Kevin Murphy’s research while affiliated with Cardiff University and other places

Velocity-selective arterial spin labelling (VSASL) MRI is insensitive to arterial transit time. This is an advantage over other perfusion measurements, where long arterial transit times can lead to bias. Therefore, VSASL can be used to study perfusion in the presence of long arterial transit times, such as in the ageing brain, in vascular pathologies, and cancer, or where arterial transit time changes, such as during measurement of cerebrovascular reactivity (CVR). However, when calculating perfusion (cerebral blood flow, CBF, in the brain) from VSASL signal, it is assumed that images are acquired before the trailing edge of the labelled blood has arrived in the imaging slice. The arrival of the trailing edge of the labelled bolus of blood will cause an underestimation of perfusion. Here we measure bolus duration in young, healthy human brains, both at rest and during elevated CBF. Grey matter bolus duration was 1.61 +/- 0.31 s, but there was a large spatial heterogeneity, with bolus duration being lower in anterior brain regions, with some areas having bolus duration < 1.2 s. We place these results in context of recommendations from a recent consensus paper, which recommends imaging 1.4 s after the label, potentially underestimating CBF in anterior regions. Further, we observed a 0.23 +/- 0.12 s reduction in grey matter bolus duration with 5% CO2 inhalation. These results can be used to inform the experimental design of future VSASL studies, to avoid underestimating perfusion by imaging after the arrival of the trailing edge of the labelled bolus.

Introduction Oestrogen has a protective effect against neurodegenerative conditions, including glaucoma and dementia. Animal models suggest that oestrogen has a vasodilatory effect, which is a possible mechanism for this. However, the full influence of oestrogen on specific cerebrovascular functions is unclear. Aims This study aims to investigate the influence of hormonal fluctuations across a healthy menstrual cycle on measures of retinal and cortical vascular functioning. Methods 27 menstruating participants (age mean[SD]=22.94[3.52] years) completed a testing session during the early-follicular, late-follicular, and mid-luteal phase of their menstrual cycle. Bloods were taken to measure circulating hormones.Retinal vasculature was assessed using a Swept-Source OCT (TOPCON healthcare), including: • Choroidal thickness – 6mm² OCT scan • Vessel density, radius, and resistance – 3mm² OCT Angiography Cortical data were acquired on a Siemens MAGNETOM Prisma 3T MRI scanner and include: • Grey matter Cerebral Blood Flow (CBF) and Arterial Arrival Time (AAT) – MPLD-pCASL scan • Global Oxygen Extraction Fraction (OEF) – TRUST sequence Linear models investigated the amount of variance explained by circulating oestradiol. Results Oestradiol significantly decreased retinal resistance (χ²(1)=6.1218, P=0.01335), an effect which was greatest in the foveal vessels. Other retinal measures were stable across the menstrual cycle. No association was found with OEF, but oestradiol did significantly increase CBF (χ²(1)=17.801; P=2.452e-5) and AAT (χ²(1)=9.5183; P=0.002034), which was a global effect. Conclusion Evidence for oestrogen’s vasodilatory influence was demonstrated across a menstrual cycle and in multiple vascular beds. This provides information into how oestrogen influences the cerebrovascular system and highlights possible mechanisms by which oestrogen has a protective effect against neurodegenerative conditions. Acknowledgements The Wellcome Trust (WT224267)

Cystic fibrosis (CF) is a progressive inherited disorder that primarily affects the lungs. With recent breakthroughs in effective treatments for CF that increase life-expectancy, a higher prevalence of age-related comorbidities have been reported including cardiovascular disease, stroke and cognitive decline. Despite the known relationship between cardiovascular health and cerebrovascular function, very little is known about brain blood flow and oxygen metabolism in patients with CF (PwCF). In 14 PwCF and 56 healthy age / sex matched controls, we used pseudo-continuous arterial spin labelling (pCASL) to quantify cerebral perfusion in grey-matter and T2-Relaxation-Under-Spin-Tagging (TRUST) to estimate global oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2). Compared to healthy controls, PwCF showed elevated CMRO2 (p = 0.015). There were no significant between-group differences in grey-matter CBF (p = 0.342), or whole brain OEF (p = 0.091). However, regional analysis showed certain areas with higher CBF in PwCF (p < .05, FDR). This is the first study to characterise cerebrovascular function and brain oxygen metabolism in PwCF. Our findings highlight the need for early cardiovascular monitoring procedures to help maintain cerebrovascular function and combat accelerated aging effects in the brains of PwCF.

Background Genome-wide association studies demonstrate that Alzheimer’s disease (AD) has a highly polygenic architecture, where thousands of independent genetic variants explain risk with high classification accuracy. This AD polygenic risk score (AD-PRS) has been previously linked to preclinical cognitive and neuroimaging features observed in asymptomatic individuals. However, shared variance between AD-PRS and neurocognitive features are small, suggesting limited preclinical utility. Methods Here, we recruited sixteen clinically asymptomatic individuals (mean age 67; range 58–76) with either extremely low / high AD-PRS (defined as at least 2 standard deviations from the wider sample mean (N = 4504; NEFFECTIVE = 90)) with comparable age sex and education level. We assessed group differences in autobiographical memory and T1-weighted structural neuroimaging features. Results We observed marked reductions in autobiographical recollection (Cohen’s d = − 1.66; PFDR = 0.014) and midline structure (cingulate) thickness (Cohen’s d = − 1.55, PFDR = 0.05), with no difference in hippocampal volume (P > 0.3). We further confirm the negative association between AD-PRS and cingulate thickness in a larger study with a comparable age (N = 31,966, β = − 0.002, P = 0.011), supporting the validity of our approach. Conclusions These observations conform with multiple streams of prior evidence suggesting alterations in cingulate structures may occur in individuals with higher AD genetic risk. We were able to use a genetically informed research design strategy that significantly improved the efficiency and power of the study. Thus, we further demonstrate that the recall-by-genotype of AD-PRS from wider samples is a promising approach for the detection, assessment, and intervention in specific individuals with increased AD genetic risk.

