Impact of the Combination of 5-Aminolevulinic Acid–Induced Fluorescence with Intraoperative Magnetic Resonance Imaging–Guided Surgery for Glioma

Tsugu, Atsushi; Ishizaka, Hideo; Mizokami, Yoshihito; Osada, Takahiro; Baba, Tetsuya; Yoshiyama, Michitsura; Nishiyama, Jun; Matsumae, Mitsunori

doi:10.1016/j.wneu.2011.02.005

Cited by 106 publications

(60 citation statements)

References 27 publications

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“…However, due to these studies' small sample sizes no final conclusion can be drawn. 4,28 In our opinion the combined use of both techniques might increase safety of 5-ALA-guided resection close to eloquent areas and would overcome the issue of missed fluorescence in concealed regions of the resection cavity. Furthermore, the lower specificity of 5-ALA in comparison with iMRI would be balanced.…”

Section: Metastatic Lesionsmentioning

confidence: 94%

Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA–enhanced intraoperative MRI at the border of contrast-enhancing lesions: a prospective study based on histopathological assessment

Coburger¹,

Engelke²,

Scheuerle

et al. 2014

FOC

115

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Object High-grade gliomas (HGGs) and metastasis (MET) are the most common intracranial lesions in neurosurgical routine. Both of them show an invasive growth pattern extending into neural tissue beyond the margins of contrast enhancement on MRI. These “undetected” areas might be the origin of early tumor recurrence. The aim of the present study was to evaluate whether 5-aminolevulinic acid (5-ALA) fluorescence provides an additional benefit in detection of invasive tumor compared with intraoperative MRI (iMRI). Methods The authors prospectively enrolled 45 patients harboring contrast-enhancing lesions, in whom gross-total resection was intended. All patients had surgery in which iMRI and 5-ALA–guided resection were used following a specific protocol. First, a typical white light tumor resection was performed. Then, spatial location of residual fluorescence was marked. After that, an iMRI was performed and residual uptake of contrast was marked. Navigated biopsy samples were taken from all marked areas and from additional sites according to the surgeon's judgment. Cross tables and receiver operating characteristic curves were calculated, assessing performance of the imaging methods for tumor detection alone and for combined detection of infiltration zone and solid tumor (pathological tissue). Also, correlations of histopathological findings with imaging results were tested using Spearman rho. Results Thirty-four patients with HGGs and 11 with METs were enrolled. Three patients harboring a MET showed no 5-ALA enhancement and were excluded; 127 histopathological samples were harvested in the remaining patients. In HGG, sensitivity for tumor detection was significantly higher (p < 0.001) in 5-ALA (0.85) than in iMRI (0.41). Specificity was significantly lower (p < 0.001) in 5-ALA (0.43) than in iMRI (0.70). For detection of pathological tissue, 5-ALA significantly exceeded iMRI in specificity (0.80 vs 0.60) and sensitivity (0.91 vs 0.66) (p < 0.001). Imaging results of iMRI and 5-ALA did not correlate significantly; only 5-ALA showed a significant correlation with final histopathological diagnosis of the specimen and with typical histopathological features of HGGs. In METs, sensitivity and specificity for tumor detection were equal in 5-ALA and iMRI. Both techniques showed high values for sensitivity (0.75) and specificity (0.80). The odds ratio for detection of tumor tissue was 12 for both techniques. Concerning pathological tissue, no statistically significant difference was found either. Imaging results of iMRI and 5-ALA correlated significantly (p < 0.022), as with final histopathological diagnosis in METs. Conclusions In METs, due to the rate of nonenhancing lesions, the authors found no additional benefit of 5-ALA compared with iMRI. In HGG, imaging results of 5-ALA and iMRI are significantly different at the border zone; 5-ALA has a higher sensitivity and a lower specificity for tumor detection than Gd-DTPA–enhanced iMRI. For detection of infiltrating tumor at the border of the resection cavity, 5-ALA is superior to Gd-DTPA–enhanced iMRI concerning both sensitivity and specificity. Thus, use of 5-ALA in addition to iMRI might be beneficial to maximize extent of resection. Clinical synergistic effects will be evaluated in a prospective randomized trial.

