Sage Journals: Discover world-class research

Abstract

The spectrum of venous thromboembolic (VTE) disease encompasses both acute deep venous thrombosis (DVT) and chronic postthrombotic changes (CPC). A large percentage of acute DVT patients experience recurrent VTE despite adequate anticoagulation, and may progress to CPC. Further, the role of iliocaval venous obstruction (ICVO) in lower-extremity VTE has been increasingly recognized in recent years. Imaging continues to play an important role in both acute and chronic venous disease. Venous duplex ultrasound remains the gold standard for diagnosing acute VTE. However, imaging of CPC is more complex and may involve computed tomography, magnetic resonance, contrast-enhanced ultrasound, or intravascular ultrasound. In this narrative review, we aim to discuss the full spectrum of venous disease imaging for both acute and chronic venous thrombotic disease.

Keywords

Magnetic resonance imaging (MRI)post-thrombotic syndrome (PTS)ultrasound elastography chronic postthrombotic changes deep vein thrombosis (DVT)

Introduction

The spectrum of venous thrombotic disease encompasses both acute deep venous thrombosis (DVT) and its sequelae, including chronic postthrombotic changes (CPC) and postthrombotic syndrome (PTS). In addition, the significance of thrombotic or nonthrombotic iliocaval venous obstruction (ICVO) such as nonthrombotic iliac vein lesions (NIVL) has been increasingly recognized in lower-extremity venous disease. It is estimated that there are as many as 900,000 DVT cases a year in the United States.¹ Recurrent DVT is common despite treatment and the development of PTS can be burdensome for both the patients and the healthcare system.^1–5

Imaging plays a crucial role in the diagnosis and management of venous thrombotic disease. Conventional venography was the gold standard in diagnosing venous thrombotic disease, although limited by its invasiveness and contrast load for the patients. Venous duplex ultrasound (VDUS), however, is now the first-line diagnostic modality for both acute DVT and CPC. Despite this, VDUS has known technical limitations, particularly in patients with unfavorable body habitus. Its use is also limited in certain clinical scenarios, particularly for the assessment of CPC or recurrent DVT in the ipsilateral lower extremity. Advanced imaging modalities can help clarify indeterminate diagnosis, and can assess anatomical variants, extent of disease, and thrombus age, including computed tomography venography (CTV), magnetic resonance venography (MRV), MR direct thrombus imaging (MRDTI), contrast-enhanced ultrasound (CEUS), and invasive intravascular ultrasound (IVUS). In this manuscript, we aim to summarize the recent literature on VDUS and advanced imaging modalities for the diagnosis and management of lower-extremity acute and chronic venous thrombotic disease.

Sonographic evaluation of venous thrombotic disease

A variety of sonographic techniques have been described to evaluate both acute and chronic venous thrombotic diseases, including VDUS, US elastography, and CEUS.

Venous duplex ultrasound (VDUS)

VDUS remains the first-line diagnostic modality for suspected acute DVT. There are different technical approaches for performing VDUS, and the three most common methods include: (1) a limited two-point scan of the common femoral vein and the popliteal venous trifurcation; (2) a limited scan of the proximal deep venous system from the common femoral vein to the popliteal venous trifurcation; and (3) a ‘whole-extremity’ extended scan from the common femoral vein to the deep calf veins in 3 cm increments. Per recent recommendations from the Society of Radiologists in Ultrasound Consensus Conference, a whole-extremity ultrasound scan was the preferred diagnostic modality when time and resources permit.⁶ Similarly, recent trials have shown that limited or extended VDUS should be utilized in the appropriate clinical setting, depending on the pretest probability and/or D-dimer positivity.⁷ Regardless of the applied scanning technique, VDUS is a remarkably reliable diagnostic tool with sensitivities of 100% and 94% and specificities of 98% and 75% for acute proximal and distal DVT, respectively.^8,9 With a negative scan, the risk of venous thromboembolism is less than 2% (Table 1).^10–12

Table 1.

Summary of multiple modalities, including the advantages and disadvantages of each modality, in the diagnosis of acute and chronic venous thrombotic disease.

Modality	Advantage	Disadvantage	Sensitivity	Specificity
VDUS	Accessible, economical, first-line diagnostic modality for acute and chronic venous thrombotic disease.	Limited by operator experience and patient body habitus. Can be limited in assessing suprainguinal lesions.	100% for acute proximal DVT 94% for acute distal DVT.²³	98% specific for acute proximal DVT 75% for acute distal DVT.²³
US elastography	Potential ability to assess for thrombus age.	Operator-dependent.^a Time-consuming. Specialized equipment and software required.	–	–
CEUS	Potential ability to improve detection of small or partial thrombus. Potential ability for poststenting surveillance.	Expensive. Time-consuming. Requires specialized equipment and software. Unclear clinical benefit.	–	–
CTV	Superior ability to delineate anatomy above inguinal ligament for diagnostic, treatment-planning, and poststenting surveillance purposes.	Radiation dose. Contrast load. Expensive.	96% for acute DVT⁴Click or tap here to enter text.	95% for acute DVT⁴Click or tap here to enter text.
MRV	Superior ability to delineate anatomy above inguinal ligament for both diagnostic and treatment-planning purposes.	Expensive. MR contrast agent may be contraindicated in renal failure patients.	93% for acute DVT.⁵	96% for acute DVT.⁵
MRDTI	Potential ability to assess thrombus age.	Expensive. Requires specialized software.
IVUS	Provides superior delineation of intravascular dimensions and landmarks for venous stenting.	Invasive. Expensive. Requires specialized equipment and software.	–	–
Invasive venography	Considered the ‘gold standard’ in diagnosing DVT.	Invasive. Highly dependent upon operator experience. Limited by technical factors such as access site edema, no suitable access, contrast load, etc.	–^b	–^b

Certain US elastography techniques, such as strain imaging, are more operator-dependent than other techniques.

