Quantitative blood flow measurement in rat brain with multiphase arterial spin labelling magnetic resonance imaging

Abstract

Cerebral blood flow is an important parameter in many diseases and functional studies that can be accurately measured in humans using arterial spin labelling (ASL) MRI. However, although rat models are frequently used for preclinical studies of both human disease and brain function, rat CBF measurements show poor consistency between studies. This lack of reproducibility is due, partly, to the smaller size and differing head geometry of rats compared to humans, as well as the differing analysis methodologies employed and higher field strengths used for preclinical MRI. To address these issues, we have implemented, optimised and validated a multiphase pseudo-continuous ASL technique, which overcomes many of the limitations of rat CBF measurement. Three rat strains (Wistar, Sprague Dawley and Berlin Druckrey IX) were used, and CBF values validated against gold-standard autoradiography measurements. Label positioning was found to be optimal at 45°, while post-label delay was optimised to 0.55 s. Whole brain CBF measures were 109 ± 22, 111 ± 18 and 100 ± 15 mL/100 g/min by multiphase pCASL, and 108 ± 12, 116 ± 14 and 122 ± 16 mL/100 g/min by autoradiography in Wistar, SD and BDIX cohorts, respectively. Tumour model analysis shows that the developed methods also apply in disease states. Thus, optimised multiphase pCASL provides robust, reproducible and non-invasive measurement of CBF in rats.

Non-invasive measurement of choroid plexus apparent blood flow with arterial spin labeling

“…The choroid plexus blood flow of this work should be interpreted as apparent perfusion because of the partial volume effect in ASL images. Recent work showed consistent results between ASL and radiograph on rat brains [ 49 ], and our approach in this work was consistent with previous human studies [ 33 , 35 ]. Therefore, equivalent detectability was expected in this ASL study.…”

“…This problem can be caused by the underestimated arterial transit time. The latest developments of pCASL have shown the ability to detect the blood flow as low as 15 ml/100 g/min [ 53 ] and consistent quantification as in quantitative radiography [ 49 ]. The ASL used in this study had similar features as the above two latest developments.…”

13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI

“…A control contralateral injection of an equivalent volume of sterile PBS was also performed. The ENU-1564 cell line was chosen as a rat model of brain metastasis from a mammary carcinoma 109 – 112 .…”

Animal Functional Magnetic Resonance Imaging: Trends and Path Toward Standardization

“…A practical advantage of pASL is that short inversion pulses are more easily implemented in ASL protocols. To combine the higher labeling efficiency of pASL and higher sensitivity of cASL, pseudo-continuous ASL (pCASL) was developed Wu et al, 2007;Dai et al, 2008;Borogovac and Asllani, 2012), and further optimized with multi-phase image acquisitions to tackle rodent-related difficulties with variations in labeling efficiency across different vessels to prevent erroneous calculation of CBF (Larkin et al, 2018). Since EPI is the main read-out for ASL, the presence of a BOLD effect should be taken into account in ASL-based fMRI studies (Lu et al, 2006).…”