Arteriovenous Malformations Volume Research Articles

Volume-Staged Gamma Knife Radiosurgery for Large Brain Arteriovenous Malformation

Large brain arteriovenous malformations (AVMs) pose a management dilemma because of the limited success of any single treatment modality by itself. Surgery alone is associated with significant morbidity and mortality. Similarly, embolization alone has limited efficacy. Volume-staged Gamma Knife radiosurgery (VSGR) has been developed for the treatment of large AVMs to increase the efficacy and improve safety of treatment of these lesions. The aim of this study was to assess the efficacy and safety of VSGR technique for the treatment of large brain AVMs. The study included patients treated by VSGR between May 2009 and July 2015. All patients had large AVMs (>10 mL). There were 29 patients. Twenty-four patients completed radiographic follow-up, with 15 obliteration cases (62.5%). A total of 56 sessions were performed. The mean AVM volume was 16 mL (range, 10.1-29.3 mL). The mean prescription dose was 18 Gy (range, 14-22 Gy). The mean follow-up duration was 43 months (range, 21-73 months). One patient died during follow-up of an unrelated cause. Two patients had hemorrhage during follow-up. Symptomatic edema developed in 5 patients (17%). The factors affecting obliteration were smaller total volume, higher dose/stage, nondeep location, compact AVM, AVM score <3, >18 Gy dose, and <15 mL total volume. The factors affecting symptomatic edema were smaller total volume and shorter time between first and last sessions (P= 0.012). T2 image changes were affected by Spetzler-Martin grade ≥3 (P= 0.013) and AVM score ≥3 (P= 0.014). VSGR provides an effective and safe treatment option for large brain AVMs. Smaller AVM volume is associated with higher obliteration rate.

Learning-based automatic segmentation of arteriovenous malformations on contrast CT images in brain stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) is widely used to obliterate arteriovenous malformations (AVMs). Its performance relies on the accuracy of delineating the target AVM. Manual segmentation during a framed SRS procedure is time consuming and subject to inter- and intraobserver variation. To address these drawbacks, we proposed a deep learning-based method to automatically segment AVMs on CT simulation image sets. We developed a deep learning-based method using a deeply supervised three-dimensional (3D) V-Net with a compound loss function. A 3D supervision mechanism was integrated into a residual network, V-Net, to deal with the optimization difficulties when training deep networks with limited training data. The proposed compound loss function including logistic and Dice losses encouraged similarity and penalized discrepancy simultaneously between prediction and training dataset; this was utilized to supervise the 3D V-Net at different stages. To evaluate the accuracy of segmentation, we retrospectively investigated 80 AVM patients who had CT simulation and digital subtraction angiography (DSA) acquired prior to treatment. The AVM target volume was segmented by our proposed method. They were compared with clinical contours approved by physicians with regard to Dice overlapping, difference in volume and centroid, and dose coverage changes on original plan. Contours created by the proposed method demonstrated very good visual agreement to the ground truth contours. The mean Dice similarity coefficient (DSC), sensitivity and specificity of the contours delineated by our method were >0.85 among all patients. The mean centroid distance between our results and ground truth was 0.675±0.401mm, and was not significantly different in any of the three orthogonal directions. The correlation coefficient between ground truth and AVM volume resulting from the proposed method was 0.992 with statistical significance. The mean volume difference among all patients was 0.076±0.728cc; there was no statistically significant difference. The average differences in dose metrics were all less than 0.2Gy, with standard deviation less than 1Gy. No statistically significant differences were observed in any of the dose metrics. We developed a novel, deeply supervised, deep learning-based approach to automatically segment the AVM volume on CT images. We demonstrated its clinical feasibility by validating the shape and positional accuracy, and dose coverage of the automatic volume. These results demonstrate the potential of a learning-based segmentation method for delineating AVMs in the clinical setting.

Assessing the volume of large cerebral arteriovenous malformations: Can the ABC/2 formula reliably predict true volume?

