Mismatch between99mTc-DTPA aerosol and81mKr lung ventilation scintigraphy: a pitfall of radionuclide imaging

Pulmonary ventilation and perfusion scintigraphies were performed using^99mTc-MAA,^81mKr, and^99mTc-DTPA aerosol in a patient with asthma. Lung perfusion scintigraphy and^99mTc-DTPA aerosol scintigraphy showed multiple matching defects, however,^81mKr ventilation scintigraphy showed mismatch with lung perfusion scintigraphy. A pitfall of this examination was discussed.     

A simple radioaerosol generator and delivery system for pulmonary ventilation studies

Details of a simple radioaerosol generator and delivery system are presented. Aerosol streams of 99mTc-DTPA solution of different distributions were produced. The most useful distribution had an activity median aerodynamic diameter (AMAD) of 0.9 micron with a geometric standard deviation of 1.5. This distribution also had more than 96% of aerosol particles with aerodynamic diameter less than 2 micron. The system has been used for patient lung ventilation studies. The aerosol breathing-in period to achieve a satisfactory count rate was 1.8 +/- 0.38 min. The radioaerosol images were excellent and comparable to those obtained with 81mKr gas.     

Dry aerosol of monodisperse millimicrospheres for ventilation imaging: production, delivery system, and clinical results in comparison with 81m-krypton and 127-xenon

The production of monodisperse human albumin millimicrospheres (diameter less than 1 micron) and labeling with 99mTc is described. A system constructed to nebulize and deliver a dry aerosol yielded a lung delivery efficiency of approximately 25%. In 48 patients without and with varying degrees of chronic obstructive lung disease, quantitative comparison with 81mKr (penetration index, regional distribution of activity in the lungs) demonstrated similar penetration of the particles to the lung periphery (r = 0.89 and r = 0.94, respectively). Qualitative comparison with 81mKr or 127Xe showed complete or a high degree of diagnostic agreement in all but one patient. Semiquantitative scoring of hot spots as a substrate of local turbulent airflow showed a close inverse correlation (r = -0.82) with the forced expiratory volume in 1 s (FEV 1.0%), thus providing additional information about the severity of the airway obstruction. In 24 patients with suspected pulmonary embolism, complete agreement between aerosol and 81mKr images was found in all patients studied. For same-day ventilation/perfusion studies, labeling of the millimicrospheres with 111In yielded images of comparable quality to those obtained with the 99mTc-labeled aerosol.     

Dual nuclides SPECT for ventilation and perfusion study]

Dual nuclides SPECT using 81mKr and 99mTc-MAA for ventilation and perfusion study was performed in 24 subjects. Crosstalk of 81mKr to 99mTc-energy window was about 7.5% when ventilation and perfusion study were performed by 370 MBq of 81mKr gas and 185 MBq of 99mTc-MAA. Areas of low V/Q was significantly larger in SPECT study than in planar study, in 11 cases with various pulmonary diseases. High V/Q mismatches were also more clearly delineated in SPECT than in planar study. Dual nuclides SPECT study has advantages of obtaining V/Q distribution without movement artifacts and of simultaneous acquisition of ventilation and perfusion image. Area of high V/Q became larger in SPECT with crosstalk than in SPECT without crosstalk, but in the low V/Q area no significant difference was noted between SPECT with crosstalk and without crosstalk.     

A combined procedure for 99mTc aerosol ventilation and perfusion imaging

For several years, radioaerosols have been successfully used to provide detailed images of regional ventilation to aid in the differential diagnosis of pulmonary embolism. It has been widely advocated that the ventilation images should follow the perfusion scan and that the amount of aerosol deposited in the patient's lungs should be three times greater than the perfusion dose. We employed an alternative approach which avoided the deposition of an unpredictable amount of aerosol in individual patients. The aerosol study was performed first, and the activity of the microspheres used for the perfusion images was then tailored to the actual amount of aerosol which the patient had retained. This allowed a microsphere/aerosol activity ratio of 10:1 to be readily achieved, thus successfully masking the ventilation pattern by the perfusion activity. The faster biological clearance of 99mTc-DTPA aerosol from the lung fields, as compared to 99mTc-sulphur-colloid aerosol, allowed higher initial activities to be deposited in the lungs, thus enabling a high-resolution collimator to be used. When the perfusion study was delayed by 1 h (one effective half-life for the 99mTc-DTPA aerosol), it was not necessary to increase the perfusion activity required to mask the ventilation image.     

