Optimisation of planning and delivery methods for Gamma Knife Stereotactic Radiosurgery

The work presented in this dissertation is the response to a series of technical and clinical challenges encountered during the first four years of operations in the Gamma Knife Centre at Queen Square. These challenges, which are common to most contemporary Gamma Knife centres, were prospectively addressed and practical solutions were developed for the questions they posed. The dosimetric differences between the new convolution algorithm and the standard TMR 10 algorithm traditionally used for prediction of dose distribution in Gamma Knife Radiosurgery (GKR) were explored. It was demonstrated that inhomogeneity correction with the convolution algorithm results in a considerable but consistent dose shift compared to TMR 10. No significant difference in relative dose distribution was noted and it was concluded that a reduction of the prescription dose is necessary to obtain the same absolute dosimetric effect with the convolution algorithm. The stability of the stereotactic Leksell frame G in GKR was demonstrated using a comprehensive study design that involved repeated measurements of landmarks by two observers. The study provided reliable and realistic evidence of submillimetre stability of the stereotactic frame throughout the treatment procedure which is important for evaluation and development of new frameless radiosurgery systems. The technical feasibility of using a combination of three magnetic resonance angiography sequences (triple-MRA), instead of digital subtraction angiography (DSA), for visualisation and delineation of brain Arteriovenous Malformations (AVMs) for GKR targeting was demonstrated. Target volumes obtained using triple-MRA are on average 10% smaller than AVM targets obtained with the standard DSA planning method and this can potentially reduce the risk of adverse radiation effects (ARE). The treatment planning method described here has laid the way for a change in clinical practice that favours a less invasive treatment planning approach. The same principle of less invasive AVM imaging with triple-MRA was used at the post-GKR stage, when a DSA is performed to confirm AVM obliteration. Triple-MRA was found to consistently confirm or rule out residual AVMs in patients who had undergone GKR for brain AVMs, compared to DSA, and it can also be reliably used for characterisation of residual AVMs. The use of triple-MRA as a first line for assessment of obliteration after GKR is recommended

Investigating the oxygenation of brain arteriovenous malformations using quantitative susceptibility mapping

International audienceBrain 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

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)

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 calculations 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 convolution 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 necessary 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 pretreatment MRI and post-treatment CT scans and the absolute distance between the observations is reported. The measurement method was validated with an independent 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 localization 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 overall 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 difference (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

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

PurposeIntra-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).MethodsFifteen 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.ResultsAVM 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%).ConclusionThe 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

Triple Magnetic Resonance Angiography (triple-MRA) for confirmation of obliteration following Gamma Knife Radiosurgery for Arterial-Venous Malformations of the brain

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