BackgroundOutcomes of stereotactic radiosurgery in the treatment of cerebral arteriovenous malformations (AVMs) are volume-dependent. The ability to estimate AVM volume has significant value in guiding AVM management. ObjectiveTo determine whether AVM volume measurement calculated from the ABC/2 formula is accurate compared to volume calculated by a computer-assisted planimetric method for large AVMs. MethodsRetrospective review of 42 intracranial AVMs >3 cm in diameter that underwent treatment with dose-staged hypofractionated stereotactic radiotherapy (HSRT) from 2001 to 2018. Two raters independently measured pre- and post-HSRT volumes using both the ABC/2 formula and computer-assisted planimetry in a blinded fashion. Inter-rater reliability was assessed by calculation of intra-class correlation coefficient (ICC). Absolute volumes and percent volume change following HSRT as determined using the two methods were compared using paired t-tests, linear regression, and Bland-Altman plot analyses. ResultsThe ICC between the 2 raters for planimetric and ABC/2 volumes was 0.859 and 0.799, respectively. ABC/2 volumes, 26.1 ± 26.6 cm3, were statistically smaller than planimetric volumes, 28.6 ± 27.1 cm3 (P = .008). Despite differences, the two methods were highly correlated (R2 = 0.904, linear regression). The percent volume change following HSRT was significantly greater with the ABC/2 method than compared to planimetry (P = .009). ConclusionThe ABC/2 and planimetric methods are reproducible for measuring cerebral AVM volumes. Although the ABC/2 method of volume estimation underestimates planimetric AVM volume, the high correlation between the two suggests utility of the ABC/2 method if one understands its limits, particularly with respect to estimating change in AVM volume after treatment.

Dose Hypofractionated Stereotactic Radiotherapy for Intracranial Arteriovenous Malformations: A Case Series and Review of the Literature

Brain arteriovenous malformations (AVMs) are pathologic tangles of intracerebral vessels. The treatment of AVMs aims to reduce the risk of devastating intracranial hemorrhage (ICH). Hypofractionated stereotactic radiotherapy (HSRT) can be used to treat large lesions and reduce the risk of radiation toxicity to the surrounding structures. We analyzed the data from our institutional experience of the past 15 years in treating large AVMs with both 5- and 6-fraction HSRT and evaluated the pretreatment characteristics that are most predictive of the radiographic response. We included 37 patients and 42 treatments of intracranial AVMs measuring >3 cm in their largest dimension. Data were collected retrospectively by reviewing the electronic health records. The AVM volume was measured before HSRT and at the most recent follow-up appointment. Symptomatic outcomes, including treatment-related inflammation, were measured and defined categorically. Complete obliteration was achieved in 11.9% of the patients. The mean AVM volume had decreased significantly after HSRT (P= 8.7e-8). The percentage of volume reduction differed significantly between patients receiving 30-Gy fractions, (∂V=-48.7%) and those receiving 25-Gy fractions (∂V=-29.1%; P= 0.035). Patients with partial or complete obliteration were more likely to have received a total dose of 30 Gy rather than 25Gy (P= 0.056) and showed a trend toward being treatment naive (P= 0.053). HSRT can be used as a method to manage large AVMs, with obliteration in some cases and sufficient volume reduction in most others for adjuvant treatment with other modalities. The 30-Gy total dose was generally superior to 25 Gy in achieving obliteration or volume reduction. Further studies focused on longer follow-up periods are warranted.

Correlation of Appearance of MRI Perinidal T2 Hyperintensity Signal and Eventual Nidus Obliteration Following Photon Radiosurgery of Brain AVMs: Combined Results of LINAC and Gamma Knife Centers

