Impaired permeability in radiation-induced lung injury detected by technetium-99m-DTPA lung clearance.

UNLABELLED: This study evaluates the use of the 99mTc-DTPA aerosol lung clearance method to investigate radiation-induced lung changes in eight patients undergoing radiotherapy for lung or breast carcinoma. The sensitivity of the method was compared with chest radiography for detecting radiation-induced changes in the lung, regional alterations within (irradiated region) and outside (shielded region) the treatment ports, effect of irradiated lung volume, and dependence on time after radiotherapy. METHODS: Serial DTPA lung clearance studies were performed before the first radiation treatment (baseline), then weekly during a 5- to 7-wk course, and up to 12 times post-therapy over periods of 56-574 days. The total activity deposited in the lungs for each study was approximately 150 microCi (approximately 5.6 MBq). DTPA clearance, expressed in terms of the biological half-time, t 1/2, was computed from the slopes of the least-squares fit regression lines of the time-activity curves for the first 10 min for irradiated and shielded lung regions. RESULTS: Major findings include: (a) significant and early DTPA t 1/2 changes were observed in all patients during and after radiotherapy; (b) changes in DTPA t 1/2 values were observed in both irradiated and shielded lung regions in all patients suggesting a radiation-induced systemic reaction; (c) changes in DTPA t 1/2 values were correlated (p < 0.05) with the irradiated lung volumes; (d) significantly reduced DTPA t 1/2 values were observed in three patients who subsequently presented with clinical symptoms and/or radiographic changes consistent with radiation pneumonitis (t1/2 felt to 19% +/- 6% of baseline values, compared with 64% +/- 17% in the remaining patients [p < 0.01]); (e) the onset of decreased DTPA t 1/2 values in these three patients occurred 35-84 days before clinical symptoms and/or radiographic changes; and (f) DTPA t 1/2 tended to approach baseline values with time after radiotherapy, suggesting a long-term recovery in lung injury. CONCLUSION: These observations show significant and early alterations in DTPA lung clearance during and after radiotherapy that may provide a sensitive assay to monitor changes in radiation-induced lung injury and may facilitate early therapeutic intervention.

Does detoxification reverse the acute lung injury of crack smokers?

The effect on chronic crack users of a 3 month detoxification programme on lung clearance of inhaled 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA) aerosol, spirometry and gas exchange was determined in a controlled in-patient clinical treatment setting. Imaging studies were carried out in eight chronic crack users (four crack-only and four crack plus tobacco) before and after the successful completion of the detoxification programme to measure the clearance of inhaled 99Tcm-DTPA from the lungs, an index of lung epithelial permeability. 99Tcm-DTPA lung clearance, expressed in terms of the biological half-time, T1/2, was determined from the slopes of the least-squares fit regression lines of the respective time-activity plots. The mean (+/- S.D.) global T1/2 values of the crack-only (75 +/- 39 min) and crack plus tobacco users (22 +/- 10 min) were significantly shorter (P < 0.02 and P < 0.001, respectively) than from the lungs of the non-smoking controls (124 +/- 29 min). This was consistent with increased lung epithelial permeability secondary to crack-related lung injury. The mean global T1/2 value of the crack plus tobacco users was significantly shorter (P < 0.05) than that of the crack-only users. After detoxification, the abnormally rapid lung clearance became normal in two of the four crack-only users studied, improved in a third and remained unchanged in the fourth, a subject whose T1/2 value was already normal initially. However, lung clearance improved in only one of the four crack plus tobacco users studied. Faster 99Tcm-DTPA clearance was the only impairment found in seven of the eight crack users, the eighth having restrictive lung disease. Crack-related lung injury, reflected by abnormally rapid 99Tcm-DTPA lung clearance, may be at least partially reversible after a 3 month period of abstinence from crack.

Quantitative 123I IMP and 99mTc HMPAO imaging in the dog following cocaine administration.

