Acute pulmonary and splenic response in an in vivo model of whole-body low-dose X-radiation exposure.

Purpose: Diagnostic radiation is an important part of patient care in the Intensive Care Unit; however, there is little data on the acute effects of exposure to these doses. We investigated pulmonary and splenic response 30 minutes, 4 hours or 24 hours after exposure to 2 mGy, 20 mGy, 200 mGy or 4 Gy whole-body X-radiation in a Sprague Dawley rat model. Materials and methods: Lung injury was assessed via respiratory mechanics, pulmonary edema, cellular, and proteinaceous fluid infiltrate and protein expression of oxidative stress markers. The radiation effect on the spleen was determined via proliferation, apoptosis and protein expression of oxidative stress markers. Results: All measurements of the lung did not differ from sham animals except for an increase in catalase after high dose exposure. Stimulated splenocyte proliferation increased after sham and low dose exposure, did not change after 200 mGy exposure and was significantly lower after 4 Gy exposure. The number of apoptotic cells increased 4 hours after 4 Gy exposure. There were fewer apoptotic cells after low dose exposure compared to sham. Both catalase and MnSOD were increased after 4 Gy exposure. Conclusion: There was no measured effect on pulmonary function while there was an impact to the spleen after low and high dose exposure.

Effect of respiratory motion on lung counting efficiency using a 4D NURBS-based cardio-torso (NCAT) phantom.

The Human Monitoring Laboratory (Canada) has looked at parameters (lung volume, lung deposition pattern, etc.) that can affect the counting efficiency of its lung counting system. The calibration of the system is performed using the Lawrence Livermore National Laboratory (LLNL) torso phantom; however, the effect of respiratory motion cannot be accounted for using these phantoms. When measuring an internal deposition in the lungs of a subject, respiration causes a change in the volume of the lungs and the thoracic cavity and introduces a variable distance between the lungs and the detectors. These changes may have an impact on the counting efficiency and may need to be considered during a measurement. In this study, the HML has simulated the respiration motion using a 4D non-uniform rational b-spline (NURBS)-based Cardiac-Torso (NCAT) phantom and determined the impact of that motion on the counting efficiency of their lung counting system during measurement. The respiratory motion was simulated by a 16 timeframe cycled 4D NURBS-based NCAT phantom developed at the Department of Biomedical Engineering and Radiology, University of North Carolina. The counting efficiency of the four germanium detectors comprising the HML lung counting system was obtained using MCNPX version 2.6E for photon energies between 17 and 1,000 keV. The amount of uncertainty due to the breathing motion was estimated by looking at the efficiency bias, which was highest at low photon energies as expected due to attenuation and geometry effects. Also, to reduce the influence of the detectors' positioning, an array was calculated by adding the individual detector tallies for a given energy and timeframe. For photon energies of 40 keV and higher, the array efficiency bias showed an underestimation of about 5%. If compared to other parameters already studied by the HML, this value demonstrates the insignificant impact of the breathing motion.

Accounting for respiratory motion in partial breast intensity modulated radiotherapy during treatment planning: a new patient selection metric.

PURPOSE: External beam partial breast irradiation intensity modulated radiotherapy (PBI IMRT) plans experience degradation in coverage and dose homogeneity when delivered during respiration. We examine which characteristics of the breast and seroma result in unacceptable plan degradation due to respiration. METHODS: Thirty-six patient datasets were planned with inverse-optimised PBI IMRT. Population respiratory data were used to create a probability density function. This probability density function (PDF) was convolved with the static plan fluences to calculate the delivered dose with respiration. To quantify the difference between static and respiratory plan quality, we analysed the mean dose shift of the target dose volume histogram (DVH), the dose shift at 95% of the volume and the dose shift at the hotspot to 2 cm(3)of the volume. We explore which patient characteristics indicate a clinically significant degradation in delivered plan quality due to respiration. RESULTS: Dose homogeneity constraints, rather than dosimetric coverage, were the limiting factors for all patient plans. We propose the dose evaluation volume-to-planning target volume (DEV-to-PTV) ratio as a delineating metric for identifying patient plans that will be more degraded by respiratory motion. The DEV-to-PTV ratio may be a more robust metric than ipsilateral breast volume because the seroma volume is contoured more consistently between physicians and clinics. CONCLUSIONS: For patients with a DEV-to-PTV ratio less than 55% we recommend either not using PBI IMRT or employing motion management. Small DEV-to-PTV ratios occur when the seroma is close to inhomogeneities (i.e. air/lung), which exacerbates the dosimetric effect of respiratory motion. For small breast sizes it is unlikely that the DEV-to-PTV ratio will meet these criteria.

