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At least 343 records · Page 19

Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling

Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased and peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD. - Highlights: • Isoflurane induces hippocampal calcineurin activation. • Isoflurane induces hippocampal NFAT, especially NFATc4, nuclear import. • Cyclosporine A attenuates isoflurane induced aberrant calcineurin/NFAT signaling. • Cyclosporine A rescues isoflurane induced cognitive impairment. • Calcineurin/NFAT signaling is the upstream mechanism of isoflurane induced synaptic dysfunction and cognitive impairment.

60 APPLIED LIFE SCIENCES↗

Palmitic acid increases invasiveness of pancreatic cancer cells AsPC-1 through TLR4/ROS/NF-κB/MMP-9 signaling pathway

Pancreatic cancer (PC) is an aggressive malady with proclivity for early metastasis. Overexpression of toll-like receptor 4 (TLR4) in pancreatic ductal adenocarcinoma, the most common type of pancreatic malignancy, correlates to tumor size, lymph node involvement, venous invasion and pathological stage. Lipopolysaccharides (LPS) are natural TLR4 ligands that have been shown to increase the invasive ability of PC cells. However, rapid inactivation of circulating LPS and low systemic absorption of inhaled LPS from the bronchoalveolar compartment make other agonists such as saturated fatty acids more suitable to be considered for TLR4-related cell invasiveness. Interestingly, PC risk was strongly associated to intake of saturated fat from animal food sources, in particular to consumption of saturated palmitic acid (PA). In the present study, we investigated the influence of PA on the invasive capacity of human PC cells AsPC-1. Using specific inhibitors, we found that PA stimulation of these tumor cells induced a TLR4-mediated cell invasion. Our results also indicate that the signaling events downstream of TLR4 involved generation of reactive oxygen species, activation of nuclear factor-kappa beta, and secretion and activation of matrix metalloproteinase 9 (MMP-9). Furthermore, PA stimulation decreased the levels of the micro RNA 29c (miR-29c). Of note, while inhibition of miR-29c increased MMP-9 mRNA levels, MMP-9 secretion and activation, and invasiveness, miR-29c mimic abrogated all these PA-stimulated effects. These results strongly suggest that miR-29c could be an attractive potential pharmacological agent for antitumoral therapy in PC. - Highlights: • Palmitic acid stimulates TLR4-mediated pancreatic cancer cell invasion. • Activation of NF-κB by palmitic acid depends on ROS generation. • Palmitic acid decreases the level of miR-29C through NF-κB. • Inhibition of miR-29c increases MMP-9 secretion and activation, and invasiveness.

60 APPLIED LIFE SCIENCES↗

Allethrin and prallethrin stimulates MUC5AC expression through oxidative stress in human airway epithelial cells

Highlights: • Allethrin and prallethrin are implicated in modulation of airway mucin secretion. • Allethrin and prallethrin induce MUC5AC expression. • Allethrin and prallethrin induce MUC5AC expression via ROS. Pyrethroids, including allethrin and prallethrin, have been widely used as major components of the common commercial insecticides. The toxicity of allethrin and prallethrin were well established that it interfered with the way that the nerves and brain function. However, limited information was available regarding respiratory effects in humans following inhalation exposure to allethrin and prallethrin. Therefore, we demonstrated effect of allethrin and prallethrin, and the mechanism involved, on the mucin expressions in human airway epithelial cells. In human airway NCI-H292 epithelial cells, the effects of allethrin and prallethrin and its signaling pathway for airway mucin, especially MUC5AC, were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, and enzyme-linked immunosorbent assay (ELISA). The mechanism of allethrin and prallethrin-induced MUC5AC expression in airway epithelial cells was studied in terms of reactive oxygen species (ROS) by flow cytometry analysis. Allethrin and prallethrin significant increased MUC5AC expression in human airway NCI-H292 epithelial cells. We also demonstrated allethrin and prallethrin induced a marked rise of ROS production. In addition, NAC (ROS scavenger) and DPI (NADPH oxidase inhibitor) inhibited allethrin and prallethrin-induced MUC5AC expression. These results are first to describe that allethrin and prallethrin-induced MUC5AC expression through ROS in human airway epithelial cells.

