Efficacy and Safety of Gadopiclenol for Contrast-Enhanced MRI of the Central Nervous System: The PICTURE Randomized Clinical Trial.

OBJECTIVES: Developing new high relaxivity gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) allowing dose reduction while maintaining similar diagnostic efficacy is needed, especially in the context of gadolinium retention in tissues. This study aimed to demonstrate that contrast-enhanced MRI of the central nervous system (CNS) with gadopiclenol at 0.05 mmol/kg is not inferior to gadobutrol at 0.1 mmol/kg, and superior to unenhanced MRI. MATERIALS AND METHODS: PICTURE is an international, randomized, double-blinded, controlled, cross-over, phase III study, conducted between June 2019 and September 2020. Adult patients with CNS lesions were randomized to undergo 2 MRIs (interval, 2-14 days) with gadopiclenol (0.05 mmol/kg) then gadobutrol (0.1 mmol/kg) or vice versa. The primary criterion was lesion visualization based on 3 parameters (border delineation, internal morphology, and contrast enhancement), assessed by 3 off-site blinded readers. Key secondary outcomes included lesion-to-background ratio, enhancement percentage, contrast-to-noise ratio, overall diagnostic preference, and adverse events. RESULTS: Of the 256 randomized patients, 250 received at least 1 GBCA administration (mean [SD] age, 57.2 [13.8] years; 53.6% women). The statistical noninferiority of gadopiclenol (0.05 mmol/kg) to gadobutrol (0.1 mmol/kg) was achieved for all parameters and all readers (n = 236, lower limit 95% confidence interval of the difference ≥-0.06, above the noninferiority margin [-0.35], P < 0.0001), as well as its statistical superiority over unenhanced images (n = 239, lower limit 95% confidence interval of the difference ≥1.29, P < 0.0001).Enhancement percentage and lesion-to-background ratio were higher with gadopiclenol for all readers ( P < 0.0001), and contrast-to-noise ratio was higher for 2 readers ( P = 0.02 and P < 0.0001). Three blinded readers preferred images with gadopiclenol for 44.8%, 54.4%, and 57.3% of evaluations, reported no preference for 40.7%, 21.6%, and 23.2%, and preferred images with gadobutrol for 14.5%, 24.1%, and 19.5% ( P < 0.001).Adverse events reported after MRI were similar for gadopiclenol (14.6% of patients) and gadobutrol (17.6%). Adverse events considered related to gadopiclenol (4.9%) and gadobutrol (6.9%) were mainly injection site reactions, and none was serious. CONCLUSIONS: Gadopiclenol at 0.05 mmol/kg is not inferior to gadobutrol at 0.1 mmol/kg for MRI of the CNS, confirming that gadopiclenol can be used at half the gadolinium dose used for other GBCAs to achieve similar clinical efficacy.

Therapy Defining at Initial Diagnosis of Primary Brain Tumor-The Role of 18F-FET PET/CT and MRI.

Primary malignant brain tumors are heterogeneous and infrequent neoplasms. Their classification, therapeutic regimen and prognosis have undergone significant development requiring the innovation of an imaging diagnostic. The performance of enhanced magnetic resonance imaging depends on blood-brain barrier function. Several studies have demonstrated the advantages of static and dynamic amino acid PET/CT providing accurate metabolic status in the neurooncological setting. The aim of our single-center retrospective study was to test the primary diagnostic role of amino acid PET/CT compared to enhanced MRI. Emphasis was placed on cases prior to intervention, therefore, a certain natural bias was inevitable. In our analysis for newly found brain tumors 18F-FET PET/CT outperformed contrast MRI and PWI in terms of sensitivity and negative predictive value (100% vs. 52.9% and 36.36%; 100% vs. 38.46% and 41.67%), in terms of positive predictive value their performance was roughly the same (84.21 % vs. 90% and 100%), whereas regarding specificity contrast MRI and PWI were superior (40% vs. 83.33% and 100%). Based on these results the superiority of 18F-FET PET/CT seems to present incremental value during the initial diagnosis. In the case of non-enhancing tumors, it should always be suggested as a therapy-determining test.

