Abstract
In this chapter, we present a brief review of the anatomy, physiology, and pathophysiology of main relevant diseases. This will lay the ground for a more in-depth presentation of the pathophysiological basis for use of nuclear medicine techniques in disease diagnosis. This will be discussed in the context of radiopharmaceuticals commonly used to diagnose respiratory diseases followed by correlation of the patterns of radiotracer distribution as seen in nuclear scintigraphy with the pathophysiology of the disease process. The different scintigraphic methods will be explained along with relevant clinical applications.
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References
Brashers BL, Davey SS (1998) Structure and function of the pulmonary system. In: McCance KL, Huether SE (eds) Pathophysiology, the biologic basis for disease in adults and children, 3rd edn. Mosby, St Louis, pp 1131–1157
Thibodeau GA, Patton KI (1996) Anatomy and physiology, 3rd edn. Mosby, St Louis
De Nardo GL, De Nardo SJ (1984) Thelungs. In: Freeman LM, Johnson PM (eds) Clinical radionuclide imaging, 3rd edn. Grune and Stratton, Orlando, pp 1051–1139
Elgazzar AH (1997) Scintigraphic diagnosis of pulmonary embolism: unraveling the confusion seven years after PIOPED. In: Nuclear medicine annual. Lippincott, Raven, pp 69–101
Raskob GE, Angchaisuksiri P, Blanco AN, Buller H, Gallus A, Hunt BJ, Hylek EM, Kakkar A, Konstantinides SV, McCumber M, Ozaki Y, Wendelboe A, Weitz JI (2014) Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol 34:23632371
Anderson FA Jr, Zayaruzny M, Heit JA, Fidan D, Cohen AT (2007) Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism. Am J Hematol 82:777–782
Turetz M, Sideris AT, Friedman OA, Triphathi N, Horowitz JM (2018) Pulmonary embolism: epidemiology, pathophysiology, and natural history of pulmonary embolism. In: Seminars in interventional radiology, vol 35, No. 2. Thieme Medical Publishers, New York, p 92
Kucher N, Tapson VF, Goldhaber SZ, DVT FREE Steering Committee (2005) Risk factors associated with symptomatic pulmonary embolism in a large cohort of deep vein thrombosis patients. Thromb Haemost 93:494–498. https://doi.org/10.1160/TH04-09-0587. PMID: 15735800
Stein PD, Matta F, Musani MH, Diaczok B (2010) Silent pulmonary embolism in patients with deep venous thrombosis: a systematic review. Am J Med 123(5):426–431
Frieman DG, Suyemoto J, Wessler S (1965) Frequency of pulmonary thromboembolism in man. N Engl J Med 272:1278–1280
McLachlin J, Patterson JC (1961) Some basic observations on venous thrombosis and pulmonary embolism. Surg Gynecol Obstet 93:1–8
Moser KM (1990) Venous thromboembolism: state-of-the-art. Am Rev Respir Dis 141:235–249
Muñoz FJ, Mismetti P, Poggio R et al (2008) Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry. Chest 133(1):143–148
Palevsky HI, Alavi A (1991) Noninvasive strategy for management of patients suspected of pulmonary embolism. Semin Nucl Med 21:325–331
Miesbach W, Makris M (2020) COVID-19: coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin Appl Thromb Hemost 26:1076029620938149. https://doi.org/10.1177/1076029620938149. PMID: 32677459; PMCID: PMC7370334
Kipshidze N, Dangas G, White CJ, Kipshidze N, Siddiqui F, Lattimer CR, Carter CA, Fareed J (2020) Viral coagulopathy in patients with COVID-19: treatment and care. Clin Appl Thromb Hemost 26:1076029620936776. https://doi.org/10.1177/1076029620936776
