Sensitizing brain metastases to stereotactic radiosurgery using hyperbaric oxygen: A proof-of-principle study.

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.

Intra-operative emergence of occult dural arteriovenous fistula after middle meningeal artery embolization for chronic subdural hematoma: Case report and literature review.

Dural arteriovenous fistulae of the middle meningeal artery (MMA-dAVF) are high risk lesions that can lead to intracranial hemorrhage. We describe the case of an adult male that presented with chronic subdural hematomas and was treated with burr hole craniotomy plus middle meningeal artery (MMA) embolization. Although the pre-embolization angiogram showed no signs of a fistula, a fistula arising from the MMA and draining into the superior sagittal sinus emerged intra-operatively. To our knowledge, this is the first case of intra-operative emergence of occult MMA-dAVF with intracranial drainage during MMA embolization for chronic subdural hematoma treatment. This observation supports monitoring for and embolizing spontaneous MMA-dAVF following MMA embolization.

Quantifying Tumor and Vasculature Deformations during Laryngoscopy.

Retractors and scopes used in head and neck surgery to provide adequate surgical exposure also deform critical structures in the region. Surgeons typically use preoperative imaging to plan and guide their tumor resections, however the large tissue deformation resulting from placement of retractors and scopes reduces the utility of preoperative imaging as a reliable roadmap. We quantify the extent of tumor and vasculature deformation in patients with tumors of the larynx and pharynx undergoing diagnostic laryngoscopy. A mean tumor displacement of 1.02 cm was observed between the patients' pre- and intra-operative states. Mean vasculature displacement at key bifurcation points was 0.99 cm. Registration to the hyoid bone can reduce tumor displacement to 0.67 cm and improve carotid stem angle deviations but increase overall vasculature displacement. The large deformation results suggest limitations in reliance on preoperative imaging and that using specific landmarks intraoperatively or having more intraoperative information could help to compensate for these deviations and ultimately improve surgical success.

Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association.

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.

Symptomatic Lumbar Facet Synovial Cysts: Clinical Outcomes Following Percutaneous CT-Guided Cyst Rupture with Intra-articular Steroid Injection.

PURPOSE: To evaluate clinical outcomes following percutaneous rupture of symptomatic lumbar facet synovial cysts (LFSCs) with intra-articular steroid injection. MATERIALS AND METHODS: In this retrospective review, 44 consecutive patients with symptomatic LFSCs received primary treatment with CT-guided synovial cyst rupture with intra-articular steroid injection. Outcomes questionnaires were obtained before and 1, 4, 26, and 52 weeks after LFSC rupture. Assessment included pain medication use and numeric rating scale (NRS), Oswestry Disability Index (ODI), and 12-item short form health survey (SF-12) physical and mental composite scores (PCS and MCS). Clinical endpoint was 52-week survey response or surgery. RESULTS: LFSC rupture was technically successful in 84% (37/44) of cases. Clinical endpoint was reached in 68% (30/44) of patients with 82% overall 1-year follow-up. Lumbar spine surgery was performed in 25% (11/44) of patients within 1 year after procedure. Mean NRS, ODI, and SF-12 PCS demonstrated significant improvement at all follow-up time points (P < .001). At 52-week follow-up, NRS decreased from 8.1 to 3.7 (P < .001), ODI improved from 35 to 24 (P = .006), and SF-12 PCS improved from 31 to 42 (P < .001). Daily pain medication decreased from 71% (31/44) of patients before procedure to 29% (9/26) at 52-week follow-up (P = .012). History of prior lumbar intervention was associated with poorer LFSC rupture success (P = .025) and ODI (P = .047). CONCLUSIONS: NRS, ODI, and SF-12 PCS indices improved and pain medication use decreased significantly at all time points over 1-year follow-up after percutaneous rupture of symptomatic LFSCs with intra-articular steroid injection.

Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism.

Cerebral tissue oxygenation (oxygen tension, pO2) is a critical parameter that is closely linked to brain metabolism, function, and pathophysiology. In this work, we have used electron paramagnetic resonance oximetry with a deep-tissue multi-site oxygen-sensing probe, called implantable resonator, to monitor temporal changes in cerebral pO2 simultaneously at four sites in a rabbit model of ischemic stroke induced by embolic clot. The pO2 values in healthy brain were not significantly different among the four sites measured over a period of 4 weeks. During exposure to 15% O2 (hypoxia), a sudden and significant decrease in pO2 was observed in all four sites. On the other hand, brief exposure to breathing carbogen gas (95% O2 + 5% CO2) showed a significant increase in the cerebral pO2 from baseline value. During ischemic stroke, induced by embolic clot in the left brain, a significant decline in the pO2 of the left cortex (ischemic core) was observed without any change in the contralateral sites. While the pO2 in the non-infarct regions returned to baseline at 24-h post-stroke, pO2 in the infarct core was consistently lower compared to the baseline and other regions of the brain. The results demonstrated that electron paramagnetic resonance oximetry with the implantable resonator can repeatedly and simultaneously report temporal changes in cerebral pO2 at multiple sites. This oximetry approach can be used to develop interventions to rescue hypoxic/ischemic tissue by modulating cerebral pO2 during hypoxic and stroke injury.