Distinct miRNA Expression Signatures of Primary and Secondary Central Nervous System Lymphomas.

Central nervous system (CNS) lymphoma is a rare and aggressive non-Hodgkin lymphoma that might arise in the CNS (primary CNS lymphoma) or disseminates from a systemic lymphoma to the CNS (secondary CNS lymphoma). Dysregulated expression of miRNAs is associated with various pathologic processes, and miRNA expression patterns may have diagnostic, prognostic, and therapeutic implications. However, miRNA expression is understudied in CNS lymphomas. We performed expression analysis of 798 miRNAs in 73 CNS lymphoma samples using the NanoString platform, followed by an analysis to identify potential diagnostic biomarkers characterizing subgroups and to examine differences based on their primary and secondary nature, molecular subtype, mutational patterns, and survival. Thirty-one differentially expressed miRNAs were identified between primary and secondary groups. In addition, 7 more miRNAs were identified associated with a molecular subtype and 25 associated with mutation status. Using unsupervised clustering methods, a small but distinct primary CNS lymphoma subgroup, with characteristically different expression patterns compared with the rest of the cases was defined. Finally, differentially regulated pathways were identified in the above comparisons and the utility of miRNA expression patterns in predicting survival was assessed. Our study identifies a novel CNS lymphoma subgroup defined by distinct miRNAs, proves the importance of specific miRNAs and pathways in the pathogenesis of CNS lymphomas, and provides the basis for future research in defining potential biomarkers.

Supplementary valproate therapy for glioma patients: An alternative opportunity to enhance the efficiency of radio-chemotherapy / A valproátterápia túlélésre gyakorolt hatása gliomás betegekben: Alternatív terápiás lehetoség a radiokemoterápia eredményességének javítására

Összefoglaló. Bevezetés: A gliomák, ezen belül a glioblastoma kezelése továbbra is megoldatlan onkológiai problémát jelent. A szekunder szimptómás epilepsziabetegség megjelenése pozitív prognosztikai faktornak tekintheto a korai diagnosztizálás és az antiepileptikumok potenciális tumorellenes hatásának köszönhetoen. A valproát túlélést hosszabbító hatása már több mint 20 éve az alap- és klinikai kutatások tárgyát képezi. Napjainkban ismert citotoxikus, proapoptotikus, antiangiogenetikus és hiszton-deacetiláz-gátló hatásmechanizmusa. Célkituzés: Kutatásunk célja a valproát túlélést hosszabbító hatásának vizsgálata egy hazai gliomás betegcsoportban. Módszer: Egycentrumos, retrospektív klinikai vizsgálatot végeztünk. A vizsgálatba 122 felnott beteget vontunk be, akiknél 2000 januárja és 2018 januárja között supratentorialis glioma miatt mutét történt, és rohamtevékenység miatt antiepileptikumot (valproát, levetiracetám, karbamazepin) szedtek. Egyúttal gyógyszert nem szedo kontrollcsoportot is kialakítottunk. A populációt vizsgálati és kontrollcsoportokra osztottuk 28 : 52 arányban. Leíró statisztikai, Kaplan-Meier- és log-rank analízist végeztünk. Eredmények: A vizsgált szövettani kategóriák túlélési analízise az irodalmi adatokkal megegyezo értékeket mutatott. A progressziómentes (PFS: p = 0,031) és a teljes (OS: p = 0,027) túlélés tekintetében is szignifikáns eltérés mutatkozott a különbözo antiepileptikumot szedo betegcsoportok között, amely még kifejezettebbé vált a valproátot és az egyéb antiepileptikumot szedo betegek túlélési idejének összehasonlítása során (PFS: p = 0,006; OS: p = 0,015). Következtetés: Vizsgálatunkban a valproát betegeink PFS- és OS-idejének meghosszabbodását eredményezte. Az irodalmi adatok és kutatásunk alapján megfontolandónak tartjuk a valproát elso vonalban történo alkalmazását onkoterápiában részesülo, epilepsziás, agyi gliomás betegekben. Orv Hetil. 2021; 162(24): 960-967. INTRODUCTION: Gliomas still prove to be a serious oncological problem. The presence of epilepsy may present a favorable prognosis due to early diagnosis and the potential antitumor effects of antiepileptic drugs. The survival prolongation effect of valproate has been studied for more than 20 years, nowadays its proapoptotic, anti-angiogenetic, cytotoxic and histone deacetylase inhibitory effects are well known. OBJECTIVE: Our goal was to investigate the survival-enhancing effects of valproate in a Hungarian patient cohort of primary brain tumors. METHOD: A single-center based retrospective clinical trial was designed. In our study, we included 122 patients harboring supratentorial glioma who underwent surgery and experienced seizures between 2000 January and 2018 January. The patients were grouped by the antiepileptic therapies and survival analysis was performed. RESULTS: The Kaplan-Meier curves of the histological categories showed the survival values consistent with the data of the literature. The progression-free (PFS: p = 0.031) and the overall (OS: p = 0.027) survival of the antiepileptic drug categories were significantly different. It was performed by comparing the valproate group and the population formed by the other groups which also showed a significant increase in the survival values (PFS: p = 0.006; OS: p = 0.015). CONCLUSION: Our results show that valproate increases the PFS and OS period of glioma patients in comparison to other antiepileptic drugs. Our data suggest that the use of valproic acid should be considered as a first-line antiepileptic agent in certain well-selected epileptic patients with glioma as a supplement to the oncotherapy. Orv Hetil. 2021; 162(24): 960-967.

