Planning of gamma knife radiosurgery (GKR) for brain arteriovenous malformations using triple magnetic resonance angiography (triple-MRA).

PURPOSE: Intra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to evaluate whether a combination of three Magnetic Resonance Angiography sequences (triple-MRA) could be used for delineation of brain AVMs for Gamma Knife Radiosurgery (GKR). METHODS: Fifteen patients undergoing DSA for GKR targeting of brain AVMs also underwent triple-MRA: 4D Arterial Spin Labelling based angiography (ASL-MRA), Contrast-Enhanced Time-Resolved MRA (CE-MRA) and High Definition post-contrast Time-Of-Flight angiography (HD-TOF). The arterial phase of the AVM nidus was delineated on triple-MRA by an interventional neuroradiologist and a consultant neurosurgeon (triple-MRA volume). Triple-MRA volumes were compared to AVM targets delineated by the clinical team for delivery of GKR using the current planning paradigm, i.e., stereotactic DSA and volumetric MRI (DSA volume). Difference in size, degree of inclusion (DI) and concordance index (CcI) between DSA and triple-MRA volumes are reported. RESULTS: AVM target volumes delineated on triple-MRA were on average 9.8% smaller than DSA volumes (95%CI:5.6-13.9%; SD:7.14%; p = .003). DI of DSA volume in triple-MRA volume was on average 73.5% (95%CI:71.2-76; range: 65-80%). The mean percentage of triple-MRA volume not included on DSA volume was 18% (95%CI:14.7-21.3; range: 7-30%). CONCLUSION: The technical feasibility of using triple-MRA for visualisation and delineation of brain AVMs for GKR planning has been demonstrated. Tighter and more precise delineation of AVM target volumes could be achieved by using triple-MRA for radiosurgery targeting. However, further research is required to ascertain the impact this may have in obliteration rates and side effects.

Investigating the oxygenation of brain arteriovenous malformations using quantitative susceptibility mapping.

Brain arteriovenous malformations (AVMs) are congenital vascular anomalies characterized by arteriovenous shunting through a network of coiled and tortuous vessels. Because of this anatomy, the venous drainage of an AVM is hypothesized to contain more oxygenated, arterialized blood than healthy veins. By exploiting the paramagnetic properties of deoxygenated hemoglobin in venous blood using magnetic resonance imaging (MRI) quantitative susceptibility mapping (QSM), we aimed to explore venous density and oxygen saturation (SvO2) in patients with a brain AVM. We considered three groups of subjects: patients with a brain AVM before treatment using gamma knife radiosurgery (GKR); patients three or more years post-GKR treatment; and healthy volunteers. First, we investigated the appearance of AVMs on QSM images. Then, we investigated whether QSM could detect increased SvO2 in the veins draining the malformations. In patients before GKR, venous density, but not SvO2, was significantly larger in the hemisphere containing the AVM compared to the contralateral hemisphere (p = 0.03). Such asymmetry was not observed in patients after GKR or in healthy volunteers. Moreover, in all patients before GKR, the vein immediately draining the AVM nidus had a higher SvO2 than healthy veins. Therefore, QSM can be used to detect SvO2 alterations in brain AVMs. However, since factors such as flow-induced signal dephasing or the presence of hemosiderin deposits also strongly affect QSM image contrast, AVM vein segmentation must be performed based on alternative MRI acquisitions, e.g., time of flight magnetic resonance angiography or T1-weighted images. This is the first study to show, non-invasively, that AVM draining veins have a significantly larger SvO2 than healthy veins, which is a finding congruent with arteriovenous shunting.

Investigation of dosimetric differences between the TMR 10 and convolution algorithm for Gamma Knife stereotactic radiosurgery.

