Clinical evidence Spectral CT in thoracic disorders

Introduction

In daily practice, computed tomography (CT) represents the cornerstone imaging modality for the evaluation of various thoracic disorders. For many years, spectral CT has emerged as a new method of investigation for several diseases in the chest.1,2 With the benefits it provides in material decomposition, lung perfusion analysis, and improvements to image quality through artifact reduction or enhancements to iodine content in suboptimally enhanced vessels, the list of interesting and innovative applications for spectral CT continues to grow. The IQon Spectral CT was installed in our radiology department in May 2016 and has since been aiding our diagnostic capabilities. The goal of this chapter is to share our experience with this dual-layer, detector-based spectral CT system in our daily practice, and to provide a review of available literature on the topic.

Acquisition and review of chest images

In our practice, chest CT scans are obtained with a routine protocol using 120 kVp without modifying the imaging protocol or patient selection process to obtain spectral information. If the patient is obese, 140 kVp is preferred, and the mAs adjusted to keep the dose neutral. With the dual-layer, detector-based IQon Spectral CT system, SBI images (spectral base images) are captured during each CT examination. The SBI image data sets are loaded into the IntelliSpace workstation and inspected using different reconstruction algorithms. Analyzing the images using a dynamic approach is preferred. Virtual monoenergetic images can be extracted and extrapolated at wide energy levels, ranging from 40 to 200 keV, by simply sliding the cursor to the desired energy level on a dedicated workstation, or by using the Magic Glass on PACS app. The images are optimized by adjusting the contrast of the image, as well as the noise with potential reduction of artifacts. This simplified process for image acquisition and post-processing in dual-layer detector-based spectral CT may widen practical uses of spectral information in daily practice, such as for the evaluation of incidental findings or improvement of suboptimal studies. For chest image analysis, a recent study has shown that the optimal monochromatic energy level to analyze the lung parenchyma is around 50 to 55 keV.3 A set of images is systematically reconstructed at this energy and automatically sent to our PACS.

A material decomposition algorithm is also used in order to differentiate materials on the basis of the photoelectric effect within a certain density range, and by assigning colors to different materials. Iodine, Iodine no Water, and Z effective atomic number maps are generated and are used to highlight small differences in tissue composition. This allows us to obtain an instantaneous representation of a pulmonary perfusion, for example. Elimination of certain substances, such as iodine or calcium, can be performed as well to produce virtual non-contrast (VNC) or virtual non-calcium images.

General spectral CT applications

The use of virtual monoenergetic imaging

The use of virtual monochromatic dual-layer spectral CT imaging at high energy levels results in a significant reduction of streak artifacts produced by beam hardening.4 Monochromatic images obtained at higher energy simulate increased penetration of the X-ray beam and are beneficial for reducing blooming and metallic artifacts. This technical capability can be useful when high-density contrast is present in the subclavian vein or in the superior vena cava during a pulmonary CT angiography performed at a high rate of injection or with dense contrast material (Figure 1). The energy level can be used at 200 keV with a significant reduction of artifacts and better visualization of obscured areas like axillae or subclavian regions. On the other hand, when virtual monochromatic imaging is used at low energy levels, the iodinated content of the vessel can be artificially highlighted, even in retrospect. This capability is particularly interesting in daily routine because there are many potential causes affecting the pulmonary vascular enhancement in chest CT, such as technical errors, extravasation, transient interruption of contrast material due to Valsalva maneuvers, or increased circulatory volume in pregnant women. This suboptimal opacification is rarely known in advance, and the use of virtual monoenergetic imaging retrospectively can improve vascular opacification at low energy levels (Figure 2). The performance of virtual monoenergetic imaging for pulmonary CT angiography (CTA) with a reduced iodine dose has been studied by various groups 5-9 Recently released noise-optimized virtual monoenergetic imaging techniques applied to CTA for imaging various body parts have shown improved image quality compared with traditional virtual monoenergetic images, particularly at 40 or 50 keV 6-8

Chest CT angiography performed in the context of acute chest pain. Contrast medium (350 mg I/ml) was injected through a right antecubital vein at a rate of 3 ml/sec. On the left, conventional images obtained at the level of the upper chest (mediastinal window) demonstrated heavy streak artifacts related to the dense contrast medium present in the right subclavian vein and obscuring the right axillar region. On the right, the same image displayed at 200 keV showed a significant reduction of artifacts with a better analysis of the right axillar region.

