In vivo characterization of colorectal metastases in human liver using diffuse reflectance spectroscopy: toward guidance in oncological procedures

Abstract

There is a strong need to develop clinical instruments that can perform rapid tissue assessment at the tip of smart clinical instruments for a variety of oncological applications. This study presents the first in vivo real-time tissue characterization during 24 liver biopsy procedures using diffuse reflectance (DR) spectroscopy at the tip of a core biopsy needle with integrated optical fibers. DR measurements were performed along each needle path, followed by biopsy of the target lesion using the same needle. Interventional imaging was coregistered with the DR spectra. Pathology results were compared with the DR spectroscopy data at the final measurement position. Bile was the primary discriminator between normal liver tissue and tumor tissue. Relative differences in bile content matched with the tissue diagnosis based on histopathological analysis in all 24 clinical cases. Continuous DR measurements during needle insertion in three patients showed that the method can also be applied for biopsy guidance or tumor recognition during surgery. This study provides an important validation step for DR spectroscopy-based tissue characterization in the liver. Given the feasibility of the outlined approach, it is also conceivable to make integrated fiber-optic tools for other clinical procedures that rely on accurate instrument positioning.

Fig. 1

Example of added quantitative spectral functionality during routine liver biopsy (first patient 12 in Table 1). (a) Positioning of the FOBN based on CT-fluoroscopic imaging in liver tissue, at the border of the target lesion and in the target lesion prior to biopsy. (b) Coregistered DR measurements (blue dotted line) and corresponding fit curves (red lines). (c) Data for blood, ${\mathrm{stO}}_2$, bile, and ${\mu }_{\mathrm{s}}^{\prime }(800)$ represent mean values ± standard deviations. N, normal liver tissue; B, tumor border; T, tumor; and FOBN, fiber-optic biopsy needle.

Fig. 2

DR spectroscopy parameter quantification. Bar graphs show the values for (a) blood, (c) ${\mathrm{stO}}_2$, (e) bile, and (g) ${\mu }_{\mathrm{s}}^{\prime }(800)$ as measured in liver tissue (normal), at the tumor border (border) and in the target lesion (tumor). Values are given as $\text{mean values}\pm \text{standard errors}$, adjusted for repeated measurements. *$p<0.01$. NS: not significant. Corresponding receiver operating characteristics (ROC) curves (b, d, f, h) indicate the ability to distinguish tumor tissue from liver tissue. AUC: area under ROC curve.

Fig. 3

Relative changes in bile content determined for $n=24$ insertions. The relative bile content was defined as the bile content in tumor relative to the average value measured in normal liver tissue. Values are given as the $\text{mean}\pm \text{standard deviations}$. Dotted line: relative bile $\text{content}=1$.

Fig. 4

(a) Although CT-fluoroscopic imaging in subject 9 and subject 10 suggests that the tissue biopsy was taken from the target lesions, the tissue samples proved to be nondiagnostic. The samples contained only normal liver tissue, indicating that the targeted tissue was missed. No substantial change in bile content and other DR spectroscopy parameters was seen. These examples underline the importance of real-time measurements and data analysis in order to identify the transition of needle placement in a tumor based on the changes in the derived parameters. (b) Data for blood, ${\mathrm{stO}}_2$, and bile represent $\text{mean values}\pm \text{standard deviations}$. N, normal lung tissue; T, tumor; and FOBN, fiber-optic biopsy needle.

Fig. 5

Real-time tissue characterization and biopsy with the FOBN in an individual. (a) CT-fluoroscopy images during insertion of the FOBN (images I through VI). (b) DR spectroscopy parameters were extracted from the optical data along the needle path. Note that the spectral measurements were started while the FOBN was positioned in subcutaneous fat or muscle. FOBN, fiber-optic biopsy needle.