Exclusive neuronal detection of KGDHC-specific subunits in the adult human brain cortex despite pancellular protein lysine succinylation.

The ketoglutarate dehydrogenase complex (KGDHC) consists of three different subunits encoded by OGDH (or OGDHL), DLST, and DLD, combined in different stoichiometries. DLD subunit is shared between KGDHC and pyruvate dehydrogenase complex, branched-chain alpha-keto acid dehydrogenase complex, and the glycine cleavage system. Despite KGDHC's implication in neurodegenerative diseases, cell-specific localization of its subunits in the adult human brain has never been investigated. Here, we show that immunoreactivity of all known isoforms of OGDHL, OGDH, and DLST was detected exclusively in neurons of surgical human cortical tissue samples identified by their morphology and visualized by double labeling with fluorescent Nissl, while being absent from glia expressing GFAP, Aldhl1, myelin basic protein, Olig2, or IBA1. In contrast, DLD immunoreactivity was evident in both neurons and glia. Specificity of anti-KGDHC subunits antisera was verified by a decrease in staining of siRNA-treated human cancer cell lines directed against the respective coding gene products; furthermore, immunoreactivity of KGDHC subunits in human fibroblasts co-localized > 99% with mitotracker orange, while western blotting of 63 post-mortem brain samples and purified recombinant proteins afforded further assurance regarding antisera monospecificity. KGDHC subunit immunoreactivity correlated with data from the Human Protein Atlas as well as RNA-Seq data from the Allen Brain Atlas corresponding to genes coding for KGDHC components. Protein lysine succinylation, however, was immunohistochemically evident in all cortical cells; this was unexpected, because this posttranslational modification requires succinyl-CoA, the product of KGDHC. In view of the fact that glia of the human brain cortex lack succinate-CoA ligase, an enzyme producing succinyl-CoA when operating in reverse, protein lysine succinylation in these cells must exclusively rely on propionate and/or ketone body metabolism or some other yet to be discovered pathway encompassing succinyl-CoA.

Molecular Subtypes and Genomic Profile of Primary Central Nervous System Lymphoma.