The use of virtual non-contrast and material specific maps

Virtual non-contrast (VNC) can delineate calcifications that are obscured by contrast material (Figure 3). Enhanced lymph nodes can be distinguished from lymph nodes that contain calcium silicates on VNC images, a characteristic that is important in identifying residual tumor and inflammatory processes. In a few cases, heavy calcifications, particularly coarse, low-density calcifications and hematomas, mimicking endoleaks can make a diagnosis difficult, especially in patients referred for acute chest pain, but these can be differentiated on VNC images.

Emergency imaging of patient for suspected PE. Spectral CT was performed after injection of contrast medium (100 ml Xenetix 350, Codali-Guerbet, France). The patient performed a Valsalva maneuver during the CT acquisition and the opacification of pulmonary arteries was judged of poor quality. Conventional CT images (Figure 2A, upper row) reformatted in the plane of a lower lobe pulmonary artery did not reveal any clot in the course of the vessel from the proximal part down to the periphery. Z effective map (Figure 2A , lower row) revealed a perfusion defect at the periphery of the lobe (red arrow). Spectral CT data were used to generate monochromatic images at 45 keV (Figure 2B) revealing a clot in a peripheral pulmonary artery (yellow arrow). Note the increased contrast level in the pulmonary vessels compared to the conventional CT images acquired at 120 kVp.

Spectral CT seems to be a promising, noninvasive technique for the evaluation of lung morphology and functional information simultaneously, such as lung ventilation and perfusion. In literature, xenon gas (atomic number 54) has been used as an inhalation contrast agent for spectral CT of the lungs,10,11 but to the best of our knowledge, has not been studied with dual-layer CT technology. Volumetric whole lung or dynamic focal lung scan protocols can be used during the xenon wash-in and wash-out periods. Xenon-inhaled spectral CT has been applied to various pulmonary diseases including chronic obstructive pulmonary disease, asthma, and bronchiolitis obliterans. As in radionuclide ventilationperfusion scans, spectral CT may be used to depict ventilation-perfusion mismatch specifically caused by pulmonary embolism.12

Specific spectral applications

Pulmonary arteries and great vessels

The detection and risk stratification of acute pulmonary embolism (PE)

The diagnostic value of spectral CT for detecting pulmonary embolism has been demonstrated in several papers. The capability of dual-energy CT to use diagnostic information available from both low- and high-energy levels optimizes the contrast-to-noise ratio within pulmonary vessels and facilitates detection of peripheral endoluminal clots compared with images acquired at fixed energy alone (120 or 140 kVp). The low-energy acquisition can generate images with increased vascular enhancement, and therefore, can help in the detection of endovascular clots, even in non-angiographic chest CT with suboptimal opacification such as in protocols when CT acquisition is performed at the portal venous phase. Bae and colleagues have looked at whether virtual monoenergetic images of good quality obtained from dual-layer detector spectral CT can yield additional diagnostic information.9 They compared the diagnostic performance for detecting PEs with virtual monochromatic imaging at 40 keV and conventional 120 kVp images in patients with a suboptimally enhanced pulmonary artery. They found that 40 keV virtual monoenergetic images allowed for higher diagnostic accuracy in the detection of PEs versus conventional 120 kVp images. In addition to monochromatic images, produced at a lower energy if necessary, Iodine no Water or iodine maps can also help improve the diagnostic accuracy of pulmonary embolism, as mentioned before. The spectral CT lung blood volume quantification may help the clinician predict outcomes in patients with pulmonary embolism, but additional validation is needed.13 In our daily routine, the use of iodine, Iodine no Water, and Z effective atomic number maps is the first display used for the detection of small perfusion defects caused by peripheral pulmonary clots, followed by anatomical inspection of the corresponding suspicious feeding artery using the ‘Related Slice Function.’ The iodine distribution within the lung parenchyma is displayed on a gray-scale or in color with different optional color scales depending on user preference. With the advent of spectral CT, the way for diagnosing a PE has changed drastically in our daily routine.

