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ABSTRACT. Over the last few decades there has been considerable research into quantifying the cerebral microvasculature with imaging, for use in studies of the human brain and various pathologies including cerebral tumours. This review highlights key issues in dynamic contrast-enhanced CT, dynamic contrast-enhanced MRI and arterial spin labelling, the various applications of which are considered elsewhere in this special issue of the British Journal of Radiology. The tumour microvasculature can readily be imaged using X-ray, CT and MRI techniques. This review concentrates on three main methods. Dynamic contrast-enhanced CT (DCE-CT) and dynamic contrastenhanced MRI (DCE-MRI) are well-established techniques, where data acquisition and analysis are comparable despite inherent differences in signal production and mechanism of tissue contrast enhancement (reviewed in [1,2]). Although they can be performed on conventional clinical scanners, they require specialist image analysis to extract biomarkers of tumour vascular function. In distinction, arterial spin labelling (ASL) offers a highly specific method of measuring cerebral perfusion without exogenous contrast agent (CA) administration, but is at present a research technique. The practical applications of these techniques are considered elsewhere in this special issue. Basic principles of dynamic contrast-enhanced imagingDCE imaging describes the acquisition of a baseline image(s) without contrast enhancement followed by a series of images acquired over time after an intravenous bolus of conventional CA. The presence of CA within cerebral blood vessels and tissues affects measured X-ray attenuation on CT in a linear fashion and the calculated signal intensity on MRI in a non-linear manner. Thus, the temporal changes in contrast enhancement effectively provide a time-concentration curve, which can be analysed to quantify a range of physiological parameters that indicate the functional status of the vascular system within tumours and adjacent tissues. These parameters reflect the two-compartment pharmacokinetics exhibited by CA, comprising intravascular and extravascular components. During the first-pass of the CA through the circulation (typically 45-60 s after injection), CA is predominantly intravascular allowing evaluation of perfusion (i.e. blood flow per unit volume or mass of tissue), relative blood volume (rBV) and mean transit time. During the subsequent 2-10 min, there is increasing passage of CA into the extravascular space, and imaging during this delayed phase enables measurement of vascular permeability and relative extravascular volume. DCE-CT image acquisition protocolsA number of distinct DCE-CT techniques have been developed, reflecting the different analysis methodologies adopted by commercial software packages for perfusion CT. The main acquisition factors to be considered are summarised in Table 1. For DCE-CT, the need to keep the radiation burden as low as practicable is a constraint on the total number of images acquired and the X-ray exposure ...

The SARS-CoV-2 virus is primarily transmitted through virus-laden fluid particles ejected from the mouth of infected people. Face covers can mitigate the risk of virus transmission but their outward effectiveness is not fully ascertained. Objective: by using a background oriented schlieren technique, we aim to investigate the air flow ejected by a person while quietly and heavily breathing, while coughing, and with different face covers. Results: we found that all face covers without an outlet valve reduce the front flow through by at least 63% and perhaps as high as 86% if the unfiltered cough jet distance was resolved to the anticipated maximum distance of 2-3 m. However, surgical and handmade masks, and face shields, generate significant leakage jets that may present major hazards. Conclusions: the effectiveness of the masks should mostly be considered based on the generation of secondary jets rather than on the ability to mitigate the front throughflow. INDEX TERMS COVID-19 pandemic, face coverings, face masks, aerosol dispersal, aerosol generating procedures. IMPACT STATEMENT These results show the effectiveness of face coverings in mitigating aerosol dispersion and can aid policy makers to make informed decisions and PPE developers to improve their product effectiveness.

These data support further investigation of T1 -weighted OE-MRI to identify regional tumor hypoxia. The quantification of AUCOE has translational potential as a clinical biomarker of hypoxia.

A Killing tensor is one possible way of generalizing the notion of a Killing vector on a Riemannian or pseudo-Riemannian manifold. It is explained how Killing tensors may be identified with functions that are homogeneous polynomials in the fibers on the associated cotangent bundle. As such, Killing tensors may be identified with first integrals of the Hamiltonian geodesic flow, which are homogeneous polynomials in the momenta. Again using this identification, it is shown that in flat spaces the dimension of the vector space of Killing tensors is maximal and that the Killing tensors are generated by the Killing vectors. Finally, using Riemann’s model for the metric in spaces of constant curvature, a comparison argument is used to show that similar results are valid in that more general context.

The 18-kDa mitochondrial translocator protein (TSPO) is upregulated in high-grade astrocytomas and can be imaged by PET using the selective radiotracer 11 C-(R)PK11195. We investigated 11 C-(R)PK11195 binding in human gliomas and its relationship with TSPO expression in tumor tissue and glioma-associated microglia/macrophages (GAMs) within the tumors. Methods: Twenty-two glioma patients underwent dynamic 11 C-(R)PK11195 PET scans and perfusion MR imaging acquisition. Parametric maps of 11 C-(R)PK11195 binding potential (BP ND ) were generated. Coregistered MR/PET images were used to guide tumor biopsy. The tumor tissue was quantitatively assessed for TSPO expression and infiltration of GAMs using immunohistochemistry and double immunofluorescence. The imaging and histopathologic parameters were compared among different histotypes and grades and correlated with each other. Results: BP ND of 11 C-(R)PK11195 in high-grade gliomas was significantly higher than in low-grade astrocytomas and low-grade oligodendrogliomas. TSPO in gliomas was expressed predominantly by neoplastic cells, and its expression correlated positively with BP ND in the tumors. GAMs only partially contributed to the overall TSPO expression within the tumors, and TSPO expression in GAMs did not correlate with tumor BP ND . Conclusion: PET with 11 C-(R)PK11195 in human gliomas predominantly reflects TSPO expression in tumor cells. It therefore has the potential to effectively stratify patients who are suitable for TSPO-targeted treatment.

The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating monogenetic lysosomal disorders that affect children and young adults with no cure or effective treatment currently available. One of the more severe infantile forms of the disease (INCL or CLN1 disease) is due to mutations in the palmitoyl-protein thioesterase 1 ( PPT1 ) gene and severely reduces the child’s lifespan to approximately 9 years of age. In order to better translate the human condition than is possible in mice, we sought to produce a large animal model employing CRISPR/Cas9 gene editing technology. Three PPT1 homozygote sheep were generated by insertion of a disease-causing PPT1 (R151X) human mutation into the orthologous sheep locus. This resulted in a morphological, anatomical and biochemical disease phenotype that closely resembles the human condition. The homozygous sheep were found to have significantly reduced PPT1 enzyme activity and accumulate autofluorescent storage material, as is observed in CLN1 patients. Clinical signs included pronounced behavioral deficits as well as motor deficits and complete loss of vision, with a reduced lifespan of 17 ± 1 months at a humanely defined terminal endpoint. Magnetic resonance imaging (MRI) confirmed a significant decrease in motor cortical volume as well as increased ventricular volume corresponding with observed brain atrophy and a profound reduction in brain mass of 30% at necropsy, similar to alterations observed in human patients. In summary, we have generated the first CRISPR/Cas9 gene edited NCL model. This novel sheep model of CLN1 disease develops biochemical, gross morphological and in vivo brain alterations confirming the efficacy of the targeted modification and potential relevance to the human condition.

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