Nuclear spectroscopy for in situ soil elemental analysis: Monte Carlo simulations.

We developed a model to simulate a novel inelastic neutron scattering (INS) system for in situ non-destructive analysis of soil using standard Monte Carlo Neutron Photon (MCNP5a) transport code. The volumes from which 90%, 95%, and 99% of the total signal are detected were estimated to be 0.23 m3, 0.37 m3, and 0.79 m3, respectively. Similarly, we assessed the instrument's sampling footprint and depths. In addition we discuss the impact of the carbon's depth distribution on sampled depth.

Measuring partial body potassium in the legs of patients with spinal cord injury: a new approach.

Patients with acute spinal cord injury (SCI) with paralysis experience rapid and marked muscle atrophy below the level of the lesion. Muscle is lost above the lesion due to enforced bed rest associated with immobilization. Presently, there is no viable method to quantify muscle loss between the time of injury to the initiation of rehabilitation and remobilization. Furthermore, to assess the efficacy of any physical or pharmacological intervention necessitates the ability to accurately determine the impact of these treatments on muscle mass and function. Our results are presented from measurements of regional potassium (K) in the legs of persons with chronic SCI. The intracellular body K, comprising approximately 97% of the total body K, is indicative of the metabolically active cell mass, of which over 50% is located in the skeletal muscle (SM). To assess regional variations in SM mass in the legs, a partial body K (PBK) system designed for this purpose was placed on a potentially mobile cart. The SM mass measured by PBK in an able-bodied control cohort (n = 17) and in patients with chronic SCI (n = 21) was 17.6 +/- 0.86 and 11.0 +/- 0.65 kg, respectively, a difference of approximately 37.5%. However, the difference in the lean tissue mass of the legs obtained by dual-energy absorptiometry (DXA) in the same cohorts was 20.5 +/- 0.86 and 15.5 +/- 0.88 kg, respectively, or a difference of approximately 24.4%. PBK offers a novel approach to obtain regional K measurements in the legs, thus allowing the potential for early and serial assessment of muscle loss in SCI subjects during the acute and subacute periods following paralysis. The basic characteristics and performance of our PBK system and our calibration procedure are described in this preliminary report.

Measuring partial body potassium in the arm versus total body potassium.

Skeletal muscle (SM), the body's main structural support, has been implicated in metabolic, physiological, and disease processes in humans. Despite being the largest tissue in the human body, its assessment remains difficult and indirect. However, being metabolically active it contains over 50% of the total body potassium (TBK) pool. We present our preliminary results from a new system for measuring partial body K (PBK) that presently are limited to the arm yet provide a direct and specific measure of the SM. This uniquely specific quantification of the SM mass in the arm, which is shielded from the body during measurement, allows us to simplify the assumptions used in deriving the total SM, thereby possibly improving the modeling of the human body compartments. Preliminary results show that PBK measurements are consistent with those from the TBK previously obtained from the same subjects, thus offering a simpler alternative to computed tomography and magnetic resonance imaging used for the same purposes. The PBK system, which can be set up in a physician's office or bedside in a hospital, is completely passive, safe, and inexpensive; it can be used on immobilized patients, children, pregnant women, or other at-risk populations.

Analysis of potassium spectra with low counting statistics using trapezoidal and library least-squares methods.

Potassium spectra with low counting statistics were measured with a NaI detector from a water phantom, simulating a brain, and were analyzed for error propagation in determination of K employing either the Trapezoidal Method or the Library Least-Squares method. We demonstrate, using measured and synthetic spectra, that a smaller error is obtained in the analysis of potassium when using the Library Least-Squares method.

Comparison of a digital and an analog signal processing system for neutron inelastic gamma-ray spectrometry.

We compared the value of using a digital signal processing unit for gamma-ray spectroscopy with that of an analog one for in situ measurements of gamma-rays generated by inelastic neutron scattering reactions with soil elements. A large cylindrical NaI(Tl) scintillation detector, 15.24 cm high by 15.24 cm diameter was used to measure carbon (C) and oxygen (O). The performance of the systems was assessed as a function of input count rate (ICR) by monitoring the peak areas of the C, 4.43 MeV, and O, 6.13 MeV, gamma-rays. In separate experiments, the digital and the analog systems were also compared using an intense 10.3 mCi 137Cs source to vary the ICR, and the 1.17 MeV peak area of 60Co was used as the reference.

