Location
Philadelphia, PA
Start Date
9-5-2018 1:00 PM
Description
Introduction: Histopathological diagnoses are often necessary for treating neuro-oncology patients. However, stereotactic biopsy (STB), a common method for obtaining tissue from deep or eloquent brain regions, fails to yield diagnostic tissue in approximately 10% of cases. This can delay initiation of treatment and may result in further invasive procedures for patients. Here, we evaluate if coupling in vivo optical imaging with a STB system can identify diagnostic tissue at the time of biopsy.
Methods: A minimally invasive fiber optic imaging system was developed by coupling a 0.65mm diameter fiber optic fluorescence microendoscope to a STB system. Human glioma cells were transduced for stable expression of blue fluorescent protein (U251-BFP) and utilized for in vitro and in vivo experiments. In vitro, blue fluorescence was confirmed, and tumor cell delineation by sodium fluorescein (FNa) was quantified with fluorescence microscopy. Rodent xenografts implanted with U251-BFP cells (n=4) were utilized for in vivo experiments. Five weeks post-implantation, xenografts received 5-10mg/kg intravenous FNa and underwent craniotomies overlying the tumor implantation site and contralateral normal brain. A clinical STB needle containing our 0.65mm imaging fiber was passed through each craniotomy and images were collected. Fluorescence images from regions of interest (ROI) ipsilateral and contralateral to tumor implantation were analyzed.
Results: Live-cell fluorescence imaging confirmed blue fluorescence from transduced tumor cells and revealed a strong correlation between tumor cells quantified by blue fluorescence and FNa contrast (R2=0.91, p<0.001). Normalized to background, in vivo FNa fluorescence intensity was significantly greater from tumor regions, verified by blue fluorescence, compared to contralateral brain in all animals (60.65± 17.35 %, p<0.001). Fluorescein fluorescence was not significantly greater from the tumor margin compared to normal brain (p =0.096). Biopsies obtained from regions of strong fluorescein contrast were histologically consistent with tumor.
Conclusion: We found in vivo fluorescence imaging with a STB needle containing a submillimeter diameter fluorescence microendoscope provided direct visualization of neoplastic tissue in an animal brain tumor model prior to biopsy. This was confirmed in vivo and by post-hoc histological assessment. In vivo fluorescence guidance may improve the diagnostic yield of stereotactic biopsies.
Embargo Period
10-30-2018
Fluorescence-Guided Stereotactic Biopsy: A Proof-of-Concept Study
Philadelphia, PA
Introduction: Histopathological diagnoses are often necessary for treating neuro-oncology patients. However, stereotactic biopsy (STB), a common method for obtaining tissue from deep or eloquent brain regions, fails to yield diagnostic tissue in approximately 10% of cases. This can delay initiation of treatment and may result in further invasive procedures for patients. Here, we evaluate if coupling in vivo optical imaging with a STB system can identify diagnostic tissue at the time of biopsy.
Methods: A minimally invasive fiber optic imaging system was developed by coupling a 0.65mm diameter fiber optic fluorescence microendoscope to a STB system. Human glioma cells were transduced for stable expression of blue fluorescent protein (U251-BFP) and utilized for in vitro and in vivo experiments. In vitro, blue fluorescence was confirmed, and tumor cell delineation by sodium fluorescein (FNa) was quantified with fluorescence microscopy. Rodent xenografts implanted with U251-BFP cells (n=4) were utilized for in vivo experiments. Five weeks post-implantation, xenografts received 5-10mg/kg intravenous FNa and underwent craniotomies overlying the tumor implantation site and contralateral normal brain. A clinical STB needle containing our 0.65mm imaging fiber was passed through each craniotomy and images were collected. Fluorescence images from regions of interest (ROI) ipsilateral and contralateral to tumor implantation were analyzed.
Results: Live-cell fluorescence imaging confirmed blue fluorescence from transduced tumor cells and revealed a strong correlation between tumor cells quantified by blue fluorescence and FNa contrast (R2=0.91, p<0.001). Normalized to background, in vivo FNa fluorescence intensity was significantly greater from tumor regions, verified by blue fluorescence, compared to contralateral brain in all animals (60.65± 17.35 %, p<0.001). Fluorescein fluorescence was not significantly greater from the tumor margin compared to normal brain (p =0.096). Biopsies obtained from regions of strong fluorescein contrast were histologically consistent with tumor.
Conclusion: We found in vivo fluorescence imaging with a STB needle containing a submillimeter diameter fluorescence microendoscope provided direct visualization of neoplastic tissue in an animal brain tumor model prior to biopsy. This was confirmed in vivo and by post-hoc histological assessment. In vivo fluorescence guidance may improve the diagnostic yield of stereotactic biopsies.