To harmonise and compare all existing ASL acquisition methods and to shortlist and further develop a number of techniques based on the following quantitative parameters: 1. Signal-to-noise (SNR), measurement of precision and error; using large scale multicentre test-retest trials, and favouring high SNR; 2. Reproducibility and reliability; by benchmarking sequences against each other according to robustness and ease of use; 3. Measurement time and patient-friendliness; linked to the previous parameters, by optimising sequences minimising acoustic noise and maximising SNR.
All ASL techniques were reviewed, and a consensus paper was published:
Alsop DC, Detre JA, Golay X, Günther M, Hendrikse J, Hernandez-Garcia L, Lu H, MacIntosh BJ, Parkes LM, Smits M, van Osch MJ, Wang DJ, Wong EC, Zaharchuk G. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. 2015;73(1):102-106
This paper, endorsed by over 200 people, or the larger part of the world community, has led to a change in the field and an alignment of all vendors according to our recommendations. The paper has already been cited over 100 times in less than one year (Google Scholar).
To develop automatic image processing software to offer the best possible precision and reproducibility when comparing quantitative perfusion parameters. The pieces of analysis software developed within the consortium will be made freely available on the Action website, and will be developed under an Open Source BSD license, allowing everyone to use it freely for research, with the proper pathways in place to “freeze” parts of the software and make it usable by companies, thereby further translating the technology beyond the members of the Action into the general clinical community.
The most widely-used image processing pipeline for ASL has been established by Dr Michael Chappell from Oxford, and is called BASIL: http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/BASIL.
In addition, results from a STSM was published in Magnetic Resonance Imaging:
Abad VM, García-Polo P, O’Daly O, Hernández-Tamames JA, Zelaya F. ASAP (Automatic Software for ASL Processing): A toolbox for processing Arterial Spin Labeling images. Magnetic Resonance Imaging (2015) DOI: 10.1016/j.mri.2015.11.002.
To establish clinical trials to compare results obtained from ASL to FDG-PET across several European countries. Once the proper imaging methods and processing software are ready, landmark studies will be performed to compare the information obtained by ASL to that of FDG-PET or even O15-PET, which can be considered as the current gold standard.
While several publications have compared different ASL methods across different diseases, all referring the COST Action BM1103 (see next points), a few groups within the Action have undertaken studies to validate ASL against PET:
- Van Golen LW, et al (2014). Quantification of Cerebral Blood Flow in Healthy Volunteers and Type 1 Diabetic Patients: Comparison of MRI Arterial Spin Labeling and [O-15]H2O Positron Emission Tomography (PET). JMRI. 40(6):1300-9
- Verfaillie SCJ, et al. (2015). Cerebral perfusion and glucose metabolism in Alzheimer’s disease and frontotemporal dementia: two sides of the same coin? European Radiology. 25(10):3050-9
- Heijtel DF, et al. Accuracy and precision of pseudo-continuous arterial spin labeling perfusion during baseline and hypercapnia: a head-to-head comparison with 15O H2O positron emission tomography. NeuroImage. 2014. 92: 182-192.
- Schmid S, et al. Comparison of velocity- and acceleration-selective arterial spin labeling with 15O-H2O positron emission tomography. Journal of Cerebral Blood Flow & Metabolism. 2015. 35(8): 1296-1303.
- Teune LK, et al. Parkinson’s disease-related perfusion and glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET imaging. Neuroimage Clin. 2014 Jul 3;5:240-4
- Andersen JB, et al. Positron emission tomography/magnetic resonance hybrid scanner imaging of cerebral blood flow using (15)O-water positron emission tomography and arterial spin labeling magnetic resonance imaging in newborn piglets. J Cereb Blood Flow Metab 2015;35:1703–10.
To validate the technology as a biomarker of disease onset and progression, and a possible trial outcome measure. Once standard cross-sectional clinical trials have been performed, it will be important to reassess the same patients, thereby providing longitudinal data over the progression of the disease, and develop standard atlases of disease progression compared to normal ageing.
