain-binding protein 1 (LDB1) and enhances LDB1 stability to regulate gene expression. Notably, Ldb1 is essential for HSC specification during early development and maintenance in adults. We previously reported shortened lifespan and greater susceptibility to B cell lymphomas and carcinomas in Ssbp2(-/-) mice. However, whether Ssbp2 plays a regulatory role in normal HSC function and leukemogenesis is unknown. In this study, we provide several lines of evidence to demonstrate a requirement for Ssbp2 in the function and transcriptional program of hematopoietic stem and progenitor cells (HSPCs) in vivo. We found that hematopoietic tissues were hypoplastic i...
This study evaluated the secondary cancer risk from volumetric-modulated arc therapy (VMAT) for s... more This study evaluated the secondary cancer risk from volumetric-modulated arc therapy (VMAT) for spine radiotherapy compared with intensity-modulated radiotherapy (IMRT) and 3-dimensional conformal radiotherapy (3DCRT). Computed tomography images of an Radiological Physics Center spine anthropomorphic phantom were exported to a treatment planning system (Pinnacle 3 , version 9.4). Radiation treatment plans for spine were prepared using VMAT (dual-arc), 7-field IMRT (beam angles: 1101,1 301, 1501,1 8 0 1,2 1 0 1, 2301, and 2501), and 4-field 3DCRT technique. The mean and maximum doses, dosevolume histograms, and volumes receiving more than 2 and 4 Gy to organs at risk (OARs) were calculated and compared. The lifetime risk for secondary cancers was estimated according to the National Cancer Registry Programme Report 116. VMAT delivered the lowest maximum dose to the esophagus (4.03 Gy), bone (8.11 Gy), heart (2.11 Gy), spinal cord (6.45 Gy), and whole lung (5.66 Gy) as compared with other techniques (IMRT and 3DCRT). The volumes of OAR (esophagus) receiving more than 4 Gy were 0% for VMAT, 27.06% for IMRT, and up to 32.35% for 3DCRT. The estimated risk for secondary cancer in the respective OAR is considerably lower in VMAT compared with other techniques. The results of maximum doses and volumes of OARs suggest that the risk of secondary cancer induction for the spine in VMAT is lower than IMRT and 3DCRT, whereas VMAT has the best target coverage compared with the other techniques.
Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS).... more Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS). Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP) magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC), an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-¹³C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping.
Monte Carlo (MC) modeling of a 6 MV photon beam was used to study the dose perturbation from a ti... more Monte Carlo (MC) modeling of a 6 MV photon beam was used to study the dose perturbation from a titanium rod 5 mm in diameter in various small fields range from 2 × 2 to 5 × 5 cm(2). The results showed that the rod increased the dose to water by ∼6% at the water-rod interface because of electron backscattering and decreased the dose by ∼7% in the shadow of the rod because of photon attenuation. The Pinnacle(3) treatment planning system calculations matched the MC results at the depths more than 1 cm past the rod when the correct titanium density of 4.5 g cm(-3) was used, but significantly underestimated the backscattering dose at the water-rod interface. A CT-density table with a top density of 1.82 g cm(-3) (cortical bone) is a practical way to reduce the dosimetric error from the artifacts by preventing high density assignment to them, but can underestimates the attenuation by the titanium rod by 6%. However, when multi-beam with intensity modulation is used in actual patient spinal stereotactic radiosurgery treatment, the dosimetric effect of assigning 4.5 instead of 1.82 g cm(-3) to titanium implants is complicated. It ranged from minimal effect to 2% dose difference affecting 15% target volume in the study. When hardware is in the beam path, density override to the titanium hardware is recommended.
The device developed by the authors and described here enables the user to measure the depth from... more The device developed by the authors and described here enables the user to measure the depth from the water surface to the point of measurement for a cylindrical ion chamber with a waterproof plastic cap in a water phantom, free of surface-tension error with a high precision. The device seeks vertical orientation and provides the convenience of hands-free operation. The measurement process is simple and quick with a precision of 0.1 mm. (The device is currently available as a 'water phantom depth gauge' from Nuclear Associates, Division of Victoreen Inc., Clare Place, NY, USA.)
