Faculty Bibliography

OBJECT/OBJECTIVE:The extent of resection (EOR) is a known prognostic factor in patients with glioblastoma. However, gross-total resection (GTR) is not always achieved. Understanding the factors that prevent GTR is helpful in surgical planning and when counseling patients. The goal of this study was to identify demographic, tumor-related, and technical factors that influence EOR and to define the relationship between the surgeon's impression of EOR and radiographically determined EOR. METHODS:The authors performed a retrospective review of the electronic medical records to identify all patients who underwent craniotomy for glioblastoma resection between 2006 and 2009 and who had both preoperative and postoperative MRI studies. Forty-six patients were identified and were included in the study. Image analysis software (FIJI) was used to perform volumetric analysis of tumor size and EOR based on preoperative and postoperative MRI. Using multivariate analysis, the authors assessed factors associated with EOR and residual tumor volume. Perception of resectability was described using bivariate statistics, and survival was described using the log-rank test and Kaplan-Meier curves. RESULTS:The EOR was less for tumors in eloquent areas (p = 0.014) and those touching ventricles (p = 0.031). Left parietal tumors had significantly greater residual volume (p = 0.042). The average EOR was 91.0% in this series. There was MRI-demonstrable residual tumor in 69.6% of cases (16 of 23) in which GTR was perceived by the surgeon. Expert reviewers agreed that GTR could be safely achieved in 37.0% of patients (17 of 46) in this series. Among patients with safely resectable tumors, radiographically complete resection was achieved in 23.5% of patients (4 of 17). An EOR greater than 90% was associated with a significantly greater 1-year survival (76.5%) than an EOR less than 90% (p = 0.005). CONCLUSIONS:The authors' findings confirm that tumor location affects EOR and suggest that EOR may also be influenced by the surgeon's ability to judge the presence of residual tumor during surgery. The surgeon's ability to judge completeness of resection during surgery is commonly inaccurate. The authors' study confirms the impact of EOR on 1-year survival.

BACKGROUND:Incidence and predictors of neurosurgical interventions following nonsevere traumatic brain injury (TBI) with mildly abnormal head computed tomographic (CT) findings are poorly defined. Despite this, neurosurgical consultation is routinely requested in this patient population. Our objective was to determine incidence of neurosurgical intervention in this patient population and identify clinical and radiographic features predicting the subsequent need for these interventions. METHODS:We identified all consecutive adult patients with nonsevere TBI admitted from January 1, 2001, through December 31, 2010. The definitions of "mildly abnormal initial head CT findings" and "neurosurgical interventions" were determined a priori by author consensus. Cumulative incidence of neurosurgical interventions was determined, and multivariate logistic regression was used to identify independent predictors of neurosurgical intervention. RESULTS:Of 677 patients, 51 underwent neurosurgical intervention for a cumulative incidence of 7.5%. Only 1.6% required an intracranial procedure. In adjusted analysis, presence of coagulopathy (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.13-4.3; p = 0.02), suspected cerebrospinal fluid leak (OR, 11.36; 95% CI, 2.83-45.58; p = 0.001), any basal cistern or sylvian fissure subarachnoid hemorrhage (OR, 2.94; 95% CI, 1.56-5.57; p = 0.001), depressed skull fracture (OR, 2.84; 95% CI, 1.29-6.28; p = 0.01), or unstable repeated head CT findings (OR, 2.81; 95% CI, 1.52-5.2; p = 0.001) remained an independent predictor of the need for subsequent neurosurgical intervention. CONCLUSION/CONCLUSIONS:Among patients with nonsevere TBI and mildly abnormal head imaging findings in which routine neurosurgical consultation is obtained, there is a low incidence of neurosurgical interventions. Our findings suggest that routine early neurosurgical consultation in this patient population may not be necessary; however, this should be tested in a prospective, comparative study. LEVEL OF EVIDENCE/METHODS:Prognostic study, level III; therapeutic study, level IV.

Conventional histopathology with hematoxylin & eosin (H&E) has been the gold standard for histopathological diagnosis of a wide range of diseases. However, it is not performed in vivo and requires thin tissue sections obtained after tissue biopsy, which carries risk, particularly in the central nervous system. Here we describe the development of an alternative, multicolored way to visualize tissue in real-time through the use of coherent Raman imaging (CRI), without the use of dyes. CRI relies on intrinsic chemical contrast based on vibrational properties of molecules and intrinsic optical sectioning by nonlinear excitation. We demonstrate that multicolor images originating from CH(2) and CH(3) vibrations of lipids and protein, as well as two-photon absorption of hemoglobin, can be obtained with subcellular resolution from fresh tissue. These stain-free histopathological images show resolutions similar to those obtained by conventional techniques, but do not require tissue fixation, sectioning or staining of the tissue analyzed.

Neuronavigation has become an ubiquitous tool in the surgical management of brain tumors. This review describes the use and limitations of current neuronavigational systems for brain tumor biopsy and resection. Methods for integrating intraoperative imaging into neuronavigational datasets developed to address the diminishing accuracy of positional information that occurs over the course of brain tumor resection are discussed. In addition, the process of integration of functional MRI and tractography into navigational models is reviewed. Finally, emerging concepts and future challenges relating to the development and implementation of experimental imaging technologies in the navigational environment are explored.