A wide variety of radiologic changes occur within and adjacent to the nidus of arteriovenous malformations (AVMs) after stereotactic radiosurgery (SRS). Our objective was to study the magnetic resonance imaging(MRI)-defined changes following photon radiosurgery of AVMs and specifically to correlate the appearance of a perinidal T2 hyperintensity signal with the eventual angiographic obliteration of an AVM nidus in response to SRS treatment. This retrospective study was conducted on 62 patients with brain AVMs who received photon SRS treatments between 2004 and 2017, using either a technique based on a linear accelerator at the Alexandria LINAC Radiosurgery Center in Egypt (21 patients/AVMs) or a technique based on a gamma unit at the Koto Memorial Gamma Knife Center in Japan (41 patients/AVMs). All patients included in the study had serial clinical and radiologic follow-ups for ≥ 2 years after SRS treatments. In the combined study series of 62 patients/AVMs treated with photon SRS, the follow-up MRIs revealed that 50 AVMs (80.6%) showed nonvisualized nidus and 12 AVMs (19.4%) showed decreased nidus size. Radiation-induced changes, defined as appearance of perinidal T2 hyperintensities in post-SRS MRIs, occurred in 34 patients (54.8%). Of the 35 patients with available follow-up angiographic studies, 30 AVMs (85.7%) demonstrated complete nidus obliteration at a mean of 36 months (range: 8-66 months) after SRS. Of the 30 AVMs with both MRI evidence of a nonvisualized nidus and angiographic verification of complete nidus obliteration, 20 AVMs (66.7%) were associated with prior MRI evidence of the appearance of a perinidal T2 hyperintensity signal at an average of 12 months (range: 6-45 months) after SRS. Of the five AVMs with both MRI evidence of decreased nidus size and angiographic verification of partial nidus obliteration, four AVMs (80%) showed perinidal T2 hyperintensity signal on post-SRS follow-up MRIs. Lower Spetzler-Martin grade (p = 0.013), smaller AVM volume (p = 0.017), and appearance of post-SRS perinidal T2 hyperintensity signal (p = 0.007) were the statistically significant independent predictors of AVM obliteration. The appearance of perinidal T2 hyperintensity signal in the post-SRS MRIs had a sensitivity of 66.7%, a specificity of 20%, and an overall accuracy of 60% in predicting the eventual obliteration of the AVM nidus. The present study may help improve our current understanding of the mechanisms behind the radiation-induced tissue changes following AVM SRS. Because the SRS-induced hemodynamic changes within the AVM nidus initiate the cascade of the subsequent formation of perinidal vasogenic brain edema, the appearance of perinidal high T2 signal in the follow-up MRIs after SRS would be a valuable indicator of the AVM response to SRS. The development of perinidal hyperintensity was the strongest predictive factor of AVM obliteration (p = 0.007), with relatively high sensitivity (66.7%) and accuracy (60%) and fairly low specificity (20%), as a prognostic sign of eventual complete angiographic obliteration of the AVM nidus following SRS.

Efficacy and Tolerance of Sirolimus (Rapamycin) for Extracranial Arteriovenous Malformations in Children and Adults.

Managing extracranial arteriovenous malformations is challenging. Sirolimus (rapamycin) is increasingly being used when surgery and embolization are not advised. Because of its anti-angiogenic properties here we report all extracranial arteriovenous malformation cases treated with sirolimus in 2 French tertiary centers for vascular anomalies. The outcomes were efficacy (complete, partial, no response) based on arteriovenous malformation volume and necrosis/hemorrhage and side effects. We retrospectively included 10 patients (7 children). The sirolimus dose ranged from 0.6 to 3.5 mg/m2. Median (interquartile range [IQR]) treatment time was 24.5 (4.5; 35) months. Five patients showed no response and 5 showed partial response at a median (IQR) of 3 (1; 5) months followed in 2 cases by therapeutic resistance (i.e., progressive disease after 9 and 24 months of treatment). The most frequent side effect was mouth ulcers. This study shows poor efficacy of sirolimus for treating extracranial arteriovenous malformations.

A novel method to determine the natural course of unruptured brain arteriovenous malformations without the need for follow-up information.

OBJECTIVEThere is a strong clinical need to accurately determine the average annual hemorrhage risk in unruptured brain arteriovenous malformations (AVMs). This need motivated the present initiative to use data from a uniquely large patient population and design a novel methodology to achieve a risk determination with unprecedented accuracy. The authors also aimed to determine the impact of sex, pregnancy, AVM volume, and location on the risk for AVM rupture.METHODSThe present study does not consider any specific management of the AVMs, but only uses the age distribution for the first hemorrhage, the shape of which becomes universal for a sufficiently large set of patients. For this purpose, the authors collected observations, including age at first hemorrhage and AVM size and location, in 3425 patients. The average annual risk for hemorrhage could then be determined from the simple relation that the number of patients with their first hemorrhage at a specific age equals the risk for hemorrhage times the number of patients at risk at that age. For a subset of the patients, the information regarding occurrence of AVM hemorrhage after treatment of the first hemorrhage was used for further analysis of the influence on risk from AVM location and pregnancy.RESULTSThe age distribution for the first AVM hemorrhage was used to determine the average annual risk for hemorrhage in unruptured AVMs at adult ages (25-60 years). It was concluded to be 3.1% ± 0.2% and unrelated to AVM volume but influenced by its location, with the highest risk for centrally located AVMs. The hemorrhage risk was found to be significantly higher for females in their fertile years.CONCLUSIONSThe present methodology allowed the authors to determine the average annual risk for the first AVM hemorrhage at 3.1% ± 0.2% without the need for individual patient follow-up. This methodology has potential also for other similar types of investigations. The conclusion that centrally located AVMs carry a higher risk was confirmed by follow-up information. Follow-up information was also used to conclude that pregnancy causes a substantially greater AVM hemorrhage risk. The age distribution for AVM hemorrhage is incompatible with AVMs present at birth having the same hemorrhage risk as AVMs in adults. Plausibly, they instead develop in the early years of life, possibly with a lower hemorrhage risk during that time period.