A new approach to intraoperative radiation therapy led to the development of mobile linear electr... more A new approach to intraoperative radiation therapy led to the development of mobile linear electron accelerators that provide lower electron energy beams than the usual conventional accelerators commonly encountered in radiotherapy. Such mobile electron accelerators produce electron beams that have nominal energies of 4, 6, 9 and 12 MeV. This work compares the absorbed dose output calibrations using both the AAPM TG-51 and TG-21 dose calibration protocols for two types of ion chambers: a plane-parallel (PP) ionization chamber and a cylindrical ionization chamber. Our results indicate that the use of a 'Markus' PP chamber causes 2-3% overestimation in dose-output determination if accredited dosimetry-calibration laboratory based chamber factors (N(60Co)(D,w,) Nx) are used. However, if the ionization chamber factors are derived using a cross-comparison at a high-energy electron beam, then a good agreement is obtained (within 1%) with a calibrated cylindrical chamber over the entire energy range down to 4 MeV. Furthermore, even though the TG-51 does not recommend using cylindrical chambers at the low energies, our results show that the cylindrical chamber has a good agreement with the PP chamber not only at 6 MeV but also down to 4 MeV electron beams.
The strongest of five 'early' promoters of Bacillus subtilis phage SPPl was localized in a DNA re... more The strongest of five 'early' promoters of Bacillus subtilis phage SPPl was localized in a DNA restriction fragment by analysis of RNA polymerase binding and R-loop formation. The nucleotide sequence of the promoter region was established. The signal structures identified were similar to those recognized by the oS5 RNA polymerase of B. subtilis. The promoter precedes an open reading frame with 51 codons. A protein with the M , predicted from the nucleotide sequence was identified in minicells.
In 1999, the AAPM introduced a reference dosimetry protocol, known as TG51, based on an absorbed ... more In 1999, the AAPM introduced a reference dosimetry protocol, known as TG51, based on an absorbed dose standard. This replaced the previous protocol, known as TG21, which was based on an air kerma standard. A significant body of literature has emerged discussing the improved accuracy and robustness of the absorbed dose standard, and quantifying the changes in baseline dosimetry with the introduction of the absorbed dose protocol. A significant component playing a role in the overall accuracy of beam output determination is the variability due to the use of different dosimeters. This issue, not adequately addressed in the past, is the focus of the present study. This work provides a comparison of absorbed dose determinations using 21 different makes and models of ion chambers for low- and high-energy photon and electron beams. The study included 13 models of cylindrical ion chambers and eight models of plane-parallel chambers. A high degree of precision (<0.25%) resulted from measurements with all chambers in a single setting, a sufficient number of repeat readings, and the use of high quality ion chambers as external monitors. Cylindrical chambers in photon beams show an improvement in chamber-to-chamber consistency with TG51. For electron dosimetry with plane-parallel chambers, the parameters Ngas and the product ND,w x k(ecal) were each determined in two ways, based on (i) an ADCL calibration, and (ii) a cross comparison with an ADCL-calibrated cylindrical chamber in a high-energy electron beam. Plane-parallel chamber results, therefore, are presented for both methods of chamber calibration. Our electron results with technique (i) show that plane-parallel chambers, as a group, overestimate the beam output relative to cylindrical chambers by 1%-2% with either protocol. Technique (ii), by definition, normalizes the plane-parallel results to the cylindrical results. In all cases, the maximum spread in output from the various cylindrical chambers is <2% implying a standard deviation of less than 0.5%. For plane-parallel chambers, the maximum spread is somewhat larger, up to 3%. A few chambers have been identified as outliers.
A key component of the Radiological Physics Center's (RPC) on-site dosimetry review visit... more A key component of the Radiological Physics Center's (RPC) on-site dosimetry review visits are photon beam calibrations for which determination of the energy of the x ray is a key element. The ratio of ionizations, TPR20/TPR10, for a 10 cm x 10 cm field at depths of 20 and 10 cm for a constant SCD is used as a quantitative measure of beam quality in the Task Group 21 protocol. The RPC has measured both TPR20/TPR10 and the corresponding ratio of percent depth dose (D20/D10) at a constant SSD for 685 photon beams (4-25 MV) for most makes and models if accelerators. A strong correlation between TPR20/TPR10 and D20/D10 is presented which allows the determination of the TPR ratio from the measurement of the ratio of percent depth doses. An analysis of the uncertainty introduced in the TG-21 factors (L/rho, Pwall, Prepl) caused by the spread in the measured data and translated into the determination of the TPR ratio results in an insignificant error (< 0.3%). This empirical relationship provides an alternate technique for quantifying the beam quality defined in the TG-21 protocol without surrendering any loss of precision in output calibration. This technique may be found by those who calibrate at a fixed SSD to be an easier and quicker method.
