**6.1 Chronic obstructive pulmonary disease**

COPD is a major cause of both morbidity and mortality globally (Mannino et al., 2006). It is one of the few diseases that continues to rise in numbers in many countries. COPD is an inflammatory disease characterized by airflow limitation that is not fully reversible (Celli & MacNee, 2004). The airflow limitation is caused by a combination of airway obstruction and parenchymal destruction (emphysema). The pulmonary changes in COPD lead to inhomogeneous regional ventilation. V/P SPECT is sufficiently sensitive as a method to identify the functional changes in COPD. In comparison with DTPA aerosols, Technegas penetrates the lung periphery better (Jögi et al., 2010), which is especially important in COPD (exemplified in Fig 3). Technegas ventilation imaging has been shown to visualise the early changes of COPD before they can be observed with high resolution CT (HRCT) (Yokoe et al., 2006). As COPD initially affects the airways, the ventilation defects are commonly more prominent than those of perfusion. Perfusion within the lungs also becomes abnormal as the lungs attempt to adapt the regional blood flow to ventilation to preserve an efficient gas exchange. Often this adaptation is incomplete and perfused but non-ventilated areas (low V/P ratio) occur, i.e. reverse mismatch (Gottschalk et al., 1993). With progressive disease, concurrent destruction of airways and blood vessels takes place and matched defects with absence of both ventilation and perfusion are seen. Vascular remodeling in COPD may lead to regions with elevated V/P ratios. Garg et al. (1983) found that the degree of abnormality on aerosol ventilation images significantly correlated to pulmonary function tests. In a recent paper, which evaluated the role of V/P SPECT in patients with COPD, it was shown that V/P SPECT correlated significantly both to traditional lung function tests as well as the extent of emphysema as measured with HRCT (Jögi et al., 2011). It was also shown that V/P SPECT could be used to characterize the severity of COPD. Pulmonary embolism and heart failure are common comorbidities with overlapping symptoms that

Quantitative Ventilation/Perfusion Tomography:

perfusion.

treatment

**6.3 Pneumonia** 

The Foremost Technique for Pulmonary Embolism Diagnosis 197

"cephalization" of the normal dependent distribution of blood flow (Friedman & Braunwald, 1966; West et al., 1964). The inverted distribution of blood flow to nondependent lung zones seen in heart failure has been correlated to elevated pulmonary venous pressure, interstitial oedema, alveolar space flooding and, when longstanding, perivascular fibrosis (Mohsenifar et al., 1989; Pistolesi et al., 1988). Ventilation is not affected to the same degree as perfusion and mismatch in the dependent lung is therefore common. This mismatch, however, is not of a segmental character. V/P SPECT can therefore identify patients with congestive heart failure. In a study of 247 patients examined with V/P SPECT for suspected PE, we found that 15% of the patients had signs of heart failure, sometimes in combination with PE (Jögi et al., 2008). Figure 8 shows a patient who suffered from increasing breathlessness. V/P SPECT was performed to exclude PE. V/P SPECT in supine position identified redistribution of ventilation and perfusion towards ventral regions (Fig 8a). Perfusion is more affected than ventilation and mismatch is therefore observed. This is, however, non-segmental and the diagnosis was therefore reported as heart failure and not PE. After 12 days of anticongestive treatment, the patient had improved clinically and the follow-up V/P SPECT (Fig 8b) showed complete normalization of both ventilation and

Fig. 8. Patient with acute heart failure. A) In the supine patient, perfusion is redistributed to anterior parts of the lung. Ventilation is also affected but not to the same degree, which causes non-segmental perfusion defects. **B)**. Follow up after 12 days of anticongestive

