Università di Pisa
Facoltà di Medicina e Chirurgia
Scuola di Specializzazione in Radiodiagnostica
Direttore: Prof. Carlo Bartolozzi
Tesi di Specializzazione
CT pulmonary angiography with 80kV tube voltage and 40mL of
iodinated contrast material: technical feasibility and comparison
of vascular enhancement with iodixanol 320mg/mL and
iomeprol 400mg/mL
Relatore:
Chiar.mo Prof. Carlo Bartolozzi
Candidato: Rachele Pascale
ABSTRACT
PURPOSE: To compare the vascular enhancement and image quality of a low kilovoltage CT pulmonary angiography (CTPA) protocol in non-obese patients, using 40mL of a moderate concentration iso-osmolar (iodixanol 320mgI/mL) and a high concentration low-osmolar (iomeprol 400mgI/mL) iodinated contrast medium injected at the same iodine delivery rate (IDR).
MATERIALS AND METHODS: Forty-one patients (31 male, 10 female, age 58-83 years, mean 66 years) with suspected pulmonary embolism and non-small cell lung carcinoma underwent CTPA with a 64-row CT scanner using a tube voltage of 80kV. Out of them, 22 (53.7%) received 40mL of iodixanol 320mgI/ mL (Visipaque 320; GE Healthcare, Oslo, Norway) injected at a rate of 5mL/s, while the remaining 19 (46.3%) were administered an equal volume of iomeprol 400mgI/mL (Iomeron 400; Bracco, Milan, Italy) at a flow rate of 4mL/s, resulting in an identical IDR of 1.6gI/s in both groups. Intra-arterial density was measured in the common pulmonary artery trunk, the main right and left pulmonary arteries, all lobar arteries and at segmental level, for a total of 15 regions of interest per patient. The severity of beam hardening artifacts and the degree of contrast enhancement homogeneity were also visually assessed using a semiquantitative score.
RESULTS: The overall density of the pulmonary arteries was not significantly different between the two groups, although a strong trend toward higher enhancement with iodixanol 320mgI/mL was found (p=0.0504). Beam hardening artifacts were moderate and enhancement homogeneity was good with both contrast agents, with no statistically significant difference between them (p=0.9442 and p=0.8966, respectively).
CONCLUSIONS: In non-obese patients, CTPA can be successfully performed at 80kV using as low as 40mL of either iodixanol 320mgI/mL or iomeprol 400mgI/mL with comparable intravascular enhancement and image quality.
INTRODUCTION
Despite advances in prophylaxis, diagnostic modalities, and therapeutic options, pulmonary embolism (PE) remains a frequently underdiagnosed and lethal entity. PE has been estimated to occur in more than 600,000 patients annually in the United States, and is reported to cause or contribute to 50,000 to 200,000 deaths [1].
Deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively known as venous thromboembolism (VTE), are relatively common. Given its silent nature, the incidence, prevalence, and mortality rates of VTE are probably underestimated.
Cancer and its treatment are recognised risk factors for VTE. Some studies have reported a 6-fold increased risk of VTE in patients with cancer compared with those without it. Active cancer accounts for almost 20% of all new VTE events occurring in the community. The risk of VTE varies by cancer type and is especially high among patients with malignant brain tumours, and adenocarcinoma of the ovary, pancreas, colon, stomach, lung, and prostate.
Cancer patients undergo routine imaging studies much more than others; these imaging studies, which usually include computed tomography (CT) scans of the chest, are done to define the extent of the disease (staging), assess the response to cancer therapy, or to screen for metastasis. The widespread use of multislice CT (MSCT) scanners has resulted in improved resolution and much better visualisation even of peripheral pulmonary vessels. Venous thromboembolisms, including PE, in asymptomatic patients are well-recognised clinical entities, and it is believed that most fatal PE are not suspected clinically and therefore not treated.
MSCT is currently considered the gold standard for diagnosis of PE [1-2] and, in particular, MSCT equipment with 16-64 detectors rows can properly display pulmonary arteries down to subsegmental level, thus quickly providing images with voxel isotropy and maximising the efficiency of the intravenous iodinated contrast medium (CM) bolus [3-5].
