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Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomofunctional mechanisms governing human behaviour, in addition to the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. Although the ventral tegmental area has been targeted successfully with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region is not fully understood. Here, using fibre microdissections in human cadaveric hemispheres, population-based high-definition fibre tractography and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches and aggressive behaviours.
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Estimulação Encefálica Profunda , Mesencéfalo , Vias Neurais , Área Tegmentar Ventral , Humanos , Estimulação Encefálica Profunda/métodos , Vias Neurais/fisiologia , Mesencéfalo/fisiologia , Área Tegmentar Ventral/fisiologia , Área Tegmentar Ventral/diagnóstico por imagem , Masculino , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Imagem de Tensor de Difusão , Córtex Pré-Frontal/fisiologia , Feminino , Gânglios da Base/fisiologiaRESUMO
Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole (TP), both during resting-state conditions and various higher-order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neuroscience research. In this study, we investigated the connectivity of the precuneus and TP by employing parcellation-based fiber micro-dissections in human brains and fiber tractography techniques in a sample of 1065 human subjects and a sample of 41 rhesus macaques. Our results demonstrate the connectivity between the posterior precuneus area POS2 and the areas 35, 36, and TG of the TP via the fifth subcomponent of the cingulum (CB-V) also known as parahippocampal cingulum. This finding contributes to our understanding of the connections within the posteromedial cortices, facilitating a more comprehensive integration of anatomy and function in both normal and pathological brain processes. PRACTITIONER POINTS: Our investigation delves into the intricate architecture and connectivity patterns of subregions within the precuneus and temporal pole, filling a crucial gap in our knowledge. We revealed a direct axonal connection between the posterior precuneus (POS2) and specific areas (35, 35, and TG) of the temporal pole. The direct connections are part of the CB-V pathway and exhibit a significant association with the cingulum, SRF, forceps major, and ILF. Population-based human tractography and rhesus macaque fiber tractography showed consistent results that support micro-dissection outcomes.
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Imagem de Tensor de Difusão , Macaca mulatta , Vias Neurais , Lobo Parietal , Lobo Temporal , Humanos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiologia , Lobo Temporal/anatomia & histologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiologia , Lobo Parietal/anatomia & histologia , Animais , Imagem de Tensor de Difusão/métodos , Masculino , Adulto , Feminino , Vias Neurais/diagnóstico por imagem , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Adulto Jovem , Axônios/fisiologia , Conectoma , Substância Branca/diagnóstico por imagem , Substância Branca/anatomia & histologia , Substância Branca/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Giro do Cíngulo/anatomia & histologiaRESUMO
Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.
Glioblastoma (GBM) is a fast-growing brain tumor that happens in about half of all gliomas. Surgery is the first treatment for patients with newly diagnosed GBM, followed by the usual radiation and chemotherapy pills named temozolomide. Temozolomide pills are then given as a long-term treatment. The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed during surgery and mixed in the laboratory with a small DNA, IMV-001. This mix is the IGV-001 therapy that is designed to give antitumor immunity against GBM. IGV-001 is put into small biodiffusion chambers that are irradiated to stop the growth of any tumor cells in the chambers. In the phase IIb study, patients with newly diagnosed GBM are chosen and assigned to either the IGV-001 or the placebo group. A placebo does not contain any active ingredients. The small biodiffusion chambers containing either IGV-001 or placebo are surgically placed into the belly for 48 to 52 h and then removed. Patients then receive the usual radiation and chemotherapy treatment. Patients must be adults aged between 18 and 70 years. Patients also should be able to care for themselves overall, but may be unable to work or have lower ability to function. Patients with tumors on both sides of the brain are not eligible. The main point of this study is to see if IGV-001 helps patients live longer without making the illness worse compared with placebo. Clinical Trial Registration: NCT04485949 (ClinicalTrials.gov).
