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Suspected pulmonary embolism and deep venous thrombosis: A comprehensive MDCT diagnosis in the acute clinical setting
European Journal of Radiology 65 (2008) 340–349
Suspected pulmonary embolism and deep venous thrombosis: A comprehensive MDCT diagnosis in the acute clinical setting Luca Salvolini a,∗ , Mariano Scaglione b , Gian Marco Giuseppetti a , Andrea Giovagnoni a a
Radiology Department, “Umberto I” Hospital - Ospedali Riuniti - “Politecnica delle Marche” University, Via Conca, 60020 Ancona, Italy b Emergency and Trauma CT Section, Department of Radiology, Cardarelli Hospital, Via G. Merliani 31, 80127 Napoli, Italy Received 6 September 2007; received in revised form 7 September 2007; accepted 8 September 2007
Abstract Both pulmonary arterial and peripheral venous sides of venous thromboembolism (VTE) can now be efficiently and safely investigated by multi-detector CT (MDCT) at the same time by a combined CT angiography/CT venography protocol. In the emergency setting, the use of such a single test for patients suspected of suffering from VTE on a clinical grounds may considerably shorten and simplify diagnostic algorithms. The selection of patients to be submitted to MDCT must follow well-established clinical prediction rules in order to avoid generalized referral to CT on a generic clinical suspicion basis and excessive population exposure to increased ionizing radiation dose, especially in young patients. Clinical and anatomical wide-panoramic capabilities of MDCT allow identification of underlying disease that may explain patients’ symptoms in a large number of cases in which VTE is not manifest. The analysis of MDCT additional findings on cardiopulmonary status and total thrombus burden can lead to better prognostic stratification of patients and influence therapeutic options. Some controversial points such as optimal examination parameters, clinical significance of subsegmentary emboli, CT pitfalls and/or possible falsely positive diagnoses, and outcome of untreated patients in which VTE has been excluded by MDCT without additional testing, must of course be taken into careful consideration before the definite role of comprehensive MDCT VTE “one-stop-shop” diagnosis in everyday clinical practice can be ascertained. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Pulmonary embolism; Deep venous thrombosis; Venous thromboembolism; CT angiography; CT venography; MDCT
1. Introduction Venous thromboembolism (VTE) is a systemic and potentially lethal illness: pulmonary embolism (PE) and deep venous thrombosis (DVT) are two aspects of the same disease [1]. Clinical pictures vary from nearly asymptomatic to life-threatening syndromes, and presentation symptoms are quite non-specific, with broad differential diagnoses. Correct therapy must be implemented as soon as possible to be effective and also to avoid unnecessary treatments. Often both pulmonary arterial and deep venous sides of the disease have to be investigated to reach diagnosis and correct patient management. Until the early nineties this could only be accomplished by at least two different techniques. In an attempt to perform more rapid and accurate diagnoses, nearly every branch of radiology has been involved over the last decades in the diagnostic
∗
Corresponding author. Tel.: +39 71 5964078; fax: +39 71 5965009. E-mail address: [email protected] (L. Salvolini).
0720-048X/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2007.09.019
workup of VTE. First line diagnosis in a suspected PE/DVT case relied primarily on ventilation/perfusion (V/Q) scintigraphy and then ultrasound (compression ultrasound, Doppler/Echo-color Doppler) depending on clinical presentation. In a large percentage of cases, due to indeterminate and non-conclusive findings, multiple diagnostic tests were performed, often by searching for VTE as a surrogate of diagnosing the most harmful potentially associated PE; and in the patients in which it was not possible to confidently rule in or out PE due to inconclusive noninvasive tests or discordant clinical findings, invasive testing by gold-standard pulmonary angiography and/or lower limbs phlebography had to be carried out, with additional costs and time resources consumption and possible complications. With the introduction of helical CT (HCT), and then MDCT as a major technical evolution, for the first time we could rely on a technique that was capable of showing direct evidence of the presence of thrombi and emboli in both limb veins and pulmonary arteries at the same time, and it was only minimally invasive and feasible even in emergency room (ER) patients apart from echocardiography.
