1. Introduction
The pulmonary circulatory system constitutes an intricate network of blood vessels that is detailed and structured to facilitate the efficient exchange of gases, thereby enabling the delivery of oxygen to the organs and tissues of the human body [
1]. Additionally, due to the numerous variations in the arteries, physicians must have a comprehensive knowledge of their anatomy to minimize the risk of adverse intraoperative procedures [
2]. Clinicians, surgeons and radiologists must thoroughly understand the normal anatomy of the pulmonary vessels. The branching and typical imaging appearance of the pulmonary arterial tree are crucial for diagnosing and characterizing various pathologies of the pulmonary arteries. The complex variations of blood vessels within the traditional anatomical borders present significant challenges for medical specialists, particularly those specializing in cardiothoracic surgery [
3].
The pulmonary trunk originates from the heart’s right ventricle and initially moves forward, then to the back and side on the left of the ascending aorta. At the level of the aortic arch, the pulmonary trunk divides into the right and left pulmonary arteries. The right pulmonary artery passes under the aortic arch and enters the hilum of the right lung in front of the right bronchus. Meanwhile, the left pulmonary artery enters the hilum of the left lung above the left bronchus.
The branching patterns of these blood vessels differ between the lungs due to their anatomical variations, with the most significant variability reported in the branching of segmental and subsegmental arteries [
4]. Determination of the branches is an essential aspect when attempting to assess the pulmonary vascular tree. Studying the distribution of flow resistance in the arterial tree of the lung requires a comprehensive analysis of the various quantitative aspects, including the exact numbers and lengths of each branch. This task is particularly challenging due to the irregularity of the arterial tree’s structure. Identifying systematic distributed structures introduces complexity that may pose challenges for conventional morphometric research methods.
Various disorders can affect the pulmonary arteries, occasionally incidentally discovered during imaging for other reasons or as part of the work-up for symptomatic patients. Chronic thromboembolic pulmonary hypertension (CTEPH) experiences morphologic changes in the vasculature [
5]. It is a rare disease with an annual incidence of 3.1-6.0 and a prevalence – of 25.8-38.4 cases per million [
6]. It is diagnosed via invasive pulmonary angiography (PA) combined with right heart catheterization. CTEPH is also one of the pulmonary hypertension (PH) subtypes, representing Group 4 (based on the World Health Organization (WHO) classification) that can potentially be cured [
7]. Other groups include pulmonary arterial hypertension (Group 1), pulmonary hypertension associated with left-sided heart failure (Group 2), pulmonary hypertension secondary to lung disease (Group 3), and multifactorial pulmonary hypertension (Group 5). The treatment for CTEPH includes pulmonary endarterectomy ((PEA), class – I, evidence level – B) and/or balloon pulmonary angioplasty ((BPA), class – I, evidence level – B), complimented with drug therapy, if required [
8,
9]. It is essential to accurately note, label and document the stenotic and occluded lobar and segmental arteries during the diagnostic procedure to ensure the best possible treatment. In treatment via BPA, identical imaging modalities are employed; therefore, explicit preparation, which is essential during diagnostic PA, is crucial. Although the rate of complications in BPA has decreased in past years, it remains high.
The rate of complications related to pulmonary injury varies from 5.9% to 31.4% [
10,
11], while the early mortality rate is considered to be 0-14%, depending on the experience of the respective CTEPH clinical center [
12]. Serious but quite common adverse events include catheter wire-caused vascular injuries, leading to hemoptysis, vascular dissection, and balloon-induced perforation of pulmonary arteries [
13]. Older age and higher mean pulmonary artery pressure are often associated with a higher risk of complications [
14,
15]. Unexpected punctures or perforations might be related to the inability to correctly locate the course of a segmental artery, misunderstanding the bifurcation angles in different planes, or misinterpreting the original diameter of the artery as it courses dorsally.
It is essential to emphasize the significance of anatomical variations and arterial morphology in these complications. Besides, a better understanding of topographical arterial anatomy would allow the invasive specialist to perform the PA and BPA procedures quicker, decreasing the risk of complications and the dose of radiation absorbed.
This study aimed to better understand the pulmonary arteries and their branching using a dissected case and apply this knowledge to the diagnostics and treatment of CTEPH. We focused on the morphological variations of the pulmonary arteries in a cadaveric sample.
4. Discussion
Pulmonary vasculature anatomy varies among patients, including differences in the size and angulation of vessels. It’s crucial to accurately differentiate between the pulmonary arteries and veins (A/V) when diagnosing and treating pulmonary conditions [
18]. A thorough physical examination can detect around 75% of cases in high-risk populations [
19]. Fibrotic transformation of pulmonary artery thromboembolism results in chronic obstruction in the macroscopic pulmonary arteries and vascular remodeling in the microvasculature of the pulmonary system [
20]. Pulmonary artery pressure monitors enable remote assessment of cardiopulmonary hemodynamics, allowing for early intervention, and this has been proven to reduce hospitalization due to heart failure [
21,
22].