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Neoplasias Encefálicas , Combinação de Medicamentos , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Temozolomida/uso terapêutico , Oligonucleotídeos Antissenso/uso terapêutico , Intervalo Livre de Doença , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Imunoterapia , Antineoplásicos Alquilantes/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Spinal laser interstitial thermal therapy has been developed as a minimally invasive modality to treat epidural spinal tumors percutaneously. The safe and effective use of this technology requires meticulous preoperative trajectory planning and an intraoperative workflow incorporating navigation and MR thermography. Instrumented stabilization can be performed during the same operation if needed. Operative considerations and technical aspects are reviewed. The video can be found here: https://youtu.be/P--frsag6gU .
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Terapia a Laser/métodos , Compressão da Medula Espinal/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Termografia/métodos , Vértebras Torácicas/cirurgia , Adulto , Feminino , Humanos , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagemRESUMO
We recently reported SMARCE1 mutations as a cause of spinal clear cell meningiomas. Here, we have identified five further cases with non-NF2 spinal meningiomas and six with non-NF2 cranial meningiomas. Three of the spinal cases and three of the cranial cases were clear cell tumours. We screened them for SMARCE1 mutations and investigated copy number changes in all point mutation-negative samples. We identified two novel mutations in individuals with spinal clear cell meningiomas and three mutations in individuals with cranial clear cell meningiomas. Copy number analysis identified a large deletion of the 5' end of SMARCE1 in two unrelated probands with spinal clear cell meningiomas. Testing of affected and unaffected relatives of one of these individuals identified the same deletion in two affected female siblings and their unaffected father, providing further evidence of incomplete penetrance of meningioma disease in males. In addition, we found loss of SMARCE1 protein in three of 10 paraffin-embedded cranial clear cell meningiomas. Together, these results demonstrate that loss of SMARCE1 is relevant to cranial as well as spinal meningiomas. Our study broadens the spectrum of mutations in the SMARCE1 gene and expands the phenotype to include cranial clear cell meningiomas.
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Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genética , Mutação em Linhagem Germinativa , Neoplasias Meníngeas/genética , Meningioma/genética , Adolescente , Adulto , Neoplasias Encefálicas/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Dosagem de Genes , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Linhagem , Neoplasias da Coluna Vertebral/genética , Adulto JovemRESUMO
BACKGROUND: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies. Therefore, development of a consistent and simple large animal glioma xenograft model would have significant translational benefits. METHODS: Immunosuppression was induced in twelve standard Yucatan minipigs. 3 pigs received cyclosporine only, while 9 pigs received a combined regimen including cyclosporine (55 mg/kg q12 h), prednisone (25 mg, q24 h) and mycophenolate (500 mg q24 h). U87 cells (2 × 106) were stereotactically implanted into the left frontal cortex. The implanted brains were imaged by MRI for monitoring. In a separate study, tumors were grown in 5 additional pigs using the combined regimen, and pigs underwent tumor resection with intra-operative image updating to determine if the xenograft model could accurately capture the spatial tumor resection challenges seen in humans. RESULTS: Tumors were successfully implanted and grown in 11 pigs. One animal in cyclosporine only group failed to show clinical tumor growth. Clinical tumor growth, assessed by MRI, progressed slowly over the first 10 days, then rapidly over the next 10 days. The average tumor growth latency period was 20 days. Animals were monitored twice daily and detailed records were kept throughout the experimental period. Pigs were sacrificed humanely when the tumor reached 1 - 2 cm. Some pigs experienced decreased appetite and activity, however none required premature euthanasia. In the image updating study, all five pigs demonstrated brain shift after craniotomy, consistent with what is observed in humans. Intraoperative image updating was able to accurately capture and correct for this shift in all five pigs. CONCLUSION: This report demonstrates the development and use of a human intracranial glioma model in an immunosuppressed, but nongenetically modified pig. While the immunosuppression of the model may limit its utility in certain studies, the model does overcome several limitations of small animal or genetically modified models. For instance, we demonstrate use of this model for guiding surgical resection with intraoperative image-updating technologies. We further report use of a surrogate extracranial tumor that indicates growth of the intracranial tumor, allowing for relative growth assessment without radiological imaging.