Primary central nervous system lymphomas (PCNSL) are aggressive non-Hodgkin lymphomas affecting the central nervous system (CNS). Although immunophenotyping studies suggested an uniform activated B-cell (ABC) origin, more recently a spectrum of ABC and germinal center B-cell (GC) cases has been proposed, with the molecular subtypes of PCNSL still being a matter of debate. With the emergence of novel therapies demonstrating different efficacy between the ABC and GC patient groups, precise assignment of molecular subtype is becoming indispensable. To determine the molecular subtype of 77 PCNSL and 17 secondary CNS lymphoma patients, we used the NanoString Lymphoma Subtyping Test (LST), a gene expression-based assay representing a more accurate technique of subtyping compared with standard immunohistochemical (IHC) algorithms. Mutational landscapes of 14 target genes were determined using ultra-deep next-generation sequencing. Using the LST-assay, a significantly lower proportion (80% vs 95%) of PCNSL cases displayed ABC phenotype compared with the IHC-based characterization. The most frequently mutated genes included MYD88, PIM1, and KMT2D. In summary, we successfully applied the LST-assay for molecular classification of PCNSL, reporting higher proportion of cases with GC phenotype compared with IHC analyses, leading to a more precise patient stratification potentially applicable in the diagnostic algorithm of PCNSL.

[The effect of bevacizumab monotherapy on progression free survival in recurrent glioblastoma]. / A bevacizumab-monoterápia hatása a progressziómentes túlélésre rekurrens glioblastomában szenvedo betegek esetében.

BACKGROUND AND PURPOSE: Glioblastoma, WHO grade IV is the most frequent primary malignant brain tumor in adults. There are few articles and result about the efficacy of bevacizumab monotherapy. The aim of our paper is to examine the effect of bevacizumab therapy on progression free and overall survival in an extended database of recurrent glioblastoma patients. METHODS: In our retrospective study, patients with recurrent glioblastoma treated with bevacizumab had been collected. All of our patients received first line chemo-irradiation according the Stupp protocol treatment. The histological diagnosis was primary or secondary glioblastoma in every patient. The prognostic features of primary and secondary glioblastomas were statistically analyzed. RESULTS: Eighty-six patients were selected into the retrospective analysis. The histological diagnosis was primary glioblastoma in 65 patients (75.6%) and secondary glioblastoma in 21 patients (24.4%). The mean follow up period was 36.5 months. The mean second progression free survival beside bevacizumab therapy was 6.59 months and the mean overall survival was 24.55 months. In secunder glioblastoma cases, the mean second progression free survival was 6.16 months and the mean overall survival was 91.94 months. CONCLUSION: The bevacizumab therapy is a safe option in recurrent glioblastoma patients. Bevacizumab therapy has a positive effect both on progression free and overall survival and our results confirm the findings in the literature. There is no statistically significant difference in the second progression free survival between glioblastoma subtypes.

PD-L1 Expression of Lung Cancer Cells, Unlike Infiltrating Immune Cells, Is Stable and Unaffected by Therapy During Brain Metastasis.

BACKGROUND: Approximately 50% of brain metastases originate from non-small-cell lung cancer. The median survival of patients with brain metastases is 1 month without treatment. Novel immunotherapeutic strategies, such as those targeting the programmed death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) axis, are promising in patients with advanced systemic disease but are often preferentially administered to patients with tumors showing PD-L1 positivity. PATIENTS AND METHODS: Surgically resected paired primary lung adenocarcinoma and brain metastasis samples of 61 patients were analyzed. We compared the paired samples regarding the amount of peritumoral and stromal mononuclear infiltration, PD-L1 expression of tumor and immune cells, and PD-1 expression of immune cells. We investigated the effect of radiotherapy, chemotherapy, and steroid therapy on PD-L1 expression in brain metastases. RESULTS: There was significant positive correlation regarding the PD-L1 expression of tumor cells between the paired primary lung adenocarcinoma and brain metastatic samples with the use of different cutoff levels (1%, 5%, 50%). We found no impact of chemotherapy or steroid therapy on the changes of PD-L1 expression of tumor cells between the 2 sites. There is no or only limited concordance of the proportion of PD-1- or PD-L1-positive tumor-associated immune cells between the paired tumor samples, which suggests that brain metastases develop their own immune environment. CONCLUSION: We observed a strong correlation of PD-L1 positive tumor cells between primary lung adenocarcinoma cases and their corresponding brain metastases, which is not significantly influenced by chemotherapy or steroid therapy.