60 APPLIED LIFE SCIENCES↗

Adaptations for gas exchange enabled the elongation of lepidopteran proboscises

The extensive biodiversification of butterflies and moths (Lepidoptera) is partly attributed to their unique mouthparts (proboscis [Pr]) that can span in length from less than 1 mm to over 280mm in Darwin's sphinx moths. Lepi-doptera, similar to other insects, are believed to inhale and exhale respiratory gases only through valve-like spi-racles on their thorax and abdomen, making gas exchange through the narrow tracheae (Tr) challenging for the elongated Pr. How Lepidoptera overcome distance effects for gas transport to the Pr is an open question that is important to understanding how the Pr elongated over evolutionary time. Here, we show with scanning electron microscopy and X-ray imaging that distance effects on gas exchange are overcome by previously unreported micropores on the Pr surface and by superhydrophobic Tr that prevent water loss and entry. We find that the density of micropores decreases monotonically along the Pr length with the maxima proportional to the Pr length and that micropore diameters produce a Knudsen number at the boundary between the slip and transition flow regimes. By numerical estimation, we further show that the respiratory gas exchange for the Pr predominantly occurs via diffusion through the micropores. In conclusion, these adaptations are key innovations vital to Pr elongation, which likely facilitated lepidopteran biodiversification and the radiation of angiosperms by coevolutionary processes.

59 BASIC BIOLOGICAL SCIENCES↗

Microcystin-LR aerosol induces inflammatory responses in healthy human primary airway epithelium

Harmful algal blooms plague bodies of freshwater globally. These blooms are often composed of outgrowths of cyanobacteria capable of producing the heptapeptide Microcystin-LR (MC-LR) which is a well-known hepatotoxin. Recently, MC-LR has been detected in aerosols generated from lake water. However, the risk for human health effects due to MC-LR inhalation exposure have not been extensively investigated. In this study, we exposed a fully differentiated 3D human airway epithelium derived from 14 healthy donors to MC-LR-containing aerosol for 3 minutes per day for 3 days. Concentrations of MC-LR ranged from 100 pM to 1 µM. Although there were little to no detrimental alterations in measures of the airway epithelial function (i.e. cell survival, tissue integrity, mucociliary clearance, or cilia beating frequency), a distinct shift in the transcriptional activity was found. Genes related to inflammation were found to be upregulated such as C-C motif chemokine 5 (CCL5; log2FC = 0.56 , p = 0.02) and C-C chemokine receptor type 7 (CCR7; log2FC = 0.83, p = 0.03). Functionally, conditioned media from MC-LR exposed airway epithelium was also found to have significant chemo-attractive properties for primary human neutrophils. Additionally, increases were found in the concentration of secreted chemokine proteins in the conditioned media such as CCL1 (log2FC = 5.07 , p = 0.0001) and CCL5 (log2FC = 1.02, p = 0.046). These results suggest that MC-LR exposure to the human airway epithelium is capable of inducing an inflammatory response that may potentiate acute or chronic disease.

3D human airway epithelium↗

Polycyclic aromatic hydrocarbons and cannabinoids in secondhand cannabis smoke

The legalization of cannabis is exposing more people to secondhand smoke (SHS) generated during cannabis use. Given the serious health effects caused by tobacco SHS, there is a need to assess the potential health effects of exposure to cannabis SHS. As a step toward this, we measured the concentrations of cannabinoids, nicotine and polycyclic aromatic hydrocarbons (PAHs) in air samples collected in public places where cannabis was being consumed. These were compared with concentrations in exhaled aerosols from cannabis smoking and vaping, and in tobacco SHS. Tetrahydrocannabinol concentrations were 22 to 255 µg/m 3 in field samples, below the threshold for psychoactive effects. Nicotine concentrations in field samples did not exceed 1 µg/m 3 . The total PAH concentrations in field samples were from 3.2 to 80.5 ng/m 3 , depending on location type. By contrast, PAH levels averaged 72 ng/m 3 in tobacco SHS and 220 ng/m 3 in the more concentrated, exhaled cannabis aerosols. A total of 22 different PAHs were identified in field samples of cannabis aerosols, from which benz[a]anthracene (B[a]A) was present in the highest concentrations. The PAH profile of cannabis aerosols was different from that of tobacco SHS. A preliminary cancer risk evaluation showed that the dose associated with inhalation of cannabis SHS during an 8-h work shift exceeded the California No Significant Risk Level for B[a]A at all venues where cannabis was consumed primarily via smoking. In summary, the consumption of cannabis, by smoking and by vaporizing, can create aerosols that contain carcinogenic PAHs. Thus breathing secondhand cannabis aerosols increases exposure to carcinogens.