Tracers for aerosol ventilation scintigraphy: Tc-99m versus In-113m

113mIn has been proposed as a suitable tracer for aerosol ventilation scintigraphy in combination with 99mTc pulmonary perfusion scintigraphy. The high energy (393 keV) of 113mIn allows it to be detected in the presence of 99mTc, but degrades the spatial resolution which can be achieved. We have compared the resolution obtained with 99mTc and 113mIn in phantom experiments and in aerosol ventilation scans in 14 patients with airways disease. The resolution at the distances from the collimator encountered in lung scintigraphy was 10-20 mm for 99mTc and 15-40 mm for 113mIn. Aerosol ventilation images were abnormal in all patients. The 99mTc images showed peripheral defects and frequently central hot spots reflecting increased local aerosol deposition. In the 113mIn images, the lower resolution had a smoothing effect, the central hot spots were less striking, and the distribution of activity appeared more uniform, some detail was lost in the periphery. It is suggested that 113mIn is useful for ventilation scintigraphy in the diagnosis of pulmonary embolism, but that 99mTc is the tracer of choice if aerosol ventilation scintigraphy is used to study airways disease.     

Regional comparison of technetium-99m DTPA aerosol and radioactive gas ventilation (xenon and krypton) studies in patients with suspected pulmonary embolism

The regional distribution of [99mTc]DTPA aerosol was compared with that of 133Xe (n = 30) and krypton (n = 24) in a group of patients with suspected pulmonary embolism. All patients had an aerosol study using a recently available commercial generator system, a ventilation study with one of the gases, and perfusion imaging. Regional information was assessed visually on xenon, krypton, and aerosol studies independently by considering each lung as three equal-sized zones. In addition, gas ventilation findings peripheral to regions of aerosol turbulence ("hot spots") were evaluated. Only 64% of the zones were in complete agreement on xenon and aerosol. Most of the discordance between xenon and aerosol was accounted for by minor degrees of 133Xe washout retention in zones that appeared normal in the aerosol study. An agreement rate of 85% was noted between 81mKr and aerosol regionally. The regions of discordance between aerosol and gas studies, however, usually were associated with unimpressive perfusion defects that did not change the scintigraphic probability for pulmonary embolism in any patient. Regarding zones of aerosol hyperdeposition, 76% had associated washout abnormalities on xenon; however, there was no correlation between the presence of these abnormalities or perfusion abnormalities. The results confirm the high sensitivity of 133Xe washout imaging, but suggest that radioaerosol imaging will detect most parenchymal abnormalities associated with perfusion defects of significance.     

Pulmonary perfusion and ventilation scintigraphies before and after cardiac catheterization in infants with congenital heart diseases

We performed 99mTc-MAA pulmonary perfusion scintigraphies before and after catheterization of 50 infants with congenital heart disease. 81mKr ventilation scintigraphies were also performed in 41 patients. Both right and left heart catheterization (23 patients) and right heart catheterization (27 patients) were performed by Seldinger's method. Pulmonary perfusion scintigraphies showed new perfusion defects in 6 patients (12%) following catheterization. Of six patients, three had ventilation defects. Clinical characteristics, duration of catheterization, hemodynamic variables were not significantly different between patients with and without lung perfusion defects. The lung perfusion defects seemed to be due to pulmonary embolism following cardiac catheterization.     

Generation of parametric images during routine Tc-99m PYP inhalation/Tc-99m MAA perfusion lung scintigraphy. Technical note.

