Gary W. Johnson

The Columbia University Single-Ion Microbeam

Abstract Randers-Pehrson, G., Geard, C. R., Johnson, G., Elliston, C. D. and Brenner, D. J. The Columbia University Single-Ion Microbeam. Radiat. Res. 156, 210–214 (2001). A single-ion microbeam facility has been constructed at the Columbia University Radiological Research Accelerator Facility. The system was designed to deliver defined numbers of helium or hydrogen ions produced by a van de Graaff accelerator, covering a range of LET from 30 to 220 keV/μm, into an area smaller than the nuclei of human cells growing in culture on thin plastic films. The beam is collimated by a pair of laser-drilled apertures that form the beam-line exit. An integrated computer control program locates the cells and positions them for irradiation. We present details of the microbeam facility including descriptions of the collimators, hardware, control program, and the various protocols available. Various contributions to targeting and positioning precision are discussed along with our plans for future developments. Beam time for outside users is often available (see www.raraf.org).

Quantitative comparisons of continuous and pulsed low dose rate regimens in a model late-effect system

PURPOSE There is increasing interest and usage of pulsed low dose rate (PDR) brachytherapy, in which a single source is shuttled through the catheters of an implant, typically for about 10 min each hour. This study was designed to compare the late effects produced in various PDR regimens with those from the corresponding continuous low dose rate (CLDR) regimens. METHODS AND MATERIALS A model late-responding system was used, namely, cataract induction in the rat lens. This system has the advantage of being highly quantifiable. The rats eyes were exposed to a total dose of 15 Gy either continuously over 24 h, or with three different PDR regimens, all with the same total dose and overall time. We addressed three questions: (a) are late effects increased when a CLDR regimen is replaced with 10-min pulses repeated every hour? (b) Are late effects increased if hourly 10-min pulses are replaced with 10-min pulses repeated every 4 h? (c) Are late effects increased if 10-min pulses are replaced with 100-s pulses? RESULTS We found that the four regimens under test, continuous, 10-min pulses each hour, 10-min pulses every 4 h, and 100-s pulses every hour, showed no significant differences in cataractogenic potential, as estimated with the Wilcoxon-Gehan test. Power tests indicated that the experimental design was adequate to detect relatively small differences in cataractogenicity between regimens. CONCLUSIONS The equality of late effects from CLDR and PDR in these experiments must imply that sublethal damage repair is quite slow in this model late-responding system, in agreement with trends observed in the clinic for sublethal damage repair of late sequelae. Such trends would suggest that PDR is unlikely to produce significantly worse late effects than the corresponding CLDR regimen, which is in agreement with early clinical data using PDR. Caution, however, is strongly recommended.

Theoretical study of short electrostatic lens for the Columbia ion microprobe

A short probe-forming system is developed for the Columbia Microprobe that includes four electrostatic quadrupoles with a Russian quadruplet configuration. The smallest beam spot size and appropriate optimal parameters of the probe-forming systems have been found. These parameters of the system are compared with appropriate parameters of other field configurations including the electrostatic and magnetic fields with dipole, quadrupole, and rotational symmetry. The new original construction of the electrostatic quadruplet has been manufactured. The sensitivity of this quadruplet to some misalignments of the construction is investigated.

A multi-element proportional counter for radiation protection measurements

A detector incorporating about 300 individual counting volumes is described, and the results of performance tests are reported. The device can be employed for a direct measurement of the dose equivalent in an unspecified radiation field on the basis of the lineal energy spectrum in 1-micron diameter tissue regions. It is substantially smaller than a conventional tissue equivalent proportional counter yielding the same counting rate and may be useful for measurements in phantoms.

Michigan forest ecosystem vulnerability assessment and synthesis: a report from the Northwoods Climate Change Response Framework project

Forests in northern Michigan will be affected directly and indirectly by a changing climate during the next 100 years. This assessment evaluates the vulnerability of forest ecosystems in Michigans eastern Upper Peninsula and northern Lower Peninsula to a range of future climates. Information on current forest conditions, observed climate trends, projected climate changes, and impacts to forest ecosystems was considered in order to draw conclusions on climate change vulnerability. Upland spruce-fir forests were determined to be the most vulnerable, whereas oak associations and barrens were determined to be less vulnerable to projected changes in climate. Projected changes in climate and the associated ecosystem impacts and vulnerabilities will have important implications for economically valuable timber species, forest-dependent wildlife and plants, recreation, and long-range planning.

