Technegas for inhalation lung imaging.

Technegas, an aerosol generator recently devised in Australia, produces aerosol particulates called 'technegas' which have characteristics of both an aerosol and a gas. The majority of the particulate is below 200 nm in size as measured by electron microscopy. Four normal subjects and 31 patients with various lung diseases were studied by imaging the lungs following inhalation of technegas. The penetration of inhaled technegas to the lung periphery was excellent; the average alveolar deposition ratio (ALDR) was 85%. Comparative studies with lung images obtained either with an ultrasonic nebulizer or jet nebulizers also confirmed better penetration of inhaled technegas to the lung periphery. There was no significant statistical difference in the ALDRs between normals and patients. Aerosol studies were comparable to perfusion counterparts, and evaluation of regional ventilatory status was greatly facilitated. Because of the large ALDR and the low airway deposition ratio (ADR), actual imaging could be done not only immediately after aerosol inhalation but also some time later without losing too much radioactivity from the lungs. One disadvantage was that technegas immediately after generation was anoxic.     

Effect of bronchodilation on the deposition and clearance of radioaerosol in bronchial asthma in remission

Radioaerosol inhalation lung cine-scintigraphy and lung function tests were performed on ten patients with bronchial asthma in remission before and after inhalation of salbutamol following intravenously administered aminophylline. Radioaerosol inhalation lung cine-scintigraphy was very useful in revealing the changes not only in the deposition patterns of inhaled aerosol in the lungs but also in the dynamic transport of mucus on the airways. The bronchodilating effect of the combined treatment was significant; the inhaled aerosol deposited more homogeneously and less centrally in the lungs, the "penetration index" and the alveolar deposition ratio (ALDR) increased from 31 +/- 3 to 49 +/- 7%, and from 29 +/- 2% to 39 +/- 1%, respectively, while the airway deposition ratio (ADR) decreased from 72 +/- 2 to 61 +/- 1% immediately after the treatment. Lung function data including FVC, FEV 1.0, FEV 1.0%, MMF, V50 and Vp significantly improved after the treatment. There was, however, little visual or quantitative improvement in mucociliary clearance after the treatment.     

Radioaerosol inhalation lung imaging using technegas

Technegas generator using 99mTc-pertechnetate was tested on 4 normal subjects and 31 patients with various chest diseases including bronchogenic carcinoma, pneumonia, pulmonary tuberculosis, sarcoidosis, and so on. Technegas was inhaled from the RV to the TLC levels through the mouth with the nose clipped followed by breath-holding. Three deep breaths were enough to deposit 37-55.5 MBq (1 to 1.5 mCi) of technegas in the lungs. The average alveolar deposition ratio (ALDR) was 85% and penetration of inhaled technegas to the lung periphery was excellent. "Hot spots" or excessive radioactive deposition were also seen when there was airway obstruction. The former indicated the characteristic as gas and the latter, that as aerosol particles. Because of the large ALDR's the timing for imaging lungs after inhalation of technegas most likely indicated the intrapulmonary sites of effective ventilation, because respective inhalation and perfusion lung images resembled each other very much. The disadvantage of technegas was that it was anoxic right after generation.     

Urine excretion of inhaled technetium-99m-DTPA: an alternative method to assess lung epithelial transport

Technetium-99m DTPA clearance (99mTc-DTPA) clearance measured by a gamma camera or a scintillation probe not only reflects epithelial transport, but is also influenced by an unknown amount of mucociliary clearance depending on particle size and aerosol deposition. This is confirmed by factor analysis of dynamic inhalation studies. Assessment of epithelial absorption by urinary excretion of inhaled 99mTc-DTPA is largely independent of aerosol lung deposition. Twenty-four-hour excretion reflects the amount of aerosol cleared by absorption, while two-hour excretion is a quantitative measure of the aerosol absorption rate from the epithelium into blood. Urinary 99mTc-DTPA excretion of two aerosols with different particle size correlated significantly (p less than 0.001) with analysis of lung clearance curves. A very similar regression in the form of a cumulative exponential function was found with both aerosols. Two-hour urine values of nonsmokers differed significantly from those of smokers or patients with active interstitial or infectious lung disease. This alternative procedure is suited as a bedside test and holds promise for patient monitoring and follow-up.     