A simple technique is described for generating ventilation/perfusion ratio and perfusion/ventilation ratio images from the posterior Tc-99m PYP aerosol inhalation and Tc-99m MAA perfusion images obtained during routine lung scintigraphy. These images highlight areas of ventilation/perfusion incongruence--mismatch or reverse mismatch--that may sometimes be difficult to detect on conventional images.     

81mKr ventilation and 99mTc perfusion scans in chest disease: comparison with standard radiographs.

In 75 patients with various pulmonary disorders, ventilation and perfusion scans were obtained in multiple views with the 81mKr/99mTc technique and compared with an evaluation of regional ventilation and perfusion derived from the standard chest radiograph. In emphysema, the chest film correlated poorly with ventilation-perfusion scans, showing a trend to underestimate the functional impairment. In chronic bronchitis and asthma, large segmental defects observed on both ventilation and perfusion scans were associated with a normal chest radiograph. Typical findings in pulmonary embolism were segmental defects on perfusion scan with normal ventilation scan and clear lung fields on the chest film. In chronic left heart disease, plain films were inaccurate in predicting alteration of the base-to-apex perfusion gradient observed on the scan.     

Investigation of pulmonary epithelial permeability in patients after hyperbaric oxygen therapy by 99mTc diethylenetriaminepentaacetic acid aerosol inhalation lung scintigraphy

The aim of this study was to evaluate the possibility of pulmonary epithelial permeability damage in patients after hyperbaric oxygen therapy (HBOT) by 99mTc diethylenetriaminepentaacetic acid (99mTc-DTPA) aerosol inhalation lung scintigraphy. Twenty-five controls and 21 patients with normal chest X-rays and no cigarette smoking for at least 1 year were recruited for the study. 99mTc-DTPA aerosol inhalation lung scans were performed after 20 HBOT sessions in 21 patients with refractory osteomyelitis or diabetic foot. The HBOT with 100% oxygen at 2.5 atm absolute for 100 min was performed five times a week. Clearance rates (%/min) of 99mTc-DTPA aerosol in each lung field were calculated from the dynamic images for 30 min. Clearance rates of 99mTc-DTPA aerosol were compared between patients and controls by the unpaired t test. Thirteen patients who had 99mTc-DTPA aerosol lung scans before and after HBOT therapy studies were tested for statistical significance by using the paired t test. There was no statistically significant difference (P>0.05, unpaired t test) between patients and controls in every lung field. For the 13 patients who had 99mTc-DTPA aerosol studies both before and after 20 HBOT sessions, the results also showed no statistically significant difference (P>0.05, paired t test). It is concluded that there was no demonstrable pulmonary epithelial permeability change under current clinical HBOT protocol.     

Ventilation scintigraphy with lipophilic cationic compounds

OBJECTIVE: On the basis of our hypothesis that lipophilic cations may be more suitable for ventilation lung scintigraphy than the conventional technetium-99m diethylenetriamine penta-acetic acid (Tc-DTPA), comparative studies were carried out. BASIC METHODS: The nebulization potential of nine routine radiopharmaceuticals was compared on medical and scintigraphy-specific nebulizers. This was followed by ventilation scintigraphy in 14 patients with chronic obstructive airway disease (n=13) or pulmonary embolism (n=1) where either 99mTc-methoxyisobutylisonitrile (n=10) or Tc-tetrofosmin (n=4) was used. Same-patient comparison with 99mTc-DTPA ventilation scan was available in six patients using the same acquisition protocol. Comparison with 99mTc-DTPA was made with respect to the nebulization rates, radioactivity delivered per unit of radioactivity available for inhalation, and regional distribution of inhaled counts. RESULTS: Lipophilic cation solutions had a significantly higher nebulization rate compared with 99mTc-DTPA using the medical nebulizer (235%, P<0.01) and 370% on scintigraphy-specific nebulizer (P<0.01). More than three times the counts of 99mTc-methoxyisobutylisonitrile or 99mTc-tetrofosmin was deposited in the body compared with Tc-DTPA aerosol per megabecquerel activity inhaled (1.5 vs. 0.4 kcounts/MBq) (P<0.001), preferentially in the lungs (75.2 vs. 65.2%), at the expense of oropharynx and stomach. Within the lungs, about 50% more counts were deposited in the outer one-third lung with lipophilic cations. Overall, therefore, more than 12 times the radioactivity deposition was achieved in the peripheral one-third of the lungs with the lipophilic cations. CONCLUSION: Ventilation lung scanning with lipophilic cations is a viable substitute of nanoparticle scintigraphy (technegas and pertechnegas, which are expensive and technically far more demanding).     