In addition, recent studies have shown the feasibility of CT angiography with reduced tube voltage [6-12] in different vascular territories. In fact, a lower voltage increases the attenuation of iodine (and consequently, contrast enhancement) owing to lower X-ray energy and higher photoelectric effect [13-14]. This circumstance may be key for the development of CT pulmonary angiography (CTPA) protocols with low radiation dose and markedly reduced amounts of iodine. However, to this latter respect, little data exists in the literature about the amount and concentration of CM to be used for low kilovoltage CTPA, and no agreement exists about the best iodine concentration for CTPA in patients with suspected PE [5-9, 15-20].
The purpose of this study was to compare the vascular enhancement and image quality of a low kilovoltage (80kV) CTPA protocol in patients with suspected PE, using a low volume (40mL) of a moderate concentration iso-osmolar (iodixanol 320mgI/mL) and a high concentration low-osmolar (iomeprol 400mgI/mL) iodinated CM.
MATERIALS AND METHODS
Patient selection.
Between November 2009 and May 2011, all patients with suspected PE who were referred to the (BLINDED) Department of the University of (BLINDED) were considered for the study. Indication for performing CTPA was based on positive results at clinical investigation, abnormal findings at laboratory testing (blood gas analysis, plasmatic D-dimer level), abnormal results at echocardiography or electrocardiography indicative of acute right heart dysfunction, abnormal findings at lower limb ultrasonography, and findings suggestive of PE at conventional chest X-ray. Known allergy to iodinated CM, hyperthyroidism, renal insufficiency, pregnancy, age younger than 18 years old, body weight exceeding 80kg, and serum creatinine greater than 1.2mg/dL were contraindications to enrolment in the study. Forty-one patients (31 male, 10 female, age 58-83 years, mean 66 years) with suspected PE and non-small cell lung carcinoma were examined.
CTPA protocol.
All CTPA examinations were carried out using a commercially available CT scanner (LightSpeed VCT; General Electric, Milwaukee, WI) with 64 detector rows. Patients were examined in the supine position with both arms extended above the head. On the scout view image the second arch of the left heart was identified and chosen as the level of bolus tracking for the subsequent CTPA scan. This latter consisted of a spiral scan in the caudo-cranial direction, spanning the chest from 1cm above the
diaphragmatic dome up to 1cm below the lung apices with the following parameters: detector configuration 64×0.625mm, detector collimation/reconstruction interval 0.625mm/0.625mm, beam pitch 0.984:1, tube rotation time 0.6s, tube voltage 80kV, angular and longitudinal tube current modulation, current range 50-300mA, sampling field-of-view (SFOV) Medium, convolution filter Soft.
Out of the 41 patients examined, 22 (53.7%) received 40mL of iodixanol 320mgI/ mL (Visipaque 320; GE Healthcare, Oslo, Norway) injected at a rate of 5mL/s, while the remaining 19 (46.3%) were administered an equal volume of iomeprol 400mgI/mL (Iomeron 400; Bracco, Milan, Italy) at a flow rate of 4mL/s. In both cases, CM injection was followed by administration of 40mL of saline chaser at the same flow rate, in order to improve bolus compaction and optimise the overall bolus efficiency [21-23]. Injection was performed using a dual-syringe power injector (Empower CTA; Siemens Medical Systems, Erlangen, Germany). The different flow rates were selected in order to guarantee the same iodine delivery rate (IDR) of 1.6gI/ s for both protocols.
A density of 250 Hounsfield Units (HU) inside the superior vena cava was set as threshold for the beginning of the CTPA acquisition. In contrast to the conventional CTPA bolus tracking technique (in which sequential scanning is usually performed at the level of the main pulmonary artery), the superior vena cava was chosen in our study because a scan delay of 5s had to be accounted for after reaching the threshold, due to the very short CM bolus injected and to the need for CT table to be moved from the bolus tracking level to the lower limit of the CTPA volume.
Image analysis.
