Andrea Bink

Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial.

BACKGROUND Intraoperative MRI is increasingly used in neurosurgery, although there is little evidence for its use. We aimed to assess efficacy of intraoperative MRI guidance on extent of resection in patients with glioma. METHODS In our prospective, randomised, parallel-group trial, we enrolled adults (≥18 years) with contrast enhancing gliomas amenable to radiologically complete resection who presented to Goethe University (Frankfurt, Germany). We randomly assigned patients (1:1) with computer-generated blocks of four and a sealed-envelope design to undergo intraoperative MRI-guided surgery or conventional microsurgery (control group). Surgeons and patients were unmasked to treatment group allocation, but an independent neuroradiologist was masked during analysis of all preoperative and postoperative imaging data. The primary endpoint was rate of complete resections as established by early postoperative high-field MRI (1·5 T or 3·0 T). Analysis was done per protocol. This study is registered with ClinicalTrials.gov, number NCT01394692. FINDINGS We enrolled 58 patients between Oct 1, 2007, and July 1, 2010. 24 (83%) of 29 patients randomly allocated to the intraoperative MRI group and 25 (86%) of 29 controls were eligible for analysis (four patients in each group had metastasis and one patient in the intraoperative MRI group withdrew consent after randomisation). More patients in the intraoperative MRI group had complete tumour resection (23 [96%] of 24 patients) than did in the control group (17 [68%] of 25, p=0·023). Postoperative rates of new neurological deficits did not differ between patients in the intraoperative MRI group (three [13%] of 24) and controls (two [8%] of 25, p=1·0). No patient for whom use of intraoperative MRI led to continued resection of residual tumour had neurological deterioration. One patient in the control group died before 6 months. INTERPRETATION Our study provides evidence for the use of intraoperative MRI guidance in glioma surgery: such imaging helps surgeons provide the optimum extent of resection. FUNDING None.

Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Clinical article.

OBJECT Accumulating data suggest more aggressive surgery in patients with malignant glioma to improve outcome. However, extended surgery may increase morbidity. The randomized Phase III 5-aminolevulinic acid (ALA) study investigated 5-ALA-induced fluorescence as a tool for improving resections. An interim analysis demonstrated more frequent complete resections with longer progression-free survival (PFS). However, marginal differences were found regarding neurological deterioration and the frequency of additional therapies. Presently, the authors focus on the latter aspects in the final study population, and attempt to determine how safety might be affected by cytoreductive surgery. METHODS Patients with malignant gliomas were randomized for fluorescence-guided (ALA group) or conventional white light (WL) (WL group) microsurgery. The final intent-to-treat population consisted of 176 patients in the ALA and 173 in the WL group. Primary efficacy variables were contrast-enhancing tumor on early MR imaging and 6-month PFS. Among secondary outcome measures, the National Institutes of Health Stroke Scale (NIH-SS) score and the Karnofsky Performance Scale (KPS) score were used for assessing neurological function. RESULTS More frequent complete resections and improved PFS were confirmed, with higher median residual tumor volumes in the WL group (0.5 vs 0 cm(3), p = 0.001). Patients in the ALA group had more frequent deterioration on the NIH-SS at 48 hours. Patients at risk were those with deficits unresponsive to steroids. No differences were found in the KPS score. Regarding outcome, a combined end point of risks and neurological deficits was attempted, which demonstrated results in patients in the ALA group to be superior to those in participants in the WL group. Interestingly, the cumulative incidence of repeat surgery was significantly reduced in ALA patients. When stratified by completeness of resection, patients with incomplete resections were quicker to deteriorate neurologically (p = 0.0036). CONCLUSIONS Extended resections performed using a tool such as 5-ALA-derived tumor fluorescence, carries the risk of temporary impairment of neurological function. However, risks are higher in patients with deficits unresponsive to steroids.

5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging.

BACKGROUND: 5-Aminolevulinic acid is used for fluorescence-guided resections. During resection, different macroscopic fluorescence qualities (“strong,” “weak”) can be distinguished that help guide resections. OBJECTIVE: This prospective study was designed to assess the reliability of visible fluorescence qualities by spectrometry, pathology, and imaging. METHODS: Thirty-three patients with malignant gliomas received 5-aminolevulinic acid (20 mg/kg). After debulking surgery, standardized biopsies were obtained from tissues with “weak” and “strong” fluorescence and from nonfluorescing near and distant brain for blinded assessment of cell density and tissue type (necrosis, solid or infiltrating tumor, normal tissue). The positive predictive value was calculated. Unresected fluorescing tissue was navigated for blinded correlation to postoperative magnetic resonance imaging (MRI). Receiver operating characteristic curves were generated for assessing the classification efficiency of spectrometry. RESULTS: “Strong” fluorescence corresponded to greater spectrometric fluorescence, solidly proliferating tumor, and high cell densities, whereas “weak” fluorescence corresponded to lower spectrometric fluorescence, infiltrating tumor, and medium cell densities. The positive predictive value was 100% in strongly fluorescing tissue and 95% in weakly fluorescing tissue. Spectrometric fluorescence was detected in marginal tissue without macroscopic fluorescence. Depending on the threshold, spectrometry displayed greater sensitivity but lower specificity (accuracy 88.4%). Residual MRI enhancement in the tumor bed was detected in 15 of 23 (65%) patients with residual fluorescence, but in none of the patients without residual fluorescence. CONCLUSION: Macroscopic fluorescence qualities predict solid and infiltrating tumor, providing useful information during resection. Fluorescence appears superior to contrast enhancement on MRI for indicating residual tumor. Spectrometry, on the other hand, is more sensitive but less specific, depending on threshold definition. ABBREVIATIONS: 5-ALA, 5-aminolevulinic acid CI, confidence interval gamma-GT, gamma-glutamyl transpeptidase GBM, glioblastoma multiforme NPV, negative predictive value PPIX, protoporphyrin IX PPV, positive predictive value SD, standard deviation WHO, World Health Organization