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Neoplasias Encefálicas , Ciclosporinas , Glioma , Humanos , Suínos , Animais , Xenoenxertos , Reprodutibilidade dos Testes , Porco Miniatura , Glioma/tratamento farmacológico , Glioma/cirurgia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Terapia de Imunossupressão , Modelos Animais de DoençasRESUMO
Introduction: Intraoperative neuromonitoring (IONM) is crucial to preserve eloquent neurological functions during brain tumor resections. We observed a rare interlimb cortical motor facilitation phenomenon in a patient with recurrent high-grade glioma undergoing craniotomy for tumor resection; the patient's upper arm motor evoked potentials (MEPs) increased in amplitude significantly (up to 44.52 times larger, p < 0.001) following stimulation of the ipsilateral posterior tibial nerve at 2.79 Hz. With the facilitation effect, the cortical MEP stimulation threshold was reduced by 6 mA to maintain appropriate continuous motor monitoring. It likely has the benefit of reducing the occurrence of stimulation-induced seizures and other adverse events associated with excessive stimulation. Methods: We conducted a retrospective data review including 120 patients who underwent brain tumor resection with IONM at our center from 2018 to 2022. A broad range of variables collected pre-and intraoperatively were reviewed. The review aimed to determine: (1) whether we overlooked this facilitation phenomenon in the past, (2) whether this unique finding is related to any specific demographic information, clinical presentation, stimulation parameter (s) or anesthesia management, and (3) whether it is necessary to develop new techniques (such as facilitation methods) to reduce cortical stimulation intensity during intraoperative functional mapping. Results: There is no evidence suggesting that clinical presentation, stimulation configuration, or intraoperative anesthesia management of the patient with the facilitation effect were significantly different from our general patient cohort. Even though we did not identify the same facilitation effect in any of these patients, we were able to determine that stimulation thresholds for motor mapping are significantly associated with the location of stimulation (p = 0.003) and the burst suppression ratio (BSR) (p < 0.001). Stimulation-induced seizures, although infrequent (4.05%), could occur unexpectedly even when the BSR was 70%. Discussion: We postulated that functional reorganization and neuronal hyperexcitability induced by glioma progression and repeated surgeries were probable underlying mechanisms of the interlimb facilitation phenomenon. Our retrospective review also provided a practical guide to cortical motor mapping in brain tumor patients under general anesthesia. We also underscored the need for developing new techniques to reduce the stimulation intensity and, hence, seizure occurrence.
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Seizures are the initial manifestation of tuberous sclerosis complex (TSC) in 90% of individuals. The prevalence of epilepsy in TSC is 80%-90% with a large proportion refractory to antiepileptic drugs. A review of the literature of epilepsy surgery in TSC demonstrates impressive success rates for seizure-free outcomes. These studies describe a number of novel noninvasive methods for seizure localization including PET, SPECT, and magnetoencephalography. Additionally, there is a subset of patients with TSC with bilateral, multifocal, or generalized epileptiform discharges that would have previously been excluded from resection. New developments in neuroimaging and invasive monitoring with intracranial electrodes are useful methods in identifying an epileptogenic tuber in these individuals with refractory epilepsy. The authors offer a survey of the literature and description of these methods. Additionally they present an illustrative case of ictal SPECT and intracranial electroencephalography used in the preoperative evaluation of a 10-year-old girl with intractable seizures and TSC. This patient ultimately underwent resection of an epileptogenic region within the occipital lobe.