Discrepancy Between Low Levels of mTOR Activity and High Levels of P-S6 in Primary Central Nervous System Lymphoma May Be Explained by PAS Domain-Containing Serine/Threonine-Protein Kinase-Mediated Phosphorylation.

The primary aim of this study was to determine mTOR-pathway activity in primary central nervous system lymphoma (PCNSL), which could be a potential target for therapy. After demonstrating that p-S6 positivity largely exceeded mTOR activity, we aimed to identify other pathways that may lead to S6 phosphorylation. We measured mTOR activity with immunohistochemistry for p-mTOR and its downstream effectors p(T389)-p70S6K1, p-S6, and p-4E-BP1 in 31 cases of PCNSL and 51 cases of systemic diffuse large B-cell lymphoma (DLBCL) and evaluated alternative S6 phosphorylation pathways with p-RSK, p(T229)-p70S6K1, and PASK antibodies. Finally, we examined the impact of PASK inhibition on S6 phosphorylation on BHD1 cell line. mTOR-pathway activity was significantly less frequent in PCNSL compared with DLBCL. p-S6 positivity was related to mTOR-pathway in DLBCL, but not in PCNSL. Among the other kinases potentially responsible for S6 phosphorylation, PASK proved to be positive in all cases of PCNSL and DLBCL. Inhibition of PASK resulted in reduced expression of p-S6 in BHD1-cells. This is the first study demonstrating an mTOR independent p-S6 activity in PCNSL and that PASK may contribute to the phosphorylation of S6. Our findings also suggest a potential role of PASK in the pathomechanism of PCNSL and in DLBCL.

Evaluating the significance of density, localization, and PD-1/PD-L1 immunopositivity of mononuclear cells in the clinical course of lung adenocarcinoma patients with brain metastasis.

BACKGROUND: Management of lung cancer patients who suffer from brain metastases represents a major challenge. Considering the promising results with immune checkpoint inhibitor treatment, evaluating the status of immune cell (IC) infiltrates in the prognosis of brain metastasis may lead to better therapeutic strategies with these agents. The aim of this study was to characterize the distribution of ICs and determine the expression of the checkpoint molecules programmed death protein 1 (PD-1) and its ligand, PD-L1, in brain metastasis of lung adenocarcinoma (LUAD) patients and to analyze their clinicopathological correlations. METHODS: We determined the presence of peritumoral mononuclear cells (mononuclear ring) and the density of intratumoral stromal mononuclear cells on brain metastasis tissue sections of 208 LUAD patients. PD-L1/PD-1 expressions were analyzed by immunohistochemistry. RESULTS: Mononuclear rings were significantly associated with better survival after brain metastasis surgery. Cases with massive stromal IC infiltration also showed a tendency for better overall survival. Lower expression of PD-1 and PD-L1 was associated with better survival in patients who underwent surgery for the primary tumor and had multiple brain metastases. Steroid administration and chemotherapy appear not to influence the density of IC in brain metastasis. CONCLUSION: This is the first study demonstrating the independent prognostic value of mononuclear rings in LUAD cases with brain metastasis. Our results also suggest that the density of tumor-associated ICs in addition to PD-L1 expression of tumor cells and ICs as well as PD-1 expression of ICs may hold relevant information for the appropriate selection of patients who might benefit from anti-PD-L1 or anti-PD-1 therapy.

