Adjuncts for Maximizing Resection

Roberts, David W.; Valdés, Pablo; Harris, Brent T.; Hartov, Alex; Fan, Xiaoyao; Ji, Songbai; Pogue, Brian W.; Leblond, Frédéric; Tosteson, Tor D.; Wilson, Brian C.; Paulsen, Keith D.

doi:10.1227/neu.0b013e31826b2e8b

Cited by 18 publications

(14 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because of the invasive and diffusive nature of gliomas as well as the need to preserve functional tissue, achieving optimal tumor resection is difficult using standard-of-care surgical approaches based on white light visualization combined with preoperative or intraoperative MRI. [1][2][3][4] Qualitative ALA-PpIX fluorescence imaging during resection provides superior tumor-to-normal contrast, resulting in improved completeness of resection and survival outcomes for patients with high-grade glioma. [1][2][3][4] However, it has not been sufficiently robust in the case of low-grade gliomas that generally have much lower PpIX concentrations, and even in high-grade disease, the subjective and qualitative interpretation of the fluorescence imaging has limited the resection to areas of "strong" fluorescence.…”

Section: Discussionmentioning

confidence: 99%

“…Intraoperative fluorescence-guided resection (FGR) has been developed to enhance tumor visualization. 3 While applicable across many tumor sites, FGR has been most advanced in glioma surgery, where it has been used both at the beginning of surgery to define tumor/normal tissue boundaries and at the near end of surgery (after debulking) to identify residual tumor tissue in the resection bed as well as satellite tumors that have migrated beyond the resection bed. 3 Clinically, FGR has resulted in a significant increase in complete resection rates as estimated by MRI contrast enhancement postsurgery.…”

Section: Introductionmentioning

confidence: 99%

“…3 While applicable across many tumor sites, FGR has been most advanced in glioma surgery, where it has been used both at the beginning of surgery to define tumor/normal tissue boundaries and at the near end of surgery (after debulking) to identify residual tumor tissue in the resection bed as well as satellite tumors that have migrated beyond the resection bed. 3 Clinically, FGR has resulted in a significant increase in complete resection rates as estimated by MRI contrast enhancement postsurgery. 4 The most widely used fluorophore in FGR of glioma is protoporphyrin IX (PpIX), a precursor in the heme-biosynthesis pathway that preferentially accumulates in tumor cells upon administration of 5-aminolevelunic acid (ALA).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Preclinical evaluation of spatial frequency domain-enabled wide-field quantitative imaging for enhanced glioma resection

et al. 2017

Self Cite

View full text Add to dashboard Cite

5-Aminolevelunic acid-induced protoporphyrin IX (PpIX) fluorescence-guided resection (FGR) enables maximum safe resection of glioma by providing real-time tumor contrast. However, the subjective visual assessment and the variable intrinsic optical attenuation of tissue limit this technique to reliably delineating only high-grade tumors that display strong fluorescence. We have previously shown, using a fiber-optic probe, that quantitative assessment using noninvasive point spectroscopic measurements of the absolute PpIX concentration in tissue further improves the accuracy of FGR, extending it to surgically curable low-grade glioma. More recently, we have shown that implementing spatial frequency domain imaging with a fluorescent-light transport model enables recovery of two-dimensional images of [PpIX], alleviating the need for time-consuming point sampling of the brain surface. We present first results of this technique modified for

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Preclinical evaluation of spatial frequency domain-enabled wide-field quantitative imaging for enhanced glioma resection

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the extent to which this may or may not occur is somewhat controversial, there is a need for the development of instruments with increased sensitivity for the detection of intraoperative fluorescence and a need for methods to increase specificity. 21,28 Additional studies are also needed to identify therapeutic agents and intrinsic molecular characteristics that affect the metabolism of 5-ALA, such as has been seen with phenytoin, 16 cadherin 13 expression, 34 aquaporin, 33 and ferrochelatase expression. 36 Other dyes, such as methylene blue, are being studied for their ability to enhance the morphologic image; 46 however, the utility of this approach relies on the surgeon's ability to recognize sometimes subtle morphological characteristics.…”

Section: Discussionmentioning

confidence: 99%

In vivo visualization of GL261-luc2 mouse glioma cells by use of Alexa Fluor–labeled TRP-2 antibodies