Characterization of the generation of radiolabeled monodisperse albuterol particles using the spinning-top aerosol generator.

Inhaled radiolabeled aerosols provide invaluable information about in vivo drug deposition. Here, we report our methodology for radiolabeling and imaging monodisperse pharmacologic aerosols in order to study basic aerosol science concepts of drug delivery within the human airways. METHODS: We used a spinning-top aerosol generator to produce (99m)Tc-labeled monodisperse albuterol sulfate aerosols of 1.5-, 3-, and 6- micro m mass median aerodynamic diameter. RESULTS: In vitro Andersen cascade validation data showed that technetium and albuterol were coassociated on each impactor stage for all 3 aerosols, and the radiolabeling process itself did not affect their particle size distributions. Good-quality gamma-camera scintigraphic images of lung and extrathoracic deposition were obtained within an asthmatic patient. CONCLUSION: We have successfully radiolabeled and imaged monodisperse albuterol aerosols within the human lungs. This novel technique provides an important tool to relate fundamental concepts of aerosol particle behavior, in vivo deposition, and therapeutic clinical response.     

Deposition of aqueous aerosol of technetium-99m diethylene triamine penta-acetic acid generated and delivered by a novel system (AERx) in healthy subjects

Deposition of technetium-99m diethylene triamine penta-acetic acid aqueous radioaerosols generated by a novel aerosol delivery system (AERx) was studied in six healthy subjects using both planar and single-photon emission tomography (SPET) imaging. AERx is a microprocessor-controlled, bolus inhalation device that is actuated at pre-programmed values of inspiratory flow rate and volume. The aims of the study were to determine the effects of posture and inhaled volume upon deposition of the aerosol in the lungs. Each subject inhaled the radioaerosol in two positions (supine vs sitting) and with two inspiratory manoeuvres [vital capacity (VC) vs "fixed volume" of 1 l above functional residual capacity]. Simultaneous transmission-emission planar and tomographic images were acquired. The results showed diffuse deposition of the aerosol in the lung. Neither the breathing manoeuvre nor the posture was found to affect the distribution of the aerosol as measured by the ratio of the activity (counts per pixel) in the peripheral:central (penetration index, PI) or in the apex:base regions of the planar lung images (P>0.1). A small, albeit statistically significant, difference in PI (P<0.03) was found between VC and fixed volume sitting manoeuvres with SPET only. The PI values themselves indicate that the radioaerosol was well distributed in the lung, with the periphery having 45%-64% of the activity of the central region. Superposition of transmission SPET lung outline on emission SPET visually confirmed the excellent peripheral deposition of the aerosol. The AERx system showed high efficiency of delivery, with approximately 50% of the extruded dose in the device depositing in the lung. The uniformity of radioactivity distributed throughout the lung is attributed to the fine particle size (mass median aerodynamic diameter of 2 microm) of the aerosol and the electronic control of aerosol inhalation by the device. In conclusion, the AERx system can be ideal for diffuse aerosol deposition of therapeutic or diagnostic agents and is largely unaffected by inhaled volume and posture. The efficiency of the device device can limit the total radiation exposure of patients and staff administering the radioaerosols, and can make it suitable for delivery of expensive drugs.     

Deposition of aqueous aerosol of technetium-99m diethylene triamine penta-acetic acid generated and delivered by a novel system (AERx) in healthy subjects

