Ion recombination correction in carbon ion beams.

PURPOSE: In this work, ion recombination is studied as a function of energy and depth in carbon ion beams. METHODS: Measurements were performed in three different passively scattered carbon ion beams with energies of 62 MeV/n, 135 MeV/n, and 290 MeV/n using various types of plane-parallel ionization chambers. Experimental results were compared with two analytical models for initial recombination. One model is generally used for photon beams and the other model, developed by Jaffé, takes into account the ionization density along the ion track. An investigation was carried out to ascertain the effect on the ion recombination correction with varying ionization chamber orientation with respect to the direction of the ion tracks. The variation of the ion recombination correction factors as a function of depth was studied for a Markus ionization chamber in the 62 MeV/n nonmodulated carbon ion beam. This variation can be related to the depth distribution of linear energy transfer. RESULTS: Results show that the theory for photon beams is not applicable to carbon ion beams. On the other hand, by optimizing the value of the ionization density and the initial mean-square radius, good agreement is found between Jaffé's theory and the experimental results. As predicted by Jaffé's theory, the results confirm that ion recombination corrections strongly decrease with an increasing angle between the ion tracks and the electric field lines. For the Markus ionization chamber, the variation of the ion recombination correction factor with depth was modeled adequately by a sigmoid function, which is approximately constant in the plateau and strongly increasing in the Bragg peak region to values of up to 1.06. Except in the distal edge region, all experimental results are accurately described by Jaffé's theory. CONCLUSIONS: Experimental results confirm that ion recombination in the investigated carbon ion beams is dominated by initial recombination. Ion recombination corrections are found to be significant and cannot be neglected for reference dosimetry and for the determination of depth dose curves in carbon ion beams.

Feasibility of marrow harvesting from pediatric sibling donors without hematopoietic growth factors and allotransfusion.

We retrospectively studied 108 marrow harvests from 105 pediatric sibling donors. The median age of donors was 8 years (range: 1-15) and the median body weight was 27 kg (range: 10-100). The volumes of aspirated marrow were 5.0-23.8 mL/kg donor body weight, and harvested bone marrow volume exceeded 15 mL/kg in 42% of the donors. A total of 100 autologous blood donations were performed, and eight donors had red cells salvaged from their harvests reinfused. The median Hb levels before and after harvests were 12.3 g/dL (range: 10.0-14.7) and 11.0 g/dL (range: 8.9-13.8), respectively. None of the donors received allogeneic blood transfusions or hematopoietic growth factors such as EPO and G-CSF before or after collection. Transplanted dose was 1.4-10.8 × 10(8) cells/kg recipient body weight without differences due to donor age. Higher concentrations of nucleated and CD34(+) cells were obtained from younger donors. All donors tolerated the procedures well, with no serious complications. Thus, children may safely donate marrow for allogeneic transplantation, and the yields of nucleated cells for engraftment are substantial.

Carbon-ion radiotherapy: clinical aspects and related dosimetry.

The features of relativistic carbon-ion beams are attractive from the viewpoint of radiotherapy. They exhibit not only a superior physical dose distribution but also an increase in biological efficiency with depth, because energy loss of the beams increases as they penetrate the body. This paper reviews clinical aspects of carbon-beam radiotherapy using the experience at the National Institute of Radiological Sciences. The paper also outlines the dosimetry related to carbon-beam radiotherapy, including absolute dosimetry of the carbon beam, neutron measurements and radiation protection measurements.

Radiation protection system at the RIKEN RI beam factory.

The RIKEN RI (radioactive isotope) Beam Factory is scheduled to commence operations in 2006, and its maximum energy will be 400 MeV u(-1) for ions lighter than Ar and 350 MeV u(-1) for uranium. The beam intensity will be 1 pmicroA (6 x 10(12) particles s(-1)) for any element at the goal. For the hands-on-maintenance and the rational shield thickness of the building, the beam loss must be controlled with several kinds of monitors. Three types of radiation monitors will be installed. The first one consists of a neutron dose equivalent monitor and an ionisation chamber, which are commercially available area monitors. The second one is a conventional hand-held dose equivalent monitor wherein the logarithmic signal is read by a programmable logic controller based on the radiation safety interlock system (HIS). The third one is a simple plastic scintillator called a beam loss monitor. All the monitors have threshold levels for alarm and beam stop, and HIS reads all these signals.