Salabei JS, , Fishman TJ, Asnake ZT, Ali A, Iyer UG, et al (2021). COVID-19 coagulopathy: current knowledge and guidelines on anticoagulation. Heart Lung; 50: 357–360
Colling ME, Kanthi Y (2020) COVID-19-associated coagulopathy: an exploration of mechanisms. Vasc Med 25:471–478
Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B (2020) Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: a systematic review and meta-analysis. EClinicalMedicine 29–30:100639
Akel T, Qaqa F, Abuarqoub A, Shamoon F (2020) Pulmonary embolism: a complication of COVID 19 infection. Thromb Res 193:79–82
Bĕlohlávek J, Dytrych V, Linhart A (2013) Pulmonary embolism, part I: epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism. Exp Clin Cardiol 18(2):129–138
Kamel E, Mckee T, Calcagni M, Schmidt S, Markl S, Bischof Delaloye A (2005) Occult lung infarction may induce false interpretation of F19 FDG PET in primary staging of pulmonary malignancies. Eur J Nucl Med Mol Imaging 32:641–646
Manny J, Hechtman HB (1985) Vasoactive humoral factors. In: Goldhaber SZ (ed) Pulmonary embolism and deep venous thrombosis. Saunders, Philadelphia, p 283
Dass H, Hcekscher T, Anthonisen NR (1967) Regional pulmonary gas exchange in patients with pulmonary embolism. Clin Sci 33:355–364
Smith R, Alderson PO (1987) Ventilation perfusion scintigraphy in pulmonary embolism in pulmonary nuclear medicine. In: Loken MK (ed) Pulmonary nuclear medicine. Appleton and Lange, Norwalk, pp 51–79
Wolfe MW, Skibo LK, Goldhaber SZ (1993) Pulmonary embolic disease: diagnosis, pathophysiologic aspects and treatment with thrombolytic therapy. Curr Probl Cardiol XVIII:587–633
National Heart, Lung and Blood Institute (1970) Urokinase pulmonary embolism trial – phase I results. JAMA 214:2163–2172
National Heart, Lung and Blood Institute (1974) Urokinase pulmonary embolism trial – phase II results. JAMA 229:1606–1613
Elgazzar AH, Jobalia R, Subramanian P, Ryan J, Hughes JA (1994) Multiple ventilation and perfusion (V/Q) scans in patients with and without pulmonary emboli (PE). J Nucl Med 35:239
Klok FA, Mos IC, van Kralingen KW, Vahl JE, Huisman MV (2012) Chronic pulmonary embolism and pulmonary hypertension. Semin Respir Crit Care Med 33:199–204
Hoeper MM, Mayer E, Simonneau G, Rubin LJ (2006) Chronic thromboembolic pulmonary hypertension. Circulation 110:2011–2020
PIOPED Investigators (1990) Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 263:2753–2759
Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J Jr, Hobbins TE et al (1992) The clinical course of pulmonary embolism. N Engl J Med 326:1240–1245
Schober B (1980) Do pulmonary emboli lodge preferentially in prior foci? J Nucl Med 21:659–661
Hoffman JM, Lee A, Grafton S, Bellamy P, Hawkins RA, Webner M (1994) Clinical signs and symptoms in pulmonary embolism. A reassessment. Clin Nucl Med 19:803–808
Stein PD, Terrin ML, Hales CA, Palevsky HI, Saltzman HA, Thompson BT, Weg JG (1991) Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. Chest 100:598–603
Stein PD, Henry JW (1997) Prevalence of acute pulmonary embolism in central and subsegmental pulmonary arteries and relation to probability interpretation of ventilation/perfusion lung scans. Chest 111:1246–1248
Morgenthaler TI, Ryu JH (1995) Clinical characteristics of fatal pulmonary embolism in a referral hospital. Mayo Clin Proc 70:417–424
Morpurgo M, Schmid C (1995) The spectrum of pulmonary embolism. Clinicopathologic correlations. Chest 107:18S–20S
Sperry KL, Key CR, Anderson RE (1990) Towards a population-based assessment of death due to pulmonary embolism in New Mexico. Hum Pathol 21:159–165