Low field intraoperative MRI-guided surgery of gliomas: A single center experience

INTRODUCTION The aim of this article is to report on our experience in using a low field intraoperative MRI (iMRI) system in glioma surgery and to summarize the hitherto use and benefits of iMRI in glioma surgery. PATIENTS AND METHODS Between July 2004 and May 2009, a total of 103 patients harboring gliomas underwent tumor resection with the use of a mobile low field iMRI in our institution. Surgeries were performed as standard micro-neurosurgical procedures using regular instrumentarium. All patients underwent early postoperative high field MRI to determine the extent of resection. Adjuvant treatment was conducted according to histopathological grading and standard of care. RESULTS All tumors could be reliably visualized on intraoperative imaging. Intraoperative imaging revealed residual tumor tissue in 51 patients (49.5%), leading to further tumor resection in 31 patients (30.1%). Extended resection did not translate into a higher rate of neurological deficits. When analyzing survival of patients with glioblastoma, patients undergoing complete tumor resection did significantly better than patients with residual tumor (50% survival rate at 57.8 weeks vs. 33.8 weeks, log rank test p=0.003), while younger age did not influence survival (p=0.12). CONCLUSION Low field iMRI is a helpful tool in modern neurosurgery and facilitates brain tumor resection to a maximum safe extent. Its use translates into a better prognosis for these patients with devastating tumors. Future studies covering the use of iMRI will need to be conducted in a prospective, randomized fashion to prove the true benefit of iMRI in glioma surgery.

Detection of lesions in multiple sclerosis by 2D FLAIR and single-slab 3D FLAIR sequences at 3.0 T: initial results

The aim of this study was to compare conventional 2D FLAIR and single-slab 3D FLAIR sequences in the detection of lesions in patients with multiple sclerosis. Eight patients with MS were examined at 3.0 T by using a 2D FLAIR sequence and a single-slab 3D FLAIR sequence. A comparison of lesion detectability was performed for the following regions: periventricular, nonperiventricular/juxtacortical and infratentorial. The contrast-to-noise ratios (CNRs) between lesions and brain tissue and CSF were calculated for each sequence. A total of 424 lesions were found using the 2D FLAIR sequence, while with the 3D FLAIR sequence 719 lesions were found. With the 2D FLAIR sequence, 41% fewer lesions were detected than with the 3D FLAIR sequence. Further, 40% fewer supratentorial and 62.5% fewer infratentorial lesions were found with the 2D FLAIR sequence. In images acquired with the 3D FLAIR sequence, the lesions had significantly higher CNRs than in images acquired with the 2D FLAIR sequence. These are the first results using a single-slab 3D FLAIR sequence at 3.0 T for detection of lesions in patients with MS. With the 3D FLAIR sequence significantly higher CNRs were achieved and significantly more lesions in patients with MS were detected.

Long-Term Outcome after Coil Embolization of Cavernous Sinus Arteriovenous Fistulas

BACKGROUND AND PURPOSE: Cranial nerve palsies are regularly observed in patients with arteriovenous fistulas of the cavernous sinus. The purpose of our study was to determine the long-term clinical outcome—with a special focus on extra-ocular muscular dysfunctions—in patients who had undergone endovascular treatment of a cavernous sinus fistula with detachable coils. MATERIALS AND METHODS: Sixteen patients were recalled for an ophthalmoneurologic control examination (mean interval of 4.4 years). The mRS and the EQ-5D questionnaire were used for the description of general outcome. Age, duration of symptoms, character of the fistula (direct, dural), and coil volume were tested to assess their relevance for persistent symptoms. RESULTS: All patients displayed complete regression of chemosis, exophthalmus, and pulsating tinnitus with no evidence of recurrences. Oculomotor disturbances persisted in 9 of 13 patients and caused permanent diplopia in 7 patients. In 15 patients a mRS score of 1 or 2 was achieved; however, 7 patients reported some limitations in life quality (EQ-5D). A significant correlation was found between coil volume and persistent diplopia (P = .032) and persistent cranial nerve VI paresis (P = .037). CONCLUSIONS: Coil embolization of the cavernous sinus led to durable closure of AVF and reliable regression of acute symptoms. However, long-term follow-up showed a 44% rate of persistent cranial nerve deficits with disturbances of oculomotor and visual functions. This may be explained by the underlying fistula size itself and/or the space-occupying effect of the coils. As neuro-ophthalmologic outcome is crucial for control of therapeutic success, patients should be routinely examined by ophthalmologists.