Induced radioactivity in CU targets produced by high-energy heavy ions and the corresponding estimated photon dose rates.

Irradiation experiments were performed at the Heavy Ion Medical Accelerator in Chiba (HIMAC) facility, National Institute of Radiological Sciences. The radioactive spallation products in a thick Cu target were obtained for Ar(230, 400 MeV per nucleon), Si(800 MeV per nucleon), Ne(100, 230, 400 MeV per nucleon), C(100, 230, 400 MeV per nucleon), He(100, 230 MeV per nucleon), p(100, 230 MeV) ions. The gamma-ray spectra from irradiated Cu samples inserted into the composite Cu target were measured with a high-purity germanium (HPGe) detector. From the gamma-ray spectra, we obtained the spatial distribution of radioactive yields of spallation products of 40 nuclides in the Cu sample in the Cu target. From the spatial distribution of radioactive yields, we estimated the residual activity and photon dose induced in the Cu target. The residual activity and photon dose become larger with the increase in projectile energy per nucleon and the range of the projectile beam for the same projectile energy per nucleon.

Shielding experiment of heavy-ion produced neutrons using a tissue-equivalent proportional counter.

A shielding experiment was performed at the HIMAC (Heavy Ion Medical Accelerator in Chiba), of National Institute of Radiological Sciences (NIRS), to measure neutron dose using a spherical TEPC (tissue-equivalent proportional counter) of 12.55 cm inner diameter. Neutrons are produced from a 5 cm thick stopping length Cu target bombarded by 400 MeV/nucleon C6+ ions and penetrate concrete or iron shields of various thicknesses at 0 degree to the beam direction. From this shielding experiment. y-distribution, mean lineal energy, absorbed dose, dose equivalent and mean-quality factor were obtained behind the shield as a function of shield thickness. The neutron dose attenuation lengths were also obtained as 126 g cm(-2) for concrete and 211 g cm(-2) for iron. The measured results were compared with the calculated results using the MARS Monte Carlo code.

[A case of Sjögren's syndrome with dermatomyositis who died of rapidly progressive interstitial pneumonia].

We report a case of 55 year-old woman with six year history of Sjögren's syndrome developed fatal rapidly progressive interstitial pneumonia. She had been well until February 1999. She developed swelling and erythematous lesions in the cheek and hands in spring 1999. She was admitted to our hospital for investigations of skin lesions in May 1999. Physical examination on admission revealed small hemorrhagic lesions in the nailfold. Serum CK level was slightly elevated. Electromyogram and MRI suggested mild myositis in the proximal upper extremities. She was suspected to have dermatomyositis along with Sjögren's syndrome. Prednisolone 10 mg/day had been given for her skin problems since March 1999. Suddenly, dyspnea on exertion was appeared on 34th day of admission. Chest X-ray film showed an acute worsening of interstitial pneumonia. Methylprednisolone pulse therapy (1000 mg for 3 days) and cyclophosphamide pulse therapy (500 mg for a day) were started, and she was subsequently treated with 60 mg/day of prednisolone and 250 mg/day of Cyclosporin A. However, interstitial pneumonia did not respond to the treatment, and pneumomediastinum and pneumothorax have developed. She died of respiratory failure on 55th day. We consider that most likely explanation for fatal interstitial pneumonia is concomitantly occurred dermatomyositis.

Selection of endovascular approach of vein of galen aneurysmal malformation.

SUMMARY: Vein of Galen aneurysmal malformation (VGAM) is one of the most difficult intracranial vascular lesions because this disease consists of extremely high flow shunts and affects infants and small children. Thanks to the development of various diagnostic modalities, early diagnosis became possible allowing us to prepare appropriately according to the patients' general and neurological conditions. Recent improvements of endovascular techniques and materials enabled both transarterial and transvenous approaches even to the newborn infants, widening therapeutic windows. In this article, we discuss the selection of endovascular approaches based upon angioarchitecture of VGAM presenting four representative cases from our file.

Proton dosimetry intercomparison based on the ICRU report 59 protocol.