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Epilepsia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Esclerose Tuberosa/complicações , Esclerose Tuberosa/epidemiologiaRESUMO
Change in vertebral position between preoperative imaging and the surgical procedure reduces the accuracy of image-guided spinal surgery, requiring repeated imaging and surgical field registration, a process that takes time and exposes patients to additional radiation. We developed a handheld, camera-based, deformable registration system (intraoperative stereovision, iSV) to register the surgical field automatically and compensate for spinal motion during surgery without further radiation exposure. Methods: We measured motion-induced errors in image-guided lumbar pedicle screw placement in 6 whole-pig cadavers using state-of-the-art commercial spine navigation (StealthStation; Medtronic) and iSV registration that compensates for intraoperative vertebral motion. We induced spinal motion by using preoperative computed tomography (pCT) of the lumbar spine performed in the supine position with accentuated lordosis and performing surgery with the animal in the prone position. StealthStation registration of pCT occurred using metallic fiducial markers implanted in each vertebra, and iSV data were acquired to perform a deformable registration between pCT and the surgical field. Sixty-eight pedicle screws were placed in 6 whole-pig cadavers using iSV and StealthStation registrations in random order of vertebral level, relying only on image guidance without invoking the surgeon's judgment. The position of each pedicle screw was assessed with post-procedure CT and confirmed via anatomical dissection. Registration errors were assessed on the basis of implanted fiducials. Results: The frequency and severity of pedicle screw perforation were lower for iSV registration compared with StealthStation (97% versus 68% with Grade 0 medial perforation for iSV and StealthStation, respectively). Severe perforation occurred only with StealthStation (18% versus 0% for iSV). The overall time required for iSV registration (computational efficiency) was â¼10 to 15 minutes and was comparable with StealthStation registration (â¼10 min). The mean target registration error was smaller for iSV relative to StealthStation (2.81 ± 0.91 versus 8.37 ± 1.76 mm). Conclusions: Pedicle screw placement was more accurate with iSV registration compared with state-of-the-art commercial navigation based on preoperative CT when alignment of the spine changed during surgery. Clinical Relevance: The iSV system compensated for intervertebral motion, which obviated the need for repeated vertebral registration while providing efficient, accurate, radiation-free navigation during open spinal surgery.
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BACKGROUND CONTEXT: Spinal epidural abscess (SEA) is an uncommon yet serious infection, associated with significant morbidity and mortality. Patients diagnosed with SEA often require surgical interventions or critical care services that are not available at community hospitals and are therefore transferred to tertiary care centers. Little is known about the effects of interhospital transfer on acute outcomes for patients with SEA. PURPOSE: To study the effects of interhospital transfer on acute outcomes for patients with SEA. STUDY DESIGN: Cross sectional analysis using the 2009 to 2017 National Inpatient Sample (NIS). PATIENT SAMPLE: Using the 2009 to 2017 NIS, we identified cases of SEA using ICD, Ninth, or Tenth Revision diagnosis codes 324.1 & G06.1. OUTCOME MEASURES: Our primary endpoint was in hospital mortality. METHODS: The association between interhospital transfer and inpatient mortality was assessed using multivariable logistic regression to adjust for potential covariates. Patient and hospital factors associated with interhospital transfer were assessed in a secondary analysis. RESULTS: A total of 21.5% of patient with SEA were treated after transfer from another hospital. After adjusting for covariates, those who presented after transfer had higher odds of death during hospitalization (OR: 1.51, 95% CI 1.27-1.78, p<.001). Transferred patients were significantly more likely to live in rural communities (11.4 % vs. 5.3 % for nontransferred patients). CONCLUSIONS: Interhospital transfer, which occurred more frequently in patients from rural hospitals, was associated with death even after controlling for disease severity. Addressing healthcare delivery disparities across the US, including across the rural-urban spectrum, will require better understanding of the observed increased mortality of interhospital transfer as a preventable source of in-hospital mortality for SEA.
