YOUSSRIAH Y. SABRI, M.D.*; IMAN M. HAMDY, M.D.*; IRENE M. SABRY, M.D.** and ASSAD A. ALHADI, M.Sc.*

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1 Med. J. Cairo Univ., Vol. 82, No. 2, September: 15-28, Evaluation of the Role of High Resolution Computerized Tomography (HRCT) and Computerized Tomography Pulmonary Angiography (CTPA) in the Diagnosis, Differentiation and Detection of Possible Complications of Pulmonary Hypertension YOUSSRIAH Y. SABRI, M.D.*; IMAN M. HAMDY, M.D.*; IRENE M. SABRY, M.D.** and ASSAD A. ALHADI, M.Sc.* The Departments of Radiology* and Chest**, Faculty of Medicine, Sanaa and Cairo Universities Abstract Introduction: Multi-detector pulmonary CT angiography and high resolution CT are now play an important role in the diagnosis of pulmonary hypertension (PH) and are considered the first line of investigation in the diagnosis of most of the pulmonary vascular and interstitial disorders that s cause PH. Purpose: The aim of this study is to evaluate the role of Multi-detector pulmonary CT angiography (CTPA) and high resolution CT (HRCT) in the diagnosis of PH and its causes. Patients and Methods: 100 patients (diagnosed either clinically or by echocardiography to have PH) were examined using a 4-MCT scanner in the Radiology Department in Cairo University. The study population was assisted for different MDCT signs of PH, lung parenchyma, vascular and cardiac findings that help in the diagnosis of different causes of PH. Results: In all cases the main pulmonary artery (MPA) was larger than 29mm and further divided according to the size into three groups (<35mm=54%, >!35!940mm=28%, >40mm=18%). The more than 1:1 relation between segmental pulmonary artery and the bronchus in different pulmonary lobes was seen in 88% of cases. The more than 1:1 relation between the main pulmonary artery and the aorta was seen in 76% of cases. According to the other CT findings, the causes were divided into four groups. Group A (pulmonary) 36%, Group B (cardiac) 27%, Group C (vascular) 17% and Group D (idiopathic) 20%. Conclusion: CTPA and HRCT are a relatively available, minimally invasive investigation that can now be considered as an important modality that show signs of PH and the first line of investigation in diagnosis of possible causes of PH. Key Words: High resolution CT (HRCT) CT pulmonary angiography (CTPA) Pulmonary hypertension (PH). Correspondence to: Dr. Youssriah Y. Sabri, The Department of Radiology, Faculty of Medicine, Cairo University Introduction PULMONARY hypertension (PH) is hemodynamically defined as a mean pulmonary artery pressure (MPAP) greater than 25mm Hg at rest or greaterthan 30mm Hg during exercise [1]. In accordance with the established approach of pathologists, PH may be categorized aseither precapillary (with changes limited to the arterial side of the pulmonary circulation) or postcapillary (with primary findings located within the pulmonary venous circulation, between the capillary bed and the left atrium). These changes may be idiopathic but more commonly they represent a secondary response to alterations in pulmonary blood flow [2]. The diagnosis is made with clinical assessmentof hemodynamic parameters, medical history, and radiological and histologic findings [3]. However the definitive diagnosis of PH isoften delayed because of its insidious clinical onset and minimal early radiographic findings [2]. And because history and clinical features of PH are generally nonspecific, non-invasive tests are often relied on to identify raised pulmonary pressure [4]. With the increased interest in MDCT in the evaluation of pulmonary embolic disease and cardiac disease as well as the ongoing enthusiasm for high-resolution chest CT (HRCT) in the evaluation of chronic diffuse lung disease, it is evident that CT has commonly become part of the standard diagnostic work-up in patients suspected of having PH [5]. It is important to be familiar with the parenchymal, vascular and cardiac changes that can be seen in patients with PH on both primary and secondary PH [2]. 15

2 16 Evaluation of the Role of High Resolution Computerized Tomography (HRCT) A CT determined main pulmonary artery (MPA) diameter ofgreater than 29mm demonstrates 87% sensitivity and 89% specificity for predicting PH. Specificity climbs to 100% when a MPA diameter of greater than 29mm is accompanied by findings of a segmental artery-to-bronchus ratio greater than 1:1 in three of the pulmonary lobes. When the ratio of CT determined pulmonary arterydiameter to aortic diameter is greater than one, a strong correlation with elevated mean pulmonary artery pressure has been shown, particularly in patients less than 50 years of age. The comparison of the size of the pulmonary artery to the ascending aorta is a practicable and easy assessment to make on CT scans [4,6]. Aim of the work: The aim of the work is to evaluate the role of HRCT and/or CTPA in the diagnosis, differentiation and detection of both pre- and post-capillary types of idiopathic and secondary PH, with correlation to clinical and echocardiography results whenever possible. Patients and Methods