Glioma Extent of Resection and Ultra-Low-Field iMRI: Interim Analysis of a Prospective Randomized Trial

Aiming at providing high-class evidence regarding the use of intraoperative MRI (ioMRI), we are conducting a prospective randomized controlled trial. Adult patients with contrast enhancing lesions suspicious of malignant gliomas scheduled to undergo radiologically complete tumor resection are eligible to enter this trial. After giving their informed consent, patients are randomized to undergo either ioMRI-guided or conventional microneurosurgical tumor resection. To assess the extent of resection, pre- and early postoperative high-field MR images are obtained to perform volumetric analyses. Primary endpoint of the study is the rate of radiologically complete tumor resections. After the inclusion of 35 patients, we performed an interim analysis. In six patients, histopathological examination revealed metastases, so they were excluded from further analyses. Thus, data from 29 patients with gliomas could be analyzed. There were no significant differences in patient age (P=0.28) or preoperative tumor sizes (P=0.40) between the two treatment groups. We observed a trend towards a higher rate of complete tumor resections in the ioMRI-group compared to the control group (P=0.07). Postoperative tumor volumes were significantly lower in the ioMRI-group than in the control group (P<0.05). The use of ioMRI appears to be associated with a higher rate of radiographically complete as well as near total tumor resections compared to conventional microneurosurgery.

Clinical aspects of the apparent diffusion coefficient in 3He MRI: Results in healthy volunteers and patients after lung transplantation

To measure the apparent diffusion coefficient (ADC) after inhalation of hyperpolarized 3He in healthy volunteers and lung transplant recipients, and demonstrate the gravity dependence of ADC values.

Coil embolization of cavernous sinus in patients with direct and dural arteriovenous fistula

To determine technical success and acute complication rates after endovascular coil packing of the cavernous sinus. Nineteen patients presented with either direct (13) or dural (6) arteriovenous fistula (AVF) and were treated by means of coil embolization of the cavernous sinus. The aim of treatment was complete obliteration of the fistula. In a retrospective study, the degree of obliteration, regression of symptoms as well as complication rates were evaluated. Initial complete obliteration was achieved in 12 patients, subtotal occlusion of the sinus in 6 and incomplete packing with major residual fistula in 1 of the patients. Retreatment was successfully performed in two patients with early recurrence of AVF. Follow-up showed complete occlusion rates in 16 and subtotal obliteration in 3 patients. Chemosis and exophthalmus regressed rapidly in all affected patients. Persistence of cranial nerve deficits was observed in 11 cases. Postinterventional thrombosis of the ophthalmic vein was the only major acute complication (n = 2). Coil embolization of the cavernous sinus in cases with AVF is a complex procedure that is technically feasible and safe in the majority of cases. Adequate anticoagulation is recommended to avoid thrombembolic complications. Long-term outcome has to be determined by further studies.

Benefits of contrast-enhanced SWI in patients with glioblastoma multiforme.

AbstractIntroductionSWI can help to identify high-grade gliomas (HGG). The objective of this study was to analyse SWI and CE-SWI characteristics, i.e. the relationship between contrast-induced phase shifts (CIPS) and intratumoral susceptibility signals (ITSS) and their association with tumour volume in patients with glioblastoma multiforme (GBM).Materials and methodsMRI studies of 29 patients were performed to evaluate distinct susceptibility signals comparing SWI and CE-SWI characteristics. The relationship between these susceptibility signals and CE-T1w tumour volume was analysed by using Spearman’s rank correlation coefficient and Kruskal-Wallis-test. Tumour biopsies of different susceptibility signals were performed in one patient.ResultsComparison of SWI and CE-SWI demonstrated different susceptibility signals. Susceptibility signals visible on SWI images are consistent with ITSS; those only seen on CE-SWI were identified as CIPS. Correlation with CE-T1w tumour volume revealed that CIPS were especially present in small or medium-sized GBM (Spearman’s rho r = 0.843, P < 0.001). Histology identified the area with CIPS as the tumour invasion zone, while the area with ITSS represented micro-haemorrhage, highly pathological vessels and necrosis.ConclusionCE-SWI adds information to the evaluation of GBM before therapy. It might have the potential to non-invasively identify the tumour invasion zone as demonstrated by biopsies in one case.Key Points• MRI is used to help differentiate between low- and high-grade gliomas. • Contrast-enhanced susceptibility-weighted MRI (CE-SWI) helps to identify patients with glioblastoma multiforme. • CE-SWI delineates the susceptibility signal (CIPS and ITSS) more than the native SWI. • CE-SWI might have the potential to non-invasively identify the tumour invasion zone.