The water equivalency of five "water-equivalent" solid phantom materials was ev... more The water equivalency of five "water-equivalent" solid phantom materials was evaluated in terms of output calibration and energy characterization over a range of energies for both photon (Co-60 to 24 MV) and electron (6-20 MeV) beams. Evaluations compared absorbed doses calculated from ionization measurements using the same dosimeter in the solid phantom materials and in natural water (H2O). Ionization measurements were taken at various calibration depths. The Radiological Physics Center's standard dosimetry system, a Farmer-type ion chamber in a water phantom, was used. Complying with the TG-21 calibration protocol, absorbed doses were calculated using eight measurement and calculational techniques for photons and five for electrons. Results of repeat measurements taken over a period of 2 1/2 years were reproducible to within a +/- 0.3% spread. Results showed that various combinations of measurement techniques and solid phantom materials caused a spread of 3%-4% in the calculation of dose relative to the dose determined from measurements in water for all beam energies on both modalities. An energy dependence of the dose ratios was observed for both photons and electrons.
ABSTRACT Dosimetry measurements of a (131)Cs brachytherapy source have been performed in liquid w... more ABSTRACT Dosimetry measurements of a (131)Cs brachytherapy source have been performed in liquid water employing thermoluminescence dosimeters. A search of the literature reveals that this is the first time a complete set of dosimetric parameters for a brachytherapy "seed" source has been measured in liquid water. This method avoids the medium correction uncertainties introduced by the use of water-equivalent plastic phantoms. To assure confidence in the results, four different sources were employed for each parameter measured, and measurements were performed multiple times. The measured dosimetric parameters presented here are based on the AAPM Task Group 43 formalism. The dose-rate constant measured in liquid water was (1.063 +/- 0.023) cGy h(-1) U(-1) and was based on the air-kerma strength standard for this source established by the National Institute of Standards and Technology. Measured values for the 2D anisotropy function and the radial dose function are presented.
Radiation therapy dose measurements are customarily performed in liquid water. The characterizati... more Radiation therapy dose measurements are customarily performed in liquid water. The characterization of brachytherapy sources is, however, generally based on measurements made with thermoluminescence dosimeters (TLDs), for which contact with water may lead to erroneous readings. Consequently, most dosimetry parameters reported in the literature have been based on measurements in water-equivalent plastics, such as Solid Water. These previous reports employed a correction factor to transfer the dose measurements from a plastic phantom to liquid water. The correction factor most often was based on Monte Carlo calculations. The process of measuring in a water-equivalent plastic phantom whose exact composition may be different from published specifications, then correcting the results to a water medium leads to increased uncertainty in the results. A system has been designed to enable measurements with TLDs in liquid water. This system, which includes jigs to support water-tight capsules of lithium fluoride in configurations suitable for measuring several dosimetric parameters, was used to determine the correction factor from water-equivalent plastic to water. Measurements of several 125I and 131Cs prostate brachytherapy sources in liquid water and in a Solid Water phantom demonstrated a correction factor of 1.039 +/- 0.005 at 1 cm distance. These measurements are in good agreement with a published value of this correction factor for an 125I source.
Since the Gafchromic film EBT has been recently replaced by the newer model EBT2, its characteriz... more Since the Gafchromic film EBT has been recently replaced by the newer model EBT2, its characterization, especially energy dependence, has become critically important. The energy dependence of the dose response of Gafchromic EBT2 film is evaluated for a broad range of energies from different radiation sources used in radiation therapy. The beams used for this study comprised of kilovoltage x rays (75, 125, and 250 kVp), 137Cs gamma (662 KeV), 60Co gamma (1.17-1.33 MeV), megavoltage x rays (6 and 18 MV), electron beams (6 and 20 MeV), and proton beams (100 and 250 MeV). The film's response to each of the above energies was measured over the dose range of 0.4-10 Gy, which corresponds to optical densities ranging from 0.05 to 0.74 for the film reader used. The energy dependence of EBT2 was found to be relatively small within measurement uncertainties (1 sigma = +/- 4.5%) for all energies and modalities. For relative and absolute dosimetry of radiation therapy beams, the weak energy dependence of the EBT2 makes it most suitable for clinical use compared to other films.
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Papers by Ramesh Tailor