Proof-of-Principle to Measure Potassium in the Human Brain: A Feasibility Study.

We describe the results of a proof-of-principle to measure the potassium content in the human brain using the natural radioisotope (40)K that is in equilibrium with the stable isotopes of potassium, (39)K and (41)K. A fixed relationship exists between radioactive potassium and the total potassium in the brain, which in turn reflects the brain's cell mass and intracellular water compartment. Accordingly, we explored whether measurements of brain potassium could serve as possible indicators of intracellular cerebral edema. We designed, built, and then calibrated our system using a spherical phantom containing KCl salt dissolved in water at levels comparable to those in the human brain. Emitted radiation was detected using sodium iodide (Nal) and high-purity germanium (HP-Ge) detectors. Our results with phantoms and with five volunteers demonstrate the feasibility of measuring potassium at the levels normally present in human brain tissue. We plan to extend the system to detect the onset of brain edema in patients with multiple sclerosis.

Some aspects of measuring levels of potassium in the brain.

The general aim of this work is to measure brain potassium (K) levels as a marker of intracellular water content and to test the hypothesis of whether edema in multiple sclerosis (MS) is associated with increased intracellular brain water. For that purpose, a system to measure K in brain is being developed. Our specific aim is to assess the potential contribution to the K photopeak from cranial K located outside the brain. For this, a simplified spherical phantom to represent the brain, a square box to represent the cranium, and a K point source to assess the contributions due to K outside the brain were used. It is estimated that only about 1-2% of the K photopeak might be attributable to K outside the brain.

Application of TEPC microdosimetry to boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is a bimodal radiation therapy used primarily for highly malignant gliomas. Tissue-equivalent proportional counter (TEPC) microdosimetry has proven an ideal dosimetry technique for BNCT, facilitating accurate separation of the photon and neutron absorbed dose components, assessment of radiation quality and measurement of the BNC dose. A miniature dual-TEPC system has been constructed to facilitate microdosimetry measurements with excellent spatial resolution in high-flux clinical neutron capture therapy beams. A 10B-loaded TEPC allows direct measurement of the secondary charged particle spectrum resulting from the BNC reaction. A matching TEPC fabricated from brain-tissue-equivalent plastic allows evaluation of secondary charged particle spectra from photon and neutron interactions in normal brain tissue. Microdosimetric measurements performed in clinical BNCT beams using these novel miniature TEPCs are presented, and the advantages of this technique for such applications are discussed.

A conducting plastic simulating brain tissue.

A new conducting plastic has been composed which accurately simulates the photon and neutron absorption properties of brain tissue. This tissue-equivalent (TE) plastic was formulated to match the hydrogen and nitrogen constituents recommended by ICRU Report #44 for brain tissue. Its development was initiated by the inability of muscle tissue-equivalent plastic to closely approximate brain tissue with respect to low-energy neutron interactions. This new plastic is particularly useful as an electrode in TE dosimetry devices for boron neutron capture therapy (BNCT), which utilizes low-energy neutrons for radiotherapy of the brain. Absorbed dose measurements in a clinical BNCT beam using a proportional counter constructed from this TE plastic show good agreement with Monte Carlo calculations.

Gamma resonance absorption. New approach in human body composition studies.

The main stream of body elemental analysis is based on the delayed, prompt, and inelastic neutron interactions with the main elements found in the human body, and subsequent analysis of the measured delayed or prompt gamma ray spectra. This methodology traditionally was, and still is, applied for whole body analysis and requires relatively high radiation doses. A new method, based on gamma nuclear resonance absorption (GNRA), is being established at Brookhaven National Laboratory as part of its body composition program. The method is element specific with a high tomographic spatial-resolution capability, at a small fraction of the radiation dose used in the current system. The new system, with its components and capabilities, is described below.

Patient positioning in static beams for boron neutron capture therapy of malignant glioma.

