Visualizing artery-specific blood flow patterns above the circle of Willis with vessel-encoded arterial spin labeling.

PURPOSE: To establish the feasibility of using vessel-encoded pseudocontinuous arterial spin labeling (VEPCASL) for noninvasive vascular territory imaging (VTI) and artery-specific dynamic angiography of a large number of arterial branches above the circle of Willis within a clinically feasible scan time. METHODS: 3D time-of-flight angiography was used to select a labeling plane and establish 7 pairs of encoding cycles. These were used for VEPCASL VTI and dynamic 2D angiography (8 min and 3 min acquisition times, respectively) in healthy volunteers, allowing the separation of signals arising from 13 arterial branches (including extracranial arteries) in postprocessing. To demonstrate the clinical potential of this approach, VEPCASL angiography was also applied in 5 patients with brain arteriovenous malformation (AVM). RESULTS: In healthy volunteers, the artery-specific filling of the vascular tree and resulting perfusion territories were well depicted. SNRs were approximately 5 times higher than those achievable with single-artery selective methods. Blood supply to the AVMs was well visualized in all cases, showing the main feeding arteries and venous drainage. CONCLUSIONS: VEPCASL is a highly efficient method for both VTI and dynamic angiography of a large number of arterial branches, providing a comprehensive picture of vascular flow patterns and the effect on downstream tissue perfusion within an acceptable scan time. Automation of labeling plane and vessel-encoding selection would improve robustness and efficiency, and further refinement could allow quantitative blood flow measurements to be obtained. This technique shows promise for visualizing the blood supply to lesions and collateral flow patterns.

C-arm flat detector computed tomography parenchymal blood volume imaging: the nature of parenchymal blood volume parameter and the feasibility of parenchymal blood volume imaging in aneurysmal subarachnoid haemorrhage patients.

INTRODUCTION: C-arm flat detector computed tomography (FDCT) parenchymal blood volume (PBV) measurements allow assessment of cerebral haemodynamics in the neurointerventional suite. This paper explores the feasibility of C-arm computed tomography (CT) PBV imaging and the relationship between the C-arm CT PBV and the MR-PWI-derived cerebral blood volume (CBV) and cerebral blood flow (CBF) parameters in aneurysmal subarachnoid haemorrhage (SAH) patients developing delayed cerebral ischemia (DCI). METHODS: Twenty-six patients with DCI following aneurysmal SAH underwent a research C-arm CT PBV scan using a biplane angiography system and contemporaneous MR-PWI scan as part of a prospective study. Quantitative whole-brain atlas-based volume-of-interest analysis in conjunction with Pearson correlation and Bland-Altman tests was performed to explore the agreement between C-arm CT PBV and MR-derived CBV and CBF measurements. RESULTS: All patients received medical management, while eight patients (31%) underwent selective intra-arterial chemical angioplasty. Colour-coded C-arm CT PBV maps were 91% sensitive and 100% specific in detecting the perfusion abnormalities. C-arm CT rPBV demonstrated good agreement and strong correlation with both MR-rCBV and MR-rCBF measurements; the agreement and correlation were stronger for MR-rCBF relative to MR-rCBV and improved for C-arm CT PBV versus the geometric mean of MR-rCBV and MR-rCBF. Analysis of weighted means showed that the C-arm CT PBV has a preferential blood flow weighting (≈ 60% blood flow and ≈ 40% blood volume weighting). CONCLUSIONS: C-arm CT PBV imaging is feasible in DCI following aneurysmal SAH. PBV is a composite perfusion parameter incorporating both blood flow and blood volume weightings. That PBV has preferential (≈ 60%) blood flow weighting is an important finding, which is of clinical significance when interpreting the C-arm CT PBV maps, particularly in the setting of acute brain ischemia.

Volume changes of extremely large and giant intracranial aneurysms after treatment with flow diverter stents.

