Pulmonary arterial hypertension: an imaging review comparing MR pulmonary angiography and perfusion with multidetector CT angiography

Pulmonary hypertension (PH) is a progressive disease that leads to substantial morbidity and eventual death. Pulmonary multidetector CT angiography (MDCTA), pulmonary MR angiography (MRA) and MR-derived pulmonary perfusion (MRPP) imaging are non-invasive imaging techniques for the differential diagnosis of PH. MDCTA is considered the gold standard for the diagnosis of pulmonary embolism, one of the most common causes of PH. MRA and MRPP are promising techniques that do not require the use of ionising radiation or iodinated contrast material, and can be useful for patients for whom such material cannot be used. This review compares the imaging aspects of pulmonary MRA and 64-row MDCTA in patients with chronic thromboembolic or idiopathic PH.Pulmonary hypertension (PH) is an insidious and progressive disease that leads to substantial morbidity and eventual death. PH results from a number of diseases with different physiopathologies, treatments and prognoses [1]. One of the most frequent causes of PH is chronic thromboembolic pulmonary hypertension (CTEPH).The current classification of PH (2], resulted from a review of the previous classification developed at the 2003 3rd World Symposium in Venice, Italy. During the 4th World Symposium on PH, an international group of experts agreed to maintain the general philosophy and organisation of the Evian–Venice classifications. However, in response to a questionnaire regarding the previous classification, a majority (63%) of experts felt that modification of the Venice classification was required to accurately reflect information published in the past 5 years and to provide clarification in some areas [2].

Table 1

Classification of pulmonary hypertension according to the 4th World Symposium, Dana Point, CA, 2008 [2]

1. Pulmonary arterial hypertension (PAH)

1.1. Idiopathic PAH

1.2. Heritable PAH

1.2.1. Bone morphogenetic protein receptor type 2

1.2.2. Activin receptor-like kinase type 1 (ALK1)

ALK1, endoglin (with or without hereditary haemorrhagic telangiectasia)