Considered the ‘gold standard’ for diagnosing DVT.

CEUS, contrast-enhanced ultrasound; CTV, computed tomography venography; DVT, deep venous thrombosis; IVUS, intravascular ultrasound; MR, magnetic resonance; MRDTI, magnetic resonance direct thrombus imaging; MRV, magnetic resonance venography; US, ultrasound; VDUS, venous duplex ultrasound.

However, definitive differentiation between acute recurrent DVT and CPC is more challenging on VDUS. Despite treatment, more than 50% of patients demonstrate chronic postthrombotic changes 1 year after DVT, including the presence of noncompressible venous segments.^13,14 Because of the similar imaging appearance of acute recurrent DVT and CPC (Table 2), VDUS is frequently inconclusive in the identification of suspected recurrent ipsilateral DVT.¹⁵ One solution is to obtain a baseline scan after the patient has completed anticoagulation therapy. Future scans are compared to the baseline scan, and changes in sonographic findings can be used to diagnose recurrent DVT.^16,17 Another approach is to obtain a short-term follow-up scan after suspected recurrent DVT,¹⁸ as CPC rarely changes over a short timeframe (Figure 1). However, in clinical practice, a baseline scan is frequently unavailable (particularly if patients present to a different institution). Further, obtaining a baseline scan after finishing anticoagulation therapy is against the Society of Vascular Medicine Choosing Wisely recommendation to obtain a repeat VDUS in the absence of clinical changes. Unfortunately, interobserver agreement for acute recurrent DVT is moderate at best without the baseline scan.¹⁹

Table 2.

Features distinguishing acute deep venous thrombosis from chronic postthrombotic changes on various modalities.

Modality	Acute DVT	Chronic postthrombotic changes
VDUS	Loosely attached to wall; hypo- or isoechoic; distended lumen; relatively compressible (if acute thrombus); generally no collateralization.	Adherent to wall; may be hyperechoic; thickened and scarred wall; partially noncompressible; may have collateralization.
US elastography^a	Lower stiffness; lower strain ratio.	Higher stiffness; higher strain ratio.
MRV/CTV	Luminal extension; rim-enhancement; no perivascular wall changes.	Luminal narrowing; visualization of scar tissue; intra-thrombus revascularization.
MRDTI	High intra-thrombus T1 signal.	Low/absent intra-thrombus T1 signal.

Certain US elastography techniques, such as strain imaging, are more operator-dependent than other techniques.

CTV, computed tomography venography; DVT, deep venous thrombosis; MRDTI, magnetic resonance direct thrombus imaging; MRV, magnetic resonance venography; US, ultrasound; VDUS, venous duplex ultrasound.

Figure 1.

Proposed diagnostic flow chart for acute and chronic venous thrombotic disease, incorporating emerging imaging technologies.

For patients with suspected ICVO, VDUS is readily accessible and therefore considered the preferred first-line diagnostic modality for reflux and infrainguinal venous stenosis.²⁰ It is important to note that there are no established VDUS diagnostic criteria for ICVO. Direct visualization of the stenosis and flow turbulence may suggest outflow obstruction and correlate well with IVUS findings in patients with favorable body habitus.²¹ In patients with unfavorable body habitus (i.e., poor visualization of the common iliac vein), indirect imaging signs on VDUS may include continuous flow, reflux, and poor flow augmentation to Valsalva maneuver.^22,23 In general, several small studies have shown that VDUS was not a reliable diagnostic tool for assessment of ICVO.^24,25 However, in patients with significant obstructive symptoms, indirect signs of venous obstruction highly correlated with the degree of stenosis on IVUS, which is considered the gold standard.²⁶ It is also important to note that a large percentage of patients with severe obstructive symptoms may present without evidence of reflux on VDUS yet with obstructive lesions present on IVUS.²⁷ Therefore, in patients with clinically significant obstructive symptoms, VDUS should be the first-line diagnostic modality and secondary signs suggestive of ICVO should undergo further testing. Imaging modalities such as CTV, MRV, and possibly multiplanar venography with IVUS can be considered in patients with debilitating symptoms, noting there is no consensus on the most optimal modality.

Ultrasound elastography

It is important to differentiate between acute recurrent DVT and CPC, as the management differs.²⁸ Commonly used in hepatic imaging but not routinely used in vascular imaging, elastography is one emerging sonographic technique that may prove useful in determining thrombus age. As the thrombus matures its composition changes from predominantly ‘elastic’ platelets to ‘stiff’ fibrinous material and this histopathological alteration provides the basis for elastography (Figure 2). A review of various elastography techniques, however, is beyond the scope of this article. In short, elastography techniques can be generally divided into strain imaging (SI) and shear wave imaging (SWI), with the former requiring internal or external compression (which induces shape distortion, hence ‘strain’), and the latter using ultrasound-generated shear wave stimuli (i.e., mechanically generated compressive waves).²⁹

Figure 2.

A 42-year-old man with lower-extremity pain and DVT was clinically suspected. (A) Color Doppler showed a noncompressible common femoral vein with intraluminal echogenic material, in keeping with DVT. The thrombus extended down to the popliteal vein and appeared partially hypo- and partially hyperechoic, suggesting an acute on chronic etiology. (B, C) Shear wave elastography showed the difference in stiffness between the chronic and acute thrombus component. The chronic thrombi (yellow and red dots) are stiffer compared to the softer ‘acute’ component. (D) An axial CEUS image showed the complete absence of enhancement inside the CFV, thus excluding the presence of partial recanalization. (E) An overlay image with CEUS depicting the free end of the thrombus as an intraluminal freely floating tip (arrow). (F) An axial temporal MIP image showing the ‘donut’ sign (arrow), which is created by the centrally located free tip at the cephalic end of the thrombus.