INTRODUCTION: This study assessed volume changes of unruptured large and giant aneurysms (greatest diameter >20 mm) after treatment with flow diverter (FD) stents. METHODS: Clinical audit of the cases treated in a single institution, over a 5-year period. Demographic and clinical data were retrospectively collected from the hospital records. Aneurysm volumes were measured by manual outlining at sequential slices using computerised tomography (CT) or magnetic resonance (MR) angiography data. RESULTS: The audit included eight patients (seven females) with eight aneurysms. Four aneurysms involved the cavernous segment of the internal carotid artery (ICA), three the supraclinoid ICA and one the basilar artery. Seven patients presented with signs and symptoms of mass effect and one with seizures. All but one aneurysm was treated with a single FD stent; six aneurysms were also coiled (either before or simultaneously with FD placement). Minimum follow-up time was 6 months (mean 20 months). At follow-up, three aneurysms decreased in size, three were unchanged and two increased. Both aneurysms that increased in size showed persistent endosaccular flow at follow-up MR; in one case, failure was attributed to suboptimal position of the stent; in the other case, it was attributed to persistence of a side branch originating from the aneurysm (similar to the endoleak phenomenon of aortic aneurysms). At follow-up, five aneurysms were completely occluded; none of these increased in volume. CONCLUSION: Complete occlusion of the aneurysms leads, in most cases, to its shrinkage. In cases of late aneurysm growth or regrowth, consideration should be given to possible endoleak as the cause.

An approach to the symbolic representation of brain arteriovenous malformations for management and treatment planning.

INTRODUCTION: There is currently no standardised approach to arteriovenous malformation (AVM) reporting. Existing AVM classification systems focuses on angioarchitectural features and omit haemodynamic, anatomical and topological parameters intuitively used by therapists. METHODS: We introduce a symbolic vocabulary to represent the state of an AVM of the brain at different stages of treatment. The vocabulary encompasses the main anatomic and haemodynamic features of interest in treatment planning and provides shorthand symbols to represent the interventions themselves in a schematic representation. RESULTS: The method was presented to 50 neuroradiologists from 14 countries during a workshop and graded 7.34 ± 1.92 out of ten for its usefulness as means of standardising and facilitating communication between clinicians and allowing comparisons between AVM cases. Feedback from the survey was used to revise the method and improve its completeness. For an AVM test case, participants were asked to produce a conventional written report and subsequently a diagrammatic report. The two required, on average, 6.19 ± 2.05 and 5.09 ± 3.01 min, respectively. Eighteen participants said that producing the diagram changed the way they thought about the AVM test case. CONCLUSION: Introduced into routine practice, the diagrams would represent a step towards a standardised approach to AVM reporting with consequent benefits for comparative analysis and communication as well as for identifying best treatment strategies.

Does hypopituitarism recover when macroprolactinomas are treated with cabergoline?

OBJECTIVE: The frequency and the degree of recovery of anterior pituitary hormone deficits in patients with macroprolactinoma responsive to cabergoline are not clear. Our aim was to evaluate pituitary function in these patients with particular reference to an assessment of the possible restoration of pituitary deficits. SUBJECTS AND METHODS: The records of all subjects prospectively presenting to our Department with macroprolactinomas treated with cabergoline over a 2-year period were reviewed. Pituitary function was assessed at diagnosis and, if abnormal, for three consecutive years for the GH, FSH/LH and ACTH axes, and at 3 years for the TSH axis. RESULTS: Twelve patients were included. Severe GH deficiency was found in 83% at diagnosis and did not resolve in any patient at last assessment. Gonadotrophin deficiency was found in 90% at diagnosis and in 50% at last evaluation (showing reversal in 44% of deficient patients, all achieved within 1 year). ACTH deficiency was found in 17% at diagnosis and it did not reverse in any patient at last assessment. TSH deficiency was found in 36% at diagnosis and in 27% at last assessment (reversal in 25% of deficient patients). CONCLUSIONS: In our study, in a group of patients with macroprolactinoma systematically assessed at intervals, pituitary dysfunction in response to cabergoline was found to be mostly irreversible, except for the gonadotroph axis which showed restoration in a subset of subjects following achievement of normoprolactinaemia. It would appear that the reversibility of pituitary axes may be less common than previously thought.

Recurrence of hyperprolactinaemia following discontinuation of dopamine agonist therapy in patients with prolactinoma occurs commonly especially in macroprolactinoma.