1.2.3. Unknown

1.3. Drug- and toxin-induced

1.4. Associated with:

1.4.1. Connective tissue diseases

1.4.2. HIV infection

1.4.3. Portal hypertension

1.4.4. Congenital heart diseases

1.4.5. Schistosomiasis

1.4.6. Chronic haemolytic anaemia

1.5. Persistent neonatal pulmonary hypertension

1′. Pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis

2. Pulmonary hypertension due to left heart disease

2.1. Systolic dysfunction

2.2. Diastolic dysfunction

2.3. Valvular disease

3. Pulmonary hypertension due to lung diseases and/or hypoxia

3.1. Chronic obstructive pulmonary disease

3.2. Interstitial lung disease

3.3. Other pulmonary diseases with mixed restrictive and obstructive pattern

3.4. Sleep-disordered breathing

3.5. Alveolar hypoventilation disorders

3.6. Chronic exposure to high altitude

3.7. Developmental abnormalities

4. Chronic thromboembolic pulmonary hypertension

5. Pulmonary hypertension with unclear multifactorial mechanisms

5.1. Haematological disorders: myeloproliferative disorders, splenectomy

5.2. Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis

5.3. Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders

5.4. Other: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis

Open in a separate windowPH is a clinical and haemodynamic syndrome that results in increased vascular resistance in the pulmonary circulation, usually by a combination of mechanisms involving vasoconstriction and remodelling of the small vessels [3]. Haemodynamically, it is defined as a systolic pulmonary artery pressure of >35 mmHg, or a mean pulmonary artery pressure of >25 mmHg at rest or >30 mmHg with exertion [4,5]. An increase in pulmonary vascular resistance and subsequent compensatory right ventricular (RV) hypertrophy lead to elevated pulmonary pressure, which often results in increased RV afterload and failure. The disorder is progressive, leading to right heart failure and death within a median of 2.8 years after diagnosis [6,7].The development of RV failure in patients with pulmonary arterial hypertension (PAH) is an ominous sign with major adverse prognostic implications. Patients with severe PAH or right heart failure die usually within 1 year without treatment. In the National Institutes of Health registry, approximately 50% of deaths in patients with PAH are attributed to RV failure [6]. Numerous factors may indicate a poor prognosis in patients with PAH and secondary RV failure, including age >45 years at presentation, New York Heart Association (NYHA) Class III or IV functional classification, failure to improve to a lower NYHA class during treatment, pericardial effusion, large right atrial size, elevated right atrial pressure, septal shift during diastole, decreased pulmonary arterial capacitance (stroke volume/pulmonary arterial pulse pressure), increased N-terminal brain natriuretic peptide level and hypocapnia [8,9].Because patients with PH often present with non-specific symptoms, such as shortness of breath on minimal physical exertion, fatigue, chest pain and fainting, diagnosis often occurs late in the course of the disease, when the prognosis is poor and treatment options are limited [10]. A complete diagnostic evaluation includes a medical history, physical examination, pulmonary function tests, electrocardiogram, echocardiogram, cardiac catheterisation and advanced imaging. Invasive haemodynamic evaluation is mandatory, not only to confirm the diagnosis but also to address the prognosis and the patient''s eligibility for the use of calcium channel blockers through an acute vasodilator challenge. Non-invasive surrogate response markers to the acute vasodilator test have been sought. In other studies, mean pulmonary artery distensibility (mPAD) has been evaluated using MRI to assess pulmonary haemodynamics and diagnose pulmonary vascular disease [11,12]. The mPAD may reflect the degree of vascular remodelling, making it a very interesting marker for the evaluation of patients with idiopathic PAH (IPAH) [13]. Jardim et al [14] found that the cardiac index, calculated after the determination of cardiac output using MRI and pulmonary artery catheterisation, showed excellent correlation, as did right atrial pressure and the RV ejection fraction. They also found that PAD was significantly higher in acute vasodilator test responders. A receiver operating characteristic curve analysis has shown that 10% distensibility can be used to differentiate responders from non-responders with 100% sensitivity and 56% specificity. This study suggested that MRI and PAD may be useful non-invasive tools for the evaluation of patients with PH. In some cases, definitive diagnosis requires a thoracoscopic lung biopsy [3]. Because CTEPH differs considerably from other forms of PH and may be treated surgically, an accurate diagnosis is essential [15].The depiction of occluding thrombotic material and concomitant perfusion defects is a prerequisite for the correct and reliable diagnosis of CTEPH. Until recently, pulmonary perfusion could be assessed only by using radionuclide perfusion scintigraphy and conventional pulmonary angiography. The former technique has substantial limitations with respect to spatial and temporal resolution, and the latter requires invasive catheterisation of the right side of the heart and produces only two-dimensional projection images [16].Pulmonary multidetector CT angiography (MDCTA), pulmonary MR angiography (MRA), and MR-derived pulmonary perfusion (MRPP) are non-invasive imaging techniques used to assess PH-related pulmonary vessel changes in the differential diagnosis [16]. MDCTA is considered the gold standard for the diagnosis of CTEPH because it depicts the occluding thrombotic material and concomitant lung changes [16]. However, the combined use of MRA and MRPP allows the evaluation of PH-related pulmonary vessel changes and concomitant perfusion defects without ionising radiation or iodinated contrast material, and can be useful for patients in whom such material cannot be used. Few studies to date have sought to determine the accuracy of MRA in distinguishing the various causes of PH [16-18].MRI also contributes to the cardiac evaluation of patients with PH. Cardiac MRI is the gold standard technique for the assessment of ventricular function and the quantification of volumes and mass without geometric assumptions [19]. Recently, myocardial delayed enhancement after the intravenous administration of a gadolinium-based contrast agent has been shown at the insertion points of the RV free wall in the interventricular septum in patients with PAH and impaired ventricular function [20]. McCann et al [21] also suggested that the extent of hyperenhancement was not correlated with any clinical or haemodynamic variable, but was inversely correlated with RV dysfunction measured on cardiac MRI.This review aims to compare the imaging aspects of pulmonary MRA and 64-row MDCTA in patients with CTEPH and IPAH, and to highlight the main differences between these techniques. Patients with other forms of PH are not considered here because CT is superior to MRI for the evaluation of lung parenchyma.