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Section: Metastatic Lesionsmentioning

confidence: 94%

Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA–enhanced intraoperative MRI at the border of contrast-enhancing lesions: a prospective study based on histopathological assessment

Coburger¹,

Engelke²,

Scheuerle

et al. 2014

FOC

115

View full text Add to dashboard Cite

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“…To achieve the most durable long-term survival benefit for patients with gliomas, complete eradication of tumors while sparing the normal brain parenchyma remains the most challenging task for neurosurgeons (3,6,14,15). Because of this daunting task in patients with gliomas, numerous intraoperative imaging-guided surgical techniques have been developed in an effort to extend survival and improve quality of life (5,6,12,25,26). Use of a single imaging modality to guide surgery has inherent limitations and disadvantages.…”

Section: Experimental Studies: Motexafin Gadolinium-enhanced Moleculamentioning

confidence: 99%

Gliomas: Motexafin Gadolinium-enhanced Molecular MR Imaging and Optical Imaging for Potential Intraoperative Delineation of Tumor Margins

Qiu¹,

zhang²,

Shi³

et al. 2016

Radiology

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“…15,16 In Tsugu et al's study, comparison of intraoperative MRI and the 5-aminolevulinic acid (5-ALA)-guided fluorescence imaging showed that for 5-ALA-induced fluorescence-positive gliomas (including almost all the malignant gliomas), good resection effects were obtained only with 5-ALA fluorescence imagingguided resection. 17 However, conventional 5-ALA fluorescence imaging-guided surgery had a plurality of side effects, such as skin photosensitivity, and protoporphyrin IX was not produced in all the gliomas, especially in low-grade gliomas, after oral administration of the 5-ALA. 18,19 Small-molecule fluorescent probes have been applied widely in biomedical fields, due to their good optical properties and excellent biocompatibility, wherein the near-infrared fluorescent (NIRF) dye is generally adopted for optical imaging in vivo so as to minimize autofluorescence of the tissue and acquire deep penetration. Among various NIRF dyes, Cy5.5 is widely used in the biological field, due to its high molar absorbancy index, high fluorescence quantum yield, and no photosensitivity.…”

Section: +mentioning

confidence: 99%

Glioma-targeting micelles for optical/magnetic resonance dual-mode imaging

Zhou¹,

Mu²,

Jiang³

et al. 2015

IJN

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Surgical resection is the primary mode for glioma treatment, while gross total resection is difficult to achieve, due to the invasiveness of the gliomas. Meanwhile, the tumor-resection region is closely related to survival rate and life quality. Therefore, we developed optical/magnetic resonance imaging (MRI) bifunctional targeted micelles for glioma so as to delineate the glioma location before and during operation. The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol- block -polycaprolactone (PEG- b -PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the glioma-targeting ligand lactoferrin (Lf). Being encapsulated by PEG- b -PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity ( r 2 ) of micelles was 215.4 mM −1 ·s −1 , with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG- b -PCL for avoiding the fluorescence quenching caused by SPIONs. The in vivo results indicated that the nanoparticles with Lf accumulated efficiently in glioma cells and prolonged the duration of hypointensity at the tumor site over 48 hours in the MR image compared to the nontarget group. Corresponding with the MRI results, the margin of the glioma was clearly demarcated in the fluorescence image, wherein the average fluorescence intensity of the tumor was about fourfold higher than that of normal brain tissue. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0–100 μg/mL. In general, these optical/MRI bifunctional micelles can specifically target the glioma and provide guidance for surgical resection of the glioma before and during operation.

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Impact of the Combination of 5-Aminolevulinic Acid–Induced Fluorescence with Intraoperative Magnetic Resonance Imaging–Guided Surgery for Glioma

Cited by 106 publications

References 27 publications

Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA–enhanced intraoperative MRI at the border of contrast-enhancing lesions: a prospective study based on histopathological assessment

Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA–enhanced intraoperative MRI at the border of contrast-enhancing lesions: a prospective study based on histopathological assessment

Gliomas: Motexafin Gadolinium-enhanced Molecular MR Imaging and Optical Imaging for Potential Intraoperative Delineation of Tumor Margins

Glioma-targeting micelles for optical/magnetic resonance dual-mode imaging

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