The technology was first evaluated and numerous studies, all acknowledging the Action, were published:
- Mutsaerts HJ, van Osch MJ, Zelaya FO, Wang DJ, Nordhøy W, Wang Y, Wastling S, Fernandez-Seara MA, Petersen ET, Pizzini FB, Fallatah S, Hendrikse J, Geier O, Günther M, Golay X, Nederveen AJ, Bjørnerud A, Groote IR. Multi-vendor reliability of arterial spin labeling perfusion MRI using a near-identical sequence: implications for multi-center studies. Neuroimage. 2015 Jun;113:143-52.
- Steketee RME, Mutsaerts HJMM, Bron EE, Van Osch MJP, Majoie CBLM, Van der Lugt A, Nederveen AJ, Smits M. Quantitative functional arterial spin labeling (fASL) MRI – sensitivity and reproducibility of regional CBF changes using pseudo-continuous ASL product sequences. PlosOne. 2015. 10(7)
- Mutsaerts HJMM, Steketee RME, Heijtel DFR, Kuijer JPA, Van Osch MJP, Majoie CBLM, Smits M, Nederveen AJ. Reproducibility of pharmacological ASL using sequences from different vendors: implications for multi-center drug studies. Magnetic Resonance Materials in Physics, Biology and Medicine. 2015. 28(5): 427-436.
- Mutsaerts HJMM, Steketee RME, Heijtel DFR, Kuijer JPA, Van Osch MJP, Majoie CBLM, Smits M, Nederveen AJ. Inter-vendor reproducibility of arterial spin labeling at 3 Tesla. PlosOne. 2014. 9(8)
- Lövblad KO, Montandon ML, Viallon M, Rodriguez C, Toma S, Golay X, Giannakopoulos P, Haller S. Arterial Spin-Labeling Parameters Influence Signal Variability and Estimated Regional Relative Cerebral Blood Flow in Normal Aging and Mild Cognitive Impairment: FAIR versus PICORE Techniques. AJNR Am J Neuroradiol. 2015 Jul;36(7):1231-6. doi: 10.3174/ajnr.A4291.
- Clement P, Mutsaerts HJ, Václavů L, Ghariq E, Pizzini FB, Smits M, Acou M, Jovicich J, Vanninen R, Kononen M, Wiest R, Rostrup E, Bastos-Leite AJ, Larsson EM, Achten E. Understanding physiological brain perfusion variability in healthy subjects. J Cereb Blood Flow Metab Submitted (2015)
In addition, the technology was then used specifically as a diagnostic tool in dementia:
- Bron EE, Steketee RM, Houston GC, Oliver RA, Achterberg HC, Loog M, van Swieten JC, Hammers A, Niessen WJ, Smits M, Klein S; Alzheimer’s Disease Neuroimaging Initiative. Diagnostic classification of arterial spin labeling and structural MRI in presenile early stage dementia. Hum Brain Mapp. 2014 Sep;35(9):4916-31
- Fällmar D, Lilja J, Velickaite V, Danfors T, Lubberink M, Ahlgren A, van Osch MJ, Kilander L, Larsson EM. Visual Assessment of Brain Perfusion MRI Scans in Dementia: A Pilot Study. J Neuroimaging. 2015 Sep 16. doi: 10.1111/jon.12296.
- Sigurdsson S, Forsberg L, Aspelund T, van der Geest RJ, van Buchem MA, Launer LJ, Gudnason V, van Osch MJ. Feasibility of Using Pseudo-Continuous Arterial Spin Labeling Perfusion in a Geriatric Population at 1.5 Tesla. PLoS One. 2015 Dec 14;10(12):e0144743. doi: 10.1371/journal.pone.0144743.Creation of populations atlases and tools are on the way, and should be published within the next year.
To establish a pan-European ASL network, which will be the reference site for all aspects related to ASL in research and clinical routine. The ASL network will develop standard procedures and white papers for using ASL in various applications and will provide teaching and training for junior researchers. Furthermore, scientific meetings will boost the creation and distribution of new knowledge on methodological and clinical issues.
The articles above should clearly demonstrate it. In addition, this Action supported all members of the existing ASL Network (http://asl-network.org/), which provides a monthly newsletter on all topics on ASL to over 200 people around the world.