CONTEXT: The optimal duration of dopamine agonist (DA) therapy in prolactinoma is unknown. There are concerns that despite low recurrence rates in highly selected groups, high recurrence rates after DA withdrawal may occur in routine practice. OBJECTIVE: To explore recurrence of hyperprolactinaemia and predictive factors following DA withdrawal in patients with microprolactinoma and macroprolactinoma. DESIGN: A retrospective study on adult patients with confirmed prolactinoma attending the Oxford Endocrine Department. PATIENTS AND MEASUREMENTS: We identified patients with macroprolactinoma (n = 15) and microprolactinoma (n = 45) treated with DA therapy for >3 years, with a trial off DA therapy. None had other treatments. Measurements included recurrence of hyperprolactinaemia following DA withdrawal, tumour size (macroprolactinomas), duration of DA therapy, prolactin levels (baseline, during DA therapy, recurrence) and time to recurrence. Data were reported as mean (range). RESULTS: During DA therapy, prolactin levels suppressed to normal range in all patients with macroprolactinoma and microprolactinoma, and most macroprolactinomas (n = 14) had substantial tumour shrinkage. Hyperprolactinaemia recurred in 93% of macroprolactinomas (n = 14) at 8·8 months (3-36) and 64% of microprolactinomas (n = 29) at 4·8 months (3-12). Duration of DA therapy was 7·5 years (4-15) for macroprolactinomas and 4·1 years (3-10) for microprolactinomas. Prolactin levels during DA therapy were 144 mU/l (7-336) for macroprolactinomas and 278 mU/l (30-629) for microprolactinomas. For microprolactinomas, prolactin levels during DA therapy were less suppressed in those with recurrence than in those without recurrence (P < 0·05). CONCLUSIONS: In routine practice, hyperprolactinaemia recurs early in most macroprolactinomas (93%) and microprolactinomas (64%) following DA therapy discontinuation. For most macroprolactinomas, cessation of DA cannot be recommended even after 7 years of therapy.

Assessment of angiographic outcomes after flow diversion treatment of intracranial aneurysms: a new grading schema.

INTRODUCTION: Flow diverter (FD) devices have emerged as an alternative treatment for a subgroup of intracranial aneurysms. The principle of endovascular flow diversion is inherently different from endosaccular coil embolisation. To monitor the angiographic outcomes for FDs, a sensitive and reliable new measure is required. Oxford Neurovascular and Neuroradiology Research Unit developed a grading schema while conducting a registry to audit outcomes of patients treated using a particular FD (SILK flow diverter; Balt Extrusion, Montmorency, France). The aim of this study is to assess the applicability and reproducibility of the new schema. METHODS: The proposed grading schema is designed for saccular- or fusiform-shaped aneurysms. For both, it documents the degree of aneurysm occlusion using a five-point scale and the parent artery patency on a three-point scale. Two neuroradiologists used the schema to independently rate 55 angiograms showing comparable treatment and follow-up angiograms of patients treated with a FD. Inter-observer agreement was estimated using the weighted kappa co-efficient. RESULTS: Both readers found the schema easy to apply. Overall, there were ten discordant readings for degrees of aneurysm occlusion and two for parent artery patency. Inter-observer agreement was excellent for both the assessment of aneurysm occlusion (k=0.89; C.I.=0.81-0.99) and parent artery patency (k=0.90; C.I.=0.76-1.0). CONCLUSION: The proposed schema is sufficiently sensitive to register gradual aneurysm occlusion and parent artery patency on interval angiograms. It is reproducible and is applicable to both saccular and fusiform aneurysms. More data on follow-up of FD-treated aneurysms is needed to prove its efficacy in predicting the long-term behaviour of treated aneurysms.

In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials.

The cost of clinical trials is ever-increasing. In-silico trials rely on virtual populations and interventions simulated using patient-specific models and may offer a solution to lower these costs. We present the flow diverter performance assessment (FD-PASS) in-silico trial, which models the treatment of intracranial aneurysms in 164 virtual patients with 82 distinct anatomies with a flow-diverting stent, using computational fluid dynamics to quantify post-treatment flow reduction. The predicted FD-PASS flow-diversion success rates replicate the values previously reported in three clinical trials. The in-silico approach allows broader investigation of factors associated with insufficient flow reduction than feasible in a conventional trial. Our findings demonstrate that in-silico trials of endovascular medical devices can: (i) replicate findings of conventional clinical trials, and (ii) perform virtual experiments and sub-group analyses that are difficult or impossible in conventional trials to discover new insights on treatment failure, e.g. in the presence of side-branches or hypertension.

C-arm flat detector computed tomography: the technique and its applications in interventional neuro-radiology.