Effect of bismuth breast shielding on radiation dose and image quality in coronary CT angiography

BackgroundCoronary computed tomographic angiography (CCTA) is associated with high radiation dose to the female breasts. Bismuth breast shielding offers the potential to significantly reduce dose to the breasts and nearby organs, but the magnitude of this reduction and its impact on image quality and radiation dose have not been evaluated.MethodsRadiation doses from CCTA to critical organs were determined using metal-oxide-semiconductor field-effect transistors positioned in a customized anthropomorphic whole-body dosimetry verification phantom. Image noise and signal were measured in regions of interest (ROIs) including the coronary arteries.ResultsWith bismuth shielding, breast radiation dose was reduced 46%-57% depending on breast size and scanning technique, with more moderate dose reduction to the heart, lungs, and esophagus. However, shielding significantly decreased image signal (by 14.6 HU) and contrast (by 28.4 HU), modestly but significantly increased image noise in ROIs in locations of coronary arteries, and decreased contrast-to-noise ratio by 20.9%.ConclusionsWhile bismuth breast shielding can significantly decrease radiation dose to critical organs, it is associated with an increase in image noise, decrease in contrast-to-noise, and changes tissue attenuation characteristics in the location of the coronary arteries.

Forest ecosystem vulnerability assessment and synthesis for northern Wisconsin and western Upper Michigan: a report from the Northwoods Climate Change Response Framework project

Forest ecosystems across the Northwoods will face direct and indirect impacts from a changing climate over the 21st century. This assessment evaluates the vulnerability of forest ecosystems in the Laurentian Mixed Forest Province of northern Wisconsin and western Upper Michigan under a range of future climates. Information on current forest conditions, observed climate trends, projected climate changes, and impacts to forest ecosystems was considered in order to assess vulnerability to climate change. Upland spruce-fir, lowland conifers, aspen-birch, lowland-riparian hardwoods, and red pine forests were determined to be the most vulnerable ecosystems. White pine and oak forests were perceived as less vulnerable to projected changes in climate. These projected changes in climate and the associated impacts and vulnerabilities will have important implications for economically valuable timber species, forest-dependent wildlife and plants, recreation, and long-term natural resource planning.

Effect of Dose Rate on Residual γ-H2AX Levels and Frequency of Micronuclei in X-Irradiated Mouse Lymphocytes

The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

Novel neutron sources at the Radiological Research Accelerator Facility.

Since the 1960s, the Radiological Research Accelerator Facility (RARAF) has been providing researchers in biology, chemistry and physics with advanced irradiation techniques, using charged particles, photons and neutrons.We are currently developing a unique facility at RARAF, to simulate neutron spectra from an improvised nuclear device (IND), based on calculations of the neutron spectrum at 1.5 km from the epicenter of the Hiroshima atom bomb. This is significantly different from a standard fission spectrum, because the spectrum changes as the neutrons are transported through air, and is dominated by neutron energies between 0.05 and 8 MeV. This facility will be based on a mixed proton/deuteron beam impinging on a thick beryllium target.A second, novel facility under development is our new neutron microbeam. The neutron microbeam will, for the first time, provide a kinematically collimated neutron beam, 10-20 micron in diameter. This facility is based on a Proton Microbeam, impinging on a thin lithium target near the threshold of the (7)Li(p,n)(7)Be reaction. This novel neutron microbeam will enable studies of neutron damage to small targets, such as single cells, individual organs within small animals or microelectronic components.

Development of a method for assessing non-targeted radiation damage in an artificial 3D human skin model.

Purpose: Despite the increasing concern about the effect of doses below 0.5 Gy and non-targeted exposures of ionising radiation on living organisms, the majority of radiobiological studies are conducted using in vitro cell lines. In order to be able to extrapolate the in vitro results to in vivo models with confidence, it would be of great benefit to develop a reproducible tissue system suitable for critical radiobiological assays. This manuscript describes the development of a reliable protocol to harvest cells from tissue samples and investigate the radiation damage induced on a single cell basis. Materials and methods: To validate this approach as a potential tool for bystander experiments, the method focuses on analysing radiation damage in individual cells as a function of their relative position in the tissue. The experiments reported describe the micronucleus formation following partial irradiation with 3.5 MeV protons (0.1, 0.5 and 1 Gy) in an artificial human skin construct. Results: The reproducible and low background frequency of micronuclei measured in this system allows detection of small increases following radiation exposures. The effect was statistically significant at doses as low as 0.1 Gy in the directly irradiated as well as in the bystander cells. Conclusions: The data presented provide evidence of a spatially dependent bystander effect whose magnitude decrease as a function of the distance from the directly exposed area.