Initial animal studies have shown that chronic thrombi were associated with higher stiffness (measured by the degree of deformation) compared to acute thrombi.^30–32 Rubin et al. showed significant differences in stiffness between the acute and chronic thrombi (p < 10^–7) in human subjects (thrombus age measured by duration of presence on VDUS).³³ A more recent study of 149 patients has demonstrated significant differences in strain value between acute thrombi and CPC. Further, using a cutoff strain value of 4, the sensitivity and specificity were 99% and 99%, respectively, for acute DVT.³⁴

All the above studies were performed using the SI technique, which has certain limitations. External compressions are required and these are operator-dependent. In some of the studies, elastography was performed by one or two operators to minimize inherent heterogeneity. Having the same operator may be applicable within a controlled study, but this is not feasible in daily clinical practice. Secondly, a reference point is needed for SI which is arbitrarily chosen at the time of the exam and may not be reproducible in a clinical setting. In contrast, SWI is operator-independent and does not require internal reference. Therefore, SWI is likely to be more applicable in daily clinical practice. A recent study using SWI has revealed significant differences in stiffness between the acute and subacute thrombi (p < 0.001). Further, using a cutoff value of 2.85, the sensitivity and specificity were 96.3% and 91.3% for acute DVT.³⁵ However, given the small sample size, further studies are warranted to validate these results.

Contrast-enhanced ultrasound (CEUS)

CEUS is an evolving sonographic technique that excels in evaluating vascular pathologies. CEUS contrast microbubbles are strictly intravascular and enable evaluation of solid organ lesions and arterial pathologies. In essence, ultrasound microbubbles are composed of a lipid outer shell containing inert gas. It has an excellent safety profile and is usually renal or pulmonary excreted.³⁶ It should be noted that CEUS (and contrast microbubbles) has only been US Food and Drug Administration-approved for use in echocardiography and limited hepatic applications. Therefore, CEUS for DVT is currently an ‘off-label’ use in clinical practice.

CEUS should not be the first-line screening test for acute DVT. As previously discussed, VDUS remains a reliable diagnostic modality, particularly with respect to proximal acute DVT. However, VDUS is limited in certain scenarios, such as in obese patients, patients with significant soft tissue swelling, and patients with affected vessels above the inguinal ligament. Previous studies have shown that VDUS sensitivity for calf vein DVT was lower compared to proximal DVT (64% vs 95%).¹⁰

CEUS enables assessment of the entire lower-extremity deep venous system, including the calf veins and internal iliac vein.^37,38 Bucek et al. compared CEUS to VDUS in assessing calf vein thrombosis using invasive venography as the reference standard. The authors have found that CEUS reduced the rate of indeterminate scans from 55% to 20% and improved the specificity from 25% to 67%.³⁹ Similarly, Smith et al. have demonstrated superior visualization of the popliteal and femoral veins with CEUS but not the common femoral vein in patients at high risk for DVT and with a negative initial VDUS scan.⁴⁰

It must be emphasized that the added clinical utility of CEUS over VDUS in diagnosing acute DVT is unclear. The current studies have shown that CEUS might improve visualization of distal calf veins but not the proximal venous system. Unlike proximal DVT, there remains an ongoing debate regarding the optimal management strategy of calf vein DVT.⁴¹ Therefore, the added utility of better calf vein DVT visualization may not be necessarily clinically relevant. Similarly, isolated pelvic vein thrombosis is exceedingly rare, such that the added utility of CEUS is unlikely to affect clinical management.⁴² Therefore, CEUS (Figure 3) should be reserved when VDUS is inconclusive or when the clinical suspicion is high with a negative initial VDUS scan.

Figure 3.

A 45-year-old male presented with lower-extremity swelling. (A) Color Doppler of the common iliac vein suggesting occlusive thrombotic disease (arrow). (B) CEUS enabled clarification with demonstration of nonocclusive thrombus since the vessel partially opacified with contrast microbubbles (upper [green] arrow), and the nonocclusive thrombus showed lack of enhancement consistent with a bland thrombus (lower [red] arrow).

CEUS may also be helpful for poststenting surveillance in patients with ICVO. Liu et al. compared CEUS and VDUS to CTV in diagnosing in-stent stenosis and the authors found that there was a high degree of concordance between CEUS and CTV (κ = 0.884), resulting in a sensitivity and specificity of 88% and 97%, respectively, for CEUS.⁴³ It needs to be emphasized that these retrospective CEUS studies included a relatively small number of patients. Prospective trials are warranted to validate these findings.

Computed tomographic evaluation of venous thrombotic disease

Similar to CEUS, CTV should not be the first-line diagnostic modality for acute DVT but may be useful when VDUS is inconclusive and when there is suspected ICVO (Figure 1 and Table 1). Although CTV is associated with high sensitivity and specificity for acute DVT,^44,45 the major concerns are the incremental radiation dose (particularly to the pelvis) and contrast load, which may be contraindicated in patients with renal insufficiency. One mitigating strategy to decrease the contrast amount is to reduce the tube voltage while preserving imaging quality.⁴⁶ A different strategy is to combine indirect CTV with CT pulmonary angiography (CTPA) in patients with suspected PE, thus negating the need for additional contrast load. However, previous studies have shown that there was little added benefit of indirect CTV while exposing patients to increased radiation.^47–49 As bedside VDUS becomes increasingly accessible, CTV should not be the first-line diagnostic modality for acute DVT.