Fenton¹,

Martirosyan²,

Abdelwahab³

et al. 2014

FOC

View full text Add to dashboard Cite

Object For patients with glioblastoma multiforme, median survival time is approximately 14 months. Longer progression-free and overall survival times correlate with gross-total resection of tumor. The ability to identify tumor cells intraoperatively could result in an increased percentage of tumor resected and thus increased patient survival times. Available labeling methods rely on metabolic activity of tumor cells; thus, they are more robust in high-grade tumors, and their utility in low-grade tumors and metastatic tumors is not clear. The authors demonstrate intraoperative identification of tumor cells by using labeled tumor-specific antibodies. Methods GL261 mouse glioma cells exhibit high expression of a membrane-bound protein called second tyrosinase-related protein (TRP-2). The authors used these cells to establish an intracranial, immunocompetent model of malignant glioma. Antibodies to TRP-2 were labeled by using Alexa Fluor 488 fluorescent dye and injected into the tail vein of albino C57BL/6 mice. After 24 hours, a craniotomy was performed and the tissue was examined in vivo by using an Optiscan 5.1 handheld portable confocal fiber-optic microscope. Tissue was examined ex vivo by using a Pascal 5 scanning confocal microscope. Results Labeled tumor cells were visible in vivo and ex vivo under the respective microscopes. Conclusions Fluorescently labeled tumor-specific antibodies are capable of binding and identifying tumor cells in vivo, accurately and specifically. The development of labeled markers for the identification of brain tumors will facilitate the use of intraoperative fluorescence microscopy as a tool for increasing the extent of resection of a broad variety of intracranial tumors.

show abstract

“…1,2 In the last decade, this approach has been most highly developed for brain tumor surgery using the optical contrast provided by protoporphyrin IX (PpIX) that is endogenously synthesized in tumor cells following administration of the prodrug δ-aminolevulinic acid (ALA). [3][4][5][6][7] Significant improvement in survival has been demonstrated in patients with high-grade glioma, 7,8 even using qualitative visual assessment of the PpIX fluorescence to identify residual tumor after white-light resection, and we have previously reported on preclinical and clinical techniques to quantify the absolute PpIX concentration in the tissue at the time of surgery, using either a point probe spectroscopy technique 6,[9][10][11][12][13][14][15][16] or wide-field quantitative imaging of the tissue surface. 5,[17][18][19][20][21] In this and other clinical applications, the ability to detect fluorescent tumor foci lying significantly below the surface of the surgical cavity could further increase the completeness of tumor resection to impact survival and also improve patient safety by minimizing the need for blind exploratory resection.…”

mentioning

confidence: 99%

Macroscopic optical imaging technique for wide-field estimation of fluorescence depth in optically turbid media for application in brain tumor surgical guidance

et al. 2015

Self Cite

View full text Add to dashboard Cite

Abstract. A diffuse imaging method is presented that enables wide-field estimation of the depth of fluorescent molecular markers in turbid media by quantifying the deformation of the detected fluorescence spectra due to the wavelength-dependent light attenuation by overlying tissue. This is achieved by measuring the ratio of the fluorescence at two wavelengths in combination with normalization techniques based on diffuse reflectance measurements to evaluate tissue attenuation variations for different depths. It is demonstrated that fluorescence topography can be achieved up to a 5 mm depth using a near-infrared dye with millimeter depth accuracy in turbid media having optical properties representative of normal brain tissue. Wide-field depth estimates are made using optical technology integrated onto a commercial surgical microscope, making this approach feasible for real-world applications.

show abstract

Adjuncts for Maximizing Resection

Cited by 18 publications

References 13 publications

Preclinical evaluation of spatial frequency domain-enabled wide-field quantitative imaging for enhanced glioma resection

Preclinical evaluation of spatial frequency domain-enabled wide-field quantitative imaging for enhanced glioma resection

In vivo visualization of GL261-luc2 mouse glioma cells by use of Alexa Fluor–labeled TRP-2 antibodies

Macroscopic optical imaging technique for wide-field estimation of fluorescence depth in optically turbid media for application in brain tumor surgical guidance

Contact Info

Product

Resources

About