Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED)

To assess the value of perfusion lung scan in the diagnosis of pulmonary embolism, we prospectively evaluated 890 consecutive patients with suspected pulmonary embolism. Prior to lung scanning, each patient was assigned a clinical probability of pulmonary embolism (very likely, possible, unlikely). Perfusion scans were independently classified as follows: (1) normal, (2) near-normal, (3) abnormal compatible with pulmonary embolism (PE+: single or multiple wedge-shaped perfusion defects), or (4) abnormal not compatible with pulmonary embolism (PE-: perfusion defects other than wedge-shaped). The study design required pulmonary angiography and clinical and scintigraphic follow-up in all patients with abnormal scans. Of 890 scans, 220 were classified as normal/or near-normal and 670 as abnormal. A definitive diagnosis was established in 563 (84%) patients with abnormal scans. The overall prevalence of pulmonary embolism was 39%. Most patients with angiographically proven pulmonary embolism had PE+ scans (sensitivity: 92%). Conversely, most patients without emboli on angiography had PE- scans (specificity: 87%). A PE+ scan associated with a very likely or possible clinical presentation of pulmonary embolism had positive predictive values of 99 and 92%, respectively. A PE- scan paired with an unlikely clinical presentation had a negative predictive value of 97%. Clinical assessment combined with perfusion-scan evaluation established or excluded pulmonary embolism in the majority of patients with abnormal scans. Our data indicate that accurate diagnosis of pulmonary embolism is possible by perfusion scanning alone, without ventilation imaging. Combining perfusion scanning with clinical assessment helps to restrict the need for angiography to a minority of patients with suspected pulmonary embolism.     

The use of 99Tcm-Technegas in the investigation of patients with pulmonary thromboembolism

Pulmonary embolism remains a major cause of morbidity and mortality, being responsible for an estimated 200,000 deaths per annum in the USA and 21,000 per annum in the UK. Lung scintigraphy is in many instances the investigation of choice in suspected pulmonary thromboembolism. A normal perfusion lung scan excludes pulmonary embolism. An abnormal perfusion scan, while being sensitive, is of low specificity for the diagnosis of pulmonary embolism and needs to be complemented with a ventilation study. Lung ventilation has been studied using inert gases of radiolabelled aerosols. The new radiopharmaceutical 99Tcm-Technegas is a suspension of 99Tcm-labelled, ultrafine, carbon particles produced in an atmosphere of high-purity argon. The size of the particles is of the order of 0.005-0.2 microns, which assures good peripheral penetration and alveolar deposition. After inhalation, static images in multiple projections may be acquired. The resultant images are of excellent technical quality and several publications have shown the value of Technegas images as an adjunct to perfusion imaging in suspected pulmonary thromboembolism. Studies comparing Technegas images with other ventilatory radiopharmaceuticals have in the majority of instances reported comparable diagnostic qualities.     

Effect of pulmonary artery stenoses on the cardiopulmonary response to exercise following repair of tetralogy of Fallot

Data from exercise tests, echocardiograms, and lung perfusion scans were analyzed to determine whether the excessive minute ventilation (VE) often encountered among patients with tetralogy of Fallot is due to ventilation-perfusion mismatch secondary to branch pulmonary artery stenoses. Patients with branch PA stenoses had lower peak oxygen consumptions and higher VE during exercise than did patients without stenoses, and a strong correlation existed between the degree of pulmonary blood flow maldistribution on lung perfusion scan and the amount of excessive VE during exercise.     

V/Q mismatch without pulmonary emboli in children with histoplasmosis

In two children with histoplasmosis pulmonary perfusion and ventilation studies revealed mismatched abnormalities characterized by almost unilaterally absent perfusion but normal ventilation in the right lung. Chest roentgenograms demonstrated right hilar enlargement and pulmonary contrast angiograms revealed narrowing of the right pulmonary arteries by extrinsic fibrotic granulomata but no pulmonary emboli were present. Fibrosing mediastinitis due to histoplasmosis was found by mediastinoscopic examination in one of the patients. Non-embolic causes of V/Q mismatch lung imaging are discussed briefly, and the correlation with clinical findings is stressed for the diagnosis of pulmonary emboli.     