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The role of CT pulmonary angiography (CTPA) as the “workhorse” test in diagnostic evaluation of suspected PE has been widely accepted after considerable debate [2,3]. Still more controversial is the possible implementation of follow-on CT indirect venography (CTV) of the abdomen, pelvis, and inferior limbs and to search for concomitant VTE in the venous phase immediately after CTPA in routine practice. After reviewing technical principles which correct application is essential in order to achieve optimal results in diagnostic accuracy and reduce the number of inconclusive examinations, in this paper, we will analyze the effectiveness of combined CTPA/CTV as a comprehensive one-stop test in VTE diagnosis. We will also comment its advantages and possible drawbacks. Our aim is to help the reader decide if combined PE/DVT diagnosis by MDCT meets increasing demands of referring clinicians for a more effective and cost-effective approach. Should we implement such simplified protocols, or rather bear technological pressure and wait for a larger body of evidence before recommending routinely adding CTV to CTPA protocols in searching for VTE? 2. Technical issues 2.1. CT pulmonary angiography (CTPA) The introduction and continuous technical evolution of MDCT has allowed more flexible and high-performance protocols, to match diagnostic needs without compromising detail and coverage [4–6]. The precise setting of scan parameters depends on the number of slices than can simultaneously be acquired and factory presets, and so protocols differ according to different manufacturers, from 4- to 64-slice machines. In cooperative patients, 1–1.25 mm slice collimation can be sustained in most cases even with 4-/8-slice scanners, thus allowing a more detailed evaluation of subsegmentary branches. With 16- and 64-slice scanning, sub-millimetre collimation has been advocated, but halving slice width in order to keep the same noise level can lead to correspondent geometrical increase of radiation dose that we must be aware of. It is the authors opinion that in most cases 1-mm collimation is enough to permit a confident evaluation of the arterial lung tree apart from “triple rule-out” protocols. Subsecond scanning is essential to reduce possible motion artefacts and shorten scan time. With volume pitches of about 1.3 and 1–1.25 mm collimation, the whole lungs can be studied in 3–12 s by 64- and 16-slice MDCT, while the patient holds his/her breath. In ER or intensive care patients and in other such cases in which apnoea cannot be sustained, subsecond scanning and maximum pitch values reduce motion artefacts with about 2-mm collimation to rule in or out major emergent PEs. Pre-contrast scans may help in more precisely programming contrast-enhanced phase, detecting differential diagnoses in advance and adjusting study parameters, and even showing clots in some cases (Fig. 1) [4–6]. Most protocols recommend relatively high contrast bolus flow rates (3–5 ml/s) and iodine concentration (300–370 mg I/ml), with total injected volume to be adjusted according to scan duration, patients habit, and renal
Fig. 1. (A) Unenhanced axial multi-detector row CT scan shows spontaneous hyperdense clot emboli in the main and lobar pulmonary arteries, confirmed after contrast material administration (B).
function, roughly between 70 and 120 ml, and delay between 7–8 and 15–22 s depending on flow rate and total volume. CTPA bolus must be adjusted to the shortened MDCT scan duration. In order to maintain an adequate iodine inflow and thus optimal enhancement of lung vessels with a lesser scan time, the contrast bolus must be more compact: flow rate must be kept as high as 4–6 ml/s while maintaining moderately highconcentration options, and total amount of contrast can be decreased in most cases up to 60–80 ml. If we adopt followon CT venography protocols, however, as much as 110–140 ml of 300–370 mg I/ml contrast are still required for a confident evaluation of the venous district after recirculation. Saline flushing if precisely timed is a valuable option. Bolus tracking is a double-edged weapon due to the delay between ROI target vessel enhancement and the beginning of the scan. This delay must be taken into account in selecting threshold HU trigger value and ROI positioning, and the level of the tracking slice according to the first scanned slice. ECG-gating for reduction of cardiac motion artefacts is not advised due to the unacceptably low pitch with excessively prolonged scan time and increased imparted dose and until the suitability of triple rule-out protocols is not assessed. Apart from respiratory and cardiac motion, other possible pitfalls include anatomical confusing structures and flow-related artefacts that must be known and recognized [7–11]. Prognostically relevant factors such as right heart acute
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Fig. 2. (A) Near-complete occlusion of the right main pulmonary artery causing acute right heart overload (B). After therapy, restored patency of the right pulmonary artery (C) is matched to the resolution of the right ventricular dilatation (D).
Fig. 3. Contrast-enhanced multi-detector row CT scans show presence of intraluminal webs and arterial stenoses (A, arrow) and partially calcified thrombus in both pulmonary arteries (B) after chronic pulmonary embolism; post-thrombotic phlebolithiasis of the right popliteal vein is also evident (C, arrow).
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failure signs (Fig. 2) and chronic PE issues must be sought and reported (Fig. 3). Associated parenchymal findings must be evaluated on lung window images reconstructed with appropriate kernel. Moving to CT venography, non-helical sequential scanning, using slice widths between 5 and 10 mm and slice intervals up to 5 cm, bears the risk of missing shorter segmentary clots [12]. Single-slice spiral CTV protocols employ 5–10 mm slice collimation at maximum pitch. Now with MDCT, we are limited by the total number of images and increased doses if the thinner slice collimation values and continuous volumetric scan mode are employed, rather than by technical limitations. As a useful compromise, 3.75–5 mm reconstructed image thickness (by maintaining upper slice collimation to 2.5–3.75 mm) with the maximum table speed possible and carefully adjusted mA settings with automated dose modulation protocols at 120–160 mAeff can maximize diagnostic benefit at an acceptable imparted dose level. Scanning should include the deep venous district from the IVC and iliac veins down to the popliteal fossae/upper calves. In theory, caudal–cranial scanning better reflects the physiology of deep venous enhancement with prolonged scan times, but this is less of an issue with MDCT [13,14]. Ideal scan delay is comprised between 180 and
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Fig. 4. (A) Pseudo-thrombotic uneven mixing artefact in the left common femoral vein on CT images acquired after 100 s of scan delay, solved by rescanning after more appropriate 180 s delay (B).
Fig. 5. A 67-year-old patient suspected of having pulmonary embolism after surgical application of right hip prosthesis. (A and B) Coronal and sagittal multiplanar reconstructions depict extent of a “filling defect” in the right main pulmonary artery. (C) Coronal CT reformation demonstrates left iliofemoral vein and right femoral thrombosis.
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Fig. 6. Contrast-enhanced multi-detector row CT scans show massive bilateral pulmonary emboli (A) associated with intramural hematoma in the descending thoracic aorta (B).