Aerosol↗

Sheep lymph-nodes as a biological indicator of environmental exposure to fluoro-edenite

A significantly increased incidence of pleural mesothelioma in Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite (FE), a fibrous amphibole extracted from a local stone quarry. The lymph-nodes draining the pulmonary lobes of sheep grazing around the town were examined, to gain insights into fibre diffusion. The pasture areas of six sheep flocks lying about 3 km from Biancavilla were located using the global positioning system. The cranial tracheobronchial and one middle mediastinal lymph-node as well as four lung tissue samples were collected from 10 animals from each flock and from 10 control sheep for light and scanning electron microscopy (SEM) examination. The lymph-nodes from exposed sheep were enlarged and exhibited signs of anthracosis. Histologically, especially at the paracortical level, they showed lymph-follicle hyperplasia with large reactive cores and several macrophages (coniophages) containing grey-brownish particulate interspersed with elements with a fibril structure, forming aggregates of varying dimensions (coniophage nodules). Similar findings were detected in some peribronchiolar areas of the lung parenchyma. SEM examination showed that FE fibres measured 8–41 µm in length and 0.4–1.39 µm in diameter in both lymph-nodes and lung tissue. Monitoring of FE fibres in sheep lymph-nodes using appropriate techniques can help set up environmental pollution surveillance. - Highlights: • Lymph-nodes draining sheep lung were used to assess environmental fluoro-edenite exposure. • Monitoring fluoro-edenite fibres in sheep lung nodes can provide pollution surveillance. • Our findings document a risk of fluoro-edenite fibre inhalation a few kilometres from the source. • Sheep appear to be a valuable bioindicator species.

54 ENVIRONMENTAL SCIENCES↗

Natural carcinogenic fiber and pleural plaques assessment in a general population: A cross-sectional study

Natural carcinogenic fibers are asbestos and asbestiform fibers present as a natural component of soils or rocks. These fibers are released into the environment resulting in exposure of the general population. Environmental contamination by fibers are those cases occurred in: rural regions of Turkey, in Mediterranean countries and in other sites of the world, including northern Europe, USA and China. Fluoro-edenite(FE) is a natural mineral species first isolated in Biancavilla, Sicily. The fibers are similar in size and morphology to some amphibolic asbestos fibers, whose inhalation can cause chronic inflammation and cancer. The aim of the current study is to assess the presence and features of pleural plaques (PPs) in Biancavilla's general population exposed to FE through a retrospective cross-sectional study. All High-Resolution Computed Tomography (HRCT) chest scans carried out between June 2009 and June 2015 in Biancavilla municipality hospital site (exposed subjects) were reviewed. The exposed groups were 1:1 subjects, matched according to age and sex distributions, with unexposed subjects (n.1.240) randomly selected among HRCT chest scans carried out in a Hospital 30 km away from Biancavilla. Subjects from Biancavilla with PPs were significantly more numerous than the control group ones (218 vs 38). Average age of either group was >60 years; the age of exposed subjects was significantly (p=0.0312) lesser than the unexposed group. In exposed subjects, in most PPs thickness ranged between 2 and 4.9 cm(38%, n=83); while in unexposed ones PPs thickness was less than 2 cm (55%, n=21). As to the size of PPs in exposed subjects, in most cases it ranged between 1 cm and 24% of chest wall (53%, n=116); while in unexposed ones the size of PPs was lesser than 1 cm (23%, n=58). Among exposed subjects, 36 cases (17%) PPs were detected with calcification, whereas in unexposed ones only three (8%) presented calcification. 137 lung parenchymal abnormalities were observed in exposed group; whereas, 12 lung parenchymal involvement were registered in unexposed subjects. The RR for PPs is 6,74 CI 95% (4,47–9,58) p<0,0001 in the exposed population. These findings, suggested the urge to extend the screening on the possible involvement of the respiratory tract to all Biancavilla's population, particularly in those aged more than 30. Besides, it seems essential to start indoor monitoring Biancavilla's municipality. - Highlights: • High risk for pleural plaques in people exposed to fluoro-edenite. • Naturally carcinogenic fibers increase the risk of parenchymal abnormalities. • It is important to organize an extended screening to all Biancavilla's population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The U.S. Department of Veterans' Affairs depleted uranium exposed cohort at 25 Years: Longitudinal surveillance results