Hyperlucent lung secondary to homocystinuria

At 23 months of age, one of a pair of monozygotic twins with radiographic unilateral hyperlucent lung was evaluated by radionuclide ventilation/perfusion pulmonary studies, which revealed a ventilation/perfusion mismatch of an entire lung. This twin died, and autopsy revealed pulmonary arterial thrombosis and histological changes compatible with homocystinuria, which was subsequently shown to be present in the surviving twin as well. A ventilation/perfusion lung scan of the surviving twin revealed multiple ventilation/perfusion mismatched defects, suggestive of pulmonary embolism. The presenting manifestation of homocystinuria in these patients was the pulmonary thrombotic disease. Neither twin had any other stigmata of homocystinuria at the time of initial presentation.     

Two cases of Swyer-James syndrome

Case 1: 55-year-old male was admitted to our hospital for further examination of increased transparency of X-ray in the left lower lung. He had history of pneumonia in his childhood. Left bronchography revealed mild cylindrical bronchi-ectasia in the proximal bronchi but poor filling by contrast in the peripheral bronchi. Case 2: 61-year-old male was referred to our hospital with palpitation and dyspnea. Chest X-ray film revealed hyperlucency of the left lower lung. The ventilation scan showed a marked decrease in ventilation to the left lung and air trapping was present in the left lung. The perfusion scan showed a matched decrease in blood supply to the left lung. In both cases, pulmonary arteriogram showed narrowed and withered-tree-like left pulmonary arteries. From these clinical findings, we diagnosed these two cases as Swyer-James syndrome. We are reporting two cases of Swyer-James syndrome and describing the clinical feature, differential diagnosis and etiology of the syndrome.     

Bronchial adenoma resection with relief of hypoxic pulmonary vasoconstriction

Experimental airway obstruction is known to cause reflex pulmonary artery constriction, but clinical documentation of reversible bronchial obstruction and vasoconstriction is rare. A soft bronchial adenoma obstructed the left main bronchus, and scans showed minimal ventilation and perfusion on the left. Gas aspirated from beyond the tumor was hypoxic. The adenoma was removed and the lung left intact by means of a skin graft in the bronchial wall. Four months later, pulmonary function was normal, and both ventilation and perfusion of the left lung were normal. Reflex pulmonary vasoconstriction resulting from alveolar hypoxia minimizes systemic hypoxemia and also minimizes alveolar tissue hypoxia in the lung itself. The reflex is seen most frequently in perfusion scans in patients with chronic airways disease. This case in important in that it documents reversal of vasoconstriction after ventilation was restored.     

Asymmetric distribution of the pulmonary blood flow between the right and left lungs in d-transposition of the great arteries

Pulmonary angiograms, radionuclide lung images and chest roentgenograms were evaluated regarding the incidence, magnitude and natural evolution of maldistribution of the pulmonary blood flow between the lungs in 63 patients with dextrotransposition of the great arteries. Approximately half of these patients had some degree of greater perfusion of the right relative to the left lung. A significant correlation was demonstrated between the incidence of this maldistribution of blood flow and the angulation between the main and the right pulmonary arteries. For any given angulation between these vessels, additional pulmonary stenosis increased the incidence of disparity in perfusion. Our observations suggest the following developmental mechanisms: The maldistribution in flow results from the abnormal rightward inclination of the main pulmonary artery in the transposition malformation which straightens the flow axis from the main to the right pulmonary artery. Under these circumstances the momentum of the blood in the main pulmonary artery carries the blood preferentially into the right pulmonary artery. This momentum is increased when there is stenosis of the left ventricular outflow tract. Consequent differences in the mechanical properties of the two pulmonary vascular beds can increase this maldistribution. The disparity in perfusion between the lungs is not present in newborns with d-transposition, appears to be progressive in severity and in time may result in almost complete cessation of effective perfusion of the left lung. The effect of the Mustard operation on this abnormality of flow is discussed.     