Deposition of technetium-99m diethylene triamine penta-acetic acid aqueous radioaerosols generated by a novel aerosol delivery system (AER_x) was studied in six healthy subjects using both planar and single-photon emission tomography (SPET) imaging. AER_x is a microprocessor-controlled, bolus inhalation device that is actuated at pre-programmed values of inspiratory flow rate and volume. The aims of the study were to determine the effects of posture and inhaled volume upon deposition of the aerosol in the lungs. Each subject inhaled the radioaerosol in two positions (supine vs sitting) and with two inspiratory manoeuvres [vital capacity (VC) vs ”fixed volume” of 1 l above functional residual capacity]. Simultaneous transmission-emission planar and tomographic images were acquired. The results showed diffuse deposition of the aerosol in the lung. Neither the breathing manoeuvre nor the posture was found to affect the distribution of the aerosol as measured by the ratio of the activity (counts per pixel) in the peripheral:central (penetration index, PI) or in the apex:base regions of the planar lung images (P>0.1). A small, albeit statistically significant, difference in PI (P<0.03) was found between VC and fixed volume sitting manoeuvres with SPET only. The PI values themselves indicate that the radioaerosol was well distributed in the lung, with the periphery having 45%–64% of the activity of the central region. Superposition of transmission SPET lung outline on emission SPET visually confirmed the excellent peripheral deposition of the aerosol. The AER_x system showed high efficiency of delivery, with approximately 50% of the extruded dose in the device depositing in the lung. The uniformity of radioactivity distributed throughout the lung is attributed to the fine particle size (mass median aerodynamic diameter of 2 μm) of the aerosol and the electronic control of aerosol inhalation by the device. In conclusion, the AER_x system can be ideal for diffuse aerosol deposition of therapeutic or diagnostic agents and is largely unaffected by inhaled volume and posture. The efficiency of the device device can limit the total radiation exposure of patients and staff administering the radioaerosols, and can make it suitable for delivery of expensive drugs. Received 6 October and in revised form 30 November 1998     

Mucociliary clearance and transport in bronchiectasis: global and regional assessment

Global and regional mucociliary clearance and transport in the lungs was studied in 20 patients with bronchiectasis by radioaerosol inhalation lung cine-scintigraphy and the quantitative analysis following inhalation of ultrasonically-generated 99mTc-tagged human serum albumin aerosol (mass median diameter; 1.93 microns with geometric s.d. of 1.52). In bronchiectatic lung regions, deposition of inhaled aerosol was diminished or inhomogeneous. Transport of inhaled radioactivity from the bronchiectatic regions was deranged in 95% of the patients (19/20). The following abnormal mucous transport patterns were regionally observed; stasis in 12 of the 20 patients (12/20), regurgitation or reversed transport in 14/20, straying in 8/20, spiral or zigzag transport in 1/20, and/or various combinations of these four abnormal transport patterns. When coughs occurred, regurgitation and stray became more marked in the bronchiectatic regions. These regional abnormalities in mucociliary transport seem to be responsible for the development of infections and hemoptysis in the bronchiectatic regions.     

Adaptive assay of radioactive pulmonary aerosols with an external detector

The accuracy of the assay of radioactive pulmonary aerosols is influenced by the spatial distribution of the aerosol in the lungs. In general, there is considerable uncertainty in the spatial distribution of the aerosol beginning a few months after inhalation. This paper develops an adaptive approach for optimizing the assay of non-uniform spatial distributions of pulmonary aerosols. An adaptive assay is one in which the design of the assay system is modified during operation in response to measurements obtained on-line. Experimental results are presented which compare the performance of an adaptive assay with that of the standard measurement procedure. We study the assay of ²⁴¹Am distributed in the lungs of a Lawrence Livermore realistic phantom using a NaICsI Phoswich detector.     

气溶胶沉降模拟方法研究进展

对吸入颗粒物致病作用的评估,需要了解气溶胶颗粒在呼吸道中的沉积特征。由于气溶胶进入呼吸道引、发的呼吸道疾病致病机锏研究和临床药物气藩胶吸入治疗的需要,人们越发关注如气溶胶颗粒在呼吸道特定区域滞留率,研究气溶胶粒子在呼吸道中分布和沉降比例的关系。这些都需要借助沉降模型来模拟颗粒的区域沉积特征。沉降模型经过半个多世纪的发展,已经形成了成熟的分析模型。计算机流体动力学（CFD）模拟技术的出现,让沉降模拟进入了一个崭新的时代。该文综述了目前研究气溶胶沉降的主要方法和肺模型的发展趋势。     