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Abscesso Epidural , Estudos Transversais , Mortalidade Hospitalar , Hospitalização , Humanos , Transferência de Pacientes , Estudos RetrospectivosRESUMO
PURPOSE: Increased oxygen levels may enhance the radiosensitivity of brain metastases treated with stereotactic radiosurgery (SRS). This project administered hyperbaric oxygen (HBO) prior to SRS to assess feasibility, safety, and response. METHODS: 38 patients were studied, 19 with 25 brain metastases treated with HBO prior to SRS, and 19 historical controls with 27 metastases, matched for histology, GPA, resection status, and lesion size. Outcomes included time from HBO to SRS, quality-of-life (QOL) measures, local control, distant (brain) metastases, radionecrosis, and overall survival. RESULTS: The average time from HBO chamber to SRS beam-on was 8.3 ± 1.7 minutes. Solicited adverse events (AEs) were comparable between HBO and control patients; no grade III or IV serious AEs were observed. Radionecrosis-free survival (RNFS), radionecrosis-free survival before whole-brain radiation therapy (WBRT) (RNBWFS), local recurrence-free survival before WBRT (LRBWFS), distant recurrence-free survival before WBRT (DRBWFS), and overall survival (OS) were not significantly different for HBO patients and controls on Kaplan-Meier analysis, though at 1-year estimated survival rates trended in favor of SRS + HBO: RNFS - 83% vs 60%; RNBWFS - 78% vs 60%; LRBWFS - 95% vs 78%; DRBWFS - 61% vs 57%; and OS - 73% vs 56%. Multivariate Cox models indicated no significant association between HBO treatment and hazards of RN, local or distant recurrence, or mortality; however, these did show statistically significant associations (p < 0.05) for: local recurrence with higher volume, radionecrosis with tumor resection, overall survival with resection, and overall survival with higher GPA. CONCLUSION: Addition of HBO to SRS for brain metastases is feasible without evident decrement in radiation necrosis and other clinical outcomes.
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Neoplasias Encefálicas , Oxigenoterapia Hiperbárica , Lesões por Radiação , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana , Qualidade de Vida , Resultado do Tratamento , Estudos Retrospectivos , Lesões por Radiação/etiologia , OxigênioRESUMO
INTRODUCTION: As the prevalence of obesity continues to rise, there is a growing need to identify practices that protect overweight patients from injury during spine surgery. Intraoperative neurophysiological monitoring (IONM) has been recommended for complex spine surgery, but its use in obese and morbidly obese patients is understudied. CASE REPORT: This case report describes a patient with morbid obesity and ankylosing spondylitis who was treated for a T9-T10 3-column fracture with a planned, minimally invasive approach. Forty minutes after positioning the patient to prone, the IONM team identified a positive change in the patient's motor responses in the bilateral lower extremities and alerted the surgical team in a timely manner. It turned out that the pressure exerted by gravity on the patient's large pannus resulted in further dislocation of the fracture and narrowing of the spinal canal. The surgical team acknowledged the serious risk of spinal cord compression and, hence, immediately changed the surgical plan to an urgent, open approach for decompression and reduction of the fracture. The patient's lower extremities' motor responses improved after decompression. The patient was ambulatory on post-operative day 2 and pain-free at six-weeks with no other neurologic symptoms. SIGNIFICANCE: The use of IONM in this planned minimally invasive spine surgery for a patient with morbid obesity prevented potentially serious iatrogenic injury. The authors include a literature review that situates this case study in the existing literature and highlights a gap in current knowledge. There are few studies that have examined the use of IONM during spine surgery for morbidly obese patients. More research is needed to elucidate best practices for the use of IONM in spine surgery for morbidly obese patients.
