A 45-year-old man with hepatitis C was admitted with extreme volume overload, platypnea, and hypoxia. An echocardiogram showed evidence of pulmonary hypertension, no signs of heart failure, and a bubble study suggesting an extracardiac shunt. Arterial blood gas measurements repeatedly revealed hypoxemia with oxygen saturation in the range of 80% to 90%.
Bao To, MD
, Department of Radiology, University of California San
Marcia McCowin, MD
Stephen K. Gerard, MD, PhD
, San Francisco VA Medical Center and Department of Radiology,
University of California San Francisco, San Francisco, CA.
A 45-year-old man with hepatitis C was admitted with extreme
volume overload, platypnea, and hypoxia. An echocardiogram showed
evidence of pulmonary hypertension, no signs of heart failure, and
a bubble study suggesting an extracardiac shunt. Arterial blood gas
measurements repeatedly revealed hypoxemia with oxygen saturation
in the range of 80% to 90%. A ventilation/perfusion (V/Q) scan
showed a low probability for pulmonary embolism (not shown), and a
chest computed tomography (CT) scan was negative for significant
pulmonary disease (Figure 1). The patient's volume overload and
hypoxia were believed to be associated with worsening liver
failure. He was heavily diuresed and discharged. His hypoxia became
worse over time, requiring increased home oxygen support. Several
years later, a repeat echocardiogram showed resolution of pulmonary
hypertension. A liver biopsy confirmed end-stage liver disease and
hepatic cirrhosis and he was placed on the liver transplant list. A
repeat CT scan and a shunt study with intravenous (IV)
technetium-99m (Tc99m) macroaggregated albumin (MAA) (Figure 2)
were performed to evaluate his hepatopulmonary status prior to
Right-to-left shunt associated with microscopic pulmonary
arterial venous malformations (PAVMs) secondary to hepatopulmonary
High-resolution CT images showed evidence of cirrhosis and
end-stage liver disease, including a small liver with nodular
contour, abdominal ascites, and splenomegaly (Figure 1). There was
no evidence of macroscopic PAVMs or parenchymal lung abnormalities.
A shunt study with IV Tc99m-labeled MAA, using a low-particle
preparation (see below), shows activity in the kidneys and brain,
in addition to normal lung activity (Figure 2). Also noteworthy is
visualization of the spleen, consistent with splenomegaly, evident
on the CT scan (Figure 1). The thyroid gland is also seen in the
anterior view (Figure 2). Diffuse soft-tissue uptake labeling the
whole body is also best appreciated in the lateral projection.
These findings are con- sistent with a significant right-to-left
shunt. Quantitative analysis estimated a 26% shunt fraction (Figure
3). Aside from microscopic PAVMs associated with HPS in advanced
liver disease, right-to-left shunt can also be seen with
macroscopic PAVMs most frequently associated with hereditary
hemorrhagic telangiectasia (Osler-Rendu-Weber disease) and with
congenital intracardiac anomalies, including Eisenmenger's complex,
tetralogy of Fallot, Ebstein's anomaly of the tri- cuspid valve,
and pulmonic stenosis with atrial septal defect.
Whole-body nuclear imaging following IV injection of Tc99m MAA
is useful to document and quantify right-to-left shunt.
Hepatopulmonary syndrome consists of arterial hypoxemia secondary
to abnormal gas exchange in the setting of associated hepatic
dysfunction and in the absence of intrinsic cardiopulmonary
disease. Patients with HPS develop widespread vasodilation of
peripheral branches of the pulmonary vasculature, at both the
precapillary and capillary levels (15 to 150 µ in diameter), near
the gas exchange area.
The dilated capillary has an expanded diameter, limiting oxygen
diffusion capacity from adjacent alveoli for adequate red blood
These pulmonary arteriovenous communications are microscopic and
are rarely visible, as opposed to the macroscopic PAVMs seen in
hereditary hemorrhagic telangiectasia. The exact mechanism
underlying HPS and associated PAVMs remains unclear. Postulates
have included: failure of the damaged liver to clear circulating
pulmonary vasodilators; production of a circulating vasodilator or
inhibition of a circulating vasoconstrictor by the damaged liver;
blunted hypoxic pulmonary vasoconstriction; release of a substance
from the diseased liver that promotes fistula formation; and
inability of the diseased liver to metabolize various substances
present in the portal venous blood.
Other causes of HPS include trauma, schistosomiasis, metastatic
carcinoma, and actinomycosis.
The Tc99m MAA perfusion tracer used in this shunt study had a
measured radiochemical purity of 99.6%. Factors contributing to
radiochemical impurity include unbound Tc99m in the form of free
pertechnetate and albumin particles smaller than the optimal 10 to
50 µ size that could pass through the normal pulmonary
arteriolar-capillary bed. Both of these sources of impurity can
falsely elevate the measured shunt fraction, since a component of
the total Tc99m label will pass through into the systemic
circulation unrelated to a right-to-left shunt.
When performing a pulmonary perfusion study with Tc99m MAA in a
patient with a known or suspected right-to-left shunt, it has been
recommended that a low- particle preparation be used to minimize
the extent of systemic arterial embolization.
Normally, ~1 million particles 10 to 40 µ in size are injected IV
for a standard lung perfusion dose of Tc99m MAA. It is recommended
that this be reduced to 100,000 to 200,000 particles in the setting
of right-to-left shunt, as was done in this case.
Estimation of the pulmonary to systemic shunt fraction is
calculated using the equation
: 100 × (TBC - TLC)/(TBC) where TBC is total body count and TLC is
total lung count. Total body and lung counts are obtained by
placing regions of interest
(ROIs) over the posterior whole-body image that is acquired 2
minutes post-tracer injection for 15 minutes.
An alternative method of right-to-left shunt quantification
derives an estimate of total body counts from the measurement of
renal and/or cerebral activity, assuming a given fixed proportion
of total body blood flow.
While this approach may simplify determination of the total body
counts, interpatient variability of the (renal and/or cerebral) to
systemic blood flow ratios could introduce some imprecision.
Quantification of the whole-body counts directly, as was done in
this case, avoids this potential source of error.
Right-to-left shunt due to microscopic PAVMs is a manifestation
of hepatopulmonary syndrome in ad-vanced liver disease. Although
PAVMs are not readily evident radiographically, findings associated
with chronic liver failure on CT along with evidence of
right-to-left shunt determined by whole-body Tc99m MAA imaging in
the appropriate clinical setting can confirm this diagnosis