MR Imaging of the Extracranial Facial Nerve with the CISS Sequence.

BACKGROUND AND PURPOSE: MR imaging is not routinely used to image the extracranial facial nerve. The purpose of this study was to determine the extent to which this nerve can be visualized with a CISS sequence and to determine the feasibility of using that sequence for locating the nerve relative to tumor. MATERIALS AND METHODS: Thirty-two facial nerves in 16 healthy subjects and 4 facial nerves in 4 subjects with parotid gland tumors were imaged with an axial CISS sequence protocol that included 0.8-mm isotropic voxels on a 3T MR imaging system with a 64-channel head/neck coil. Four observers independently segmented the 32 healthy subject nerves. Segmentations were compared by calculating average Hausdorff distance values and Dice similarity coefficients. RESULTS: The primary bifurcation of the extracranial facial nerve into the superior temporofacial and inferior cervicofacial trunks was visible on all 128 segmentations. The mean of the average Hausdorff distances was 1.2 mm (range, 0.3-4.6 mm). Dice coefficients ranged from 0.40 to 0.82. The relative position of the facial nerve to the tumor could be inferred in all 4 tumor cases. CONCLUSIONS: The facial nerve can be seen on CISS images from the stylomastoid foramen to the temporofacial and cervicofacial trunks, proximal to the parotid plexus. Use of a CISS protocol is feasible in the clinical setting to determine the location of the facial nerve relative to tumor.

Standardization of Temporal Bone CT Planes across a Multisite Academic Institution.

BACKGROUND AND PURPOSE: Variable head positioning in the CT gantry results in variable and inconsistent temporal bone imaging planes. Our aim was to evaluate whether an automated postprocessing algorithm or an educational intervention with postprocessing by a technologist could result in consistent temporal bone image reformations into planes referenced to the lateral semicircular canal. MATERIALS AND METHODS: Instructions to reformat small-FOV images in planes referenced to the lateral semicircular canal were posted at 12 CT scanner consoles and e-mailed to 65 CT technologists at a single multisite institution. Automated reformatted images were also produced. The angles between the technologist- and automated-reformatted axial image planes and lateral semicircular canal planes were measured. Group differences were calculated with Mann-Whitney-Wilcoxon tests. Differences in homogeneity of variances were calculated with Fligner-Killeen tests. RESULTS: Two hundred ten temporal bones were imaged in 4 months following the intervention. Reformats by technologists were accurate in 87% of the axial and 81% of the coronal planes, with a trend toward improvement with time. Eighty percent of incorrectly reformatted images occurred at off-site, inpatient, and emergency department scanners. The error angle was significantly lower for technologist-reformatted images (median, 4.9°) than for acquisition plane images (median, 14.6°; P = 3 × 10-14) or automated-reformatted images (median, 13.8°; P = 9 × 10-13). The angle error variance was significantly more homogeneous for technologist-reformatted images (P = 3 × 10-8) and automated-reformatted images (P = 1 × 10-5) than for acquisition plane images. CONCLUSIONS: Both technologist and automated reformatting of temporal bone images resulted in significantly less imaging plane variance compared with images reformatted in the acquisition plane, but reformatting by technologists remains necessary at our institution given our preference for standardized planes referencing the lateral semicircular canals.

MR Imaging of the Facial Nerve through the Temporal Bone at 3T with a Noncontrast Ultrashort Echo Time Sequence.

The pointwise encoding time reduction with radial acquisition (PETRA) ultrashort echo time MR imaging sequence at 3T enables visualization of the facial nerve from the brain stem, through the temporal bone, to the stylomastoid foramen without intravenous contrast. Use of the PETRA sequence, or other ultrashort echo time sequences, should be considered in the MR imaging evaluation of certain skull base tumors and perhaps other facial nerve and temporal bone pathologies.

Spine Cryoablation: A Multimodality Image-Guided Approach for Tumors Adjacent to Major Neural Elements.

We report percutaneous cryoablation of spine tumors in 7 consecutive patients (5 men, 2 women [mean age, 47 years; range, 17-68 years]) by using intraprocedural image monitoring of ice ball margins to protect adjacent neural elements. Complete tumor ablation was achieved in all patients without neurologic complication. Pain relief was achieved in 4 of 5 (80%) patients; the patient with persistent pain was later found to have enlarging metastases at other sites.

The association between cardiorespiratory fitness and abdominal adiposity in postmenopausal, physically inactive South Asian women.

