A comparison of magnetic resonance venography findings and venous occlusion plethysmography variables in postthrombotic syndrome

Abstract

Objective

The relation between venous morphology and venous function in postthrombotic syndrome is poorly understood. The aim of this study was to compare obstruction and collateralization as seen with magnetic resonance venography with variables of venous occlusion plethysmography in patients with postthrombotic syndrome.

Methods

Medical records, magnetic resonance venography and venous occlusion plethysmography data were analyzed in 28 patients (33 legs). Magnetic resonance venography images were scored for degree of obstruction and collateralization in segments of pelvic and abdominal veins and correlated to venous occlusion plethysmography data.

Results

Obstruction of the inferior vena cava correlated with an overall increase of collaterals (p < 0.001). The summary scores of collaterals or obstructions did not correlate with venous occlusion plethysmography variables. Relative expelled volume at 4 s correlated inversely with obstruction of the inferior vena cava (p = 0.045) and vertebral collateralization (p = 0.033).

Conclusions

Modest correlations were found between magnetic resonance venography scores and venous occlusion plethysmography variables. Prospective studies with refined scoring and magnetic resonance venography techniques may increase our knowledge further.

Keywords

Postthrombotic syndrome chronic venous disease magnetic resonance venography venous occlusion plethysmography proximal venous obstruction venous collaterals

Introduction

Endovascular treatment of postthrombotic changes with stenting of pelvic and abdominal deep veins is increasingly used to treat patients with postthrombotic syndrome, i.e. with venous ulcers, venous skin changes, or venous claudication. In experienced hands, the long-term results are excellent.^1–3 However, many patients that are conservatively treated after a proximal deep venous thrombosis (DVT) also have excellent clinical results at long-term follow-up.^4,5 Patient selection for venous stenting may be difficult, as no clear correlations between specific morphological patterns and clinical symptoms and signs have been found so far, and no correlations between hemodynamic tests such as pressure measurements and venography findings of degree of stenosis with or without collaterals.^6,7 Thus, venous physiology is often not accounted for in the work-up before stenting, and clinicians base their decisions on clinical factors and anatomy.

A noninvasive alternative to venography is magnetic resonance imaging (MRV) of the deep veins, which has much improved recently with specific contrast media that gives detailed imaging of postthrombotic changes and collaterals.⁸ The amount of data from a MRV study is vast and the technique is under continuous evolution. The role of MRV in the selection of patients for stenting is not defined yet.⁹

In a previous study, we have shown that patients with venous claudication attributable to remaining post-thrombotic iliofemoral obstructive disease are characterized by a functional disturbance shown with venous occlusion plethysmography (VOP).¹⁰ The results suggest that VOP can be a valuable tool in the preoperative workup for selection of patients with iliofemoral vein obstruction that may benefit from venous intervention.

The aim of this study was to compare the degree of obstruction with the collateralization as seen with magnetic resonance venography (MRV), and to investigate the importance of the specified anatomical segments of obstructions and collaterals for venous function as examined with variables of venous occlusion plethysmography (VOP).

Patients and methods

Patients

Medical records were studied for consecutive patients with PTS investigated with both VOP and MRV at the Department of Vascular Surgery at Karolinska University Hospital, 2010–2012. Information was collected regarding age, sex, side (right, left, or both), the presence of skin changes, venous ulcer, edema, and claudication.

In clinical routine, most patients considered for venous stenting were sent to preoperative MRV at the department of Radiology, Karolinska University Hospital, some were examined at neighboring hospitals. VOP examinations were performed at the Department of Clinical Physiology, Södersjukhuset.

Magnetic resonance imaging and score

The MRV examinations were done at any of our systems including: 1,5-T (Ingenia, Philips Medical Systems, Best, The Netherlands), 1,5-T (Aera, Siemens Medical Systems, Erlangen, Germany), and 3,0-T (Verio, Siemens Medical Systems, Erlangen, Germany). A body coil 12 element combined with a spine coil was used. A dose of 0.2 mL/kg bodyweight gadoterate meglumine (Dotarem, Guerbet, Bloomington, IN, USA) was given for contrast-enhanced sequences by a hand injection followed by 20 mL saline flush in generally the cubital vein. The area covered was from above renal vein inflow to caval vein, down to below trochanter minor. Two or three stations were done depending on patient size. The sequences were steady-state free position (SSFP) axial planes in three stations, GRE time-of-flight flow axial sensitive to vein flow in two to three stations, and T1 weighted axial GRE 3D with fat saturation after gadolinium injection in two stations.

The MRV findings for obstructions were divided in the following anatomical segments: the common femoral vein, the common and external iliac veins, and the inferior vena cava (IVC). The deep veins were classified in to four groups: open without, open with minor (< 50% reduction of lumen) or major (> 50% reduction of lumen) postthrombotic changes and occluded.

Collaterals were divided in vertebral, inferior epigastric, and superficial epigastric collaterals and presacral plexus, which were further defined as proximal collaterals, and internal pudendal, external pudendal, and circumflex femoral collaterals, which were defined as distal collaterals. Collaterals were classified qualitatively in three groups: normal or slightly dilated, moderately dilated, and grossly dilated.