Recently, some researchers in China14 evaluated 30 consecutive patients with enhanced chest CT. They evaluated the quality of enhancement within the superior vena cava (SVC) at different energy levels, and found that the optimal imaging of the SVC can be achieved on monoenergetic reconstructions at 40 keV by using the dual-layer IQon Spectral CT. For the aorta, the use of VNC can potentially eliminate the need for a true non-enhanced phase and can be useful for the detection of intramural hematoma or for the follow-up of aortic endografts.2

Patient imaged for lung cancer workup. The CT scan was directly acquired after injection of contrast medium. On image A (conventional CT), we can observe a right upper lung nodule (arrow) containing a high-density structure. Differentiation between calcium and iodine was not obvious. A lymphadenopathy was present in station 4R (arrow). On the VNC image (image B), it was demonstrated clearly that the dense material within the nodule was due to calcium and not iodine. This type of calcification (coarse) can be observed in lung cancer. On image C (Iodine map), iodine uptake was noted in the right upper lung nodule (1.44 mg Iodine/ml) and also in the right mediastinal adenopathy (0.58 mg Iodine/ml). Pathology revealed a right upper lobe lung adenocarcinoma and a metastatic adenopathy located in the station 4R. The same information was displayed in color on the Z effective map (image D).

Lung nodule characterization and follow-up

Spectral CT imaging has recently emerged as a promising imaging method for characterizing lung nodules. Spectral CT scans can simultaneously provide VNC images and an iodineenhanced image from a single scan performed after iodine contrast administration, allowing both measurement of nodule enhancement and detection of calcifications. Iodine map and Z effective maps can be generated, allowing quantification of iodine load within the nodule for further characterization (Figures 3 and 4). Another recent study15 has shown that spectral CT could help to demonstrate blood supply and indicate the invasion extent of pure “ground glass” nodules. The authors have demonstrated that monochromatic CT numbers of higher energy (especially 140 keV) would be better for diagnosing minimally invasive carcinoma versus lower energies. The advantages of this technique include reducing radiation exposure to patients by obviating baseline unenhanced scans, and reducing measurement error due to variation in regions of interest during subtraction of an unenhanced image from its enhanced counterpart. This technique may have applications in contrast-enhanced dynamic CT and perfusion CT for the differentiation of benign and malignant nodules. Some authors16 have demonstrated different patterns of iodine distribution on Z effective maps in various inflammatory and noninflammatory lesions of the lungs. Inflammatory lesions showed a tendency to have an increased enhancement of iodine compared to neoplasms. In contrast, pulmonary infarctions demonstrate homogeneous low iodine distribution on iodine map images, and pneumonia demonstrates heterogeneously decreased or increased iodine distribution. Lung abscess and other necrotic lung lesions do not demonstrate iodine distribution on iodine map images.

Mediastinal abnormalities

Spectral CT using a quantitative analytical method based on measurement of iodine concentration can be used to differentiate different types of mediastinal masses. A preliminary study17 showed that this technique was able to differentiate thymic epithelial tumors using single-phase scanning. Spectral CT and perfusion imaging that can detect the tumor microenvironment have not been extensively studied in the context of lymphoma, but there are a few studies on perfusion imaging showing decreased tumor perfusion values and normalization of peak tumor perfusion after treatment of lymphoma.18-20 Thyroid gland and parathyroid glands demonstrate highly vascularized tumors. Spectral CT performed in this clinical setting has the potential to further enhance diagnostic accuracy for mediastinal ectopic parathyroid adenoma and endothoracic goiter using iodine maps.21-22 Some authors have shown promising results for identification of benign and malignant thyroid nodules by in vivo iodine concentration measurement using spectral CT.21

Lung cancer and lymph nodes

Recently, several studies have indicated that intra-tumor iodine concentration measured by enhanced spectral CT is correlated with malignancy, histopathology, lymph node metastasis, gene expression, and therapeutic efficacy following radiation or chemotherapy in primary lung cancer.23-25 Iwano et al. first reported that intra-tumor iodine concentration is correlated with degree of tumor differentiation, and that high-grade tumors tend to have lower iodine concentrations.24