Development of a small animal model to simulate clinical stereotactic body radiotherapy-induced central and peripheral lung injuries.

Given the tremendous potential of stereotactic body radiotherapy (SBRT), investigations of the underlying radiobiology associated with SBRT-induced normal tissue injury are of paramount importance. This study was designed to develop an animal model that simulates centrally and peripherally located clinical SBRT-induced lung injuries. A 90-Gy irradiation dose was focally delivered to the central and peripheral areas of the left mouse lung with an image-guided small-animal irradiation system. At 1, 2 and 4 weeks after irradiation, micro-computed tomography (micro-CT) images of the lung were taken. Lung function measurements were performed with the Flexivent® system (SCIREQ©, Montreal, Canada). For the histopathological analysis, the lungs were fixed by perfusing with formalin, and paraffin sections were stained with hematoxylin and eosin and Masson's Trichrome. Gross inspection clearly indicated local lung injury confined to the central and peripheral areas of the left lung. Typical histopathological alterations corresponding to clinical manifestations were observed. The micro-CT analysis results appeared to correlate with the histopathological findings. Mouse lung tissue damping increased dramatically at central settings, compared with that at the control or peripheral settings. An animal model to simulate clinical SBRT-induced central and peripheral lung injuries was developed and validated with histopathological, radiological and functional analyses. This model increases our understanding of SBRT-induced central and peripheral lung injuries and will help to improve radiation therapy in the future.

Radioprotection of lung tissue by soy isoflavones.

INTRODUCTION: Radiation-induced pneumonitis and fibrosis have restricted radiotherapy for lung cancer. In a preclinical lung tumor model, soy isoflavones showed the potential to enhance radiation damage in tumor nodules and simultaneously protect normal lung from radiation injury. We have further dissected the role of soy isoflavones in the radioprotection of lung tissue. METHODS: Naive Balb/c mice were treated with oral soy isoflavones for 3 days before and up to 4 months after radiation. Radiation was administered to the left lung at 12 Gy. Mice were monitored for toxicity and breathing rates at 2, 3, and 4 months after radiation. Lung tissues were processed for histology for in situ evaluation of response. RESULTS: Radiation caused damage to normal hair follicles, leading to hair loss in the irradiated left thoracic area. Supplementation with soy isoflavones protected mice against radiation-induced skin injury and hair loss. Lung irradiation also caused an increase in mouse breathing rate that was more pronounced by 4 months after radiation, probably because of the late effects of radiation-induced injury to normal lung tissue. However, this effect was mitigated by soy isoflavones. Histological examination of irradiated lungs revealed a chronic inflammatory infiltration involving alveoli and bronchioles and a progressive increase in fibrosis. These adverse effects of radiation were alleviated by soy isoflavones. CONCLUSION: Soy isoflavones given pre- and postradiation protected the lungs against adverse effects of radiation including skin injury, hair loss, increased breathing rates, inflammation, pneumonitis and fibrosis, providing evidence for a radioprotective effect of soy.

Mitigation of radiation-induced lung injury by genistein and EUK-207.