SPECT and associated imaging procedures were used in beagle dogs to (1) evaluate the uptake, distribution, and clearance properties of i.v.-injected 123I IMP (IMP) and 99mTc HMPAO (HMPAO) in the brain, lungs, liver, and kidneys; (2) quantify the acute effects (after 15 sec) of very low doses (0.5 or 1.0 mg/kg) cocaine on the kinetics and localization properties of IMP and HMPAO; and (3) evaluate comparative imaging properties of IMP and HMPAO for measuring regional cerebral blood flow (rCBF). Regional and global uptake and localization of IMP or HMPAO were evaluated in control studies using dynamic planar (0-30 min) and SPECT imaging (at 35 min). The regional distribution properties of IMP and HMPAO in the brain were estimated from regions of interest (ROIs) drawn around anatomic structures on MR slices and manually registered with corresponding SPECT slices. Cocaine significantly reduced the 30-min IMP uptake in the brain and lungs by approximately 15%, but only slightly changed HMPAO uptake in the brain and other organs. In the control studies, the respective uptakes of IMP in the brain and lungs were 9 and 39% greater (p < 0.01) than those of HMPAO. In control SPECT studies, the highest uptake of IMP was observed in the thalamus and progressively less activity was observed in the parietal lobe, frontal lobe, cerebellum, occipital lobe, and entire brain; activity in the olfactory bulb was lower than in all other regions. Cocaine reduced IMP uptake in the cerebellum (p < 0.01), occipital lobe (p < 0.01), and entire brain (p < 0.05). IMP uptake (cpm/pixel-mCi) in the different brain regions was 1.3 to 2.1 times greater than that of HMPAO (p < 0.001). HMPAO uptake was more homogeneous throughout the gray matter of the brain; no significant uptake differences were observed among flagged regions. Results indicate that single, acute doses of cocaine, 0.5 and 1.0 mg/kg, significantly altered the uptake and localization properties of IMP in the dog's brain, lungs, liver, and kidneys. Variations in regional uptake of IMP in the parietal, frontal, and occipital lobes, cerebellum, and thalamus were greater than with HMPAO.

Pinhole SPECT: an approach to in vivo high resolution SPECT imaging in small laboratory animals.

UNLABELLED: The performance of pinhole SPECT and the application of this technology to investigate the localization properties of radiopharmaceuticals in vivo in small laboratory animals are presented. METHODS: System sensitivity and spatial resolution measurements of a rotating scintillation camera system are made for a low-energy pinhole collimator equipped with 1.0-, 2.0- and 3.3-mm aperture pinhole inserts. The spatial detail offered by pinhole SPECT for in vivo imaging was investigated in studies of the brain and heart in Fisher 344 rats by administering 201TICI, 99mTc-HMPAO, 99mTc-DTPA and 99mTc-MIBI. Image acquisition is performed using a rotating scintillation camera equipped with a pinhole collimator; projection data are acquired in conventional step-and-shoot mode as the camera is rotated 360 degrees around the subject. Pinhole SPECT images are reconstructed using a modified cone-beam algorithm developed from a two-dimensional fanbeam filtered backprojection algorithm. RESULTS: The reconstructed transaxial resolution of 2.8 mm FWHM and system sensitivity of 0.086 c/s/kBq with the 2.0-mm pinhole collimator aperture provide excellent spatial detail and adequate sensitivity for imaging the regional uptake of the radiopharmaceuticals in tumor, organs and other tissues in small laboratory animals. CONCLUSION: The resolution properties of pinhole SPECT are superior to those which have been achieved thus far with conventional SPECT or PET imaging technologies. Pinhole SPECT provides an important approach for investigating localization properties of radiopharmaceuticals in vivo.

SPECT and planar brain imaging in crack abuse: iodine-123-iodoamphetamine uptake and localization.