Some researchers have studied the potential interest of this technique in the field of response to therapy in lung cancer, but no extensive data exists in the literature. Baxa et al. demonstrated beneficial aspects of spectral CT in the functional evaluation of mediastinal lymph nodes by determining the arterial enhancement fraction with the dual-phase spectral CT approach.26-27 The authors have showed that there was a decrease in vascularization in the primary tumors with favorable response to anti-EGFR therapy following the failure of standard chemotherapy.

Patient with a history of papillary cancer of the thyroid gland underwent an enhanced chest CT. On the conventional CT image (Image A), a small lung nodule is observed in the left upper lobe. Monoenergetic images (Image B) displayed at 70 keV demonstrated the same image quality compared to 120 kV, and further characterization of the lung nodule was not possible. Iodine map (Image C) demonstrated a high value of iodine content (3.2 mg Iodine/ml). Z effective image (Image D) confirmed this high iodinated content within the lung nodule. Pathology revealed a metastasis of the thyroid carcinoma.

Spectral CT may also have potential applications in the pre- and postoperative evaluation of lung cancer. In patients with lung cancer, especially central lung cancer, spectral CT can depict the presence and extent of perfusion or ventilation defects and collateral ventilation when the mass involves the hilar vessels or bronchi, aiding in the preoperative prediction of postoperative pulmonary perfusion and ventilation function. The currently available spectral CT techniques available include iodine-based contrast-enhanced lung perfusion imaging and xenon- or krypton-enhanced spectral CT lung ventilation imaging. This latter technique holds promise for depicting ventilation patterns in lung diseases and ventilation/perfusion mismatch in pulmonary embolism, but requires further validation.

Pleural disorders, chest wall, and incidental findings

From our clinical experience, pleural enhancing nodules comprising primary or secondary tumors of the pleura, enhancing pleura encountered in empyema, may benefit directly from virtual monoenergetic imaging and improve the visualization of iodinated contrast uptake with a lesser amount of contrast medium. A recent study performed in 29 patients showed that CT values of the benign and malignant pleural effusions were statistically different (p < 0.05) at both 40 keV (43.15 versus 39.42 HU for benign and malignant pleural effusions respectively), and 100 keV monochromatic spectral CT images (9.11 versus 6.52 HU for benign and malignant pleural effusions respectively).28 The effective atomic number value of benign pleural effusion was also statistically different from that of malignant pleural effusion (p <0.05).

Other incidental findings localized in the chest wall, breasts (Figure 5), adrenal, and thyroid gland discovered during a routine chest CT examination or oncologic workup would benefit from this technique. Some authors have demonstrated that incidental adrenal nodules discovered during a contrast-enhanced spectral CT examination of the abdomen may avoid additional imaging studies for further nodule characterization.29

Conclusion

The dual-layer, detector-based spectral CT technology found only with the IQon Spectral CT enables on-demand retrospective spectral CT analysis, including virtual monochromatic imaging, Z effective and iodine mapping, and represents a significant step forward for various thoracic disorder workups. Our experience with this system revealed that this unique mode of spectral CT data acquisition has allowed us to improve our diagnostic accuracy and diagnostic confidence. At the present time, the most added value of this technology resides in the vascular domain, enabling the reduction of contrast medium dose, and improvement of vascular contrast enhancement. Future research is needed to demonstrate the clinical usefulness of this technology in the characterization of lung nodules and the potential role of iodine quantification in the evaluation of lung or mediastinal tumors before and after therapy. Undoubtedly, incidental chest findings will benefit from this retrospective spectral CT analysis.

Conventional CT scan with contrast (Image A) showed a focus (arrow) of subtle increased density in left breast. Virtual monoenergetic image at 45 keV (Image B) demonstrated the lesion with higher contrast (blue arrow) as well as left axillary lymph nodes (white arrow). Iodine density map (Image C) quantitatively demonstrated the higher iodine uptake of the breast lesion (2.05 mg/ml) and the lymph node (2.65 mg/ml) compared to normal appearing adjacent breast tissue (0.59 mg/ml). Z effective map (Image D) demonstrated higher effective atomic numbers of the breast mass and the the lymph node (8.38 and 8.73, respectively) compared to normal appearing adjacent breast tissue (7.64). Biopsy revealed invasive ductal carcinoma grade 2.

