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

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>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).</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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 &lt; 0.001) in 5-ALA (0.85) than in iMRI (0.41). Specificity was significantly lower (p &lt; 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 &lt; 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 &lt; 0.022), as with final histopathological diagnosis in METs.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p></jats:sec>

Accuracy of High-Field Intraoperative MRI in the Detectability of Residual Tumor in Glioma Grade IV Resections

“…In accordance with Coburger et al and Akbari et al, [1,28,29] we believe that a multimodality approach including T2, FLAIR, DTI and spectroscopic imaging as well as dynamic T1-weighted imaging will further improve the sensitivity and specificity of ioMRI and might lead to an improved detection rate and that advanced imaging like dynamic T1-weighed imaging might increase the accura-▶ Table 2 The sensitivity for all tumors was calculated as 95 % and the specificity as 69.5 %. The negative predictive value was 88 %, and the positive predictive value was 86 %.…”

“…Improved resection grade of contrast-enhancing tissue [1 -7] prolongs the patient survival rate and preserves eloquent brain function and life quality [1 -9]. Studies dealing with the accuracy of fluorescence-guided resection detected a sensitivity of about 90 % and a negative predictive value of 76 -91 % [1,10,11]. However a negative predictive value of 0.26 in the study of Roberts et al also showed that there are deficits in fluorescence-guided resection with respect to the detection of residual tumorous tissue in normal appearing resection borders [11] so that there is a need for additional intraoperative resection control.…”

The Use of 5-ALA in Glioblastoma Resection: Two Cases with Long-Term Progression-Free Survival

“…Aldave and colleagues found that patients who underwent 5-ALA-FGR beyond what was seen on contrast-enhancing MRIs had longer overall survival compared with patients with residual fluorescent tissue [16]. Moreover, Coburger, et al [17] have recently demonstrated that 5-ALA is superior to Gd-DTPA-enhanced iMRI for detection of infiltrating tumor at the border of the resection cavity. These studies indicate that resections beyond the 5-ALA-positive tissue can prolong survival in GBM patients.…”

Editorial: Use of 5-aminolevulinic acid helps see the way beyond MRI

“…Coburger et al 2 present the results of a study in which they demonstrate that 5-aminolevulinic acid (5-ALA) is superior to Gd-DTPA-enhanced intraoperative MRI for histological tumor detection during the course of resection for high-grade gliomas. It doesn't seem to make a difference for metastatic tumors, which is not surprising.…”