In this preliminary study, we have demonstrated the feasibility of measuring in vivo spleen stiffness by MR elastography in patients with chronic liver disease as well as healthy individuals. In addition to observing that spleen stiffness increases with higher degrees of hepatic fibrosis, we also noted a strong linear relationship between liver and spleen stiffness values in the entire cohort. Furthermore, a preliminary observation suggested that a mean spleen stiffness value ≥10.5 kPa with compensated cirrhosis was associated with esophageal varices in 100% of cases
The anatomy and microcirculation of the spleen is well-characterized (7
). Splenic tissue is comprised primarily of red pulp tissue with lesser degrees of white pulp. Within the red pulp, blood is received by the penicillar arterioles which then open directly into venous sinuses and trabecular veins. Blood then exits via the splenic vein into the splanchnic venous circulation. White pulp is comprised of a central artery surrounded by lymphoid tissue. Penicillar arterioles originate form the central arteries outside the white pulp and drain into venous sinuses and the red pulp. In this study, healthy individuals were observed to have a consistently narrow range of spleen stiffness values. Spleen stiffness was unrelated to age, sex, or body mass index. It could be expected that spleen stiffness in normal adults retains its elasticity throughout life, as is observed with spleen volume when measured by cross-sectional imaging techniques (25
). However, the effect of normal tissue architecture on dynamic or elastic properties of splenic tissue over time remains unknown.
For patients with chronic liver disease, a greater mean spleen stiffness value was observed compared to healthy individuals. Furthermore, the mean spleen stiffness was observed to be significantly increased as the degree of hepatic fibrosis also increased. the greatest values were seen among patients with histological stages III and IV hepatic fibrosis. In chronic liver disease, the spleen undergoes architectural and dynamic circulatory alterations including pulp hyperplasia, congestion from increased blood flow, and even fibrosis (6
). This has led to hypotheses implicating portal venous hypertension as a cause of these morphologic changes observed in with cirrhosis. Studies to date suggest that portal venous pressure remains within physiological values until architectural changes from bridging (or stage 3) fibrosis ensues (28
). Whether local alterations in splenic hemodynamics preceding the development of clinically significant portal hypertension are responsible for increased spleen stiffness remains speculative at this point.
Despite the association between splenomegaly and portal hypertension, previous studies have failed to demonstrate a consistent relationship between splenomegaly and quantitative portal venous pressure measurement (2
). Mean splenic blood flow by Doppler ultrasound (5
) has not correlated with portal venous pressure. Furthermore, an inverse relationship between splenic arterial blood flow and hepatic venous pressure gradient (HVPG) using CT imaging is reported (30
). The finding of increased splenic blood flow supports the hypothesis, however, that splenic hemodynamics are not characterized only by passive congestion alone (24
). Increased phagocytic cell mass within the spleen, which corresponds with volumetric growth in patients with chronic liver disease, may also play a role in determining tissue stiffness (32
The relationship between liver stiffness measurement by ultrasound-based transient elastography and clinically significant portal hypertension assessed by HVPG has been reported (15
). A strong relationship between HVPG < 10 mm Hg and liver stiffness consistent with mild to moderate degrees of liver fibrosis (15
). However, there has been a less than robust correlation between liver stiffness value and the presence of esophageal varices in patients with cirrhosis (17
). Similarly, our preliminary results did not identify a significant relationship between mean liver stiffness value and esophageal varices. In contrast, we did observe a statistically significant relationship between mean spleen stiffness and the presence of esophageal varices. With a mean spleen stiffness values ≥ 10.5 kPa, we also noted a detection rate of 100%. for esophageal varices in patients with compensated cirrhosis This observation remained independent of serum platelet count including values < 140,000/mm3
which is known to have modest ability for predicting esophageal varices (34
). While liver stiffness measurement appears to capture the effect of elevated intrahepatic vascular resistance from advanced fibrosis (35
), it is possible that spleen stiffness provides additional information about the hemodynamic alterations within splenic and splanchnic arterial circulations as portal venous pressure increases over time.
Our study was recognized to have some limitations. Mean liver and spleen stiffness measurements were performed in 2-dimensions using cross-sectional images in all subjects. Greater accuracy in tissue stiffness measurement may be possible with the availability of 3-dimensonal wave analysis in MRE which is awaited. The correlation between mean spleen stiffness and portal venous pressure measurement by HVPG was not performed in this preliminary study. Based on preliminary results suggesting a relationship between spleen stiffness and esophageal varices, the measurement of HVGP and comparison with spleen and liver stiffness is being pursued. Finally, our results concerning the predictive ability of mean spleen stiffness for detecting esophageal varices in patients with compensated cirrhosis remains preliminary. In turn, we did not examine the performance of other non-invasive detection methods for esophageal varices such as platelet count/spleen diameter ratio which has some evidence of external validity among independent populations (36
In conclusion, our results demonstrate the feasibility of spleen stiffness measurement in healthy individuals and patients with chronic liver disease with MRE. Among patients with advanced fibrosis and compensated cirrhosis, mean spleen stiffness could serve a potential role to improve the appropriate selection of patients for endoscopic screening to detect esophageal varices. Further studies, however, are needed to define the feasibility and diagnostic performance of mean spleen stiffness measurement in clinical practice.