SPECT images after intravenous injection of 99mTc-DTPA in lung tumors--comparison with delayed 123I-IMP lung scintigraphy

The aim of this study was to assess the efficacy of SPECT imaging of the thorax with 99mTc-DTPA, which accumulates at sites of increased capillary permeability and expanded extracellular space, by comparing it with delayed 123I-IMP lung scintigraphy. We have previously reported that increased uptake on delayed 123I-IMP lung scintigraphy was associated with atelectasis and inflammation. Thirteen patients with lung cancer (4 with atelectasis and 3 with pleurisy), one patient with malignant lymphoma complicated by pneumonia and pleurisy, and one patient with pneumonia were studied. 99mTc-DTPA scintigraphy was performed twice, 20-160 minutes and 2-4 hours after the intravenous administration of 370 MBq of 99mTc-DTPA. 123I-IMP scintigraphy was performed 24 hours after the intravenous injection of 111 MBq of 123I-IMP. SPECT images were obtained with both types of scintigraphy. 99mTc-DTPA scintigraphy was compared with 123I-IMP scintigraphy for its ability to detect atelectasis and pneumonia. All patients showed increased accumulation corresponding to the lesions on both 123I-IMP and 99mTc-DTPA scintigraphy. 123I-IMP scintigraphy showed a defect corresponding to the tumor with increased accumulation around the tumor, whereas 99mTc-DTPA scintigraphy showed accumulation corresponding to the tumor. Ten of 11 tumors showed accumulation of an intensity equal to that of the soft tissue of the chest wall on 20-60 min 99mTc-DTPA images. The 2-4 hr images showed that 99mTc-DTPA leaked from the periphery of the tumor toward its center. All the patients with pleurisy showed increased accumulation in effusion on 2-4 hr 99mTc-DTPA scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Tracers for aerosol ventilation scintigraphy: Tc-99m versus In-113m

^113mIn has been proposed as a suitable tracer for aerosol ventilation scintigraphy in combination with ^99mTc pulmonary perfusion scintigraphy. The high energy (393 keV) of^113mIn allows it to be detected in the presence of ^99mTc, but degrades the spatial resolution which can be achieved. We have compared the resolution obtained with ^99mTc and ^113mIn in phantom experiments and in aerosol ventilation scans in 14 patients with airways disease. The resolution at the distances from the collimator encountered in lung scintigraphy was 10–20 mm for ^99mTc and 15–40 mm for ^113mIn. Aerosol ventilation images were abnormal in all patients. The ^99mTc images showed peripheral defects and frequently central hot spots reflecting increased local aerosol deposition. In the ^113mIn images, the lower resolution had a smoothing effect, the central hot spots were less striking, and the distribution of activity appeared more uniform, some detail was lost in the periphery. It is suggested that ^113mIn is useful for ventilation scintigraphy in the diagnosis of pulmonary embolism, but that ^99mTc is the tracer of choice if aerosol ventilation scintigraphy is used to study airways disease.     

Comprehensive ventilation/perfusion SPECT.

