A single centre retrospective analysis of short- and medium-term outcomes using the Woven EndoBridge (WEB) device and identification of the device-to-aneurysm volume ratio as a potential predictor of aneurysm occlusion status.

BACKGROUND: The Woven EndoBridge (WEB) is a potential treatment option in patients with wide-necked bifurcation aneurysms (WNBAs). We analysed our WEB device outcomes (occlusion rates and complications) and studied factors that may predict aneurysm occlusion status at short- and medium-term follow-up. METHODS: 74 patients with ruptured and unruptured aneurysms underwent treatment with the WEB device over a 5-year period. Simple hypothesis tests assessed differences between treated ruptured and unruptured aneurysms. Univariable binary logistic regression was used to assess the effect of age, gender, and aneurysm location on the likelihood of adequate occlusion at six months. Aneurysm dimentions including device-to-aneurysm volume (DAV) ratios were compared between adequately and inadequately occluded aneurysms. RESULTS: The mean age at the time of the procedure was 58.2 years (SD 12.2; range 34-88) and the male to female ratio was 1:2.7. Middle cerebral artery (MCA) was the most commonly treated aneurysm. There was no significant difference in occlusion rates between ruptured and unruptured aneurysms. The six- and 18-month angiographic follow-up data was available for 61 and 32 patients respectively with adequate occlusion rates of 78.7% (48/61) and 78.1% (25/32). Procedure-related complications occurred in 6 patients (8.1%). Baseline DAV ratio was found to be significantly higher in aneurysms that were adequately occluded at both short- (p-value 0.015) and medium-term (p-value 0.047) follow-up. CONCLUSIONS: WEB devices are a safe and effective endovascular treatment option for WNBAs. WEB device selection incorporating the peri-procedural DAV ratio may help improve the accuracy of device sizing thereby improving the successful occlusion rate.

Radiological follow-up of endovascularly treated intracranial aneurysms: a survey of current practice in the UK and Ireland.

PURPOSE: Due to the risk of intracranial aneurysm (IA) recurrence and the potential requirement for re-treatment following endovascular treatment (EVT), radiological follow-up of these aneurysms is necessary. There is little evidence to guide the duration and frequency of this follow-up. The aim of this study was to establish the current practice in neurosurgical units in the UK and Ireland. METHODS: A survey was designed with input from interventional neuroradiologists and neurosurgeons. Neurovascular consultants in each of the 30 neurosurgical units providing a neurovascular service in the UK and Ireland were contacted and asked to respond to questions regarding the follow-up practice for IA treated with EVT in their department. RESULTS: Responses were obtained from 28/30 (94%) of departments. There was evidence of wide variations in the duration and frequency of follow-up, with a minimum follow-up duration for ruptured IA that varied from 18 months in 5/28 (18%) units to 5 years in 11/28 (39%) of units. Young patient age, previous subarachnoid haemorrhage and incomplete IA occlusion were cited as factors that would prompt more intensive surveillance, although larger and broad-necked IA were not followed-up more closely in the majority of departments. CONCLUSIONS: There is a wide variation in the radiological follow-up of IA treated with EVT in the UK and Ireland. Further standardisation of this aspect of patient care is likely to be beneficial, but further evidence on the behaviour of IA following EVT is required in order to inform this process.

Therapeutic Response Evaluation in Advanced Melanoma Patients Incorporating Plasma cfDNA, LDH, VEGF, PD-L1, and IFN-γ Measurements.

BACKGROUND/AIM: Current treatment strategies for advanced melanoma require serial assessment of disease status in affected patients. In this study, we sought to examine the relationship between radiographic tumour burden and blood borne biomarkers including plasma cfDNA, serum LDH, plasma VEGF, PD-L1 and IFN-γ in advanced melanoma patients receiving immunotherapy. We hypothesized that a combination of these explanatory variables in a suitable regression analysis model may predict changes in tumour burden during patient treatment. MATERIALS AND METHODS: We extracted and quantified circulating cfDNA, LDH, VEGF, PD-L1, and IFN-γ from thirty patients with stage IV melanoma at baseline and at six months. All participating patients were evaluated with paired blood sample collection and CT scan assessments during treatment. RESULTS: Changes in radiographic tumour burden correlated with changes in levels of cfDNA (p≤0.001), LDH (p≤0.001), VEGF (p≤0.001), and PD-L1 (p<0.05) during treatment. Multiple regression analysis consisting of the follow-up to baseline assessment ratios of cfDNA, LDH, VEGF and PD-L1 explained changes in tumour burden (F (4, 23)=32.05, p<0.001); with an R2 of 0.8479 (Y=ß0+ß1*B+ß2*C+ß3*D+ß4*E). CONCLUSION: A quantitative measure of cfDNA, LDH, VEGF and PD-L1 may complement current methods of assessing tumour burden in advanced melanoma patients.