Increased peripheral pulmonary vascular resistance can significantly impact cases of pulmonary hypertension (PH) [
23]. The right main pulmonary artery runs horizontally in the human body and is presented perpendicular to the right lung. This position creates a right angle with the pulmonary artery trunk, potentially leading to smoother blood flow and increased vulnerability to the effects of PH. On the other hand, the curved trajectory of the left main pulmonary artery may make it comparatively less susceptible to the impact of PH when compared to the right main pulmonary artery. In a study with animals, Harper et al. [
24] state that the pulmonary artery is not a source of increased resistance.
A wide range of congenital and acquired conditions can affect the pulmonary arteries, some of which are familiar in clinical practice and others rare. Organized blood clots cause chronic thromboembolic pulmonary hypertension (CTEPH) in the pulmonary arteries. Diagnosing can take 1 to 2 years, which results in higher mortality rates [
25,
26]. It is recommended that every patient undergoes evaluation at a specialized center with experience in pulmonary arterial endarterectomy (PEA), a potentially curative surgical technique [
27]. Patients that are considered inoperable (up to 1/3 of patients) or have blockages in distal parts of the pulmonary arterial tree (segmental and subsegmental arteries) undergo a different type of treatment – balloon pulmonary angioplasty (BPA), which is performed in 2D radiographic control [
28]. In BPA, knowledge of the topographical anatomy of pulmonary arteries is key to successful treatment via the dilation of narrowed arteries. CTEPH is determined when there is a sustained increase in mean pulmonary artery pressure (at least 20 mm Hg at rest) and evidence of chronic pulmonary embolism on CT, MRI, V/Q scan or PA. A multidetector computed tomography (CT) angiography is typically used to identify indirect (an uneven blood flow pattern in the lungs and the presence of enlarged bronchial arteries) and direct (organized blood clots, partially filled or wholly blocked pulmonary arteries, and thin bands and membranes) signs of CTEPH [
9]. Mahammedi et al. [
29] found a significant relationship between CT scan measurements of the pulmonary arteries and the severity of PH. MRI is a sensitive and reliable tool for assessing the diagnosis of CTEPH; however, it is rarely used in practice due to the high cost of the examination. V/Q scan is usually performed to rule out CTEPH and diagnose other forms of pulmonary hypertension. It does not reveal specific lobar and segmental arterial branching and precise occlusions, yet it clearly and with high sensitivity demonstrates perfusion defects in lungs that are present in cases of CTEPH.
Diagnosis of CTEPH typically requires invasive pulmonary angiography and right heart catheterization to assess pulmonary arterial pressure [
30]. A chronic thromboembolic disease (CTED) diagnosis, distinct from CTEPH, is made if clotting is present without elevated mean pulmonary arterial pressure. As the pulmonary arterial pressures are not determined in CT pulmonary angiography (CTPA), it is not possible to differentiate CTED from CTEPH via CTPA. Besides it is crucial to have a highly experienced radiologist review the CT angiography results, as the test is known to have low sensitivity [
31].
The field of PH would greatly benefit from more well-designed studies to improve our understanding of how various conditions contribute to disease development [
32]. Evidence has shown that delays in diagnosing and managing CTEPH are associated with poor outcomes [
33]. Conventional two-dimensional (2D) imaging-pulmonary angiography may introduce several potential errors when assessing the pulmonary vasculature. However, three-dimensional (3D) chest reconstruction, which involves converting 2D imaging data from CT scans into virtual 3D structures using specialized 3D visualization software, provides a more comprehensive and detailed view of the chest anatomy. Radiography can often reveal enlarged central pulmonary arteries and identify congenital pathology with feasible measurements for clinicians without intravascular contrast material or specialized software [
34]. It’s important to note that although CT pulmonary angiography (CTPA) is a valuable tool, there are more specific and conclusive methods for diagnosing CTEPH. In routine the first step that leads to the diagnosis of CTEPH is V/Q scan, which is then followed by right heart catheterization and pulmonary angiography to confirm the diagnosis and assess the severity of the disease.
Comprehending the intricate structure and standard imaging features of the pulmonary arterial tree is essential. Pathologies impacting the pulmonary artery can be categorized into five primary groups: congenital conditions, pulmonary artery dilatation, narrowing, filling defects and PH [
35]. These conditions are generally identifiable through chest CT or magnetic resonance imaging (MRI). Treatment options exist for almost all variations of this disease [
36].