某铜矿山巷道内气溶胶浓度与粒径分布的测量和分析

目的 定性了解矿山巷道内气溶胶的浓度和粒径分布特性。方法 在巷道内的不同区间,分别用凝结核颗粒计数器和个人气溶胶测量仪巡测气溶胶的粒子数和质量浓度,并通过质量浓度的分级测量定性评价微米级气溶胶的粒径分布;在调度室内外,用金属丝网筛扩散法测量亚微米级气溶胶的粒径分布。结果 巷道内可吸入颗粒物(PM10)的平均质量浓度为0.42 mg/m³,其量值大小因工作断面而异,且受人工活动影响变化较大;巷道内粒径大于1.0 μm的颗粒物广泛存在,而粒子直径小于5 nm的气溶胶基本上未被检出。结论 矿山巷道内气溶胶特性因工作断面、人工活动和通风条件的不同而变化明显,在开展内照射剂量评价时应考虑粒径大于1.0 μm放射性气溶胶粒子的剂量贡献。     

Technegas and Pertechnegas particle size distribution

Technegas and Pertechnegas are radioactive aerosols produced in a commercial generator and used for lung scintigraphy. The aerosols are produced by first evaporating to dryness standard technetium-99m generator eluate (^99m-TcO₄ in normal saline) in a graphite crucible (thesimmer stage) and then heating this to 2500° C (the burn stage). The aim of this work was to measure the particle size distributions of these agents and relate this to regional lung deposition. Factors that may vary during production of the aerosol in routine use were investigated to determine whether they influenced the particle size. Activity size distributions were measured using a serial wire-screen diffusion battery. The Technegas size distribution was approximately log-normal with an activity median diameter of 158 nm and a geometric standard deviation of 1.5. The results for Pertechnegas were similar. The median size increased with the number of simmers and with the time from generation. The increase in size with the number of simmers is thought to be due to the increased salt content in the crucible prior to the burn. The predicted lung deposition is 37% in the alveolar region and 5% in the bronchial region. Significant changes in deposition are not predicted over the range of particle sizes measured.     

潜艇内放射性气溶胶浓度及粒度分布的测定与评价

目的为估算艇员内照射剂量和评价吸入危害防护提供参数。方法用DK-2A空气采样器在艇内各舱室采样,通过α、β放射性计数测量并计算艇内放射性气溶胶的浓度,使用WM—2型级联撞击器测定了艇内Ⅲ舱和Ⅴ舱的放射性气溶胶粒度分布。结果潜艇水下航行时,艇内的放射性气溶胶逐渐升高;气溶胶粒度的活度中值空气动力学直径(AMAD)的平均值是(0.22±0.02)μm;几何标准偏差的平均值是(2.57±0.25)。结论潜艇水下航行的时间是影响艇员内照射剂量的重要因素;气溶胶粒度的谱型是由小粒子占优势的分布较窄的多分散相;气溶胶的粒度分布与其浓度的变化无关。     

Mucociliary clearance mechanism in smoking and nonsmoking normal subjects

Mucociliary clearance mechanisms were evaluated in 17 normal subjects visually and qualitatively by radioaerosol inhalation cinescintigraphy of the lung, and quantitatively by calculating the following indices: (a) overall or regional lung retention ratio; (b) airway deposition ratio; (c) airway retention ratio; (d) airway clearance efficiency; and (e) alveolar deposition ratio. The inhaled aerosol deposited homogeneously throughout the lungs, and mucus transport was always cephalad in direction and constant in velocity, although a temporary stasis of mucus was seen in smokers. Overall lung retention ratio was significantly smaller and airway deposition ratio was significantly larger in the smokers than in nonsmokers, but there was no difference between the groups in airway retention ratio or airway clearance efficiency. There was an inverse relationship between alveolar deposition ratio and cigarette consumption. Mucociliary clearance mechanisms were well maintained in the normal subjects, but in the smokers inhaled aerosol tended to deposit more proximally.     

The APE nebuliser--a new delivery system for the alveolar targeting of particulate technetium 99m diethylene triamine penta-acetic acid