BACKGROUND AND PURPOSE: A new protocol for calibration of proton beams was established by the ICRU in report 59 on proton dosimetry. In this paper we report the results of an international proton dosimetry intercomparison, which was held at Loma Linda University Medical Center. The goals of the intercomparison were, first, to estimate the level of consistency in absorbed dose delivered to patients if proton beams at various clinics were calibrated with the new ICRU protocol, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration factors. MATERIALS AND METHODS: Eleven institutions participated in the intercomparison. Measurements were performed in a polystyrene phantom at a depth of 10.27 cm water equivalent thickness in a 6-cm modulated proton beam with an accelerator energy of 155 MeV and an incident energy of approximately 135 MeV. Most participants used ionization chambers calibrated in terms of exposure or air kerma. Four ionization chambers had 60Co-based calibration in terms of absorbed dose-to-water. Two chambers were calibrated in a 60Co beam at the NIST both in terms of air kerma and absorbed dose-to-water to provide a comparison of ionization chambers with different calibrations. RESULTS: The intercomparison showed that use of the ICRU report 59 protocol would result in absorbed doses being delivered to patients at their participating institutions to within +/-0.9% (one standard deviation). The maximum difference between doses determined by the participants was found to be 2.9%. Differences between proton doses derived from the measurements with ionization chambers with N(K)-, or N(W) - calibration type depended on chamber type. CONCLUSIONS: Using ionization chambers with 60Co calibration factors traceable to standard laboratories and the ICRU report 59 protocol, a distribution of stated proton absorbed dose is achieved with a difference less than 3%. The ICRU protocol should be adopted for clinical proton beam calibration. A comparison of proton doses derived from measurements with different chambers indicates that the difference in results cannot be explained only by differences in 60Co calibration factors.

Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy.

PURPOSE: The irradiation system and biophysical characteristics of carbon beams are examined regarding radiation therapy. METHODS AND MATERIALS: An irradiation system was developed for heavy-ion radiotherapy. Wobbler magnets and a scatterer were used for flattening the radiation field. A patient-positioning system using X ray and image intensifiers was also installed in the irradiation system. The depth-dose distributions of the carbon beams were modified to make a spread-out Bragg peak, which was designed based on the biophysical characteristics of monoenergetic beams. A dosimetry system for heavy-ion radiotherapy was established to deliver heavy-ion doses safely to the patients according to the treatment planning. A carbon beam of 80 keV/microm in the spread-out Bragg peak was found to be equivalent in biological responses to the neutron beam that is produced at cyclotron facility in National Institute Radiological Sciences (NIRS) by bombarding 30-MeV deuteron beam on beryllium target. The fractionation schedule of the NIRS neutron therapy was adapted for the first clinical trials using carbon beams. RESULTS: Carbon beams, 290, 350, and 400 MeV/u, were used for a clinical trial from June of 1994. Over 300 patients have already been treated by this irradiation system by the end of 1997.

Carbon beam dosimetry intercomparison at HIMAC.

To verify international uniformity in carbon beam dosimetry, an intercomparison programme was carried out at the heavy ion medical accelerator (HIMAC). Dose measurements with ionization chambers were performed for both unmodulated and 6 cm modulated 290 MeV/nucleon carbon beams. Although two different dosimetry procedures were employed, the evaluated values of absorbed dose were in good agreement. This comparison established a common framework for ionization chamber dosimetry between two different carbon beam therapy facilities.

Ground-based simulations of cosmic ray heavy ion interactions in spacecraft and planetary habitat shielding materials.

This paper surveys some recent accelerator-based measurements of the nuclear fragmentation of high energy nuclei in shielding and tissue-equivalent materials. These data are needed to make accurate predictions of the radiation field produced at depth in spacecraft and planetary habitat shielding materials and in the human body by heavy charged particles in the galactic cosmic radiation. Projectile-target combinations include 1 GeV/nucleon 56Fe incident on aluminum and graphite and 600 MeV/nucleon 56Fe and 290 MeV/nucleon 12C on polyethylene. We present examples of the dependence of fragmentation on material type and thickness, of a comparison between data and a fragmentation model, and of multiple fragments produced along the beam axis.

Dosimetry and measured differential W values of air for heavy ions.

Heavy-ion irradiation systems were designed and constructed at two cyclotron facilities in Japan for use in various fields of radiation physics and radiation biology. A 135 MeV/u carbon beam as well as 12 MeV/u carbon and helium-3 beams were first used in experiments. We have established a systematic method for heavy-ion dosimetry at both high and low incident energies involving measurements of fluences. We also obtained differential W values (w) of air for those beams by comparing the results of fluence measurement dosimetry with ionization chamber dosimetry. The differential W values of air were found to be 36.2 +/- 1.0, 34.5 +/- 1.0, and 33.7 +/- 0.9 eV for 6.7 MeV/u carbon ions, 10.3 MeV/u 3He ions, and 129.4 MeV/u carbon ions, respectively. The w value for high-energy heavy ions approaches the W value for high-energy electron or photon beams. In ionization chamber dosimetry for a heavy-ion beam, we found a track-size effect. A difference in the track sizes of heavy ions in the gas and solid phases affected the output current of the ion chamber in the case of high-energy heavy ions.