Venous Stenosis and Hemorrhage After Radiosurgery for Cerebral Arteriovenous Malformations

The risk of hemorrhage remains after radiosurgery for patients with arteriovenous malformations (AVMs), especially during the latency period. The effect of venous outflow stenosis on postradiosurgery AVM hemorrhage has been understudied. The present study sought to clarify the effect of venous stenosis on postradiation hemorrhage. We retrospectively reviewed the records of patients with AVM seen at our institution from 1990 to 2015. Patients who had undergone radiosurgery were included, and those without sufficient data were excluded. We performed multivariable Cox regression to evaluate the predictors of postradiosurgery hemorrhage, with specific emphasis on venous stenosis. Patients were censored from the first radiosurgery to hemorrhage or the last follow-up visit. The baseline and angiographic characteristics were compared between those with venous stenosis and those without to address potential confounders. The present study included 240 patients, of whom 29 (12.1%) had venous stenosis. The venous stenosis cohort included more patients with venous varices (P= 0.009) and fewer with deep venous drainage (P= 0.048) compared with those without venous stenosis. Most patients had grade III or higher AVMs (63.2%), with an obliteration rate of 32.9%. In an all-inclusive multivariable Cox regression, hemorrhage risk was associated with venous stenosis (hazard ratio [HR], 3.70; P= 0.034), age (HR, 1.05; P= 0.002), AVM volume (HR, 1.04; P= 0.004), and hemorrhage before treatment (HR, 4.11; P= 0.014). Male gender was protective (HR, 0.31; P= 0.036) against hemorrhage. We identified statistically significant risk factors for postradiosurgery AVM hemorrhage, which included advanced age, female gender, the presence of venous stenosis, a larger AVM volume, and previous hemorrhage. We recommend cautious selection of patients for radiosurgery with close follow-up after treatment, especially for patients with these risk factors.

Contrast Time-Density Time on Digital Subtraction Angiography Correlates With Cerebral Arteriovenous Malformation Flow Measured by Quantitative Magnetic Resonance Angiography, Angioarchitecture, and Hemorrhage.

Digital subtraction angiography (DSA) currently provides angioarchitectural features of cerebral arteriovenous malformations (AVMs) but its role in the hemodynamic evaluation of AVMs is poorly understood. To assess contrast time-density time (TT) on DSA relative to AVM flow measured using quantitative magnetic resonance angiography (QMRA). Patients seen at our institution between 2007 and 2014 with a supratentorial AVM and DSA and QMRA obtained prior to any treatment were retrospectively reviewed. Regions of interest were selected on the draining veins at the point closest to the nidus. TT on DSA was defined as time needed for contrast to change image intensity from 10% to 100%, 100% to 10%, and 25% to 25%. TT was correlated to AVM total flow, angioarchitectural features, and hemorrhage. Twenty-eight patients (mean age 35.6 yr) were included. Six patients presented with hemorrhage. Mean AVM volume was 11.42 mL (range 0.3-57.7 mL). Higher total AVM flow significantly correlated with shorter TT100%-10% and TT25%-25% (P = .02, .02, respectively). Presence of venous stenosis correlated significantly with shorter TT100%-10% (P = .04) and TT25%-25% (P = .04). AVMs with a single draining vein exhibited longer TT25%-25% compared to those with multiple draining veins (P = .04). Ruptured AVMs had significantly shorter TT10%-100% compared to unruptured AVMs (P = .05). TT on DSA correlates with cerebral AVM flow measured using QMRA and with AVM angioarchitecture and hemorrhagic presentation. Thus, TT may be used to indirectly estimate AVM flow during angiography in real-time and may also be an indicator of important AVM characteristics associated with outflow resistance and increased rupture risk, such as venous stenosis.

ABC/2 Method Does not Accurately Predict Cerebral Arteriovenous Malformation Volume.

Stereotactic radiosurgery (SRS) is a treatment option for cerebral arteriovenous malformations (AVMs) to prevent intracranial hemorrhage. The decision to proceed with SRS is usually based on calculated nidal volume. Physicians commonly use the ABC/2 formula, based on digital subtraction angiography (DSA), when counseling patients for SRS. To determine whether AVM volume calculated using the ABC/2 method on DSA is accurate when compared to the exact volume calculated from thin-cut axial sections used for SRS planning. Retrospective search of neurovascular database to identify AVMs treated with SRS from 1995 to 2015. Maximum nidal diameters in orthogonal planes on DSA images were recorded to determine volume using ABC/2 formula. Nidal target volume was extracted from operative reports of SRS. Volumes were then compared using descriptive statistics and paired t-tests. Ninety intracranial AVMs were identified. Median volume was 4.96 cm3 [interquartile range (IQR) 1.79-8.85] with SRS planning methods and 6.07 cm3 (IQR 1.3-13.6) with ABC/2 methodology. Moderate correlation was seen between SRS and ABC/2 (r = 0.662; P < .001). Paired sample t-tests revealed significant differences between SRS volume and ABC/2 (t = -3.2; P = .002). When AVMs were dichotomized based on ABC/2 volume, significant differences remained (t = 3.1, P = .003 for ABC/2 volume < 7 cm3; t = -4.4, P < .001 for ABC/2 volume > 7 cm3). The ABC/2 method overestimates cerebral AVM volume when compared to volumetric analysis from SRS planning software. For AVMs > 7 cm3, the overestimation is even greater. SRS planning techniques were also significantly different than values derived from equations for cones and cylinders.

Management of a complex intracranial arteriovenous malformation with gamma knife radiosurgery: A case report with review of literature

The risks and benefits of arteriovenous malformation (AVM) treatment should be considered cautiously in each patient since management strategy of it depends on various factors including age of the patient, location and volume of AVM and presence of other vascular abnormalities. Current management options of AVM include observation, endovascular embolization, radiosurgery and microsurgical resection or in combination of any two of the above procedures. Here, we have discussed a case of intracranial AVM with radiation induced early cyst formation, and performed a literature review to determine the optimum treatment of complex intracranial AVM. Standard search strategies were performed in PubMed/Medline using appropriate terms such as “intracranial arteriovenous malformation” radiosurgery, embolization and microsurgical resection as well as medical subject headings. The particular case in this study was retrospectively reviewed. Literature review revealed that the mean marginal radiation dose used by the different authors was 19 Gy, cysts were developed in 3.6% patients, the average time to form cyst was 6.6 years, average volume of cyst was 6.7 ml and maximum cysts were removed by resection. In our case, the cyst was developed 2.5 years after radiosurgery. Radiation induced cyst formation is a delayed complication of AVM management. However, cyst formation in this case was comparatively earlier in our case. Therefore, continuous follow-up after radiosurgery is required for early detection of cyst formation. In addition, the review revealed that embolization before radiosurgery was a poor strategy.

Modern robot-assisted radiosurgery of cerebral angiomas-own experiences, system comparisons, and comprehensive literature overview.

