Finding the anaplastic focus in diffuse gliomas: The value of Gd-DTPA enhanced MRI, FET-PET, and intraoperative, ALA-derived tissue fluorescence
Introduction
Diffuse gliomas sometimes harbor anaplastic foci which determine final histopathological grading, are an indicator of prognosis and dictate adjuvant therapies such as radio- or chemotherapy. Undergrading as a consequence of sampling non-representative tumor may result in necessary therapies being deferred. Gadolinium-enhanced MRI is not always sensitive for detecting anaplastic foci. Metabolic imaging of brain tumors with radiolabeled amino acids has been shown to be a valuable complementary method to improve the diagnostic yield of anatomical radiological methods such as MRI [7], [10]. 18F-labeled amino acids such as O-(2-[18F]fluoroethyl)-l-tyrosine (FET) allow a widespread use of amino acid imaging due to the longer half-life of 18F (109 min vs. 20 min for 11C) [5], [11], [12], [17], [24]. A comparison of FET and MET imaging in patients with brain tumors showed a significant correlation of tumor-to-brain ratios and similar intracerebral kinetics for both tracers [23], [32]. In contrast to MRI alone, advantages of FET PET combined with MRI in the work-up for cerebral gliomas are improved guidance of biopsies, improved planning of surgery and radiation therapy, and the differentiation of tumor recurrence from unspecific post-therapeutic tissue changes [13], [16]. Furthermore, FET PET appears to be particularly valuable in the prognosis of low-grade gliomas [4].
On the other hand, 5-aminolevulinic acid (5-ALA) is a natural biochemical precursor of haemoglobin that elicits synthesis and accumulation of fluorescent porphyrins within malignant glioma tissue [24], [25], [29]. However, the value of fluorescence-guided resection in low grade gliomas and in low grade gliomas with anaplastic foci has not been determined so far. Conceivably, ALA-derived tumor fluorescence may be of value for intra-operative identification of “hot spots” visible on pre-operative imaging through FET-PET-hypermetabolism or contrast-enhancement on MRI. It was the aim of the present study to prospectively determine the interdependency of FET imaging, contrast-enhancement on MRI and intraoperative fluorescence findings in diffuse gliomas with or without focal enhancement.
Section snippets
Materials and methods
Between November 2004 and July 2008, MR imaging and FET PET investigations with subsequent biopsies during gross cytoreductive surgery were conducted in 30 patients with MR imaging suggestive for diffuse gliomas with or without areas of focal contrast-enhancement. All patients gave written informed consent for participation in diagnostic procedures and surgery. FET PET imaging and cytoreductive surgery using fluorescence-guided resections with 5-ALA was performed within 4 weeks of diagnosis.
Results
Mean patient age was 42.1 years. The tumor was located frontally in 16 patients, in the parietal lobe in 1 patient, temporally in 2 patients, in the insula in 2 patients and in more than one lobe in 8 patients (fronto-parietal, fronto-temporal, temporo-parietal). Furthermore, the gliomas were located in the left hemisphere in 17 patients and in the right hemispheres in 13 patients, accordingly. Tumor volume, as determined from the FLAIR image was less than 5 ml in all patients. Histological
Discussion
The aim of this study was to determine the interrelationship between FET uptake in low and high grade gliomas and 5-ALA-derived tissue fluorescence and thus to assess the usefulness of 5-ALA-derived fluorescence for identifying “hot spots” intra-operatively. If 5-ALA were to highlight “hot spots” identified on MRI by their contrast-enhancement or by FET-PET, this would reduce the worry of missing the hot spot and possibly undergrading a glioma.
Several authors have confirmed the usefulness of
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