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Auditory display for fluorescence-guided open brain tumor surgery.

ABSTRACT: Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon.The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training.The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate.The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful.

SUBMITTER: Black D

PROVIDER: S-EPMC5772873 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Auditory display for fluorescence-guided open brain tumor surgery.

Black David D Hahn Horst K HK Kikinis Ron R Wårdell Karin K Haj-Hosseini Neda N

International journal of computer assisted radiology and surgery 20170919 1

<h4>Purpose</h4>Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed a ...[more]

PMID: 28929305

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Project description:Objective: Fluorescence dyes are increasingly used in brain tumor surgeries, and thus the development of simulation models is important for teaching neurosurgery trainees how to perform fluorescence-guided operations. We aimed to create a tumor model for fluorescence-guided surgery in high-grade glioma (HGG). Methods: The tumor model was generated by the following steps: creating a tumor gel with a similar consistency to HGG, selecting fluorophores at optimal concentrations with realistic color, mixing the fluorophores with tumor gel, injecting the gel into fresh pig/sheep brain, and testing resection of the tumor model under a fluorescence microscope. The optimal tumor gel was selected among different combinations of agar and gelatin. The fluorophores included fluorescein, indocyanine green (ICG), europium, chlorin e6 (Ce6), and protoporphyrin IX (PpIX). The tumor model was tested by neurosurgeons and neurosurgery trainees, and a survey was used to assess the validity of the model. In addition, the photobleaching phenomenon was studied to evaluate its influence on fluorescence detection. Results: The best tumor gel formula in terms of consistency and tactile response was created using 100 mL water at 100°C, 0.5 g of agar, and 3 g of gelatin mixed thoroughly for 3 min. An additional 1 g of agar was added when the tumor gel cooled to 50°C. The optimal fluorophore concentration ranges were fluorescein 1.9 × 10-4 to 3.8 × 10-4 mg/mL, ICG 4.9 × 10-3 to 9.8 × 10-3 mg/mL, europium 7.0 × 10-2 to 1.4 × 10-1 mg/mL, Ce6 2.2 × 10-3 to 4.4 × 10-3 mg/mL, and PpIX 1.8 × 10-2 to 3.5 × 10-2 mg/mL. No statistical differences among fluorophores were found for face validity, content validity, and fluorophore preference. Europium, ICG, and fluorescein were shown to be relatively stable during photobleaching experiments, while chlorin e6 and PpIX had lower stability. Conclusions: The model can efficiently highlight the "tumor" with 3 different colors-green, yellow, or infrared green with color overlay. These models showed high face and content validity, although there was no significant difference among the models regarding the degree of simulation and training effectiveness. They are useful educational tools for teaching the key concepts of intra-axial tumor resection techniques, such as subpial dissection and nuances of fluorescence-guided surgery.

Project description:Fluorescence image-guided surgery combined with intraoperative therapeutic modalities has great potential for intraoperative detection of oncologic targets and eradication of unresectable cancer residues. Therefore, we have developed an activatable theranostic nanoplatform that can be used concurrently for two purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence signal during surgery, and (2) intraoperative targeted treatment to further eliminate unresected disease sites by non-toxic phototherapy. Methods: The developed nanoplatform is based on a single agent, silicon naphthalocyanine (SiNc), encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(ɛ-caprolactone)) nanoparticles. It is engineered to be non-fluorescent initially via dense SiNc packing within the nanoparticle's hydrophobic core, with NIR fluorescence activation after accumulation at the tumor site. The activatable nanoplatform was evaluated in vitro and in two different murine cancer models, including an ovarian intraperitoneal metastasis-mimicking model. Furthermore, fluorescence image-guided surgery mediated by this nanoplatform was performed on the employed animal models using a Fluobeam® 800 imaging system. Finally, the phototherapeutic efficacy of the developed nanoplatform was demonstrated in vivo. Results: Our in vitro data suggest that the intracellular environment of cancer cells is capable of compromising the integrity of self-assembled nanoparticles and thus causes disruption of the tight dye packing inside the hydrophobic cores and activation of the NIR fluorescence. Animal studies demonstrated accumulation of activatable nanoparticles at the tumor site following systemic administration, as well as release and fluorescence recovery of SiNc from the polymeric carrier. It was also validated that the developed nanoparticles are compatible with the intraoperative imaging system Fluobeam® 800, and nanoparticle-mediated image-guided surgery provides successful resection of cancer tumors. Finally, in vivo studies revealed that combinatorial phototherapy mediated by the nanoparticles could efficiently eradicate chemoresistant ovarian cancer tumors. Conclusion: The revealed properties of the activatable nanoplatform make it highly promising for further application in clinical image-guided surgery and combined phototherapy, facilitating a potential translation to clinical studies.

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Auditory display for fluorescence-guided open brain tumor surgery.

Publications

Auditory display for fluorescence-guided open brain tumor surgery.

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