Brain mechanical property measurement using MRE with intrinsic activation.

Many pathologies alter the mechanical properties of tissue. Magnetic resonance elastography (MRE) has been developed to noninvasively characterize these quantities in vivo. Typically, small vibrations are induced in the tissue of interest with an external mechanical actuator. The resulting displacements are measured with phase contrast sequences and are then used to estimate the underlying mechanical property distribution. Several MRE studies have quantified brain tissue properties. However, the cranium and meninges, especially the dura, are very effective at damping externally applied vibrations from penetrating deeply into the brain. Here, we report a method, termed 'intrinsic activation', that eliminates the requirement for external vibrations by measuring the motion generated by natural blood vessel pulsation. A retrospectively gated phase contrast MR angiography sequence was used to record the tissue velocity at eight phases of the cardiac cycle. The velocities were numerically integrated via the Fourier transform to produce the harmonic displacements at each position within the brain. The displacements were then reconstructed into images of the shear modulus based on both linear elastic and poroelastic models. The mechanical properties produced fall within the range of brain tissue estimates reported in the literature and, equally important, the technique yielded highly reproducible results. The mean shear modulus was 8.1 kPa for linear elastic reconstructions and 2.4 kPa for poroelastic reconstructions where fluid pressure carries a portion of the stress. Gross structures of the brain were visualized, particularly in the poroelastic reconstructions. Intra-subject variability was significantly less than the inter-subject variability in a study of six asymptomatic individuals. Further, larger changes in mechanical properties were observed in individuals when examined over time than when the MRE procedures were repeated on the same day. Cardiac pulsation, termed intrinsic activation, produces sufficient motion to allow mechanical properties to be recovered. The poroelastic model is more consistent with the measured data from brain at low frequencies than the linear elastic model. Intrinsic activation allows MRE to be performed without a device shaking the head so the patient notices no differences between it and the other sequences in an MR examination.

Absence of abnormal vessels in the subarachnoid space on conventional magnetic resonance imaging in patients with spinal dural arteriovenous fistulas.

Spinal dural arteriovenous fistula (DAVF) is an uncommon condition that can be difficult to diagnose. This often results in misdiagnosis and treatment delay. Although conventional MRI plays an important role in the initial screening for the disease, the typical MRI findings may be absent. In this article, the authors present a series of 4 cases involving patients with angiographically proven spinal DAVFs who demonstrated cord T2 prolongation on conventional MRI but without abnormal subarachnoid flow voids or enhancement. These cases suggest that spinal DAVF cannot be excluded in symptomatic patients with cord edema based on conventional MRI findings alone. Dynamic Gd-enhanced MR angiography (MRA) was successful in demonstrating abnormal spinal vasculature in all 4 cases. This limited experience provides support for the role of spinal MRA in patients with abnormal cord signal and symptoms suggestive of DAVF even when typical MRI findings of a DAVF are absent.

Tumor bed dynamics after surgical resection of brain metastases: implications for postoperative radiosurgery.

PURPOSE: To analyze 2 factors that influence timing of radiosurgery after surgical resection of brain metastases: target volume dynamics and intracranial tumor progression in the interval between surgery and cavity stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Three diagnostic magnetic resonance imaging (MRI) scans were retrospectively analyzed for 41 patients with a total of 43 resected brain metastases: preoperative MRI scan (MRI-1), MRI scan within 24 hours after surgery (MRI-2), and MRI scan for radiosurgery planning, which is generally performed ≤1 week before SRS (MRI-3). Tumors were contoured on MRI-1 scans, and resection cavities were contoured on MRI-2 and MRI-3 scans. RESULTS: The mean tumor volume before surgery was 14.23 cm3, and the mean cavity volume was 8.53 cm3 immediately after surgery and 8.77 cm3 before SRS. In the interval between surgery and SRS, 20 cavities (46.5%) were stable in size, defined as a change of ≤2 cm3; 10 cavities (23.3%) collapsed by >2 cm3; and 13 cavities (30.2%) increased by >2 cm3. The unexpected increase in cavity size was a result of local progression (2 cavities), accumulation of cyst-like fluid or blood (9 cavities), and nonspecific postsurgical changes (2 cavities). Finally, in the interval between surgery and SRS, 5 cavities showed definite local tumor progression, 4 patients had progression elsewhere in the brain, 1 patient had both local progression and progression elsewhere, and 33 patients had stable intracranial disease. CONCLUSIONS: In the interval between surgical resection and delivery of SRS, surgical cavities are dynamic in size; however, most cavities do not collapse, and nearly one-third are larger at the time of SRS. These observations support obtaining imaging for radiosurgery planning as close to SRS delivery as possible and suggest that delaying SRS after surgery does not offer the benefit of cavity collapse in most patients. A prospective, multi-institutional trial will provide more guidance to the optimal timing of cavity SRS.