Gender-affirming hormone replacement therapy (gaHRT) is an important step for many in the gender diverse community, associated with increased quality-of-life and lower self-reported scores of depression and anxiety. However, considering the interactions that the involved sex hormones have on vasculature (with oestrogen and testosterone demonstrating vasodilatory and vasoconstricting properties, respectively), it is important for transgender healthcare research to examine how the manipulation of these hormones interact with cerebrovascular structure and functioning. There is a stark lack of research in this area. This mini-review outlines the research suggesting a vascular impact of these sex hormones using evidence from a range of cohorts (e.g., menopause, polycystic ovary syndrome) and discusses the work that has been done into cerebrovascular changes following gaHRT. Finally, recommendations for future research into cerebrovascular health in transgender cohorts following gaHRT are outlined.

Global cerebral blood flow (gCBF) and cerebrovascular reactivity to hypercapnia (CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$) are modulated by gonadal hormone activity, while insulin‐like growth factor 1 facilitates exercise‐mediated cerebral angiogenesis in adults. Whether critical periods of heightened hormonal and neural development during puberty represent an opportunity to further enhance gCBF and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ is currently unknown. Therefore, we used duplex ultrasound to assess gCBF and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ in n = 128 adolescents characterised as endurance‐exercise trained (males: n = 30, females: n = 36) or untrained (males: n = 29, females: n = 33). Participants were further categorised as pre‐ (males: n = 35, females: n = 33) or post‐ (males: n = 24, females: n = 36) peak height velocity (PHV) to determine pubertal or ‘maturity’ status. Three‐factor ANOVA was used to identify main and interaction effects of maturity status, biological sex and training status on gCBF and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$. Data are reported as group means (SD). Pre‐PHV youth demonstrated elevated gCBF and slower CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ mean response times than post‐PHV counterparts (both: P ≤ 0.001). gCBF was only elevated in post‐PHV trained males when compared to untrained counterparts (634 (43) vs. 578 (46) ml min⁻¹; P = 0.007). However, CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ mean response time was faster in pre‐ (72 (20) vs. 95 (29) s; P ≤ 0.001), but not post‐PHV (P = 0.721) trained youth when compared to untrained counterparts. Cardiorespiratory fitness was associated with gCBF in post‐PHV youth (r² = 0.19; P ≤ 0.001) and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ mean response time in pre‐PHV youth (r² = 0.13; P = 0.014). Higher cardiorespiratory fitness during adolescence can elevate gCBF while exercise training during childhood primes the development of cerebrovascular function, highlighting the importance of exercise training during the early stages of life in shaping the cerebrovascular phenotype.

The British and Irish Chapter of the International Society for Magnetic Resonance in Medicine (BIC‐ISMRM) held a workshop entitled “Steps on the path to clinical translation” in Cardiff, UK, on 7th September 2022. The aim of the workshop was to promote discussion within the MR community about the problems and potential solutions for translating quantitative MR (qMR) imaging and spectroscopic biomarkers into clinical application and drug studies. Invited speakers presented the perspectives of radiologists, radiographers, clinical physicists, vendors, imaging Contract/Clinical Research Organizations (CROs), open science networks, metrologists, imaging networks, and those developing consensus methods. A round‐table discussion was held in which workshop participants discussed a range of questions pertinent to clinical translation of qMR imaging and spectroscopic biomarkers. Each group summarized their findings via three main conclusions and three further questions. These questions were used as the basis of an online survey of the broader UK MR community.

Purpose This study investigated the artifacts arising from different types of head motion in brain MR images and how well these artifacts can be compensated using retrospective correction based on two different motion‐tracking techniques. Methods MPRAGE images were acquired using a 3 T MR scanner on a cohort of nine healthy participants. Subjects moved their head to generate circular motion (4 or 6 cycles/min), stepwise motion (small and large) and “simulated realistic” motion (nodding and slow diagonal motion), based on visual instructions. One MPRAGE scan without deliberate motion was always acquired as a “no motion” reference. Three dimensional fat‐navigator (FatNavs) and a Tracoline markerless device (TracInnovations) were used to obtain motion estimates and images were separately reconstructed retrospectively from the raw data based on these different motion estimates. Results Image quality was recovered from both motion tracking techniques in our stepwise and slow diagonal motion scenarios in almost all cases, with the apparent visual image quality comparable to the no‐motion case. FatNav‐based motion correction was further improved in the case of stepwise motion using a skull masking procedure to exclude non‐rigid motion of the neck from the co‐registration step. In the case of circular motion, both methods struggled to correct for all motion artifacts. Conclusion High image quality could be recovered in cases of stepwise and slow diagonal motion using both motion estimation techniques. The circular motion scenario led to more severe image artifacts that could not be fully compensated by the retrospective motion correction techniques used.