Pulmonary Functional Imaging: Part 1-State-of-the-Art Technical and Physiologic Underpinnings

Abstract

Over the past few decades, pulmonary imaging technologies have advanced from chest radiography and nuclear medicine methods to high-spatial-resolution or low-dose chest CT and MRI. It is currently possible to identify and measure pulmonary pathologic changes before these are obvious even to patients or depicted on conventional morphologic images. Here, key technological advances are described, including multiparametric CT image processing methods, inhaled hyperpolarized and fluorinated gas MRI, and four-dimensional free-breathing CT and MRI methods to measure regional ventilation, perfusion, gas exchange, and biomechanics. The basic anatomic and physiologic underpinnings of these pulmonary functional imaging techniques are explained. In addition, advances in image analysis and computational and artificial intelligence (machine learning) methods pertinent to functional lung imaging are discussed. The clinical applications of pulmonary functional imaging, including both the opportunities and challenges for clinical translation and deployment, will be discussed in part 2 of this review. Given the technical advances in these sophisticated imaging methods and the wealth of information they can provide, it is anticipated that pulmonary functional imaging will be increasingly used in the care of patients with lung disease. © RSNA, 2021 Online supplemental material is available for this article.

Graphical abstract

Figure 1:

CT scan in lower lung areas in an 83-year-old male patient with coronavirus disease 2019 pneumonia and severe hypoxemia. Bilateral multifocal patchy ground-glass opacities with peripheral distribution are visible (arrows).

Figure 2:

Schematic rendering of the functional anatomic unit of gas exchange. The respiratory bronchiole (RespBr) terminating in a group of alveolar sacs (orange) and their associated sac walls (ASW; yellow colored pencil) with pulmonary artery capillaries (red colored pencil) carrying deoxygenated blood to the alveolar walls. Within the alveolar sac plasma carbon dioxide (CO₂; orange arrow) undergoes gas exchange and oxygen (O₂) diffuses (yellow arrow) into the pulmonary capillary venules to be bound by hemoglobin in the red blood cells. The oxygenated blood then flows into the pulmonary veins (dark blue) back to the left atrium.

Figure 3a:

Anatomic basis for understanding pulmonary functional physiologic structure. (a) Magnified view of alveolar ducts and alveoli with orifices in a healthy patient. Alveoli are polygonal in shape and have orifices into alveolar ductal spaces. (b) Histologic sample of the healthy lung with hematoxylin-eosin stain. The divergence from terminal to respiratory bronchioles is shown. (c, d) A radiograph of 1-mm-thick specimen demonstrates the secondary lobules. The pulmonary arteries are located in the center, and pulmonary veins are located in the periphery of the secondary pulmonary lobule. The terminal and respiratory bronchioles are observed as tubular structures accompanying the pulmonary arteries. The primary lobules are indicated as yellow dashed circles in d. (Parts a–d adapted, with permission, from reference 10.) (e) Diagram shows anatomy and dimensions of secondary lobule and pulmonary acinus. Two secondary pulmonary lobules in the lung periphery are illustrated, with approximate dimensions of their components indicated. (Reprinted, with permission, from reference 12.)

Figure 3b:

Anatomic basis for understanding pulmonary functional physiologic structure. (a) Magnified view of alveolar ducts and alveoli with orifices in a healthy patient. Alveoli are polygonal in shape and have orifices into alveolar ductal spaces. (b) Histologic sample of the healthy lung with hematoxylin-eosin stain. The divergence from terminal to respiratory bronchioles is shown. (c, d) A radiograph of 1-mm-thick specimen demonstrates the secondary lobules. The pulmonary arteries are located in the center, and pulmonary veins are located in the periphery of the secondary pulmonary lobule. The terminal and respiratory bronchioles are observed as tubular structures accompanying the pulmonary arteries. The primary lobules are indicated as yellow dashed circles in d. (Parts a–d adapted, with permission, from reference 10.) (e) Diagram shows anatomy and dimensions of secondary lobule and pulmonary acinus. Two secondary pulmonary lobules in the lung periphery are illustrated, with approximate dimensions of their components indicated. (Reprinted, with permission, from reference 12.)