PURPOSE: To develop a procedure for the optimum patient positioning and immobilization during boron neutron capture therapy (BNCT) of glioblastoma multiforme (GBM) at the Brookhaven medical research reactor (BMRR). METHODS: A replica of the treatment room in the BMRR was constructed to simulate patient position. A unique feature is a transparent opening in wall to simulate the location of the beam port and to provide a beam-eye view of the head. A portable stereotactic frame was built to facilitate head markings. These marking provide critical reference points for determining the entry point of the central beam axis and patient positioning coordinates calculated relative to these points. RESULT: This patient positioning and immobilization system has proven to be satisfactory in minimizing the variations from the planned BNCT radiation doses. CONCLUSION: The approach described herein has been satisfactory in treating patients with GBM. These patients are minimally sedated during BNCT lasting from 38 to 73 minutes.

Boron neutron capture therapy for glioblastoma multiforme: interim results from the phase I/II dose-escalation studies

OBJECTIVE: The primary objective of these Phase I/II dose-escalation studies is to evaluate the safety of boronophenylalanine (BPA)-fructose-mediated boron neutron capture therapy (BNCT) for patients with glioblastoma multiforme (GBM). A secondary purpose is to assess the palliation of GBM by BNCT, if possible. METHODS: Thirty-eight patients with GBM have been treated. Subtotal or gross total resection of GBM was performed for 38 patients (median age, 56 yr) before BNCT. BPA-fructose (250 or 290 mg BPA/kg body weight) was infused intravenously, in 2 hours, approximately 3 to 5 weeks after surgery. Neutron irradiation was begun between 34 and 82 minutes after the end of the BPA infusion and lasted 38 to 65 minutes. RESULTS: Toxicity related to BPA-fructose was not observed. The maximal radiation dose to normal brain varied from 8.9 to 14.8 Gy-Eq. The volume-weighted average radiation dose to normal brain tissues ranged from 1.9 to 6.0 Gy-Eq. No BNCT-related Grade 3 or 4 toxicity was observed, although milder toxicities were seen. Twenty-five of 37 assessable patients are dead, all as a result of progressive GBM. No radiation-induced damage to normal brain tissue was observed in postmortem examinations of seven brains. The minimal tumor volume doses ranged from 18 to 55 Gy-Eq. The median time to tumor progression and the median survival time from diagnosis (from Kaplan-Meier curves) were 31.6 weeks and 13.0 months, respectively. CONCLUSION: The BNCT procedure used has been safe for all patients treated to date. Our limited clinical evaluation suggests that the palliation offered by a single session of BNCT is comparable to that provided by fractionated photon therapy. Additional studies with further escalation of radiation doses are in progress.

The effect of high-linear energy transfer ions on the electron paramagnetic resonance signal induced in alanine.

Microcrystalline samples of L-alanine irradiated with energetic high-LET cobalt and iron ions had different EPR spectra compared to alanine samples irradiated with low-LET photons. The differences in the shapes of the EPR spectra and their dependence on the microwave power are related to the differences in the microwave power saturation of the radicals induced by the various types of ionizing radiation. The changes in the shape of the EPR spectra, which were caused by increasing microwave power, were more pronounced in samples irradiated with low-LET radiation than with high-LET particles. This effect showed a long-term stability and can be used to monitor radiation quality.

Boron neutron-capture therapy (BNCT) for glioblastoma multiforme (GBM) using the epithermal neutron beam at the Brookhaven National Laboratory.