Karwinski B, Svendsen E (1989) Comparison of clinical and postmortem diagnosis of pulmonary embolism. J Clin Pathol 42:135–139
Gross JS, Neufeld RR, Libow LS, Gerber I, Rodstein M (1988) Autopsy study of the elderly institutionalized patient: review of 234 autopsies. Arch Intern Med 1:173–176
Dismuke SE, Wagner EH (1986) Pulmonary embolism as a cause of death. JAMA 225:2039–2042
Goldhaber SZ, Hennekens CH, Evans DA, Newton EC, Goldleski JJ (1982) Factors associated with correct antemortem diagnosis of major pulmonary embolism. Am J Med 73:822–826
Rubio-Jurado B, Albores-Arguijo RC, Guerra-Soto A, Plasencia-Ortiz T, Tavarez-Macías G, Huerta-Hernández J et al (2020) Concordance between clinical diagnosis of pulmonary thromboembolism at hospital discharge and anatomopathological diagnosis. Int J Immunopathol Pharmacol 34:2058738420942390
Timmons S, Kingston M, Hussain M, Kelly H, Liston R (2003) Pulmonary embolism: differences in presentation between older and younger patients. Age Ageing 32:601–605
Berman AR, Arnsten JH (2003) Diagnosis and treatment of pulmonary embolism in the elderly. Clin Geriatr Med 19:157–175
Paraskos JA, Adelstein SJ, Smith RE, Rickman FD, Grossman W, Dexter L, Dalen JE (1973) Late prognosis of acute pulmonary embolism. N Engl J Med 239:55–58
Stein PD, Athanasoulis C, Alavi A, Greenspan RH, Hales CA, Saltzman HA, Vreim CE, Terrin ML, Weg JG (1992) Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation 85:462–468
Righini M, Le Gal G, De Lucia S, Roy PM, Meyer G, Aujesky D, Bounameaux H, Perrier A (2006) Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism. Thromb Haemost 95:715719
Douma RA, Mos IC, Erkens PM, Nizet TA, Durian MF et al (2011) Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann Intern Med 154:709718
Miron MJ, Perrier A, Bounameaux H, de Moerloose P, Slosman DO, Didier D, Junod A (1999) Contribution of noninvasive evaluation to the diagnosis of pulmonary embolism in hospitalized patients. Eur Respir J 13:13651370
Chabloz P, Reber G, Boehlen F, Hohlfeld P, De Moerloose P (2001) TAFI antigen and D-dimer levels during normal pregnancy and at delivery. Br J Haematol 115(1):150–152
Bajc M, Schümichen C, Grüning T, Lindqvist A, Le Roux PY, Alatri A et al (2019) EANM guideline for ventilation/perfusion single-photon emission computed tomography (SPECT) for diagnosis of pulmonary embolism and beyond. Eur J Nucl Med Mol Imaging 46(12):2429–2451
Schoepf UJ, Goldhaber SZ, Costello P (2004) Spiral computed tomography for acute pulmonary embolism. Circulation 109:2160–2167
Radan L, Mor M, Gips S, Schlang-Eisenberg D, Lurie Y, Dickstein K, Bitterman H, Ben-Haim S (2004) The added value of spiral computed tomographic angiography after lung scintigraphy for the diagnosis of pulmonary embolism. Clin Nucl Med 29:255–261
Wiener RS, Schwartz LM, Woloshin S (2013) When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found. BMJ 347:3368
Aviram G, Levy G, Fishman JE, Blank A, Graif M (2004) Pitfalls in the diagnosis of acute pulmonary embolism on spiral computed tomography. Curr Probl Diagn Radiol 33:74–84
Perrier A (2001) Pulmonary embolism: from clinical presentation to clinical probability assessment. Semin Vasc Med 1:147–154
Kanne JP, Lalani TA (2004) Role of computed tomography and magnetic resonance imaging for deep venous thrombosis and pulmonary embolism. Circulation 109(12 Suppl 1):115–121