However, in cases of suspected ICVO, CTV is useful in the diagnosis, treatment planning, and posttreatment surveillance. It is important to note that CTV should not be the first-line screening test for ICVO and CTV should be reserved for patients with convincing signs of ICVO.⁵⁰ CTV was able to demonstrate anatomic abnormalities in the iliofemoral veins and inferior vena cava, including vascular and nonvascular etiologies, such as iliac vein compression, pelvic malignancy, or benign masses.^51,52 Liu et al. have found CTV to be highly sensitive and specific in diagnosing ICVO and in differentiating thrombotic and nonthrombotic iliac compression syndrome. CTV was able to delineate the precise venous anatomy, collateral flow, and extent of iliac thrombosis.⁵³ In comparison to VDUS, CTV requires decreased exam time and can more readily detect underlying abnormality, particularly within the pelvis.⁵⁴ In comparison to IVUS, recent evidence has shown that CTV results were comparable when the degree of venous outflow stenosis exceeded 50%.⁵⁵ However, other studies have shown IVUS to be superior to CTV in assessing the degree of stenosis in patients with significant obstructive symptoms.⁵⁶ Therefore, in patients with high clinical suspicion and negative CTV results, IVUS may be considered as a reasonable next step.

Poststenting, CTV enabled characterization of morphological changes, including stent occlusion, collapse, and neointimal hyperplasia.⁵⁷ Furthermore, as reflux is often uncorrected with iliac vein stenting (thus limiting the utility of VDUS on poststenting surveillance, as the patient will continue to demonstrate reflux),²⁷ CTV should be used to assess for the presence of new lesions and/or re-stenosis in patients with recurrent or persistent symptoms after initial stenting.

Magnetic resonance evaluation of venous thrombotic disease

MR evaluation of venous thrombotic disease includes MRV and MRDTI. Both techniques can provide valuable information on both the diagnosis and the characterization of DVT.

Magnetic resonance venography (MRV)

MRV with and without contrast is similar to CTV with the obvious benefit of mitigated radiation exposure. MRV can be used to diagnose acute DVT when VDUS is inconclusive. Various MRV techniques have been described, including time-of-flight (TOF), phase contrast (PC) sequence, fresh-blood imaging (FBI), steady-state free precession sequence (SSFP), and contrast-enhanced T1-weighted gradient echo sequence using gadolinium-based contrast agents. A detailed discussion of various MRV techniques is beyond the scope of the article, although MRV has been demonstrated to have adequate sensitivity and specificity (Table 1).⁵⁸

Although not definitive, MRV features can be used to differentiate between acute DVT and CPC (Table 2 and Figure 4), which carries important prognostic implications. In the recent post hoc analysis of the Dutch CAVA trial, MRV could differentiate between acute, subacute, and chronic thrombi. In particular, it is noteworthy that 91.7% of self-reported chronic thrombi were re-categorized into acute or subacute thrombi by MRV, though 4% of the self-reported acute thrombi were chronic thrombi by MRV. Further, MRV categories were predictive of procedural duration and success rate: the average durations for catheter-directed thrombolysis (CDT) were 23 hours, 43 hours, and 85 hours for acute, subacute, and chronic thrombi, as defined by MRV (p < 0.0001). CDT was successful in 68.2% of the acute and subacute DVT group versus 16.7% of the chronic thrombus group (OR = 10.71; 95% CI, 2.07 to 55.5; p = 0.006).⁵⁹

Figure 4.

Stages of venous thrombosis by MRI. A normal vein shows a homogeneously opacified vein lumen with normal diameter. An acutely thrombosed vein is dilated with a low signal intensity lumen and a small enhancing rim. A subacutely thrombosed vein is dilated with a low-intensity lumen and a thick enhancing rim of contrast representing the venous wall. There might be small hyperintense areas within the thrombus as a sign of partial recanalization. Over time, the venous luminal size normalizes with a partially patent lumen and peripheral, low signal intensity thrombus (‘old’ thrombosed vein). With chronic postthrombotic changes, the vein lumen is reduced in comparison with a normal vein. There might be intraluminal webs or scars.

Similar to CTV, recent investigative studies have shown that MRV could be used to assess ICVO (Figures 5 and 6). Massenburg et al. retrospectively compared 2D TOF MRV with IVUS and venography findings. The authors have found that MRV had a sensitivity of 100% and specificity of 22.7% in diagnosing the underlying etiology.⁶⁰ Similarly, Shi et al. compared multimodal MRV to venography and found that MR imaging yielded an accuracy of 96%, a sensitivity of 97%, and a specificity of 89% in diagnosing ICVO.⁶¹ With regards to posttreatment surveillance, the use of MRV is limited due to venous stent susceptibility artifacts.

Figure 5.

A 58-year-old woman with thrombotic disease of the left common and external iliac vein. (A, B) An axial MRV showed a severely narrowed and scarred left common iliac vein (arrow) coursing behind the right common iliac artery. These findings suggest May–Thurner physiology. (C, D) An axial MRV at different levels demonstrating an acute thrombotic component extending from the distal left common iliac vein to the femoral vein (arrows). The veins appear dilated with a central location of the thrombus without contrast enhancement of the lumen, suggestive of acute thrombosis caused by the central stenosis.

Figure 6.

A 44-year-old male with chronic postthrombotic syndrome with occlusive disease of the right common and external iliac veins. (A) An axial MRV showed patent IVC without evidence of thrombosis or stenosis. (B, C, D) An axial MRV at different levels showing postthrombotic changes of the right common and external iliac veins, noting venous synechiae and scarring. The veins appear atretic and narrowed (arrows). This constellation of findings is consistent with chronic thrombotic disease with functional occlusion. Note the left common and external iliac veins are patent without evidence of thrombosis (dashed arrow in C).