Diagnosis of deep venous thrombosis and pulmonary embolism

Diagnostic evaluation in the patient with suspected deep vein thrombosis (DVT) and pulmonary embolism (PE) includes a clear correlation between clinical probability, test selection and test interpretation. Real-time B-mode ultrasound with color Doppler remains the imaging technique of choice in suspected DVT. The ventilation/perfusion (V/Q) lung scan is the preferred diagnostic modality in suspected PE. The D-dimer assay may be useful in excluding PA. New diagnostic techniques, including spiral computerized tomography may further modify the diagnostic algorithm.     

Seven new cases of Cayler cardiofacial syndrome with chromosome 22q11.2 deletion, including a familial case

Pulmonary lymphangitic carcinomatosis (PLC) is an unusual presentation of diffuse infiltrative lung disease. In this report we present two cases secondary to breast cancer; the diagnosis was made by means of transbronchial lung biopsy or postmortem examination. The goal of this study was to analyze the scintigraphic pattern of pulmonary perfusion performed with technetium-99m macroaggregated albumin (99mTc-MAA) in the hope of achieving improved recognition of PLC and its subsequent diagnosis. Upon admission, both patients underwent routine clinical exams followed by chest X-rays. The second patient also underwent CT examination, and both were ultimately examined using pulmonary perfusion scintigraphy with 99mTc-MAA. In the various exams performed, the most reliable and easily identified diagnostic finding turned out to be a characteristic 'fragmented' lung pattern revealed with the perfusion lung scan. Unfortunately, in both cases the patients' conditions rapidly worsened and death occurred shortly following scintigraphy. We were able to conclude that the recognition of the mentioned fragmented scintigraphic lung pattern may be useful in suspected PLC, whereas the nonspecific clinical presentation of this pathology makes diagnosis extremely difficult, with the most significant results being achieved through a comparison of scintigraphic and high resolution CT data.     

Isolated lung perfusion with doxorubicin prolongs survival in a rodent model of pulmonary metastases

BACKGROUND: We developed a rodent model of unilateral pulmonary metastases to evaluate long-term survival after isolated lung perfusion with doxorubicin. METHODS: In the model development study, on day 0, two groups of F344 rats (n = 15) underwent transient right pulmonary artery occlusion for either 5 or 10 minutes at the time of intravenous injection of methylcholantrene-induced sarcoma cells. On day 14, all animals were sacrificed and lung nodules counted. In the survival study, on day 0, 21 rats received intravenous injection of sarcoma cells with concomitant 10-minute right pulmonary artery occlusion. On day 7, eight rats underwent left isolated lung perfusion with doxorubicin (6.4 mg/kg); five rats underwent perfusion with buffered Hespan; six untreated rats were studied as controls. RESULTS: Ten of fifteen animals (67%) in the model study with 5-minute pulmonary artery occlusion had right-sided tumor nodules. Ten-minute occlusion resulted in a tumor-free right lung in all animals. In the survival study, all animals in the Hespan and control groups died of massive tumor replacement of the left lung, with median survival times of 20 and 18 days, respectively. The median survival time of 36 days for the animals undergoing isolated lung perfusion with doxorubicin was significantly longer (p < 0.00001). The left lung of two of the doxorubicin perfused rats was tumor-free at 6 weeks. CONCLUSIONS: Isolated lung perfusion with doxorubicin results in a durable response and prolongs survival in the treatment of experimental sarcoma pulmonary metastases.     

The efficacy of pulmonary thromboendarterectomy on long-term gas exchange

It has not been delineated in detail how pulmonary thromboendarterectomy (PTE) affects gas exchange through long-term follow-up. In Japan, this surgery has been undertaken in a limited number of institutions, and the results of PTE have not been well publicized. A total of 25 patients were operated on during the period from 1985 to 1996 at our institution, and the overall mortality rate was 16%. Our criteria for PTE were based on the following: 1) thrombi surgically accessible as judged by angiographic study; 2) mean pulmonary arterial pressure > or = 30 mmHg. The efficacies of PTE were analysed on haemodynamics as well as gas exchange at one month postsurgery and during follow-up (6-24 months). Significant haemodynamic improvement was obtained as early as 1 month after surgery. Improvement of gas exchange lagged, but was then observed during follow-up, and the improvement level of pulmonary haemodynamics was sustained. The early postoperative restrictive impairment and ventilation-perfusion abnormality on lung perfusion scan resolved during the follow-up period. It was concluded that the early postoperative efficacy of pulmonary throm-boendarterectomy was mainly achieved due to the reduction of pulmonary hypertension, whereas improvement in gas exchange was obtained over the longer term.     

Evaluation of contrast echocardiography and lung perfusion scan in detecting intrapulmonary vascular dilatation in normoxemic patients with early liver cirrhosis

BACKGROUND/AIMS: Intrapulmonary vascular dilatations (IPVD) are extrahepatic complications occurring in liver transplant candidates, that can result in severe hypoxemia. The aim of this study was to compare the use of two diagnostic modalities, contrast echocardiography and lung perfusion scan, in detecting IPVD in normoxemic patients with early liver cirrhosis. METHODOLOGY: Fifty-six consecutive outpatients with biopsy-proven cirrhosis had contrast-echocardiography, a lung perfusion scan, pulmonary function tests, and arterial blood gas estimations. All patients were grade A or B according to the Child-Pugh classification. Patients with chronic intrinsic lung disease, heart failure or malignancy were excluded from the study. RESULTS: All patients had normal arterial blood-gas analyses. Eight out of 56 patients (14.3%) had a positive contrast echocardiogram, all with a decreased diffusion capacity (DLCO < 75% of the predicted value). An isolated DLCO impairment was observed in 40% of the patients with normal spirometry. None of the patients with echocardiography-proven IPVD had a positive lung perfusion scan (p<0.005). CONCLUSIONS: In normoxemic cirrhotic patients, subclinical pulmonary vasodilatation and gas-exchange abnormalities can occur. Contrast-enhanced echocardiography is the most valuable screening test in detecting IPVD in the early stages of hepatic insufficiency.     

Isolated lung perfusion with melphalan and tumor necrosis factor for metastatic pulmonary adenocarcinoma

BACKGROUND: Isolated left lung perfusion with melphalan and human tumor necrosis factor-alpha for pulmonary metastatic adenocarcinoma in the WAG/Rij rat was studied. METHODS: Survival was determined for melphalan, human tumor necrosis-alpha. Lung, pulmonary effluent, and serum melphalan were analyzed by chromatography after isolated lung perfusion or intravenous injection. On day 0, rats were injected with 2.0 x 10(6) CC531S cells intravenously. On day 7, rats underwent sham thoracotomy, received melphalan intravenously, or underwent isolated left lung perfusion with saline, melphalan, tumor necrosis factor, and a combination of the latter two. On day 14, tumor nodules were counted. RESULTS: For the doses of 400 microg tumor necrosis factor, 1,000 microg tumor necrosis factor, or both melphalan and tumor necrosis factor (2 mg + 200 microg), survival rates after contralateral pneumonectomy were 33%, 17%, and 80%, respectively. Survival in all other groups was 100%. Left lung melphalan level was significantly higher after isolated lung perfusion compared to intravenous administration. Significantly fewer left lung nodules were found for 0.5 mg isolated lung perfusion with melphalan (28+/-17) compared to isolated administration (200+/-0) (p = 0.001), and for 1.0 mg intravenous lung perfusion with melphalan (16+/-10) compared to controls (171+/-65) (p = 0.00047). Tumor necrosis factor showed no significant effect. CONCLUSIONS: Isolated lung perfusion with melphalan is an effective treatment for pulmonary metastases from adenocarcinoma in the rat.     