Lung scintigraphy is the primary tool for diagnostics of pulmonary embolism. A perfusion study is often complemented by a ventilation study. Intermediate probability scans are frequent. Our goal was to develop a fast method for tomographic ventilation and perfusion scintigraphy to improve the diagnostic value of lung scintigraphy. METHODS: SPECT was performed with a dual-head gamma camera. Acquisition parameters were determined using a thorax phantom. Ventilation tomography after inhalation of 30 MBq (99m)Tc-diethylenetriaminepentaacetate (DTPA) aerosol was, without patient movement, followed by perfusion tomography after an intravenous injection of 100 MBq (99m)Tc-labeled macroaggregated albumin (MAA). Total SPECT acquisition time was 20 min. (99m)Tc-DTPA clearance, calculated from initial and final SPECT projections, was used for correction of the ventilation projection set before iterative reconstruction of ventilation and perfusion. The ventilation background was subtracted from the perfusion tomograms. A normalized ventilation/perfusion quotient (V/P quotient) image set was calculated. The method was evaluated on a trial group of 15 patients. RESULTS: Ventilation and perfusion images had adequate quality and showed ventilation/perfusion (V/Q quotient) relationships more clearly than did planar images. Frontal and sagittal slices were superior to planar scintigraphy for characterization of embolized areas. The V/Q quotient was supportive, particularly in the patients with chronic obstructive pulmonary disease. CONCLUSION: Fast, high-quality, ventilation/perfusion SPECT with standard isotopes doses is feasible and may contribute to higher objectivity in evaluating lung embolism as well as other lung diseases. The costs for the procedure and patient care until diagnosis are low because of the comprehensive system for the study and, particularly, the short time for its completion.     

99mTc particle perfusion/99mTc aerosol ventilation imaging using a subtraction technique in suspected pulmonary embolism

It is generally acknowledged that ventilation-perfusion mismatch is diagnostic of pulmonary embolism. Lung ventilation imaging with radioactive gases is a good method for the detection of pulmonary embolism, but it is not in widespread use because of the limited availability of 81mKr gas and the poor physical properties of 133Xe. Aerosols have been proposed, instead of gases for use in lung ventilation imaging. As perfusion and ventilation distributions may change very rapidly, the two imaging procedures should be done in rapid succession. The cheapest way to perform the combined perfusion-ventilation (Q/V) imaging is to use 99mTc-labelled macroaggregates and aerosols. In our method the perfusion imaging was done first, immediately followed by the ventilation imaging with 99mTc-labelled aerosols. A computer program was used to subtract the contribution of the perfusion from the combined Q/V image so that the pure ventilation image alone was obtained. The method was tested in 41 patients with suspected pulmonary embolism.     

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.     

Lung ventilation/perfusion SPECT in the artificially embolized pig.

Planar lung scintigraphy is a standard method used for the diagnosis of lung embolism, but it is hampered by the high incidence of nondiagnostic tests. Ventilation/perfusion SPECT may possibly improve this situation. The objective of this study was to compare planar lung scintigraphy with ventilation/perfusion SPECT using pigs with artificially engendered lung emboli labeled with (201)Tl. METHODS: Sixteen anesthetized pigs were each injected with zero to 4 latex emboli. Cylindric emboli were used in the first 7 pigs and flat 3-tailed emboli were used in the remaining 9 pigs. The pigs spontaneously inhaled 30 MBq (99m)Tc-diethylenetriaminepentaacetic acid aerosol for ventilation scintigraphy. Planar scintigraphy and SPECT were performed using a double-head gamma camera in (99m)Tc and (201)Tl windows. Immediately thereafter, 100 MBq (99m)Tc-labeled macroaggregated albumin were injected intravenously followed by SPECT and, finally, planar scintigraphy. The ventilation background was subtracted from the perfusion tomograms for calculation of a normalized ventilation/perfusion (V/P) quotient image set. RESULTS: The cylindric emboli caused artifacts in the ventilation images; therefore, these were excluded from the final analysis. However, for the planar perfusion images of these pigs, sensitivity and specificity were 71% and 91%, respectively, whereas SPECT yielded 100% for both. For the 3-tailed emboli and ventilation/perfusion images, the sensitivity and specificity were 64% and 79%, respectively, for the planar modality, whereas SPECT yielded values of 91% and 87%, respectively. CONCLUSION: V/P SPECT may improve the diagnostic power of lung scintigraphy.     

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.