Time-of-Flight MRA of Intracranial Aneurysms with Interval Surveillance, Clinical Segmentation and Annotations.

Intracranial aneurysms (IAs) are present in 2-6% of the global population and can be catastrophic upon rupture with a mortality rate of 30-50%. IAs are commonly detected through time-of-flight magnetic resonance angiography (TOF-MRA), however, this data is rarely available for research and training purposes. The provision of imaging resources such as TOF-MRA images is imperative to develop new strategies for IA detection, rupture prediction, and surgical training. To support efforts in addressing data availability bottlenecks, we provide an open-access TOF-MRA dataset comprising 63 patients, of which 24 underwent interval surveillance imaging by TOF-MRA. Patient scans were evaluated by a neuroradiologist, providing aneurysm and vessel segmentations, clinical annotations, 3D models, in addition to 3D Slicer software environments containing all this data for each patient. This dataset is the first to provide interval surveillance imaging for supporting the understanding of IA growth and stability. This dataset will support computational and experimental research into IA dynamics and assist surgical and radiology training in IA treatment.

Detection of clustered anomalies in single-voxel morphometry as a rapid automated method for identifying intracranial aneurysms.

Unruptured intracranial aneurysms (UIAs) are prevalent neurovascular anomalies which, in rare circumstances, rupture to cause a catastrophic subarachnoid haemorrhage. Although surgical management can reduce rupture risk, the majority of UIAs exist undiscovered until rupture. Current clinical practice in the detection of UIAs relies heavily on manual radiological review of standard imaging modalities. Recent computer-aided UIA diagnoses can sensitively detect and measure UIAs within cranial angiograms but remain limited to low specificities whose output also requires considerable radiologist interpretation not amenable to broad screening efforts. To address these limitations, we have developed a novel automatic pipeline algorithm which inputs medical images and outputs detected UIAs by characterising single-voxel morphometry of segmented neurovasculature. Once neurovascular anatomy of a specified resolution is segmented, correlations between voxel-specific morphometries are estimated and spatially-clustered outliers are identified as UIA candidates. Our automated solution detects UIAs within magnetic resonance angiograms (MRA) at unmatched 86% specificity and 81% sensitivity using 3 min on a conventional laptop. Our approach does not rely on interpatient comparisons or training datasets which could be difficult to amass and process for rare incidentally discovered UIAs within large MRA files, and in doing so, is versatile to user-defined segmentation quality, to detection sensitivity, and across a range of imaging resolutions and modalities. We propose this method as a unique tool to aid UIA screening, characterisation of abnormal vasculature in at-risk patients, morphometry-based rupture risk prediction, and identification of other vascular abnormalities.

Incidence and outcome of subarachnoid haemorrhage in the general and emergency department populations in Queensland from 2010 to 2014.

OBJECTIVES: To determine: (i) incidence and outcome of subarachnoid haemorrhage (SAH) in the general population; and (ii) proportions of SAH in both the general ED population and in ED patients presenting with headache. METHODS: A population-based study in Queensland from January 2010 to December 2014 was conducted. Data were sourced from the Australian Bureau of Statistics, Queensland Hospital Admitted Patient Data Collection linked to the Queensland death registry and ED Information System. Admitted patients with SAH were identified from ICD-10-AM codes. Inter-hospital transfers and repeat admissions for previously diagnosed SAH were excluded. Pre-hospital deaths from SAH were included. ED patients with headache were identified from ICD-10-AM codes and finding 'headache' in the triage free-text entry. The incidence of SAH, in-hospital mortality, proportions of SAH in the general ED population and ED patients with headache were calculated. RESULTS: There were 1975 incident cases of SAH in admitted patients and 294 pre-hospital deaths from SAH. The incidence of SAH was 9.9 (95% confidence interval [CI] 9.5-10.4) per 100 000 person-years. The incidence standardised to the 'World Standard Population' was 7.0 per 100 000 person-years. The in-hospital mortality was 23.8% (95% CI 22.0-25.8%). SAH was found in 1407 (1.9%, 95% CI 1.8-2.0) of ED patients with headache. Overall, there were 2.4 (95% CI 2.3-2.5) SAH per 10 000 of all ED attendances. CONCLUSIONS: The incidence of SAH was similar to that previously reported for Australia. One in 50 ED patients with headache had SAH. Ten in 50 000 ED attendances had a SAH. These estimates can assist in the risk assessment for SAH.