Acquired pulmonary artery variations can lead to different symptoms and expressions. CTEPH often involves the central vasculature, which affects the segmental or subsegmental vessels in other cases. Radiologists and medical specialists should identify vascular differences and communicate their significance to surgeons [
37]. During a pulmonary lobectomy, particularly in video-assisted thoracic surgery (VATS), surgeons may encounter technical challenges stemming from variations in the anatomy of the pulmonary arterial tree [
38]. Such anatomical diversity can pose complex and intricate obstacles that require careful navigation during the surgical procedure. Performing the intricate dissection, isolation, and closure of the artery branches in a lung lobe to be resected is also one of the most complex steps in a standard pulmonary lobectomy.
Anatomical cadaveric dissections have long been integral to research, significantly enhancing the understanding of vascular anatomy for many years. Only a handful of studies in the existing literature delve into lung dissections focused on preserving arterial trees. In contrast, others concentrate on elucidating the morphology of the tracheobronchial tree [
39]. The most common branching variations described superficially in most articles give a basic understanding of pulmonary arterial anatomy by describing the segmental branches of each lobe [
40]. Murlimanju et al. [
41] observed that the variations were higher in the left than in the right lung. Their study detected variations in 16.1% of the right lungs and 48.2% of the left lungs. George et al. [
42] found that 67.69% of right lungs have two pulmonary arteries, whereas 3.07% possess three. Other researchers offer more detailed and well-explained branching variations of a single lobe. There are often described up to 8 different branching variations in a lobe [
43,
44,
45,
46]. Unfortunately, for this research, it was impossible to combine all these variations as in each of the articles, only a single lobe was described, and the criteria for each author in differentiating segmental arteries may be different. Research performed by Michaud et al. [
17], which fully describes both lungs, is quite detailed. It presents up to three branching variations for each lobe or cluster of segments. The most common variations usually represent 70-75% of cases, rarer variants were noted in 14-15%, and the rarest occur in less than 10% of cases.
Advanced technology enables the utilization of specialized software to measure digital vascular parameters. Singhal et al. [
47] have developed a technique for organizing these measurements using the Strahler order concept. According to this concept, the most distal arteries are designated 1st order. When two arteries of equal size connect, the resulting artery is categorized as a second-order artery. This classification continues for subsequent connections. Our study adjusted the numbering system due to the inaccessibility of the smallest and most distal arteries. For instance, the pulmonary trunk was considered a 1st generation artery, with its primary branches labeled as 2nd generation, and so on. While this approach has been utilized in prior studies, it may not be as comprehensive as the Strahler-order method [
48,
49].
First, it is essential to note the branching pattern of the right and left pulmonary arteries. They form two distinct structures that cannot be compared, and assumptions should not be made in cases of low-quality PA. There are segmental differences between the lungs. As the segments are supplied by segmental pulmonary arteries running primarily parallel to segmental bronchi, the venous blood supply differs between the lungs [
39]. The dissected case shows some excellent examples. After coursing horizontally for a few centimeters, the right pulmonary artery splits into the anterior trunk and interlobar artery.
In contrast, the left pulmonary artery does not split into two major branches – the anterior trunk is absent. It is a common finding, and the anterior trunk is not recognized as a structure in the left lung [
17,
40]. In cases where segmental branches, such as S4 and S5, share the exact numbering, it is essential to understand the topography of pulmonary segments. S4 and S5 have different lung positions. Thereby, the course of segmental arteries will be different in both – in the right lung from the common trunk of A4+A5, where A4 branches off laterally, while A5 – medially; however, in the left lung – A4 branches off superiorly, while A5 – inferiorly. Another reason for not comparing the two branching patterns is apparent in the dissected case. The interlobar artery terminates in a trifurcation in both lungs, exhibiting a bilaterally symmetrical pattern. However, these three end branches are not the same in both lungs. In the right lung were A7, A8 and the trunk of A9+10, but in the left – A8, A9 and A10. The dissected model determined that the revealed subsegmental arteries course to the location of each pulmonary segment. However, this may cause difficulties in reading PAs, especially if they are done in only one projection. It could lead to an imprecise diagnosis and a higher probability of complications during procedures.
As conventional pulmonary angiography is a 2D picturing examination, many factors can contribute to an inaccurate reading of the angiogram. Often, the arteries overlap, and it might be challenging to differentiate them, especially in the lower lobes of the lungs. Besides, many branching variations are recorded – up to 8 in each lobe [
17,
28,
43,
44,
45,
46]. A few rare variations were recorded in the dissected case based on Michaud’s representation. Most commonly, the interlobar artery in both lungs ends in bifurcation – in the right – in A7+A8 and A9+A10, while in the left – in A8 and A10+A9. In our case, trifurcations, as mentioned above, were noted. Also, although the anterior trunk is a common finding in the upper lobe of the right lung, it can be absent [
17]. Furthermore, for patients with severe CTEPH and thromboembolic blockages, low cardiac output and inability to hold their breath for a few seconds, the quality of pulmonary angiogram can be deficient. In such situations, the invasive specialist must be aware of the possible anatomical variations and differences in the course of the arteries in these variations. 3D models could be a helpful tool for studying the possible variations, differentiating the segmental arteries and looking at different artery courses in other models. Acquiring data from CT pulmonary angiography is another option for a comprehensive study of 3D anatomy. However, a tangible dissected case represents the most accurate variant of human pulmonary arteries with a size ratio 1:1.