We report the validation of a new delivery system--aerosol production equipment (known by the acronym APE), which generates a particulate aerosol of technetium 99m diethylene triamine penta-acetic acid (DTPA) with a mass-median aerodynamic diameter of 0.35 microns and a geometric standard deviation of 1.8 Twenty subjects were studied; in group 1 were 12 healthy men with normal spirometry; in group 2 were 8 men with AIDS who had mildly abnormal lung function following an episode of pneumocystis pneumonia-spirometry FEV1 3.08 (0.73) L, FVC 4.83 (0.82) L [mean (SD)]. The APE nebulizer was used to form a particulate aerosol with 200 MBq of 99mTc DTPA, which was collected in a 35 1 reservoir of air, which was subsequently inhaled. The mean (SD) inhalation time was 4.7 (0.44) min. The output of the nebulizer (% of activity inhaled) was 82%. Using planar imaging, the penetration index (right lung) in group 1 was 0.93 (0.18), mean (SD), and in group 2 it was 0.91 (0.12). There was virtually no tracheal deposition and extrapulmonary deposition (oropharynx and stomach) was less than 5% of the aerosol delivered. Single-photon emission tomography (SPET) studies carried out in five patients from group 1 confirmed homogeneous intrapulmonary deposition of 99mTc-DTPA. In view of the excellent intrapulmonary deposition of 99mTc-DTPA produced by the APE nebulizer, it may provide an alternative to conventional ventilation studies using radioactive gases.     

Usefulness and pitfalls of planar gamma-scintigraphy for measuring aerosol deposition in the lungs: a Monte Carlo investigation.

Planar gamma-scintigraphy is often used to quantify pulmonary deposition patterns from aerosol inhalers. The results are quite different from those obtained using 3-dimensional PET and SPECT. The purpose of this study was to characterize the effects of scatter and tissue attenuation on the distribution of radiolabeled aerosol as measured by planar scintigraphy using Monte Carlo simulations. This study also investigated the applicability of a few correction methods used in inhalation studies. METHODS: Body density maps were derived from CT scans. Regions of interest-lungs, major airways, and esophagus-were defined from the same CT volume. Two radioactivity source distribution patterns in the lung, uniform and nonuniform, were used. A Monte Carlo program, SIMIND, was used to generate anterior and posterior gamma-images of the composed inhalation distributions for 2 energy windows, photopeak (127-153 keV) and scatter (92-125 keV). The effects of scatter and attenuation were estimated on the basis of the imaging components separated from the simulation. A scatter correction method and 2 attenuation correction methods, all applied to inhalation scintigraphy, were evaluated using the simulated images. RESULTS: The amount of scatter ranges from 24% to approximately 29% in the lungs and from 29% to approximately 35% in the central (airway or esophagus) region on the planar images. Significant differences were found among regions and between source distributions (P < 0.05). The fraction k used for dual-energy-based scatter correction also varied and was found to be less than the commonly used k = 0.5. The simplified narrow-beam attenuation correction and the effective (broad-beam) correction methods were found to either under- or overcorrect the regional activities. CONCLUSION: The amount of scatter and tissue attenuation in the thorax region depends on source distribution and body attenuation. In applying planar scintigraphy for aerosol inhalation studies, it is difficult to obtain precise quantitative measurements because of the uncertainties associated with scatter and attenuation corrections. Accurate corrections require knowledge of both source and density distributions.     

循环呼吸模式对人体气管支气管内气流运动影响的仿真分析

目的：研究人体气管支气管内的气流运动特性,了解有毒气溶胶或药物治疗气溶胶在人体气管支气管内不同部位的沉积模式。方法：应用计算流体动力学方法对人体在循环呼吸模式下气管支气管内的气流运动特性进行数值模拟,分析循环呼吸模式对气管支气管内的气流组织形式以及气流运动对呼吸道壁面的影响。结果：在吸气加速阶段,气管支气管平面内逐渐形成抛物线型的速度分布,气管支气管内各个截面上逐渐形成二次涡流运动,内壁形成高剪应力区。在呼气阶段,支气管内的二次气流运动经历了从2个涡流到4个涡流的运动变化过程。气流经过多级分支的效果是使速度的分布均匀化,特别使在同级两个支气管轴线共处的平面内的速度分布,在经过几级汇合后,轴线处的速度峰值分布现象会消失而变得均匀。结论：循环呼吸模式下壁面受到的剪应力周期性改变方向,引起壁面劳损和组织损伤的可能性增大,同时在这些部位容易造成气溶胶的沉积。     

The APE nebuliser — a new delivery system for the alveolar targeting of particulate technetium 99m diethylene triamine penta-acetic acid