In South Asians, a unique obesity phenotype of high abdominal fat is associated with increased cardiovascular risk. Low cardiorespiratory fitness (CRF) is associated with abdominal fat and an increased risk of cardiovascular disease. The purpose of this paper is to determine whether CRF as assessed by VO2 peak, in post-menopausal South Asian women, was associated with body fat distribution and abdominal fat. Physically inactive post-menopausal South Asian women (n = 55) from the Greater Vancouver area were recruited and assessed from January to August 2014. At baseline, VO2 peak was measured with the Bruce Protocol, abdominal fat with CT imaging, and body composition with dual energy X-ray absorptiometry. ANOVA was used to assess differences in subcutaneous abdominal adipose tissue (SAAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) between tertiles of CRF. Bivariate correlation and multiple linear regression analyses explored the association between VO2 peak with SAAT, VAT, TAAT and body composition. Models were further adjusted for body fat and body mass index (BMI). Compared to women in the lowest tertile of VO2 peak (13.8-21.8 mL/kg/min), women in the highest tertile (25.0-27.7 mL/kg/min) had significantly lower waist circumference, BMI, total body fat, body fat percentage, lean mass, SAAT, VAT and TAAT (p < 0.05). We found VO2 peak to be negatively associated with SAAT, VAT and TAAT, independent of age and body fatness but not independent of BMI. Further research is necessary to assess whether exercise and therefore improvements in CRF would alter SAAT, VAT and TAAT in post-menopausal South Asian women.

Controlled-frequency breath swimming improves swimming performance and running economy.

Respiratory muscle fatigue can negatively impact athletic performance, but swimming has beneficial effects on the respiratory system and may reduce susceptibility to fatigue. Limiting breath frequency during swimming further stresses the respiratory system through hypercapnia and mechanical loading and may lead to appreciable improvements in respiratory muscle strength. This study assessed the effects of controlled-frequency breath (CFB) swimming on pulmonary function. Eighteen subjects (10 men), average (standard deviation) age 25 (6) years, body mass index 24.4 (3.7) kg/m(2), underwent baseline testing to assess pulmonary function, running economy, aerobic capacity, and swimming performance. Subjects were then randomized to either CFB or stroke-matched (SM) condition. Subjects completed 12 training sessions, in which CFB subjects took two breaths per length and SM subjects took seven. Post-training, maximum expiratory pressure improved by 11% (15) for all 18 subjects (P < 0.05) while maximum inspiratory pressure was unchanged. Running economy improved by 6 (9)% in CFB following training (P < 0.05). Forced vital capacity increased by 4% (4) in SM (P < 0.05) and was unchanged in CFB. These findings suggest that limiting breath frequency during swimming may improve muscular oxygen utilization during terrestrial exercise in novice swimmers.

Physiological consequences of a high work of breathing during heavy exercise in humans.

The healthy respiratory system has a remarkable capacity for meeting the metabolic demands placed upon it during strenuous exercise. For example, in order to regulate alveolar partial pressure of oxygen and carbon dioxide during heavy workloads, a 20-fold increase in alveolar ventilation can occur. The high metabolic costs and subsequent increased work of breathing associated with this ventilatory increase can result in a number of limitations to the healthy respiratory system. Two examples of respiratory system limitations that are associated with a high work of breathing are expiratory flow limitation and exercise-induced diaphragmatic fatigue. Expiratory flow limitation can lead to an inability to increase alveolar ventilation (V (A)) in the face of increasing metabolic demands, resulting in gas exchange impairment and diminished endurance exercise performance. Furthermore, the high ventilatory requirements of endurance athletes and the inherent anatomical differences in females could make these groups more susceptible to expiratory flow limitation. Fatigue of the diaphragm has also been documented after strenuous exercise and may be related to a mechanism which increases sympathetic vasoconstrictor outflow and reduces limb blood flow during prolonged exercise. This competition between the muscles of respiration and locomotion for a limited cardiac output may have dramatic consequences for exercise performance. This brief review summarizes the literature as it pertains to the work of breathing, expiratory flow limitation, and exercise-induced diaphragmatic fatigue in healthy humans.

Intense hypoxic cycle exercise does not alter lung density in competitive male cyclists.

