Matthias Millesi

Analysis of 5-aminolevulinic acid–induced fluorescence in 55 different spinal tumors

OBJECT Subtotal resection (STR) of spinal tumors can result in tumor recurrence. Currently, no clinically reliable marker is available for intraoperative visualization of spinal tumor tissue. Protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) is capable of visualizing malignant gliomas. Fluorescence-guided resections of malignant cerebral gliomas using 5-ALA have resulted in an increased rate of complete tumor removal. Recently, the application of 5-ALA has also been described in the first cases of spinal tumors. Therefore, the aim of this observational study was to systematically investigate 5-ALA-induced fluorescence characteristics in different spinal tumor entities. METHODS Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of PpIX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification. RESULTS Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy. CONCLUSIONS In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci.

Local image variance of 7 Tesla SWI is a new technique for preoperative characterization of diffusely infiltrating gliomas: correlation with tumour grade and IDH1 mutational status

ObjectivesTo investigate the value of local image variance (LIV) as a new technique for quantification of hypointense microvascular susceptibility-weighted imaging (SWI) structures at 7 Tesla for preoperative glioma characterization.MethodsAdult patients with neuroradiologically suspected diffusely infiltrating gliomas were prospectively recruited and 7 Tesla SWI was performed in addition to standard imaging. After tumour segmentation, quantification of intratumoural SWI hypointensities was conducted by the SWI-LIV technique. Following surgery, the histopathological tumour grade and isocitrate dehydrogenase 1 (IDH1)-R132H mutational status was determined and SWI-LIV values were compared between low-grade gliomas (LGG) and high-grade gliomas (HGG), IDH1-R132H negative and positive tumours, as well as gliomas with significant and non-significant contrast-enhancement (CE) on MRI.ResultsIn 30 patients, 9 LGG and 21 HGG were diagnosed. The calculation of SWI-LIV values was feasible in all tumours. Significantly higher mean SWI-LIV values were found in HGG compared to LGG (92.7 versus 30.8; p < 0.0001), IDH1-R132H negative compared to IDH1-R132H positive gliomas (109.9 versus 38.3; p < 0.0001) and tumours with significant CE compared to non-significant CE (120.1 versus 39.0; p < 0.0001).ConclusionsOur data indicate that 7 Tesla SWI-LIV might improve preoperative characterization of diffusely infiltrating gliomas and thus optimize patient management by quantification of hypointense microvascular structures.Key Points• 7 Tesla local image variance helps to quantify hypointense susceptibility-weighted imaging structures.• SWI-LIV is significantly increased in high-grade and IDH1-R132H negative gliomas.• SWI-LIV is a promising technique for improved preoperative glioma characterization.• Preoperative management of diffusely infiltrating gliomas will be optimized.

De Novo Aneurysm Formation at the Anastomosis Site Incidentally Detected 2 Years after Single-Barrel STA-MCA Bypass Surgery: Case Report and Review of the Literature

This case report describes the de novo aneurysm formation at the anastomosis site 2 years after single-barrel superficial temporal artery to middle cerebral artery bypass surgery. Correct bypass patency and morphology of the anastomosis site was documented intraoperatively and immediately postoperatively by indocyanine green videoangiography and digital subtraction angiography (DSA). Aneurysmatic dilatation at the anastomosis site was observed 2 years postoperatively upon computed tomography angiographic follow-up examination. After repeat DSA, the patient underwent microsurgical reexploration and clip ligation of the aneurysmatic portion of the donor artery. The possible underlying mechanisms are discussed and the current literature is reviewed.

Systematic histopathological analysis of different 5-aminolevulinic acid–induced fluorescence levels in newly diagnosed glioblastomas