The uptake, distribution, and clearance properties of 123I-IMP in the brain were evaluated in controls and asymptomatic crack users to investigate cerebral blood flow alterations in crack abuse. Serial dynamic planar images of the brain (0-25 min), SPECT of the brain (0.5 hr and 4 hr) and whole-body scans (75 min) were obtained in 21 crack abusers and 21 control subjects. Major observations include: (a) foci of abnormally reduced 123I-IMP activity mainly in the frontal and parieto-occipital cortex or marked irregularities in the uptake of 123I-IMP throughout the cerebral cortex consistent with moderate to severe disruption in regional cerebral blood flow were observed on the 0.5 hr SPECT images of 16/21 asymptomatic crack users; (b) no correlation could be demonstrated between the incidence or severity of SPECT perfusion abnormality with the frequency, amount or length of time of crack use; (c) focal perfusion defects observed in 6/21 crack users on the 0.5-hr SPECT images partially or completely filled-in on delayed SPECT at 4 hr in four of six subjects; (d) the rate of cerebral uptake of 123I-IMP in crack users averaged 23% less than observed in control subjects over the first 25 min after tracer administration; and (e) 123I-IMP activity reaching the brain of cigarette smoking control subjects (n = 14) at 25 min after injection averaged 42.5% less than in nonsmoking controls (n = 7). Quantitative measurements of the uptake and distribution properties of 123I-IMP in the brain proved to be an objective, sensitive and useful measure of regional cerebral blood flow in crack abuse.

Lung inflammation in coal miners assessed by uptake of 67Ga-citrate and clearance of inhaled 99mTc-labeled diethylenetriamine pentaacetate aerosol.

We compared the diffuse lung uptake of 67Ga-citrate, an index of inflammatory lung activity, with the lung clearance of inhaled 99mTc-labeled diethylenetriamine pentaacetate (DTPA) aerosol, an index of pulmonary epithelial permeability, in a group of 19 West Virginia coal miners whose pulmonary status was compatible with coal worker's pneumoconiosis. 99mTc-DTPA clearance alone and 67Ga-citrate uptake alone were measured in nine and five additional subjects, respectively. The objective of this study was to determine if increased 99mTc-DTPA lung clearance was caused by inflammation at the lung epithelial surfaces. Subjects inhaled approximately 150 microCi (approximately 5.6 MBq) of 99mTc-DTPA aerosol, and quantitative gamma camera images of the lungs were acquired at 1-min increments for 25 min. Regions of interest (ROI) were selected to include (1) both lungs; (2) each individual lung; and (3) the upper, middle, and lower thirds of each lung. 99mTc-DTPA clearance was determined from the slopes of the respective time-activity plots for the different ROI. Each subject was intravenously administered 50 miCroCk (1.9 MBq)/kg 67Ga-citrate 48 to 72 h before imaging the body between neck and pelvis. The extent of 67Ga-citrate lung uptake was expressed as the gallium index (GI). Mean radioaerosol clearance half-time (T1/2) for the six nonsmoking coal miners (60.6 +/- 16.0 min) was significantly shorter (p less than 0.001) than for the nonsmoking control group (123.8 +/- 28.7 min). T1/2 for the 12 smoking miners (18.4 +/- 10.2 min) was shorter than for the smoking control group (33.1 +/- 17.8 min), but the difference did not attain statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased lung permeability following long-term use of free-base cocaine (crack).

The clearance of inhaled 99mTc DTPA aerosol from the lungs is used as an index of lung epithelial permeability. Using the radioaerosol method, we investigated the effects of long-term "crack" (free-base cocaine) inhalation on lung permeability in 23 subjects. Eighteen control subjects (12 nonsmokers and 6 cigarette smokers) with no history of drug use were also studied. Subjects inhaled approximately 150 muCi (approximately 5.6 MBq) of 99mTc DTPA aerosol and quantitative gamma camera images of the lungs were acquired at 1-min increments for 25 minutes. Regions of interest (ROIs) were selected to include the following: (1) both lungs; (2) each individual lung; and (3) the upper, middle, and lower thirds of each lung. 99mTc DTPA lung clearance was determined from the slopes of the respective time-activity plots for the different RIOs. Radioaerosol clearance half-times (T1/2) for the seven nonsmoking crack users (61.5 +/- 18.3 minutes) were longer than for the seven cigarette-smoking crack users (27.9 +/- 16.9 minutes) and nine cigarette-smoking crack plus marijuana users (33.5 +/- 21.6 minutes). T1/2 for the nonsmoking crack users was significantly shorter (p less than 0.001) than for the nonsmoking control group (123.8 +/- 28.7 minutes). T1/2 for the cigarette-smoking drug users was similar to that of the cigarette-smoking control group (33.1 +/- 17.8 minutes), suggesting a similar mechanism of damage from the smoke of crack and tobacco. From these groups, one nonsmoker and 11 cigarette smokers displayed biexponential 99mTc DTPA clearances, indicative of greater lung injury than found in the usual cases of monoexponential clearance. The upper lungs of all crack users groups cleared faster than the lower lungs. The faster and biexponential clearance properties of inhaled 99mTc DTPA aerosol were the principal functional abnormalities found in all the drug users. In contrast, 19 of 23 crack users had normal spirometry and gas exchange. These results indicate that 99mTc DTPA may provide a sensitive and useful assay to evaluate the physiologic effects of cocaine inhalation in the lung.