Invasive interventional management of post-hemorrhagic cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

Current clinical practice standards are addressed for the invasive interventional management of post-hemorrhagic cerebral vasospasm (PHCV) in patients with aneurysmal subarachnoid hemorrhage. The conclusions, based on an assessment by the Standards Committee of the Society of Neurointerventional Surgery, included a critical review of the literature using guidelines for evidence based medicine proposed by the Stroke Council of the American Heart Association and the University of Oxford, Centre for Evidence Based Medicine. Specifically examined were the safety and efficacy of established invasive interventional therapies, including transluminal balloon angioplasty (TBA) and intra-arterial vasodilator infusion therapy (IAVT). The assessment shows that these invasive interventional therapies may be beneficial and may be considered for PHCV-that is, symptomatic with cerebral ischemia and refractory to maximal medical management. As outlined in this document, IAVT may be beneficial for the management of PHCV involving the proximal and/or distal intradural cerebral circulation. TBA may be beneficial for the management of PHCV that involves the proximal intradural cerebral circulation. The assessment shows that for the indications described above, TBA and IAVT are classified as Class IIb, Level B interventions according to the American Heart Association guidelines, and Level 4, Grade C interventions according to the University of Oxford Centre for Evidence Based Medicine guidelines.

Reporting standards for angiographic evaluation and endovascular treatment of cerebral arteriovenous malformations.

These guidelines were developed by consensus of a multidisciplinary panel of specialists interested in the evaluation and treatment of patients with arteriovenous malformations (AVMs) of the CNS. The reporting criteria described will serve as a template for trial design and for clinical investigators who wish to report on endovascular therapy of cerebral AVMs. Direct comparison of various treatment paradigms is important to standardization of care, maximization of good treatment outcomes, assessment of new methods and technologies.

Hemorrhagic stroke.

When patients present to the emergency room with sudden onset of focal neurologic symptoms or altered consciousness, hemorrhagic stroke is a major focus of emergency diagnostic evaluation. The entities that compose hemorrhagic stroke, intracerebral and subarachnoid hemorrhage, are readily diagnosed with advanced imaging. This article reviews current imaging options for the detection of acute hemorrhage, along with the expected imaging findings for each modality. Common and unusual causes and their distinguishing imaging features are discussed. Imaging strategies and recent work in specific imaging findings that may guide patient management in the future are also addressed.

Computed tomographic angiography as an adjunct to digital subtraction angiography for the pre-operative assessment of cerebral aneurysms.

OBJECTIVES: Computerized tomographic angiography (CTA) has emerged as a valuable diagnostic tool for the management of patients with cerebrovascular disease. The use of CTA in lieu of, or as an adjunct to, conventional cerebral angiography in the management of cerebral aneurysms awaits further experience. In this study, we evaluated the role of CTA specifically for the pre-operative assessment and planning of cerebral aneurysm surgery. PATIENTS AND METHODS: We reviewed the relevant neuroimaging of all patients treated at Dartmouth Hitchcock Medical Center between January, 2001 and December, 2004 with a diagnosis of cerebral aneurysm and diagnostic evaluation with both CTA and conventional digital subtraction angiography (DSA) using standard imaging protocols. 32 patients underwent both CTA and DSA during the study period for a total of 36 aneurysms. Images were independently re-assesed by two neurosurgeons for information valuable for pre-operative surgical planning. RESULTS: In 26 of 36 aneurysms (72%), the CTA was felt to provide the best image quality in defining the morphology of the aneurysm. In 14 aneurysms (39%), CTA provided clinically valuable anatomic detail not demonstrated on DSA, largely due to better visualization of parent and perforating vessel relationships at the aneurysm neck. There were no instances where a lesion was seen on DSA but missed on CTA. The DSA was of most clinical value in determining flow dynamics, such as the arterial supply of an anterior communicating artery aneurysm and distal anterior cerebral branches via the two A1 segments. CONCLUSION: CTA with three-dimensional reconstructions is a valuable adjunct to the preoperative evaluation of cerebral aneurysms. We advocate routine use of CTA in all patients in whom surgical aneurysm repair is planned, even when DSA has already been performed.