CTPA datasets were transferred via PACS to a dedicated workstation (Advantage Windows 4.5; GE Healthcare, Milwaukee, WI). From each dataset, multiplanar reconstructions (MPR) were generated on the standard three orthogonal planes (axial, coronal, sagittal), and circular regions of interest were traced inside the following vessels: common trunk of the pulmonary artery, right and left main pulmonary arteries, lobar arteries [right and left upper lobes (RUL, LUL), middle lobe (ML), interlobar artery, right and left lower lobes (RLL, LLL)], and the following segmental arteries: anterior segmental artery of the RUL and LUL, medial segmental artery of ML, posterobasal artery of the RLL and LLL, and anterior segmental artery of the lingula), for a total of 15 ROI per patient. For each vessel, ROI were placed on the MPR view displaying the widest cross-sectional area of the artery under investigation. Moreover, each ROI were as large as to include the largest number of voxels for an accurate and reproducible density measurement, but reached a distance no less than 10% of the vessel diameter in order to avoid measurement errors due to partial volume phenomena. All ROI were placed in consensus by two radiologists experienced in thoracic radiology [BLINDED] halfway between the beginning and the end of every vessel under investigation. All CT numbers were expressed in HU.
In addition, the severity of beam hardening artifacts due to pooling of CM in the central venous system and the right heart was visually evaluated using a semiquantitative scale (1=mild, 2=moderate, 3=severe). As a third step, the homogeneity of intravascular density was also measured visually by means of
a semiquantitative scale (1=poor, 2=good, 3=excellent). Both scores were assigned in consensus by two radiologists experienced in thoracic radiology [BLINDED], other than those who placed ROI in the pulmonary arteries.
Data analysis.
Data are expressed in terms of mean ± standard deviation. Intravascular densities obtained with the two protocols were compared using the two-tailed Student t test, while the severity of beam hardening artifacts and the degree of contrast enhancement homogeneity were compared using the two-tailed Mann-Whitney test. A p-value less than 0.05 was considered statistically significant.
Statistical analysis was performed using software (GraphPad Prism version 5, www.graphpad.com).
RESULTS
Intravascular densities of each branch of the pulmonary artery with iodixanol 320mgI/mL and iomeprol 400mgI/mL are tabulated in Table 1. The overall vascular density of the pulmonary arteries was higher with iodixanol 320mgI/mL than with iomeprol 400mgI/mL: this difference was not statistically significant, yet it showed a strong trend towards significance (p=0.0504) (Figure 1).
In all cases, vascular densities for each segment were greater with iodixanol 320mgI/ mL than with iomeprol 400mgI/mL, and this difference was statistically significant at the level of the arteries for the LUL (p=0.0481), the anterior segment of the LUL (p=0.0075), the medial segment of the ML (p=0.0425), and the posterobasal segment of the LLL (p=0.0126), respectively (Figure 2).
Beam hardening artifacts were moderate with both contrast agents (respectively 2.22±0.97 with iodixanol 320mgI/mL and 2.20±0.84 with iomeprol 400mgI/mL, p=0.9442) and have never significantly affected the visibility of pulmonary arterial structures.
The homogeneity of contrast enhancement was good with both iodixanol 320mgI/ m L a n d i o m e p r o l 4 0 0 m g I / m L ( 2 . 6 7 ± 0 . 5 0 a n d 2 . 6 0 ± 0 . 5 5 , respectively; p=0.8966) down to subsegmental level (Table 2 and Figure 3). The overall DLP was 288.32±102.71 mGy×cm, corresponding to 4.24±1.51 mSv using a chest CT conversion factor of 0.0147mSv×mGy-1×cm-1 [24].
DISCUSSION
Our results show the absence of a significant difference in the overall enhancement of pulmonary vessels at central and segmental level using the same volume (40mL) of iodixanol 320mgI/mL and iomeprol 400mgI/mL injected with the same IDR; moreover, both protocols provided good homogeneity of intravascular enhancement without significant beam hardening artifacts.