We tested the hypothesis that intense short duration hypoxic exercise would result in an increase in extravascular lung water (EVLW), as evidenced by an increase in lung density. Using computed tomography (CT), baseline lung density was obtained in eight highly trained male cyclists (mean +/- SD: age = 28 +/- 8 years; height = 180 +/- 9 cm; mass = 71.6 +/- 8.2 kg; VO2max= 65.0 +/- 5.2 ml kg min(-1)). Subjects then completed an intense hypoxic exercise challenge on a cycle ergometer and metabolic data, HR and %S(p)O2 were recorded throughout. While breathing 15% O2, subjects performed five 3 km cycling intervals (mean power, 286 +/- 20 W; HR = 91 +/- 4% HRmax) separated by 5 min of recovery. From a resting hypoxic S(p)O2 of 92 +/- 4%, subjects further desaturated during exercise to 76 +/- 3%. CT scans were repeated 76 +/- 10 min (range 63-88 min) following the completion of exercise. There was no change in lung density from pre (0.18 +/- 0.02 g ml(-1)) to post-exercise (0.18 +/- 0.04 g ml(-1)). The substantial reduction in S(p)O2 may be explained by a number of potential mechanisms, including decreased pulmonary diffusion capacity, alveolar hypoventilation, reduced red cell transit time, ventilation/perfusion inequality or a temperature and pH induced rightward-shift in the oxyhaemoglobin dissociation curve. Alternatively, the integrity of the blood gas barrier may have been disrupted without any measurable increase in lung density.

90-day repeated inhalation exposure of surfactant Protein-C/tumor necrosis factor-alpha, (SP-C/TNF-alpha) transgenic mice to air pollutants.

Tumor necrosis factor (TNF)-alpha, a cytokine present in inflammed lungs, is known to mediate some of the adverse effects of ozone and inhaled particles. The authors evaluated transgenic mice with constitutive pulmonary expression of TNF-alpha under transcriptional regulation of the surfactant protein-C promoter as an animal model of biological susceptibility to air pollutants. To simulate a repeated, episodic exposure to air pollutants, wild-type and TNF mice inhaled air or a mixture of ozone (0.4 ppm) and urban particles (EHC-93, 4.8 mg/m3) for 4 h, once per week, for 12 consecutive weeks and were sacrificed 20 h after last exposure. TNF mice exhibited chronic lung inflammation with septal thickening, alveolar enlargement, and elevated protein and cellularity in bronchoalveolar lavage fluid (genotype main effect, p < .001). Repeated exposure to pollutants did not result in measurable inflammatory changes in wild-type mice and did not exacerbate the inflammation in TNF mice. The pollutants decreased recovery of alveolar macrophages in tavage fluid of both wild-type and TNF mice (exposure main effect, p < .001). Exacerbation of the rate of protein nitration reactions specifically in the lungs of TNF mice was revealed by the high ratio of 3-nitrotyrosine to L-DOPA after exposure to the air pollutants (Genotype x Exposure factor interaction, p = .014). Serum creatine kinase-MM isoform increased in TNF mice exposed to pollutants (Genotype X Exposure factor interaction, p = .043). The marked pollutant-related nitration in the lungs of the TNF mice reveals basic differences in free radical generation and scavenging in the inflamed lungs in response to pollutants. Furthermore, elevation of circulating creatine kinase-MM isoform specifically in TNF mice exposed to pollutants suggests systemic adverse impacts from lung inflammatory mediators, possibly on muscles and the cardiovascular system.

Hydroxyl radical adduct of 5-aminosalicylic acid: a potential marker of ozone-induced oxidative stress.

The use of 5-aminosalicylic acid in assessment of reactive oxygen species formation was investigated by in vitro Fenton and ozonation reactions, and by in vivo ozone-exposure experiments. Enzymatic hydroxylation was evaluated by a microsomal assay. Fischer 344 male rats (250 g) injected with 5-aminosalicylic acid (100 mg x kg(-1) i.p.; 30 min) were exposed to ozone (0, 1, 2 ppm; nose only, 2 h); bronchoalveolar lavage, lung homogenates, and plasma were recovered. Oxidation products of 5-aminosalicylic acid were as follows: salicylic acid, by deamination; 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid, from radical or enzymatic hydroxylation; 5-amino-2-hydroxy-N,N'-bis(3-carboxy-4-hydroxyphenyl)-1,4-benzoquinonediimine, a condensation product of oxidized 5-aminosalicylic acid; and 5-amino-2,3,4,6-tetrahydroxybenzoic acid, attributed to hydroxyl radical attack without deamination, identified by HPLC electrochemical (HPLC-EC) detector system analysis and by GC-MS analysis of trimethylsilyl derivatives. 5-Aminotetrahydroxybenzoic acid was not formed enzymatically. 5-Aminotetrahydroxybenzoic acid, but not 5-aminosalicylic acid, was significantly elevated in bronchoalveolar lavage (+86%) and lung homogenates (+56%) in response to 2 ppm ozone (p < 0.05); no significant changes were detected in plasma. The data indicate that hydroxylation of 5-aminosalicylic acid is a potential specific probe for in vivo oxidative stress.

Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats.

Wistar rats were exposed for 4 hours by nose-only inhalation to clean air, resuspended Ottawa ambient particles (EHC-93*, 48 mg/m3), the water-leached particles (EHC-93L, 49 mg/m3), diesel soot (5 mg/m3), or carbon black (5 mg/m3). Continuous data for physiologic endpoints (heart rate, blood pressure, body temperature, animal's activity) were captured by telemetry before and after exposure. Blood was sampled from jugular cannulas 1 to 3 days before exposure and at 2 and 24 hours after exposure, and by heart puncture on termination at 32 hours (histology group) or 48 hours (telemetry group) after exposure. Lung injury was assessed by 3H-thymidine autoradiography after the rats were killed. We measured endothelins (plasma ET-1, big ET-1, ET-2, ET-3) to assess the vasopressor components; nitric oxide (NO)-related metabolites (blood nitrate, nitrite, nitrosyl compounds, and plasma 3-nitrotyrosine) to assess the vasodilator components; and catecholamines (epinephrine, norepinephrine, L-DOPA, dopamine) and oxidative stressors (m- and o-tyrosine) for additional insight into possible stress components. Lung cell labeling was uniformly low in all treatment groups, which indicates an absence of acute lung injury. Inhalation of EHC-93 caused statistically significant elevations (P < 0.05) of blood pressure on day 2 after exposure, plasma ET-1 at 32 hours after exposure, and ET-3 at 2, 32, and 48 hours after exposure. In contrast, the modified EHC-93L particles, from which soluble components had been extracted, did not affect blood pressure. The EHC-93L particles caused early elevation (P < 0.05) of the plasma levels of ET-1, ET-2, and ET-3 at 2 hours after exposure, but the endothelins returned to basal levels 32 hours after exposure. Exposure to diesel soot, but not carbon black, caused an elevation (P < 0.05) of plasma ET-3 at 36 hours after exposure; blood pressure was not affected by diesel soot. Our results indicate that inhalation of the urban particles EHC-93 can affect blood levels of ET-1 and ET-3 and cause a vasopressor response in Wistar rats without causing acute lung injury. Furthermore, the potency of the particles to influence hemodynamic changes appears to be modified by removing polar organic compounds and soluble elements. Because the pathophysiologic significance of elevated endothelins has been clinically established in humans, our observations suggest a novel mechanism by which inhaled particles may cause cardiovascular effects. These findings in rats contribute to the weight of evidence in favor of a biologically plausible epidemiologic association between ambient particulate matter and cardiovascular morbidity and mortality in human populations.

Acute effects of inhaled urban particles and ozone: lung morphology, macrophage activity, and plasma endothelin-1.

We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 microm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) resulted in increased neutrophils and protein in lung lavage fluid. Ozone alone also decreased phagocytosis and nitric oxide production and stimulated endothelin-1 secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2. Co-exposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measurable exacerbation of the ozone-related alveolar neutrophilia and permeability to protein detected by lung lavage. The enhanced septal thickening was associated with elevated production of both macrophage inflammatory protein-2 and endothelin-1 by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-1, but this response was not influenced by the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the distally distributed particulate dose on capillary endothelial production or filtration of the vasoconstrictor. Overall, equivalent patterns of effects were observed after a single exposure or three consecutive daily exposures to the pollutants. The experimental data are consistent with epidemiological evidence for acute pulmonary effects of ozone and respirable particulate matter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects of respirable particulate matter from ambient air appear related to paracrine/endocrine disruption mechanisms.

Acute pulmonary toxicity of urban particulate matter and ozone.

We have investigated the acute lung toxicity of urban particulate matter in interaction with ozone. Rats were exposed for 4 hours to clean air, ozone (0.8 ppm), the urban dust EHC-93 (5 mg/m3 or 50 mg/m3), or ozone in combination with urban dust. The animals were returned to clean air for 32 hours and then injected (intraperitoneally) with [3H]thymidine to label proliferating cells and killed after 90 minutes. The lungs were fixed by inflation, embedded in glycol methacrylate, and processed for light microscopy autoradiography. Cell labeling was low in bronchioles (0.14 +/- 0.04%) and parenchyma (0.13 +/- 0.02%) of air control animals. Inhalation of EHC-93 alone did not induce cell labeling. Ozone alone increased (P < 0.05) cell labeling (bronchioles, 0.42 +/- 0.16%; parenchyma, 0.57 +/- 0.21%), in line with an acute reparative cell proliferation. The effects of ozone were clearly potentiated by co-exposure with either the low (3.31 +/- 0.31%; 0.99 +/- 0.18%) or the high (4.45 +/- 0.51%; 1.47 +/- 0.18%) concentrations of urban dust (ozone X EHC-93, P < 0.05). Cellular changes were most notable in the epithelia of terminal bronchioles and alveolar ducts and did not distribute to the distal parenchyma. Enhanced DNA synthesis indicates that particulate matter from ambient air can exacerbate epithelial lesions in the lungs. This may extend beyond air pollutant interactions, such as to effects of inhaled particles in the lungs of compromised individuals.

