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Journal of Computer Assisted Tomography:
doi: 10.1097/RCT.0000000000000091
Thoracic Imaging

Pulmonary Hypertension Detection Using Dynamic and Static Measurable Parameters on CT Angiography

Siegel, Yoel MD*†; Mirpuri, Tarun MD

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Author Information

From the *University of Miami, Miller School of Medicine; and †Jackson Memorial Hospital, Miami, FL.

Received for publication November 20, 2013; accepted February 24, 2014.

Reprints: Yoel Siegel, MD, University of Miami Miller School of Medicine; and Jackson Memorial Hospital, West Wing 279, 1611 NW 12th Ave, Miami, FL 33136 (e-mail: ysiegel@med.miami.edu).

The authors declare no conflict of interest.

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Abstract

Objective

The aim was to assess dynamic and static parameters on routine computed tomography pulmonary angiography (CTPA) that may detect pulmonary hypertension (PH).

Methods

Fifty patients underwent CTPA and echocardiograms. Twenty-six patients had PH, and 24 patients did not have PH. The following parameters were measured on CTPA: density of the pulmonary artery (PA), ratio between the density in the PA and the thoracic aorta (TA), the time between the start of contrast injection to the time the scan trigger density was reached, and PA diameter.

Results

All measured parameters showed significant correlation with PH detected by echocardiogram. The best combination of parameters for detection of PH was contrast density ratio between PA and thoracic aorta of greater than or equal to 1.5 and/or a time to scan trigger of greater than or equal to 8 seconds.

Conclusions

The parameters measured correlate well with PH by echocardiography. This suggests that CTPA can potentially be used to detect PH.

Pulmonary hypertension (PH) is defined by hemodynamic criteria that include a mean pulmonary artery (PA) pressure over 25 mm at rest or 30 mm Hg during exercise at catheterization.1 The most common reference method for diagnosis is by catheterization of the PA and pressure measurement. There are a variety of diseases that can cause PH. These were classified in 1998 during the Second World Symposium on Pulmonary Hypertension and revised in 2003. According to the World Health Organization, there are 5 main categories purposed: pulmonary arterial hypertension, PH with left heart disease, PH associated with lung diseases and/or hypoxemia, PH caused by chronic thrombotic or embolic disease, and miscellaneous disease such as sarcoidosis and histiocytosis X.2,3 The exact prevalence of PH is unknown, although the estimated prevalence of primary PH in the general population is 1 to 2 cases per million.4,5 One study found a PH prevalence of 0.326% in patients undergoing echocardiograms.6 Regardless of the etiology, PH is a debilitating disease with high morbidity and mortality. The estimated survival from primary PH from the time of diagnosis is 2.5 years. However, prognosis improves in patients that can benefit from prescribed treatment.6–8 Multiple studies have assessed parameters on cross-sectional imaging that correlate with PH such as central pulmonary arteries size, tapering vasculature, right ventricular size, and thoracic vascular ratios.9,10 In addition, echocardiogram can screen for PH by estimating the pulmonary arterial pressure. This is achieved by measuring the regurgitant jet velocity at the tricuspid valve and determining the right atrial pressure by assessing the inferior vena cava collapsibility during the respiratory cycle. This method is a widely used technique to assess pulmonary pressure and is considered a key tool in the screening algorithm for diagnosis.11 The symptoms of PH are nonspecific and can include fatigability, dyspnea, angina, and syncope. This nonspecific presentation may lead to a variety of diagnostic procedures before diagnosis such as CT angiography of the pulmonary arteries (CTPA). Many studies to date have evaluated static findings on CT that can suggest PH; however, dynamic parameters with intravenous (IV) contrast-enhanced CT have not been widely studied. The aim of this study was to identify and assess measurable dynamic parameters on routine CTPA that may detect PH. The study rational is based on the CTPA IV bolus that is timed to maximally opacify the pulmonary arteries. This bolus time to peak will likely be delayed in patients with elevated pulmonary pressure compared to those without PH. In addition, in patients with PH, the increased pulmonary pressure would cause both an increase in pooling of opacified blood in the pulmonary arterial system as well as increased transit time from the right heart system to the left. We also assessed the PA diameter as a static parameter.