This study included 100 patients with known or suspected PH (26 males and 74 females), their age ranging from 17 days to 84 years (mean 42 years). Patients were referred to the Radiology Department of Cairo University Hospital from the Chest, ICU, internal medicine, rheumatology, cardiology, surgical and natal care units to perform HRCT (55 cases) or CTPA (45 cases) for different diagnostic purposes from October 2010 till February Data acquisition: - History: All patients were subjected to complete history taking including: The onset, course and duration of the main symptoms as: Cough, dyspnea, chest pain, hemoptysis and fatigue. In addition to: Personal history. History of other diseases. Medications. Previous operations. Family history. Occupational history. The history was taken in certain questionnaire form prepared and used in Thoracic Imaging Unit Kaser Al-Ainy Hospital for all cases that underwent HRCT or CTPA (Tables 1,2). - Clinical examination: All cases were subjected to clinical examination by their clinician and suspected to have PH. - Laboratory studies: Routine laboratory studies were done to patient (e.g. complete blood count). For those who underwent CTPA kidney function test is done (urea and serum creatinine). - Other investigations: Echocardiography: Table (1): Questionnaire form for patients who underwent HRCT examination. 1- Personal history: Name: Age: Sex: Occupation: Residence: Special habits: Marital status: 2- Complaint: 3- Present history: Analysis of complaint: o Onset o Course o Duration Associated symptoms: o Cough o Expectoration o Dyspnea o Wheeze o Hemoptysis o Constitutional o Chest pain o Congestion o Cyanosis Other systems HRCT of the Chest Sheet 4- Past history: Allergy T.B. Prolonged medication (anti T.B., steroids, chemo/radiotherapy, others) Operation 5- Family history: 6- Clinical examination and previous imaging: In nearly half of population of the study (49 patients), echocardiography was done, requested or presented at time of study.

3 Youssriah Y. Sabri, et al. 17 Other investigations: Done according to patient s condition e.g. pulmonary function test, lung biopsy. - MDCT examination: All patients either went through HRCT or CTPA examination. The procedure was conducted using a multi-detector row helical scanner with four detector arrays (Light Speed Plus; GE medical systems, Milwaukee, Wisconsin, USA) in Radiology Department, Cairo University. Technique of CTPA and HRCT Examination: - CTPA Technique: Table (2): Questionnaire form for patients who underwent CTPA examination. 1 - Personal history: Name: Age: Sex: Occupation: Residence: Special habits: Marital status: 2- Complaint: 3- Present history: Analysis of complaint: o Onset o Course o Duration Associated symptoms: o Cough o Expectoration o Dyspnea o Wheeze o Hemoptysis o Constitutional o Chest pain o Congestion o Cyanosis CTPA Sheet Other systems: Risk factors: DVT Connective tissue disorders Vasculitis Immobilization Estrogen therapy Obesity 4- Past history: Similar attacks Prolonged medication (steroids, chemotherapy) Operation or trauma 5- Investigations: Urea Serum creatinine PT&CT D-dimer V/Q scan 6- Family history: 7- Clinical examination and previous imaging: I- Points to be checked before starting the examination: Patient s laboratory findings, mainly the renal function tests. Revise the patient s file for previous investigations and helpful data. Make sure patient s fasting for 4-6 hours. Insure a functioning flexible venous cannula (18- or 20- Gauge) is inserted in an antecubital vein. II- Steps regarding the automated pump and contrast material: Check the automated injector and make sure it is connected and well-functioning. Fill the pump with 2 vials (50ml each) of nonionic contrast media (80-100ml) ( mg iodine/ml). The flow rate of injection of contrast material is 4ml/sec. The pressure limit was 150mm Hg in adults and 100mm Hg in children. Connect the disposable extension tube of the injector to the cannula and make sure there are no air bubbles. Set the pump ready for use. III- Instructions and preparations regarding the patient: Inform the patient of the procedure steps and reassure him/her. Train the patient how to hold breath and how to listen and follow the instructions from the recorded voice in the machine. Patients who were unable to hold their breath were instructed to breath as shallow as possible during the acquisition. Make sure the patient s calm and prepare him/her to tolerate the warm feeling, burning sensation and nausea that might occur during the contrast injection. IV- Procedure: Patient lies supine with the arms above his heads. Take AP scout. The region of interest was taken from the lung apices to the diaphragm downwards. V- Scanning delay adjustment: Smart prep technique was used in most of the cases in order to ensure scanning during maximum contrast in the pulmonary artery. The level of the pulmonary artery from the scout was chosen. Axial CT cut taken in the chosen level and put the ROI in the region of the MPA to ensure