OBJECTIVE: Boron neutron-capture therapy (BNCT) is a binary form of radiation therapy based on the nuclear reactions that occur when boron (10B) is exposed to thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy of p-boronophenylalanine (BPA)-based BNCT. The objectives of the Phase I/II trial were to study the feasibility and safety of single-fraction BNCT in patients with GBM. MATERIALS AND METHODS: The trial design required (a) a BPA biodistribution study performed at the time of craniotomy; and (b) BNCT within approximately 4 weeks of the biodistribution study. From September 1994 to July 1995, 10 patients were treated. For biodistribution, patients received a 2-hour intravenous (i.v.) infusion of BPA-fructose complex (BPA-F). Blood samples, taken during and after infusion, and multiple tissue samples collected during surgical debulking were analyzed for 10B concentration. For BNCT, all patients received a dose of 250 mg BPA/kg administered by a 2-hour i.v. infusion of BPA-F, followed by neutron beam irradiation at the Brookhaven Medical Research Reactor (BMRR). The average blood 10B concentrations measured before and during treatment were used to calculate the time of reactor irradiation that would deliver the prescribed dose. RESULTS: 10B concentrations in specimens of scalp and tumor were higher than in blood by factors of approximately 1.5 and approximately 3.5, respectively. The 10B concentration in the normal brain was < or = that in the blood; however, for purposes of estimating radiation doses to normal brain endothelium, it was always assumed to be equal to blood. BNCT doses are expressed as gray-equivalent (Gy-Eq), which is the sum of the various physical dose components multiplied to appropriate biologic effectiveness factors. The dose to a 1-cm3 volume where the thermal flux reached a maximum was 10.6 +/- 0.3 Gy-Eq in 9 patients and 13.8 Gy-Eq in 1 patient. The minimum dose in tumor ranged from 20 to 32.3 Gy-Eq. The minimum dose in the target volume (tumor plus 2 cm margin) ranged from 7.8 to 16.2 Gy-Eq. Dose to scalp ranged from 10 to 16 Gy-Eq. All patients experienced in-field alopecia. No CNS toxicity attributed to BNCT was observed. The median time to local disease progression following BNCT was 6 months (range 2.7 to 9.0). The median time to local disease progression was longer in patients who received a higher tumor dose. The median survival time from diagnosis was 13.5 months. CONCLUSION: It is feasible to safely deliver a single fraction of BPA-based BNCT. At the dose prescribed, the patients did not experience any morbidity. To further evaluate the therapeutic efficacy of BNCT, a dose-escalation study delivering a minimum target volume dose of 17 Gy-Eq is in progress.

Boron neutron capture therapy: re-irradiation response of the rat spinal cord.

PURPOSE: To evaluate the retreatment response of the CNS to BNC irradiation using a rat spinal cord model. MATERIALS AND METHODS: Fischer 344 rats were irradiated with single doses of 6 MeV X-rays which were 22, 40 or 80% of a total effect (TE). An additional group of rats was irradiated with a single exposure of thermal neutrons in the presence of the neutron capture agent boronophenylalanine (BPA) to a dose that represented 82% of the TE. After an interval of 26 weeks, animals were re-irradiated using various single doses of thermal neutrons in combination with BPA. RESULTS: The re-irradiation ED50 doses represented 77, 80 or 50% of the TE after an initial X-ray dose of 22, 40 or 80% of the TE, respectively. The re-irradiation ED50 dose was 55% of the TE after an initial BNC irradiation dose representing 82% of the TE. CONCLUSION: The level of the initial radiation damage had a direct bearing on the re-irradiation response. Recovery following initial treatment with BNC irradiation was similar to that after initial irradiation with X-rays.

Impaired permeability in radiation-induced lung injury detected by technetium-99m-DTPA lung clearance.

UNLABELLED: This study evaluates the use of the 99mTc-DTPA aerosol lung clearance method to investigate radiation-induced lung changes in eight patients undergoing radiotherapy for lung or breast carcinoma. The sensitivity of the method was compared with chest radiography for detecting radiation-induced changes in the lung, regional alterations within (irradiated region) and outside (shielded region) the treatment ports, effect of irradiated lung volume, and dependence on time after radiotherapy. METHODS: Serial DTPA lung clearance studies were performed before the first radiation treatment (baseline), then weekly during a 5- to 7-wk course, and up to 12 times post-therapy over periods of 56-574 days. The total activity deposited in the lungs for each study was approximately 150 microCi (approximately 5.6 MBq). DTPA clearance, expressed in terms of the biological half-time, t 1/2, was computed from the slopes of the least-squares fit regression lines of the time-activity curves for the first 10 min for irradiated and shielded lung regions. RESULTS: Major findings include: (a) significant and early DTPA t 1/2 changes were observed in all patients during and after radiotherapy; (b) changes in DTPA t 1/2 values were observed in both irradiated and shielded lung regions in all patients suggesting a radiation-induced systemic reaction; (c) changes in DTPA t 1/2 values were correlated (p < 0.05) with the irradiated lung volumes; (d) significantly reduced DTPA t 1/2 values were observed in three patients who subsequently presented with clinical symptoms and/or radiographic changes consistent with radiation pneumonitis (t1/2 felt to 19% +/- 6% of baseline values, compared with 64% +/- 17% in the remaining patients [p < 0.01]); (e) the onset of decreased DTPA t 1/2 values in these three patients occurred 35-84 days before clinical symptoms and/or radiographic changes; and (f) DTPA t 1/2 tended to approach baseline values with time after radiotherapy, suggesting a long-term recovery in lung injury. CONCLUSION: These observations show significant and early alterations in DTPA lung clearance during and after radiotherapy that may provide a sensitive assay to monitor changes in radiation-induced lung injury and may facilitate early therapeutic intervention.