A summary score was calculated for the four deep vein segments (stenotic score) and for the seven collateral segments (collateral score).

Venous occlusion plethysmography

Measurements of venous volume and outflow were performed using a computerized strain-gage plethysmograph (S.I. Veintest 2, Sels Instruments N.V., Vorselaar, Belgium). The patients were in a supine position with the heels resting on a support elevating the lower limbs 40 cm above bed level and the knee angle in approximately 90°. Inflatable cuffs were wrapped around the upper part of the thighs and the strain-gage wires were placed around the largest part of each calf. Venous volume (V, mL per 100 mL) was measured during venous occlusion imposed by thigh cuffs inflated to a pressure of 60 mmHg by use of the capacitance mode as earlier described.¹¹ Venous emptying was expressed as the outflow rate during the first second after cuff release (VE, mL per 100 mL × min) and expelled volume after 4 s (EV4, mL per 100 mL). Outflow relative to venous volume was expressed as EV4/V. The mean of two determinations was used for each variable. The coefficient of variations for repeated measurements of these plethysmographic variables is between 5% and 6%.

Statistics and ethics

The Spearman's rho test was used to assess relationships between plethysmographic variables and MRV findings. To avoid potential errors by multiple testing, the level of significance should be p < 0.01; however, as trend values may be interesting, correlations with a significance level of p < 0.05 are also presented in the following section.

The statistical analyses were performed using SPSS version 22 (IBM SPSS Statistics, Armonk, NY, USA).

The study was approved by the local ethics committee and conducted according to the Declaration of Helsinki.

Results

Clinical data

The demographic and clinical data are presented in Table 1. The five patients with bilateral symptoms were all male and all five had postthrombotic changes in the IVC. Male patients were older. In females, the left side was more common and there were less skin changes and ulcers. Twenty-three patients had symptoms from one leg, five of them had IVC changes.

Table 1.

Demographics and clinical data for patients included in the study.

	All	Male	Female
No. of patients	28	13	15
Age, years, mean (range)	44 (20–69)	48 (20–69)	40 (29–67)
DVT side bilateral/ right/left, N	5/5/18	5/3/5	0/2/13
No. of legs	33	18	15
Venous claudication, N (%)	19 (58)	10 (56)	9 (60)
Edema, N (%)	23 (70)	11 (61)	12 (80)
Skin changes, N (%)	24 (73)	16 (89)	8 (53)
Active or healed ulcer, N (%)	10 (30)	9 (50)	1 (7)

The MRV-scores for the different anatomical segments are shown in Table 2 and plethysmographic results in Table 3.

Table 2.

MRV findings in 33 legs with postthrombotic disease.

Distribution of veins with postthrombotic changes
Common femoral	31 (94%)
External iliac	31 (94%)
Common iliac	26 (79%)
Inferior vena cava	15 (45%)
Summary stenotic score (median and range)	6 (0–11)
Distribution of significantly dilated collaterals
Vertebral	17 (52%)
Inferior epigastric	8 (24%)
Superficial epigastric	19 (58%)
Circumflex femoral	11 (33%)
Internal pudendal	13 (39%)
External pudendal	21 (64%)
Presacral plexus	16 (48%)
Summary collateral score (median and range)	4 (0–9)

Table 3.

Plethysmographic results in 33 legs with postthrombotic disease.

	Patients	Ref. values¹¹
VE, venous emptying (mL per 100 mL × min)	75 (24)	62–158
V, venous volume(mL per 100 mL)	6.0 (1.7)	3.4–9.0
EV₄, expelled volume after 4 s (mL per 100 mL)	3.2 (0.9)	2.6–6.7
EV₄/V	0.55 (0.11)	0.62–0.90
Number of patients with reduced VE ( < 62)	8 (24%)
Number of patients with reduced EV₄ ( < 2.6)	7 (21%)
Number of patients with reduced EV₄/V ( < 0.62)	23 (70%)

Results in mean and SD or number and percent.

Correlations between anatomical findings of obstructions and collaterals on MRV

The number and degree of obstructed deep veins and the degree of collateralization as calculated with summary scores correlated significantly (r = 0.600, p < 0.001) (Figure 1).

Figure 1.

Correlation between summary scores for obstructed segments and collaterals.

Correlations between the presence of collaterals and obstructions in different anatomic locations on magnetic resonance venography images are summarized in Table 4. As shown in the table, obstruction of the IVC correlated most to increased collateralization of the presacral plexus and vertebral veins, and obstructions of the femoral veins with vertebral and circumflex femoral veins.

Table 4.

Correlations between the presence of collaterals and obstructions in different anatomic locations on magnetic resonance venography images.

	Degree of correlation
	Obstructed veins
Collaterals	a	b
Proximal	Common iliac	Inferior vena cava
Vertebral	–	Inferior vena cava
Vertebral	–	Femoral
Inferior epigastric	–	–
Superficial epigastric	Femoral	–
Presacral plexus	–	Inferior vena cava
Distal	External iliac	–
Internal pudendal	–	–
External pudendal	External iliac	–
Circumflex femoral	Inferior vena cava	Femoral

The Spearman's rho.