4 18 Evaluation of the Role of High Resolution Computerized Tomography (HRCT) scanning when maximum contrast is in the pulmonary artery. In few patients, the smart prep technique wasn t functioning, we had to use the delay technique and an average of 9-12sec. delay was used. It was increased in patients with known cardiac medical problems. VI- Data acquisition: (Table 3) VII- Data processing and reconstruction: Scanning was during a single breath hold. Axial cuts were sent to the workstation for post processing and reconstruction. Mediastinal window is adjusted at WL 50 and WW 300. Table (3): Parameters used in this study for CTPA. Scout Kv120 ma20 Holding breath Protocol of CTPA Scan type Helical Scan range From lung apices to diaphragm Scan direction Cranio-caudal Detector Row 4 Slice thickness 1.25mm Slice interval 0.8mm Pitch 1.5:1 Detector configuration 4x1.25 Beam collimation 5.0 Gantry tilt 0.0 FOV Depends on patients size kv 140 ma 380 Reconstruction thickness 1-1.5mm Scan duration 22-30sec Contiguous transverse 1.5mm-thick images were routinely reconstructed at mediastinal and lung window settings (coronal and sagittal). MIP axial and coronal reconstructions are done in all patients that are of high value in identifying small vascular structures and the ones with an oblique course. Complementary lung window is also taken at WL 500 and WW 1500 to evaluate any lung lesion. - HRCT Technique: I- Points to be checked before starting the examination: Revise the patient s file for previous investigations and helpful data. There is no need for specific preparation or contrast. II- Instructions and preparations regarding the patient: Inform the patient of the procedure steps and reassure him/her. Train the patient how to hold breath and how to listen and follow the instructions from the recorded voice in the machine. Patients who were unable to hold their breath were instructed to breath as shallow as possible during the acquisition. III- Procedure: Patient lies supine with the arms above his heads. Take AP scouts. The region of interest was taken from below the diaphragm upwards to the lung apices. Table (4): Parameters used in this study for HRCT. Scout Kv120 ma20 Holding breath Protocol of CTPA Scan type Helical Scan range From lung apices to diaphragm Scan direction Caudo-crainal Detector Row 4 Slice Thickness 1.25mm Slice Interval 1.0mm Pitch 1.5:1 Detector configuration 4x1.25 Beam collimation 5.0 Gantry tilt 0.0 FOV Depends on patients size kv ma Reconstruction thickness 1-1.5mm Total exposure time IV- Data acquisition: (Table 4) V- Data processing and reconstruction: Axial cuts were sent to the workstation for post processing and reconstruction. For lung window images the windows are adjusted at WL 700 and WW Axial, sagittal and coronal reconstructed images are taken. Mediastinal window is also taken at WL 50 and WW 300 to evaluate mediastinal structures.

5 Youssriah Y. Sabri, et al. 19 Data analysis and interpretation: In each case the following was considered: - CT criteria of the PH: A- Measuring of the widest diameter of MPA at the site of bifurcation, which was divided into: i - 3.5cm. ii - > 3.5 <4cm. iii- 4cm. B- Relation between segmental pulmonary arteries and bronchus in different lung lobes, which was divided into: i - Normal (when it is = 1:1 in all lobes). ii - One (when it is >1:1 in one lobe). iii- Two (when it is >1:1 in two lobes). iv- Three (when it is >1:1 in three lobes). C- Relation between MPA and adjacent AO, which was divided into: i - Normal (when it is <1:1). ii- Increased (when it is > 1:1). Other CT findings: This includes CT signs that considered as cause for or present with PH. It divided into: A- Lung parenchyma. B- Vascular. C- Cardiac. Results In this study, 100 patients underwent HRCT (55 cases) or CTPA (45 cases), using a 4-MDCT scanner for evaluation of their pulmonary parenchyma, pulmonary vasculature and mediastinal structures to detect different diagnostic criteria, types and causes of PH. The study included 74 females and 26 males, their age ranging from 17 days to 85 years, mean (42.5 years). CT Criteriaof PH (Fig. 1): 1- Measurement of the MPA (Table 5). 2- Relation between segmental pulmonary arteries and bronchi (Table 6). 3- Relation between MPA and adjacent AO (Table 7). (A) (B) Fig. (1): A 42 year-old female patient complained of gradual progressive dyspnea and dry cough. Echocardiography showed PH. CTPA shows: A- Axial section mediastinal window shows dilated MPA (31mm), 1:1 ratio between MPA and nearby AO. B- Axial section lung window (zoomed image) shows 1:1 relation between segmental pulmonary artery and bronchus. No parenchymal lung abnormality detected. Table (5): Measurement of MPA diameter. MPA diameter Male Female Total 3.5cm >3.5<4cm cm Table (6): Relation between segmental pulmonary arteries and bronchi. Relation between segmental pulmonary arteries and bronchus Male Female Total Normal (=1:1) >1:1 in one lobe >1:1 in two lobe >1:1 in three lobe

