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Maria Teresa Pedro, Gregor Antoniadis, Angelika Scheuerle, Mirko Pham, Christian Rainer Wirtz and Ralph W. Koenig

The diagnostic workup and surgical therapy for peripheral nerve tumors and tumorlike lesions are challenging. Magnetic resonance imaging is the standard diagnostic tool in the preoperative workup. However, even with advanced pulse sequences such as diffusion tensor imaging for MR neurography, the ability to differentiate tumor entities based on histological features remains limited. In particular, rare tumor entities different from schwannomas and neurofibromas are difficult to anticipate before surgical exploration and histological confirmation. High-resolution ultrasound (HRU) has become another important tool in the preoperative evaluation of peripheral nerves. Ongoing software and technical developments with transducers of up to 17–18 MHz enable high spatial resolution with tissue-differentiating properties. Unfortunately, high-frequency ultrasound provides low tissue penetration. The authors developed a setting in which intraoperative HRU was used and in which the direct sterile contact between the ultrasound transducer and the surgically exposed nerve pathology was enabled to increase structural resolution and contrast. In a case-guided fashion, the authors report the sonographic characteristics of rare tumor entities shown by intraoperative HRU and contrast-enhanced ultrasound.

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Jan Coburger, Jens Engelke, Angelika Scheuerle, Dietmar R. Thal, Michal Hlavac, Christian Rainer Wirtz and Ralph König


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).


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.


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.


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.