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PURPOSES: Accurate and efficient spine registration is crucial to success of spine image guidance. However, changes in spine pose cause intervertebral motion that can lead to significant registration errors. In this study, we develop a geometrical rectification technique via nonlinear principal component analysis (NLPCA) to achieve level-wise vertebral registration that is robust to large changes in spine pose. METHODS: We used explanted porcine spines and live pigs to develop and test our technique. Each sample was scanned with preoperative CT (pCT) in an initial pose and rescanned with intraoperative stereovision (iSV) in a different surgical posture. Patient registration rectified arbitrary spinal postures in pCT and iSV into a common, neutral pose through a parameterized moving-frame approach. Topologically encoded depth projection 2D images were then generated to establish invertible point-to-pixel correspondences. Level-wise point correspondences between pCT and iSV vertebral surfaces were generated via 2D image registration. Finally, closed-form vertebral level-wise rigid registration was obtained by directly mapping 3D surface point pairs. Implanted mini-screws were used as fiducial markers to measure registration accuracy. RESULTS: In seven explanted porcine spines and two live animal surgeries (maximum in-spine pose change of 87.5 mm and 32.7 degrees averaged from all spines), average target registration errors (TRE) of 1.70 ± 0.15 mm and 1.85 ± 0.16 mm were achieved, respectively. The automated spine rectification took 3-5 min, followed by an additional 30 secs for depth image projection and level-wise registration. CONCLUSIONS: Accuracy and efficiency of the proposed level-wise spine registration support its application in human open spine surgeries. The registration framework, itself, may also be applicable to other intraoperative imaging modalities such as ultrasound and MRI, which may expand utility of the approach in spine registration in general.
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Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Doenças da Coluna Vertebral/diagnóstico , Coluna Vertebral/diagnóstico por imagem , Cirurgia Assistida por Computador/métodos , Ultrassonografia/métodos , Animais , Modelos Animais de Doenças , Marcadores Fiduciais , Humanos , Doenças da Coluna Vertebral/cirurgia , Coluna Vertebral/cirurgia , SuínosRESUMO
Objective The objective of this study was to identify factors associated with improved tumor control at individual sites of recurrence and to define the role of stereotactic radiosurgery (SRS) in the management of local or distant progression following prior radiotherapy. Study Design Clinical data of patients with recurrent skull base chordoma following prior radiotherapy were retrospectively reviewed. Setting and Participants This is a single-center retrospective study including 16 patients from the University of Texas MD Anderson Cancer Center Houston, Texas, United States. Main Outcome Measures Each site of recurrence was considered independently, and the primary outcome was freedom from treatment site progression (FFTSP). Results There were 40 episodes of either local or distant progression treated in 16 patients with skull base chordoma. Tumor recurrence was classified as either local, distant, or both local and distant involving the skull base, spinal column, or leptomeninges. Patients were treated with repeat surgical resection ( n = 16), SRS ( n = 21), or chemotherapy ( n = 25). In multivariate analysis, SRS was the only treatment modality associated with improved FFTSP ( p = 0.006). For tumors treated with SRS, there was no evidence of tumor progression or adverse radiation events. Other factors associated with worse FFTSP included the number of progressive episodes (>3), tumor histology, and leptomeningeal disease. Conclusions For local recurrence following prior radiotherapy, SRS was associated with improved FFTSP. SRS may represent an effective palliative treatment offering durable tumor control at the treated site without significant treatment-related morbidity.
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BACKGROUND: Image guidance in open spinal surgery is compromised by changes in spinal alignment between preoperative images and surgical positioning. We evaluated registration of stereo-views of the surgical field to compensate for vertebral alignment changes. OBJECTIVE: To assess accuracy and efficiency of an optically tracked hand-held stereovision (HHS) system to acquire images of the exposed spine during surgery. METHODS: Standard midline posterior approach exposed L1 to L6 in 6 cadaver porcine spines. Fiducial markers were placed on each vertebra as "ground truth" locations. Spines were positioned supine with accentuated lordosis, and preoperative computed tomography (pCT) was acquired. Spines were re-positioned in a neutral prone posture, and locations of fiducials were acquired with a tracked stylus. Intraoperative stereovision (iSV) images were acquired and 3-dimensional (3D) surfaces of the exposed spine were reconstructed. HHS accuracy was assessed in terms of distances between reconstructed fiducial marker locations and their tracked counterparts. Level-wise registrations aligned pCT with iSV to account for changes in spine posture. Accuracy of updated computed tomography (uCT) was assessed using fiducial markers and other landmarks. RESULTS: Acquisition time for each image pair was <1 s. Mean reconstruction time was <1 s for each image pair using batch processing, and mean accuracy was 1.2 ± 0.6 mm across 6 cases. Mean errors of uCT were 3.1 ± 0.7 and 2.0 ± 0.5 mm on the dorsal and ventral sides, respectively. CONCLUSION: Results suggest that a portable HHS system offers potential to acquire accurate image data from the surgical field to facilitate surgical navigation during open spine surgery.