Combined two-photon imaging, electrophysiological, and anatomical investigation of the human neocortex in vitro.

Spontaneous synchronous population activity (SPA) can be detected by electrophysiological methods in cortical slices of epileptic patients, maintained in a physiological medium in vitro. In order to gain additional spatial information about the network mechanisms involved in the SPA generation, we combined electrophysiological studies with two-photon imaging. Neocortical slices prepared from postoperative tissue of epileptic and tumor patients were maintained in a dual perfusion chamber in a physiological incubation medium. SPA was recorded with a 24-channel extracellular linear microelectrode covering all neocortical layers. After identifying the electrophysiologically active regions of the slice, bolus loading of neuronal and glial markers was applied on the tissue. SPA-related [Formula: see text] transients were detected in a large population of neighboring neurons with two-photon microscopy, simultaneous with extracellular SPA and intracellular whole-cell patch-clamp recordings. The intracellularly recorded cells were filled for subsequent anatomy. The cells were reconstructed in three dimensions and examined with light- and transmission electron microscopy. Combining high spatial resolution two-photon [Formula: see text] imaging techniques and high temporal resolution extra- and intracellular electrophysiology with cellular anatomy may permit a deeper understanding of the structural and functional properties of the human neocortex.

[Results of postoperative radiochemotherapy of glioblastoma multiforme]. / Glioblastoma multiforme posztoperatív radio-kemoterápiájának eredményei.

Glioblastoma multiforme has one of the worst prognoses of all cancers. A substantial progression in its treatment has been achieved only eight years ago when a new adjuvant radiochemotherapy regimen containing temozolomid has been introduced to the clinical practice. In this paper we evaluate the treatment results in adjuvant radiochemotherapy of glioblastoma carried out by two neurosurgery and oncology centers in Budapest, Hungary and we compared our results to the data of the reference phase III registration trial of the EORTC/NCIC. We analyzed the data of 210 patients treated for glioblastoma between 2005 and 2013. The primary endpoints of our study were overall survival and side effects. We studied and statistically analyzed the influence of multiple factors on survival. We compared our results with the data of the reference study and other results published in the literature. The median follow-up for the surviving patients in our study was 52 months. The median age of our patients was 58 (18-79) years. Seventy-two women and 138 men have been treated. The median overall survival was 17 (3-96) months, the progression-free survival 11 (3-96) months. The radiochemotherapy phase was completed in 95.2% and the monotherapy phase in 68% of all cases.Univariate analysis showed that age, ECOG status and RPA class had significant influence on survival. In multivariate analysis only RPA class remained statistically significant (RR 1.86, 95% CI 1.14-3.05). The proportion of grade III and worse side effects during the chemoradiation phase was 3.8% and in the monotherapy phase 1.9%. These were hematological side effects only. Serious hematological sequelae occurred nearly exclusively in women. Comparing to the reference study the demographic distribution of the patients was similar in our study but among our patients there were less patients with unfavorable prognosis (ECOG 2 or RPA V), and it resulted in a longer median survival than in the original trial (17 vs. 14.6 months). With this analysis of our patients treated according to the Stupp-protocol for glioblastoma multiforme we validated the results of the original EORTC/NCIC study in a Hungarian patient population. Moreover, this comparison proves that the comprehensive Hungarian neuro-oncology service is not at all inferior when compared to any of the developed countries in Europe.

Paralemniscal TIP39 is induced in rat dams and may participate in maternal functions.

