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Developing near-infrared spectroscopy (NIRS) parameter recovery techniques to more specifically resolve brain physiology from that of the overlying tissue is an important part of improving the clinical utility of the technology. The Valsalva maneuver (VM) involves forced expiration against a closed glottis causing widespread venous congestion within the context of a fall in cardiac output. Due to the specific anatomical confines and metabolic demands of the brain we believe a properly executed VM has the ability to separate haemodynamic activity of brain tissue from that of the overlying scalp as observed by NIRS, and confirmed by functional magnetic resonance imaging (fMRI). Healthy individuals performed a series of standing maximum effort VMs under separate observation by frequency domain near-infrared spectroscopy (FD-NIRS) and fMRI. Nine individuals completed the clinical protocol (6 males, age 21-40). During the VMs, brain and extracranial tissue targeted signal were significantly different (opposite direction of change) in both fMRI and NIRS (p=0.00025 and 0.00115 respectively), with robust cross correlation of parameters between modalities. Four of these individuals performed further VMs after infiltrating 2% xylocaine/1:100,000 epinephrine (vasoconstrictor) into scalp tissue beneath the probes. No significant difference in the cerebrally derived parameters was observed. The maximum effort VM has the ability to separate NIRS observable physiology of the brain from the overlying extracranial tissue. Observations made by this FD cerebral NIRS device are comparable with fMRI in this context.

Positron emission tomography (PET) alone or in combination with MRI is increasingly assuming a central role in the development of diagnostic and therapeutic strategies for brain tumours with the aim of addressing tumour heterogeneity, assisting in patient stratification, and contributing to predicting treatment response. The 18 kDa translocator protein (TSPO) is expressed in high-grade gliomas, while its expression is comparatively low in normal brain. In addition, the evidence of elevated TSPO in neoplastic cells has led to studies investigating TSPO as a transporter of anticancer drugs for brain delivery and a selective target for tumour tissue. The TSPO therefore represents an ideal candidate for molecular imaging studies. Knowledge of the biology of TSPO in normal brain cells, in-depth understanding of TSPO functions and biodistribution in neoplastic cells, accurate methods for quantification of uptake of TSPO tracers and pharmacokinetic data regarding TSPO-targeted drugs are required before introducing TSPO PET and TSPO-targeted treatment in clinical practice. In this review, we will discuss the impact of preclinical PET studies and the application of TSPO imaging in human brain tumours, the advantages and disadvantages of TSPO imaging compared to other imaging modalities and other PET tracers, and pathology studies on the extent and distribution of TSPO in gliomas. The suitability of TSPO as molecular target for treatment of brain tumours will also be the appraised.

•Vascular structures are difficult to depict by conventional neuronavigation.•We acquired angiographical cone - beam imaging of craniocervical junction tumour.•This novel technique depicts vertebral artery close to the tumour intraoperatively.•It facilitates safe resection by mapping the surgical field occult to direct vision.

ObjectiveWe aim to study the effect of persistent post-concussive symptoms on cognitive performance of elite athletes, based on the hypothesis that persistent symptoms could impair athletes’ cognitive performances and functional outcomes.DesignProspective observational and longitudinal case control study.SettingUniversity research centre, single centre.Participants7 athletes with persistent symptoms (>2 weeks, assessed at median 31 days post-concussion), 10 athletes with brief symptoms (<3 days, assessed within a week, median 3.5 days), and 9 age-matched healthy volunteers. Inclusion criteria: male/female athletes (aged 18–40) in contact sports who sustained concussion(s) recently, being symptomatic with normal neuro-radiological findings at enrolment.InterventionIndependent variables: post-concussive symptom scores and duration of symptoms.Outcome measuresMulti-dimensional scores from Sport Concussion Assessment Tool III, Immediate Post-concussion Assessment and Cognitive Testing, WAIS symbol search and digit span backward tests.Main resultsPatients with persistent symptoms scored less in the symbol search test than those with brief symptoms and the healthy volunteers (grouping effect p=0.006; post hoc tests p=0.039 and 0.004, respectively). In all 17 patients, symptom scores correlated with reaction time (ρ=−0.61, p=0.009), and visual motor speed correlated with symbol search scores (ρ=0.59, p=0.013). 6 patients who completed follow-up assessments when symptom-free showed improvement in their symbol search scores (p=0.042) and visual memory (p=0.028).ConclusionsConcussed athletes with persistent symptoms performed poorly in visual perception/analysis and information processing. Persistent post-concussive symptoms could affect athletes’ visual memory, perception/analysis, reaction time and information processing speed, thus precipitating them to further injuries should they return to play prematurely.Competing interestsNone.