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History

Benefits or pitfalls of dual-energy CT

Key images

Findings

77-year-old male with metastatic non-small cell lung cancer. Follow-up CT after chemotherapy.

Demonstration of lack of perfusion and perfusion deficit in lung parenchyma.

Axial and coronal images

Conventional CT scan with contrast showed wedge-shaped consolidation and “ground glass” opacities in the right upper lobe. Right lower lobe pulmonary arteries were encased by the hilar mass. Iodine density and Z effective images demonstrated wedge-shaped area with lack of iodine in the right upper lobe indicating pulmonary infarct and perfusion decrease in the right lower lobe.

Discussion

Iodine density images allow quantification of iodine, which may help to assess the severity of the pulmonary perfusion defects and could be useful to identify occlusive defects/pulmonary infarct.

Conventional CT, coronal image: lung window shows an area of consolidation in the right upper lobe (arrow) without any parenchymal density change in the right lower lobe.

Iodine density coronal image: lack of iodine in the right upper lobe (0.0 mg/ml, blue arrow), decreased iodine in the right lower lobe (0.3 mg/ml, white arrow) compared to the left lung (1.0 mg/ml, open arrow).

Z effective coronal image: lower effective atomic number (7.17) in the right upper lobe lung area color coded in yellow and red (blue arrow) show no iodine content. Right lower lobe with lower effective atomic number (8.83) and lower iodine content color coded in light blue and yellow (white arrow) compared to left lung with a higher effective atomic number (10.66) color coded in dark blue (open arrow) which corresponds to higher iodine content.

History Benefits or pitfalls of dual-energy CT

Key images Findings

50-year-old female with a history of left breast invasive carcinoma (2001) and a relapse in 2012. Follow-up imaging with spectral CT for a suspicion of distant metastasis.

Demonstration of iodine uptake of irregular pleural thickening with low keV, iodine density, and iodine overlay images, better evaluation of the local invasion of the lesion.

Axial and sagittal images

Conventional CT scan with contrast showed left-sided pleural thickening predominantly at the base of the lung. These lesions were considered as pleural carcinomatosis due to patient’s primary breast carcinoma. Biopsy results showed mesothelioma. Low keV (40 keV) monoenergetic images, iodine overlay images, Z effective, and iodine maps suggested diaphragmatic invasion which was later confirmed by MRI and histology.

Discussion

Spectral CT could be useful in quantitative demonstration of iodine content of pleural lesions and could indicate local invasion to adjacent structures such as diaphragm.

Conventional CT with contrast, mediastinal window, axial image: (a) demonstrated pleural thickening (arrows). Pleural thickening was more prominent on low keV (40 keV) image (b) (arrows). Iodine density map: (c) quantitatively demonstrated iodine uptake of thickened pleura (2.67 mg/ml and 2.36 mg/ml, arrows). Pleural thickening shown on iodine overlay image (d) (arrows).

Z effective sagittal image (a) demonstrated the relation of the pleural lesion that had high iodine content (color coded in dark blue, blue arrow) with diaphragm (color coded in light blue, white arrow). Iodine density sagittal image: (b) quantitatively showed higher iodine content of the lesion (2.52 mg/ml, blue arrow) compared to adjacent diaphragm (1.40 mg/ml, white arrow) suggesting invasion of the diaphragm. Iodine overlay sagittal image: (c) demonstrated the relation of the pleural lesion (blue arrow) with diaphragm (white arrow) suggesting invasion.

PET-CT coronal images: high metabolic activity of left basal pleura (SUVmax: 9.3, blue arrows). Note also the focus in left breast with slightly increased metabolic activity (SUVmax: 4.1, red arrows) which turned out to be a second relapse of breast carcinoma.

History

Benefits or pitfalls of dual-energy CT

Key images Findings