Mitchell AM, Kline JA (2007) Contrast nephropathy following computed tomography angiography of the chest for pulmonary embolism in the emergency department. J Thromb Haemost 5:50–54
Smith-Bindman R, Lipson J, Marcus R et al (2009) Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med 169:2078–2086
Altes TA, Mai VM, Munger TM, Brookeman JR, Hagspiel KD (2005) Pulmonary embolism: comprehensive evaluation with MR ventilation and perfusion scanning with hyperpolarized helium-3, arterial spin tagging, and contrast-enhanced MRA. J Vasc Interv Radiol 16:999–1005
Mudge CS, Healey TT, Atalay MK, Pezzullo JA (2013) Feasibility of detecting pulmonary embolism using noncontrast MRI. Radiology 2013:1–5
Benson DG, Schiebler ML, Repplinger MD, François CJ, Grist TM, Reeder SB, Nagle SK (2017) Contrast-enhanced pulmonary MRA for the primary diagnosis of pulmonary embolism: current state of the art and future directions. Br J Radiol 90(1074):20160901. https://doi.org/10.1259/bjr.20160901. Epub 2017 Apr 12. PMID: 28306332; PMCID: PMC5602179
Biello DR, Mattar AG, McKnight RC, Siegel BA (1979) Ventilation-perfusion studies in suspected pulmonary embolism. AJR Am J Roentgenol 103:1033–1037
Hull RD, Hirsh J, Carter CJ, Jay RM, Dodd PE, Ockelford PA, Coates G, Gill GJ, Turpie AG, Doyle DJ, Buller HR, Raskob GE (1983) Pulmonary angiography, ventilation lung scanning, and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan. Ann Intern Med 98:891–899
Onyedika C, Glaser JE, Freeman LM (2010) Pulmonary embolism: role of ventilation-perfusion scintigraphy. Semin Nucl Med 43(2):82–87
Freeman LM, Glaser JE, Haramati LB (2012) Planar V/Q imaging for pulmonary embolism: the case for “outcomes” medicine. Semin Nucl Med 42(1):3–10
Burns SK, Haramati LB (2012) Diagnostic imaging and risk stratification of patients with acute pulmonary embolism. Cardiol Rev 20:15–24
Stein PD, Coleman ER, Gottscalk A, Saltzman H, Terrin ML, Weg JG (1991) Diagnostic utility of ventilation/perfusion lung scans in acute pulmonary embolism is not diminished by pre-existing cardiac or pulmonary disease. Chest 100:604–606
Harris B, Bailey D, Miles S, Bailey E, Rogers K, Roach P, Thomas P, Hensley M, King GG (2007) Objective analysis of tomographic ventilation–perfusion scintigraphy in pulmonary embolism. Am J Respir Crit Care Med 175:1173–1180
Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, Jonson B (2009) EANM guidelines for ventilation/perfusion scintigraphy. Part 1. Pulmonary imaging with ventilation/perfusion single photon emission tomography. Eur J Nucl Med Mol Imaging 36:1056–1070
Glaser JE, Chamarthy M, Haramati LB, Esses D, Freeman LM (2011) Successful and safe implementation of a trinary interpretation and reporting strategy for V/Q lung scintigraphy. J Nucl Med 52:1508–1512
Sostman HD, Pistolesi M (2011) Scintigraphy for pulmonary embolism: too old to rock ‘n’ roll, too young to die? J Nucl Med 52:11A–12A
Bhargavan M, Sunshine JH, Lewis RS, Jha S, Owen JB, Vializ J (2010) Frequency of use of imaging tests in the diagnosis of pulmonary embolism: effects of physician specialty, patient characteristics, and region. AJR Am J Roentgenol 194:1018–1026
The Task Force for the Diagnosis and Management (2008) Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 29:2276–2315
Wazir JF, Ansari NA (2004) Pneumocystis carinii infection: update and review. Arch Pathol Lab Med 128:1023–1027
Feldman C (2005) Pneumonia associated with HIV infection. Curr Opin Infect Dis 18:165–170