Clinical audit comparing radiation dose metrics between WEB and coil embolisation in the treatment of intracranial aneurysms.

INTRODUCTION: Intrasaccular flow disruption is a new and effective endovascular treatment for intracranial aneurysms. While endovascular treatment is a minimally invasive procedure, it does carry a radiation risk. As radiation dose should be kept as low as reasonably achievable (ALARA), the main objective of this study was to analyse KAP (kerma area product), fluoroscopy and procedure time during the treatment of aneurysms treated with coiling and the Woven-EndoBridge (WEB) device. A secondary objective was to look at the reference air kerma (RAK) to determine if the patient receives a dose that could cause tissue effects. METHODS: KAP, fluoroscopy and procedure time were retrospectively analysed in patients who had an aneurysm treatment. Aneurysms with diameters of 4-11mm, over a four-year period, in the anterior and posterior circulation of the brain were analysed in this study. Patients were treated by coiling or WEB. RAK were summed together in the working projection to give an estimated entrance surface dose (ESD) in cases with the highest KAP. RESULTS: A total of 47 aneurysms treated with WEB and 104 aneurysms treated with coiling techniques met the inclusion criteria. The average KAP was 6884.1 ± 2774.4µGym2 with coiling techniques and 5658.7 ± 1602.5µGym2 with WEB (p=0.006; CI =363-2086µGym2). This demonstrates an 18% reduction with WEB. Mean fluoroscopy time for coiling was 63.5 ± 42.6minutes and 33.8 ± 28.8minutes for WEB (p=<0.001; CI=16-43minutes). Fluoroscopy time was reduced by nearly 50% with WEB. On average, there was a 27-minute reduction of procedure time when using WEB compared to coiling. The RAK determined for the working projections did not exceed the 2Gy threshold for tissue effects. CONCLUSION: Treatment of aneurysms using the WEB shows a reduction in KAP, fluoroscopy, and procedure time. This study further demonstrates the benefits of intrasaccular flow disruption for treatment of intracranial aneurysms.

The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study.

BACKGROUND: Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA. METHODS: Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled. RESULTS: BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p < 0.001, versus control). GZMB and HLA-A genes were significantly over-expressed in high-grade glioma patients (p < 0.001, versus low-grade glioma patients). Moreover, the fold change of the BCL2L1 gene was observed to be higher in patients with high-grade glioma (p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p < 0.05). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of the CSF3 gene (r = 0.9813, n = 20, p < 0.001). CONCLUSION: We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.

Plasma circulating cell free messenger RNA as a potential biomarker of melanoma.

BACKGROUND: Blood borne cell free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with a low disease burden or therapeutic response. METHODS: Pathway focussed gene expression analysis was performed using cDNA derived from the plasma circulating cell free messenger ribonucleic acid (ccfmRNA) samples of twenty-two patients with advanced melanoma. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. RESULTS: We identified several genes which were significantly over-expressed in patients with a low disease burden or therapeutic response; BCL2L1, CXCL9, IDO1, IL13, MIF, MYD88 and TLR4 (p ≤ 0.001, versus high disease burden). There was an increase in the magnitude of fold change (2^ (-dd CT)) of BCL2L1 (p = 0.031), CCL4 (p = 0.001), CCL5 (p = 0.043), CXCL9 (p = 0.012), GZMB (p = 0.023) and TNFSF10 (p = 0.039) genes in patients with therapeutic response at 3 months follow up assessment relative to baseline assessment. Moreover, in stage IV melanoma patients with brain metastases, CCL18, CCR1, CCR4, CD274, CSF2, EGF, and PTGS2 genes were significantly over-expressed (p < 0.001, versus patients without melanoma brain metastasis). CONCLUSION: Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma.