240 s after the beginning of contrast bolus administration during previous CTPA phase, and might be even more prolonged in case of impaired cardiac function. Shorter delays can lead to false-positive pseudo-thrombotic findings due to incomplete recirculation and uneven mixing of injected contrast into the venous blood pool (Fig. 4) [15–18]. For the same reason, it is not recommended to split the bolus, but it is better to administer the total amount at a single time during the arterial study. Elastic stockings may be recommended in order to enhance deep venous filling, but this does not seem a practical option, particularly in critically ill patients [19]. Other pitfalls that we should be aware of may come from orthopaedic hardware, near cortical bone, and anatomical and pathological structures that can mimic thrombosed veins [20–22]. High-density thrombus may indicate acute DVT and so better prognosis on resolution of clots by immediate therapy (Fig. 1) [23]. Interactive console viewing of reconstructed CTPA/CTV images is essential to scroll images following every single vessel adjusting window/level, by cine-viewing and real-time multiplanar evaluation. MPR reformats may be useful in depicting the extent of pathology on anatomically oriented images (Fig. 5), but multi-voxel-thick MIP/MPVR reconstructions should be avoided so as not to miss thin emboli. 3. Discussion: advocates and drawbacks The actual status of CT in VTE diagnosis in clinical practice is that of an “unofficial” gold standard—that is, CT represents
the basis of PE diagnosis in most emergency departments worldwide, even if clinicians are often sceptical of its role as one-step ruling out diagnostic test [24]. Adding follow-on DVT testing to CT protocols further complicates the question, as its suitability is still under considerable debate and CTV is not yet included in standardized protocols. At least in symptomatic patients, a first scan for DVT by compression ultrasound (CUS) was considered an effective approach. Conventional diagnostic work-up of VTE in the pre-CT era required much time, considerable resources, multiple and often overlapping diagnostic tests, and could not be achieved in all centres and cases, especially in emergency situations in which massive PE could only be indirectly investigated by bedside echocardiography. That is why HCT pulmonary angiography deserved nearly immediate attention and application, being easy to perform, reproducible, non-invasive or minimally invasive, based on rapidly widespread technique, and allowing direct demonstration of emboli and alternative diagnoses. Initial enthusiastic reports on CTPA accuracy, however, were not universally confirmed, especially if subsegmental arteries were included in diagnostic evaluation [25–32]. Nevertheless, CT appeared to be a more discriminating technique. First costeffectiveness analyses published showed positive results for CT-based protocols not only in ruling-in PE, but also as a definitive, clinical-evidence-based ruling-out test, as all effective strategies were based on CTPA, preceeded by clinical/D-dimer screening and eventually complemented by US at slightly higher cost-per-life saved but attaining further marginal reduction in mortality [33–36]. In this picture, since the late 1990s, after having demonstrated the suitability of CTPA not only as a firstline diagnostic test in PE but also in substituting for invasive pulmonary angiography as the current standard of care and reference, then CTV began being investigated. The relatively limited performance of the first spiral CTs prevented CTV in being effectively proposed as a follow-on adjunct to CTPA from the beginning, apart from few pioneers. As technical evolution progressed and comprehensive CT evaluation became feasible, after a few years, first convincing efforts were made to evaluate and propose the possible role of additional CTV as a valuable option to allow complete one-step evaluation of VTE, being the reported values of sensitivity and specificity and adopted goldstandards in first series quite non-homogeneous, as did proposed protocols [18]. The rationale for follow-on CTV after CTPA is threefold. Firstly, HCT diagnostic accuracy could be refined both by recovering VTE diagnoses in a considerable percentage of patients (in the range from 15% to 38% excepting isolated lower and higher peaks) with negative CTPA but positive CTV, and by confirming CTPA negativity lessening the need for additional DVT testing by US [12,22,37–39]. Secondly, CTV represents a more efficient utilization of resources than have already been employed for CTPA, since helical CTV requires little additional time, employs the contrast bolus previously injected in the pulmonary arterial phase thus optimizing its use, and the patient is still lying on the CT table and so considerable time and resources are spared in evaluating the deep venous district without patient referral to other techniques, and without additional cost. Thirdly, since
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Fig. 7. Missed US diagnosis of deep venous thrombosis associated with pulmonary embolism due to thrombotic fragments in the left external iliac vein (A), coming from clots in distal tributary sub-popliteal leg veins (B, arrows), from incompletely occluding thrombus in the superficial thigh veins (C, thrombosis of the left saphena) and from very small remnants in the femoropopliteal and tibial districts (D–F, arrow).