Energy loss of 70 MeV protons in organic polymers.

Using Bragg ionization curves, measurements of the average stopping power of organic polymers relative to that of water have been made for 70 MeV protons losing about 30 MeV in the absorbers. By comparing calculated curves to experimental ones, I-values for the polymers were obtained, relative to the I-value for A1. For repeated measurements with A-150 tissue equivalent plastic, the standard deviation of the ratio of the average stopping powers q was +/- 0.06%. It was found that q depends on the year of production of A-150. For other absorbers, the uncertainty of q is estimated to be +/- 0.2%, with a corresponding uncertainty of the I-values of +/- 1.5%. Most measured I-values exceed values calculated with the additivity rule by about 10%. During the course of the measurements, fluctuations of the proton energy from the cyclotron of up to 0.8% were found.

Amplitude abnormalities in the scalp far-field N18 of SSEPs to median nerve stimulation in patients with midbrain-pontine lesion.

Various amplitude ratios were measured in 20 normal controls and 36 patients with midbrain-pontine, thalamic or putaminal lesions in order to evaluate the amplitude abnormalities in scalp far-field N18 following median nerve stimulation. A study of normal controls showed that the distributions of P9/N18, P14/N18 and N18/P14 + N18 resembled a gaussian distribution and could be used as criteria for determining the decrease in N18 amplitude in each patient. There was a decrease in N18 amplitude, or the absence of N18, in patients with midbrain-pontine lesions, but not in those with thalamic or putaminal lesions. Nine amplitude ratios (P11/P9, P14/P9, N18/P9, P9/P11, P9/P14, P9/N18, N18/P14, P14/N18 and N18/P14 + N18) were compared statistically for normal controls and 3 groups of patients based on non-parametric, Wilcoxon's non-pairs and signed-rank tests. A decrease in N18 amplitude in midbrain-pontine lesion was shown by significant changes in N18/P9, P9/N18, N18/P14, P14/N18 and N18/P14 + N18, no amplitude decreases in P11 and P14 being found from the amplitude ratios of P11/P9, P9/P11, P14/P9 and P9/P14. No significant changes were seen in any of the 9 amplitude ratios when the normal controls and patients with thalamic and putaminal lesions were compared. The amplitude ratios of N18 can be used to detect a decrease in N18 amplitude in patients with midbrain-pontine lesions. The data obtained support the hypothesis that N18 originates in the midbrain-pontine region and that neither the thalamus nor thalamocortical radiation make major contributions to the formation of the N18 peak.

Determination of ion recombination loss by two-voltage method for pulsed radiation beams.

The ion recombination loss is one of the most important correction factors for dosimetry using ionization chamber especially for the measurement of high-intensity pulsed radiation beam. The two-voltage method has been used frequently for the correction of ion recombination loss. Several ways to approximate the method are presented. Comparisons were carried out to check the validity of the approximation. Using four ionization chambers of different types and shapes, measurements were made to obtain the optimal value of the ratio for the two voltages.

Lipid peroxidation and concentration of glutathione in erythrocytes from workers exposed to lead.

Lipoperoxide concentration in erythrocytes from workers occupationally exposed to lead (mean blood lead concentration 57.1 (SD 17.6) micrograms/dl) was significantly higher than that in controls. It was not different in plasma from the two groups. The activity of superoxide dismutase (SOD) and catalase in erythrocytes from workers exposed to lead was significantly lower than that of control subjects. The effect of lead was also seen in the glutathione concentration of erythrocytes from lead exposed workers, which was reduced to 69% of that found in erythrocytes from control workers. The increase in methaemoglobin content of erythrocytes from workers exposed to lead was less than expected and not significantly different from that of controls. A positive correlation between lipoperoxide concentration in erythrocytes and lead concentration in blood and a negative correlation between glutathione concentration in erythrocytes and blood lead concentration were found. Incubation of erythrocytes for 24 hours at 37 degrees C in the presence of lead (100 micrograms/dl) produced no changes in glutathione and lipoperoxide concentrations, although there was inhibition of activity of SOD (14.3%), catalase (10.1%), and glutathione peroxidase (35.1%). A similar experiment with heparinised whole blood showed increased haemolysis with no changes in membrane lipid peroxidation of erythrocytes. It is postulated that the lowered concentration of glutathione and decreased activity of SOD, catalase, and glutathione peroxidase in erythrocytes from workers exposed to lead may play a part in the increased membrane lipid peroxidation. Furthermore, the results suggest the possibility that leucocytes, or platelets, or both, may induce haemolysis in the presence of lead.