Magnetic resonance direct thrombus imaging (MRDTI)

MRDTI is a novel technique that enables evaluation of the thrombus age, which may have important therapeutic implications. MRDTI is a T1-weighted gradient echo sequence that assesses the changing oxygenation of hemoglobin within the thrombus. The intra-thrombi signal normalized after 6 months, thus providing the basis for differentiating between acute DVT and CPC.⁶² Previous studies have shown that MRDTI could accurately diagnose acute DVT above and below the knee with sensitivities and specificities of 87% and 95%, and 97% and 100%, respectively.⁶³ Similarly, Westerbeek et al. have shown that MRDTI had a sensitivity of 95.3% in identifying acute DVT.⁶² In the subsequent study, Tan et al. have demonstrated that MRDTI could accurately differentiate between acute recurrent DVT and CPC with a sensitivity of 95% and a specificity of 100%. The authors have also shown an excellent interobserver agreement (κ = 0.98).⁶⁴

Accurate MRDTI assessment of thrombus age carries significant therapeutic implications. In a recent prospective trial, van Dam et al. have evaluated the predictive value of MRDTI in ruling out acute recurrent DVT. A total of 305 patients with suspected recurrent ipsilateral DVT were included in the study. In patients with negative MRDTI findings, no new anticoagulation regimen was initiated, whereas patients with positive MRDTI findings underwent an anticoagulation regimen. Only two patients had inconclusive MRDTI findings secondary to prosthesis and venous stent placement. In patients with negative MRDTI, 1.7% of the patients developed recurrent DVT (95% CI, 0.20% to 5.9%).⁶⁵

Intravascular ultrasound evaluation of venous thrombotic disease

IVUS should not be used for acute DVT diagnosis given its invasive nature and high costs. As discussed above, VDUS is likely the most appropriate first-line diagnostic modality for suspected ICVO. However, in patients with significant venous obstructive symptoms and equivalent imaging findings on CTV/MRV/VDUS, or those who have failed conservative management, IVUS was highly sensitive in detecting obstructive lesions (Figure 7).⁶⁶ Further, in comparison with other modalities such as CTV and MRV, IVUS has significant advantages given its intravascular nature and ability to assess key parameters and important landmarks.⁶⁷ A previous paper has shown that IVUS could assess fine mural details, including venous trabeculations and webs, which may be too small to delineate on CTV or MRV.⁶⁸ In comparison to multiplanar venography, a recent study has shown that IVUS was more sensitive in identifying venous stenotic lesions. Further, venography was found to underestimate the degree of stenosis in comparison to IVUS (p < 0.001), which resulted in management changes in 28% of the patients based on IVUS findings.⁶⁹ Similarly, Montminy et al. have found that venography failed to identify stenotic lesions in 19% of the assessed limbs in comparison to IVUS. IVUS could better identify key parameters for stenting. For example, the iliocaval junction was on average one vertebral level higher on IVUS compared to venography. Accurate assessment of key landmarks is critical to ensure correct stent sizing and placement.⁷⁰

Figure 7.

A 46-year-old woman presenting with chronic pelvic pain and left flank pain. (A, B) Axial MRV showed compression of the left common iliac vein by the right and left common iliac artery, noting prestenotic dilatation of the left common iliac vein (arrowheads). (C) Axial MRV showing dilated left ovarian vein (arrowhead). (D, E, F, G) Serial IVUS images showed narrowed left common iliac vein (left [white] arrowhead) while coursing behind the left common iliac artery (right [red] arrowhead). (H) The patient underwent iliac stenting with marked improvement of symptomatology, noting good stent apposition on IVUS. (I, J) A follow-up CT venogram depicting a widely patent left common iliac venous stent.

IVUS could be used to assess treatment adequacy and to predict clinical outcome. Previous studies have shown that residual thrombus burden within the iliofemoral segment was associated with worse patient symptomology.⁷¹ At the conclusion of the procedure, IVUS is able to assess for residual thrombus burden and, therefore, subsequent treatment planning. A previous study has shown that IVUS was more sensitive in detecting residual thrombus than venography (p = 0.03).⁷² Murphy et al. have found that the residual stenosis was more severe on IVUS than venography (20% vs 10%, p < 0.05). Further, in 36% of the patients, residual thrombotic disease was only visualized on IVUS.⁷³ With regards to predicting procedure outcome, Gagne et al. examined the relationship between baseline IVUS stenosis and clinical outcomes. The authors have found that greater than 54% stenosis was the optimal threshold for treatment.⁷⁴

Most importantly, recent evidence has shown that the use of IVUS is associated with improved patient outcomes. Tran et al. compared IVUS and multiplanar venography to venography alone in the management of thrombotic and nonthrombotic iliofemoral venous disease. The authors have found the additional use of IVUS was associated with a longer total length of the stent and a higher rate of infrainguinal stent extension. Further, the mean diameter of the stent was larger when IVUS was used. Both 30-day and 2-year primary patency rates were significantly higher in the IVUS with venography group (p = 0.02 and 0.03, respectively).⁷⁵

Invasive venography of venous thrombotic disease

Invasive venography has been considered the ‘gold standard’ for diagnosing acute DVT. The four cardinal signs of DVT include constant filling defects, abrupt termination of the contrast column, nonfilling of the venous system, and diversion of flow, as described in the original paper by Rabinov and Paulin.⁷⁶ However, venography remains technically challenging and in up to 30% of the cases, venography failed to visualize some of the venous segments.⁷⁷ In addition, venography is limited secondary to its invasiveness and association with large contrast load, which can be contraindicated in certain patient populations.

With regards to iliac vein stenting for ICVO, venography, and in particular multiplanar venography, remains an important modality. As discussed above, IVUS has been shown to be superior in its ability to delineate landmarks and key parameters for iliac venous stenting. However, venography can offer a more ‘global’ view of the diseased segment, including visualization of collateral flow and its ‘road-mapping’ ability in recanalizing chronically occluded venous segment. Venous stenting is routinely performed with both venography and IVUS with clinical benefits for the patients.