INTRODUCTION: Flat detector computed tomography (FDCT) is an imaging tool that generates three-dimensional (3-D) volumes from data obtained during C-arm rotation using CT-like reconstruction algorithms. The technique is relatively new and, at current levels of performance, lags behind conventional CT in terms of image quality. However, the advantage of its availability in the interventional room has prompted neuro-radiologists to identify clinical settings where its role is uniquely beneficial. METHODS: We performed a search of the online literature databases to identify studies reporting experience with FDCT in interventional neuro-radiology. The studies were systematically reviewed and their findings grouped according to specific clinical situation addressed. RESULTS: FDCT images allow detection of procedural complications, evaluation of low-radiopacity stents and assessment of endosaccular coil packing in intra-cranial aneurysms. Additional roles are 3-D angiography that provides an accurate depiction of vessel morphology with low concentrations of radiographic contrast media and a potential for perfusion imaging due to its dynamic scanning capability. A single scan combining soft tissue and angiographic examinations reduces radiation dose and examination time. Ongoing developments in flat detector technology and reconstruction algorithms are expected to further enhance its performance and increase this range of applications. CONCLUSION: FDCT images provide useful information in neuro-interventional setting. If current research confirms its potential for assessing cerebral haemodynamics by perfusion scanning, the combination would redefine it as an invaluable tool for interventional neuro-radiology procedures. This facility and its existing capabilities of parenchymal and angiographic imaging would also extend its use to the triage of acute stroke patients.

Aneurysm Treatment With Woven EndoBridge in the Cumulative Population of 3 Prospective, Multicenter Series: 2-Year Follow-Up.

BACKGROUND: Woven EndoBridge (WEB; Sequent Medical) treatment is an innovative endovascular approach for treatment of wide-neck bifurcation aneurysms. Initial studies have shown high safety with good efficacy at short term confirmed by trials conducted in United States (WEB-Intrasaccular Therapy) and in Europe (WEB Clinical Assessment of Intrasaccular Aneurysm Therapy [WEBCAST], French Observatory, and WEBCAST-2). OBJECTIVE: To report the 2-yr clinical and anatomical results of WEB treatment in the combined population of 3 European trials. METHODS: In a French Observatory, 2-yr clinical and anatomical data were collected. In WEBCAST and WEBCAST-2, 2-yr follow-up was optional, and data were collected when follow-up was performed. Aneurysm occlusion was evaluated using a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant. RESULTS: The population for safety was 138/168 patients (82.1%), including 89 females (64.5%), with mean age of 55.5 ± 10.2 yr. The population for efficacy was 121/169 aneurysms (71.6%). Aneurysm locations were middle cerebral artery in 65/121 aneurysms (53.7%), anterior-communicating artery in 25/121 (20.7%), basilar artery in 17/121 (14.0%), and internal carotid artery terminus in 14/121 (11.6%). No clinically relevant adverse events occurred between years 1 and 2. At 2 yr, complete occlusion was observed in 62/121 (51.2%) aneurysms, neck remnant in 36/121 (29.8%) aneurysms, and aneurysm remnant in 23/121 (19.0%) aneurysms. The global retreatment rate at 2 yr was 9.3%. CONCLUSION: This analysis confirms the high safety profile of WEB treatment at 2 yr. Aneurysm occlusion is generally stable at 2 yr, and the retreatment rate between 1 yr and 2 yr is low (2.0%).

Substantial observer variability in the differentiation between primary intracerebral hemorrhage and hemorrhagic transformation of infarction on CT brain imaging.

BACKGROUND AND PURPOSE: CT remains the most commonly used imaging technique in acute stroke but is often delayed after minor stroke. Interobserver reliability in distinguishing hemorrhagic transformation of infarction from intracerebral hemorrhage may depend on delays to CT but has not been reported previously despite the clinical importance of this distinction. METHODS: Initial CT scans with intraparenchymal hematoma from the first 1000 patients with stroke in the Oxford Vascular Study were independently categorized as intracerebral hemorrhage or hemorrhagic transformation of infarction by 5 neuroradiologists, both blinded and unblinded to clinical history. Thirty scans were reviewed twice. Agreement was quantified by the kappa statistic. RESULTS: Seventy-eight scans showed intraparenchymal hematoma. Blinded pairwise interrater agreements for a diagnosis of intracerebral hemorrhage ranged from kappa=0.15 to 0.48 with poor overall agreement (kappa=0.35; 95% CI, 0.15 to 0.54) even after unblinding (kappa=0.41; 0.21 to 0.60). Blinded intrarater agreements ranged from kappa=0.21 to 0.92. Lack of consensus after unblinding was greatest in patients scanned >or=24 hours after stroke onset (67% versus 25%, P=0.001) and in minor stroke (National Institutes of Health Stroke Scale or=24 hours after minor stroke and in 48% of all 30-day stroke survivors in whom reliable diagnosis would be expected to influence long-term management. CONCLUSIONS: Reliability of diagnosis of intraparenchymal hematoma on CT brain scan in minor stroke is poor, particularly if scanning is delayed. Immediate brain imaging is justified in patients with minor stroke.