most fatal PE events are recurrent PEs from persisting DVT that can be present in a large percentage of patients, and the cranial extension of venous thrombi and the presence of venous anatomical anomalies and variants influence therapeutic options such as VCI filter positioning, estimating total clot burden and extension, nearly impossible in US, could be more of an issue in VTE regarding prognostic stratification and therapeutic management rather than seeking minimal isolated lung emboli. Associated
DVT can be demonstrated by CTV in up to 50% (13–93% in the literature as peak values) of patients affected by PE on CTPA [38,40,41]. Another strength of HCT is the capacity to explain the clinical emergent picture by showing alternative diagnoses or additional findings, which can be clinically relevant and affect therapeutic choices (Fig. 6), not only in the chest but also in the abdominal district, thus allowing a correct patient management even in
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many non-VTE cases, up to 40–75%, and avoiding further referral to CT searching for occult tumours that are often associated to VTE [10,42–45]. So the one-stop role of CT is a single test that can be used to solve different questions in critically ill patients, and to depict multiple aspects of the same disease in a single case [46]. In this context, perfusion scintigraphy may be an alternative option due to its low cost and low radiation dose and clinicians’ reluctance to abandon well-established scintigraphy-based protocols; however, in the emergency patients, scintigraphy is often either unfeasible or unreliable [1,47]. So if we want to rely on a fast, reproducible and accurate test widely available in most hospitals on a 24-h basis, then CTPA with follow-on CTV could considerably simplify and shorten diagnostic evaluation following evidence-based criteria and the “golden hour” principle [48,49]. And in addition, even without cardiac gating, CTPA images include a considerable amount of information about the status of the right side of the heart, pulmonary hypertension, and the extent of pulmonary arterial bed obstruction, that should be concomitantly evaluated because patient prognostic stratification may be as important as diagnosis itself [24,50–56]. Today MDCT is also proposed as a standardized approach for CTPA/CTV, with consistent diagnostic accuracy [14,57–61], and with excellent results in the follow-up of untreated patients. The improved longitudinal and temporal resolution of multislice/subsecond scanning allow a better evaluation of the more peripheral branches [25,62–68]. However, if we compare HCT
to MDCT as to the detection of subsegmentary and peripheral branches from an anatomical and clinical viewpoint, MDCT pulmonary angiography does not give more relevant information in patient management [69,70]: it is the additional detection rate of DVT by CTV that is even higher in MDCT than in HCT, allowing more VTE diagnoses to be made. The strong arm of CT may not only be submillimetric resolution, but its panoramic features and time-efficiency leading to more confident and faster diagnosis. A negative issue is the additional radiation dose imparted with CTV after CTPA, especially in younger patients. Even if detector augmented efficiency and dose-modulation protocols in MDCT allow lesser increase in imparted Rx dose in comparison with HCT, this issue has to be adequately considered. Several studies have analyzed irradiation doses; reported values account for an incremental absorbed dose of about 50% by adding CTV to CTPA, from low values up to about 8–12 mSv [71–76]. However, in comparison with old diagnostic protocols based on invasive testing, the adoption of CT has lead to only a marginal increase (about 4%) in total effective dose, which may even diminish with the latest generation MDCTs [77,78]. To avoid unnecessary Rx overexposure, it has been proposed to reserve CTV scanning to CTPA-positive cases in which a complete evaluation of the venous district may favourably influence patient management [78], but doing so the additional benefit of recovered VTE diagnoses would be lost. CTV may be of less
Fig. 8. Contrast-enhanced high-resolution three-dimensional magnetic resonance angiography shows small emboli in the right posterior (A) and left posterior (B) inferior lower lobar pulmonary arterial branches, and concomitant left iliofemoral deep venous thrombosis is depicted by steady-state free-precession fat-suppressed FIESTA fast sequence (C) and subsequent contrast-enhanced MRA (D), using intravascular contrast agent.
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tory findings must be adopted in order to prevent over-referral of patients to MDCT, to avoid unjustified radiation exposure. On the other side, MR may emerge as a strong competitor in the next few years because it allows the detection of VTE without using X-rays and contrast media (Figs. 8 and 9). Triple-ruleout protocols are beginning to be proposed, thanks to cardiac gating to investigate aortic and coronary emergencies together with PE in a single test. CT perfusion maps are at the beginning of clinical application and could further refine diagnostic evaluation by the functional point of view, in addition to cardiac gating in evaluating heart function by time-resolved 4D imaging. But for now, MDCT is yet a formidable weapon in PE/VTE diagnostic management. We have learned how to use it, and we are still continuing to attain an even more effective and timeeffective application of MDCT in everyday emergency clinical practice. References
Fig. 9. Three-dimensional time-resolved ultrafast TRICKS contrast-enhanced magnetic resonance angiography sequence shows complete occlusion of the left lower lobe artery distally to the apical and lingular branches (A) complemented by pulmonary perfusion color-coded map showing large left lung base hypoperfused area (B).
value in patients presenting with DVT symptoms rather than PE symptoms and/or low-risk cases, if they are first examined by US [79]. CT, however, is even more accurate, standardized, reproducible and panoramic than US in studying abdominal and pelvic, superficial and calf veins less confidently approached by US and/or not always included in standard protocols. It gives better depiction of the upper extent of venous thrombi in the iliac veins and cava, eventually indicating the need for IVC filter positioning, and showing even minimal remnants of culprit thrombus that could be found in the limbs (Fig. 7) [80]. MDCT has another important quality: the simpler the protocols, the easier their implementation in real clinical practice, since more complicated algorithms may not always be followed in everyday routine. 4. Conclusions The adoption of CT as the current standard technique in diagnosing PE led both to better patient management and to a better understanding of the overall physiology of VTE disease. By refining our protocols including follow-on CTV to CTPA, we can considerably shorten and simplify the diagnostic pathways, that cannot be redundant especially in the emergency department in where time can make the difference in saving lives. Panoramic features of MDCT can be exploited in emergent issues in diagnosis, depicting the whole extent of disease and associated/alternative findings. With regard to prognosis, it can grade the severity of pulmonary bed obstruction and right heart overload. Clinical prediction rules based on clinical and labora-
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Suspected pulmonary embolism and deep venous thrombosis: A comprehensive MDCT diagnosis in the acute clinical setting Luca Salvolini a,∗ , Mariano Scaglione b , Gian Marco Giuseppetti a , Andrea Giovagnoni a a
Radiology Department, “Umberto I” Hospital - Ospedali Riuniti - “Politecnica delle Marche” University, Via Conca, 60020 Ancona, Italy b Emergency and Trauma CT Section, Department of Radiology, Cardarelli Hospital, Via G. Merliani 31, 80127 Napoli, Italy Received 6 September 2007; received in revised form 7 September 2007; accepted 8 September 2007
Abstract Both pulmonary arterial and peripheral venous sides of venous thromboembolism (VTE) can now be efficiently and safely investigated by multi-detector CT (MDCT) at the same time by a combined CT angiography/CT venography protocol. In the emergency setting, the use of such a single test for patients suspected of suffering from VTE on a clinical grounds may considerably shorten and simplify diagnostic algorithms. The selection of patients to be submitted to MDCT must follow well-established clinical prediction rules in order to avoid generalized referral to CT on a generic clinical suspicion basis and excessive population exposure to increased ionizing radiation dose, especially in young patients. Clinical and anatomical wide-panoramic capabilities of MDCT allow identification of underlying disease that may explain patients’ symptoms in a large number of cases in which VTE is not manifest. The analysis of MDCT additional findings on cardiopulmonary status and total thrombus burden can lead to better prognostic stratification of patients and influence therapeutic options. Some controversial points such as optimal examination parameters, clinical significance of subsegmentary emboli, CT pitfalls and/or possible falsely positive diagnoses, and outcome of untreated patients in which VTE has been excluded by MDCT without additional testing, must of course be taken into careful consideration before the definite role of comprehensive MDCT VTE “one-stop-shop” diagnosis in everyday clinical practice can be ascertained. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Pulmonary embolism; Deep venous thrombosis; Venous thromboembolism; CT angiography; CT venography; MDCT
1. Introduction Venous thromboembolism (VTE) is a systemic and potentially lethal illness: pulmonary embolism (PE) and deep venous thrombosis (DVT) are two aspects of the same disease [1]. Clinical pictures vary from nearly asymptomatic to life-threatening syndromes, and presentation symptoms are quite non-specific, with broad differential diagnoses. Correct therapy must be implemented as soon as possible to be effective and also to avoid unnecessary treatments. Often both pulmonary arterial and deep venous sides of the disease have to be investigated to reach diagnosis and correct patient management. Until the early nineties this could only be accomplished by at least two different techniques. In an attempt to perform more rapid and accurate diagnoses, nearly every branch of radiology has been involved over the last decades in the diagnostic
∗
Corresponding author. Tel.: +39 71 5964078; fax: +39 71 5965009. E-mail address: [email protected] (L. Salvolini).
0720-048X/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2007.09.019
workup of VTE. First line diagnosis in a suspected PE/DVT case relied primarily on ventilation/perfusion (V/Q) scintigraphy and then ultrasound (compression ultrasound, Doppler/Echo-color Doppler) depending on clinical presentation. In a large percentage of cases, due to indeterminate and non-conclusive findings, multiple diagnostic tests were performed, often by searching for VTE as a surrogate of diagnosing the most harmful potentially associated PE; and in the patients in which it was not possible to confidently rule in or out PE due to inconclusive noninvasive tests or discordant clinical findings, invasive testing by gold-standard pulmonary angiography and/or lower limbs phlebography had to be carried out, with additional costs and time resources consumption and possible complications. With the introduction of helical CT (HCT), and then MDCT as a major technical evolution, for the first time we could rely on a technique that was capable of showing direct evidence of the presence of thrombi and emboli in both limb veins and pulmonary arteries at the same time, and it was only minimally invasive and feasible even in emergency room (ER) patients apart from echocardiography.
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The role of CT pulmonary angiography (CTPA) as the “workhorse” test in diagnostic evaluation of suspected PE has been widely accepted after considerable debate [2,3]. Still more controversial is the possible implementation of follow-on CT indirect venography (CTV) of the abdomen, pelvis, and inferior limbs and to search for concomitant VTE in the venous phase immediately after CTPA in routine practice. After reviewing technical principles which correct application is essential in order to achieve optimal results in diagnostic accuracy and reduce the number of inconclusive examinations, in this paper, we will analyze the effectiveness of combined CTPA/CTV as a comprehensive one-stop test in VTE diagnosis. We will also comment its advantages and possible drawbacks. Our aim is to help the reader decide if combined PE/DVT diagnosis by MDCT meets increasing demands of referring clinicians for a more effective and cost-effective approach. Should we implement such simplified protocols, or rather bear technological pressure and wait for a larger body of evidence before recommending routinely adding CTV to CTPA protocols in searching for VTE? 2. Technical issues 2.1. CT pulmonary angiography (CTPA) The introduction and continuous technical evolution of MDCT has allowed more flexible and high-performance protocols, to match diagnostic needs without compromising detail and coverage [4–6]. The precise setting of scan parameters depends on the number of slices than can simultaneously be acquired and factory presets, and so protocols differ according to different manufacturers, from 4- to 64-slice machines. In cooperative patients, 1–1.25 mm slice collimation can be sustained in most cases even with 4-/8-slice scanners, thus allowing a more detailed evaluation of subsegmentary branches. With 16- and 64-slice scanning, sub-millimetre collimation has been advocated, but halving slice width in order to keep the same noise level can lead to correspondent geometrical increase of radiation dose that we must be aware of. It is the authors opinion that in most cases 1-mm collimation is enough to permit a confident evaluation of the arterial lung tree apart from “triple rule-out” protocols. Subsecond scanning is essential to reduce possible motion artefacts and shorten scan time. With volume pitches of about 1.3 and 1–1.25 mm collimation, the whole lungs can be studied in 3–12 s by 64- and 16-slice MDCT, while the patient holds his/her breath. In ER or intensive care patients and in other such cases in which apnoea cannot be sustained, subsecond scanning and maximum pitch values reduce motion artefacts with about 2-mm collimation to rule in or out major emergent PEs. Pre-contrast scans may help in more precisely programming contrast-enhanced phase, detecting differential diagnoses in advance and adjusting study parameters, and even showing clots in some cases (Fig. 1) [4–6]. Most protocols recommend relatively high contrast bolus flow rates (3–5 ml/s) and iodine concentration (300–370 mg I/ml), with total injected volume to be adjusted according to scan duration, patients habit, and renal
Fig. 1. (A) Unenhanced axial multi-detector row CT scan shows spontaneous hyperdense clot emboli in the main and lobar pulmonary arteries, confirmed after contrast material administration (B).
function, roughly between 70 and 120 ml, and delay between 7–8 and 15–22 s depending on flow rate and total volume. CTPA bolus must be adjusted to the shortened MDCT scan duration. In order to maintain an adequate iodine inflow and thus optimal enhancement of lung vessels with a lesser scan time, the contrast bolus must be more compact: flow rate must be kept as high as 4–6 ml/s while maintaining moderately highconcentration options, and total amount of contrast can be decreased in most cases up to 60–80 ml. If we adopt followon CT venography protocols, however, as much as 110–140 ml of 300–370 mg I/ml contrast are still required for a confident evaluation of the venous district after recirculation. Saline flushing if precisely timed is a valuable option. Bolus tracking is a double-edged weapon due to the delay between ROI target vessel enhancement and the beginning of the scan. This delay must be taken into account in selecting threshold HU trigger value and ROI positioning, and the level of the tracking slice according to the first scanned slice. ECG-gating for reduction of cardiac motion artefacts is not advised due to the unacceptably low pitch with excessively prolonged scan time and increased imparted dose and until the suitability of triple rule-out protocols is not assessed. Apart from respiratory and cardiac motion, other possible pitfalls include anatomical confusing structures and flow-related artefacts that must be known and recognized [7–11]. Prognostically relevant factors such as right heart acute
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Fig. 2. (A) Near-complete occlusion of the right main pulmonary artery causing acute right heart overload (B). After therapy, restored patency of the right pulmonary artery (C) is matched to the resolution of the right ventricular dilatation (D).
Fig. 3. Contrast-enhanced multi-detector row CT scans show presence of intraluminal webs and arterial stenoses (A, arrow) and partially calcified thrombus in both pulmonary arteries (B) after chronic pulmonary embolism; post-thrombotic phlebolithiasis of the right popliteal vein is also evident (C, arrow).
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failure signs (Fig. 2) and chronic PE issues must be sought and reported (Fig. 3). Associated parenchymal findings must be evaluated on lung window images reconstructed with appropriate kernel. Moving to CT venography, non-helical sequential scanning, using slice widths between 5 and 10 mm and slice intervals up to 5 cm, bears the risk of missing shorter segmentary clots [12]. Single-slice spiral CTV protocols employ 5–10 mm slice collimation at maximum pitch. Now with MDCT, we are limited by the total number of images and increased doses if the thinner slice collimation values and continuous volumetric scan mode are employed, rather than by technical limitations. As a useful compromise, 3.75–5 mm reconstructed image thickness (by maintaining upper slice collimation to 2.5–3.75 mm) with the maximum table speed possible and carefully adjusted mA settings with automated dose modulation protocols at 120–160 mAeff can maximize diagnostic benefit at an acceptable imparted dose level. Scanning should include the deep venous district from the IVC and iliac veins down to the popliteal fossae/upper calves. In theory, caudal–cranial scanning better reflects the physiology of deep venous enhancement with prolonged scan times, but this is less of an issue with MDCT [13,14]. Ideal scan delay is comprised between 180 and
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Fig. 4. (A) Pseudo-thrombotic uneven mixing artefact in the left common femoral vein on CT images acquired after 100 s of scan delay, solved by rescanning after more appropriate 180 s delay (B).
Fig. 5. A 67-year-old patient suspected of having pulmonary embolism after surgical application of right hip prosthesis. (A and B) Coronal and sagittal multiplanar reconstructions depict extent of a “filling defect” in the right main pulmonary artery. (C) Coronal CT reformation demonstrates left iliofemoral vein and right femoral thrombosis.
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Fig. 6. Contrast-enhanced multi-detector row CT scans show massive bilateral pulmonary emboli (A) associated with intramural hematoma in the descending thoracic aorta (B).
240 s after the beginning of contrast bolus administration during previous CTPA phase, and might be even more prolonged in case of impaired cardiac function. Shorter delays can lead to false-positive pseudo-thrombotic findings due to incomplete recirculation and uneven mixing of injected contrast into the venous blood pool (Fig. 4) [15–18]. For the same reason, it is not recommended to split the bolus, but it is better to administer the total amount at a single time during the arterial study. Elastic stockings may be recommended in order to enhance deep venous filling, but this does not seem a practical option, particularly in critically ill patients [19]. Other pitfalls that we should be aware of may come from orthopaedic hardware, near cortical bone, and anatomical and pathological structures that can mimic thrombosed veins [20–22]. High-density thrombus may indicate acute DVT and so better prognosis on resolution of clots by immediate therapy (Fig. 1) [23]. Interactive console viewing of reconstructed CTPA/CTV images is essential to scroll images following every single vessel adjusting window/level, by cine-viewing and real-time multiplanar evaluation. MPR reformats may be useful in depicting the extent of pathology on anatomically oriented images (Fig. 5), but multi-voxel-thick MIP/MPVR reconstructions should be avoided so as not to miss thin emboli. 3. Discussion: advocates and drawbacks The actual status of CT in VTE diagnosis in clinical practice is that of an “unofficial” gold standard—that is, CT represents
the basis of PE diagnosis in most emergency departments worldwide, even if clinicians are often sceptical of its role as one-step ruling out diagnostic test [24]. Adding follow-on DVT testing to CT protocols further complicates the question, as its suitability is still under considerable debate and CTV is not yet included in standardized protocols. At least in symptomatic patients, a first scan for DVT by compression ultrasound (CUS) was considered an effective approach. Conventional diagnostic work-up of VTE in the pre-CT era required much time, considerable resources, multiple and often overlapping diagnostic tests, and could not be achieved in all centres and cases, especially in emergency situations in which massive PE could only be indirectly investigated by bedside echocardiography. That is why HCT pulmonary angiography deserved nearly immediate attention and application, being easy to perform, reproducible, non-invasive or minimally invasive, based on rapidly widespread technique, and allowing direct demonstration of emboli and alternative diagnoses. Initial enthusiastic reports on CTPA accuracy, however, were not universally confirmed, especially if subsegmental arteries were included in diagnostic evaluation [25–32]. Nevertheless, CT appeared to be a more discriminating technique. First costeffectiveness analyses published showed positive results for CT-based protocols not only in ruling-in PE, but also as a definitive, clinical-evidence-based ruling-out test, as all effective strategies were based on CTPA, preceeded by clinical/D-dimer screening and eventually complemented by US at slightly higher cost-per-life saved but attaining further marginal reduction in mortality [33–36]. In this picture, since the late 1990s, after having demonstrated the suitability of CTPA not only as a firstline diagnostic test in PE but also in substituting for invasive pulmonary angiography as the current standard of care and reference, then CTV began being investigated. The relatively limited performance of the first spiral CTs prevented CTV in being effectively proposed as a follow-on adjunct to CTPA from the beginning, apart from few pioneers. As technical evolution progressed and comprehensive CT evaluation became feasible, after a few years, first convincing efforts were made to evaluate and propose the possible role of additional CTV as a valuable option to allow complete one-step evaluation of VTE, being the reported values of sensitivity and specificity and adopted goldstandards in first series quite non-homogeneous, as did proposed protocols [18]. The rationale for follow-on CTV after CTPA is threefold. Firstly, HCT diagnostic accuracy could be refined both by recovering VTE diagnoses in a considerable percentage of patients (in the range from 15% to 38% excepting isolated lower and higher peaks) with negative CTPA but positive CTV, and by confirming CTPA negativity lessening the need for additional DVT testing by US [12,22,37–39]. Secondly, CTV represents a more efficient utilization of resources than have already been employed for CTPA, since helical CTV requires little additional time, employs the contrast bolus previously injected in the pulmonary arterial phase thus optimizing its use, and the patient is still lying on the CT table and so considerable time and resources are spared in evaluating the deep venous district without patient referral to other techniques, and without additional cost. Thirdly, since
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Fig. 7. Missed US diagnosis of deep venous thrombosis associated with pulmonary embolism due to thrombotic fragments in the left external iliac vein (A), coming from clots in distal tributary sub-popliteal leg veins (B, arrows), from incompletely occluding thrombus in the superficial thigh veins (C, thrombosis of the left saphena) and from very small remnants in the femoropopliteal and tibial districts (D–F, arrow).