Background: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. Methods: During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. Results: On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations. The DU isotopic signature is observed principally in participants possessing embedded fragments. Those with only an inhalation exposure have lower urine U concentration and a natural isotopic signature. Conclusions: At 25 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As U body burden continues to accrue from in-situ mobilization from metal fragment depots, and increases with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort. - Highlights: • Gulf War I veterans wounded with depleted uranium are monitored for health changes. • In 2015 in-patient clinical surveillance was performed on 36 members of the cohort. • Mobilization of U from embedded fragments is evidenced by elevated U in urine. • This cohort of continues to show no U-related health effects.

54 ENVIRONMENTAL SCIENCES↗

Lead intoxicated children in Kabwe, Zambia

Highlights: • Kabwe's soil is highly contaminated with lead due to former lead mining. • Children from highly contaminated townships showed high blood lead levels. • They need to be treated and the exposure must be considerably reduced. Kabwe is a lead contaminated mining town in Zambia. Kabwe has extensive lead contaminated soil and children in Kabwe ingest and inhale high quantities of this toxic dust. The aim of this paper is to analyze the health impact of this exposure for children. Health data from three existing studies were re-analyzed. Over 95% of children living in the most affected townships had high blood lead levels (BLLs) > 10 µg/dL. Approximately 50% of those children had BLLs ≥ 45 µg/dL. The existing data clearly establishes the presence of a severe environmental health crisis in Kabwe which warrants immediate attention.

54 ENVIRONMENTAL SCIENCES↗

Plasticizer, di(2-ethylhexyl)phthalate (DEHP) enhances cockroach allergen extract-driven airway inflammation by enhancing pulmonary Th2 as well as Th17 immune responses in mice

Highlights: • DEHP enhances CE-induced airway inflammation/mucus secretion in mice. • DEHP enhances expression of costimulatory molecules on dendritic cells. • DEHP enhances expression of pro-inflammatory cytokines in dendritic cells. • DEHP down regulates expression of E-cadherin in airway epithelial cells. In recent decades, there has been a gradual increase in the prevalence of asthma. Various factors including environmental pollutants have contributed to this phenomenon. Plasticizer, di(2-ethylhexyl)phthalate (DEHP) is one of the commonest environmental pollutants due to its association with plastic products. DEHP gets released from plastic products easily leading to respiratory exposure in humans. As a consequence, DEHP is associated with allergic asthma in humans and animals. DEHP is reported to act as an adjuvant in ovalbumin-induced mouse models of asthma at high doses. However, these studies mostly looked into the role of DEHP on Th2 cytokines/eosinophilic inflammation without investigating the role of airway epithelial cells (AECs)/dendritic cells (DCs)/Th17 cells. Its adjuvant activity with natural allergens such as cockroach allergens at tolerable daily intake needs to be explored. Cockroach allergens and DEHP may be inhaled together due to their coexistence in work place as well as household environments. Therefore, effect of DEHP was assessed in cockroach allergens extract (CE)-induced mouse model of asthma. Airway inflammation, histopathology, mucus secretion, and immune responses related to Th2/Th17/DCs and AECs were assessed in mice with DEHP exposure alone and in combination with CE. Our study shows that DEHP converts CE-induced eosinophilic inflammation into mixed granulocytic inflammation by promoting Th2 as well as Th17 immune responses. This was probably due to downregulation of E-cadherin in AECs, and enhancement of costimulatory molecules (MHCII/CD86/CD40)/pro-inflammatory cytokines (IL-6/MCP-1) in DCs by DEHP. This suggests that DEHP facilitates development of mixed granulocytic airway inflammation in the presence of a natural allergen.

