Joint Program in Nuclear Medicine

Lung Uptake of Gallium in ARDS

James P. Strain, MD
David E. Drum, MD PhD

December 14, 1999

Presentation

A 49 year-old, diabetic male was admitted 10 days prior to the scan for debridement of his right foot ulcer. Following the procedure the patient had persistent fevers, leukocytosis and worsening respiratory function. A gallium scan was requested to localize a source of infection.

Imaging Technique

Forty-eight hours following the administration of 6 mCi gallium citrate whole body planar images were obtained. Delayed images were not possible due to the patient's demise.

Imaging Findings

Gallium scintigraphy showed diffuse gallium localization in the lungs (shown by arrows) consistent with unsuspected Acute Respiratory Distress Syndrome (ARDS).
An AP chest radiograph obtained at the same time of the gallium scan showed diffuse bilateral opacity consistent with ARDS.

Differential Diagnosis

Granulomatous Disease (TB, Histoplasmosis, Sarcoid)
Idiopathic Pulmonary Fibrosis
Infection (PCP, CMV, and interstitial pneumonia)
Pneumoconioses (asbestosis, silicosis)
Drug Toxicity (bleomycin, busulfan)
Tumor (lymphoma, leukemia, and metastatic disease)

Diagnosis

Acute Respiratory Distress Syndrome (ARDS)

Discussion

A catastrophic acute lung injury that affects more than 150,000 patients a year, Acute Respiratory Distress Syndrome (ARDS) is a syndrome of inflammation and increased pulmonary alveolar permeability associated with a constellation of clinical, radiologic and physiologic abnormalities. The functional lung injury is identified histologically as diffuse damage to the alveolar-capillary unit. Disruption of the endothelial barrier in the pulmonary alveolocapillary membrane leads to non-cardiogenic pulmonary edema through increased vascular permeability. Gas exchange and mechanical properties of the lung are impaired as fluid fills the alveoli. When functional lung injury is severe, the patient clinically manifests ARDS.

The Consensus Panel Definition of ARDS

In 1994, the American-European Consensus Conference established the defining criteria:

New, bilateral, diffuse, patchy or homogeneous pulmonary infiltrates on radiograph
Occurring in the appropriate clinical setting with one or more recognized risk factors
Without clinical evidence of heart failure, fluid overload or chronic lung disease
(pulmonary arterial occlusion "wedge" pressure <18 mmHg)
Impaired oxygenation defined as the ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) <200 regardless of the level of PEEP

Numerous predisposing factors associated with ARDS are well known. Some etiologies like aspiration or other inhalation injuries act directly. Other causes such as bacterial sepsis or pancreatitis affect the lungs indirectly. In some cases (for example in those patients with gastric aspiration or bacterial sepsis) the risk of ARDS is substantial - up to 30 or 40 percent - and may increase if other associated factors are present. Mortality from ARDS remains above 50 percent and is usually attributed to the underlying predisposing illness, sepsis, or multi-organ failure.

Chest X-ray

In ARDS, bilateral, diffuse pulmonary alveolar opacities usually appear within 24 hours of the first radiographic abnormality. While some investigators have argued that opacity due to ARDS can be distinguish from that of pulmonary edema by a peripheral and non-gravity dependent distribution, these findings have not been uniformly reproducible. The alveolar edema may progress to near total "white-out" of the lungs.

CT

Despite the extensive appearance of the chest opacity by radiograph, CT often reveals patchy areas of infiltrate interspersed with normal-appearing lung. Studies have successfully correlated the extent of lung involvement on CT with the compliance and gas exchange of the lung in the acute and the chronic setting. CT may also reveal complications not detected by the chest film such as pneumothorax, abscess, or empyema.

Gallium Scintigraphy

Although no specific test of acute lung injury and function is available, the integrity of the alveolocapillary membrane can be assessed by measuring the protein content of the alveolar fluid or by measuring the flux of radiolabeled proteins from the blood to the alveolus. Goeneveld et al studied Gallium-67 prospectively in 17 patients as a marker of increased permeability edema to assess the severity and course of ARDS.* Conversely, investigators such as Passamonte strongly believe that interstitial inflammation and repair of pulmonary tissue (and not increased alveolocapillary permeability) are the primary mechanisms of gallium uptake in the lung.

*Goeneveld's Technique: Autologous Tc-99m red-blood cells (300 uCi labeled by a modified in vivo method) were administered ten minutes prior to Gallium-67 citrate injection (100uCi, labeled in vivo). A lung/blood ratio was calculated (Ga-67 lung/Tc-99mlung)/(Ga-67blood/Tc-99mblood) using a probe over each upper lung and peripheral vascular lines.

Probably a combination of both theories is correct since multiple factors are known to affect the localization of gallium. Ga-67 is delivered to tissue by increased blood flow and vessel permeability. Neutrophils accumulate gallium (which is thought to adhere to the plasma surface membrane since uptake remains high even with non-viable cells). In addition to the cellular mechanism, gallium localizes to lactoferrin in the inflammatory exudate. Thus, lung uptake of gallium (as well as the chest radiographic appearance) can be explained by increased vascular permeability, migration of neutrophils to the alveoli, and the resultant inflammatory exudate.

The complex interplay of many mechanisms explains the clinical appearance of gallium scans in ARDS. Excess pulmonary uptake of gallium in ARDS is well documented in the literature. In these case reports, uptake is always bilateral, symmetric, and diffuse throughout the lungs and correlates with the pattern of opacity on radiograph. Pulmonary gallium localization is typically as intense or more intense than liver uptake.

Conclusions

Gallium imaging is important in the diagnosis of ARDS. Often the observation of lung uptake consistent with ARDS is fortuitous and confirms the clinical suspicions of disease. The role of gallium in the prognosis of lung injury remains to be defined.

References

Wyncoll DL, Evans TW. Acute respiratory distress syndrome. Lancet 1999 7;354(9177):497
Kollef MH, Schuster DP. The acute respiratory distress syndrome. NEJM 1995;332(1):27-34
Owens CM, Evans TW, Keogh BJ, Hansell DM. Computed tomography in established adult respiratory distress syndrome. Correlation with lung injury score. Chest 1994;106(6):1815
Groenfeld AB, Raijmakers PG, Eule GJ, Thijs LG. The gallium-67 pulmonary leak index in assessing the severity and course of the adult respiratory distress syndrome. Crit Care Med 1996;24(9):1467-72
Passamonte PM, Marinez AJ, Singh A. Pulmonary gallium concentration in the adult respiratory distress syndrome. Chest 1984;85(6):828-30
Hardoff R et al. Ga-67 lung uptake in patients with adult respiratory distress syndrome: Association with lung infection and patient prognosis. Clin Nucl Med 1992;(17):853-858.

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J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu