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OBJECTIVEThe aim of this study was to evaluate the safety of 3-T MRI in patients with implanted deep brain stimulation (DBS) systems.METHODSThis study was performed in 2 phases. In an initial phantom study, a Lucite phantom filled with tissue-mimicking gel was assembled. The system was equipped with a single DBS electrode connected to an internal pulse generator. The tip of the electrode was coupled to a fiber optic thermometer with a temperature resolution of 0.1°C. Both anatomical (T1- and T2-weighted) and functional MRI sequences were tested. A temperature change within 2°C from baseline was considered safe. After findings from the phantom study suggested safety, 10 patients with implanted DBS systems targeting various brain areas provided informed consent and underwent 3-T MRI using the same imaging sequences. Detailed neurological evaluations and internal pulse generator interrogations were performed before and after imaging.RESULTSDuring phantom testing, the maximum temperature increase was registered using the T2-weighted sequence. The maximal temperature changes at the tip of the DBS electrode were < 1°C for all sequences tested. In all patients, adequate images were obtained with structural imaging, although a significant artifact from lead connectors interfered with functional imaging quality. No heating, warmth, or adverse neurological effects were observed.CONCLUSIONSTo the authors' knowledge, this was the first study to assess the clinical safety of 3-T MRI in patients with a fully implanted DBS system (electrodes, extensions, and pulse generator). It provided preliminary data that will allow further examination and assessment of the safety of 3-T imaging studies in patients with implanted DBS systems. The authors cannot advocate widespread use of this type of imaging in patients with DBS implants until more safety data are obtained.

Object Oligodendrogliomas that enhance on MR images are associated with poor prognosis. However, the importance of the volume of enhancing tumor tissue, and the extent of its resection, is uncertain. The authors examined the prognostic significance of preoperative and residual postoperative enhancing tissue volumes in a large single-center series of patients with oligodendroglioma. They also examined the relationship between enhancement and characteristic genetic signatures in oligodendroglial tumors, specifically deletion of 1p and 19q (del 1p/19q). Methods The authors retrospectively analyzed 100 consecutive cases of oligodendroglioma involving patients who had undergone T1-weighted gadolinium-enhanced MRI at diagnosis and immediately after initial surgical intervention. The presence of preoperative enhancement was determined by consensus. Preoperative and residual postoperative volumes were measured using a quantitative, semiautomated method by a single blinded observer. Intrarater reliability for preoperative volumes was confirmed by remeasurement in a subset of patients 3 months later. Intrarater and interrater reliability for residual postoperative volumes was confirmed by remeasurement of these volumes by both the original and a second blinded observer. Multivariate analysis was used to assess the influence of contrast enhancement at diagnosis and the volume of pre- and postoperative contrast-enhancing tumor tissue on time to relapse (TTR) and overall survival (OS), while controlling for confounding clinical, pathological, and genetic factors. Results Sixty-three of 100 patients had enhancing tumors at initial presentation. Presence of contrast enhancement at diagnosis was related to reduced TTR and OS on univariate analysis but was not significantly related on multivariate analysis. In enhancing tumors, however, greater initial volume of enhancing tissue correlated with shortened TTR (p = 0.00070). Reduced postoperative residual enhancing volume and a relatively greater resection of enhancing tissue correlated with longer OS (p = 0.0012 and 0.0041, respectively). Interestingly, patients in whom 100% of enhancing tumor was resected had significantly longer TTR (174 vs 64 weeks) and OS (392 vs 135 weeks) than those with any residual enhancing tumor postoperatively. This prognostic benefit was not consistently maintained with greater than 90% or even greater than 95% resection of enhancing tissue. There was no relationship between presence or volume of enhancement and del 1p/19q. Conclusions In enhancing oligodendrogliomas, completely resecting enhancing tissue independently improves outcome, irrespective of histological grade or genetic status. This finding supports aggressive resection and may impact treatment planning for patients with these tumors.