Conclusion

Lower-extremity venous thrombotic disease encompasses both acute and chronic thrombotic disease and can lead to significant morbidity and mortality. In particular, PTS has been increasingly recognized as a major quality of life issue in the recent decade. As endovascular therapy has evolved, there is a need for superior pre- and postoperative assessment of venous thrombotic disease. VDUS remains the first-line diagnostic tool given its ease of access and cost effectiveness. Further, it is a remarkably reliable modality for acute DVT diagnosis. However, its role in assessing chronic or recurrent DVT, and ICVO, is less clear. More advanced imaging modalities, including various sonographic techniques, CTV, MRV, MRDTI, and IVUS, have been shown to provide added utility in certain clinical scenarios. In particular, CEUS, US elastography, and MRDTI may prove useful in cases of diagnostic uncertainties and to provide additional information regarding the thrombus composition/age. CTV and MRV are particularly useful in delineating underlying etiologies in venous outflow obstruction. Lastly, IVUS is critically important in assessing venous stenosis and endovenous pathology, which is important for iliac stenting. Although promising, current studies are including a relatively small and heterogeneous patient population. Future clinical trials are required to further validate the role of various imaging techniques in the management of acute and chronic lower-extremity venous thrombotic disease.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Vasileios Rafailidis

Sasan Partovi

References

Beckman

Hooper

Critchley

Ortel

. Venous thromboembolism: A public health concern. Am J Prev Med 2010; 38: S495–S501.

Prandoni

Lensing

Prins

. Long-term outcomes after deep venous thrombosis of the lower extremities. Vasc Med 1998; 3: 57–60.

Mickley

Schwagierek

Rilinger

, et al. Left iliac venous thrombosis caused by venous spur: Treatment with thrombectomy and stent implantation. J Vasc Surg 1998; 28: 492–497.

Kahn

Galanaud

Vedantham

Ginsberg

. Guidance for the prevention and treatment of the post-thrombotic syndrome. J Thromb Thrombolysis 2016; 41: 144–153.

MacDougall

Feliu

Boccuzzi

Lin

. Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. Am J Health Syst Pharm 2006; 63: S5–S15.

Needleman

Cronan

Lilly

, et al. Ultrasound for lower extremity deep venous thrombosis: Multidisciplinary recommendations from the Society of Radiologists in Ultrasound Consensus Conference. Circulation 2018; 137: 1505–1515.

Riva

Camporese

Iotti

, et al. Age-adjusted D-dimer to rule out deep vein thrombosis: Findings from the PALLADIO algorithm. J Thromb Haemost 2018; 16: 271–278.

Seidel

Cavalheri

Jr Miranda

Jr.

The role of duplex ultrasonography in the diagnosis of lower-extremity deep vein thrombosis in non-hospitalized patients. Int Angiol 2008; 27: 377–384.

De Oliveira

França

Vidal

, et al. Duplex scan in patients with clinical suspicion of deep venous thrombosis. Cardiovasc Ultrasound 2008; 6: 53.

10.

Goodacre

Sampson

Thomas

, et al. Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis. BMC Med Imaging 2005; 5: 6.

11.

Johnson

Stevens

Woller

, et al. Risk of deep vein thrombosis following a single negative whole-leg compression ultrasound: A systematic review and meta-analysis. JAMA 2010; 303: 438–445.

12.

Kraaijpoel

Carrier

Le Gal

, et al. Diagnostic accuracy of three ultrasonography strategies for deep vein thrombosis of the lower extremity: A systematic review and meta-analysis. PLoS One 2020; 15: e0228788.

13.

Piovella

Crippa

Barone

, et al. Normalization rates of compression ultrasonography in patients with a first episode of deep vein thrombosis of the lower limbs: Association with recurrence and new thrombosis. Haematologica 2002; 87: 515–522.

14.

Ageno

Squizzato

Wells

, et al. The diagnosis of symptomatic recurrent pulmonary embolism and deep vein thrombosis: Guidance from the SSC of the ISTH. J Thromb Haemost 2013; 11: 1597–1602.

15.

Tan

Velthuis

Westerbeek

, et al. High percentage of non-diagnostic compression ultrasonography results and the diagnosis of ipsilateral recurrent proximal deep vein thrombosis. J Thromb Haemost 2010; 8: 848–850.

16.

Hamadah

Alwasaidi

Le Gal

, et al. Baseline imaging after therapy for unprovoked venous thromboembolism: A randomized controlled comparison of baseline imaging for diagnosis of suspected recurrence. J Thromb Haemost 2011; 9: 2406–2410.

17.

Le Gal

Kovacs

Carrier

, et al. Validation of a diagnostic approach to exclude recurrent venous thromboembolism. J Thromb Haemost 2009; 7: 752–759.

18.

Bates

Jaeschke

Stevens

, et al. Diagnosis of DVT: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e351S–e418S.

19.

Linkins

Stretton

Probyn

Kearon

. Interobserver agreement on ultrasound measurements of residual vein diameter, thrombus echogenicity and Doppler venous flow in patients with previous venous thrombosis. Thromb Res 2006; 117: 241–247.

20.

Khilnani

Meissner

Vedanatham

, et al. The evidence supporting treatment of reflux and obstruction in chronic venous disease. J Vasc Surg Venous Lymphat Disord 2017; 5: 399–412.

21.

Villalba

Larkin

. Transabdominal duplex ultrasound and intravascular ultrasound planimetry measures of common iliac vein stenosis are significantly correlated in a symptomatic population. J Vasc Surg Venous Lymphat Disord 2021; 9: 1273–1281.

22.

Butros

Liu

Oliveira

, et al. Venous compression syndromes: Clinical features, imaging findings and management. Br J Radiol 2013; 86: 20130284

23.

Weinberg

Vedantham

Salter

, et al. Relationships between the use of pharmacomechanical catheter-directed thrombolysis, sonographic findings, and clinical outcomes in patients with acute proximal DVT: Results from the ATTRACT Multicenter Randomized Trial. Vasc Med 2019; 24: 442–451.

24.

Jain

Soult

Resnick

, et al. Detecting iliac vein thrombosis with current protocols of lower extremity venous duplex ultrasound. J Vasc Surg Venous Lymphat Disord 2018; 6: 724–729.

25.