Cerebral arteriovenous malformations (AVMs) are rare vascular lesions potentially responsible for substantial neurological morbidity and mortality. Over the past four decades, radiosurgery has become a valid therapeutic option for many patients with small intracranial AVMs, but reports describing the use of robotic stereotactic radiosurgery (SRS) are rare. The purposes of this study are to describe the efficacy and toxicity of robotic SRS for AVMs and to review the literature. The reports of 48 consecutive patients treated with SRS were reviewed. A total dose of 18Gy in a single fraction was prescribed to the 70% isodose line. Efficacy (i.e., total obliteration of the AVM) and toxicity were analyzed. Literature search was performed on Embase and PubMed for the terms "Radiosurgery and AVMs", "Cyberknife and AVMs" and "Radiation therapy and AVMs." The median follow-up was 41months. The median AVM volume was 2.62cm3. The incidence of obliteration was 59% at 3years. Regarding toxicity, 92% of patients remained symptom-free, 66% developed radiogenic edema on MRI, and none developed radionecrosis. Forty-one patients (85%) had embolization prior to SRS. Our study was incorporated in an exhaustive review of 25 trials categorized by SRS technique. In this review, the median follow-up was 60months. The median nidus volume was 2cm3. The median overall obliteration rate for SRS was 68% (range 36 to 92). The median embolization rate prior to SRS was 31% (range 8.23 to 90). Compared to other studies, tolerability was excellent and the obliteration rate was acceptable but probably affected by the high embolization rate prior to radiosurgery. Our study suggests that a higher dose is feasible. A larger cohort with a longer follow-up period will be needed to confirm the safety and effectiveness, and subsequently validate different prognosis and predictive scores with this treatment modality to maximize the benefits of this technology for selected patients in the long term.

In-room assessment of intravascular velocity from time-resolved rotational angiography in patients with arteriovenous malformation: a pilot study

BackgroundTime-resolved rotational angiography (t-RA) enables interventionists to better comprehend complex arteriovenous malformations (AVMs), thereby facilitating endovascular treatment. However, its use in evaluating hemodynamic changes has rarely been explored.ObjectiveThis study uses...

373 Risk of Hemorrhage Following Radiosurgery for Cerebral Arteriovenous Malformations (AVMs) Is Associated with Venous Stenosis

Abstract INTRODUCTION Approximately 6% of all patients who undergo radiosurgery experience subsequent hemorrhage, even in those with obliterated lesions. Little information has been presented in existing literature about risk modifiers of post-radiosurgery hemorrhage. Associated aneurysms, venous drainage pattern, size of AVM and prescription dose were previously reported as risk factors. Here, we aim to elucidate the effect of venous stenosis on risk of hemorrhage after radiosurgery. METHODS We retrospectively reviewed medical records of all AVM patients evaluated at our institution from 1990–2015, and those who were treated with radiosurgery were included. We excluded patients without baseline or follow-up data, nor information about treatment and angiographic results. Baseline and angiographic characteristics were compared between those with venous stenosis and those without to elicit confounding factors. We then proceeded with univariable and multivariable Cox regression analysis looking at predictors of post-radiosurgery hemorrhage, with inclusion of confounding factors. Patients were censored from first radiosurgery to hemorrhage or to last follow-up. RESULTS &gt;We included 240 patients in this study. Twenty-nine (12.1%) had venous stenosis; there were more AVMs with venous varices(P = 0.009) and fewer with deep venous drainage (P = 0.048) compared to those without venous stenosis. Univariable analysis on post-radiosurgery hemorrhage showed age, gender, AVM volume, venous stenosis, and unrelated aneurysm were associated with increased risk of hemorrhage. In an all-inclusive model multivariable Cox regression, increased risk of hemorrhage was associated with venous stenosis (HR:3.70, P = 0.034), age (HR:1.05, P = 0.002), AVM volume (HR:1.04, P = 0.004), and hemorrhage before treatment (HR:4.11, P = 0.014). Male gender appears protective (HR:0.31, P = 0.036) against hemorrhage. CONCLUSION We found multiple factors associated with increased risk of AVM hemorrhage after radiosurgery. We recommend that selection of radiosurgery should proceed with caution with close follow-up after treatment, especially in patients with venous stenosis combined with advanced age, female gender, large AVM volume, and previous rupture.