Hydroxylation of salicylate in lungs of Fischer 344 rats: effects of aging and ozone exposure.

The formation of 2,3-dihydroxybenzoic acid (DHBA) from salicylate was measured in the lungs and plasma to assay for the .OH in juvenile (2 mo), adult (9 mo), and senescent (24 mo) Fischer 344 male rats exposed to clean air, 1 part/million (ppm) ozone, or 2 ppm ozone for 2 h. Similar rates of distribution of salicylic acid in plasma and to the lungs were observed among air control animals of all age groups. Levels of 2,3-DHBA were about twice as high in the lungs of air control senescent rats compared with juvenile and adult rats (P < 0.05). Exposure to ozone resulted in 1.5- to 2-fold elevation of 2,3-DHBA in lungs and plasma of all age groups (P < 0.05), whereas levels of 2,5-DHBA were not changed significantly. There was no effect of age on the magnitude of 2,3-DHBA increase in the lungs or plasma after ozone exposure. The postulated source of .OH is chemical reduction of H2O2, which could be generated from increased age-dependent endogenous oxidant production or the age-independent reaction of ozone or macrophage-derived oxidants with the surfactant lining.

Spin trapping study in the lungs and liver of F344 rats after exposure to ozone.

Fischer 344 rats were injected with the spin traps C-phenyl N-tert-butyl nitrone (PBN, 150 mg/kg bw, ip) or 4-pyridine-N-oxide N-tert-butyl nitrone (POBN, 775 mg/kg bw, ip), and exposed to clean air or 2 ppm ozone for two hours. The presence of spin adducts was determined by electron paramagnetic resonance (EPR) spectroscopy of chloroform extracts of lung and liver homogenates. No significant levels of adducts were detected in the lungs of air control animals. Benzoyl N-tert-butyl aminoxyl, attributed to direct reaction of ozone with PBN, and tert-butyl hydroaminoxyl, the scission product of the hydroxyl adduct of PBN, were detected in the lungs of ozone exposed rats. EPR signals for carbon-centred alkoxyl and alkyl adducts were also detected with PBN in the lungs and liver of animals exposed to ozone. With POBN, only carbon-centred alkyl radicals were detected. Senescent, 24 months old rats were found to retain about twice more 14C-PBN in blood, heart and lungs by comparison to juvenile, 2 months old animals. Accordingly, the EPR signals were generally stronger in the lungs of the senescent rats by comparison to juvenile rats. Together, the observations were consistent with the previously proposed notion that a significant flux of hydrogen peroxide produced from the reaction of ozone with lipids of the extracellular lining, or from activated macrophages in the lungs could be a source of biologically relevant amounts of hydroxyl radical.

Sensitivity of lungs of aging Fischer 344 rats to ozone: assessment by bronchoalveolar lavage.

Biological effects indicators in bronchoalveolar lavage fluid were studied in Fischer 344 rats of different ages after exposure to 0.4-0.8 ppm ozone for periods of 2-6 h on a single day or on 4 consecutive days. The magnitude of alveolar protein transudation induced by ozone was not different between age groups, but the interindividual variability of protein changes was higher in senescent (24-mo-old) rats. By comparison to juvenile (2-mo-old) and adult (9-mo-old) rats, senescent animals had higher increases of interleukin-6 (up to 10-fold higher) and N-acetyl-beta-D-glucosaminidase (NAGA; 2-fold higher) in lung lavage after ozone. Ascorbic acid was lower in lungs of senescent rats (one-half of juvenile values), and acute ozone exposure brought a further decrease in lung ascorbate. Whereas alveolar protein transudation was attenuated after ozone exposure on 4 days, persistent elevation of NAGA in senescent rats suggested only partial adaptation. Injection of endotoxin did not modify the patterns of effects. Incorporation of 18O-ozone into macrophages and surfactant was not different between age groups, indicating that the magnified biological responses in senescent rats were not dominated by differences in internal dose of ozone. The results indicate that senescent rats respond differently than juvenile and adult rats to lung injury.