Pneumonia is an inflammatory condition of the lung parenchyma, especially affecting the alveoli. There are both infectious and non-infectious causes. The pneumonic regions of the lung become non-ventilated although the blood flow is often maintained to some extent. This can cause shunting and lead to hypoxemia. As the ventilation defect often exceeds the perfusion defect, reverse mismatch is a common finding (Carvalho & Lavender, 1989). In a study by Li et al. (1994) reverse mismatch represented pneumonia in 81% of the cases. In

complicate the manifestation of COPD. The prevalence of PE in patients hospitalized with exacerbation has been reported to be as high as 25% but is generally under-diagnosed (Mispelaere et al., 2002; Tillie-Leblond et al., 2006). In patients with stable COPD, PE accounts for 10% of deaths (Schonhofer & Kohler, 1998). The prevalence of heart failure among patients with stable COPD has been reported to be about 20% and even higher in patients with exacerbation (Rizkallah et al., 2009; Rutten et al., 2006). The previous finding of the PIOPED study that V/P scintigraphy cannot be used to diagnose PE among patients with pathology of ventilation is an outdated belief (1990). Figure 7 shows extensive PE in a patient with COPD. This heavy smoker had a short history of progressive dyspnea. V/P SPECT showed uneven ventilation and perfusion with a pattern that is typical for COPD. Moreover, extensive perfusion defects were seen in areas with preserved ventilation. V/P quotient images could be used to quantify the extent of PE to approximately 70% of the lung parenchyma.

Fig. 7. Patient with severe COPD and chronic PE. Frontal slices; ventilation is very uneven in the whole lung. In addition, multiple perfusion defects are seen in ventilated areas. Mismatches are highlighted in V/Pquotient images.

#### **6.2 Heart failure**

Left heart failure is a complex clinical syndrome that can result from any cardiac disorder that affects the ability of the left ventricle to function as a pump. When the left chamber is unable to meet the functional demands of the body, symptoms such as dyspnea and fatigue, as well as signs of pulmonary fluid retention appear. In patients with heart failure the risk of developing venous thromboembolic disease, including PE, is elevated (Anderson & Spencer, 2003). As early as the 1960s, Friedman and Braunwald, West and others demonstrated that patients with mitral valve disease and left heart failure showed an inversion or

complicate the manifestation of COPD. The prevalence of PE in patients hospitalized with exacerbation has been reported to be as high as 25% but is generally under-diagnosed (Mispelaere et al., 2002; Tillie-Leblond et al., 2006). In patients with stable COPD, PE accounts for 10% of deaths (Schonhofer & Kohler, 1998). The prevalence of heart failure among patients with stable COPD has been reported to be about 20% and even higher in patients with exacerbation (Rizkallah et al., 2009; Rutten et al., 2006). The previous finding of the PIOPED study that V/P scintigraphy cannot be used to diagnose PE among patients with pathology of ventilation is an outdated belief (1990). Figure 7 shows extensive PE in a patient with COPD. This heavy smoker had a short history of progressive dyspnea. V/P SPECT showed uneven ventilation and perfusion with a pattern that is typical for COPD. Moreover, extensive perfusion defects were seen in areas with preserved ventilation. V/P quotient images could be used to quantify the extent of PE to approximately 70% of the lung

Fig. 7. Patient with severe COPD and chronic PE. Frontal slices; ventilation is very uneven in

Left heart failure is a complex clinical syndrome that can result from any cardiac disorder that affects the ability of the left ventricle to function as a pump. When the left chamber is unable to meet the functional demands of the body, symptoms such as dyspnea and fatigue, as well as signs of pulmonary fluid retention appear. In patients with heart failure the risk of developing venous thromboembolic disease, including PE, is elevated (Anderson & Spencer, 2003). As early as the 1960s, Friedman and Braunwald, West and others demonstrated that patients with mitral valve disease and left heart failure showed an inversion or

the whole lung. In addition, multiple perfusion defects are seen in ventilated areas.

Mismatches are highlighted in V/Pquotient images.

**6.2 Heart failure** 

parenchyma.