PURPOSE: We examined the effects of genistein and/or Eukarion (EUK)-207 on radiation-induced lung damage and investigated whether treatment for 0-14 weeks (wks) post-irradiation (PI) would mitigate late lung injury. MATERIALS AND METHODS: The lungs of female Sprague-Dawley (SD) rats were irradiated with 10 Gy. EUK-207 was delivered by infusion and genistein was delivered as a dietary supplement starting immediately after irradiation (post irradiation [PI]) and continuing until 14 wks PI. Rats were sacrificed at 0, 4, 8, 14 and 28 wks PI. Breathing rate was monitored and lung fibrosis assessed by lung hydroxyproline content at 28 wks. DNA damage was assessed by micronucleus (MN) assay and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. The expression of the cytokines Interleukin (IL)-1α, IL-1ß, IL-6, Tumor necrosis factor (TNF)-α and Transforming growth factor (TGF)-ß1, and macrophage activation were analyzed by immunohistochemistry. RESULTS: Increases in breathing rate observed in the irradiated rats were significantly reduced by both drug treatments during the pneumonitis phase and the later fibrosis phase. The drug treatments decreased micronuclei (MN) formation from 4-14 wks but by 28 wks the MN levels had increased again. The 8-OHdG levels were lower in the drug treated animals at all time points. Hydroxyproline content and levels of activated macrophages were decreased at 28 wks in all drug treated rats. The treatments had limited effects on the expression of the cytokines. CONCLUSION: Genistein and EUK-207 can provide partial mitigation of radiation-induced lung damage out to at least 28 wks PI even after cessation of treatment at 14 wks PI.

4D-PET data sorting into different number of phases: a NEMA IQ phantom study.

This study aims at evaluating the dependence of 4D-PET data sorting on the number of phases in which the respiratory cycle can be divided. The issue is to find the best compromise to reduce the conflicting effects induced by increasing the number of phases: lesion motion on each set of images decreases, but on the other hand image noise increases. The IQ NEMA 2001 IEC body phantom was used to simulate the movement of neoplastic lesions in the thorax and abdomen, investigating the effect of target size (10-37 mm), lesion to background activity concentrations ratio (4-to-1 and 8-to-1), total acquisition time (3, 6, 12, 20 min) and number of phase partition (1, 2, 4, 6, 8, 10, 13). The phantom was moved in a cranial-caudal direction with an excursion of 25 mm and with a period of 4.0 s. Five parameters associated to lesion volume and activity concentration were considered to assess the capability of the 4D-PET technique to "freeze" the phantom motion. The results for all the parameters showed the capability of the 4D-PET acquisition technique to "freeze" the lesion motion. The division into 6 phases was found to be the best compromise between temporal resolution and image noise for the phase where the "lesions" move faster, whereas the partition into 4 phases could be used if a stable breathing phase is considered.

Renin-Angiotensin system suppression mitigates experimental radiation pneumonitis.

PURPOSE: To find the mitigators of pneumonitis induced by moderate doses of thoracic radiation (10-15 Gy). METHODS AND MATERIALS: Unanesthetized WAG/RijCmcr female rats received a single dose of X-irradiation (10, 12, or 15 Gy at 1.615 Gy/min) to the thorax. Captopril (an angiotensin-converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in the drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating the breathing rate, ex vivo vascular reactivity, and histopathologic findings. Survival analysis was undertaken on all animals, except those scheduled for death. RESULTS: Survival after a dose of 10 Gy to the thorax was not different from that of unirradiated rats for

An analysis of thoracic and abdominal tumour motion for stereotactic body radiotherapy patients.

An analysis of thoracic and abdominal tumour motion for stereotactic body radiotherapy patients was performed using more than 70 h of tumour motion estimated from the correlation between the external and internal motion for 143 treatment fractions in 42 patients. The tumour sites included lungs (30 patients) and retroperitoneum (12 patients). The overall mean respiratory-induced peak-to-trough distance was 0.48 cm, with individual treatment fraction means ranging from 0.02 to 1.44 cm. The overall mean respiratory period was 3.8 s, with individual treatment fraction means ranging from 2.2 to 6.4 s. In 57 treatment fractions (40%), the mean respiratory-induced peak-to-trough distance was greater than 0.5 cm. In general, tumour motion was predominantly superior-inferior (60% of all the treatment fractions), while anterior-posterior and left-right motion were 22% and 18%, respectively. The motion was predominantly linear, and the overall mean of the first principal component was 94%. However, for motion magnitude, direction and linearity, large variations were observed from patient to patient, fraction to fraction and cycle to cycle.