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Disrafismo Espinal , Cirurgia Assistida por Computador , Animais , Marcadores Fiduciais , Humanos , Imageamento Tridimensional , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , SuínosRESUMO
OBJECTIVE: 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is an effective surgical adjunct for the intraoperative identification of tumor tissue during resection of high-grade gliomas. The use of 5-ALA-induced PpIX fluorescence in glioblastoma (GBM) has been shown to double the extent of gross-total resection and 6-month progression-free survival. The heterogeneity of 5-ALA-induced PpIX fluorescence observed during surgery presents a technical and diagnostic challenge when utilizing this tool intraoperatively. While some regions show bright fluorescence after 5-ALA administration, other regions do not, despite that both regions of the tumor may be histopathologically indistinguishable. The authors examined the biological basis of this heterogeneity using computational methods. METHODS: The authors collected both fluorescent and nonfluorescent GBM specimens from a total of 14 patients undergoing surgery and examined their gene expression profiles. RESULTS: In this study, the authors found that the gene expression patterns characterizing fluorescent and nonfluorescent GBM surgical specimens were profoundly different and were associated with distinct cellular functions and different biological pathways. Nonfluorescent tumor tissue tended to resemble the neural subtype of GBM; meanwhile, fluorescent tumor tissue did not exhibit a prominent pattern corresponding to known subtypes of GBM. Consistent with this observation, neural GBM samples from The Cancer Genome Atlas database exhibited a significantly lower fluorescence score than nonneural GBM samples as determined by a fluorescence gene signature developed by the authors. CONCLUSIONS: These results provide a greater understanding regarding the biological basis of differential fluorescence observed intraoperatively and can provide a basis to identify novel strategies to maximize the effectiveness of fluorescence agents.
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BACKGROUND: Three patients enrolled in a clinical trial of 5-aminolevulinic-acid (5-ALA)-induced fluorescence-guidance, which has been demonstrated to facilitate intracranial tumor resection, were found on neuropathological examination to have focal cortical dysplasia (FCD). OBJECTIVE: To evaluate in this case series visible fluorescence and quantitative levels of protoporphyrin IX (PpIX) during surgery and correlate these findings with preoperative magnetic resonance imaging (MRI) and histopathology. METHODS: Patients were administered 5-ALA (20 mg/kg) approximately 3 h prior to surgery and underwent image-guided, microsurgical resection of their MRI- and electrophysiologically identified lesions. Intraoperative visible fluorescence was evaluated using an operating microscope adapted with a commercially available blue light module. Quantitative PpIX levels were assessed using a handheld fiber-optic probe and a wide-field imaging spectrometer. Sites of fluorescence measurements were co-registered with both preoperative MRI and histopathological analysis. RESULTS: Three patients with a pathologically confirmed diagnosis of FCD (Types 1b, 2a, and 2b) underwent surgery. All patients demonstrated some degree of visible fluorescence (faint or moderate), and all patients had quantitatively elevated concentrations of PpIX. No evidence of neoplasia was identified on histopathology, and in 1 patient, the highest concentrations of PpIX were found at a tissue site with marked gliosis but no typical histological features of FCD. CONCLUSION: FCD has been found to be associated with intraoperative 5-ALA-induced visible fluorescence and quantitatively confirmed elevated concentrations of the fluorophore PpIX in 3 patients. This finding suggests that there may be a role for fluorescence-guidance during surgical intervention for epilepsy-associated FCD.