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MATERIALS AND METHODS

The study received institutional review board approval. Using computer-based archived data between May 2011 and March 2012, we identified 108 patients who presented to the emergency department and had both CTPA and echocardiogram studies within 6 months of each other. In each patient, the echocardiogram report was evaluated to determine whether the pulmonary pressure was assessed and if it was reported. The CTPA scans were also evaluated to determine if they were adequately performed and if all necessary images and data were available in the picture archiving and communication systems (PACS) for the propose of analysis for this study. Computed tomography pulmonary angiography studies at our institution during the study period were performed according to a standardized protocol. The protocol varies slightly according to patient’s weight; however, a specific set of scanning parameters are followed. All CTPA scans are done on either a 64-channel Somatom Sensation or a 128-channel Definition DS (Siemens Healthcare machines, Forchheim, Germany). The nonionic iodinated IV contrast used was 100 to 140 mL of Optiray 320 (Mallinckrodt Pharmaceuticals, St. Louis, MO) injected at a rate of 3.5 cc per second. The scanning parameters were as follows: kilovolt (peak), 120; effective milliampere second, 140 to 220 (Care dose used); Gantry rotation time, 0.5 second; and slice collimation, 0.6 mm. Before IV contrast administration, a single noncontrast axial image through the level of the main PA is obtained, after which the region of interest (ROI) is placed over the main pulmonary artery (MPA). Subsequently, a SMART PREP technique is used in which after initiation of intravenous contrast administration there is repeated scanning at the level of ROI every second. This is continued until the density in the MPA reaches a threshold of 120 Hounsfield units (HU; Fig. 1). At this point, the CT begins to scan the patient automatically without the technologist’s intervention, unless there is an indication to override the computer. The scan is performed at maximal inspiration. The CTPA scans included in the study were assessed for the following static and dynamic parameters that were measured or calculated: (1) Maximum density of contrast (in HU) in the MPA. This was measured from the CTPA scan itself and not the SMART PREP. (2) A ratio value obtained by dividing the HU value in the MPA by the HU value in the ascending thoracic aorta at the level of the MPA (PA/TA ratio). This was also measured on the CTPA scan itself and not the SMART PREP. (3) The time it took during the monitoring phase for the trigger threshold of 120 HU to be reached. This was derived from a graph that tracked the SMART PREP images as the density was measured. (4) Pulmonary artery diameter measured from the CTPA scan. Figures 1 to 4 depict these measured parameters. The echocardiographic studies at our institution are performed in a standardized format. Three- to 5-MHz sector probes are typically used, with standard views of the heart assessed. The echocardiographic reports of the patients in the study were evaluated to see if PH was present or not. For the purpose of the study, we did not record the specific measurement of the pulmonary pressure if it was stated in the report or the etiology of PH; rather, we assessed if the report stated whether PH was present or not. Statistical analysis was performed using statistical software (Statistical Package for the Social Sciences version 20; SPSS Inc, Chicago, Ill). The Student t test was used to compare the mean values of all parameters measured on CTPA between patients with or without PH on echocardiogram. Logistic regression analysis was performed on all variables. In addition, discriminate analysis was used with multivariant backward elimination method to find the variables that best predicted PH. To find clinically useful values for the parameters studies, different values and combinations were studied and their sensitivity and specificity for detection of PH were assessed. P < 0.05 was considered significant.

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RESULTS

Of the 108 patients, 58 patients were excluded from the study for a variety of reasons that were related to both CTPA and echocardiogram. Twenty patients were excluded because the data regarding bolus tracking and time to trigger were not submitted to PACS and therefore could not be analyzed. In 7 patients, the CTPA contrast bolus was diagnostically inadequate and deemed of unreliable technique. In 2 cases, the scan was triggered manually by the technologist. In one patient, the trigger ROI was placed erroneously over the aorta; and in one patient, motion artifices were so severe the scan could not be assessed properly. Of the echocardiograms, 12 patients were excluded because the echocardiogram report deemed the study technically limited owing to patient-related issues such as limited patient cooperation or body habitus. In 15 patients, the echocardiogram report did not specifically state whether the patient did or did not have evidence of PH and therefore could not be used for the study. Overall, 27 patients were excluded for echocardiogram reason and 31 for CTPA. Fifty patients were included in the study. Of these, 26 were identified as having PH on echocardiography and 24 patients did not have evidence of PH. Of those with PH on echocardiogram, there were 13 men and 13 women; and of those without PH on echocardiogram, there were 11 men and 13 women (Table 1). All 4 parameters measured showed significant mean value differences between patients with and without PH (Table 2). In addition, the logistic regression analysis revealed a statistically significant correlation between the variables and PH (Table 2). When implementing discriminate analysis, the best predictors for PH were the PA/TA ratio and the pulmonary diameter. The software was able to predict correctly the presence or absence of PH in 40 (80%) of the 50 patients when using this combination. We also tried to identify quantifiable threshold criteria that may be useful in the clinical setting. Several values were assessed; the most sensitive and specific ones analyzed are presented in Table 3. When combining parameters, the combination of time to trigger of 8 seconds or more or a PA/TA ratio of more than 1.5 yielded a sensitivity of 88.5% and specificity of 79.2%, whereas a combination of PA/TA ratio of 1.5 or greater and a diameter of 2.9 cm or greater yielded a sensitivity of 84.6% but a specificity of only 62.5%.

