Evaluation of a Fiber-Optic Fluorescence Spectroscopy System to Assist Neurosurgical Tumor Resections (original) (raw)
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Optical touch pointer for fluorescence guided glioblastoma resection using 5-aminolevulinic acid
Lasers in Surgery and Medicine, 2010
Background and Objective: Total tumor resection in patients with glioblastoma multiforme (GBM) is difficult to achieve due to the tumor's infiltrative way of growing and morphological similarity to the surrounding functioning brain tissue. The diagnosis is usually subjectively performed using a surgical microscope. The objective of this study was to develop and evaluate a hand-held optical touch pointer using a fluorescence spectroscopy system to quantitatively distinguish healthy from malignant brain tissue intraoperatively. Study Design/Materials and Methods: A fluorescence spectroscopy system with pulsed modulation was designed considering optimum energy delivery to the tissue, minimal photobleaching of PpIX and omission of the ambient light background in the operating room (OR). 5-aminolevulinic acid (5-ALA) of 5 mg/kg body weight was given to the patients with a presumed glioblastoma multiforme prior to surgery. During the surgery a laser pulse at 405 nm was delivered to the tissue. PpIX in glioblastoma tumor cells assigned with peaks at 635 nm and 704 nm was detected using a fiber optical probe. Results/Conclusion: By using the pulsed fluorescence spectroscopy, PpIX fluorescence is quantitatively detected in the glioblastoma multiforme. An effective suppression of low power lamp background from the recorded spectra in addition to a significant reduction of high power surgical lights is achieved.
Photochemistry and Photobiology, 2003
The intrinsic autofluorescence properties of biological tissues can be affected by the occurrence of histological and biochemical alterations induced by pathological processes. In this study the potential of autofluorescence to distinguish tumor from normal tissues was investigated with the view of a real-time diagnostic application in neurosurgery to delineate glioblastoma resection margins. The autofluorescence properties of nonneoplastic and neoplastic tissues were analyzed on tissue sections and homogenates by means of a microspectrofluorometer, and directly on patients affected by glioblastoma multiforme, during surgery, with a fiber-optic probe. Scanmicrospectrofluorometric analysis on tissue sections evidenced a reduction of emission intensity and a broadening of the main emission band, along with a redshift of the peak position, from peritumoral nonneoplastic to neoplastic tissues. Differences in both spectral shape and signal amplitude were found in patients when the glioblastoma lesion autofluorescence was compared with those of cortex and white matter taken as healthy tissues. Both biochemical composition and histological organization contribute to modify the autofluorescence emission of neoplastic, with respect to nonneoplastic, brain tissues. The differences found in the in vivo analysis confirm the prospects for improving the efficacy of tumor resection margin delineation in neurosurgery.
Protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (5-ALA) is increasingly used as a fluorescent marker for fluorescence-guided resection of malignant gliomas. Understanding how the properties of the excitation light source and PpIX fluorescence interact with the surgical microscope is critical for effective use of the fluorescence-guided tumor resection technique. In this study, we performed a detailed assessment of the intensity of the emitted blue light and white light and the light beam profile of clinical grade operating microscopes used for PpIX visualization. These measurements revealed both recognized fluorescence photobleaching limitations and unrecognized limitations that may alter quantitative observations of PpIX fluorescence obtained with the operating microscope with potential impact on research and clinical uses. We also evaluated the optical properties of a photostable fluorescent standard with an excitation-emission profile similar to PpIX. In addition, we measured the time-dependent dynamics of 5-ALA-induced PpIX fluorescence in an animal glioma model. Finally, we developed a ratiometric method for quantification of the PpIX fluorescence that uses the photostable fluorescent standard to normalize PpIX fluorescence intensity. This method increases accuracy and allows reproducible and direct comparability of the measurements from multiple samples. Operating microscopes are commonplace within the neurosurgical operating theater and are a mainstay of surgical procedures for brain tumor removal 1. As the most important visualization tool in daily use for neurosurgery, operating microscopes are gaining advanced functionality by means of innovative illumination modes. To ensure surgical success, the neurosurgeon must fully understand the illumination properties and functionality of the microscope, especially within the context of fluorescence-guided tumor resection. The principle of fluorescence-guided tumor resection relies on the use of targeting agents with fluorescent properties that can be administered to patients before or during surgery. These agents are intended to accumulate within and around the tumor tissue or within the cells of the tumor, depending on the selectivity and actions of the fluorophore. The desired diagnostic result is to augment visual differentiation and detection of the tumor tissue margins during surgery based on fluorescence. The most notable recent example of a fluorescent agent developed for tumor detection in neurosurgery is 5-aminolevulinic acid (5-ALA), which is used to indicate the presence of tumors and the border regions of malignant gliomas 2. 5-ALA was recently designated as the first US Food and Drug Administration-approved agent for fluorescence-guided resection of high-grade gliomas 3. This prodrug results in fluorescent PpIX accumulation in tumors through a distortion in the metabolic conversion of 5-ALA to heme 4. Understanding both the nuances of its fluorescent properties and the effects that occur with changes in excitation intensity and duration of light