Development and implementation of an ultralow-dose CT protocol for the assessment of cerebrospinal shunts in adult hydrocephalus.

BACKGROUND: Cerebrospinal fluid shunts in the treatment of hydrocephalus, although associated with clinical benefit, have a high failure rate with repeat computed tomography (CT) imaging resulting in a substantial cumulative radiation dose. Therefore, we sought to develop a whole-body ultralow-dose (ULD) CT protocol for the investigation of shunt malfunction and compare it with the reference standard, plain radiographic shunt series (PRSS). METHODS: Following ethical approval, using an anthropomorphic phantom and a human cadaveric ventriculoperitoneal shunt model, a whole-body ULD-CT protocol incorporating two iterative reconstruction (IR) algorithms, pure IR and hybrid IR, including 60% filtered back projection and 40% IR was evaluated in 18 adult patients post new shunt implantation or where shunt malfunction was suspected. Effective dose (ED) and image quality were analysed. RESULTS: ULD-CT permitted a 36% radiation dose reduction (median ED 0.16 mSv, range 0.07-0.17, versus 0.25 mSv (0.06-1.69 mSv) for PRSS (p = 0.002). Shunt visualisation in the thoracoabdominal cavities was improved with ULD-CT with pure IR (p = 0.004 and p = 0.031, respectively) and, in contrast to PRSS, permitted visualisation of the entire shunt course (p < 0.001), the distal shunt entry point and location of the shunt tip in all cases. For shunt complications, ULD-CT had a perfect specificity. False positives (3/22, 13.6%) were observed with PRSS. CONCLUSIONS: At a significantly reduced radiation dose, whole body ULD-CT with pure IR demonstrated diagnostic superiority over PRSS in the evaluation of cerebrospinal fluid shunt malfunction.

Focal Cerebral Arteriopathy in Young Adult Patients With Stroke.

Background and Purpose- Focal cerebral arteriopathy is monophasic inflammatory stenosis of the distal internal carotid artery or the proximal segment of the middle cerebral artery. It is one of the most common causes of acute arterial ischemic stroke in young children but is a less familiar entity for adult neurologists. Methods- We retrospectively reviewed stroke service radiology records at a tertiary referral center from January 2013 to December 2014. Focal cerebral arteriopathy was defined as nonprogressive unifocal and unilateral stenosis/irregularity of the distal internal carotid artery or its proximal branches. Only patients aged 16 to 55 years with stroke were included. Results- There were 5 cases of focal cerebral arteriopathy: 2 males and 3 females. Three cases were from the cohort of 123 acute presentations of young stroke, and 2 cases were outpatient referrals. The mean age (range) was 43 (32-55) years. The majority presented with recurrent transient ischemic attacks/minor strokes within a single vascular territory over days to weeks. All cases had characteristic radiological features. Interval imaging demonstrated resolution in 1 case and improvement in 3 cases. Functional outcome was excellent with discharge modified Rankin Scale score ranging from 0 to 1. Recurrence occurred in 1 case. Conclusions- Focal cerebral arteriopathy is a rare cause of arterial ischemic stroke in young adults. Follow-up intracranial imaging is essential to differentiate from progressive arteriopathies. Evidence-based treatment warrants further investigation. Prognosis is favorable.

Monitoring neurointerventional radiation doses using dose-tracking software: implications for the establishment of local diagnostic reference levels.