Evaluation of the combined effects of target size, respiratory motion and background activity on 3D and 4D PET/CT images.

Gated (4D) PET/CT has the potential to greatly improve the accuracy of radiotherapy at treatment sites where internal organ motion is significant. However, the best methodology for applying 4D-PET/CT to target definition is not currently well established. With the goal of better understanding how to best apply 4D information to radiotherapy, initial studies were performed to investigate the effect of target size, respiratory motion and target-to-background activity concentration ratio (TBR) on 3D (ungated) and 4D PET images. Using a PET/CT scanner with 4D or gating capability, a full 3D-PET scan corrected with a 3D attenuation map from 3D-CT scan and a respiratory gated (4D) PET scan corrected with corresponding attenuation maps from 4D-CT were performed by imaging spherical targets (0.5-26.5 mL) filled with (18)F-FDG in a dynamic thorax phantom and NEMA IEC body phantom at different TBRs (infinite, 8 and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior-inferior direction with amplitudes of 0, 1 and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PET images. In addition, gating methods using different numbers of gating bins (1-20 bins) were evaluated with image noise and temporal resolution. For evaluation, volume recovery coefficient, signal-to-noise ratio and contrast-to-noise ratio were calculated as a function of the number of gating bins. Moreover, the optimum thresholds which give accurate moving target volumes were obtained for 3D and 4D images. The partial volume effect and signal loss in the 3D-PET images due to the limited PET resolution and the respiratory motion, respectively were measured. The results show that signal loss depends on both the amplitude and pattern of respiratory motion. However, the 4D-PET successfully recovers most of the loss induced by the respiratory motion. The 5-bin gating method gives the best temporal resolution with acceptable image noise. The results based on the 4D scan protocols can be used to improve the accuracy of determining the gross tumor volume for tumors in the lung and abdomen.

Safety of human MRI at static fields above the FDA 8 T guideline: sodium imaging at 9.4 T does not affect vital signs or cognitive ability.

PURPOSE: To assess whether exposure to a 9.4 T static magnetic field during sodium imaging at 105.92 MHz affects human vital signs and cognitive function. MATERIALS AND METHODS: Measurements of human vital signs and cognitive ability made before and after exposure to a 9.4 T MR scanner and a mock scanner with no magnetic field are compared using a protocol approved by the U.S. Food and Drug Administration (FDA). RESULTS: Exposure to a 9.4 T static magnetic field during sodium imaging did not result in a statistically significant change in the vital signs or cognitive ability of healthy normal volunteers. CONCLUSION: Vital sign and cognitive ability measurements made before and after sodium imaging at 9.4 T suggest that performing human MRI at 105.92 MHz in a 9.4 T static magnetic field does not pose a health risk.

[Comparative study and clinical implementation of two breathing-adapted radiotherapy techniques: dosimetric benefits for lung cancer treatment]. / Etude comparative et mise en oeuvre clinique de deux systèmes de radiothérapie asservie à la respiration : bénéfice dosimétrique pour le traitement du cancer du poumon.

Breathing can lead to organ motions up to several centimeters. For radiotherapy of lung, these motions are generally taken into account by adding a specific margin around the target. Thus, treated volumes are often too large to allow for the high-dose values requested for local control. To manage respiratory motion, deep-inspiration breath-hold technique (DIBH) and gated radiotherapy are starting being used clinically. DIBH consists in asking the patient to perform breath-hold during the treatment and the image acquisition, DIBH level being measured by a spirometer. Gated radiotherapy consists in treating the patient at a certain phase of the free breathing. Linac is synchronized with the motion of a marker located on the patient chest. Planning images are obtained by a four-dimensional CT (4D-CT) using the same marker. We have assessed the value of these two methods. For lung treatment, compared to a standard treatment, toxicity reduction was mainly due to the lung total volume increase. It is therefore more significant for breath-hold approach. It is also due to the reduction of safety margins, which is similar for both methods. These two techniques, which have specific advantages and drawbacks, are used routinely at Curie Institute for a large proportion of lung patients, but also for some breast, liver or even Hodgkin disease treatments.

Assessment of environmental radon hazard using human respiratory tract models.