Increased brain tumor resection using fluorescence image guidance in a preclinical model
Lasers in Surgery and Medicine, 2004
Background and ObjectivesFluorescence image-guided brain tumor resection is thought to assist neurosurgeons by visualizing those tumor margins that merge imperceptibly into normal brain tissue and, hence, are difficult to identify. We compared resection completeness and residual tumor, determined by histopathology, after white light resection (WLR) using an operating microscope versus additional fluorescence guided resection (FGR).Fluorescence image-guided brain tumor resection is thought to assist neurosurgeons by visualizing those tumor margins that merge imperceptibly into normal brain tissue and, hence, are difficult to identify. We compared resection completeness and residual tumor, determined by histopathology, after white light resection (WLR) using an operating microscope versus additional fluorescence guided resection (FGR).Study Design/Materials and MethodsWe employed an intracranial VX2 tumor in a preclinical rabbit model and a fluorescence imaging/spectroscopy system, exciting and detecting the fluorescence of protoporphyrin IX (PpIX) induced endogenously by administering 5-aminolevulinic acid (ALA) at 4 hours before surgery.We employed an intracranial VX2 tumor in a preclinical rabbit model and a fluorescence imaging/spectroscopy system, exciting and detecting the fluorescence of protoporphyrin IX (PpIX) induced endogenously by administering 5-aminolevulinic acid (ALA) at 4 hours before surgery.ResultsUsing FGR in addition to WLR significantly increased resection completeness by a factor 1.4 from 68±38 to 98±3.5%, and decreased the amount of residual tumor post-resection by a factor 16 from 32±38 to 2.0±3.5% of the initial tumor volume.Using FGR in addition to WLR significantly increased resection completeness by a factor 1.4 from 68±38 to 98±3.5%, and decreased the amount of residual tumor post-resection by a factor 16 from 32±38 to 2.0±3.5% of the initial tumor volume.ConclusionsAdditional FGR increased completeness of resection and enabled more consistent resections between cases. Lasers Surg. Med. 35:181–190, 2004. © 2004 Wiley-Liss, Inc.Additional FGR increased completeness of resection and enabled more consistent resections between cases. Lasers Surg. Med. 35:181–190, 2004. © 2004 Wiley-Liss, Inc.
Neurophotonics, 2016
Advances in image-guided therapy enable physicians to obtain real-time information on neurological disorders such as brain tumors to improve resection accuracy. Image guidance data include the location, size, shape, type, and extent of tumors. Recent technological advances in neurophotonic engineering have enabled the development of techniques for minimally invasive neurosurgery. Incorporation of these methods in intraoperative imaging decreases surgical procedure time and allows neurosurgeons to find remaining or hidden tumor or epileptic lesions. This facilitates more complete resection and improved topology information for postsurgical therapy (i.e., radiation). We review the clinical application of recent advances in neurophotonic technologies including Raman spectroscopy, thermal imaging, optical coherence tomography, and fluorescence spectroscopy, highlighting the importance of these technologies in live intraoperative tissue mapping during neurosurgery. While these technologies need further validation in larger clinical trials, they show remarkable promise in their ability to help surgeons to better visualize the areas of abnormality and enable safe and successful removal of malignancies.
Improved sensitivity to fluorescence for cancer detection in wide-field image-guided neurosurgery
Biomedical optics express, 2015
In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX sensitivity in wide-field fluorescence imaging may improve the residual tumor detection during surgery with consequent impact on survival.
FluoRa - a System for Combined Fluorescence and Microcirculation Measurements in Brain Tumor Surgery
2021 43rd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), 2021
In brain tumor surgery it is difficult to distinguish the marginal zone with the naked eye. Fluorescence techniques can help identifying tumor tissue in the zone during resection and biopsy procedures. In this paper a novel system for combined real-time measurements of PpIX-fluorescence, microcirculation and tissue grey-whiteness is presented and experimentally evaluated. The system consists of a fluorescence hardware with a sensitive CCD spectrometer for PpIX peak detection, a laser Doppler system, optical probes, and a LabView software. System evaluation was done on static fluorescing material, human skin, and brain tumor tissue. The static material indicates reproducibility, the skin measurements exemplify simultaneous fluorescence and microcirculation measurement in real-time, and the tumor tissue showed PpIX peaks. These decreased over time, as expected, due to photo bleaching. In addition, the system was prepared for clinical use and thus laser-and electrical safety issues were considered. In summary, a system for multiparameter measurements during neurosurgery was successfully evaluated in an experimental environment. As a next step the system will be applied in clinical brain tumor biopsies and resections.