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Original Research |
1 Department of Radiology, CB 7510, University of North Carolina Hospitals, 101
Manning Dr., Chapel Hill, NC 27599-7510.
2 Present address: Department of Radiology, Saint Joseph's Hospital, Atlanta,
GA.
3 Present address: Interventional Services, Wake Radiology Diagnostic Imaging,
Inc., Cary, NC.
Received September 24, 2006;
accepted after revision December 18, 2006.
Address correspondence to W. K. Chong.
Abstract
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MATERIALS AND METHODS. A retrospective review was performed of Doppler sonographic studies and angiograms in 94 liver transplant cases (72 whole liver, 22 lobar) with suspected vascular obstruction. The angiograms were classified as normal, occluded, or stenosed on the basis of appearance and elevated pressure gradient. Sonography was correlated with angiography. The following Doppler parameters were evaluated: for the portal vein, peak anastomotic velocity and anastomotic-to-preanastomotic velocity ratio; and for the outflow veins, venous pulsatility index. Receiver operating characteristic curves were constructed and optimum thresholds for stenosis were defined.
RESULTS. There were 16 cases of portal vein obstruction (11 stenosis, five occlusion) and 35 cases of outflow vein obstruction (34 stenoses, one occlusion). Mean peak anastomotic velocity in normal portal veins was 58 cm/s, whereas mean peak anastomotic velocity in stenosed veins was 155 cm/s (p = 0.0007). Peak anastomotic velocity threshold of > 125 cm/s was 73% sensitive and 95% specific for stenosis. Mean anastomotic-to-preanastomotic velocity ratio in normal portal veins was 1.5, and mean anastomotic-to-preanastomotic velocity ratio in stenosed veins was 4.69 (p = 0.001). A 3:1 ratio was 73% sensitive and 100% specific for stenosis. Mean venous pulsatility index for normal outflow veins was 0.75, and mean venous pulsatility index in stenosed veins was 0.39. A venous pulsatility index of < 0.45 was 95.7% specific for stenosis. The areas under the receiver operating characteristic curve were 0.83 for peak anastomotic velocity, 0.86 for anastomotic-to-preanastomotic velocity ratio, and 0.84 for venous pulsatility index, indicating good correlation.
CONCLUSION. Peak anastomotic velocity, anastomotic-to-preanastomotic velocity ratio, and venous pulsatility index are useful parameters for diagnosing venous stenosis in liver transplants.
Keywords: Doppler sonography hepatobiliary imaging liver transplantation venography venous obstruction
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Patients
The records of 456 patients who had liver transplants at our institution
between 1996 and 2003 were reviewed. The patients' ages ranged from 1 to 67
years (mean age, 41 years; SD, 18.2 years). Forty-four patients had partial or
lobar liver transplants and 412 patients had whole-liver transplants. The
records showed that 97 angiograms of the portal vein or hepatic vein/IVC were
performed on these patients after transplantation. The angiograms were
obtained because arterial or venous obstruction was suspected on clinical
grounds or because Doppler sonography suggested the presence of arterial or
venous obstruction. Three patients were excluded because their venogram was
not preceded by a recent Doppler study (defined as 7 days). The remaining 94
patients made up the study population.
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The angiograms were classified as normal, significantly stenosed, or completely occluded or thrombosed. Significant stenosis was defined as a morphologic stenosis that required stent placement and angioplasty (as was the case in all but three patients in the stenosed group; the exceptions were not stented because their stenoses were caused by extrinsic compression from hematoma or an edematous liver); or as a pressure gradient across the stenosis of 3 mm Hg or greater. The median pressure gradient was 8 mm Hg in the stenosed group. Angiography was used as the reference standard.
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Protocol
The main, right, and left portal veins were imaged with color Doppler
sonography. Angle-corrected velocities in the main portal vein proximal to,
at, and distal to the anastomosis were measured. Turbulence and aliasing on
color Doppler sonography were used to identify the area of peak velocity.
Measurements were made in suspended inspiration. The portal vein anastomosis
was identified by a change in caliber of the vein and the presence of surgical
clips or sutures. Gain and filter settings were optimized for abdominal venous
flow. Color Doppler images and Doppler spectra were obtained from the right,
middle, and left hepatic veins and the IVC in whole-liver transplants. In
partial transplants, spectra were obtained from the solitary hepatic vein and
the IVC. Hepatic vein spectra were obtained 35 cm from the junction
with the IVC.
Measurements
The sonography studies for the normal and stenosed groups were compared.