Determining the incidence of intracerebral hemorrhagic complications caused by functional neurosurgical procedures—and what should be done to avoid them—has proven to be a controversial issue since the early days of stereotaxy. Most surgeons performing modern functional neurosurgery would probably agree, thankfully, that hemorrhages are rare events. Nevertheless, the real potential for these uncommon occurrences to produce devastating neurological morbidity or death in patients with degenerative but otherwise nonlethal conditions, rightly continues to be a source of concern. In their study, “Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review,” Zrinzo et al.1 bring their considerable institutional experience to bear on the issue. The study consists of 2 parts. In the first, the authors report on the incidence of hemorrhagic complications in their own consecutive series of 214 patients they have treated with “image-guided ” implantation of deep brain stimulation (DBS) systems since 2002. Secondly, they perform a “systematic review” of series published over the past decade—including both DBS and lesioning procedures—to compute a literature-wide incidence of hemorrhage in modern functional neurosurgery and to address the relative contribution to hemorrhagic risk of several clinical and surgical factors. Ultimately, they find that the incidence of hemorrhage following functional neurosurgical interventions is about 5%, with symptomatic or permanently disabling hemorrhages being even less likely (2.1% and 1.1%, respectively). Hypertension and increasing age appear to be the most significant patient-related risk factors. The authors also conclude that using microelectrode recording (MER) or transgressing either sulci or the ventricles during surgery may increase the risk of hemorrhage and can be avoided by adopting an “image-guided” technique such as theirs. Zrinzo et al.1 are to be congratulated for the record of safety they have achieved over the past decade at their institution during surgery for DBS. As they point out, their hemorrhage rate of 0.9% per patient is among the lowest reported to date. They should also be commended for attempting to sort through the substantial literature related to hemorrhage risk in functional neurosurgery, which consists almost entirely of retrospective series of variable size and quality. Tabulating these individual series in a single paper provides a useful resource for functional neurosurgeons. Furthermore, their division of risk factors for hemorrhage into patient-related and surgical categories is a logical approach that authors of future studies would be wise to adopt. As they point out, their study does have a number of important limitations. Among others, publication bias, noncontemporaneous series, varying levels of expertise of the treating center, the learning curve across centers, differences in patient selection, and the omission of data on long-term efficacy and nonhemorrhagic side effects limit the conclusions that can be drawn from this kind of analysis. Perhaps the most salient is that in a retrospective review of the literature all kinds of observations can be made but their significance can be sometimes rather dubious. Specific findings can be associative rather than causal. As a famous example, 99% of patients with cancer have eaten pickles, but not too many would go as far as to say that this is the cause of their cancer. Similarly, the observation that there are more reports of patients with some intrinsic or extrinsic attribute (for example, pickle eaters) who have had a particular negative outcome such as hemorrhage does not prove causation. No doubt the meticulous use of MR imaging–based planning as Zrinzo et al.1 advocate has the potential to reduce the number of passes made into the brain by surgical instruments, theoretically providing less occasion to induce hemorrhage. But this theoretical advantage may be offset by the need to reposition suboptimally placed electrodes or by diminished therapeutic efficacy, which is why physiological targeting using MER remains so widespread even in this era of rapid improvements in imaging quality. Functional neurosurgery is still waiting for an unbiased, methodologically sound study that establishes the superiority of one approach over the other. Unfortunately, it is unlikely that a randomized controlled trial designed to ascertain the true hemorrhage risk conferred by various clinical and surgical factors will ever be undertaken; any such trial is doomed to be underpowered because hemorrhage is such a rare outcome and open to criticism because surgical methods are far from standardized across functional neurosurgery centers. As a result, all we can really say is that Zrinzo and colleagues have made a good attempt to address this issue, that their particular brand of “image-guided” approach to DBS surgery works well for them, and that the debate goes on.