Uptake of lead by human red blood cells and intracellular distribution.

Lead added to plasma was rapidly incorporated into suspended human red blood cells at 37 degrees C. The rate of lead uptake into the cells reached a maximum of 35 micrograms (0.17 mumole)/10(10) cells/h. The rate of lead uptake with resealed ghosts was comparable to that of intact cells. These findings indicate that the transport of lead across the erythrocyte membrane is, energy-independent, carrier-mediated passive transport, which confirms the conclusion of Simons. On the other hand, little release of incorporated lead from the cells in lead-free plasma was observed. Some 98% of intracellular lead was in cytoplasm, mostly in protein-bound form, and only 2% was in the membrane fraction. When red blood cells were incubated in plasma containing lead at about 10 mg/dl concentration for 24 hours at 37 degrees C, no progressive accumulation of lead and protein in the membrane fraction was observed. Thus, lead-protein complexes in cytosol are unlikely to associate with membranes. Human haemoglobin had forty-five binding sites for lead with the dissociation constant of 0.5 x 10(-6) M. The binding of lead to oxyhaemoglobin did not show any effect on the iron atom in the heme.

Skin and epidural recording of spinal somatosensory evoked potentials following median nerve stimulation: correlation between the absence of spinal N13 and impaired pain sense.

A clinical lesion study and intraoperative epidural recordings were made to test the origin and clinical significance of the spinal N13 and P13 of somatosensory evoked potentials (SEP) that follow median nerve stimulation. Intraoperatively, the respective peak latencies of spinal P13 and N13 coincided with those of the N1 component of the dorsal cord potential and its phase reversed positivity. On both the ventral and dorsal sides of the cervical epidural space, maximal amplitude was at the C5 vertebral level to which nerve input from the C6 dermatome is the main contributor. The modality of sensory impairment in the hand dermatome was examined in selected patients with cervical lesions, who showed such normal conventional SEP components as Erb N9, far-field P9, P11, P14, N18 and cortical N20, with or without loss of spinal N13. Statistically, the loss of spinal N13 was associated with decrease of pain sensation in the C6 dermatome. This was interpreted as being due to damage to the central grey matter of the cord, including the dorsal horn. Our results suggest the spinal N13 and P13 originate from the same source in the C6 spinal cord segment and that they are good indicators for the detection of centromedullary cervical cord damage.

[Diagnostic value of short latency somatosensory evoked potentials for various intracranial lesions].

Diagnostic value of short latency somatosensory evoked potentials (SSEP) was studied in 124 patients with various intracranial lesions. Abnormal SSEPs were recorded in 58 of 124 patients (46.8%) and were classified into three types. Type I (6 cases) showed abnormality of late components with N18 being preserved. All patients with type I abnormality had cortical or subcortical lesions in the parietal lobe. Type II (20 cases) was characterized by abnormality of N18 and late components with N16 being preserved, and mainly seen in patients with a lesion involving thalamus and internal capsule. Type III (31 cases) showed abnormality of N16 and N18 which was elicited by unilateral stimulation (IIIa: 11 cases), or bilateral stimulation (IIIb: 21 cases), and this indicated brainstem impairment. The incidence of SSEP abnormality was as high as 93.1% in patients with sensory disturbance, and 23.1% in patients without such disturbance, and it was suggested that SSEP is useful to detect subclinical dysfunction in the somatosensory pathway. The SSEP grades defined by Anderson et al were found to be well correlated with the outcome of patients with severe head injury, and the SSEP was more reliable for predicting the outcome of patients than the auditory brainstem evoked responses. The SSEP grades were also fairly well correlated with the outcome of patients with cerebrovascular accidents, although the outcome was not consistent in patients with moderately abnormal SSEP.