Since its inception, doses applied using Gamma Knife Radiosurgery (GKR) have been calculated using a simple TMR algorithm, which assumes the patient's head is of even density, the same as water. This results in a significant approximation of the dose delivered by the Gamma Knife. We investigated how GKR dose cal-culations varied when using a new convolution algorithm clinically available for GKR planning that takes into account density variations in the head compared with the established calculation algorithm. Fifty-five patients undergoing GKR and harboring 85 lesions were voluntarily and prospectively enrolled into the study. Their clinical treatment plans were created and delivered using TMR 10, but were then recalculated using the density correction algorithm. Dosimetric differences between the planning algorithms were noted. Beam on time (BOT), which is directly proportional to dose, was the main value investigated. Changes of mean and maximum dose to organs at risk (OAR) were also assessed. Phantom studies were performed to investigate the effect of frame and pin materials on dose calculation using the convolution algorithm. Convolution yielded a mean increase in BOT of 7.4% (3.6%-11.6%). However, approximately 1.5% of this amount was due to the head contour being derived from the CT scans, as opposed to measurements using the Skull Scaling Instrument with TMR. Dose to the cochlea calculated with the convolution algorithm was approximately 7% lower than with the TMR 10 algorithm. No significant difference in relative dose distribution was noted and CT artifact typically caused by the stereotactic frame, glue embolization material or different fixation pin materials did not systematically affect convolu-tion isodoses. Nonetheless, substantial error was introduced to the convolution calculation in one target located exactly in the area of major CT artifact caused by a fixation pin. Inhomogeneity correction using the convolution algorithm results in a considerable, but consistent, dose shift compared to the TMR 10 algorithm traditionally used for GKR. A reduction of the prescription dose may be neces-sary to obtain the same clinical effect with the convolution algorithm. Head shape definition using CT outlining can reduce treatment uncertainty from head shape approximations.

Evaluation of the stability of the stereotactic Leksell Frame G in Gamma Knife radiosurgery.

The purpose of this study was to evaluate the stability of the Leksell Frame G in Gamma Knife radiosurgery (GKR). Forty patients undergoing GKR underwent pretreatment stereotactic MRI for GKR planning and stereotactic CT immediately after GKR. The stereotactic coordinates of four anatomical landmarks (cochlear apertures and the summits of the anterior post of the superior semicircular canals, bilaterally) were measured by two evaluators on two separate occasions in the pre-treatment MRI and post-treatment CT scans and the absolute distance between the observations is reported. The measurement method was validated with an indepen-dent group of patients who underwent both stereotactic MRI and CT imaging before treatment (negative controls; n: 5). Patients undergoing GKR for arteriovenous malformations (AVM) also underwent digital subtraction angiography (DSA), which could result in extra stresses on the frame. The distance between landmark local-ization in the scans for the negative control group (0.63 mm; 95% CI: 0.57-0.70; SD: 0.29) represents the overall consistency of the evaluation method and provides an estimate of the minimum displacement that could be detected by the study. Two patients in the study group had the fiducial indicator box accidentally misplaced at post-treatment CT scanning. This simulated the scenario of a frame displacement, and these cases were used as positive controls to demonstrate that the evaluation method is capable of detecting a discrepancy between the MRI and CT scans, if there was one. The mean distance between the location of the landmarks in the pretreatment MRI and post-treatment CT scans for the study group was 0.71 mm (95% CI: 0.68-0.74; SD:0.32), which was not statistically different from the over-all uncertainty of the evaluation method observed in the negative control group (p = 0.06). The subgroup of patients with AVM (n: 9), who also underwent DSA, showed a statistically significant difference between the location of the landmarks compared to subjects with no additional imaging: 0.78 mm (95% CI: 0.72-0.84) vs. 0.69 mm (95% CI: 0.66-0.72), p = 0.016. This is however a minimal differ-ence (0.1 mm) and the mean difference in landmark location for each AVM patient remained submillimeter. This study demonstrates submillimeter stability of the Leksell Frame G in GKR throughout the treatment procedure.

A systematic review of middle meningeal artery embolization for minimally symptomatic chronic subdural haematomas that do not require immediate evacuation.

Introduction: Embolization of the Middle Meningeal Artery (EMMA) is an emerging treatment option for patients with Chronic Subdural Haematoma (CSDH). Questions: (1) Can EMMA change the natural history of untreated minimally symptomatic CSDH which do not require immediate evacuation? (2) What is the role of EMMA in the prevention of recurrence following surgical treatment? (3) Can the procedure be performed under local anaesthetic? Material and methods: Systematic literature review. No randomised clinical trials available on EMMA for meta-analysis. Results: Six unique large cohorts with more than 50 embolisations were identified (evidence: 3b-4). EMMA can control the progression of surgically naïve CSDH in 91.1-100% of the patients, in which haematoma expansion is halted, or the lesion decreases and resolves. Treatment failure requiring surgery occurs in 0-4.1% of the patients having EMMA as the primary and only treatment. Treatment failure requiring surgery goes up slightly to 6.8% if post-surgical patients are included. When EMMA is used as postsurgical adjunctive the risk of recurrence is 1.4-8.9% compared to 10-20% in surgical series. EMMA has minimal morbidity and it is feasible under local anaesthesia or slight sedation in the majority of cases. Conclusion: There is cumulative low-quality evidence in the literature that EMMA may be able to modify the natural course of the disease. It appears effective in controlling progression of CSDHs in patients having it as a primary standing alone treatment and it reduces the risk of recurrence and the need for surgical intervention in refractory postsurgical cases or as a postsurgical adjunctive treatment with minimal morbidity (recommendation: C).