OBJECTIVES: There is potential for high radiation exposure during neurointerventional procedures. Increasing regulatory requirements mandate dose monitoring of patients and staff, and justification of high levels of radiation exposure. This paper demonstrates the potential to use radiation dose-tracking software to establish local diagnostic reference levels. METHODS: Consecutive neurointerventional procedures, performed in a single institution within a one-year period, were retrospectively studied. Dose area product (DAP) data were collected using dose-tracking software and clinical data obtained from a prospectively generated patient treatment database. RESULTS: Two hundred and sixty-four procedures met the selection criteria. Median DAP was 100 Gy.cm2 for aneurysm coiling procedures, 259 Gy.cm2 for arteriovenous malformation (AVM) embolisation procedures, 87 Gy.cm2 for stroke thrombolysis/thrombectomy, and 74 Gy.cm2 for four-vessel angiography. One hundred and nine aneurysm coiling procedures were further studied. Six significant variables were assessed using stepwise regression analysis to determine effect on DAP. Aneurysm location (anterior vs posterior circulation) had the single biggest effect (p = 0.004). CONCLUSIONS: This paper confirms variable radiation exposures during neurointerventional procedures. The 75th percentile (used to define diagnostic reference levels) of DAP measurements represents a reasonable guidance metric for monitoring purposes. Results indicate that aneurysm location has the greatest impact on dose during coiling procedures and that anterior and posterior circulation coiling procedures should have separate diagnostic reference levels. KEY POINTS: • Dose-tracking software is useful for monitoring patient radiation dose during neurointerventional procedures • This paper provides a template for methodology applicable to any interventional suite • Local diagnostic reference levels were defined by using the 75th percentile of DAP as per International Commission on Radiological Protection recommendations • Aneurysm location is the biggest determinant of radiation dose during coiling procedures. • Anterior and posterior circulation coiling procedures should have separate diagnostic reference levels.

CT of the head for acute stroke: Diagnostic performance of a tablet computer prior to intravenous thrombolysis.

INTRODUCTION: The authors propose that tablet computers could benefit patients with acute stroke in the remote care setting, where time to and accuracy of CT interpretation greatly influences patient outcome. METHODS: One hundred and fifty consecutive patients who presented to the Emergency Department of a tertiary referral neurosciences centre within a time window suitable for intravenous thrombolytic therapy were included. Images were wirelessly transmitted to a tablet computer (iPad 3rd Generation, model = A1430, Apple, Cupertino, CA) and were reviewed by radiologists with three levels of experience for signs of intracranial haemorrhage, large vessel occlusion and parenchymal infarction. Reference standard interpretation was performed by two neuroradiologists using a diagnostic monochrome display. RESULTS: Consensus neuroradiologist review on the tablet display found and correctly classified all of the 23 cases of intracranial haemorrhage including 21 cases of parenchymal haematoma, two cases of petechial haemorrhage and one patient with an acute subdural haematoma. Less experienced readers missed cases of petechial and subdural haematomas. There was excellent agreement between the tablet and diagnostic monochrome display in cases with no infarct or extensive parenchymal infarction. CONCLUSIONS: Tablet computers can be used to facilitate rapid preliminary CT interpretation in patients with acute stroke in the remote setting.

Low-Dose Carotid Computed Tomography Angiography Using Pure Iterative Reconstruction.

UNLABELLED: The aim of this study was to assess if a low-dose carotid computed tomography angiography (CTA) performed with pure iterative reconstruction (IR) is comparable to a conventional dose CTA protocol. METHODS: Twenty patients were included. Radiation dose was divided into a low-dose acquisition reconstructed with pure IR and a conventional dose acquisition reconstructed with 40% hybrid IR. Dose, image noise, contrast resolution, spatial resolution, and carotid artery stenosis were measured. RESULTS: Mean effective dose was significantly lower for low-dose than conventional dose studies (1.84 versus 3.71 mSv; P < 0.001). Subjective image noise, contrast resolution, and spatial resolution were significantly higher for the low-dose studies. There was excellent agreement for stenosis grading accuracy between low- and conventional dose studies (Cohen κ = 0.806). CONCLUSIONS: A low-dose carotid CTA protocol reconstructed with pure IR is comparable to a conventional dose CTA protocol in terms of image quality and diagnostic accuracy while enabling a dose reduction of 49.6%.

Aneurysmal wall enhancement and perianeurysmal edema after endovascular treatment of unruptured cerebral aneurysms.