The paralemniscal area, situated between the pontine reticular formation and the lateral lemniscus in the pontomesencephalic tegmentum contains some tuberoinfundibular peptide of 39 residues (TIP39)-expressing neurons. In the present study, we measured a 4 times increase in the level of TIP39 mRNA in the paralemniscal area of lactating mothers as opposed to nulliparous females and mothers deprived of pups using real-time RT-PCR. In situ hybridization histochemistry and immunolabeling demonstrated that the induction of TIP39 in mothers takes place within the medial paralemniscal nucleus, a cytoarchitectonically distinct part of the paralemniscal area, and that the increase in TIP39 mRNA levels translates into elevated peptide levels in dams. The paralemniscal area has been implicated in maternal control as well as in pain perception. To establish the function of induced TIP39, we investigated the activation of TIP39 neurons in response to pup exposure as maternal, and formalin injection as noxious stimulus. Both stimuli elicited c-fos expression in the paralemniscal area. Subsequent double labeling demonstrated that 95% of neurons expressing Fos in response to pup exposure also contained TIP39 immunoreactivity and 91% of TIP39 neurons showed c-fos activation by pup exposure. In contrast, formalin-induced Fos does not co-localize with TIP39. Instead, most formalin-activated neurons are situated medial to the TIP39 cell group. Our data indicate that paralemniscal neurons may be involved in the processing of maternal and nociceptive information. However, two different groups of paralemniscal neurons participate in the two functions. In particular, TIP39 neurons may participate in the control of maternal functions.

Neuronavigation and fluoroscopy-assisted subdural strip electrode positioning: a simple method to increase intraoperative accuracy of strip localization in epilepsy surgery.

For localization of the epileptogenic zone in cases of focal epilepsy, detailed clinical investigations, imaging studies, and electrophysiological methods are used. If the noninvasive presurgical evaluation provides insufficient data, intracranial electrodes are necessary. Computed tomography and MR imaging techniques are the gold standard for localization of the postoperative position of the implanted intracranial electrode contacts. If the electrode strips are inserted through a bur hole, however, the exact localization of the electrode contacts on the patient's brain remains uncertain for the surgeon during insertion. Therefore, the authors developed a simple method to visualize the electrodes during the procedure. In this method they combine neuronavigation and intraoperative fluoroscopy for parallel visualization of the cortex, electrodes, and the navigation probe. The target region is searched with neuronavigation, a bur hole is made over the optimal entry point, and using real-time fluoroscopy the strip electrode is slid to the tip of the navigation probe, which was kept over the area of interest. At the authors' institution 26 strips in 8 patients have been inserted with this technique, and none of the strips had to be repositioned. There were no complications with this procedure and the prolongation of surgery time is acceptable. Compared to previously published electrode placement methods, this one enhances the accuracy of electrode placement at occipital, parietal, frontal, or interhemispheric regions as well. Intraoperative visualization of the electrodes with fluoroscopy combined with neuronavigation during positioning through a bur hole gives the neurosurgeon the ability to control the real position of the electrode over the gyri during the procedure.

Single-dose contrast agent for intraoperative MR imaging of intrinsic brain tumors by using ferumoxtran-10.

BACKGROUND AND PURPOSE: Intraoperative MR imaging (IMRI) has advantages over conventional framed and frameless techniques. IMRI, however, also has some drawbacks, especially related to interpretation of gadolinium-enhanced intraoperative imaging resulting from surgically induced blood brain barrier injury, vascular changes, and hemorrhage. Ultra-small superparamagnetic iron particles like ferumoxtran-10 have a long plasma half-life and are trapped by reactive cells within the tumor. These trapped particles provide a method to demonstrate enhancing lesions without the artifact of repeat gadolinium administration in the face of blood brain barrier and vascular injury. METHODS: We present a review of the literature and the cases of two patients who underwent surgery in which IMRI with ferumoxtran-10 was used. RESULTS: Ultra-small superparamagnetic iron particles represent a method to demonstrate enhancing intrinsic brain tumors without the drawbacks of intraoperative gadolinium enhancement. These lesions appear even on low-field strength IMRI. Ferumoxtran-10, administered preoperatively, provides a stable imaging marker, even after surgical manipulation of the brain. CONCLUSION: Fermumoxtran-10 provides a way to lessen artifactual enhancement during IMRI related to the administration of gadolinium.