54 ENVIRONMENTAL SCIENCES↗

The effect of flavor content in e-liquids on e-cigarette emissions of carbonyl compounds

Highlights: • Electronic cigarettes (e-cigarettes or ECs) are designed to deliver nicotine to a smoker. • The flavorings in e-liquids were considered safe but raised concerns due to potential toxicity. • In this study, we investigated the effects of flavor content on CC emissions from EC vaping. • The CC amounts (before/during vaping) was estimated from the flavor content in the e-liquid. • The effects of flavor content in e-liquids on vaping CC emissions warrant attention. The effect of flavors on carbonyl compound (CC) emission factors (EF) from electronic cigarettes (ECs) vaping was investigated at the default vaping (voltage) setting in all experiments using a total of 21 lab-made e-liquid samples (five different types of retail flavorant bases: beverage/dessert/fruit/mint/tobacco). Each flavorant base was added to a separate unflavored base composed of a 1:1 mixture of propylene glycol/vegetable glycerol (PG/VG) at four levels (5/10/30/50% (v/v)). The e-liquid CC levels increased linearly with flavorant base content, 1.3–10.5 times (R{sup 2}: 0.762–0.999). The vaping CC EFs increased linearly with flavorant base content (if ≥ 10%) from 1.0 to 92 times (R{sup 2}: 0.431–0.998). For flavorant base content of 0%, 5%, and 10%, the EFs ranged from undetected to 0.11 μg puff{sup −1} (acetone). The 40-year cancer risk due to formaldehyde (70 kg EC user inhaling 5% flavorant base content e-liquid: 120 puffs day{sup −1}) is estimated to be 2.0E-06 (highest) compared to 1.0E-06 for the 1:1 PG:VG base. Most formaldehyde vaped from the fruit flavored e-liquid was the flavorant base. The CC concentrations in EC liquids (before vaping) were approximately linear with e-liquid flavorant base content. Retail e-liquid product information labels should be guided to provide a complete list of all ingredients, their concentrations, and carbonyl compound EFs.

54 ENVIRONMENTAL SCIENCES↗

Bio-distribution and deposition of wildfire smoke chemicals into olfactory bulb and brain of rats after intranasal instillation

Epidemiological and experimental studies suggest wildfire smoke is a potential contributor to neurological dysfunction and associated with neuroinflammation. Using doses comparable to those encountered during intense wildfire events (200-300 μg/m 3 ), we explore the absorption, distribution, metabolism, and elimination (ADME) and pharmacokinetics of representative members of major chemical classes (acid, phenol, PAH, aldehyde) in inhaled wood smoke condensates. Male Sprague Dawley rats were intranasally instilled with smoldering eucalyptus woodsmoke extract (WSE) reconstituted in saline spiked with 14 C-labeled palmitic acid (PA), benzo[a]pyrene (B[a]P), catechol (CAT) or benzaldehyde (BZ). Serum was collected from 5 min to 2 weeks after exposure and tissues were collected at 0.5, 2, 4, 24 h and 2 weeks after exposure. Urine was collected over the 24 h exposure. Tissues were collected, rinsed in PBS and analyzed by accelerator mass spectrometry (AMS) for 14C-labeled chemicals. PA and B[a]P entered circulation slowly, reached maximum concentration (C max ) near 15 ng/mL at 2 h, and had circulating concentrations near 1/3 C max 24 h after exposure. CAT and BZ rapidly entered circulation and were mostly cleared at 2 h. Excess 14 C from all four chemicals was detected in olfactory bulb and brain over the first 24 h but only PA (or its metabolites) was retained in olfactory bulb, brain and kidney at 2 weeks post exposure. All excess 14 C was cleared from the lung at 2 weeks. Metabolite analysis of urine (CAT, BZ and B(a)P) dosed samples did not detect any parent compound. CAT and BZ were rapidly cleared. The slower uptake and clearance of PA or B[a]P or their reactive metabolites when dosed with WSE in brain and olfactory bulb potentially provide greater opportunity for inflammatory response. This study suggests that wildfire smoke chemicals can enter the brain directly from the nasal cavity to the olfactory bulb and via systemic circulation.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Metal-sulfide mineral ores, Fenton chemistry and disease. Particle induced inflammatory stress response in lung cells