Comparison between morphologic changes seen on high-resolution CT and regional pulmonary perfusion seen on SPECT in patients with cystic fibrosis

OBJECTIVE: To evaluate the relationship between morphologic findings seen on high-resolution computed tomography (HRCT) of the lung and regional lung perfusion depicted on single photon-emission computed tomography (SPECT) pulmonary perfusion imaging in patients with cystic fibrosis. MATERIALS AND METHODS: Ten HRCT and 10 technetium-99 m macroaggregated albumin SPECT pulmonary perfusion imaging studies were performed on eight young adult patients who were considered to be clinically well and have mild to moderate cystic fibrosis. HRCT scans of the chest were evaluated using a CT scoring system which included grading of bronchiectasis, peribronchial thickening, hyperlucency, bullae, collapse/consolidation, and mucus plugging. Each lung was divided into six anatomic zones which were independently scored. A lung perfusion score (between 0 and 100), reflecting the percentage of compromised lung, was estimated for each zone. Axial lung perfusion SPECT images were matched anatomically to HRCT images. Lung function was considered compromised when the counts per pixel were less than 25 % of the count level seen in an area of the same patient's lung which was judged to be normal. RESULTS: There was a statistically significant relationship (P = 0.0001) between HRCT total scores and SPECT lung perfusion scores as well as between hyperlucency scores by HRCT and the SPECT lung perfusion scores. However, the HRCT score was a poor predictor of the lung perfusion score in zones with intermediate HRCT scores, which constituted 106 of 120 zones. CONCLUSION: Morphologic changes depicted by HRCT correlate with decreased lung pefusion on SPECT. However, HRCT changes accurately predict regional lung function only in the most normal and severely diseased lung zones.     

Stratification of patients according to prior cardiopulmonary disease and probability assessment based on the number of mismatched segmental equivalent perfusion defects. Approaches to strengthen the diagnostic value of ventilation/perfusion lung scans in acute pulmonary embolism

A categorical diagnosis of "high probability" or "intermediate probability" encompasses a spectrum of diagnostic probabilities of pulmonary embolism (PE) that is not communicated to the referring physician. The diagnostic value of ventilation/perfusion lung scans, in the present investigation, was strengthened by use of a table to determine the likelihood of PE in individual patients on the basis of the observed number of mismatched segmental equivalent perfusion defects. In addition, we tested the hypothesis that stratification of patients according to the presence or absence of prior cardiopulmonary disease may enhance the ventilation/perfusion scan assessment of the probability of PE among both of these clinical categories of patients. Data were derived from the collaborative study of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). Ventilation/perfusion lung scans were evaluated in 378 patients with acute PE and 672 patients in whom suspected PE was excluded. Among patients with no prior cardiopulmonary disease, > or = 1.0 mismatched segmental equivalents was indicative of PE in 102 of 118 (86 percent) vs 113 of 155 (73 percent) among patients with prior cardiopulmonary disease (p < 0.02). Among patients with prior cardiopulmonary disease, > or = 2 mismatched segmental equivalents were required to indicate > or = 80 percent probability of PE. Stratification on the basis of the presence or absence of prior cardiopulmonary disease, therefore, enhanced the ability of ventilation/perfusion scan readers to assign an accurate positive predictive value and specificity to individual patients based on the observed number of mismatched segmental equivalent defects. Among patients with no prior cardiopulmonary disease, fewer mismatched segmental equivalent defects were required to indicate a high probability of PE than were required by PIOPED criteria. The findings from some of these patients, by PIOPED criteria, would have indicated intermediate probability. Some indeterminate probability readings, therefore, will be eliminated among patients stratified with no prior cardiopulmonary disease.     

Neovascularization and HGF: neovascularization in proliferative diabetic retinopathy and intraocular HGF

We experienced a case of multiple bilateral giant bullae of the lungs and treated by thoracoscopic bilateral resection. A 46-year-old male was admitted to our hospital on the diagnosis of bilateral giant bullae of the lungs. Chest CT scan and lung perfusion scintigraphy showed giant bullae at the apex of both lungs and at the left lower lobe. The border of the bullae was relatively clear, and the other lung was almost normal although it was compressed by the bullae. We evaluated this case and found that it was a good indication for a thoracoscopic bilateral resection. The patient was positioned on his back, and a successful thoracoscopic bilateral resection was performed. The patient was discharged from the hospital on the 10th day postoperatively. Chest CT scan, lung perfusion scintigraphy and respiratory function test performed 2 months postoperatively, showed remarkable improvement. We would recommend this surgical technique in patients with similar diagnosis.     