Hui

Goldman

Mabud

, et al. Diagnostic performance of lower extremity Doppler ultrasound in detecting iliocaval obstruction. J Vasc Surg Venous Lymphat Disord 2020; 8: 821–830.

26.

Metzger

Rossi

Kambara

, et al. Criteria for detecting significant chronic iliac venous obstructions with duplex ultrasound. J Vasc Surg Venous Lymphat Disord 2016; 4: 18–27.

27.

Raju

Darcey

Neglén

. Unexpected major role for venous stenting in deep reflux disease. J Vasc Surg 2010; 51: 401–408.

28.

Serhal

Barnes

. Venous thromboembolism: A clinician update. Vasc Med 2019; 24: 122–131.

29.

Sigrist

RMS

Liau

Kaffas

, et al. Ultrasound elastography: Review of techniques and clinical applications. Theranostics 2017; 7: 1303–1329.

30.

Emelianov

Chen

O’Donnell

, et al. Triplex ultrasound: Elasticity imaging to age deep venous thrombosis. Ultrasound Med Biol 2002; 28: 757–767.

31.

Geier

Barbera

Muth-Werthmann

, et al. Ultrasound elastography for the age determination of venous thrombi. Evaluation in an animal model of venous thrombosis. Thromb Haemost 2005; 93: 368–374.

32.

Xie

Kim

Aglyamov

, et al. Staging deep venous thrombosis using ultrasound elasticity imaging: Animal model. Ultrasound Med Biol 2004; 30: 1385–1396.

33.

Rubin

Xie

Kim

, et al. Sonographic elasticity imaging of acute and chronic deep venous thrombosis in humans. J Ultrasound Med 2006; 25: 1179–1186.

34.

Mumoli

Mastroiacovo

Giorgi-Pierfranceschi

, et al. Ultrasound elastography is useful to distinguish acute and chronic deep vein thrombosis. J Thromb Haemost 2018; 16: 2482–2491.

35.

Durmaz

Gultekin

. Efficacy of shear wave elastography in the differentiation of acute and subacute deep venous thrombosis. Ultrasound Q 2021; 37: 168–172.

36.

Rafailidis

Sidhu

, et al. Contrast imaging ultrasound for the detection and characterization of carotid vulnerable plaque. Cardiovasc Diagn Ther 2020; 10: 965–981.

37.

Spiss

Loizides

Plaikner

, et al. Contrast enhanced ultrasound of the lower limb deep venous system: A technical feasibility study. Technical innovation. Med Ultrason 2011; 13: 267–271.

38.

de Perrot

Righini

Bounameaux

Poletti

. Contrast-enhanced sonographic diagnosis of unsuspected internal iliac vein thrombosis. J Clin Ultrasound 2011; 39: 553–555.

39.

Bucek

Kos

Schober

, et al. Ultrasound with Levovist in the diagnosis of suspected calf vein thrombosis. Ultrasound Med Biol 2001; 27: 455–460.

40.

Smith

Parker

Byass

Chiu

. Contrast sonovenography – Is this the answer to complex deep vein thrombosis imaging? Ultrasound 2016; 24: 17–22.

41.

Robert-Ebadi

Righini

. Management of distal deep vein thrombosis. Thromb Res 2017; 149: 48–55.

42.

Spritzer

Arata

Freed

. Isolated pelvic deep venous thrombosis: Relative frequency as detected with MR imaging. Radiology 2001; 219: 521–525.

43.

Liu

Wang

Zhao

, et al. Doppler ultrasound and contrast-enhanced ultrasound in detection of stent stenosis after iliac vein stenting. BMC Cardiovasc Disord 2021; 21: 42.

44.

Thomas

Goodacre

Sampson

van Beek

. Diagnostic value of CT for deep vein thrombosis: Results of a systematic review and meta-analysis. Clin Radiol 2008; 63: 299–304.

45.

Goodman

Stein

Matta

, et al. CT venography and compression sonography are diagnostically equivalent: Data from PIOPED II. AJR Am J Roentgenol 2007; 189: 1071–1076.

46.

Cho

Chung

Kim

, et al. CT venography for deep vein thrombosis using a low tube voltage (100 kVp) setting could increase venous enhancement and reduce the amount of administered iodine. Korean J Radiol 2013; 14: 183–193.

47.

Loud

Katz

Bruce

, et al. Deep venous thrombosis with suspected pulmonary embolism: Detection with combined CT venography and pulmonary angiography. Radiology 2001; 219: 498–502.

48.

Reichert

Henzler

Krissak

, et al. Venous thromboembolism: Additional diagnostic value and radiation dose of pelvic CT venography in patients with suspected pulmonary embolism. Eur J Radiol 2011; 80: 50–53.

49.

Douek

Rotzinger

Meuli

, et al. Impact of CT venography added to CT pulmonary angiography for the detection of deep venous thrombosis and relevant incidental CT findings. Eur J Radiol 2020; 133: 109388.

50.

Finkelstein

Crist

Shao

, et al. The utility of computed tomography venography in the routine evaluation of patients who present to a lymphedema center with lower extremity edema. J Vasc Surg Venous Lymphat Disord 2023; 11: 1055–1062.

51.

Chung

Yoon

Jung

, et al. Acute iliofemoral deep vein thrombosis: Evaluation of underlying anatomic abnormalities by spiral CT venography. J Vasc Interv Radiol 2004; 15: 249–256.

52.

Oguzkurt

Tercan

Pourbagher

, et al. Computed tomography findings in 10 cases of iliac vein compression (May-Thurner) syndrome. Eur J Radiol 2005; 55: 421–425.

53.

Liu

Gao

Shen

, et al. Endovascular treatment for symptomatic iliac vein compression syndrome: A prospective consecutive series of 48 patients. Ann Vasc Surg 2014; 28: 695–704.

54.

Liu

Peng

Zheng

, et al. Application of computed tomography venography in the diagnosis and severity assessment of iliac vein compression syndrome: A retrospective study. Medicine (Baltimore) 2018; 97: e12002.

