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Detection of Pulmonary Embolism

Rationale and Objectives

The purpose of this study was to compare the efficacy of dual-energy computed tomography (DECT), time-resolved magnetic resonance (MR) imaging (MRI) perfusion measurements, and high-resolution MR angiography (MRA) for the detection of pulmonary embolism (PE) in a rabbit model.

Materials and Methods

Two hours after Gelfoam ( n = 16) or saline ( n = 2) injection into the femoral vein, 18 rabbits were first imaged using dual-energy computed tomographic pulmonary angiography (CTPA), from which blood flow imaging (BFI) were produced. Next, the rabbits underwent time-resolved MR perfusion measurements and MRA using a 3.0-T scanner. Two radiologists who were blinded to histopathologic findings independently evaluated the results of CTPA, BFI, time-resolved MR perfusion, and MRA for each rabbit and recorded the locations and number of pulmonary clots on a per lobe basis. Immediately after MRI examination, pathologic determination of the locations and numbers of lung lobes with PE was recorded. Histopathologic results served as the reference standard to determine the sensitivity and specificity of DECT (BFI and CTPA) and MRI (time-resolved MR perfusion and high-resolution MRA) for the detection of PE.

Results

The induction of PE was successful in all animals, but three rabbits were excluded because of death prior to MRI procedures (caused by complications during the embolization procedure); only data from the remaining 15 rabbits were included in the final analysis. Histopathology demonstrated 24 lobes with clots and 51 lobes without clots. CTPA, BFI, and MRI correctly identified PE in 23, 23, and 20 lobes, respectively, and the absence of emboli in 48, 46, and 46 lobes, respectively; these results corresponded to sensitivities of 95.8%, 95.8%, and 83.3% and specificities of 94.1%, 90.2%, and 90.2% for reader 1 and sensitivities of 91.7%, 91.7%, and 87.5% and specificities of 90.2%, 88.2%, and 88.2% for reader 2 for CTPA, BFI, and MRI, respectively. Good or excellent intermodality and interreader agreement among CTPA, BFI, and MRI were found.

Conclusions

DECT can simultaneously provide high-resolution pulmonary artery and lung iodine mapping with slightly high diagnostic accuracy for the detection of PE compared to MRI in an experimental rabbit model of PE. This improvement was not statistically significant given the study sample size.

Pulmonary embolism (PE) is the third most common cause of cardiovascular death in the United States, with an annual incidence of 300,000 to 600,000 per year . Despite its high prevalence, PE is difficult to diagnose, with only 43 to 53 patients per 100,000 being accurately diagnosed and up to 70% of clinically unsuspected PE diagnosed at autopsy. Death occurs in up to 90% of patients with unrecognized PE, whereas in treated patients, PE accounts for <10% of deaths . The main reasons for this high rate of nondiagnosis are that the clinical signs and symptoms of PE are not specific to the condition and that the presentation is variable.

Imaging plays a crucial role in the diagnosis of PE. Currently, multidetector computed tomographic (CT) pulmonary angiography (CTPA) has largely replaced lung scintigraphy and conventional pulmonary angiography for the assessment of possible PE; in 2007, CTPA was accepted as the reference standard for the diagnosis of acute PE . In contrast to single-source computed tomography, dual-source CT scanners, with two orthogonally mounted detectors and tube arrays operating simultaneously at different tube potentials (80 and 140 kVp), allow for the performance of dual-energy computed tomography (DECT) with minimal patient motion registration artifacts . Contrast-enhanced lung DECT can simultaneously provide both lung anatomic (including lung parenchyma and vessels) and functional information, opening new horizons in the imaging of acute pulmonary thromboembolism ( ).

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Materials and methods

Animal Model

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Scan Protocols

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Image Reconstruction and Analysis

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Time-resolved MR Perfusion and MRA

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Pathologic Processing

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Statistical Analysis

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Results

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Table 1

Lobar Location of Pulmonary Emboli as Determined by DECT, MRI, and Histopathology

Right Lung Left Lung Reader Modality Upper Middle Lower Upper Lower Overall 1 CTPA 0 2 (1 ∗ ) 10 (1 ∗ , 1 † ) 1 13 (1 ∗ ) 26 BFI 0 4 (3 ∗ ) 10 (1 ∗ , 1 † ) 1 13 (1 ∗ ) 28 DECT 0 2 (1 ∗ ) 10 (1 ∗ , 1 † ) 1 13 (1 ∗ ) 26 MRA 0 1 (1 ∗ , 1 † ) 10 (2 ∗ , 2 † ) 0 (1 † ) 14 (2 ∗ ) 25 2 CTPA 0 4 (3 ∗ ) 10 (1 ∗ , 1 † ) 0 (1 † ) 13 (1 ∗ ) 27 BFI 0 5 (4 ∗ ) 10 (1 ∗ , 1 † ) 0 (1 † ) 13 (1 ∗ ) 28 DECT 0 4 (3 ∗ ) 10 (1 ∗ , 1 † ) 0 (1 † ) 13 (1 ∗ ) 27 MRA 0 2 (2 ∗ , 1 † ) 11 (2 ∗ , 1 † ) 0 (1 † ) 14 (2 ∗ ) 27 Pathology 0 1 10 1 12 24

BFI, blood flow imaging; CTPA, computed tomographic pulmonary angiography; DECT, dual-energy computed tomography; MRA, magnetic resonance angiography.