6 20 Evaluation of the Role of High Resolution Computerized Tomography (HRCT) Table (7): Relation between MPA and adjacent A. Relation between MPA and aorta Male Female Total Normal (< 1: 1) Increased (>1:1) Echocardiography: 49 patients are those whom underwent echocardiography (7 male and 42 female) of these 40 are having PH by echocardiography and only 9 are normal. 24 patients of those with PH by echocardiography had MPA diameter 3.5cm. The 9 patients whom are normal negative by echocardiography had MPA diameter 3.5cm. 26 patients of those with PH by echocardiography had 1: 1 bronchio-arterial ratio in more than three lobe and 35 patients of those with PH by echocardiography had 1: 1 between the PA and the aorta. The study population was divided according to the suspected causes of PH into four groups (Table 8): 1- Group (A): Including patients with PH due to pulmonary causes (corpolmonale) (Fig. 2). 2- Group (B): Including patients with PH due to cardiac causes (Fig. 3). 3- Group (C): Including patients with PH due to vascular causes (Fig. 4). 4- Group (D): Including patients with PH due to unknown causes (idiopathic) (Fig. 5). Table (8): Different groups with the main findings other than the PH criteria. Group No. of patients Group A 36 Bilateral coarse reticulation (21 patients) Group B 27 Cardiac enlargement Group C Group D Main findings other than PH criteria (27 patients) 17 Pulmonary artery filling defect (12 patients) 20 Normal (11 patients) (A) (B) (C) Fig. (2): A 50 year-old complained of progressive dyspnea and cough. By clinical examination she was suspected to have PH due to interstitial lung disease. HRCT shows: A- Axial section mediastinal window shows dilated MPA (3 8.5mm), the AO measured 31.5mm ( 1: 1 ratio between MPA and nearby AO). B- Axial section lung window zoomed image (HRCT) shows 1: 1 relation between segmental pulmonary artery and bronchus. C, D- Axial (C) and coronal (D) sections lung window (HRCT) show bilateral diffuse ground glass opacities with bibasal coarse reticulations (fibrosis). (D)

7 Youssriah Y. Sabri, et al. 21 Discussion Pulmonary hypertension is a challenge for clinicians and radiologists, with a variety of possible underlying causes, each with its own specific treatment. MDCT can play a vital role in elucidating underlying cardiac, vascular, and pulmonary causes [7]. The clinical classification system for PH was updated at the fourth World Symposium on PH in Dana Point, California, in In patients with suspected PH, the diagnostic approach includes four stages: Suspicion, detection, classification, and functional evaluation [8]. Many conditions that cause PH have suggestive findings at MDCT; some causes may be surgically treatable, whereas others may demonstrate adverse reactions to vasodilator therapies used during the course of treatment. Therefore, the radiologist plays an important role in evaluating patients with this disease [8]. The aim of this study is to evaluate the role of MDCT (as a highly sensitive and specific modality) in diagnosis of PH and to be familiar with the radiological picture of its causes (pre or postcapillary), idiopathic and secondary. In the current study 100 patients (74 females and 26 males) were examined by either HRCT or CTPA using a 4-multidetector CT scanner (Light Speed Plus; GE medical systems, Milwaukee, Wisconsin, USA) in the Radiology Department, Cairo University Hospital. (A) (B) (C) (D) Fig. (3): A 34 year-old female patient (known case of mitral valve replacement) presented with dyspnea, chest pain and cough. She was diagnosed and treated as congestive heart failure. Echocardiography showed mitral valve and tricuspid regurge and PH. CTPA shows: A- Axial section mediastinal window shows increase MPA diameter (43.5mm) with >_ 1:1 ratio between MPA and nearby AO. Sternotomy is noted. B- Axial section lung window (zoomed image) shows >_ 1:1 relation between segmental pulmonary artery and bronchus. C, D- Axial section mediastinal window show all chamber enlargement, hyperdense structure noted at the site of mitral valve due to MVR.

8 22 Evaluation of the Role of High Resolution Computerized Tomography (HRCT) (A) (B) (C) (D) Fig. (4): A 46 year-old female patient presented with dyspnea, hemoptysis, chest pain and lower limb edema. Doppler revealed bilateral lower limb DVT. By clinical examination diagnosis was suspicious PH and thrombosis. CTPA shows: A- Axial section mediastinal window shows increase in the diameter of MPA (38.1mm) with 1:1 ratio between MPA and nearby AO. Filling defect (thromboembolism) noted in right and left pulmonary arteries. Mild pericardial effusion is seen. B, C- Sagittal mediastinal window sections (b- R & c- L) show the filling defect within the right and left pulmonary arteries. It also shows the subpleural consolidations (infarctions). D- Axial section lung window (zoomed image) shows >_ 1:1 relation between segmental pulmonary artery and bronchus. (A) (B) Fig. (5): A 50 year-old female patient presented with progressive dyspnea. Case diagnosed clinically as PH and possible interstitial lung disease was suspected HRCT shows: A- Axial section mediastinal window show dilated MPA (31. 1mm), the AO measured 31.9mm. B- Axial section lung window shows 1:1 relation between segmental pulmonary artery and bronchus. No parenchymal lung abnormality.