The importance of morphological parameters in diagnosis, pathophysiology, and treatment is not much described in the literature. There is some proof of dysregulation in endothelial cells when the shear stress on the vessel wall in pulmonary arteries is present [
50]. Shear stress can also be caused by unusual branching patterns in the pulmonary vasculature. It is not yet known what angles and in which lobes of the lungs would be predisposed to CTEPH due to shear stress (or maybe other factors). However, if systematic evaluation of each pulmonary angiography was performed, some conclusions could be drawn – that is the aim for future studies. Abbasi et al. [
51] discovered that there is a significant decrease in the primary pulmonary artery bifurcation angle in patients developing CTEPH.
The branching angles have their role in complications in diagnosing, treating CTEPH and right heart catheterization when the catheter is directed through the pulmonary arteries. Complications include hemoptysis, pulmonary artery perforation and pulmonary artery injury [
10,
13,
15,
52]. While specific causes for the injuries are not extensively outlined, unforeseen angling of the pulmonary arteries could be one of the contributing factors. Our results show that some branches of the interlobar arteries form angles close to 90 degrees. As the anatomy course changes direction to almost perpendicular, there is an increased risk of vascular injury when the catheter is inserted into the vessel wall. No evidence has been established regarding the relationship between the angle and complications. However, the invasive specialist should always exercise caution when directing the catheter into the pulmonary arteries. Further research is needed to investigate the complication rate and variations in pulmonary arterial anatomy.
The invasive specialist performing PA and balloon pulmonary angioplasty (BPA) must also be aware of differences in the sizes of pulmonary segmental arteries. Our study showed a vast difference in the diameters of the segmental arteries (3.04-9.29 mm). Other authors have noted quite an extensive variety in segmental arteries’ diameters [
47,
49]. During BPA, the narrowed segmental artery is expanded by inflating a balloon. The specialist performing the procedure must be conscientious as the segmental arteries, especially having fibrotic/thromboembolic material in their wall, are very fragile and can perforate [
15]. As the risk of perforation is high, each specialist must know the differences in morphology of segmental arteries and treat each stenotic or occluded artery separately by not overestimating its original diameter. Improved knowledge and studying of pulmonary arterial morphology might enhance the quality of the provided treatment and decrease the rate of complications.
Summing up the knowledge from the dissected material and other authors’ work in describing pulmonary arterial tree anatomy [
17,
40,
43,
44,
45,
46,
53,
54], a detailed sketch of the pulmonary arterial tree was meticulously rendered, showcasing intricate and accurate details. The sketch is now used in clinical practice to document precise CTEPH diagnosis by labeling the stenotic or occluded arteries. After the initial PA assessment, the invasive cardiologist identifies and marks the affected arteries. A sketch of the marked arteries is placed in the patient’s medical records for reference in devising further treatment and evaluating the patient’s case. That could be a great practice in every hospital for convenient documentation of the disease’s diagnosis and/or progression. Furthermore, this approach allows for a systematic review of the CTEPH phenotype, identifying the most affected and less commonly affected arteries. That would allow us to do further research on the pathophysiology and risk factors of CTEPH and review already pronounced hypotheses, e.g., about thromboembolic material forming more prominently in the arteries of the right lung [
55].
The study also has certain limitations that should be considered. One obstacle is that the natural variations in human anatomy can lead to unpredictability in the results. Tracing pulmonary artery branching at the macroscopic level through intrapulmonary tissue may have limited our understanding of microscopic branching patterns. Another limitation is that we only had access to a single sample of two lungs, preventing us from conducting a comparative analysis. The dissection procedure was also time-consuming. Furthermore, using preserved, embalmed tissues may not accurately replicate the conditions of live situations. The manual revision of the vascular system and the delicate measuring processes may also risk damaging smaller vessels if not performed with maximal care. There are numerous branching variations, so reviewing a single case does not explain all possible variants. The various morphologies of pulmonary arteries are generally not linked to the pathophysiology of several pulmonary diseases, including CTEPH. Consequently, limited research has been dedicated to this area, resulting in a scarcity of detailed information on pulmonary arterial anatomical morphology. The lack of literature on dissected cadaveric pulmonary arteries and their branching patterns further limits the ability to compare our results with those of other studies. Developing an effective system for processing and interpreting the data becomes a paramount concern in light of these complexities, demanding a detailed and comprehensive approach. More extensive research is needed to understand the variations in the population fully.