Processing of Xe-127 regional pulmonary ventilation by factor analysis and compartmental modeling.

A regional lung ventilation was modeled in five cases using Xe-127 during the first 3 min of wash-out. A factor analysis of the dynamic structures algorithm allowed estimation of the elementary kinetics and their respective proportions contained in time series images. Each factor was interpreted as the sampling of a compartment. It was associated to a factor image representing its spatial distribution and to a percentage of the total collected information. In the study, three factors were estimated: a fast clearance in the lower lung regions (28.9%), a slower clearance in the upper regions (33.4%), and a slow kinetics in blood and tissues containing dissolved xenon (37%). Estimates of the kinematics components obtained from a factor analysis of dynamic structures (FADSs) were used for compartmental analysis. The authors applied this method to the study of the regional ventilation distribution to establish the model and some possible variations. (FADSs) and region of interest results were used for modeling and compared.

Lung scintigraphy clustering by texture analysis.

The efficiency of texture analysis parameters, describing the organization of grey level variations of an image, was studied for lung scintigraphic data classification. Twenty one patients received a 99mTc-MAA perfusion scan and 81mKr and 127Xe ventilation scans. Scans were scaled to 64 grey levels and 100 k events for inter subject comparison. The texture index was the average of the absolute difference between a pixel and its neighbors. Energy, entropy, correlation, local homogeneity and inertia were computed using co-occurrence matrices. A principal component analysis was carried out on each parameter for each type of scan and the first principal components were selected as clustering indices. Validation was achieved by simulating 2 series of 20 increasingly heterogeneous perfusion and ventilation scans. For most of the texture parameters, one principal component could summarize the patients data since it corresponded to the relative variances of 67%-88% for perfusion scans, 53%-99% for 81mKr scans and 38%-97% for 127Xe scans. The simulated series demonstrated a linear relationship between the heterogeneity and the first principal component for texture index, energy, entropy and inertia. This was not the case for correlation and local homogeneity. We conclude that heterogeneity of lung scans may be quantified by texture analysis. The texture index is the easiest to compute and provides the most efficient results for clinical purpose.

Effect of PEEP on regional ventilation and perfusion in the mechanically ventilated preterm lamb.

Improvement of gas exchange through closer matching of regional ventilation (V) and lung perfusion (Q) with the application of positive end-expiratory pressure (PEEP) was evaluated in vivo in six mechanically ventilated preterm lambs (107-126 days/145 days gestation). Changes in V and Q were determined from in vivo scintigraphic measurements in four lung regions with inhaled radioactive 81mKr, and infused 81mKr/dextrose and/or [99mTc]MAA as PEEP was applied at 2, 4, and 6 cm H2O in each animal. Dynamic compliance varied between 0.02 and 0.40 ml/cm H2O, which was consistent with surfactant deficiency. As PEEP was increased, the regional distribution of Q shifted from the rostral to the caudal lung regions (p less than 0.02 to less than 0.05), while that of V remained unchanged. Regional V/Q matching improved together with a trend towards improvement of arterial blood gases as PEEP was increased from 2 to 4 cm H2O. Pulmonary scintigraphy offers a noninvasive methodology for the quantitative assessment of regional V and Q matching in preterm lambs and may be clinically applicable to ventilated neonates.

Heterogeneous ventilation and perfusion: a sensitive indicator of lung impairment in nonsmoking coal miners.