124 Repeat Stereotactic Radiosurgery for Incompletely Obliterated Arteriovenous Malformations

Abstract INTRODUCTION To evaluate the outcomes and risks of repeat stereotactic radiosurgery (SRS) for incompletely obliterated cerebral arteriovenous malformations (AVM). METHODS Six participating centers of the International Gamma Knife Research Foundation (IGKRF) identified 335 patients who had incompletely obliterated AVMs at a median follow-up of 45.6 months after initial SRS (range, 15–283 months). The median AVM target volume at initial SRS was 4.3 cc but was reduced to 1.4cc at the time of the second procedure. The median margin dose at both initial SRS and repeat SRS was 20 Gy. The median follow-up after repeat SRS was 64 months (range, 6–218 months). RESULTS &gt;The actuarial rate of total obliteration by angiography or MRI after repeat SRS was 31%, 50%, 61%, and 80% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration were smaller residual AVM target volume, and &gt;50% of volume reduction after the initial procedure. The cumulative actuarial rates of new AVM hemorrhage after repeat SRS were 1.8%, 4.5%, 6.6%, 8.9% and 14.9% at 1, 2, 3, 5, and 10 years. Factors associated with a higher risk of hemorrhage after repeat SRS were a larger number of a prior hemorrhages, larger AVM target volume, and initial AVM volume reduction &lt;50%. Symptomatic adverse radiation effect (ARE) developed in 29 patients (8.6%) after initial SRS and 27 patients (8.1%) after repeat SRS. CONCLUSION Repeat SRS for incompletely obliterated AVMs increases the eventual obliteration rate but patients remain at risk of hemorrhage until obliteration occurs. The best results for incompletely obliterated AVMs were seen in patients with a smaller residual AVM volume and no prior hemorrhages.

Volume-staged stereotactic radiosurgery for large intracranial arteriovenous malformations

Stereotactic radiosurgery (SRS) is an effective treatment option for intracranial arteriovenous malformations (AVM). However, the treatment of large AVMs (nidus volume ≥12cm3) with single-session SRS alone yields generally poor outcomes. Volume-staged SRS (VS-SRS) is a therapeutic strategy for large AVMs which seeks to avoid the disadvantages of single-session SRS, but reports regarding its efficacy remain limited. The aim of this retrospective cohort study is to assess the outcomes of VS-SRS for large AVMs. We identified all AVM patients who underwent VS-SRS at our institution from 2000 to 2015 with ≥12months follow-up. Baseline and outcomes data were analyzed. A total of 12 patients were selected for the study cohort, with a median age of 30years. The median maximum AVM diameter and nidus volume were 4.3cm and 13.6cm3, respectively. The Spetzler–Martin grade was III and IV each in six AVMs (50%). All patients underwent VS-SRS in two stages, and the median margin dose was 17Gy for both VS-SRS procedures. The median time interval between the two procedures was three months. After a median radiologic follow-up duration of 39months, the median degree of AVM volume reduction (evaluable in nine patients) was 87% (range 12–99%). The rates of radiologically evident, symptomatic, and permanent radiation-induced changes were 58%, 25%, and 8%, respectively. There were no cases of post-SRS hemorrhage. VS-SRS substantially reduces the size of large AVMs. A potential role for VS-SRS may be to facilitate subsequent definitive intervention to obliterate a shrunken, residual nidus.

Volume-Staged Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: Outcomes Based on an 18-Year Experience.

Radiation-based treatment options of large intracranial arteriovenous malformations (AVM) must balance the likelihood of obliteration with the risk of adverse radiation effects (ARE). To analyze the efficacy and risks of volume-staged stereotactic radiosurgery (VS-SRS) for AVM. Retrospective study of 34 AVM patients having VS-SRS between 1997 and 2012. A median of 2 stages (range, 2-4) was used to treat a median AVM volume of 22.2 cm 3 (range, 7.4-56.7). The median AVM margin dose was 16 Gy (range, 14-18); the median radiosurgery-based AVM score was 2.81 (range, 1.54-6.45). The median follow-up after VS-SRS was 8.2 years (range, 3-13.3). Nidus obliteration was noted in 18 patients (53%) after VS-SRS. The rate of obliteration was 14% at 3 years, 54% at 5 years, and 75% at 7 years. Six patients (18%) had 11 bleeds after VS-SRS. Two patients (6%) remained neurologically stable, 2 (6%) patients had significant deficits, and 2 patients (6%) died. The actuarial risk of a first bleed after VS-SRS was 6% at 1 year, 12% at 3 years, and 19% at 7 years. Six patients (18%) underwent repeat SRS; all achieved nidus obliteration for an overall cure rate of 71%. Two patients (6%) had a permanent ARE after VS-SRS or repeat SRS. VS-SRS permitted large volume intracranial AVM to be treated with a low rate of ARE. Further study is needed on dose escalation and decreasing the treatment volume per stage to determine if this will increase the rate of obliteration with this technique.