'Talk and die' patients presenting to a major trauma centre over a 10 year period: a critical review.

'Talk and die patients' describes a small number of patients who present with a mild head injury (Glasgow Coma Scale [GCS] 13-15) and then subsequently deteriorate and die from intracranial causes. We analysed the medical records of all those adult patients whose primary diagnosis as the cause of death was head injury, as determined by the coroner, who were admitted to a major Australian trauma centre between January 1994 and December 2003 (a 10-year period). The clinical profile of those patients who fulfilled the criteria of 'talk and die' were documented, including age, mode of injury, initial GCS, lucid interval, CT scan reports, operation performed, post mortem findings and intracranial cause of death. Factors considered potentially contributory to the patients' deterioration, such as delays in CT scanning or patient transfer, coagulopathy or hypoxic episodes were also noted. The incidence of 'talk and die' patients was 2.6% (15 out of 569) overall and the annual incidence did not significantly alter over the 10-year period of the study. The small number of patients precludes inferences regarding causal relationships, although potentially preventable factors, which could have been contributory to patient deterioration, were identified.

Current controversies in the management of patients with severe traumatic brain injury.

BACKGROUND: Traumatic brain injury is a major cause of mortality and morbidity, particularly among young men. The efficacy and safety of most of the interventions used in the management of patients with traumatic brain injury remain unproven. Examples include the 'cerebral perfusion pressure-targeted' and 'volume-targeted' management strategies for optimizing cerebrovascular haemodynamics and specific interventions, such as hyperventilation, osmotherapy, cerebrospinal fluid drainage, barbiturates, decompressive craniectomy, therapeutic hypothermia, normobaric hyperoxia and hyperbaric oxygen therapy. METHODS: A review of the literature was performed to examine the evidence base behind each intervention. RESULTS: There is no class I evidence to support the routine use of any of the therapies examined. CONCLUSION: Well-designed, large, randomized controlled trials are needed to determine therapies that are safe and effective from those that are ineffective or harmful.

A microdialysis method for the recovery of IL-1beta, IL-6 and nerve growth factor from human brain in vivo.

Intracerebral microdialysis is used extensively as a research tool in the investigation of the neurochemical and metabolic changes that occur following acute brain injury. Microdialysis has enabled elucidation of intra-cerebral levels of substances such as lactate, pyruvate and glycerol but, as yet, has not been used effectively to recover macromolecules from the human brain. Traumatic brain injury is known to result in the generation of cytokines and neurotrophins into extracellular fluid compartment of the brain, with effects on neuronal damage and repair. We have developed a technique of in vivo sampling of the interstitial fluid of the brain of patients with severe head injuries which has allowed the measurement of IL-1beta, IL-6 and nerve growth factor. This report confirms the safety and effectiveness of this modified microdialysis method in the clinical setting of a neurological intensive care unit. The technique provides a timely addition to the armamentarium of the clinical scientist and will potentially lead to a greater understanding of neuroinflammation following acute traumatic brain injury.

Elevated plasma S100B levels in high altitude hypobaric hypoxia do not correlate with acute mountain sickness.