Assuntos
Ácido Aminolevulínico/administração & dosagem , Monitorização Neurofisiológica Intraoperatória/métodos , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/cirurgia , Microcirurgia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Fluorescência , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Malformações do Desenvolvimento Cortical/complicações , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination. METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620-640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis. RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery. CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional blue-light excitation. Clinical trial registration no.: NCT02191488 (clinicaltrials.gov).
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Corantes Fluorescentes/química , Glioma/diagnóstico por imagem , Glioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Protoporfirinas/química , Adulto , Idoso , Craniotomia , Feminino , Fluorescência , Humanos , Processamento de Imagem Assistida por Computador , Ácidos Levulínicos/farmacologia , Imageamento por Ressonância Magnética , Masculino , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Microscopia de Fluorescência , Pessoa de Meia-Idade , Estimulação Luminosa , Adulto Jovem , Ácido AminolevulínicoRESUMO
BACKGROUND: The use of image guidance during spinal surgery has been limited by several anatomic factors such as intervertebral segment motion and ineffective spine immobilization. In its current form, the surgical field is coregistered with a preoperative computed tomography (CT), often obtained in a different spinal confirmation, or with intraoperative cross-sectional imaging. Stereovision offers an alternative method of registration. OBJECTIVE: To demonstrate the feasibility of stereovision-mediated coregistration of a human spinal surgical field using a proof-of-principle study, and to provide preliminary assessments of the technique's accuracy. METHODS: A total of 9 subjects undergoing image-guided pedicle screw placement also underwent stereovision-mediated coregistration with preoperative CT imaging. Stereoscopic images were acquired using a tracked, calibrated stereoscopic camera system mounted on an operating microscope. Images were processed, reconstructed, and segmented in a semi-automated manner. A multistart registration of the reconstructed spinal surface with preoperative CT was performed. Registration accuracy, measured as surface-to-surface distance error, was compared between stereovision registration and a standard registration. RESULTS: The mean surface reconstruction error of the stereovision-acquired surface was 2.20 ± 0.89 mm. Intraoperative coregistration with stereovision was performed with a mean error of 1.48 ± 0.35 mm compared to 2.03 ± 0.28 mm using a standard point-based registration method. The average computational time for registration with stereovision was 95 ± 46 s (range 33-184 s) vs 10to 20 min for standard point-based registration. CONCLUSION: Semi-automated registration of a spinal surgical field using stereovision is possible with accuracy that is at least comparable to current landmark-based techniques.
Assuntos
Imageamento Tridimensional/métodos , Laminectomia/métodos , Medula Espinal/cirurgia , Fusão Vertebral/métodos , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Parafusos Pediculares , Resultado do TratamentoRESUMO
BACKGROUND: Current methods of spine registration for image guidance have a variety of limitations related to accuracy, efficiency, and cost. OBJECTIVE: To define the accuracy of stereovision-mediated co-registration of a spinal surgical field. METHODS: A total of 10 explanted porcine spines were used. Dorsal soft tissue was removed to a variable degree. Bone screw fiducials were placed in each spine and high-resolution computed tomography (CT) scanning performed. Stereoscopic images were then obtained using a tracked, calibrated stereoscopic camera system; images were processed, reconstructed, and segmented in a semi-automated manner. A multistart registration of the reconstructed spinal surface with preoperative CT was performed. Target registration error (TRE) in the region of the laminae and facets was then determined, using bone screw fiducials not included in the original registration process. Each spine also underwent multilevel laminectomy, and TRE was then recalculated for varying amounts of bone removal. RESULTS: The mean TRE of stereovision registration was 2.19 ± 0.69 mm when all soft tissue was removed and 2.49 ± 0.74 mm when limited soft tissue removal was performed. Accuracy of the registration process was not adversely affected by laminectomy. CONCLUSION: Stereovision offers a promising means of registering an open, dorsal spinal surgical field. In this study, overall mean accuracy of the registration was 2.21 mm, even when bony anatomy was partially obscured by soft tissue or when partial midline laminectomy had been performed.