Quantification of gastric mucosal microcirculation as a surrogate marker of portal hypertension by spatially resolved subdiffuse reflectance spectroscopy in diagnosis of cirrhosis: a proof-of-concept study

Abstract

Background and aims: Portal pressure can be used to identify patients with chronic liver disease who have progressed to cirrhosis. Portal pressure can also provide accurate prognostication for patients with cirrhosis. However, there are no practical means for assessment of portal pressure. Although it is well established that the gastric mucosal blood supply increases in patients with cirrhosis, this has been difficult to quantify reproducibly. Our group has developed a novel spectroscopic technology called spatially resolved subdiffuse reflectance spectroscopy (SRSRS), which enables quantification of mucosal microcirculation. We aim to ascertain if quantification of the gastric mucosal microcirculation with SRSRS correlates with clinical evidence of portal hypertension.

Methods: Patients undergoing EGD for clinical indications had 10 measurements taken in the endoscopically normal gastric fundus via SRSRS probe to assess the microcirculation. Cases were defined as patients with cirrhosis (n = 18), and controls were those without evidence of liver disease (n = 18); this was corroborated with transient elastography.

Results: The blood volume fraction (P = .06) and subdiffuse reflectance (P = .02) from a shallow depth in the gastric fundus were higher in patients with cirrhosis than those without. These markers were combined to yield an overall optical marker that can differentiate patients with cirrhosis from controls with a sensitivity of 72% and specificity of 94% (area under receiver operating curve, 0.82).

Conclusions: Spectroscopic quantification of gastric fundal mucosal microcirculation is a promising surrogate of clinical correlates of portal hypertension. This approach may represent a less-intrusive surrogate biomarker for liver disease prognostication and potentially response to therapy.

Figure 1.

Spatially resolved subdiffuse reflectance spectroscopy (SRSRS) instrumentation and probe. A, SRSRS optical fiber arrangement. B, SRSRS instrumentation, including the spectrophotometer and central processing unit (CPU). C, The SRSRS probe in the accessory channel of the endoscope.

Figure 2.

Penetration depth of spatially resolved subdiffuse reflectance spectroscopy (SRSRS) probe fibers. The probability density function for the depths sampled by the 3 fibers. This demonstrates that although each fiber samples a broad range of depths, the calculated expected value for a single photon (photon origination depth) would be ∼150, ∼230, and ∼285 μm for the 3 fibers.

Figure 3.

Spatially resolved subdiffuse reflectance spectroscopy (SRSRS) biomarkers in the fundus of the stomach with cases (cirrhotics) and controls. A, Blood volume fraction; B, blood vessel radius; C, subdiffuse reflectance in controls (patients without cirrhosis) and cases.

Figure 4.

A, The combination spatially resolved subdiffuse reflectance spectroscopy (SRSRS) biomarker that integrated blood volume fraction and subdiffuse reflectance was significantly different in controls (patients without cirrhosis) compared with cases (patients with cirrhosis). B, The combination spectroscopic biomarker had good accuracy (area under the receiver operator characteristic curve [AUC] = 0.82) for the diagnosis of cirrhosis.