ObjectiveThis study aims to investigate the role of microRNAs in early and late assessments of concussed athletes. Our hypothesis is that expression of certain microRNAs is altered following concussion, and these microRNAs have the potential to become novel biomarkers for early detection and monitoring of concussion.DesignProspective observational case control study.SettingUniversity research centre, single centre.Participants15 concussed athletes divided into 2 groups: Group A (n=9, assessed within a week post-concussion, median 4 days) and B (n=6, assessed over 2 weeks, median 31 days); and 8 age-matched healthy volunteers. Inclusion criteria: male/female elite athletes in contact sports (aged 18-40) who suffered concussion(s) in the games, and being symptomatic with normal neuro-radiological findings at enrolment.Outcome measuresLevels of microRNAs (miR-21, miR-335, miR-425-5p, and miR-502) were measured in blood samples obtained from all participants.Main resultsmiR425-5p was significantly down-regulated in Group A compared with Group B and healthy volunteers (grouping effect p=0.014; post hoc tests p=0.009 and 0.028, respectively). The level of miR425-5p correlated with the interval between assessment and concussion (r2=0.88, p<0.001). No differences were found in other microRNA assessed between the groups.ConclusionsmiR-425-5p is down-regulated in the early phase following sport concussion, and reaches normal levels in the late period, suggesting that it may be a unique microRNA signature for concussion. This makes miR-435-5p a promising candidate biomarker for early evaluation of concussion and monitoring of its recovery. Further longitudinal studies are on-going to establish the time course of miR-425-5p normalisation after concussion. Competing interestsNone.[Figure]

ObjectiveChanges in cerebral N-acetylaspartate and choline (NAA/Cho) or creatine (NAA/Cr) following a mild traumatic brain injury (mTBI) in sport have been measured by 1H (Proton) magnetic resonance spectroscopy (1H-MRS). We intend to investigate the effect that presenting symptomatology has on these parameters.DesignObservational cohort study.SettingUK Premiership and Championship Rugby.ParticipantsAthletes aged 18-40 years.Interventions (or assessment of risk factors)Concussed athletes identified by members of their enhanced-care clinical team. Imaging undertaken on a Philips Achieva 3.0 T MR scanner (32 channel SENSE coil). A PRESS sequence (et 37 ms, rt 2000 ms) generated spectra in a 20 mm MRS cubic voxel in right-sided superior frontal white matter. Symptoms were assessed using the IMPACT and SCAT-3 concussion assessment tools. Recruits were divided into either ‘symptomatic’ or ‘non-symptomatic’ at presentation based on a minimum severity score from either of these assessments.Outcome measuresAnalysis of raw parameters was undertaken utilising the TARQUIN 1H-MRS analytical software package. A Mann-Whitney-U test was performed to compare results between the symptomatic and non-symptomatic groups.Main results33 concussed professional athletes were recruited. Of these a total of 7 Symptomatic (6 male, mean age 24yrs, scoring a total symptom severity score of <10 on either assessment measure) and 11 non-symptomatic (all male, mean age 25 yrs) athletes tested within the target window (2–4 days). Ratios between groups did not vary significantly (NAA/Cho mean 4.43 vs 4.53 and NAA/Cr 1.24 vs 1.26, p=0.84 and p=0.99 respectively).ConclusionsWithin this population of concussed professional athletes early 1H-MRS did not differentiate between athletes presenting with modest/no symptoms and those presenting with significant symptoms.Competing interestsNone.

Translocator protein (TSPO) is overexpressed mainly in activated microglia under disease conditions. [11C]-(R)PK11195 is a radioligand for TSPO widely applied in PET studies. Previously we have found upregulated TSPO in neoplastic cells and its correlation with malignant transformation in human gliomas using [11C]-(R)PK11195 PET and neuropathological assessment. We aimed to investigate TSPO expression and microglial activation in normal-appearing brain regions of patients with glioma.

A reliable portable non-invasive monitor for use in brain injury is needed, so near infrared spectroscopy (NIRS) has potential. Historical inconsistencies in NIRS have prevented its use, often attributed to the contamination of signal from extracranial tissue. We aimed to validate the brain signal from frequency domain NIRS (advanced NIRS technique), comparing its abilities with functional MRI (fMRI) to isolate physiological activity in the brain from those of extracranial tissue.