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DECT

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Figure 1, True-positive pulmonary embolism case demonstrated by histopathology (rabbit 5). (a) Blood flow image shows decreased lung perfusion in the left lower lobe. (b) Maximum-intensity projection image with 5-mm slice thickness shows the termination of contrast-filled lumen of the left peripheral pulmonary artery (arrow). (c) High-resolution magnetic resonance (MR) angiography also showing the enhancement cutoff of the left peripheral pulmonary artery (arrow). (d) Photomicrograph (hematoxylin and eosin staining, 200×) shows the gelatin sponge in the left lower pulmonary artery (arrow). Four gelatin sponges 2 × 2 × 10 mm in size were injected into the right femoral vein 2 hours before these dual-energy computed tomographic and MR imaging examinations were performed.

Figure 2, True-positive pulmonary embolism case demonstrated by histopathology (rabbit 11). (a, b) Coronal blood flow images (BFIs) show decreased lung perfusion color coded as blue in the bilateral lower lobes (ovals). (c) Sagittal BFI shows decreased lung perfusion color coded as blue in the right lower lobe (oval). (d) Computed tomographic pulmonary angiography with maximum-intensity projection reformation with slice thickness of 5 mm showing the termination of contrast-filled lumen of the left lower pulmonary artery (yellow arrow) and decreased enhancement of the right lower pulmonary artery (red arrow). Note that the enhancement of the distal right lower pulmonary artery disappeared (arrowhead). (e) Magnetic resonance (MR) angiography shows the enhancement cutoff of the bilateral lower pulmonary arteries (arrows). (f) Time-resolved MR perfusion measurements showing the perfusion defect in the left lower lobe (oval). Photomicrograph showing the gelatin sponge (arrow) in the (g) right (hematoxylin and eosin [H&E] staining, original magnification), (h) right (H&E staining, original magnification, 400×), and (i) left (H&E staining, original magnification, 400×) lower pulmonary arteries.

Figure 3, False-positive cases on dual-energy computed tomography and magnetic resonance angiography (MRA) (rabbit 2). (a) Coronal blood flow image shows decreased lung perfusion color coded as blue in the bilateral lower lobes (ovals). (b) Computed tomographic pulmonary angiography with maximum-intensity projection reformation with slice thickness of 5 mm shows the enhancement cutoff of the bilateral lower pulmonary arteries (arrows). (c) MRA shows the enhancement cutoff of the bilateral lower pulmonary arteries (arrows). (d) Photograph of the gross pathologic specimen shows a dark red discoloration of the left lower lung lobe; no marked discoloration of the right lower lung lobe was shown. Four gelatin sponges 2 × 2 × 10 mm in size were injected into the right femoral vein 2 hours before these dual-energy computed tomographic and magnetic resonance imaging examinations were performed.

Table 2

Accuracy of DECT and MRI for the Detection of Pulmonary Embolism

Results (n) Statistical Analysis (%) Reader Modality TP TN FP FN Sensitivity Specificity PPV NPV Accuracy 1 CTPA 23 48 3 1 95.8 (23/24) 94.1 (48/51) 88.5 (23/26) 98.0 (48/49) 94.7 (71/75) BFI 23 46 5 1 95.8 (23/24) 90.2 (46/51) 82.1 (23/28) 97.9 (46/47) 92.0 (69/75) DECT 23 48 3 1 95.8 (23/24) 94.1 (48/51) 88.5 (23/26) 98.0 (48/49) 94.7 (71/75) MRA 20 46 5 4 83.3 (20/24) 90.2 (46/51) 80.0 (20/25) 92.0 (46/50) 88.0 (66/75) 2 CTPA 22 46 5 2 91.7 (22/24) 90.2 (46/51) 81.5 (22/27) 95.8 (46/48) 90.7 (68/75) BFI 22 45 6 2 91.7 (22/24) 88.2 (45/51) 78.6 (22/28) 95.7 (45/47) 89.3 (67/75) DECT 22 46 5 2 91.7 (22/24) 90.2 (46/51) 81.5 (22/27) 95.8 (46/48) 90.7 (68/75) MRA 21 45 6 3 87.5 (21/24) 88.2 (45/51) 77.8 (21/27) 93.8 (45/48) 88.0 (66/75)

BFI, blood flow imaging; CTPA, computed tomographic pulmonary angiography; DECT, dual-energy computed tomography; FN, false-negative; FP, false-positive; MRA, magnetic resonance angiography; NPV, negative predictive value; PPV, positive predictive value; TN, true-negative; TP, true-positive.

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MRI

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Figure 4, One false-positive case on magnetic resonance angiography (MRA) (rabbit 15). (a) Coronal blood flow image shows homogeneous iodine mapping in both lungs. (b) Computed tomographic pulmonary angiography with maximum-intensity projection reformation with slice thickness of 5 mm shows the normal tapering of the pulmonary arteries. (c) The enhancement cutoff of bilateral pulmonary arteries was observed on high-resolution MRA (arrows). Photographs of (d) gross specimen, (e) hematoxylin and eosin staining (original magnification), and (f) microscopy (hematoxylin and eosin staining, original magnification, 100×) show the pink surface of both lungs and no gelatin sponge clots in the pulmonary arteries (arrows) which were located in the right ventricle.

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Discussion

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Conclusions

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Acknowledgment

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