The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleterious nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002 m 2 /mL stock) and exposure periods (beginning at 30 min and measured systematically for up to 24 h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. Furthermore, this study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.

59 BASIC BIOLOGICAL SCIENCES↗

Quantification of Esophageal Tumor Motion on Cine-Magnetic Resonance Imaging

Purpose: To quantify the movement of esophageal tumors noninvasively on cine-magnetic resonance imaging (MRI) by use of a semiautomatic method to visualize tumor movement directly throughout multiple breathing cycles. Methods and Materials: Thirty-six patients with esophageal tumors underwent MRI. Tumors were located in the upper (8), middle (7), and lower (21) esophagus. Cine-MR images were collected in the coronal and sagittal plane during 60 seconds at a rate of 2 Hz. An adaptive correlation filter was used to automatically track a previously marked reference point. Tumor movement was measured in the craniocaudal (CC), left–right (LR), and anteroposterior (AP) directions and its relationship along the longitudinal axis of the esophagus was investigated. Results: Tumor registration within the individual images was typically done at a millisecond time scale. The mean (SD) peak-to-peak displacements in the CC, AP, and LR directions were 13.3 (5.2) mm, 4.9 (2.5) mm, and 2.7 (1.2) mm, respectively. The bandwidth to cover 95% of excursions from the mean position (c95) was also calculated to exclude outliers caused by sporadic movements. The mean (SD) c95 values were 10.1 (3.8) mm, 3.7 (1.9) mm, and 2.0 (0.9) mm in the CC, AP, and LR dimensions. The end-exhale phase provided a stable position in the respiratory cycle, compared with more variety in the end-inhale phase. Furthermore, lower tumors showed more movement than did higher tumors in the CC and AP directions. Conclusions: Intrafraction tumor movement was highly variable between patients. Tumor position proved the most stable during the respiratory cycle in the end-exhale phase. A better understanding of tumor motion makes it possible to individualize radiation delivery strategies accordingly. Cine-MRI is a successful noninvasive modality to analyze motion for this purpose in the future.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Intrafraction Variability and Deformation Quantification in the Breast

Purpose: To evaluate intrafraction variability and deformation of the lumpectomy cavity (LC), breast, and nearby organs. Methods and Materials: Sixteen left-sided postlumpectomy and 1 bilateral breast cancer cases underwent free-breathing CT (FBCT) and 10-phase 4-dimensional CT (4DCT). Deformable image registration was used for deformation analysis and contour propagation of breast, heart, lungs, and LC between end-exhale and end-inhale 4DCT phases. Respiration-induced motion was calculated via centroid analysis. Two planning target volumes (PTVs) were compared: PTV{sub FBCT} from the FBCT volume with an isotropic 10 mm expansion (5 mm excursion and 5 mm setup error) and PTV{sub 4DCT} generated from the union of 4DCT contours with isotropic 5 mm margin for setup error. Volume and geometry were evaluated via percent difference and bounding box analysis, respectively. Deformation correlations between breast/cavity, breast/lung, and breast/heart were evaluated. Associations were tested between cavity deformation and proximity to chest wall and breast surface. Results: Population-based 3-dimensional vector excursions were 2.5 ± 1.0 mm (range, 0.8-3.8 mm) for the cavity and 2.0 ± 0.8 mm (range, 0.7-3.0 mm) for the ipsilateral breast. Cavity excursion was predominantly in the anterior and superior directions (1.0 ± 0.8 mm and −1.8 ± 1.2 mm, respectively). Similarly, for all cases, LCs and ipsilateral breasts yielded median deformation values in the superior direction. For 14 of 17 patients, the LCs and breast interquartile ranges tended toward the anterior direction. The PTV{sub FBCT} was 51.5% ± 10.8% larger (P<.01) than PTV{sub 4DCT}. Bounding box analysis revealed that PTV{sub FBCT} was 9.8 ± 1.2 (lateral), 9.0 ± 2.2 (anterior–posterior), and 3.9 ± 1.8 (superior–inferior) mm larger than PTV{sub 4DCT}. Significant associations between breast and cavity deformation were found for 6 of 9 axes. No dependency was found between cavity deformation and proximity to chest wall or breast surface. Conclusions: Lumpectomy cavity and breast deformation and motion demonstrated large variability. A PTV{sub 4DCT} approach showed value in patient-specific margins, particularly if robust interfraction setup analysis can be performed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Multi-institutional Validation Study of Commercially Available Deformable Image Registration Software for Thoracic Images