Our experience is in line with that of other authors who evaluated intravascular enhancement at CT angiography of thoracic vessels [15-18] and confirmed that IDR, rather than iodine concentration alone, is the major determinant of arterial enhancement. Indeed, a high IDR value is fundamental in CT angiography to obtain adequate arterial enhancement [21-22], and in CTPA it is essential to achieve optimal visualisation of the most distal arterial branches and demonstration of peripheral thromboembolism [19]. Modern MSCT scanners with 64 detector rows and beyond can cover the entire chest in less than 5 seconds, allowing to decrease the duration of the bolus and to reduce the CM bolus by increasing the injection rate. This way, high IDR values can be reached without raising iodine concentration (and hence the iodine load) [21], with consequent benefits in terms of patient safety and healthcare costs. Moreover, in contrast with similar studies in which IDR values and iodine load were kept constant [17-18], in our study the same volume of contrast medium was administered in both patient groups. This means that, by injecting 40mL of iodixanol 320mgI/mL, it was possible to obtain diagnostic results with a 20% reduction in iodine load compared with iomeprol 400mgI/mL at the same IDR.
Langenberger et al [20] compared two CTPA acquisition protocols based on the administration of an equal, rather large iodine dose (48gI) of iomeprol 400mgI/mL and iodixanol 320mgI/mL injected at the same flow rate of 4mL/s. They achieved greater intravascular attenuation using the CM with higher iodine concentration; however, the two CM were injected at different IDR (1.6gI/s for iomeprol 400mgI/ mL and 1.2gI/s for iodixanol 320mgI/mL, respectively), which are likely to be responsible for the higher intravascular enhancement with iomeprol 400mgI/mL. Moreover, the high dose of iodine introduced (corresponding to 120mL of iomeprol 400mgI/mL and 150mL of iodixanol 320mgI/mL) can hardly be justified using a 64-row MSCT scanner, because the scan duration would be much longer than that of the CM bolus.
Furthermore, by injecting small volumes of intravenous CM (either iodixanol 320mgI/mL and iomeprol 400mgI/mL) at high flow rates, high bolus compaction can be achieved. This contributes to increase contrast enhancement of the pulmonary arteries without wasting CM in the venous system, as well as to reduce beam hardening artifacts due to pooling of CM in the superior vena cava and in the right heart [21-23].
The possibility to obtain comparable diagnostic results with iodixanol 320mgI/mL (an iso-osmolar iodinated CM) may be beneficial in terms of safety in patients with impaired renal function and/or cardiovascular complications, as suggested by several studies [25-26].
In an attempt to minimise the CM dose administered for CTPA in patients with renal failure, Holmquist et al [8-9] have reported the use of a quantity of 200mgI/kg of
iodixanol 320mgI/mL with 16-channel CT and with a fixed scan duration of 15 seconds and variable flow rate, depending on patient's weight (50mL at 3.3mL/s for a maximum weight of 80kV); in a similar study, Krinstiansson et al have used even lower doses (150mgI/kg) [7]. However, usage of such low doses of CM with slower CT equipment implied that flow rate (and hence, IDR) be reduced in order to avoid outrunning the bolus, resulting in overall reduced contrast enhancement (around 350HU, i.e. noticeably lower than our mean value of 531.2HU). Furthermore, in those studies intravascular density was measured in two arterial branches only (the common trunk and a segmental branch of the LLL), with no systematic information about contrast enhancement in both main pulmonary arteries, all lobar arteries, and multiple segmental vessels.
Our aim was to develop a CTPA injection protocol that yields adequate enhancement of pulmonary vessels down to subsegmental level, by giving a mean total amount of iodine comparable to the experience of Holmquist et al (188-235mgI/kg) with a tube voltage of 80kV [8-9]. We preferred not to decrease CM volume below 40mL, as this would have carried the risk of missing the bolus at a high injection rate of 4-5mL/s and with a scan delay of 5s, even despite using a faster 64-row MSCT.