Value of immediate preprocedure magnetic resonance imaging in patients scheduled to undergo vertebroplasty or kyphoplasty.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To determine the incidence of additional vertebral compression fractures diagnosed with repeat MRI immediately before vertebroplasty or kyphoplasty. SUMMARY OF BACKGROUND DATA: Vertebral compression fractures, which occur frequently in the elderly, are more likely in patients with prior vertebral compression fracture. When patients are evaluated for vertebroplasty, it is important to identify all unhealed fractures for effective treatment planning. METHODS: In a retrospective study, we reviewed the records of all patients (n = 194) treated with vertebroplasty or kyphoplasty over a 6-year period at our institution, and identified all patients who had undergone a repeat MRI within 7 days of vertebroplasty or kyphoplasty. These studies were obtained as part of a clinical protocol prescribing a repeat MRI for any patient whose MRI had been obtained more than 3 months before the evaluation, or who had a change in their pain between referral and evaluation. RESULTS: Twenty patients met inclusion criteria for the immediate preprocedure MRI protocol. A total of 14 new fractures in 11 patients were discovered on the immediate preprocedure MRI. Of these 14, 6 had less than 15% loss of height, making them potentially occult on radiographs; 3 fractures developed in 2 patients who had no change in back pain. CONCLUSION: In select candidates for vertebroplasty or kyphoplasty, a repeat preprocedure MRI obtained within 1 week can help ensure that all painful fractures are treated. There is demonstrable value in this protocol for patients with an imaging evaluation over 3 months old or who have had any change in symptoms since the initial imaging workup.

Quick-brain magnetic resonance imaging for nonhydrocephalus indications.

OBJECT: In 2002, "quick-brain" (QB) MR imaging (ultrafast spin echo T2-weighted imaging) was introduced as an alternative technique to CT scanning for assessing children with hydrocephalus. The authors have observed high patient and physician satisfaction with this technique at their institution, which has led to an increasing frequency of its use for nonhydrocephalic indications. The goal in this study was to characterize, quantitate, and assess the use of QB MR imaging for these additional indications. METHODS: Between February 2003 and December 2007, 1146 consecutive QB MR imaging studies were performed, and the findings were entered prospectively into a radiology database. All available clinical records were retrospectively reviewed to assign > or = 1 of the following indications to each study: hydrocephalus, macrocephaly, Chiari malformation, intracranial cyst, screening prior to lumbar puncture, screening for congenital anomalies, trauma, and other. Changes in the distribution of indications over time and clinical experience for each indication were reviewed. RESULTS: The total number of QB imaging studies performed increased each year. The proportion of studies performed for nonhydrocephalic indications also increased (from 23 to 50%). The most common indication was screening for macrocephaly, and all other indications were nearly evenly distributed. Quick-brain MR imaging was used extensively for the initial evaluation and follow-up in patients with little need for additional studies. Its false-negative rate, however, remains unknown. CONCLUSIONS: The role of QB MR imaging for nonhydrocephalic indications is expanding, and it appears promising for a number of screening and surveillance paradigms. "Quick-brain plus" protocols for specific indications may add sensitivity and are under development.

A phase II study of thalidomide and irinotecan for treatment of glioblastoma multiforme.

PURPOSE: Irinotecan is a cytotoxic agent with activity against gliomas. Thalidomide, an antiangiogenic agent, may play a role in the treatment of glioblastoma multiforme (GBM). To evaluate the combination of thalidomide and irinotecan, we conducted a phase II trial in adults with newly-diagnosed or recurrent GBM. PATIENTS AND METHODS: Thalidomide was given at a dose of 100 mg/day, followed by dose escalation every 2 weeks by 100 mg/day to a target of 400 mg/day. Irinotecan was administered on day 1 of each 3 week cycle. Irinotecan dose was 700 mg/m(2) for patients taking enzyme-inducing anticonvulsants and 350 mg/m(2) for all others. The primary endpoint was tumor response, assessed by MRI. Secondary endpoints were toxicity, progression-free survival, and overall survival. RESULTS: Twenty-six patients with a median age of 55 years were enrolled, with fourteen evaluable for the primary outcome, although all patients were included for secondary endpoints. One patient (7%) exhibited a partial response after twelve cycles, and eleven patients (79%) had stable disease. The intention to treat group with recurrent disease included 16 patients who had a 6-month PFS of 19% (95% CI: 4-46%) and with newly-diagnosed disease included 10 patients who had a 6-month PFS of 40% (95% CI: 12-74%). Gastrointestinal (GI) toxicity was mild, but six patients (23%) experienced a venous thromboembolic complication. Two patients had Grade 4 treatment-related serious adverse events that required hospitalization. There were no treatment-related deaths. CONCLUSION: The combination of irinotecan and thalidomide has limited activity against GBM. Mild GI toxicity was observed, but venous thromboembolic complications were common.