Radon is a natural radioactive gas derived from geological materials. It has been estimated that about half of the total effective dose received by human beings from all sources of ionizing radiation is attributed to 222Rn and its short-lived progeny. In this paper, the use of human respiratory tract models to assess the health hazard from environmental radon is reviewed. A short history of dosimetric models for the human respiratory tract from the International Commission on Radiological Protection (ICRP) is first presented. The most important features of the newest model published by ICRP in 1994 (as ICRP Publication 66) are then described, including the morphometric model, physiological parameters, radiation biology, deposition of aerosols, clearance model and dose weighting. Comparison between different morphometric models and comparison between different deposition models are then given. Finally, the significance of various parameters in the lung model is discussed, including aerosol parameters, subject related parameters, target and cell related parameters, and parameters that define the absorption of radon from the lungs to blood. Dosimetric calculations gave a dose conversion coefficient of 15 mSv/WLM, which is higher than the value 5 mSv/WLM derived from epidemiological studies. ICRP stated that dosimetric models should only be used for comparison of doses in the human lungs resulted from different exposure conditions.

Effect of concurrent radiation therapy and chemotherapy on pulmonary function in patients with esophageal cancer: dose-volume histogram analysis.

PURPOSE: The pulmonary effects of concurrent radiation therapy and chemotherapy were studied in patients enrolled in a phase I trial for esophageal cancer. MATERIALS AND METHODS: Pulmonary function tests were performed prospectively before and after combined-modality therapy (oxaliplatin, 5-fluorouracil, and radiation therapy) in 20 patients with esophageal cancer. Cumulative and differential lung DVH analysis from 0 to 5400 cGy in 25-cGy intervals was performed for the last 15 patients. Correlation between radiation exposure in various dose ranges and percent reduction in pulmonary function tests was calculated as an exploratory analysis. RESULTS: Significant reductions in carbon monoxide diffusion capacity corrected for hemoglobin (12.3%) and total lung capacity (2.5%) were evident at a median of 15.5 days after radiation therapy. DVH analysis revealed that the single dose of maximum correlation between lung volume radiation exposure and lung function reduction was less than 1000 cGy for all pulmonary functions. The percent lung volume that received a total dose between 700 and 1000 cGy maximally correlated with the percent reductions in total lung capacity and vital capacity, and the absolute lung volume that received a total dose between 700 and 1000 cGy maximally correlated with the percent reductions in total lung capacity, vital capacity, and carbon monoxide diffusion capacity. DISCUSSION: Significant declines in carbon monoxide diffusion capacity and total lung capacity are evident immediately after the administration of conformal radiation therapy, oxaliplatin, and 5-fluorouracil for esophageal cancer. Other lung functions remain statistically unchanged. The percent or absolute lung volume that received a total dose between 700 and 1000 cGy may be significantly correlated with the percent decline of carbon monoxide diffusion capacity, total lung capacity, and vital capacity. These associations will be evaluated further in a follow-up study.

Demodulaçäo em amplitude do EGC para obtençäo do sinal respiratório: análise comparativa entre as derivaçöes DI, DII, DIII, V1, V2 e V6 / Detection in amplitude of ECG for obtain respiratory sign: comparative analysis between the derivations DI, DII, DIII, V1, V2 e V6

Baseado na demodulação em amplitude do ECG para obtenção do sinal respiratório, este trabalho apresenta um estudo comparativo para identificar qual, dentre algumas derivações do ECG, a mais sensível aos movimentos respiratórios. A análise é feita no domínio do tempo e da freqüência, sendo esta última a que apresenta melhores resultados. Entre as derivações comparadas, a que oferece maior taxa de modulação é a derivação DI.

Abstract - On the basis of amplitude demodulation of ECG to obtain the respiratory signaL this work presents a comparative study to identify which ECG lead presents the best breath movement sensibility. The analysis is done in temporal and frequency domain. The best results are obtained in the frequency domain. Among the signals compared, the most representative of respiratory movements is DI

Effect of radioiodine therapy on pulmonary alveolar-capillary membrane integrity.

