Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS): study protocol for a randomised controlled trial

Pauls, Mathilde; Clarke, Natasha; Trippier, Sarah; Betteridge, Shai; Howe, Franklyn A.; Kruuse, Christina; Madigan, Jeremy; Moynihan, Barry; Pereira, Anthony; Rolfe, Debbie; Rostrup, Egill; Haig, Caroline; Barrick, Thomas R.; Isaacs, Jeremy D.; Hainsworth, Atticus H.

doi:10.1186/s13063-017-1973-9

Cited by 19 publications

(29 citation statements)

References 22 publications

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“…ASL has also been used to identify the networks affected by Gamma hydroxybutarate (GHB) in a double-blind, randomized cross-over design trial (Bosch et al, 2017). As another example, a randomised, double-blind, crossover phase II study is underway to examine the use of Tadalafil as a treatment for small vessel disease (SVD) and vascular cognitive impairment (VCI) (Pauls et al, 2017).…”

Section: Resting State Functional Connectivitymentioning

confidence: 99%

Recent progress in ASL

2019

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This article aims to provide the reader with an overview of recent developments in Arterial Spin Labeling (ASL) MRI techniques. A great deal of progress has been made in recent years in terms of the SNR and acquisition speed. New strategies have been introduced to improve labeling efficiency, reduce artefacts, and estimate other relevant physiological parameters besides perfusion. As a result, ASL techniques has become a reliable workhorse for researchers as well as clinicians. After a brief overview of the technique's fundamentals, this article will review new trends and variants in ASL including vascular territory mapping and velocity selective ASL, as well as arterial blood volume imaging techniques. This article will also review recent processing techniques to reduce partial volume effects and physiological noise. Next the article will examine how ASL techniques can be leveraged to calculate additional physiological parameters beyond perfusion and finally, it will review a few recent applications of ASL in the literature.

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Section: Resting State Functional Connectivitymentioning

confidence: 99%

Recent progress in ASL

2019

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“…even calibrated BOLD [2][3][4] and many longitudinal FMRI studies have used ASL acquisitions (for examples, see refs [5][6][7][8] ).…”

Section: Magnetic Resonance In Medicinementioning

confidence: 99%

Improved sensitivity and temporal resolution in perfusion FMRI using velocity selective inversion ASL

Hernandez‐García

Nielsen

Noll

2018

Magnetic Resonance in Med

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“…Our results generate hypotheses for future larger studies. A parallel clinical trial was conducted in a similar population group as our study, which applied a single dose of tadalafil and used arterial spin labelling MRI (clinical trial number: NCT02450253) ( Pauls et al , 2017 ). This study aimed to detect regional CBF changes in deep brain areas, but results are not yet published.…”

Section: Discussionmentioning

confidence: 99%

Tadalafil may improve cerebral perfusion in small-vessel occlusion stroke—a pilot study

Ölmestig

Marlet

Hansen

et al. 2020

Brain Communications

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New treatments for cerebral small-vessel disease are needed to reduce the risk of small-vessel occlusion stroke and vascular cognitive impairment. We investigated an approach targeted to the signalling molecule cyclic guanosine monophosphate, using the phosphodiesterase 5 inhibitor tadalafil, to explore if it improves cerebral blood flow and endothelial function in patients with cerebral small-vessel disease and stroke. In a randomized, double-blinded, placebo-controlled, cross-over pilot trial (NCT02801032), we included patients who had a previous (>6 months) small-vessel occlusion stroke. They received a single dose of either 20 mg tadalafil or placebo on 2 separate days at least 1 week apart. We measured the following: baseline MRI for lesion load, repeated measurements of blood flow velocity in the middle cerebral artery by transcranial Doppler, blood oxygen saturation in the cortical microvasculature by near-infrared spectroscopy, peripheral endothelial response by EndoPAT and endothelial-specific blood biomarkers. Twenty patients with cerebral small-vessel disease stroke (3 women, 17 men), mean age 67.1 ± 9.6, were included. The baseline mean values ± standard deviations were as follows: blood flow velocity in the middle cerebral artery, 57.4 ± 10.8 cm/s; blood oxygen saturation in the cortical microvasculature, 67.0 ± 8.2%; systolic blood pressure, 145.8 ± 19.5 mmHg; and diastolic blood pressure, 81.3 ± 9.1 mmHg. We found that tadalafil significantly increased blood oxygen saturation in the cortical microvasculature at 180 min post-administration with a mean difference of 1.57 ± 3.02%. However, we saw no significant differences in transcranial Doppler measurements over time. Tadalafil had no effects on peripheral endothelial function assessed by EndoPAT and endothelial biomarker results conflicted. Our findings suggest that tadalafil may improve vascular parameters in patients with cerebral small-vessel disease stroke, although the effect size was small. Increased oxygenation of cerebral microvasculature during tadalafil treatment indicated improved perfusion in the cerebral microvasculature, theoretically presenting an attractive new therapeutic target in cerebral small-vessel disease. Future studies of the effect of long-term tadalafil treatment on cerebrovascular reactivity and endothelial function are needed to evaluate general microvascular changes and effects in cerebral small-vessel disease and stroke.

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Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS): study protocol for a randomised controlled trial

Cited by 19 publications

References 22 publications

Recent progress in ASL

Recent progress in ASL

Improved sensitivity and temporal resolution in perfusion FMRI using velocity selective inversion ASL

Tadalafil may improve cerebral perfusion in small-vessel occlusion stroke—a pilot study

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