Factors affecting outcome after endovascular treatment of intracranial aneurysms.

PURPOSE OF REVIEW: This brief review highlights some factors affecting the short-term and long-term outcomes after endovascular treatment (EVT) of patients with intracranial aneurysms. RECENT FINDINGS: The principal procedural risks associated with EVT are symptomatic thromboembolic events affecting 2.4-5.2% of treatments, and aneurysm perforation which occurs in 0.5-2.4% of the patients with unruptured aneurysms and 2.3-6.5% of patients with subarachnoid haemorrhage. The risk of subsequent aneurysm recurrence requiring retreatment is about 10% and does not negate the morbidity advantage (relative to surgical clipping) of the initial EVT. This risk is about three-fold greater in aneurysms with a neck width more than 4 mm and sac maximum diameter greater than 10 mm. The incidence of rebleeding after EVT is 0.11-0.32% per annum and is probably lower if EVT achieves complete occlusion. SUMMARY: EVT dramatically reduces the risk of rebleeding in patients with subarachnoid haemorrhage. Treatment risks and rates of incomplete occlusions are increased in ruptured in comparison with unruptured aneurysms. Large aneurysms have higher risk of procedural thromboembolism, incomplete treatment and rate of recurrences with strong interdependence between these variables. The low risk of rebleeding in patients with subarachnoid haemorrhage is probably increased in incompletely treated aneurysms and in patients revealing aneurysm growth over time.

The safety and effectiveness of the Woven EndoBridge (WEB) system for the treatment of wide-necked bifurcation aneurysms: final 12-month results of the pivotal WEB Intrasaccular Therapy (WEB-IT) Study.

INTRODUCTION: The Woven EndoBridge Intrasaccular Therapy (WEB-IT) Study is a pivotal, prospective, single-arm, investigational device exemption study designed to evaluate the safety and effectiveness of the WEB device for the treatment of wide-neck bifurcation aneurysms. METHODS: One-hundred and fifty patients with wide-neck bifurcation aneurysms were enrolled at 21 US and six international centers. Angiograms from the index procedure, and 6-month and 1-year follow-up visits were all reviewed by a core laboratory. All adverse events were reviewed and adjudicated by a clinical events adjudicator. A data monitoring committee provided oversight during the trial to ensure subject safety. RESULTS: One-hundred and forty-eight patients received the WEB implant. One (0.7%) primary safety event occurred during the study-a delayed ipsilateral parenchymal hemorrhage-on postoperative day 22. No primary safety events occurred after 30 days through 1 year. At the 12-month angiographic follow-up, 77/143 patients (53.8%) had complete aneurysm occlusion. Adequate occlusion was achieved in 121/143 (84.6%) subjects. CONCLUSIONS: The prespecified safety and effectiveness endpoints for the aneurysms studied in the WEB-IT trial were met. The results of this trial suggest that the WEB device provides an option for patients with wide-neck bifurcation aneurysms that is as effective as currently available therapies and markedly safer. TRIAL REGISTRATION NUMBER: NCT02191618.

Endovascular treatment of intracranial microarteriovenous malformations.

OBJECT: Microarteriovenous malformations (micro-AVMs) are an uncommon subgroup of brain AVMs defined by a nidus measuring < 1 cm in diameter. The clinical features, angiographic characteristics, and outcomes in patients with micro-AVMs who had been treated endovascularly after presenting with hemorrhage were reviewed to identify common features affecting prognosis. METHODS: Between 1997 and 2006, 25 patients (12 females and 13 males) with 26 micro-AVMs were treated. Twenty-four patients presented with intracerebral hematoma and 1 with subarachnoid hemorrhage only. All patients underwent CT on admission, diagnostic cerebral angiography, and 1 session of endovascular treatment during the acute phase. RESULTS: Procedure-related complications occurred in 3 patients (12%), which caused temporary hemiparesis in 1 (4%) and no clinical sequelae in 2 patients (8%). Complete nidus obliteration was achieved at the end of the embolization in 22 (84.6%) of 26 lesions. Two recurrences were evident on follow-up angiography 6 months postembolization, resulting in a complete obliteration rate of 77% (20 of 26 lesions) after a single treatment. Late angiography was performed in 12 patients, and no further recurrences were identified. CONCLUSIONS: Immediate complete obliteration of a micro-AVM with a high permanent cure and low morbidity rates was accomplished using endovascular treatment. Early embolization after bleeding should be considered as an alternative to resection.