Figure 3c:

Anatomic basis for understanding pulmonary functional physiologic structure. (a) Magnified view of alveolar ducts and alveoli with orifices in a healthy patient. Alveoli are polygonal in shape and have orifices into alveolar ductal spaces. (b) Histologic sample of the healthy lung with hematoxylin-eosin stain. The divergence from terminal to respiratory bronchioles is shown. (c, d) A radiograph of 1-mm-thick specimen demonstrates the secondary lobules. The pulmonary arteries are located in the center, and pulmonary veins are located in the periphery of the secondary pulmonary lobule. The terminal and respiratory bronchioles are observed as tubular structures accompanying the pulmonary arteries. The primary lobules are indicated as yellow dashed circles in d. (Parts a–d adapted, with permission, from reference 10.) (e) Diagram shows anatomy and dimensions of secondary lobule and pulmonary acinus. Two secondary pulmonary lobules in the lung periphery are illustrated, with approximate dimensions of their components indicated. (Reprinted, with permission, from reference 12.)

Figure 3d:

Anatomic basis for understanding pulmonary functional physiologic structure. (a) Magnified view of alveolar ducts and alveoli with orifices in a healthy patient. Alveoli are polygonal in shape and have orifices into alveolar ductal spaces. (b) Histologic sample of the healthy lung with hematoxylin-eosin stain. The divergence from terminal to respiratory bronchioles is shown. (c, d) A radiograph of 1-mm-thick specimen demonstrates the secondary lobules. The pulmonary arteries are located in the center, and pulmonary veins are located in the periphery of the secondary pulmonary lobule. The terminal and respiratory bronchioles are observed as tubular structures accompanying the pulmonary arteries. The primary lobules are indicated as yellow dashed circles in d. (Parts a–d adapted, with permission, from reference 10.) (e) Diagram shows anatomy and dimensions of secondary lobule and pulmonary acinus. Two secondary pulmonary lobules in the lung periphery are illustrated, with approximate dimensions of their components indicated. (Reprinted, with permission, from reference 12.)

Figure 3e:

Anatomic basis for understanding pulmonary functional physiologic structure. (a) Magnified view of alveolar ducts and alveoli with orifices in a healthy patient. Alveoli are polygonal in shape and have orifices into alveolar ductal spaces. (b) Histologic sample of the healthy lung with hematoxylin-eosin stain. The divergence from terminal to respiratory bronchioles is shown. (c, d) A radiograph of 1-mm-thick specimen demonstrates the secondary lobules. The pulmonary arteries are located in the center, and pulmonary veins are located in the periphery of the secondary pulmonary lobule. The terminal and respiratory bronchioles are observed as tubular structures accompanying the pulmonary arteries. The primary lobules are indicated as yellow dashed circles in d. (Parts a–d adapted, with permission, from reference 10.) (e) Diagram shows anatomy and dimensions of secondary lobule and pulmonary acinus. Two secondary pulmonary lobules in the lung periphery are illustrated, with approximate dimensions of their components indicated. (Reprinted, with permission, from reference 12.)

Figure 4:

Summary schematic for the available pulmonary functional imaging methods. This schematic does not include molecular imaging and its major contributions to lung cancer imaging and treatment response. ADC = apparent diffusion coefficient, ASL = arterial spin labeling, DCE = dynamic contrast enhancement, DECT = dual-energy CT, Exp = expiratory, FD = Fourier decomposition imaging, FDG = fluorodeoxyglucose, HP = hyperpolarized, Insp = inspiratory, NM = nuclear medicine, RBC = red blood cell, VDP = ventilation defect percentage.