To maximise contrast enhancement without further increasing the IDR, a tube voltage of 80kV was chosen instead of the conventional value of 120kV. X-rays generated by a tube voltage of 80kV have a significantly lower energy than at 120kV, close to the k-edge of iodine (33.2keV). This allows to maximise photoelectric effect, with a consequent increase of contrast enhancement and a contrast-to-noise ratio about twice than at 140kV [13, 27]. Besides, usage of a tube voltage of 80kV results in a
radiation dose reduction of 2.8 times compared with 120kV, owing to the lower X-ray energy [27].
One limitation of our study is that, in analogy with other works based on usage of a low tube voltage [6-9], CTPA examinations were performed on non-obese patients only, in whom it is possible to obtain diagnostic results even with a drastic reduction of tube voltage and iodine load. Indeed, it is likely that on larger patients, the signal-to-noise ratio would have been unacceptably low. Still, this limitation could be partially overcome with the availability of X-ray tubes with greater current capacity or dual-source CT equipment [28].
In conclusion, our results show that, in non-obese patients, it is possible to perform CT angiography of the pulmonary vessels at 80kV tube voltage using a small volume of iodinated CM (40mL) injected with the same IDR, with comparable enhancement between iodixanol 320mgI/mL and iomeprol 400mgI/mL. The applicability of such protocol on larger patients requires further investigation.
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Tables.
PA branches IODIXANOL 320mgI/mL IOMEPROL 400mgI/mL p Common PA trunk 639.7±182.4 573.4±183.8 0.2548 Right main PA 622.3±159.8 540.5±153.2 0.1028 RUL 594.8±169.5 467.9±165.6 0.0237* ML 573.7±181.7 448.6±175.4 0.0309* Interlobar trunk 555.7±161.7 475.3±189.9 0.1568 RLL 623.8±184.7 550.0±186.8 0.2126 Left main PA 576.1±182.3 468.5±155.3 0.0481* LUL 595.1±187.1 515.9±161.9 0.1542 LLL 583.4±177.4 489.4±172.4 0.0939 Anterior segment of RUL 527.8±146.2 435.6±169.6 0.0751 Medial segment of ML 527.7±193.3 405.4±179.7 0.0425* Posterobasal segment of RLL 500.1±186.3 433.2±186.4 0.2589
Anterior segment of LUL 571.1±183.9 421.5±155.9 0.0075* Superior lingular segment 580.5±198.4 488.5±172.2 0.1201 Posterobasal segment of LLL 562.6±180.1 420.1±168.4 0.0126* Table 1: intravascular enhancement with iodixanol 320mgI/mL and iomeprol 400mgI/mL (expressed as mean±standard deviation). *p<0.05 indicates statistical significance.
IODIXANOL 320mgI/mL
IOMEPROL
400mgI/mL p Beam hardening artifacts 2.22±0.97 2.20±0.84 0.9442 Contrast enhancement homogeneity 2.67±0.50 2.60±0.55 0.8966
Table 2: severity of beam hardening artifacts and homogeneity of intravascular enhancement with iodixanol 320mgI/mL and iomeprol 400mgI/mL. Data are expressed as mean±standard deviation.
Figures.
Figure 1a: CTPA with 40mL of iodixanol 320mgI/mL injected at 5mL/s (IDR=1.6gI/ s).
Figure 1b: CTPA with 40mL of iomeprol 400mgI/mL injected at 4mL/s (IDR=1.6gI/ s).
Figure 2a: CTPA with 40mL of iodixanol 320mgI/mL injected at 5mL/s. Notice absence of significant beam hardening artifacts due to pooling of hyperconcentrated contrast medium in the central venous system.
Figure 2b: CTPA with 40mL of iomeprol 400mgI/mL injected at 4mL/s. Notice mild beam hardening artifacts due to pooling of hyperconcentrated contrast medium in the superior vena cava, that do not significantly affect the visibility of pulmonary arteries.
Figure 3a: CTPA with 40mL of iodixanol 320mgI/mL injected at 5mL/s. Notice high homogeneity of intra-arterial enhancement down to subpleural level.
Figure 3b: CTPA with 40mL of iomeprol 400mgI/mL injected at 4mL/s. Notice high homogeneity of intra-arterial enhancement down to subpleural level.