Validation of cerebral arteriovenous malformation hemodynamics assessed by DSA using quantitative magnetic resonance angiography: preliminary study

BackgroundThe hemodynamic evaluation of cerebral arteriovenous malformations (AVMs) using DSA has not been validated against true flow measurements.ObjectiveTo validate AVM hemodynamics assessed by DSA using quantitative magnetic resonance angiography (QMRA).Materials...

Abstract 122: Transit Time on Digital Subtraction Angiography Correlates with Cerebral Arteriovenous Malformation Flow Measured by Quantitative Magnetic Resonance Angiography

Introduction: Digital subtraction angiography (DSA) currently provides angioarchitectural features of cerebral arteriovenous malformations (AVMs) but its role in the hemodynamic evaluation of AVMs is poorly understood. Here, we assess transit time (TT) of contrast on DSA relative to AVM flow measured using quantitative magnetic resonance angiography (QMRA). Methods: Patients seen at our institution between 2007 and 2014 with a cerebral AVM and DSA and QMRA obtained prior to any treatment were retrospectively reviewed. TT on DSA was defined as time needed for contrast to change image intensity from 10%-100%, 100%-10%, and 25%-25%. TT was correlated to AVM total flow and angio-architectural features. Results: 33 patients (mean age 34.8 years) were included. 7 patients presented with hemorrhage. Mean AVM volume was 13.61 mL (range 0.28-84.2 mL). Higher total flow significantly correlated with shorter TT100%-10% and TT25%-25% (P=0.04, P=0.03, respectively). Total flow was also significantly related to the ratio sum of draining vein diameters/TT (TT10%-100% P=0.04, TT100%-10% P=0.01, TT25%-25% P=0.02). Presence of venous stenosis (P=0.01) and arterial ectasia (P=0.03) correlated significantly with TT100%-10%. TT was not significantly related to hemorrhagic presentation, deep drainage, single draining vein, or Spetzler-Martin grade. Conclusions: TT and the ratio sum of draining vein diameters/TT correlated significantly with AVM total flow measured using QMRA, and so TT along with venous diameters determined from DSA may be used as a surrogate for AVM flow.

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations on daily or alternate day schedule outside the linear quadratic model: Proof of concept and early results. A substitute to volume fractionation.

To evaluate the feasibility, safety and efficacy of dose fractionated gamma knife radiosurgery (DFGKRS) on a daily schedule beyond the linear quadratic (LQ) model, for large volume arteriovenous malformations (AVMs). Between 2012-16, 14 patients of large AVMs (median volume 26.5 cc) unsuitable for surgery or embolization were treated in 2-3 of DFGKRS sessions. The Leksell G frame was kept in situ during the whole procedure. 86% (n = 12) patients had radiologic evidence of bleed, and 43% (n = 6) had presented with a history of seizures. 57% (n = 8) patients received a daily treatment for 3 days and 43% (n = 6) were on an alternate day (2 fractions) regimen. The marginal dose was split into 2 or 3 fractions of the ideal prescription dose of a single fraction of 23-25 Gy. The median follow up period was 35.6 months (8-57 months). In the three-fraction scheme, the marginal dose ranged from 8.9-11.5 Gy, while in the two-fraction scheme, the marginal dose ranged from 11.3-15 Gy at 50% per fraction. Headache (43%, n = 6) was the most common early postoperative complication, which was controlled with short course steroids. Follow up evaluation of at least three years was achieved in seven patients, who have shown complete nidus obliteration in 43% patients while the obliteration has been in the range of 50-99% in rest of the patients. Overall, there was a 67.8% reduction in the AVM volume at 3 years. Nidus obliteration at 3 years showed a significant rank order correlation with the cumulative prescription dose (p 0.95, P value 0.01), with attainment of near-total (more than 95%) obliteration rates beyond 29 Gy of the cumulative prescription dose. No patient receiving a cumulative prescription dose of less than 31 Gy had any severe adverse reaction. In co-variate adjusted ordinal regression, only the cumulative prescription dose had a significant correlation with common terminology criteria for adverse events (CTCAE) severity (P value 0.04), independent of age, AVM volume, number of fractions and volume of brain receiving atleast 8 Gy of radiation. DFGKRS is feasible for large AVMs with a fair nidus obliteration rate and acceptable toxicity. Cumulative prescription dose seems to be the most significant independent predictor for outcome following DFGKRS with 29-30 Gy resulting in a fair nidus obliteration with least adverse events.