Figure 5:

Xenon (Xe) ventilation dual-energy CT in patients with, A, B, chronic obstructive pulmonary disease and mild emphysema and with, C, D, moderate to severe emphysema. A, Dual-energy CT image shows minimal centrilobular emphysema in right lower lobe on axial weighted average image and, B, homogeneous Xe enhancement on Xe ventilation map in both lungs. C, Axial weighted average image shows severe emphysema with bronchial wall thickening in both upper lobes. D, On Xe ventilation map, the inhomogeneously decreased Xe enhancement is identified in both upper lobes, whereas Xe ventilation is relatively preserved in the central areas of both upper lobes (arrows).

Figure 6:

Images in a 43-year-old male patient with pulmonary emphysema and bullae. A, Thin-section coronal image at lung window setting (left) and quantitatively assessed thin-section multiplanar reconstruction image with density-masked CT technique (right). Emphysematous lung in right upper lung (small arrow) and giant bulla in the left upper lung (large arrow) are clearly demonstrated. On quantitatively assessed thin-section multiplanar reconstruction image, healthy lung appears as green, and emphysematous lung or bullae appears as red with applying threshold value 2950 HU. B, Oxygen-enhanced MRI scan shown as a relative-enhancement map (gray scale, 0% [black] and 50% [white]). Emphysematous lung in right upper lung (small arrow) and giant bulla in the left upper lung (large arrow) are clearly demonstrated as black areas. In addition, the remainder of both lungs are heterogeneously enhanced because of emphysematous lung and airflow limitations.

Figure 7:

Example of dual-energy CT angiography in a patient with acute pulmonary embolism. A, Axial CT pulmonary arteriographic image shows saddle emboli in the main pulmonary artery and right and left pulmonary arteries (arrowheads) and small clots in a segmental pulmonary artery in the right lower lobe (arrow). B, Axial fusion image of pulmonary blood volume map of dual-energy CT shows large wedge-shaped perfusion defects in the right lower lobe (arrowheads).

Figure 8:

Images in a 73-year-old male patient with invasive adenocarcinoma (arrows) in the left lower lobe. Thin-section coronal multiplanar reconstruction image and quantitatively assessed whole-lung perfusion CT image (left) displayed as total perfusion map (right; combination of pulmonary arterial blood supply and systemic arterial blood supply from bronchial artery). Invasive adenocarcinoma (arrows) appears as part-solid nodule and decreased perfusion area compared with normal lungs. In addition, solid component shows relatively higher perfusion than ground-glass opacity. Whole-lung perfusion map was generated from two dynamic contrast-enhanced area-detector CT data sets by using our proprietary software.

Figure 9:

Raw perfusion coronal MRI scan from a movie by using the differential subsampling with Cartesian ordering technique (water images) after the bolus administration of contrast material (Multihance; Bracco) shows the dextrophase and levophase of cardiovascular, pulmonary, and great vessel contrast enhancement (arrows).

Figure 10:

Demonstration of gas diffusion block in interstitial lung disease. Xenon 129 (¹²⁹Xe) gas is soluble in the tissue and plasma and red blood cells (RBCs) from the alveolar airspace into the tissue-capillary interface. This results in measurable chemical shifts for the tissue and plasma and red blood cell compartments approximately 200 ppm downfield from the gas resonance (upper right). Spectroscopic imaging can be fused with anatomic ultrashort echo time (UTE) images (lower left) in fibrotic lung disease to demonstrate diffusion block in which the tissues and plasma take up the ¹²⁹Xe homogeneously (lower middle), but red blood cell uptake is heterogeneous (lower right) or not present (lower row arrows) in a region of apparent honeycombing. (Upper left image used with permission from reference 111).

Figure 11:

Still image capture from four-dimensional flow MRI movie file shows the right ventricular outflow track (yellow arrow) and the left ventricular outflow track (orange arrow).

Figure 12:

Artificial intelligence–based automatic quantification of regional disease pattern on CT images. A, The original image and, B, parametric map of thin-section CT of interstitial lung disease show that deep learning–based automatic quantification of local disease pattern is possible. Red on the parametric map represents the areas of honeycombing; yellow, reticulation; and green, ground-glass opacity.