55.

Rossi

Kambara

Rodrigues

, et al. Comparison of computed tomography venography and intravascular ultrasound in screening and classification of iliac vein obstruction in patients with chronic venous disease. J Vasc Surg Venous Lymphat Disord 2020; 8: 413–422.

56.

Toh

Damodharan

Lim

HHMN

Tang

. Computed tomography venography versus intravascular ultrasound in the diagnosis of iliofemoral vein stenosis. Vasa 2021; 50: 38–44.

57.

Jeon

Chung

Jae

, et al. May-Thurner syndrome complicated by acute iliofemoral vein thrombosis: Helical CT venography for evaluation of long-term stent patency and changes in the iliac vein. AJR Am J Roentgenol 2010; 195: 751–757.

58.

Abdalla

Fawzi Matuk

Venugopal

, et al. The diagnostic accuracy of magnetic resonance venography in the detection of deep venous thrombosis: A systematic review and meta-analysis. Clin Radiol 2015; 70: 858–871.

59.

Arnoldussen

CWKP

Notten

Brans

, et al. Clinical impact of assessing thrombus age using magnetic resonance venography prior to catheter-directed thrombolysis. Eur Radiol 2022; 32: 4555–4564.

60.

Massenburg

Himel

Blue

, et al. Magnetic resonance imaging in proximal venous outflow obstruction. Ann Vasc Surg 2015; 29: 1619–1624.

61.

Shi

Xue

Chen

. Non-enhanced multimodal magnetic resonance imaging in assessment of iliac vein obstruction with or without thrombosis. Abdom Radiol (NY) 2021; 46: 4432–4439.

62.

Westerbeek

Van Rooden

Tan

, et al. Magnetic resonance direct thrombus imaging of the evolution of acute deep vein thrombosis of the leg. J Thromb Haemost 2008; 6: 1087–1092.

63.

Fraser

DGW

Moody

Morgan

, et al. Diagnosis of lower-limb deep venous thrombosis: A prospective blinded study of magnetic resonance direct thrombus imaging. Ann Intern Med 2002; 136: 89–98.

64.

Tan

Mol

Van Rooden

, et al. Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis. Blood 2014; 124: 623–627.

65.

Van Dam

Dronkers

CEA

Gautam

, et al. Magnetic resonance imaging for diagnosis of recurrent ipsilateral deep vein thrombosis. Blood 2020; 135: 1377–1385.

66.

Saleem

Knight

Raju

. Diagnostic yield of intravascular ultrasound in patients with clinical signs and symptoms of lower extremity venous disease. J Vasc Surg Venous Lymphat Disord 2020; 8: 634–639.

67.

D’Amico

Quintini

, et al. Intravascular ultrasound in the diagnosis and treatment of central venous diseases. Vasa 2021; 50: 2–10.

68.

Neglén

Raju

. Intravascular ultrasound scan evaluation of the obstructed vein. J Vasc Surg 2002; 35: 694–700.

69.

Gagne

Tahara

Fastabend

, et al. Venography versus intravascular ultrasound for diagnosing and treating iliofemoral vein obstruction (VIDIO): Report from a multicenter, prospective study of iliofemoral vein interventions. J Vasc Surg Venous Lymphat Disord 2017; 5: 678–687.

70.

Montminy

Thomasson

Tanaka

, et al. A comparison between intravascular ultrasound and venography in identifying key parameters essential for iliac vein stenting. J Vasc Surg Venous Lymphat Disord 2019; 7: 801–807.

71.

Razavi

Salter

Goldhaber

, et al. Correlation between post-procedure residual thrombus and clinical outcome in deep vein thrombosis patients receiving pharmacomechanical thrombolysis in a multicenter randomized trial. J Vasc Interv Radiol 2020; 31: 1517–1528.e2.

72.

Raju

Davis

Martin

. Assessment of residual thrombus after venous thrombolytic regimens. J Vasc Surg Venous Lymphat Disord 2014; 2: 148–154.

73.

Murphy

Broker

Johnson

, et al. Device and imaging-specific volumetric analysis of clot lysis after percutaneous mechanical thrombectomy for iliofemoral DVT. J Endovasc Ther 2010; 17: 423–433.

74.

Gagne

Gasparis

Black

, et al. Analysis of threshold stenosis by multiplanar venogram and intravascular ultrasound examination for predicting clinical improvement after iliofemoral vein stenting in the VIDIO trial. J Vasc Surg Venous Lymphat Disord 2018; 6: 48–56.e1.

75.

Tran

Zaghloul

, et al. Intravascular ultrasound evaluation during iliofemoral venous stenting is associated with improved midterm patency outcomes. J Vasc Surg Venous Lymphat Disord 2022; 10: 1294–1303.

76.

Rabinov

Paulin

. Roentgen diagnosis of venous thrombosis in the leg. Arch Surg 1972; 104: 134–144.

77.

Rogers

Cipolle

Velmahos

, et al. Practice management guidelines for the prevention of venous thromboembolism in trauma patients: The EAST practice management guidelines work group. J Trauma 2002; 53: 142–164.

Noninvasive and invasive imaging of lower-extremity acute and chronic venous thrombotic disease

Abstract

Keywords

Introduction

Sonographic evaluation of venous thrombotic disease

Venous duplex ultrasound (VDUS)

Ultrasound elastography

Contrast-enhanced ultrasound (CEUS)

Computed tomographic evaluation of venous thrombotic disease

Magnetic resonance evaluation of venous thrombotic disease

Magnetic resonance venography (MRV)

Magnetic resonance direct thrombus imaging (MRDTI)

Intravascular ultrasound evaluation of venous thrombotic disease

Invasive venography of venous thrombotic disease

Conclusion

Footnotes

Declaration of conflicting interests

Funding

ORCID iDs

References