Effect of labelling plane angulation and position on labelling efficiency and cerebral blood flow quantification in pseudo-continuous arterial spin labelling.

Pseudo-continuous arterial spin labelling (pCASL) is the MRI method of choice for non-invasive perfusion measurement in research and clinical practice. Knowledge of the labelling efficiency, α, is essential for accurate quantification of cerebral blood flow (CBF). Typically, a theoretical α value is used, based on an idealistic model and an assumption of spins flowing perpendicularly to the labelling plane. The aim of this work was to investigate the effect of violating this assumption, and to characterize the influence of labelling plane angulation with respect to the vessel direction on labelling efficiency and measured CBF. The effect of labelling plane angulation on labelling efficiency was demonstrated using a numerical simulation of spins at different velocities. Acquisitions from healthy volunteers were used to test the effect of a range of angulation offsets. Additional sub-optimal positions of the labelling plane with respect to the vertebral arteries, at locations where the direction of flow changes significantly from the head-foot direction, were also considered. No significant change in the measured CBF was seen when the labelling plane was angled up to 60° to the labelled vessel or when it was placed in sub-optimal positions. This study shows that in adult subjects, the efficiency of pCASL is robust to the angulation and positioning of the labelling plane beyond the range of potential operator error.

Cirugía, radioterapia y quimioterapia, ¿cómo cada uno contribuye al resultado del tratamiento en adultos con glioblastoma? / How surgery, radiotherapy and chemotherapy each contribute to the outcome of treatment for adult patients with Glioblastoma?

Introduction: glioblastoma is a common condition associated with high morbidity and mortality; most of newly diagnosed patients will die within two years. The current standard therapy is maximal surgical resection followed by radiotherapy plus concomitant and adjuvant temozolamide. Objective: it is the aim of this review to evaluate how determinant surgical resection, radiotherapy and chemotherapy are to the outcome of patients with glioblastoma. Methods: a literature search is done to identify trials evaluating the outcome of adults with glioblastoma after being treated with surgery, radiotherapy or chemotherapy. The Oxford Centre for Evidence-based Medicine Levels of Evidence model is used to grade the quality of the available evidence. Results: 18 articles, reporting results of 15 studies were included. Five trials evaluated the effect to surgery in survival. Surgical provides as much as 4.9 months benefit in overall survival in cases in which complete resection is possible. A systematic review and four clinical trials reported that radiotherapy increases the mean overall survival in a range from three to five months. The European Organization for research and treatment of Cancer and The National Cancer Institute of Canada Clinical Trials Group (EORT-NCIC) described in 2005 an increase of the survival by two- three months on patients receiving concomitant and adjuvant TMZ compared to patients receiving radiotherapy alone. Addition of a novel chemotherapeutic agent seems to improve the outcome of patients compared to the current standard of care. Conclusion: surgery, radiotherapy and chemotherapy, each have a modest effect in the outcome of adults with glioblastoma.

Introducción: el glioblastoma es un tumor frecuente asociado a alta morbilidad y mortalidad, la mayoría de pacientes antes de 2 años desde el diagnóstico. La terapia estándar actual es resección quirúrgica máxima asociada a radioterapia más temozolomida concomitante y coadyuvante. Objetivo: evaluar qué tan determinantes son la resección quirúrgica, radioterapia y quimioterapia para el resultado del tratamiento en pacientes con glioblastoma. Metodología de búsqueda: una revisión de la literatura es hecha para identificar estudios que evalúen el resultado del tratamiento de adultos con glioblastoma tras ser tratados con cirugía, radioterapia o quimioterapia. El modelo de niveles de evidencia del Centro de Medicina basada en la evidencia de Oxford es usado para calificar la calidad de la evidencia encontrada. Resultados: 18 artículos, reportando resultados de 15 estudios son incluidos. Cinco estudios evaluar el efecto de cirugía en la sobrevida. La resección quirúrgica provee un beneficio tan alto como 4,9 meses en la sobrevida global en los casos en que la resección máxima es posible. Una revisión sistemática y cuatro ensayos clínicos han reportado que la radioterapia incrementa el promedio de sobrevida global en un rango de tres a cinco meses. La organización Europea para la investigación y manejo del Cáncer y el Grupo Ensayos Clínicos del Instituto Nacional de Cáncer de Canadá (EORT-NCIC) describió en el 2005 un incremento en la sobrevida global en dos a tres meses en pacientes que reciben tratamiento concomitante y coadyuvante con temozolomida en comparación con pacientes que sólo reciben radioterapia. La adición de uno de los nuevos agentes quimioterapéuticos parece mejorar el resultado del manejo comparado con el actual tratamiento estándar. Conclusión: el tratamiento quirúrgico, la radioterapia y la quimioterapia; cada uno tiene un efecto modesto en el resultado del tratamiento de pacientes con glioblastoma.