9 Youssriah Y. Sabri, et al. 23 The study population was divided according to clinical and MDCT findings into four groups. Group A including patients with PH due to pulmonary causes (corpolmonale), group B including patients with PH due to cardiac causes, group C including patients with PH due to vascular causes and group D including patients with PH due to unknown causes (idiopathic). This classification is highly matching with the classification adopted in the 4 th world symposium on PH: Perspectives for practice [9]. In this study guided by Frazier et al., (2000), Grosse and Grosse (2010) and Peña et al., (2012) we used the following criteria to diagnose and assess PH: 1- Measuring of MPA: The measurement of MPA was the first criteria we used in CT diagnosis of PH. This was also the first criteria used in diagnosis of pulmonary hypertension in the study done by Devaraj et al. [10], Grosse and Grosse (2010) [11] and Peña et al., [8]. Grosse and Grosse (2010) [11] stated that a pulmonary artery with a diameter more than 29mm has a positive predictive value of 97%, sensitivity of 87%, and specificity of 89% for the diagnosing PH [11]. However, in all our cases the MPA was more than 29mm in its widest dimension (except one case 17 days old female with MPA measure 1.5cm). For easier assessment and correlation this was further divided into three categories. This division was derived from the study done by Devaraj et al., (2010) [10], in which they correlated the dimension of the MPA with AO and nearby vertebral body (assumed to be 3cm) [10]. The MPA diameter was measured in workstation using electronic caliper. - First category is <_3.5cm (n=54, percentage 54%). - Second category is between >3.5<4cm (n=28, percentage 28%). - Third categoryis >_4cm (n=18, percentage 18%). The first category is the largest; likely this result was because mostly our cases presented early, and while the third category is the smallest as most of cases in the third category are advance stage of the disease. In patients with mild PH, the pulmonary artery may be only slightly dilated, and the findings overlap with those in control subjects without pulmonary hypertension [12]. 2- Relation between segmental pulmonary arteries and bronchi: The relation between the segmental pulmonary arteries and their neighboring bronchi is the second criteria we checked. In this criterion we compared the measurement of the segmental pulmonary artery with its neighboring nearby bronchus, which is normally 1:1. When the pulmonary blood pressure increases the ratio also increases. Also the numbers of lobes in which these relations are present increases. The enlargement of the segmental arteries, measured by making a subjective comparison with the size of the adjacent bronchus, occurs in patients with PH [13]. Also the study done by Devaraj et al., [10] suggests that segmental arterial size is a reliable marker of MPAP and in practice the comparison with adjacent bronchus is more convenient [10]. According to Grosse and Grosse [11] and Peña et al. [8], PH can be reliably predicted when the CT demonstrated diameter of the MPA is greater than 29mm and the segmental artery-to-bronchus ratio is greater than 1:1 in three of four pulmonary lobes (specificity, 100%). The presence of this relation in three lobes is seen in 53% (n=53) of our cases so we can predict PH with specificity 100% in these cases, however, this relation was seen only in two lobes in 20% (n=20) and in one lobe in lobe in 15% (n=15) of the cases. The normal artery/bronchus ratio, however, was found in only 12% (n=12) of the cases, all of whom were of the first category (MPA diameter <_3.5cm). 3- Relation between MPA and AO: The third criterion is the relation between the MPA and the AO. The AO is the largest artery in the body and normally the MPA is smaller in diameter than the aorta. When there is increase in the pulmonary pressure the MPA artery diameter may become larger than aorta and the relation become more than 1:1. Devaraj et al., [10] suggested that the ratio of the diameter of the MPA to the diameter of the AO is an accurate marker of MPAP because confounding variables, such as patient size, influence the size of the pulmonary artery and ascending aorta equally, enabling a form of internal correction [10]. In this study the increase ratio between MPA and the AO is seen in 76% (n=76) of cases. In one of these cases (patient with 17 days old with

10 24 Evaluation of the Role of High Resolution Computerized Tomography (HRCT) congenital heart disease) the increase ratio between MPA and AO was the main criterion of the PH as the diameter of MPA was only 1.5cm. The ratio was normal in 24% (n=24) of our cases. All of them were older than 45 years, and the measurement of the MPA was less than 3.5cm. At CTPA, a MPA diameter larger than that of the AO is also a sign of pulmonary hypertension, with a positive predictive value of 96% and specificity of 92%, especially in patients younger than 50 years old [8]. The results in this study were correlated with the echocardiography results whenever possible. From the 100 cases in this study 49 cases did echocardiography. 82% (n=40) of the cases who did echocardiography had PH (positive) by echocardiography and 18% (n=9) were normal (negative). In all negative cases the MPA diameter was less than 3.5cm. The normal segmental pulmonary artery/bronchus relation was seen in 8% (n=3) of the positive cases and 67% (n=6) of the negative cases. In the rest of the normal cases [the remaining 33% (n=3)] the segmental pulmonary artery was enlarged compared to the adjacent bronchus in one lobe (two cases), and two lobes (one case) but no cases showed three lobes affection. The normal relation between MPA and AO was seen 13% (n=5) of the positive echocardiography cases, in all of them the MPA measurement was!^3.5cm. Four of these five cases were older than 45 years old (one is 46 and three are ^!60 years old; as the measuring of the AO increases with age) and one was 30 year old. In the study done by Mao et al., they measured the AO in 1442 cases. 