The evolution of neurosurgery has in many ways paralleled the evolution of technology used to image the nervous system. It is no exaggeration to say that safe and effective modern neurosurgery has largely been made possible by advances in structural neuroimaging that permit evermore precise delineation of normal and abnormal anatomy in the brain and spine. Within the last 2 decades, and in particular since the turn of the century, structural imaging is increasingly being complemented by imaging approaches that allow the neurosurgeon to observe and measure neural activity and connectivity. These functional imaging techniques span multiple modalities and can assist the neurosurgeon in diagnosing neurosurgical conditions, selecting appropriate patients for neurosurgical intervention, performing preoperative and intraoperative brain mapping to avoid damage to eloquent areas of the brain during surgery, and assessing neuroplasticity during postsurgical recovery. In effect, the marriage of structural and functional imaging is ushering in a new era of neurosurgical practice that could be called—to borrow terminology from the technology world—Neurosurgery 2.0. It is, of course, impossible to cover all neurosurgically relevant aspects of functional imaging in a single issue of Neurosurgical Focus. Our aim is simply to provide an effective introduction to several functional imaging approaches in the neurosurgical armamentarium. The articles are ordered in such a way as to take the reader from current and established applications of functional imaging to emerging applications to exciting preclinical work with translational potential. We begin with a review by Abdullah et al. summarizing the published literature on diffusion tensor imaging (DTI) as an adjunct to the resection of gliomas. In many centers, DTI acquisition is now a routine component of preoperative MRI in patients with brain tumors, and DT images are widely used for planning the surgical approach and during intraoperative neuronavigation. This paper is followed by a review on functional imaging in the setting of intracerebral hemorrhage by McDowell et al., which emphasizes its role in assessing the evolution, prognosis, and pathophysiology of this common neurosurgical condition. Takahashi et al. introduce the technique of navigated transcranial magnetic stimulation (nTMS), and they review its application to presurgical motor mapping in patients with perirolandic brain tumors. By critically assessing 11 published series in which nTMS mapping was performed, the authors show that the accuracy of nTMS for motor mapping compares favorably with both intraoperative direct cortical stimulation and functional MRI (fMRI). The next 2 papers represent single-institution experiences with selected applications of functional imaging to specific neurosurgical disorders. Sommer et al. pre sent a sizable series of patients with lesional extratemporal epilepsy in whom resection was guided by integrated DTI and fMRI. The superb seizure outcomes they report speak to the value of multimodal functional imaging in preventing neurological deficit while maximizing lesion resection. Similarly, Conti et al. describe their successful multimodal imaging approach to stereotactic CyberKnife radiosurgery, in which they combine not only fMRI and DTI but also nTMS to shape the treatment plan. Three retrospective series follow on the specific application of fMRI to preoperative sensorimotor and language mapping. Kundu et al. examine whether postoperative language outcomes after tumor surgery can be predicted by the proximity of tumors to preoperative language activations in the Broca and Wernicke areas. Voss Introduction

Object Axonal regeneration may be hindered following spinal cord injury (SCI) by a limited immune response and insufficient macrophage recruitment. This limitation has been partially surmounted in small-mammal models of SCI by implanting activated autologous macrophages (AAMs). The authors sought to replicate these results in a canine model of partial SCI. Methods Six dogs underwent left T-13 spinal cord hemisection. The AAMs were implanted at both ends of the lesion in 4 dogs, and 2 other dogs received sham implantations of cell media. Cortical motor evoked potentials (MEPs) were used to assess electrophysiological recovery. Functional motor recovery was assessed with a modified Tarlov Scale. After 9 months, animals were injected with wheat germ agglutinin–horseradish peroxidase at L-2 and killed for histological assessment. Results Three of the 4 dogs that received AAM implants and 1 of the 2 negative control dogs showed clear recovery of MEP response. Behavioral assessment showed no difference in motor function between the AAM-treated and control groups. Histological investigation with an axonal retrograde tracer showed neither local fiber crossing nor significant uptake in the contralateral red nucleus in both implanted and negative control groups. Conclusions In a large-animal model of partial SCI treated with implanted AAMs, the authors saw no morphological or histological evidence of axonal regeneration. Although they observed partial electrophysiological and functional motor recovery in all dogs, this recovery was not enhanced in animals treated with implanted AAMs. Furthermore, there was no morphological or histological evidence of axonal regeneration in animals with implants that accounted for the observed recovery. The explanation for this finding is probably multifactorial, but the authors believe that the AAM implantation does not produce axonal regeneration, and therefore is a technology that requires further investigation before it can be clinically relied on to ameliorate SCI.