Abciximab for thrombolysis during intracranial aneurysm coiling.

INTRODUCTION: Thrombotic events are a common and severe complication of endovascular aneurysm treatment with significant impact on patients' outcome. This study evaluates risk factors for thrombus formation and assesses the efficacy and safety of abciximab for clot dissolution. MATERIALS AND METHODS: All patients treated with abciximab during (41 patients) or shortly after (22 patients) intracranial aneurysm coil embolisation were retrieved from the institutional database (2000 to 2007, 1,250 patients). Sixty-three patients (mean age, 55.3 years, +/- 12.8) had received either intra-arterial or intravenous abciximab. Risk factors for clot formation were assessed and the angiographic and clinical outcome evaluated. RESULTS: No aneurysm rupture occurred during or after abciximab application. The intra-procedural rate of total recanalisation was 68.3%. Thromboembolic complications were frequently found in aneurysms of the Acom complex and of the basilar artery, whilst internal carotid artery aneurysms were underrepresented. Two patients died of treatment-related intracranial haemorrhages into preexisting cerebral infarcts. Two patients developed a symptomatic groin haematoma. CONCLUSIONS: Abciximab is efficacious and safe for thrombolysis during and after endovascular intracranial aneurysm treatment in the absence of preexisting ischaemic stroke.

Magnetic resonance measurement of blood and CSF flow rates with phase contrast--normal values, repeatability and CO2 reactivity.

BACKGROUND: Similarity in flow pulsatility has been proposed as a basis for semi-automated segmentation of vessel lumens for MR-based flow measurement, but re-examinations of salient aspects of the methodology have not been widely reported. METHODS: 12 normal control subjects underwent repeated (3*Baseline+1*5%CO2) phase contrast measurements of CSF flow through the cerebral aqueduct and foramen magnum, and CBF through the 6 large cranial vessels at the level of the 1st vertebra. Average flows were calculated for regions temporally correlated (0.3 < or = Rthreshold < or = 0.95) to user defined seed points and their 3 x 3 neighbours. RESULTS: Arterial CBF averaged 710ml/min, with low variability (+/- 4%/17%, intra-individual/group CV respectively) and was the only flow to respond significantly to 5%/mmHg CO2. Venous outflow was much smaller (298ml/min +/- 10%/ 72%), possibly due to the weak venous pulse and variable venous anatomy. Average CSF flows exceeded the classical 0.4ml/min CSF production rate and were highly variable--aqueduct: 0.6ml/min (+/- 50%/93%), foramen magnum: -2.7ml/min (+/- 158%/226%). CONCLUSIONS: This preliminary analysis identified procedural steps that can improve the accuracy and repeatability of MR flow measurements, but the process remains user-dependent for the weakly pulsatile foramen magnum CSF and venous flows where variability remains a significant confound even to relatively large perturbations such as CO2 administration.

Thrombosis in Cerebral Aneurysms and the Computational Modeling Thereof: A Review.

Thrombosis is a condition closely related to cerebral aneurysms and controlled thrombosis is the main purpose of endovascular embolization treatment. The mechanisms governing thrombus initiation and evolution in cerebral aneurysms have not been fully elucidated and this presents challenges for interventional planning. Significant effort has been directed towards developing computational methods aimed at streamlining the interventional planning process for unruptured cerebral aneurysm treatment. Included in these methods are computational models of thrombus development following endovascular device placement. The main challenge with developing computational models for thrombosis in disease cases is that there exists a wide body of literature that addresses various aspects of the clotting process, but it may not be obvious what information is of direct consequence for what modeling purpose (e.g., for understanding the effect of endovascular therapies). The aim of this review is to present the information so it will be of benefit to the community attempting to model cerebral aneurysm thrombosis for interventional planning purposes, in a simplified yet appropriate manner. The paper begins by explaining current understanding of physiological coagulation and highlights the documented distinctions between the physiological process and cerebral aneurysm thrombosis. Clinical observations of thrombosis following endovascular device placement are then presented. This is followed by a section detailing the demands placed on computational models developed for interventional planning. Finally, existing computational models of thrombosis are presented. This last section begins with description and discussion of physiological computational clotting models, as they are of immense value in understanding how to construct a general computational model of clotting. This is then followed by a review of computational models of clotting in cerebral aneurysms, specifically. Even though some progress has been made towards computational predictions of thrombosis following device placement in cerebral aneurysms, many gaps still remain. Answering the key questions will require the combined efforts of the clinical, experimental and computational communities.

Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the International Subarachnoid Aneurysm Trial (ISAT).

BACKGROUND AND PURPOSE: Because the long-term security of endovascular treatments remains uncertain, a follow-up study of the patients treated in the International Subarachnoid Aneurysm Trial was performed to compare the frequency, timing, and consequences of aneurysm recurrence. METHODS: Patient data were reclassified by actual treatment performed. Aneurysm and patient characteristics, including occlusion grades, time and type of retreatment, and clinical outcomes, were compared. The relationship between these variables and late retreatment as a surrogate for recurrence was analyzed by means of the Cox proportional hazards model. RESULTS: Retreatment was performed in 191 of 1096 (17.4%) patients after primary endovascular coiling (EVT) and in 39 of 1012 patients (3.8%) after neurosurgical clipping. After EVT, 97 (8.8%) patients were retreated early and 94 (9.0%) late, 7 (0.6%) after rebleeding and 87 (8.3%) without. The mean time to late retreatment was 20.7 months. After neurosurgical clipping, 30 (2.9%) patients were retreated early and 9 (0.85%) late, 3 (0.3%) after rebleeding and 6 (0.6%) without. The mean time to late retreatment was 5.7 months. The hazard ratio (HR) for retreatment after EVT was 6.9 (95% CI=3.4 to 14.1) after adjustment for age (P=0.001, HR=0.97, 95% CI=0.95 to 0.98), lumen size (P=0.006, HR=1.1, 95% CI=1.03 to 1.18), and incomplete occlusion (P<0.001, HR=7.6, 95% CI=3.3 to 17.5). CONCLUSIONS: Late retreatment was 6.9 times more likely after EVT. Younger age, larger lumen size, and incomplete occlusion were risk factors for late retreatment after EVT. After neurosurgical clipping, retreatments were earlier; whereas EVT retreatments continued to be performed throughout the follow-up period. Short-term follow-up imaging is therefore insufficient to detect recurrences after EVT.

Outcome of Nonfunctioning Pituitary Adenomas That Regrow After Primary Treatment: A Study From Two Large UK Centers.

Context: Despite the major risk of regrowth of clinically nonfunctioning pituitary adenomas (CNFAs) after primary treatment, systematic data on the probability of further tumor progression and the effectiveness of management approaches are lacking. Objective: To assess the probability of further regrowth(s), predictive factors, and outcomes of management approaches in patients with CNFA diagnosed with adenoma regrowth after primary treatment. Patients, Design, and Setting: Retrospective cohort study of 237 patients with regrown CNFA managed in two UK centers. Results: Median follow-up was 5.9 years (range, 0.4 to 37.7 years). The 5-year second regrowth rate was 35.3% (36.2% after surgery; 12.5% after radiotherapy; 12.7% after surgery combined with radiotherapy; 63.4% with monitoring). Of those managed with monitoring, 34.8% eventually were offered intervention. Type of management and sex were risk factors for second regrowth. Among those with second adenoma regrowth, the 5-year third regrowth rate was 26.4% (24.4% after surgery; 0% after radiotherapy; 0% after surgery combined with radiotherapy; 48.3% with monitoring). Overall, patients with a CNFA regrowth had a 4.4% probability of a third regrowth at 5 years and a 10.0% probability at 10 years; type of management of the first regrowth was the only risk factor. Malignant transformation was diagnosed in two patients. Conclusions: Patients with regrown CNFA after primary treatment continue to carry considerable risk of tumor progression, necessitating long-term follow-up. Management approach to the regrowth was the major factor determining this risk; monitoring had >60% risk of progression at 5 years, and a substantial number of patients ultimately required intervention.