INTRODUCTION: Perianeurysmal edema and aneurysm wall enhancement are previously described phenomenon after coil embolization attributed to inflammatory reaction. We aimed to demonstrate the prevalence and natural course of these phenomena in unruptured aneurysms after endovascular treatment and to identify factors that contributed to their development. METHODS: We performed a retrospective analysis of consecutively treated unruptured aneurysms between January 2000 and December 2011. The presence and evolution of wall enhancement and perianeurysmal edema on MRI after endovascular treatment were analyzed. Variable factors were compared among aneurysms with and without edema. RESULTS: One hundred thirty-two unruptured aneurysms in 124 patients underwent endovascular treatment. Eighty-five (64.4 %) aneurysms had wall enhancement, and 9 (6.8 %) aneurysms had perianeurysmal brain edema. Wall enhancement tends to persist for years with two patterns identified. Larger aneurysms and brain-embedded aneurysms were significantly associated with wall enhancement. In all edema cases, the aneurysms were embedded within the brain and had wall enhancement. Progressive thickening of wall enhancement was significantly associated with edema. Edema can be symptomatic when in eloquent brain and stabilizes or resolves over the years. CONCLUSIONS: Our study demonstrates the prevalence and some appreciation of the natural history of aneurysmal wall enhancement and perianeurysmal brain edema following endovascular treatment of unruptured aneurysms. Aneurysmal wall enhancement is a common phenomenon while perianeurysmal edema is rare. These phenomena are likely related to the presence of inflammatory reaction near the aneurysmal wall. Both phenomena are usually asymptomatic and self-limited, and prophylactic treatment is not recommended.

Solitaire FR stent as an adjunctive tool for pipeline stent deployment in the treatment of giant intracranial aneurysms.

BACKGROUND AND IMPORTANCE: The use of flow-diverting stents has gained acceptance during the past few years for the treatment of numerous intracranial aneurysms, especially large or giant ones. However, successful catheterization of the distal parent artery in giant intracranial aneurysms with a microcatheter can be extremely challenging. Forming a microcatheter loop in the aneurysm sac can aid distal catheterization. CLINICAL PRESENTATION: We report the use of a Solitaire FR stent as an adjunctive tool in the successful treatment of 2 giant intracranial unruptured aneurysms with a Pipeline Embolization Device. After having formed a loop inside the aneurysm sac, the microcatheter was anchored distally by a Solitaire FR stent. With the Solitaire FR device opened, the loop in the giant aneurysm sac was completely reduced without loss of the microcatheter position in the distal parent artery. A Pipeline Embolization Device could be delivered in both cases without any difficulty. There were no complications. CONCLUSION: The technique described results in ideal microcatheter alignment with a secure distal position before deployment of a flow-diverting stent.

Emergency CT brain: preliminary interpretation with a tablet device: image quality and diagnostic performance of the Apple iPad.

Tablet devices have recently been used in radiological image interpretation because they have a display resolution comparable to desktop LCD monitors. We identified a need to examine tablet display performance prior to their use in preliminary interpretation of radiological images. We compared the spatial and contrast resolution of a commercially available tablet display with a diagnostic grade 2 megapixel monochrome LCD using a contrast detail phantom. We also recorded reporting discrepancies, using the ACR RADPEER system, between preliminary interpretation of 100 emergency CT brain examinations on the tablet display and formal review on a diagnostic LCD. The iPad display performed inferiorly to the diagnostic monochrome display without the ability to zoom. When the software zoom function was enabled on the tablet device, comparable contrast detail phantom scores of 163 vs 165 points were achieved. No reporting discrepancies were encountered during the interpretation of 43 normal examinations and five cases of acute intracranial hemorrhage. There were seven RADPEER2 (understandable) misses when using the iPad display and 12 with the diagnostic LCD. Use of software zoom in the tablet device improved its contrast detail phantom score. The tablet allowed satisfactory identification of acute CT brain findings, but additional research will be required to examine the cause of "understandable" reporting discrepancies that occur when using tablet devices.

Superior cerebellar aneurysm causing subarachnoid haemorrhage in a 17-year-old with alagille syndrome.

Alagille syndrome is a rare autosomal dominant condition characterised by mutation in Jagged1 gene. Intracranial aneurysms may be seen in this condition and may present as subarachnoid hemorrhage. We describe the first case of superior cerebellar aneurysm rupture causing WFNS grade 1 subarachnoid haemorrhage in a 17-year-old girl. The clinical condition and management of this rare occurrence is discussed with a review of literature.