Study on antifertility effect of a novel LHRH antagonist in male rats

The diagnosis of pulmonary embolism is even in contemporary clinical practice problematical. Pulmonary angiography is used in our departments very little due to its invasive character. The method of choice for diagnosis remains therefore perfusion scintigraphy of the lungs, in this country frequently without ventilation scintigraphy as it is not available in the majority of our departments of nuclear medicine. In recent years in the diagnostic algorithms also assessment of D-dimers was started, i.e. assessment of products of fibrinolysis assessed by monoclonal antibodies. The authors tried to find out how many patients admitted to the medical department for diagnosis of pulmonary embolization may have a false positive diagnosis on the basis of pulmonary scintigraphy. During the period III/96 to V/96 a total of 18 patients from the medical clinic with suspected pulmonary embolism were examined where the value of D-dimers(latex test) was assessed and at the same time perfusion scintigraphy was performed. With regard to the highly negative predictive value of D-dimer assessment the authors focused their attention on patients with a suspect or positive lung scan (i.e. treated on account of pulmonary embolism) while D-dimers were negative. Of 13 patients with suspect or possible pulmonary embolism, as assessed by scintigraphy, four had negative dimers(30%). With regard to the 90% reported negative predictive value, based on the literature, thus three of these patients were unnecessarily admitted to hospital and treated. The authors assume that assessment of D-dimers should be part of the examination protocol due to its non-pretentious character and low price as compared with costs of hospitalization.     

Clinical diagnosis and management of the patient with deep venous thromboembolism and acute pulmonary embolism

Pulmonary embolism is the third most common acute cause of death in the United States. There are approximately 500,000 cases annually in this country, leading to death in 50,000. Subjective symptoms and objective findings can oftentimes be confusing and nonspecific. A pulmonary embolism is defined as an occlusion of one or more pulmonary vessels by material that has traveled there from outside of the lung and is usually caused by a dislodged thrombus that originated in the deep veins of the legs or pelvis. Risk factors include older age, prior thromboembolism, immobility, cancer, chronic disease, congestive heart failure, pelvic and lower extremity surgery, varicosities, obesity, and oral contraception. This article will discuss current modalities that are used in the evaluation of deep venous thromboembolism and pulmonary embolism and include ventilation/perfusion scan, ultrasonography, impedance plethysmography, pulmonary angiography, and newer tests including D-dimer assays and spiral computed tomography. Medical management including simple and complex decision making, anticoagulation, and thrombolytic therapy will also be discussed. An ounce of prevention is worth a pound of gold--identification of risk factors and the use of appropriate therapeutic measures can reduce an individual's risk for deep venous thromboembolism and pulmonary embolism.     

Evaluation of pulmonary vascular anatomy and blood flow by magnetic resonance

Rapidly evolving magnetic resonance (MR) imaging techniques provide noninvasive approaches to evaluating morphology and quantitative physiologic information about blood flow in the pulmonary circulation. Important clinical applications currently include the preoperative and postoperative evaluation of congenital abnormalities, assessment of vascular involvement by extrinsic and intrinsic tumors, identification of central thromboemboli, and diagnosis of vascular lung lesions. Ongoing refinements in pulmonary MR angiography may make it possible to use the technique for the noninvasive detection of acute pulmonary emboli in the near future. Quantitative measurements based upon MR flow-encoding sequences are promising for the evaluation of patients with abnormal degrees or distributions of pulmonary blood flow, for example, those with unilateral lung transplants or pulmonary arterial stenoses. MR contrast agents currently under development also show promise for quantitative measurements of regional pulmonary ventilation and perfusion. The coupling of high-resolution anatomic and functional images renders MR a uniquely attractive and powerful method for evaluating the pulmonary vasculature.