We report the validation of a new delivery system — aerosol production equipment (known by the acronym APE), which generates a particulate aerosol of technetium 99m diethylene triamine penta-acetic acid (DTPA) with a mass-median aerodynamic diameter of 0.35 m and a geometric standard deviation of 1.8 Twenty subjects were studied; in group 1 were 12 healthy men with normal spirometry; in group 2 were 8 men with AIDS who had mildly abnormal lung function following an episode of pneumocystis pneumonia-spirometry FEV₁ 3.08 (0.73) L, FVC 4.83 (0.82) L [mean (SD)]. The APE nebulizer was used to form a particulate aerosol with 200 MBq of^99mTc DTPA, which was collected in a 351 reservoir of air, which was subsequently inhaled. The mean (SD) inhalation time was 4.7 (0.44) min. The output of the nebulizer (% of activity inhaled) was 82%. Using planar imaging, the penetration index (right lung) in group 1 was 0.93 (0.18), mean (SD), and in group 2 it was 0.91 (0.12). There was virtually no tracheal deposition and extrapulmonary deposition (oropharynx and stomach) was less than 5% of the aerosol delivered. Single-photon emission tomography (SPET) studies carried out in five patients from group 1 confirmed homogeneous intrapulmonary deposition of^99mTc-DTPA. In view of the excellent intrapulmonary deposition of^99mTc-DTPA produced by the APE nebulizer, it may provide an alternative to conventional ventilation studies using radioactive gases.     

Pulmonary clearance of 99mTc-HMPAO aerosol

The clearance rate of inhaled aerosols of a lipophilic substance, 99mTc-HMPAO (Hexamethyl propylene amine oxime) was studied and compared to that of hydrophilic substances in 6 normal volunteers and 18 patients with lung diseases. The subject in sitting position inhaled a single deep breath of 99mTc-HMPAO aerosols, and held his breath about 30 sec. Then he continued to breath aerosols again for about 3 min. Radioactivity rapidly falls down during breath holding, to about 60% of the peak value (fast phase), with T 1/2 of 3.75 +/- 2.22 sec in 6 normal volunteers. This rapid phase was not appeared in hydrophilic aerosols with 99mTc-DTPA and 99mTc-pertechnetate and in lipophilic aerosol with 123I-IMP aerosol. The clearance of residual activity of 99mTc-HMPAO was slow with T 1/2 of 17.4 +/- 4.0 min. The T 1/2 of 99mTc-DTPA, 99mTc-pertechnetate and 123I-IMP were 50.2 +/- 20.9 min, 11.4 +/- 4.3, and 62.5 +/- 20.8 min respectively. 99mTc-HMPAO may cross transcellularly using the whole alveolar surface. The clearance of aerosols in the fast phase is rapid and depend on the regional perfusion. On the other hand, hydrophilic aerosol pass by an intercellular pathway and the clearance will be diffusion limited. As conclusion, inhalation study of 99mTc-HMPAO might be a new method to evaluate perfusion following ventilation study.     

Sites of deposition of aqueous aerosols: a study of efficiency of delivery systems for lung ventilation imaging in man

A study was made of the deposition of 99Tcm-DTPA aerosol in the components of a jet nebulizer-based aerosol production system. Three impaction devices were compared: a ball-bearing separator, a virtual impactor and a step separator. In addition a comparison was made of two types of tubing which carried aerosol from nebulizer to mouthpiece: corrugated and smooth-walled tubing. The retention of aerosol following inhalation was measured in five normal volunteers using different patterns of breathing. Using an aerosol production system which included a ball-bearing separator only a mean of 11% of the radioactivity loaded into the nebulizer was emitted as an aerosol. Some 18% remained in the ball-bearing separator. The ball-bearing and step separators produced similar total outputs (7% and 6% minimum), the step separator producing marginally higher mean output/min. The virtual impactor produced a lower output than the other two impactors studied, only 1%. A larger proportion of the aerosol output was deposited on corrugated tubing (7%) compared with smooth-walled tubing (1%). The retained fraction of the aerosol inhaled by subjects ranged from 16% to 43%. A higher fraction was retained when subjects inhaled deeply and held their breath for 10 s between each breath. The efficiency of radionuclide deposition from aerosol generator to patient ranged from 1.1% to 6% and was determined more by the retention in the subject than by choice of separator or tubing.