"cephalization" of the normal dependent distribution of blood flow (Friedman & Braunwald, 1966; West et al., 1964). The inverted distribution of blood flow to nondependent lung zones seen in heart failure has been correlated to elevated pulmonary venous pressure, interstitial oedema, alveolar space flooding and, when longstanding, perivascular fibrosis (Mohsenifar et al., 1989; Pistolesi et al., 1988). Ventilation is not affected to the same degree as perfusion and mismatch in the dependent lung is therefore common. This mismatch, however, is not of a segmental character. V/P SPECT can therefore identify patients with congestive heart failure. In a study of 247 patients examined with V/P SPECT for suspected PE, we found that 15% of the patients had signs of heart failure, sometimes in combination with PE (Jögi et al., 2008). Figure 8 shows a patient who suffered from increasing breathlessness. V/P SPECT was performed to exclude PE. V/P SPECT in supine position identified redistribution of ventilation and perfusion towards ventral regions (Fig 8a). Perfusion is more affected than ventilation and mismatch is therefore observed. This is, however, non-segmental and the diagnosis was therefore reported as heart failure and not PE. After 12 days of anticongestive treatment, the patient had improved clinically and the follow-up V/P SPECT (Fig 8b) showed complete normalization of both ventilation and perfusion.

Fig. 8. Patient with acute heart failure. A) In the supine patient, perfusion is redistributed to anterior parts of the lung. Ventilation is also affected but not to the same degree, which causes non-segmental perfusion defects. **B)**. Follow up after 12 days of anticongestive treatment

### **6.3 Pneumonia**

Pneumonia is an inflammatory condition of the lung parenchyma, especially affecting the alveoli. There are both infectious and non-infectious causes. The pneumonic regions of the lung become non-ventilated although the blood flow is often maintained to some extent. This can cause shunting and lead to hypoxemia. As the ventilation defect often exceeds the perfusion defect, reverse mismatch is a common finding (Carvalho & Lavender, 1989). In a study by Li et al. (1994) reverse mismatch represented pneumonia in 81% of the cases. In

Quantitative Ventilation/Perfusion Tomography:

**9. References** 

The Foremost Technique for Pulmonary Embolism Diagnosis 199

The above mentioned advantages of V/P SPECT for studying PE lead to the conclusion that it is the only suitable technique both for follow-up in patients with PE as well as for

Anderson, F.A., Jr., and Spencer, F.A. (2003). Risk factors for venous thromboembolism.

Bajc, M., Albrechtsson, U., Olsson, C.G., Olsson, B., and Jonson, B. (2002a). Comparison of

Bajc, M., Bitzen, U., Olsson, B., Perez de Sa, V., Palmer, J., and Jonson, B. (2002b). Lung

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Bajc, M., Olsson, C.G., Olsson, B., Palmer, J., and Jonson, B. (2004). Diagnostic evaluation of

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Celli, B.R., and MacNee, W. (2004). Standards for the diagnosis and treatment of patients

Elliott, C.G., Goldhaber, S.Z., Visani, L., and DeRosa, M. (2000). Chest radiographs in acute

Friedman, W.F., and Braunwald, E. (1966). Alterations in regional pulmonary blood flow in

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ventilation/perfusion scintigraphy and helical CT for diagnosis of pulmonary embolism; strategy using clinical data and ancillary findings. *Clin Physiol Funct* 

ventilation/perfusion SPECT in the artificially embolized pig. *J Nucl Med*, Vol. 43,

EANM guidelines for ventilation/perfusion scintigraphy : Part 1. Pulmonary imaging with ventilation/perfusion single photon emission tomography. *Eur J Nucl* 

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severe cases both ventilation and perfusion are reduced or abolished and matched defects are then frequently found (Li et al., 1994). Another sign of pneumonia that often has been described is the "stripe sign" (Sostman & Gottschalk, 1982, 1992). The "stripe sign" refers to the observation of a stripe of a relatively well preserved perfusion adjacent to the pleural surface, by contrast with the more pronounced perfusion defects within the pneumonic lesion. This distinguishes pneumonia from the segmental perfusion defects found in PE. The enhanced performance of V/P SPECT compared to planar imaging has facilitated the detection of the stripe sign (Pace & Goris, 1998).

Hampson as well as the ICOPER study illustrated that the risk of PE is increased in patients with pneumonia or other coexisting diseases (Elliott et al., 2000; Hampson, 1995). In the ICOPER study, 17% of 2000 patients with confirmed PE had infiltrates on chest X-ray. Pneumonia has also been shown to be a common finding in patients with autopsy proven PE (Mandelli et al., 1997).