900 cases of whom; aged between 41 and 60 years, the AO measured between (30-34mm) in females and (33-37) in males, and in 434 cases ^!60 years old the AO measured (32-36mm) in females and (35-38mm) in males [14]. From the correlation of our CT findings in this study with the echocardiography results; PH can be predicted in 82% of cases depending on the measurement of MPA alone, in 87% of cases if there is also associated increase in the relation between MPA and aorta (regardless of the age) and in 92% of cases if there is associated increase in the ratio between segmental pulmonary arteries and bronchus in at least one lobe. From our results PH can be predicated with 100% specificity and sensitivity in cases where MPA diameter >35mm with increase in relation between MPA and aorta and at least 3 lobes show increase ratio between segmental artery and bronchus. In study done by Devaraj et al., [10] showed that a combination of CT and echocardiographic markers of PH in the form of a composite index is more strongly related to MPAP than either test in isolation [10]. In this study 36 patients (25 females and 11 males) were included in group A. They were clinically diagnosed as PH and were all referred from different hospital departments to perform either HRCT or CTPA to detect an underlying lung etiology. This group represents 36% (n=36) of the study. It is the largest group in this study. The female represents 69.4% (n=2 5) and male 3 0.6% (n= 11), age range years (the mean age is 51 years). 91.6% (n=33) of the cases did HRCT and 8.4% (n=3) did CTPA. The HRCT cases were suspected to have interstitial lung diseases. While the other 3 cases (8.4%) gave history of dyspnea and chest pain, and were suspected to have pulmonary embolism thus were referred to do CTPA, however, no evidence of embolism was detected instead interstitial findings were seen in the lung window. In this group we found diffuse bilateral lung lesions. Of these cases 92% (n=33) showed HRCT signs of interstitial disease. The main HRCT findingswere bilateral coarse reticulation seen in 58.2% of cases (n=21), bilateral ground glass opacity in 25.2% (n=9) of the cases and bilateral fibrosis 8.3% (n=3). Emphysematous changes were detected in 8.3% (n=3). In all these cases based on our CT findings the PH was attributed to lung disease. Thus the diagnoses of corpulmonale were given in these cases with PH. According to Grosse and Grosse, lung disease is the most common cause of PH [11]. On correlating our results with study done by Devaraj et al., the interstitial lung disease causing PH represent 50% of their 77 cases; however, the cardiac causes were not included in their study. The mean age of their patients was 55.6 years. In their study the IPF represented 70% of the interstitial lung disease causing PH [10]. In our study the IPF taking the upper hand in the diagnosis 83.3% (n=30) of the cases in group A.

11 Youssriah Y. Sabri, et al. 25 The main HRCT finding suggestive of IPF in our study was bilateral basal fairly symmetrical coarse reticulation with traction bronchiectasis and traction bronchiolectasis which was seen 58.2% (n=21) of cases of this group. This agrees with what Souza et al., stated that on HRCT, a confident diagnosis of IPF is based on the presence of bilateral, predominantly subpleural, and basal reticular opacities with associated traction bronchiectasis and honeycombing [15]. In 25.2% (n=9) of cases of group A, bilateral basal ground glass opacity was the predominant feature denoting early cases of IPF. Behr and Ryu (2008) [16] mentioned that PH can exist with mild IPF denoted by the presence of predominant ground-glass basal opacity [16]. Of Group A cases, three cases (8.3%) showed massive lung fibrosis in sarcoid patients.there was bilateral apical fibrosis and mediastinal lymph nodes. In the study done by Devaraj et al., the sarcoidosis represented 14% of the interstitial lung disease in their cases causing PH [10]. In the study done by Baughman et al. [17], on 53 sarcoid cases, 26 cases (49%) of them were found to have PH. They also stated that percentage of patients with PH in patient with sarcoidosis is higher than that with IPF in those cases waiting for lung transplantation [17]. The remaining cases 8.3% (n=3) were diagnosed as COPD with emphysematous changes. In the study done by Devaraj et al. [10], the COPD represented 6% of causes of PH in their cases [10]. According to Wright et al. [18], the actual incidence of PH in COPD is not known, although early studies estimated that 6% of patients with COPD would develop corpulmonale each year [18]. Group B in this study includes 27 patients (24 females and 3 males). They were all referred from the different hospital departments to perform either HRCT or CTPA. They were suspected to have cardiac disease causing PH clinically and by other radiological examination e.g. CXR or by echocardiography. The cardiac causes of PH are particularly important from both diagnostic and therapeutic standpoints, as many lesions are readily repairable with corrective surgery. Often, PH may be drastically reduced, or even returned to baseline, after surgical correction [19]. This group represents 27% (n=27) of the study. It is the second largest group in this study. The female represents 88.9% (n=24) and male 11.1% (n=3). The age range from 17 days to 85 years (mean age is 42). Hoey et al., [20] mentioned the Left-sided heart disease as one of the most common causes of PH [20]. While Tang (2009) [21] said that over two thirds of patients with chronic systolic heart failure or symptomatic valvular stenosis have associated PH. Degree of PH often correlates with symptoms (e.g. mitral stenosis) [21]. 17 (63%) of these cases did CTPA to assess for the pulmonary vasculature in known cardiac patients, while 10 cases (37%) did HRCT as they came with the possibility of interstitial lung disease with PH, but we found none, instead cardiomegaly suggesting cardiac disease were found and was proved latter. According to Hoey et al. [20], CTPA is widely utilized in the workup of patients with suspected pulmonary vascular disease and can identify both pulmonary and cardiac causes [20]. Our cardiac cases were divided into 23 (85%) acquired cases secondary to left heart disease and 4 (15%) congenital cases of shunt. Hoey et al. [20] stated that; the cardiac causes of PH are diverse and include multiple congenital and acquired cardiac diseases. They are subclassified into congenital systemic to pulmonary shunts and secondary to left heart disease [20]. In 85% (n=23) of our cardiac cases the main CT manifestation was left atrial enlargement either alone or with other chambers. According to Zeeb and Green [22] CT can be useful for analyzing cardiac chambers to determine their size, shape and thickness. Normal left atrium should have an AP dimension of approximately 4.5cm [22]. The remaining of our cardiac cases were due to congenital cardiac lesion 15% (n=4) and they were diagnosed by echocardiography. One had patent ductus arteriosus with patent foramen ovale, second one had ventricular septal defect and two cases had patent ductus arteriosus only. All these cases had left to right shunt. Grosse and Grosse mentioned that PH due to sustained cardiac left-to-right shunt can be seen in patients with congenital cardiac abnormalities such as ventricular septal defect, atrial septal defect and patent ductus arteriosus [11].