OBJECTIVE Glioblastoma (GBM) is characterized by distinct intratumoral histopathological heterogeneity with regard to variable tumor morphology, cell proliferation, and microvascularity. Maximum resection of a GBM results in an improved prognosis and thus represents the aim of surgery in the majority of cases. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is currently widely applied for improved intraoperative tumor visualization in patients with a GBM. Three intratumoral fluorescence levels (i.e., strong, vague, or no fluorescence) can usually be distinguished during surgery. So far, however, their exact histopathological correlates and their surgical relevance have not been clarified sufficiently. Thus, the aim of this study was to systematically analyze tissue samples from newly diagnosed GBMs with different fluorescence levels according to relevant histopathological parameters. METHODS This prospective study recruited patients who underwent 5-ALA fluorescence-guided resection of a newly diagnosed radiologically suspected GBM. Each patient received 5-ALA approximately 3 hours before surgery, and a modified neurosurgical microscope was applied for intraoperative visualization of 5-ALA-induced fluorescence. During surgery, tissue samples with strong, vague, or no fluorescence were collected. For each sample, the presence of tumor tissue, quality of tissue (compact, infiltrative, or no tumor), histopathological criteria of malignancy (cell density, nuclear pleomorphism, mitotic activity, and presence of microvascular proliferation/necrosis), proliferation rate (MIB-1 labeling index [LI]), and microvessel density (using CD34 staining) were investigated. RESULTS Altogether, 77 patients with a newly diagnosed, histopathologically confirmed GBM were included, and 131 samples with strong fluorescence, 69 samples with vague fluorescence, and 67 samples with no fluorescence were collected. Tumor tissue was detected in all 131 (100%) of the samples with strong fluorescence and in 65 (94%) of the 69 samples with vague fluorescence. However, mostly infiltrative tumor tissue was still found in 33 (49%) of 67 samples despite their lack of fluorescence. Strong fluorescence corresponded to compact tumors in 109 (83%) of 131 samples, whereas vague fluorescence was consistent with infiltrative tumors in 44 (64%) of 69 samples. In terms of the histopathological criteria of malignancy, a significant positive correlation of all analyzed parameters comprising cell density, nuclear pleomorphism, mitotic activity, microvascular proliferation, and necrosis with the 3 fluorescence levels was observed (p < 0.001). Furthermore, the proliferation rate significantly and positively correlated with strong (MIB-1 LI 28.3%), vague (MIB-1 LI 16.7%), and no (MIB-1 LI 8.8%) fluorescence (p < 0.001). Last, a significantly higher microvessel density was detected in samples with strong fluorescence (CD34 125.5 vessels/0.25 mm2) than in those with vague (CD34 82.8 vessels/0.25 mm2) or no (CD34 68.6 vessels/0.25 mm2) fluorescence (p < 0.001). CONCLUSIONS Strong and vague 5-ALA-induced fluorescence enables visualization of intratumoral areas with specific histopathological features and thus supports neurosurgeons in improving the extent of resection in patients with a newly diagnosed GBM. Despite the lack of fluorescence, tumor tissue was still observed in approximately half of the cases. To overcome this current limitation, the promising approach of complementary spectroscopic measurement of fluorescence should be investigated further.

The Superior Thalamic Vein and its Variations: A Proposed Classification

BACKGROUND The superior thalamic vein (STV) was first described comprehensively by Ferner in 1958 as the most prominent thalamic vein; it originates from the central superior portion of the thalamus, coursing medially to the third ventricular thalamic surface, where it turns posteriorly to parallel the internal cerebral vein (ICV) before ending into its posterior portion. Since historical anatomic and angiographic studies in the pre-computed tomography (CT)/magnetic resonance imaging era, the STV has not been investigated. OBJECTIVE To describe the anatomic course of the STV with its variations, and to propose a classification system based on its draining pattern. METHODS We retrospectively screened our imaging database for 50 patients who had a CT-angiography with predefined parameters. The images were independently reviewed by 3 neurosurgeons and 1 neuroradiologist to classify the STV into 4 types: type 1A-drainage into the anterior portion of the ICV, type 1B-drainage into the posterior portion of the ICV, type 2-drainage into the vein of Rosenthal, type 3-drainage into a medial (3A) or lateral (3B) atrial vein, and type 4-drainage into the vein of Galen. RESULTS In 50 patients, we could identify 96 STVs. In 2 hemispheres, the STV was doubled. The 92 single STVs were classified as type 1A in 25 hemispheres (27.2%), type 1B in 45 (48.9%), type 2 in 12 (13.0%), type 3A in 8 (8.7%), type 3B in 1 (1.1%), and type 4 in 1 (1.1%). CONCLUSION The draining pattern of the STV varies widely from the initial description.

Commentary: Giuseppe Campani (1635-1715, Rome, Italy): the First Use of a Microscope in Medicine and Surgery

Abstract Giuseppe Campani (1635‐1715) was a polymath in Rome, Italy, during the Scientific Revolution in the XVIIth century. In particular, he forged the screw barrel microscope and was manufacturing his own lenses for microscopes and telescopes. He mastered the art of lens grinding. Those lenses have been analyzed with modern methods and turned out to be of extremely good quality, shining light on the fact that Giuseppe Campani mastered the theories of optics. Moreover, in a letter that Giuseppe Campani sent to Pope Innocent XI, he clearly described the use of a microscope for the examination of wounds of legs. This letter dates back to 15 August 1686 and is the first evidence of the use of microscopes to analyze wounds, sores, and anatomic specimens in medical and surgical settings. MG Yasargil previously showed the lithography accompanying this letter and was the first to recognize its great importance. We accessed this original letter in the Vatican Library, and for the first time we have translated it from Latin to English in order to unveil its significance in the context of the Scientific Revolution and the history of medicine and surgery.