UNLABELLED: The effects of large doses of radioiodine on the pulmonary alveolar-capillary membrane using 99mTc-DTPA clearance as an index of pulmonary damage in subjects with pulmonary metastases of differentiated thyroid carcinoma were studied. METHODS: Technetium-99m-DTPA radioaerosols were generated by a dry aerosol generator. Data were acquired and analyzed for clearance half-time from the lungs with a scintillation camera. The study was carried out on 35 thyroid cancer patients with pulmonary metastases and on 32 patients without metastases; the results were compared to those of a control group comprising 52 subjects. The radiation dose delivered to the lungs from the therapeutic dose was calculated using MIRD methodology. RESULTS: Cumulative radioiodine doses varied from 5.9 to 44.2 GBq (158-1194 mCi). The half-time clearance of 99mTc-DTPA was comparable in both patient groups and was not related to the total administered radioiodine dosage or to the radiation dose delivered to the lungs. No changes were observed for periods up to 5 yr after receiving the last radioiodine dosage. Seven patients followed at regular intervals from 6 mo to 2 yr did not show abnormal 99mTc-DTPA clearance values. One patient did show low 99mTc-DTPA clearance half-time values, which were symptomatic radiation pneumonitis. She had received a total dose of 34 GBq (922 mCi) over a 4-yr period. CONCLUSION: The incidence of pulmonary damage resulting from radioiodine therapy for lung metastases of differentiated thyroid cancer is negligible, as evidenced by the normal pulmonary clearance half-time of 99mTc-DTPA aerosols.

Influence of age and duration of follow-up on lung function after combined chemotherapy for Hodgkin's disease.

Pulmonary function was studied in 48 patients 4-13 yrs after treatment for Hodgkin's disease with mantle-field irradiation followed by standard mechlorethamine, Oncovin, procarbazine and prednisone (MOPP) chemotherapy. The patients were found to have a restrictive lung disease suggestive of pulmonary fibrosis. Low age at therapy (less than or equal to 30 yrs, median 24 yrs) was associated with a significantly more pronounced restrictive lung function impairment than older age (greater than 30 yrs, median 40 yrs) suggesting a higher susceptibility to the pulmonary side-effects of therapy. In addition younger smokers had a significantly greater reduction in diffusion capacity and forced expiratory volume in one second than older smokers, suggesting a higher susceptibility to the additional adverse effect of smoking. With longer follow-up nonsmokers had an increase in static lung volumes. It is suggested that this may be the result of more frequent pulmonary infections in such patients as compared with the general population. However, the duration of follow-up was not associated with changes in other indices of lung function.

Prospective study of long-term pulmonary manifestations of mantle irradiation.

Given the high cure rate of patients with Hodgkin's disease, the complications related to therapy take on great significance. Mantle irradiation to the thorax is used in virtually all patients with early stage Hodgkin's disease. Prior studies of patients receiving mantle irradiation demonstrated short-term (up to 24 months) abnormalities of pulmonary function. In the present study, we prospectively studied 13 patients for up to 60 months after irradiation only with serial pulmonary function tests, arterial blood gas tests, diffusing capacity of carbon monoxide, chest radiographs, and ventilation-perfusion scans. No respiratory symptoms attributable to therapy were noted. Frequent radiographic changes (62%) were found consisting of apical fibrosis, paramediastinal fibrosis, or pleural thickening. Two patients developed an asymptomatic spontaneous pneumothorax that resolved with conservative management. Ventilation-perfusion scans often (73%) revealed decreased perfusion to the lung apices with associated ventilatory deficits in one-half of these patients. Patients with intrathoracic disease had decreased lung volumes prior to therapy, and lung volumes did not change following irradiation. Lung mechanics were normal throughout the study. Gas exchange at rest was normal in patients with extrathoracic disease. Patients with intrathoracic disease often presented with an abnormal arterial PO2 and widened alveolar-arterial partial pressure gradient for oxygen. However, these parameters normalized by 9 months after therapy. Despite the frequent development of radiographic and V/Q scan abnormalities in the lung apices, patients tolerated mantle radiotherapy remarkably well. In fact, patients with intrathoracic disease demonstrated improved gas exchange at rest following therapy.