12 26 Evaluation of the Role of High Resolution Computerized Tomography (HRCT) The third group (Group C) included 17 patients (9 females and 8 males). They were all referred from different hospital departments to perform mainly CTPA. They were either suspected of having PH due to PE or other vascular causes. 12 of whom had Doppler of lower limbs showing DVT. This group represented 17% (n=17) of the study. It is the smallest group according to the size. The female represents 52.9% (n=9) and male 47.1% (n=8). The age range from 25 years to 77 years (mean age is 51). Nearly all cases did CTPA; 15 cases (88.2%) to investigate pulmonary vasculature. According to Wildberger et al. [23], four-slice MDCT showed promising results regarding PE diagnosis. From a radiological point of view, CTPA has effectively became the first imaging test in clinical routine, as patients with a high-quality negative CTPA do not require further examination or treatment for suspected PE [23]. In all those cases the vascular and parenchymal signs of PE were evaluated. The main vascular sign was filling defect in the pulmonary artery which was seen 70.6% (n=12) of cases and the main parenchymal CT radiological manifestation was multiple subpleural wedge shape consolidation seen in 47% (n=8) of the cases representing pulmonary infarctions and mosaic perfusion in 5.9% (one case). Reichelt et al., [24] mentioned that CTEPH is a rare but serious consequence of recurrent PE which can often be treated by PEA [24]. In study done by Devaraj et al., the CTEPH represent 8% of the patient with PH [10]. In study done by Remy-Jardin et al. [25], they named two categories of CT features of chronic PE, the vascular and parenchymal signs of chronic PE. The vascular signs were the filling defects and the parenchymal signs were mosaic perfusion and lung infarction with its sequelae namely the parenchymal scarring [25]. In 11.8% (n=2) of our cases in this group there were multiple bilateral lung nodules due to metastasis with multiple subpleural wedge shape consolidation considered as infarctions. Frazier et al., [2] described PH association with metastasis as enlarged central pulmonary arteries and cardiomegaly compatible with PH with illdefined nodular and confluent peripheral parenchymal opacities presenting multiple pulmonary infarcts [2]. One of the cases (5.9%) was a known case of schistosomiasis that showed CT vascular signs of PH. According to Graham et al. [26], schistosomiasis is a critical underlying etiology in many forms of severe PH [26]. Frazier et al., said that; HRCT of pulmonary schistosomiasis may show nodules, interstitial thickening, and patchy ground-glass attenuation in addition to dilatation of the central pulmonary arteries, right atrium and right ventricle [2]. Only 2 cases did HRCT (11.8%) to investigate lung parenchyma in cases of SLE in which PH was found and considered vasculitis as the cause of increase pulmonary pressure in both cases. Both cases showed no HRCT evidence of interstitial lung disease. Highland and Gilkeson [27] mentioned pulmonary vasculitis as one of the causes of the PH in SLE with or without alveolar hemorrhage [27]. Group D included 20 patients with PH due to unknown causes (idiopathic) (16 females and 4 males). They were sent for HRCT and CTPA in attempt to reveal the causes of their symptoms or to prove or exclude certain diagnoses. They presented by either clinical manifestation or radiological signs of PH. This group represented 20% (n=20) of the study and this makes it the third group in the study regarding the number. There were 16 females (80%) and 4 males (20%), the age range from 16 to 79 years (mean age is 47.5 years). In the study done by Devaraj et al., [10] on 77 patient, the idiopathic causes represent 22% of the patient with PH (patient with cardiac causes were not included in their study) [10]. This group together with group B contained the youngest mean age in our study, and the female to male ratio was 4:1. This agrees with Grosse and Grosse [11], who stated that IPAH is generally considered a disease of young adulthood, occurring most often in those between the ages of 20 and 45 years. Women are more commonly affected than men [11]. 50% (n=10) of the cases did HRCT and the other 50% did CTPA in which we found CT signs of PH without any other radiological signs to explain them so we considered these cases as idiopathic.