Morris A, Lundgren JD, Masur H, Walzer PD, Hanson DL, Frederick T, Huang L, Beard CB, Kaplan JE (2004) Current epidemiology of Pneumocystis pneumonia. Emerg Infect Dis 10:1713–1720
Medrano FJ, Montes-Cano M, Conde M, de la Horra C, Respaldiza N, Gasch A, Perez-Lozano MJ, Varela JM, Calderon EJ (2005) Pneumocystis jirovecii in general population. Emerg Infect Dis 11:245–250
Al Soub H, Taha RY, El Deeb Y, Almaslamani M, Al Khuwaiter JY (2004) Pneumocystis carinii pneumonia in a patient without a predisposing illness: case report and review. Scand J Infect Dis 36:618–621
Kramer EL, Sanger JJ (1989) Detection of thoracic infections by nuclear medicine techniques in the acquired immunodeficiency syndrome. Radiol Clin N Am 27:1067–1075
Woolfenden JM, Carrasquillo JA, Larson SM, Simmons JT, Masur H, Smith PD, Shelhamer JH, Ognibene FP (1987) Acquired immunodeficiency syndrome: Ga-67 citrate imaging. Radiology 162:383–387
Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J et al (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183:788–824
Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA et al (2013) An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 188:733–748
Noble PW, Homer RJ (2004) Idiopathic pulmonary fibrosis: new insights into pathogenesis. Clin Chest Med 25:749–758
Line BR, Fulmer JD, Reynolds HY, Roberts WC, Jones AE, Harris EK, Crystal RG (1978) Gallium-67 citrate scanning in the staging of idiopathic pulmonary fibrosis: correlation with physiologic and morphologic features and bronchoalveolar lavage. Am Rev Respir Dis 118:355–365
Baughman RP (2004) Pulmonary sarcoidosis. Clin Chest Med 25:521–530
Culver DA, Valeyre D (2016) Emerging ideas about sarcoidosis pathophysiology. Curr Opin Pulm Med 22:466–468. https://doi.org/10.1097/MCP.0000000000000310]
Mandel J, Weinberger SE (2001) Clinical insights and basic science correlates in sarcoidosis. Am J Med Sci 321:99–107
ACCESS Research Group (1999) Design of a case control etiologic study of sarcoidosis (ACCESS). J Clin Epidemiol 52:1173–1186
Scadding JG (1961) Prognosis of intrathoracic sarcoidosis in England. Br Med J 4:1165–1172
Gupta RG, Beckerman C, Silcian L et al (1982) Gallium citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis. Radiology 144:895–899
Prabhakar HB, Rabinowitz CB, Gibbons FK, O’Donnell WJ, Shepard JA, Aquino SL (2008) Imaging features of sarcoidosis on MDCT, FDG PET, and PET/CT. AJR Am J Roentgenol 190:s1–s6
Elgazzar AH, Silberstien EB, Hughes J (1995) Perfusion and ventilation scans in patients with diffuse obstructive airway disease: utility of single breath (wash in) xenon-103. J Nucl Med 36:64–67
Anthonisen NR, Martin RR (1977) Regional lung function in pleural effusion. Am Rev Respir Dis 116:201–207
American Cancer Society (2013) Cancer fact & figures. American Cancer Society, Atlanta, p 2013
Higashi K, Ueda Y, Sakuma T et al (2001) Comparison of [(18)F]FDG PET and (201)Tl SPECT in evaluation of pulmonary nodules. J Nucl Med 42:1489–1496
Tümkaya E, Büyükdereli G (2013) The role of F-18-FDG PET and PET/CT in lung cancer. Arch Med Rev J 22:470–485
Kristersson S (1974) Prediction of lung function after lung surgery. A Xe-133 radiospirometric study of regional lung function in bronchial cancer. Scand J Thorac Cardiovasc Surg 18(Suppl):5–44
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Elgazzar, A.H., Alnafisi, N. (2022). Respiratory System. In: Elgazzar, A.H. (eds) The Pathophysiologic Basis of Nuclear Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-96252-4_8
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