TABLE 1
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TABLE 2
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TABLE 3
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DISCUSSION

Pulmonary hypertension is usually diagnosed by direct pressure measurements of the right heart and PA. This is an invasive procedure. Ideally, the number of patients without PH having this procedure would be minimal. In addition, if PH is present in a patient, early detection is a priority; therefore, noninvasive studies that can credibly detect PH should be studied. The goal of this study was to examine several measurable parameters on routine CTPA that may detect PH. Computed tomography pulmonary angiography is frequently used to evaluate for pulmonary embolism; however, the data presented here suggest that it may also be used to identify the presence of PH in undiagnosed patients. Both static measurement, such as PA size, and dynamic parameters, such as bolus tracking and density ratio between the MPA and the aorta, seem to correlate with PH. Furthermore, in this study, we tried to find clinically useful threshold values on routine CTPA scans that can help identify patients who warrant a diagnostic study for PH. Potentially, these measurable parameters can be readily used by radiologists in routine clinical work. The anatomical size of the pulmonary arterial vasculature and its correlation to PH has been assessed in many studies and has shown variable correlation. Tan et al found that when measured in patients with parenchymal lung disease, the diameter of the MPA of 2.9 cm or greater correlates well with PH. The correlation was even stronger when combined with segmental arterial to bronchus ratio of greater than 1.12 We also found a significant correlation between PA size and PH, although the sensitivity and specificity we found were lower than some previously reported. On the other hand, several other studies using MPA diameter on CT and MRI did not find a useful diameter measurement that correlates with PH and did not find that the PA diameter can predict PH.13–16 Other studies focused on additional static measurements that can indicate PH and have reported varying levels of correlation as well.17 In comparison, studies of dynamic changes in the pulmonary system on CTPA have received less attention in the literature to date. Alford et al studied pulmonary perfusion by assessing mean transit time and pulmonary blood flow with CT. In that study, patients with and without emphysema were compared by measuring density in the lung parenchyma on electrocardiogram-gated CTPA. Specific conditions were used such as scanning during expiration with high flow contrast bolus to allow maximal flow through the pulmonary capillary bed.18. In our study, we assessed several parameters measured in the main pulmonary and systemic circulation on routine non–EGC-gated CTPA scans without using specific extraordinary conditions. We were interested in identifying tools that may be used in routine clinical work. Of these measurable dynamic parameters, the single most sensitive and specific one was the density ratio of the PA/TA of 1.5 or greater. Although the sensitivity was only 73%, the specificity was quite high at 91.7%. By combining 2 parameters, PA/TA ratio or time to trigger of 8 seconds or more, a sensitivity of 88.5%, and a specificity of 79.2% were achieved, suggesting that this combination can identify a large percent of patients with PH. This combination was superior to the PA/TA ratio and PA size at 2.9 cm or greater. There are a variety of diseases that can lead to PH such as the pulmonary arterial disease, lung parenchymal disease, and left heart disease. Nevertheless, the end result is elevated MPA pressure.2,3,19. The hypothesis we studied is based on the premise that an elevated pulmonary pressure will lead to hemodynamic changes affecting IV contrast flow in the main arterial vessels. As pressure rises in the PA back pressure will cause increased pooling of IV contrast at the prearteriolar level of the pulmonary bed, thus increasing density in the MPA. Additionally, this can cause increased IV contrast transit time leading to relatively late aortic opacification, hence an elevated PA/TA density ratio. The imaging findings of these pathophysiological changes have been studied on MRI.20,21 Skrok et al demonstrated that on MRI, both transit time and time to peak of IV contrast are increased in patients with PH, indicating that these are markers for pulmonary hemodynamics and cardiac function and may help determining prognosis. The results of this study support these previous studies and offer CT as a possible tool both for detecting PH and potentially following patients with a diagnosis of PH that are not suitable for MRI surveillance. Furthermore, the density ratio and time to trigger can be achieved by acquiring only several images through the level of the MPA and do not need a complete lung CTPA. Therefore, this can potentially be a tool to assess PH with a very limited and focused CTA study with minimal dose to the patient.

There are several limitations to this study. The reference study was not direct PA catheterization but rather an echocardiogram. Although this is a weakness, the statistical results are strong and suggest that these 2 imaging modalities, CTPA and echocardiogram, correlate highly with regard to PH. It is unlikely that the findings are incidental or that the correlation with a direct catheterization would not be significant. Nevertheless, a future study comparing CTPA with right heart and PA catheterization measurements is needed. A second weakness is that the study cohort is relatively small. Many of the patients were disqualified owing to lack of data on the report or in PACS. However, the stringent criteria used were to make the study as accurate as possible. If meticulous CTPA technique is followed and accurate data is collected the yield will likely be high. In addition, it may be that the parameters collected from CTPA scans can be measured on routine nonangiography chest CT scans, although this can be studied separately.

In summary, presented here are several dynamic parameters on CTPA that correlate well with PH diagnosed on echocardiogram. The strength of the findings is that dynamic parameters have not been extensively studied in CT. Also offered are threshold criteria that can potentially be a tool used by radiologists, and if met, merit further investigation of PH. These findings are preliminary in that correlation between dynamic parameters on CTPA and direct catheterization pressure measurements of the right heart and PA are needed to establish this relationship.

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ACKNOWLEDGMENTS

The authors thank Professor Noam Alperin, PhD, and Mr Lee Sang for their assistance in the statistical analysis.

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Keywords:

pulmonary hypertension; pulmonary artery CT angiography

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