13 Youssriah Y. Sabri, et al. 27 Grosse and Grosse [11] said that characteristic vascular features of IPAH depicted at CT are central pulmonary artery dilatation, usually in the absence of detectable intraluminal thrombi [11]. Castañer et al., mentioned only the mosaic lung attenuation as the main parenchymal findings and they stated that it is hardly ever seen in those with IPAH [28]. Conclusion: Pulmonary hypertension, either primary or secondary, is a significant cause of morbidity and mortality. Although right heart catheterization is the gold standard for measurement of pulmonary artery pressure, this procedure is not without risk and expense. As a result, noninvasive estimation of MPAP is of particular interest and valuable for identifying the prognosis especially in patients with lung disease; and for planning specific therapy. The MDCT namely HRCT and CTPA are promising and easily reproducible methods in investigation of PH with good positive predictive value ranging from 82% to 92%. The radiologist must be familiar with the different CT signs of PH especially if we know that the sensitivity and specificity of prediction of PH increases when the different criteria are present at the same time. The importance of MDCT lies not only in diagnosis of PH but also in detecting the type, causes and complications of PH and according to this treatment and prognosis are differing significantly. The causes of PH can be summarized as pulmonary, cardiac, vascular and idiopathic. The pulmonary is the commonest cause of PH with the interstitial lung disease on top of the list and the main radiological investigation is HRCT. For cardiac (the second commonest cause) and the vascular causes the main radiological investigation is CTPA. The main complication of PH is right sided heart failure this also can be predicted if we are familiar with their CT signs. CT and echocardiography are providing complementary information about regarding PH. References 1- BURKE A.P., FARB A. and VIRMANI R.: The pathology of primary pulmonary hypertension. Mod. Pathol., 4: , FRAZIER A.A., GALVIN J.R., FRANKS T.J., et al.: Pulmonary vasculature: Hypertension and infarction. Radio graphics, March, 20: , BURKE A. and VIRMANI R.: Mini-symposium: Pulmonary pathology-evaluation of pulmonary hypertension in biopsies of the lung. Curr. Diagn. Pathol., 3: 14-26, DEVARAJ A., WELLS A.U., MEISTER M.G., et al.: The effect of diffuse pulmonary fibrosis on the reliability of CT signs of pulmonary hypertension. Radiology, 249 (3): , REVEL M.P., FAIVRE J.B., REMY-JARDIN M., et al.: Pulmonary hypertension: ECG-gated 64-section CT angiographic evaluation of new functional parameters as diagnostic criteria. Radiology, 250 (2): , NG C.S., WELLS A.U. and PADLEY S.P.G.: A CT sign of chronic pulmonary arterial hypertension: The ratio of main pulmonary artery to aortic diameter. J. Thorac. Imaging, 14: , TSAI C., TSAI W.L., WANG K.Y., et al.: Comprehensive MDCT evaluation of patients with pulmonary hypertension: Diagnosing underlying causes with the updated dana point 2008 Classification. AJR September, 197 (3): W471- W481, PEÑA E., DENNIE C., VEINOT J., et al.: Pulmonary hypertension: How the radiologist can help. Radio. Graphics, January, 32: 9-32, ROBBINS I.M.: Epidemiology and classification of pulmonary hypertension. Advances in pulmonary hypertension, Official Journal of the Pulmonary Hypertension Association. Summer, 8 (2): 77-78, DEVARAJ A., WELLS A.U., MEISTER M.G., et al.: Detection of pulmonary hypertension with multidetector CT and echocardiography alone and in combination. Radiology, February, 254 (2): , GROSSE C. and GROSSE A.: CT Findings in diseases associated with pulmonary hypertension: A current review. Radio. Graphics, 30: , DEVARAJ A. and HANSELL D.M.: Computed tomography signs of pulmonary hypertension: Old and new observations. Clinical Radiology, 64: , PEREZ-ENGUIX D., MORALES P., TOMAS J.M., et al.: Computed tomographic screening of pulmonary arterial hypertension in candidates for lung transplantation. Transplant. Proc., 39 (7): , MAO S.S., AHMADI N., SHAH B., et al.: Normal thoracic aorta diameter on cardiac computed tomography in healthy asymptomatic adultlt; Impact of age and gender. Acad. Radiol. July, 15 (7): , SOUZA C.A., MÜLLER N.L., FLINT J., et al.: Idiopathic pulmonary fibrosis: Spectrum of high-resolution CT findings. AJR, 185: , BEHR J. and RYU J.H.: Pulmonary hypertension in interstitial lung disease. Eur. Respir. J., 3: , BAUGHMAN R.P., ENGEL P.J., MEYER C.A., et al.: Pulmonary hypertension in sarcoidosis. Sarcoidosis vasculitis and Diffuse Lung Diseases, 23: , WRIGHT J.L., LEVY R.D. and CHURG A.: Pulmonary hypertension in chronic obstructive pulmonary disease: Current theories of pathogenesis and their implications for treatment. Thorax., 60: , 2005.

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