Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas

Montcel, Bruno; Mahieu-Williame, Laurent; Armoiry, Xavier; Meyronet, David; Guyotat, Jacques

doi:10.1364/boe.4.000548

Cited by 63 publications

(87 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We measured in extracted tumor tissues a dedoubled emission peaks feature due to multiple photochemical states of PpIX [8,9] inducing non-uniqueness of the measured PpIX concentration in gliomas and in the infiltrative compound of glioblastomas. We propose new measured parameters allowing identifying and overcoming non-uniqueness [12]. Our results suggest that the inability of the current ALA-induced PpIX method to evaluate the infiltrative compound of gliomas may be more due to a fundamental limitation to consider the de-doubled emission peaks rather than to a lack of sensitivity.…”

Section: Introductionmentioning

confidence: 99%

“…However its accuracy remains limited because of a still low sensitivity [2][3][4] to evaluate infiltrative compound of high grade glioma (HGG) and low grade glioma (LGG). The current method is based on intraoperative surgical fluorescence microscopy [5] or optical fiber systems that allow a local emission spectrum measurement [3,6,12], or a quantification [2,7] of 5-ALA-induced PpIX concentration ( ). The PpIX emission peak at 634 nm is known to be predominant in HGG [2,3,6,7].…”

Section: Introductionmentioning

confidence: 99%

“…The PpIX emission peak at 634 nm is known to be predominant in HGG [2,3,6,7]. However some results indicate that the emission spectrum can be more complicated [12,13,14,15] due to either a shift in the position of the emission maximum towards shorter wavelength or the presence of photoproducts. We measured in extracted tumor tissues a dedoubled emission peaks feature due to multiple photochemical states of PpIX [8,9] inducing non-uniqueness of the measured PpIX concentration in gliomas and in the infiltrative compound of glioblastomas.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

5-ALA-induced PpIX fluorescence in gliomas resection: spectral complexity of the emission spectrum in the infiltrative compound

et al. 2013

Self Cite

View full text Add to dashboard Cite

5-ALA-induced protoporphyrin IX (PpIX) fluorescence enables to guiding in intra-operative surgical glioma resection. However at present, it has yet to be shown that this method is able to identify infiltrative component of glioma. In extracted tumor tissues we measured a two-peaked emission in low grade gliomas and in the infiltrative component of glioblastomas due to multiple photochemical states of PpIX. This spectral complexity of the fluorescence emission spectrum brings new limits in the sensibility of current methods to measured PpIX concentration. We propose new measured parameters, by taking into consideration the spectral complexity, to overcome these limitations in sensitivity. These parameters clearly distinguish the solid component of glioblastomas from low grade gliomas and infiltrative component of glioblastomas.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

5-ALA-induced PpIX fluorescence in gliomas resection: spectral complexity of the emission spectrum in the infiltrative compound

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…1,7,10,11,13,15,17,20,29,30,34,35,41,47,49,52 However, the vast majority of clinical studies on fluorescence-guided neurosurgery have only considered the qualitative, visible PpIX emissions. In these investigations, a surgical microscope modified for fluorescence imaging is typically deployed and provides a violet-blue light excitation mode (λ = 405 nm) with fluorescence collection via a long-pass filter (λ = 450–720 nm).…”

mentioning

confidence: 99%

Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

Valdés

Jacobs

Harris

et al. 2015

JNS

145

137

View full text Add to dashboard Cite

OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were detected quantitatively. CONCLUSIONS The authors’ initial experience with ALA-induced PpIX fluorescence in LGGs concurs with other literature reports that the resulting visual fluorescence has poor diagnostic accuracy. However, the authors also found that diagnostically significant levels of CPpIX do accumulate in LGGs, and the resulting fluorescence emissions are very often below the detection threshold of current visual fluorescence imaging methods. Indeed, at least in the authors’ initial experience reported here, if quantitative detection methods are deployed, the diagnostic performance of ALA-induced PpIX fluorescence in LGGs approaches the accuracy associated with visual fluorescence in HGGs.

show abstract

“…Additionally, a broad and characteristic emission spectrum is induced, allowing the extraction of valuable spectral information. [46,47] Moreover, the use of a 405 nm light source also leads to the excitation of tissue autofluorescence, which could be used as an additional parameter for tissue discrimination [48][49][50] or serve as reference for the normalization of PpIX signals [27].…”

Section: Resultsmentioning

confidence: 99%

405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence‐guided stereotactic biopsy of brain tumors

Markwardt

Haj‐Hosseini

Hollnburger

et al. 2015

Journal of Biophotonics

View full text Add to dashboard Cite

Fluorescence diagnosis may be used to improve the safety and reliability of stereotactic brain tumor biopsies using biopsy needles with integrated fiber optics. Based on 5-aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence, vital tumor tissue can be localized in-vivo during the excision procedure to reduce the number of necessary samples for a reliable diagnosis.In this study, the practical suitability of two different PpIX excitation wavelengths (405 nm, 633 nm) was investigated on optical phantoms. Violet excitation at 405 nm provides a 50-fold higher sensitivity for the bulk tumor; this factor increases up to 100 with decreasing fluorescent volume as shown by ray tracing simulations. Red excitation at 633 nm, however, is noticeably superior with regard to blood layers obscuring the fluorescence. Experimental results on the signal attenuation through blood layers of well-defined thicknesses could be confirmed by ray tracing simulations. Typical interstitial fiber probe measurements were mimicked on agarose-gel phantoms. Even in direct contact, blood layers of 20 -40 µm between probe and tissue must be expected, obscuring 405-nm-excited PpIX fluorescence almost completely, but reducing the 633-nm-excited signal only by 25.5%. Thus, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of highgrade gliomas in stereotactic biopsy.

show abstract

Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas

Cited by 63 publications

References 21 publications

5-ALA-induced PpIX fluorescence in gliomas resection: spectral complexity of the emission spectrum in the infiltrative compound

5-ALA-induced PpIX fluorescence in gliomas resection: spectral complexity of the emission spectrum in the infiltrative compound

Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence‐guided stereotactic biopsy of brain tumors

Contact Info

Product

Resources

About