Current misinterpretations of the linear no-threshold hypothesis.

Contrary to the "linear no-threshold hypothesis," which implies that "any amount, however small" of radiation energy is a serious cancer threat, it is shown here that only relatively quite large amounts of such energy can pose such a threat to a person or population. Key to doing this is to make a sharp distinction between the actual amount of the radiation agent imparted energy, epsilon, which must be expressed in units of joules, and the average concentration or density of energy, epsilon/m (i.e., absorbed dose), which is expressed in units of Gy. With any cellular system, e.g., in tissue culture, one can easily adjust the numbers of cells used at each dose point so that a clearly significant number of radiation-induced quantal responses (e.g., mutations, chromosome aberrations, malignant transformations, cell death), in the absorbed dose range of about 0.7 to 3 or more Gy, can be observed. However, if the number of cells is held constant as the absorbed dose is progressively reduced, a point is reached at which no significant excess is observable. This situation is frequently "remedied" by including more cells at that point, which, of course, can increase the number of malignant transformations sufficiently to render the excess statistically valid. However, because both axes are expressed in relative terms, the data point, despite having gained statistical significance, remains at the same location on the graph. This gives the false impression that no more of the agent energy was added or needed to achieve significance. However, if both coordinates are put in absolute terms, i.e., the actual number of quantal responses vs. imparted energy, and the same exercise of "improving the statistics" at low exposures is attempted, it then becomes evident that any point thus rendered significant must be relocated at a substantially higher energy point on the graph. This demonstrates unequivocally the fallacy in the proof of the "linear hypothesis" which is based on agent concentration response curves and not agent amount. It shows that the smaller the agent concentration (absorbed dose; epsilon/m), the larger the amount of radiation energy that must be added to the system in order to demonstrate a radiation-induced response. This suggests a minimum average energy requirement for production of a radiation-attributable cancer. It Ls concluded that the "linear hypothesis" should be abandoned as the cornerstone of radiation protection and practice.

The effects of boron on the electron paramagnetic resonance spectra of alanine irradiated with thermal neutrons.

The effects of boric acid admixture on the intensity and line structure of EPR spectra of free radicals produced in alanine by thermal neutrons are presented. The EPR signal enhancement, up to a factor of 40 depending on the boron concentration, is related to additional energy deposition in alanine crystals by the disintegration products resulting from the capture of a thermal neutron by boron, 10B(n,alpha)7Li. The changes in the shape of the EPR spectra observed by changing the microwave power are due to the differences in the microwave power saturation of the free radicals produced by a low-LET radiation and those produced by the high-LET components of the radiation after the neutron capture reaction.

A novel comprehensive quality control instrument for medical accelerators.

A comprehensive quality control instrument for calibration of medical accelerators that use photon, electron, or proton beams in teleradiotherapy is described. It employs a fluorescence screen, mounted on a central stage with four degrees of freedom, monitored by a CCD camera. A single set-up of the instrument enables one to perform mechanical, light laser, and radiation tests, at arbitrary angles of the accelerator gantry. The new device provides for quantitative evaluation of the tests performed and provides for documentation of the test results in real time. The device provides significant time savings with concurrent improvement in accuracy for tests performed during installation and acceptance processes, and the implementation of quality control procedures for medical accelerators.