most fatal PE events are recurrent PEs from persisting DVT that can be present in a large percentage of patients, and the cranial extension of venous thrombi and the presence of venous anatomical anomalies and variants influence therapeutic options such as VCI filter positioning, estimating total clot burden and extension, nearly impossible in US, could be more of an issue in VTE regarding prognostic stratification and therapeutic management rather than seeking minimal isolated lung emboli. Associated
DVT can be demonstrated by CTV in up to 50% (13–93% in the literature as peak values) of patients affected by PE on CTPA [38,40,41]. Another strength of HCT is the capacity to explain the clinical emergent picture by showing alternative diagnoses or additional findings, which can be clinically relevant and affect therapeutic choices (Fig. 6), not only in the chest but also in the abdominal district, thus allowing a correct patient management even in
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many non-VTE cases, up to 40–75%, and avoiding further referral to CT searching for occult tumours that are often associated to VTE [10,42–45]. So the one-stop role of CT is a single test that can be used to solve different questions in critically ill patients, and to depict multiple aspects of the same disease in a single case [46]. In this context, perfusion scintigraphy may be an alternative option due to its low cost and low radiation dose and clinicians’ reluctance to abandon well-established scintigraphy-based protocols; however, in the emergency patients, scintigraphy is often either unfeasible or unreliable [1,47]. So if we want to rely on a fast, reproducible and accurate test widely available in most hospitals on a 24-h basis, then CTPA with follow-on CTV could considerably simplify and shorten diagnostic evaluation following evidence-based criteria and the “golden hour” principle [48,49]. And in addition, even without cardiac gating, CTPA images include a considerable amount of information about the status of the right side of the heart, pulmonary hypertension, and the extent of pulmonary arterial bed obstruction, that should be concomitantly evaluated because patient prognostic stratification may be as important as diagnosis itself [24,50–56]. Today MDCT is also proposed as a standardized approach for CTPA/CTV, with consistent diagnostic accuracy [14,57–61], and with excellent results in the follow-up of untreated patients. The improved longitudinal and temporal resolution of multislice/subsecond scanning allow a better evaluation of the more peripheral branches [25,62–68]. However, if we compare HCT
to MDCT as to the detection of subsegmentary and peripheral branches from an anatomical and clinical viewpoint, MDCT pulmonary angiography does not give more relevant information in patient management [69,70]: it is the additional detection rate of DVT by CTV that is even higher in MDCT than in HCT, allowing more VTE diagnoses to be made. The strong arm of CT may not only be submillimetric resolution, but its panoramic features and time-efficiency leading to more confident and faster diagnosis. A negative issue is the additional radiation dose imparted with CTV after CTPA, especially in younger patients. Even if detector augmented efficiency and dose-modulation protocols in MDCT allow lesser increase in imparted Rx dose in comparison with HCT, this issue has to be adequately considered. Several studies have analyzed irradiation doses; reported values account for an incremental absorbed dose of about 50% by adding CTV to CTPA, from low values up to about 8–12 mSv [71–76]. However, in comparison with old diagnostic protocols based on invasive testing, the adoption of CT has lead to only a marginal increase (about 4%) in total effective dose, which may even diminish with the latest generation MDCTs [77,78]. To avoid unnecessary Rx overexposure, it has been proposed to reserve CTV scanning to CTPA-positive cases in which a complete evaluation of the venous district may favourably influence patient management [78], but doing so the additional benefit of recovered VTE diagnoses would be lost. CTV may be of less
Fig. 8. Contrast-enhanced high-resolution three-dimensional magnetic resonance angiography shows small emboli in the right posterior (A) and left posterior (B) inferior lower lobar pulmonary arterial branches, and concomitant left iliofemoral deep venous thrombosis is depicted by steady-state free-precession fat-suppressed FIESTA fast sequence (C) and subsequent contrast-enhanced MRA (D), using intravascular contrast agent.
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tory findings must be adopted in order to prevent over-referral of patients to MDCT, to avoid unjustified radiation exposure. On the other side, MR may emerge as a strong competitor in the next few years because it allows the detection of VTE without using X-rays and contrast media (Figs. 8 and 9). Triple-ruleout protocols are beginning to be proposed, thanks to cardiac gating to investigate aortic and coronary emergencies together with PE in a single test. CT perfusion maps are at the beginning of clinical application and could further refine diagnostic evaluation by the functional point of view, in addition to cardiac gating in evaluating heart function by time-resolved 4D imaging. But for now, MDCT is yet a formidable weapon in PE/VTE diagnostic management. We have learned how to use it, and we are still continuing to attain an even more effective and timeeffective application of MDCT in everyday emergency clinical practice. References
Fig. 9. Three-dimensional time-resolved ultrafast TRICKS contrast-enhanced magnetic resonance angiography sequence shows complete occlusion of the left lower lobe artery distally to the apical and lingular branches (A) complemented by pulmonary perfusion color-coded map showing large left lung base hypoperfused area (B).
value in patients presenting with DVT symptoms rather than PE symptoms and/or low-risk cases, if they are first examined by US [79]. CT, however, is even more accurate, standardized, reproducible and panoramic than US in studying abdominal and pelvic, superficial and calf veins less confidently approached by US and/or not always included in standard protocols. It gives better depiction of the upper extent of venous thrombi in the iliac veins and cava, eventually indicating the need for IVC filter positioning, and showing even minimal remnants of culprit thrombus that could be found in the limbs (Fig. 7) [80]. MDCT has another important quality: the simpler the protocols, the easier their implementation in real clinical practice, since more complicated algorithms may not always be followed in everyday routine. 4. Conclusions The adoption of CT as the current standard technique in diagnosing PE led both to better patient management and to a better understanding of the overall physiology of VTE disease. By refining our protocols including follow-on CTV to CTPA, we can considerably shorten and simplify the diagnostic pathways, that cannot be redundant especially in the emergency department in where time can make the difference in saving lives. Panoramic features of MDCT can be exploited in emergent issues in diagnosis, depicting the whole extent of disease and associated/alternative findings. With regard to prognosis, it can grade the severity of pulmonary bed obstruction and right heart overload. Clinical prediction rules based on clinical and labora-
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