The sonography study performed closest in time to the angiogram was used for
analysis. Maximum and minimum velocities were measured on representative
waveforms from each vein. To quantify the phasicity of the hepatic venous
waveform, the venous pulsatility index for the right, middle, and left hepatic
veins and the IVC was retrospectively calculated. This was performed by
downloading the hepatic vein and IVC spectra to a PC and measuring the venous
pulsatility index using a commercially available software package (Carnoy,
Plant Systematic). A single individual performed the analysis. The venous
pulsatility index was defined as the difference between the maximum and
minimum frequency shifts in the venous waveform in a cardiac cycle, divided by
the maximum. A completely monophasic (flat) waveform has a venous pulsatility
index of 0. A biphasic waveform has a venous pulsatility index between 0 and
1. A triphasic waveform has a venous pulsatility index of > 1
(Fig. 1). The mean venous
pulsatility index, which was obtained from averaging the venous pulsatility
indexes of each hepatic vein and the IVC, was used for analysis.
In the portal vein, we measured the following parameters: portal vein peak anastomotic velocity and the ratio of the portal vein anastomotic velocity to the preanastomotic velocity, which we called the portal vein velocity ratio (anastomotic-to-preanastomotic velocity ratio).
Patients with complete occlusion had no flow on Doppler sonography and consequently were not included in this analysis.
Statistical Analysis
A Student's t test for the difference of means was performed first
to confirm the validity of receiver operating characteristic (ROC) analysis.
ROC curves were then constructed for peak anastomotic velocity,
anastomotic-to-preanastomotic velocity ratio, and venous pulsatility index
using Medicalc software (Mariakerke). Sensitivity, specificity, and likelihood
ratios for anastomotic-to-preanastomotic velocity ratio and peak anastomotic
velocity threshold values were calculated from the ROC. Likelihood ratios were
used instead of predictive values because the sample size is relatively small
and prevalence (which determines predictive values) will vary in different
institutions.
Because the venous pulsatility index numbers were means obtained by averaging the venous pulsatility index from each hepatic vein and the IVC, we took the additional step of calculating venous pulsatility index thresholds by performing the Student's t test for each of the averages against the software derived optimum at a 95% confidence level.
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All cases of portal vein stenosis were caused by anastomotic strictures. The mean portal vein velocity at the anastomosis was 58 cm/s in patients with angiographically normal portal veins. The mean ratio of portal vein velocity at the anastomosis to the velocity before anastomosis was 1.5:1. The mean portal vein velocity at the anastomosis in patients with portal vein stenosis was 155 cm/s. The mean ratio of portal vein velocity at the anastomosis to the velocity preanastomosis was 4.69:1 (Fig. 3A, 3B, 3C, 3D).
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For peak portal vein anastomotic velocity, comparison of stenosed with normal veins showed p = 0.0007 using the Student's t test for difference of means, assuming unequal variances. This indicated that an ROC analysis was valid given the sample size. The ROC analysis is shown in Figure 5. The area under the ROC curve was 0.83 (SE, 0.084; 95% CI, 0.630.93). The optimum peak anastomotic velocity threshold is > 87 cm/s, which has a sensitivity of 82% and specificity of 90% for stenosis. A threshold of 125 cm/s is 73% sensitive and 95% specific, whereas a threshold of > 200 cm/s is 100% specific but only 18% sensitive (Table 2).
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Outflow Veins (Hepatic Veins and IVC)
Among the 58 hepatic venograms were 34 cases of outflow vein stenosis and
one case of thrombotic occlusion. Eleven cases of stenosis occurred in
partial-liver transplants and 23 in whole-liver transplants. In all except six
cases, the stenosis was caused by an anastomotic stricture. Of the exceptions,
three cases were due to extrinsic compression by hematoma or edematous liver,
two cases due to torsion of the transplant, and one case had a partial
thrombus. The mean pressure gradient in patients with outflow vein stenosis
was 9.6 mm Hg. The mean pressure gradient in normal venograms was 2.4 mm Hg.
There were 23 normal venograms, five in partial-liver transplants and 18 in
whole-liver transplants.
Only one patient with hepatic vein or IVC stenosis showed a triphasic waveform.
The mean venous pulsatility index for patients with normal outflow veins was 0.75. The mean venous pulsatility index for patients with stenosis was 0.39. For venous pulsatility index, comparison of stenosed with normal veins showed p = 0.0002 using the Student's t test for the difference of means, assuming unequal variances. This indicated that an ROC analysis was valid given the sample size. The results of the ROC analysis are shown in Figure 6. The area under the curve was 0.84 (SE, 0.058; 95% CI, 0.7140.921), indicating a good correlation.
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Doppler sonography accurately identified all cases of complete venous obstruction in our study. This is consistent with prior studies [14].