Cuál es la evidencia, de comportamiento y datos de imágenes, que podemos predecir cómo se recupera la gente después de un accidente cerebrovascular isquémico? / What is the evidence, from behavioural and imaging data, that we can predict how well people recover after ischemic stroke?

Background: the incidence of stroke in developing countries is increasing and it is the leading cause of longstanding disability in developed countries. Early prediction of future functional abilities is important for stroke management. It is intended to review whether the initial severity of the deficit and the imaging findings could predict long term recovering after ischemic stroke. Methods: the PubMed database was searched to identify studies evaluating how the initial neurological deficit and the imaging findings could predict long term recovery after ischemic stroke. 35 articles were selected to develop a non systematic review and the Oxford Centre for Evidence-based Medicine Levels of Evidence model was used to grade the quality of the found evidence. Results: age and initial deficit evaluated with the National Institutes of Health Stroke Scale were the best predictors of long term recovery after ischemic stroke. The severity of the deficit in specific categories such as upper limb functions, walking and activities of the daily life had a lower level of evidence on prediction of post-stroke disability. Not a definite prognostic value had been convincingly demonstrated for size of infarction. Location of the lesion, particularly the compromise of the cortico-spinal tract evaluated with diffusion tensor imaging appeared to be a good predictor of recovery, and the pattern of brain activation after stroke evaluated with functional magnetic resonance imaging or positron emission tomography scan had a moderate level of evidence as predictor of recovery after stroke. Conclusion: the severity of the initial deficit can be used to predict how well subjects will recover from an ischemic stroke and novel imaging techniques are very promising tools to predict long time recovery after ischemic stroke..

Introducción: la incidencia de enfermedad cerebro vascular en países desarrollados está en aumento y es la primera causa de discapacidad permanente en países desarrollados. La predicción temprana de futura funcionalidad es importante para el tratamiento de la enfermedad cerebro vascular. Se pretende revisar si la severidad del déficit inicial y los hallazgos radiológicos podrían predecir la recuperación funcional a largo plazo tras un accidente cerebro vascular isquémico. Metodología de búsqueda: se desarrolló una búsqueda bibliográfica en la base de datos PubMed, para identificar estudios que evalúen cómo el déficit neurológico inicial y los hallazgos radiológicos pueden predecir la recuperación a largo plazo en accidente cerebro vascular isquémico. Se seleccionaron 35 artículos para desarrollar una revisión no sistemática de la literatura y se usó como modelo de niveles de evidencia del centro de medicina basada en la evidencia de Oxford, para evaluar la calidad de la literatura encontrada. Resultados: la edad y el déficit inicial evaluado con la escala de enfermedad cerebro vascular de los Institutos Nacionales de Salud, fueron los mejores predictores de recuperación a largo plazo tras un accidente cerebro vascular isquémico. La severidad del déficit en categorías específicas, como por ejemplo, función del miembro superior, marcha y actividades de la vida diaria, tuvieron un nivel menor de evidencia en predicción de discapacidad posaccidente cerebro vascular. Un valor pronóstico definitivo para el tamaño del infarto no ha sido convincentemente demostrado. La localización de la lesión, particularmente el compromiso del tracto cortico espinal evaluado con imágenes de difusión por tensión, parece ser un buen predictor de recuperación. El patrón de activación cerebral tras un accidente cerebro vascular evaluado con resonancia magnética funcional y tomografía por emisión de positrones tuvo un moderado nivel de evidencia como predictor de recuperación tras un accidente cerebro vascular. Conclusiones: la severidad del déficit inicial puede ser usado para predecir recuperación neurológica tras un accidente cerebro vascular isquémico y nuevas técnicas radiológicas son muy prometedoras en la predicción de recuperación a largo plazo de la enfermedad cerebro vascular isquémica..