Twenty life-long nonsmoking West Virginia coal-miners participated in a study to amplify the role of focal irregularities on regional ventilation (V) and perfusion (Q) and to develop an improved method for the early detection of coal-workers' pneumoconiosis. Their mean age was 59.3 yr and they averaged 35.2 years' exposure to coal dust. Conventional pulmonary function tests were supplemented by measurement of V, Q and lung volume (V), using radioactive Kr-81m, Tc-99m MAA and Xe-127, respectively, to determine regional abnormalities in lung function. A computer analysis of the regional distributions of V/V, Q/V and V/Q was performed, and their topographical distributions and indices of heterogeneity (HI) computed. V/V and Q/V were significantly reduced in the lower third, and increased in the upper two-thirds of the miners' lungs; V/Q was reduced in the upper half. The miners' V/V and Q/V were more heterogeneous (p less than 0.001) than that of eleven age-matched controls, with mean ventilation HI values of 0.190 +/- 0.027 and 0.133 +/- 0.011, respectively, and mean perfusion HI values of 0.206 +/- 0.022 and 0.164 +/- 0.041, respectively. P(A-a)O2 correlated positively (r = 0.72; p less than 0.001) with ventilation HI. Gas exchange was the most significant functional measurement, being abnormal in 19/20 subjects. In contrast, conventional spirometric measurements were within the predicted normal limits in all but four miners.

Measurement of lung volume with 81Krm in a dynamic scintigram.

The meaning of 81Krm counts obtained in a dynamic series of gated lung ventilation scans was evaluated in terms of flow rate, lung volume, or the flow/volume ratio. Flow and volume signals were recorded together with scintigraphic events in 29 subjects breathing 81Krm and after its decay, 127Xe as a tracer of lung volume. Gated ventilation scans and respiratory signals were reconstructed. Statistical analyses were carried out for linear regressions between total normalized counts detected by the gamma camera and (1) flow rate, (2) lung volume and (3) flow/volume ratio. Inspiration and expiration were analysed separately. For both isotopes, the best correlation was obtained between counts and lung volume (r greater than 0.93). No correlation was obtained between counts and flow rate or flow/volume ratio. Thus, we conclude that 81Krm count variations in gated scans correlate well with tidal volume.

Quantitative comparison of regional distributions of inhaled Tc-99m DTPA aerosol and Kr-81m gas in coal miners' lungs.

Regional distributions of deposited Tc-99m diethylenetriamine pentaacetate aerosol (DPTA) and of Kr-81m were compared in the upright lungs of 22 coal miners with nonembolic pulmonary disease. Pixel-by-pixel distributions of Kr-81m and DPTA corrected for lung volume, as well as DTPA/Kr-81m ratios, were determined by computer analysis in each lung and plotted against lung position. DTPA was preferentially deposited in the basal regions of 36/44 lungs. In the same lungs, Kr-81m was preferentially distributed in the apical regions of 18 lungs, bilaterally in six subjects. Similar DTPA and Kr-81m regional distributions throughout both lungs were obtained in only 11 (50%) subjects. No significant correlations were found between regional particle deposition and pulmonary function measurements. The effects of gravity-related lung pressure gradients and ventilation-related particle residence time on the deposition of DTPA may limit its usefulness when quantitative information is required to evaluate subtle changes in ventilation in nonembolic pulmonary patients and for basic studies of ventilation and perfusion.

Regional distribution of ventilation assessed by Kr-81m scintigraphy employing temporal Fourier transform.