^aCorrelation is significant at the 0.05 level (2-tailed).

^bCorrelation is significant at the 0.01 level (2-tailed).

Proximal collaterals were vertebral, inferior epigastric and superficial epigastric collaterals, and presacral plexus. Internal pudendal, external pudendal, and circumflex femoral collaterals were defined as distal collaterals.

Correlations between MRV findings and VOP variables

When separate anatomic segments where compared with VOP variables, EV4/V was negatively correlated with the degree of stenosis of IVC (r = −0.351, p = 0.045) and the amount of vertebral collaterals (r = −0.373, p = 0.033).

There was no significant correlation between the summary scores for obstruction or collaterals and the VOP variables, neither when the summary score for collaterals was deducted from the summary score for stenosis and the resulting figure was compared with the VOP variables.

Discussion

In this attempt to correlate morphology and venous function as examined with MRV and VOP, we found that collaterals overall increased with increasing number of postthrombotic venous segments, but this did not correspond with the deteriorating VOP variables; however, the presence of increasing IVC obstruction caused a specific reduction of EV4/V. Obstruction of specified venous segments caused increased collateralization around them.

We have previously shown that EV4/V is particularly important when assessing patients with proximal venous obstruction and venous claudication.¹⁰ Increased collateralization may in a varying degree compensate for the anatomical obstruction and in this way diminish the functional obstruction. It may be presumed that this compensation has least importance at the level of the IVC, and then the relation to impaired EV4/V becomes more evident.

The significance of collateralization is not fully understood. After a proximal DVT venous flow may be spontaneously improved by recanalization of the affected veins or by the enlargement of collaterals. This process considerably differs between individuals. Collaterals can open up in different segments i.e. in IVC obstruction they can be intraabdominal or in the abdominal wall or both. Certain collaterals may be more important than others for improved venous outflow. In this study, there was a correlation between specified obstructed segments and adjacent collateral systems but some collaterals i.e. vertebral, increased with both femoral and IVC obstructions. It may be speculated that collaterals adjacent to the obstruction will develop first, but the proximal outflow vary depending on the extent of postthrombotic changes and unknown individual factors. A femoral obstruction may thus increase collaterals locally only or deviate most of the venous outflow through vertebral or superficial veins.

This small pilot study failed, however, to demonstrate a correlation between VOP variables and summary scores of obstruction and collateralization. There are potential sources of errors for our results.

A major difficulty is the scoring of the morphological changes. We used a crude score, and after the study started, other scores have been suggested.¹² None of the scores take into consideration that there may be anatomical segments that are more important than others, both regarding obstructive lesions and collateral flow.

The role and optimal amount of collaterals to compensate for an obstructed venous segment is not known.¹³ In the study, we tried to score collaterals and obstructions and deduct them from each other in an attempt to calculate if few collaterals and more obstructions would lead to deteriorated venous function. As VOP measures global changes in the venous outflow, summary scores, including for groups of proximal and distal collaterals and obstructions, were compared with VOP variables. No such correlations were found, either because there is no such correlation or because the score was too crude.

Patient groups with PTS are by nature heterogeneous with a mixture of deep and superficial disease, of reflux and obstruction, and of infra- and suprainguinal disease. This makes it difficult to get “clean” groups to compare. Including substantially more patients in the study would make it possible to study subgroups better, and also including more asymptomatic postthrombotic patients as they presumably would have more collaterals.

Veins depicted on MRV represent a snapshot of possible states of dilation and volume that are influenced by temperature, body posture, dehydration, previous exercise, etc. This study is retrospective and the MRV examinations were performed in clinical practice, thus changes in venous diameter may have been missed. A prospective study with a more specified protocol for MRV, may detect more subtle changes. With new techniques for MRV, there are possibilities to calculate volume and time of venous transit, which will add extra knowledge.

The prevailing concept about the selection of patients for stenting is rather nihilistic regarding venous physiology, as venous function and anatomy has not been shown to correlate in previous studies, and our findings were also modest.^6,7 However, venous physiology is difficult to interpret, and maybe we have not asked the right questions. The correlation between venous anatomy and function is intriguing and deserves further studies.

Conclusion

In this first attempt to compare postthrombotic venous morphology as seen with MRV with venous function as examined with VOP, we found no correlation between VOP variables and increasing amount of collaterals or obstructions, but the IVC was the anatomical segment where obstruction correlated most with an overall increase of collaterals, and also with deteriorated relative expelled venous volume at 4 s. Prospective studies with refined scoring and MRV techniques may clarify results, but studies with other techniques are also needed about the clinical and hemodynamic significance of specified segments of venous stenosis and degree of collateral formation, in order to improve the selection of patients for treatment of postthrombotic syndrome.

Footnotes

Declaration of conflicting interests

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

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by Mats Klebergs foundation.

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