OBJECTIVES: Ascent to high altitude may result in a hypobaric hypoxic brain injury. The development of acute mountain sickness (AMS) is considered a multifactorial process with hypoxia-induced blood-brain barrier (BBB) dysfunction and resultant vasogenic oedema cited as one potential mechanism. Peripheral S100B is considered a biomarker of BBB dysfunction. This study aims to investigate the S100B release profile secondary to hypoxic brain injury and comment on BBB disturbance and AMS. METHODS: A prospective field study of 12 subjects who ascended Mt Fuji (3700 m) was undertaken. RESULTS: The mean baseline plasma S100B level was 0·11 µg/l (95% CI 0·09-0·12), which increased to 0·22 µg/l (95% CI 0·17-0·27) at the average of three high altitude levels (2590, 3700, and 2590 m on descent) (P < 0·001). The mean level for the seven subjects who experienced AMS rose from 0·10 to 0·19 µg/l compared to 0·12 to 0·25 µg/l for the five subjects who did not develop AMS (P  =  0·33). CONCLUSION: Ascending to 3700 m resulted in elevated plasma S100B levels but this was not associated with AMS.

Computational fluid dynamic analysis of intracranial aneurysmal bleb formation.

BACKGROUND: The management of unruptured aneurysms is controversial, with the decision to treat influenced by aneurysm characteristics including size and morphology. Aneurysmal bleb formation is thought to be associated with an increased risk of rupture. OBJECTIVE: To correlate computational fluid dynamic (CFD) indices with bleb formation. METHODS: Anatomic models were constructed from 3-dimensional rotational angiography data in 27 patients with cerebral aneurysms harboring a single bleb. Additional models representing the aneurysm before bleb formation were constructed by digitally removing the bleb. We characterized hemodynamic features of models both with and without the blebs using CFDs. Flow structure, wall shear stress (WSS), pressure, and oscillatory shear index (OSI) were analyzed. RESULTS: There was a statistically significant association between bleb location at or adjacent to the point of maximal WSS (74%, P = .019), irrespective of rupture status. Aneurysmal blebs were related to the inflow or outflow jet in 89% of cases (P < .001), whereas 11% were unrelated. Maximal wall pressure and OSI were not significantly related to bleb location. The bleb region attained a lower WSS after its formation in 96% of cases (P < .001) and was also lower than the average aneurysm WSS in 86% of cases (P < .001). CONCLUSION: Cerebral aneurysm blebs generally form at or adjacent to the point of maximal WSS and are aligned with major flow structures. Wall pressure and OSI do not contribute to determining bleb location. The measurement of WSS using CFD models may potentially predict bleb formation and thus improve the assessment of rupture risk in unruptured aneurysms.

Raised parenchymal interleukin-6 levels correlate with improved outcome after traumatic brain injury.

Previous studies have suggested that an increased production of the pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) can influence patient outcome following a severe head injury. However, these studies have relied upon measurements of cytokine levels in CSF or serum, rather than the brain parenchyma itself. Recently, a method of intracranial microdialysis has been developed which permits the efficient recovery of macromolecules from the parenchyma. We have used this technique to investigate whether there is a correlation between patient outcome and parenchymally derived cytokines. Fourteen patients who were admitted to the Wessex Neurological Centre with severe head injury were selected for the study. This group of patients consisted of seven males and seven females with an age range of 21-77 years. Patients were treated according to standard protocols including emergency craniotomy where necessary. Microdialysis probes were implanted into the frontal region contralateral to the site of the primary injury. Approximately 200 micro l of dialysate was recovered every 8-12 h, and the concentrations of IL-6, IL-1beta and nerve growth factor (NGF) were determined by commercial enzyme-linked immunosorbent assays. Patients were assessed initially using the Glasgow coma score, and survivors were assessed after 6 months using the Glasgow outcome scale. Significantly (P = 0.04) higher levels of IL-6 were found in patients who survived compared with those who died. Also, there was a significant correlation between peak IL-6 levels and Glasgow outcome scores (r(2) = 0.34, P = 0.03, n = 14). The levels of IL-1beta and NGF were similar in both groups of patients. From these data, we suggest that IL-6 is an endogenous neuroprotective cytokine produced in response to severe head trauma.