Temporal Fourier analysis was applied to Kr-81m ventilation scintigraphy to determine the amplitude (AMP1) and phase (PHA1) of the first harmonic of a single composite respiratory cycle and to compare regional patterns in subjects with obstructive pulmonary disease (COPD) and nonobstructed subjects. Six nonobstructed subjects, three subjects with small airway disease, six subjects with COPD, and one subject with restrictive disease were investigated. The mean value of the functional PHA1 image (PHA1m) correlated negatively with 1-second forced expiratory volume (FEV1) (r = -0.801, P less than .001), with %FEV1/FVC (r = -0.636, P less than .01) and maximum midexpiratory flow rate (FEF25-75%) (r = -0.723, P less than .002), and correlated positively with residual volume (r = 0.640, P less than .01). PHA1m values for the six subjects with COPD were significantly higher (t = 2.359, P less than .05) than for the ten nonobstructed subjects. Display of phase and amplitude functional images permits a visual evaluation of the regional distribution of ventilation to be made. Regional abnormalities of air flow were detected in obstructed subjects, and the presence of airway obstruction could be predicted. Dynamic ventilation imaging, therefore, appears to be a potentially useful noninvasive technique to assess lung impairment on a localized level.

Effect of respiratory motion on pulmonary activity determinations by positron tomography in dogs.

The effect of respiratory motion on pulmonary activity determinations by positron emission tomography (PET) was studied in dogs with experimentally created pulmonary emboli (PE). The location of the PE was evaluated by planar 99mTc lung imaging to determine the appropriate sites for transaxial PET scans. PET scans of the lung then were obtained after i.v. injection of 68Ga-labeled microspheres. PET scans were acquired during slow (15 breaths/min) and fast (30 breaths/min) breathing with the same minute ventilation and then postmortem. Lung perfusion patterns were documented by i.v. injection of India ink before sacrifice. Cross sections of the excised lungs were made at the same levels as the PET scans, and eight sections containing 14 perfusion defects were analyzed. The scans obtained during slow breathing consistently showed edge blurring and demonstrated defects less well than scans obtained during fast breathing or postmortem. The normal-to-defect activity ratios during fast breathing and on the postmortem studies were similar and approximately 17% higher (P less than .01) than in scans obtained in the same animals during slow breathing. The results demonstrate the need for motion correction during quantitative analysis of regional lung activity by positron tomography, and suggest that high-frequency respiration at small tidal volumes may be one means for obtaining this correction.

Obesity alters regional ventilation in lateral decubitus position.

Alterations of regional ventilation were determined as a function of body position in five morbidly obese subjects using 81mKr to assess ventilation (V) and 127Xe at equilibrium to determine lung volume (V). With subjects in seated and supine positions, the left lung contributed an average of 43% of the total V/V. When the apical-basal gradient within each lung was examined in subjects in the seated position, V/V was greatest in the dependent (basal) regions in half of the subjects, whereas the others showed greater V/V near the upper lung regions. All obese subjects preferentially ventilated the nondependent lung in both the left and right lateral decubitus positions. In a control group of three nonobese subjects, V/V was found to be equally distributed between left and right lungs in both the seated and supine positions. In contrast with the results in the obese group, V/V was slightly greater in the dependent lung in both lateral decubitus positions. Although the combination of 127Xe images and He-dilution measurement of functional residual capacity in the lateral decubitus positions indicated a reduction in the volume of the dependent lung of the obese when compared with values in the seated position, other factors affecting the mechanical function of either the diaphragm or the intercostal muscles could also have produced these positional alterations of ventilation.

Assessment of elastase-induced structural and functional changes in sheep lungs.

A large-animal model of elastase-induced emphysema is being developed, which permits the evaluation of corresponding changes in lung structure and function under controlled conditions. Varying doses of elastase were instilled intrabronchially into the lower right lobes of 12 sheep. Changes in regional distribution of lung perfusion (Q) and ventilation (V), corrected for lung volume, were determined from in vivo measurements with radioactive Tc-99m MAA, Kr-81m and Xe-127, respectively, before and four weeks after elastase treatment. Lung injury was assessed by histological examinations of tissue removed post mortem. A positive correlation (r = 0.74; p less than 0.01) was observed between the dose of instilled elastase (range: 800-8,000 units) and a reduction in Q. A decrease in Q also correlated significantly (r = 0.63; p less than 0.05) with an increase in alveolar mean linear intercept (Lm). V also decreased with increasing dose of elastase and with increasing Lm, but the results did not attain statistical significance. These results suggest that computer analysis of regional Q and V by radionuclide imaging techniques represents a reliable, sensitive and non-invasive means of assessing elastase-induced pulmonary injury in the sheep.