Portal Vein Stenosis
The area under the ROC curve was 0.83 for peak anastomotic velocity and
0.86 for velocity ratio, indicating a good correlation between these
parameters and portal vein stenosis. Accelerated portal vein anastomotic
velocities have previously been shown to indicate stenosis in pediatric
reduced-size transplants (average age, 2.5 years)
[15]. We have found that this
parameter applies to all transplants. Peak velocities of > 125 cm/s or an
anastomotic-to-preanastomotic velocity ratio of 3:1 have a specificity of 95%
or better for portal vein anastomotic stenosis (Tables
1 and
2).
Outflow Vein Stenosis
Venous pulsatility in hepatic veins has usually been assessed by
characterizing the waveform as monophasic, biphasic, or triphasic. Reduced
pulsatility has been associated with parenchymal liver disease
[16,
17] and Budd-Chiari syndrome
[18]. Reduced pulsatility is
also associated with transplant hepatic vein stenosis
[19]; in a small series of
patients, monophasic waveforms were found to indicate stenosis
[20]. However the mono/bi/tri
classification is qualitative; in practice, venous phasicity is a continuum
and there is no clear distinction between monophasic and biphasic waveforms.
The venous pulsatility index, first described by Coulden et al.
[21], is a means of
quantifying venous pulsatility. It has not previously been used to evaluate
liver transplants.
Our ROC analysis showed a good correlation between venous pulsatility index and outflow vein stenosis: The lower the venous pulsatility index, the greater the chance of stenosis. Figure 7A, 7B, 7C illustrates how the venous pulsatility index can be more precise than the mono/bi/tri classification for evaluating stenosis. The Doppler waveform in a patient with outflow vein stenosis on angiography (pressure gradient, 7 mm Hg) shows a weak biphasic waveform and low venous pulsatility index. After angioplasty, angiographic improvement and disappearance of the pressure gradient were seen. The postangioplasty Doppler waveform is still biphasic, but it is clearly more pulsatile, as shown by an increase in the venous pulsatility index.
We did not use peak anastomotic velocities in the outlet veins in our protocol because we could not reliably get a good Doppler angle at the caval anastomosis as a result of its course and depth. However, elevated anastomotic velocities were incidentally seen in a few patients with stenosis, and this may be another useful parameter of obstruction.
Doppler findings should be interpreted with caution in the immediate postoperative period. We have observed transient elevation of portal vein velocities and ratios and reduced hepatic vein pulsatility during this time that resolve spontaneously after a few days. Veins are easily compressible, and these findings are likely due to temporary narrowing resulting from postoperative inflammation [22] or compression from fluid collections.
Limitations
The limitations of this study are its retrospective nature and the fact
that the study population includes partial- and whole-liver transplants. A
selection bias exists in the study population because angiograms were
performed only on transplants that had clinical or Doppler evidence of
vascular obstruction. However, we are confident that all patients with venous
obstruction in our transplant population were included because it is extremely
unlikely that significant venous obstruction would be present in the absence
of clinical, biochemical, or sonographic abnormality. Even if selection bias
were present, it should not affect the outcome of this study, which was
designed to delineate the relationship between Doppler sonography and
angiography. We used angiography and elevated pressure as the sole reference
standards, and we did not address the clinical significance of these
standards.
Another possible complicating factor is that some patients with normal venograms had hepatic artery obstruction, which could theoretically increase overall portal venous flow and therefore portal velocity as well. Nevertheless, the patients with portal vein stenosis still had significantly higher peak velocity than the normal group, even though the normal group contained cases of arterial obstruction. Arterial obstruction should not affect portal velocity ratio or venous pulsatility index. Another consideration is that hepatic vein pulsatility is altered by factors other than venous stenosis; for instance, venous pulsatility is accentuated in cardiac failure.
Conclusion
In conclusion, we found a strong correlation between peak portal vein
velocities, velocity ratios, and portal vein stenosis and between venous
pulsatility indexes and hepatic vein stenosis. Elevated portal vein
anastomotic velocities and velocity ratios are good indicators of stenosis.
Peak anastomotic velocity of > 125 cm/s or a ratio of 3:1 at the portal
vein anastomosis are > 95% specific for portal venous obstruction. Use of
the venous pulsatility index enables greater precision in measuring hepatic
vein pulsatility: The lower the venous pulsatility index, the greater the
possibility of stenosis. A venous pulsatility index of 0.66 is 67.6% sensitive
and 78.3% specific for stenosis, whereas a venous pulsatility index < 0.45
is > 95% specific for stenosis.
Routine use of these parameters may aid in the evaluation of portal vein and outflow vein obstruction in transplants. These findings on sonography should merit consideration of performing angiography if clinical abnormalities are present that can be attributed to venous obstruction.
Acknowledgments
We acknowledge the assistance of Zeynap Firat with data collection and M.
Radu-Rosu with statistical analysis.
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