First described for use in mapping the human visual cortex in 1991, functional magnetic resonance imaging (fMRI) is based on blood-oxygen level dependent (BOLD) changes in cortical regions that occur during specific tasks. Typically, an overabundance of oxygenated (arterial) blood is supplied during activation of brain areas. Consequently, the venous outflow from the activated areas contains a higher concentration of oxyhemoglobin, which changes the paramagnetic properties of the tissue that can be detected during a T2-star acquisition. fMRI data can be acquired in response to specific tasks or in the resting state. fMRI has been widely applied to studying physiologic and pathophysiologic diseases of the brain. This review will discuss the most common current clinical applications of fMRI as well as emerging directions.

Delineation of tumor margins is a critical and challenging objective during brain cancer surgery. A tumor-targeting deep-blue nanoparticle-based visible contrast agent is described, which, for the first time, offers in vivo tumor-specific visible color staining. This technology thus enables color-guided tumor resection in real time, with no need for extra equipment or special lighting conditions. The visual contrast agent consists of polyacrylamide nanoparticles covalently linked to Coomassie Blue molecules (for nonleachable blue color contrast), which are surface-conjugated with polyethylene glycol and F3 peptides for efficient in vivo circulation and tumor targeting, respectively.

Thoracic vertebral compression fractures are a known complication of generalized tetanus. The authors report the first known case of an L-2 burst fracture leading to cauda equina syndrome, as a result of generalized tetanus. This 51-year-old man had generalized tetanus with a constellation of symptoms including compartment syndrome requiring fasciotomies, severe axial spasms and spasms of the extremities, autonomic dysreflexia, hypercarbic respiratory failure, and rhabdomyolysis. During the course of his illness, areflexic paraparesis developed in his lower extremities. He was found to have an L-2 burst fracture with retropulsion of a bone fragment resulting in cauda equina syndrome. Operative intervention was undertaken to decompress the cauda equina and stabilize the spine. The natural progression of tetanus can be complex, with a mixed picture ranging from spasms plus increased tone and reflexes to reduced tone and reflexes as presynaptic nerve terminals become damaged. The authors suggest that all sudden changes in the neurological examination should prompt consideration of diagnostic imaging before attributing such changes to natural progression of the disease.

Distinguishing a tumor from non-neoplastic tissue is a challenging task during cancer surgery. Several attempts have been made to use visible or fluorescent agents to aid in the visualization of a tumor during surgery. We describe a novel method to delineate brain tumors, using a highly sensitive photoacoustic imaging technique that is enhanced by tumor-targeting blue nanoparticles serving as a contrast agent. Experiments on phantoms and on rat brains, ex vivo, demonstrate the high sensitivity of photoacoustic imaging in delineating tumors containing contrast agent at a concentration much lower than needed for visualization by the naked eye. The limit of detection of the system for the nanoparticles is about 0.77 μg/mL in water (equivalent to 0.84 μmol/L Coomassie Blue dye). The present exploratory study suggests that photoacoustic imaging, when used with strongly optical absorbing contrast agents, could facilitate cancer surgery intraoperatively by revealing the distribution and extent of the tumor.

Methylene blue-conjugated polyacrylamide nanoparticles are prepared through a microemulsion polymerization, after conjugation of the dye with a monomer. The nanoparticles have a 50-60 nm diameter in solution. This conjugation method enables a large increase in loading of methylene blue per nanoparticle and also minimizes dye leaching out of the nanoparticle. Furthermore, the dye content can be controlled by variation of the dye amount, enabling a more refined control of the singlet oxygen production ability. The nanoparticles are coated with F3 peptides, which give specific targeting to selected tumor cells, 9L, MDA-MB-435, and F98, in vitro. In addition, MTT assays reveal that the nanoparticles have no dark toxicity but excellent PDT efficacy increasing with the nanoparticle dose and irradiation time.

Transorbital penetrating injury (TPI), an uncommon subset of head trauma, requires prompt multidisciplinary surgical intervention. While numerous case reports appear in the literature, there is a lack of discrete recommendations for initial evaluation, surgical intervention, and postoperative care of patients with TPI. A retrospective review of 4 cases of TPI at the University of Michigan Health System was undertaken to assess for diagnosis, treatment, and follow-up. In addition, a PubMed search using the terms "penetrating orbital trauma," "penetrating orbital injury," "transorbital penetration," and "transorbital penetrating injury" were used to search for articles discussing the presentation and management of penetrating orbital trauma. All 4 of the patients at the University of Michigan underwent focused physical examination performed by a multidisciplinary trauma team followed by dedicated maxillofacial and head CT scanning. The patients' treatments varied, depending on the mechanism and extent of the injury. An analysis of the case series presented here as well as other published cases suggests an algorithm for diagnosis and treatment for patients with TPI, which includes focused evaluation, diagnostic imaging with maxillofacial CT scanning, and management of the injury that focuses on the path of penetration and the presence of the foreign body in situ at the time of presentation. Magnetic resonance imaging is indicated in patients who have indwelling wooden foreign bodies. Angiography should be performed in patients with suspected vascular injury. Treatment decisions should be made by a multidisciplinary team with input from neurosurgery, ophthalmology, otolaryngology, and maxillofacial surgery.