Purpose: To assess the accuracy of the commercially available deformable image registration (DIR) software for thoracic images at multiple institutions. Methods and Materials: Thoracic 4-dimensional (4D) CT images of 10 patients with esophageal or lung cancer were used. Datasets for these patients were provided by DIR-lab ( (dir-lab.com)) and included a coordinate list of anatomic landmarks (300 bronchial bifurcations) that had been manually identified. Deformable image registration was performed between the peak-inhale and -exhale images. Deformable image registration error was determined by calculating the difference at each landmark point between the displacement calculated by DIR software and that calculated by the landmark. Results: Eleven institutions participated in this study: 4 used RayStation (RaySearch Laboratories, Stockholm, Sweden), 5 used MIM Software (Cleveland, OH), and 3 used Velocity (Varian Medical Systems, Palo Alto, CA). The ranges of the average absolute registration errors over all cases were as follows: 0.48 to 1.51 mm (right-left), 0.53 to 2.86 mm (anterior-posterior), 0.85 to 4.46 mm (superior-inferior), and 1.26 to 6.20 mm (3-dimensional). For each DIR software package, the average 3-dimensional registration error (range) was as follows: RayStation, 3.28 mm (1.26-3.91 mm); MIM Software, 3.29 mm (2.17-3.61 mm); and Velocity, 5.01 mm (4.02-6.20 mm). These results demonstrate that there was moderate variation among institutions, although the DIR software was the same. Conclusions: We evaluated the commercially available DIR software using thoracic 4D-CT images from multiple centers. Our results demonstrated that DIR accuracy differed among institutions because it was dependent on both the DIR software and procedure. Our results could be helpful for establishing prospective clinical trials and for the widespread use of DIR software. In addition, for clinical care, we should try to find the optimal DIR procedure using thoracic 4D-CT data.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Adhesion and aerodynamic forces for the resuspension of non-spherical particles in outdoor environments

Particles deposited on an outdoor surface can be resuspended by wind gusts, become airborne, and be inhaled if small enough. If toxic or infectious, these particles may be dangerous for the populace health. It is therefore important to determine under which weather conditions a deposit of particle could be resuspended to implement the best response actions and plan clean-up. To this scope, one needs to consider the competing forces acting on the particle keeping it attached to the surface (gravity and adhesion) or trying to remove it (aerodynamic forces, i.e., lift and drag). Here, this article reviews the current understanding of the aforementioned forces for colloidal spherical particles and extends the existing theories to rod-shaped particles, representative for instance of Bacillus spores. In particular, for the adhesion force, the Derjaguin approximation was used and the adhesion force was computed from the radii of curvature of the particle and the surface at the point of closest approach. For the aerodynamic forces, we re-derived the equations for the drag and lift forces accounting for the shape of the particle. Both smooth and rough surfaces will be discussed, the former as idealized cases, the latter as more representative of real outdoor surfaces.

54 ENVIRONMENTAL SCIENCES↗