Arterial spin labelling

Short description: Magnetic resonance imaging technique

Arterial spin labeling (ASL), also known as arterial spin tagging, is a magnetic resonance imaging technique used to quantify cerebral blood perfusion by labelling blood water as it flows throughout the brain. ASL specifically refers to magnetic labeling of arterial blood below or in the imaging slab, without the need of gadolinium contrast.[1] A number of ASL schemes are possible, the simplest being flow alternating inversion recovery (FAIR) which requires two acquisitions of identical parameters with the exception of the out-of-slice saturation; the difference in the two images is theoretically only from inflowing spins, and may be considered a 'perfusion map'.[2] The ASL technique was developed by John S. Leigh Jr, John A. Detre, Donald S. Williams, and Alan P. Koretsky in 1992.[3][4][5][6]

## Contents

* 1 Physics
* 1.1 Continuous arterial spin labelling
* 1.2 Pulsed arterial spin labelling
* 1.3 Velocity selective arterial spin labelling
* 1.4 Diffusion prepared pseudocontinuous arterial spin labelling (DP-pCASL)
* 2 Analysis of ASL images
* 3 Comparison with fMRI
* 4 Clinical use
* 5 Safety
* 6 References
* 7 External links

## Physics

Arterial spin labeling utilizes the water molecules circulating with the brain, and using a radiofrequency pulse, tracks the blood water as it circulates throughout the brain. After a period of time in microseconds (enough to allow the blood to circulate through the brain), a 'label' image is captured. A 'control' image is also acquired before the labeling of the blood water. A subtraction technique gives a measurement of perfusion. In order to increase SNR, collections of control and label images can be averaged. There are also other specifications in the MRI that can increase SNR, like the amount of head coils of the MRI, or a stronger field strength (3 T is standard, but 1.5 T is satisfactory). In order to properly scale the perfusion values into cerebral blood flow units (CBF, ml/100g/1 min), a separate proton density map with the same parameters (but longer TR to fully relax the blood spins) is recommended to be acquired as well. Alternatively, the average control image can be used to generate CBF, which is the case for Phillips pCASL readouts. Usually background suppression is also applied to increase the SNR. Due to the different variations of each implementations, it is recommended that a large multi-scanner study should design a protocol minimizing the variety of readout methods used by each scanner.

One study has shown that although there are voxel differences when different readout methods are used, average gray matter CBF are still comparable. Differences in SNR are apparent when each voxel compared, but collectively are negligible.[7]Template:Importance example

### Continuous arterial spin labelling

In continuous arterial spin labeling (CASL), the blood water is inverted as it flows through the brain in one plane. CASL is characterized by one single long pulse (around 1–3) seconds. This may be disadvantageous for certain scanners that are not designed to maintain a radiofrequency pulse that long, and therefore would require adjustments to a RF amplifier. This is rectified in pseudo-continuous arterial spin labeling (pCASL), where a single long pulse is replaced with multiple (up to a thousand) millisecond pulses. This leads to a higher labelling efficiency. pCASL is the preferred implementation of ASL.[8] There are different readout modules for pCASL, depending on the scanner used, with 2D pCASL usually being implemented for all scanners and 3D pCASL stack of spirals implemented in GE scanners.

### Pulsed arterial spin labelling

In pulse arterial spin labeling (PASL), blood water is inverted as it passes through a labeling slab (of 15 to 20 cm) instead of a plane. There are different variations of this implementations, including EPISTAR and PICORE and PULSAR. Most scanners have been designed to have PASL work out-of-the-box for research use.

### Velocity selective arterial spin labelling

Velocity selective arterial spin labeling is a strategy that still requires validation. Velocity selective arterial spin labeling is advantageous in a population where blood flow may be impeded (e.g. stroke), because the labeling occurs closer to the capillaries. This allows the post labeling decay to be shorter.[9]

### Diffusion prepared pseudocontinuous arterial spin labelling (DP-pCASL)

Diffusion-prepared pseudocontinuous ASL (DP-pCASL) is a more recent ASL variant sequence that magnetically labels water molecules and measures their movement across the blood-brain barrier complex, which allows for the calculation of the water exchange rate (kw).[10][11] kw is used as a surrogate for BBB function and permeability. Water exchange across the BBB is mediated by a number of processes, including passive diffusion, active co-transport through the endothelial membrane, and predominantly by facilitated diffusion through the dedicated water channel aquaporin-4 (AQP4). Several studies have investigated the use of DP-pCASL in cerebrovascular diseases, including acute ischemic stroke,[12] CADASIL,[13] hereditary cerebral small vessel disease [14] as well as in animal models.[15]

## Analysis of ASL images

ASL maps can mainly be analyzed using the same tools to analyze fMRI and VBM. Many ASL-specific toolboxes have been developed to assist in ASL analysis, such as BASIL (Bayesian inference for arterial spin labelling MRI), part of the FSL neuroimaging package and also Ze Wang's ASL toolbox (using MATLAB) to assist in the subtraction and averaging of the tagged/control pairs.[16] A visual quality check is often needed to make sure that the perfusion map is valid (such as correct registration, or correct segmentation of non-cerebral materials such as the dura mater). A whole brain/voxel-wise approach can be analyzed by registering the ASL map into MNI space for group comparisons. A region of interest approach can be analyzed by registering the ASL map into a selected cluster, or an atlas, like a standard (such as the Harvard-Oxford Cortical atlas) or an individual atlas developed by software like FreeSurfer. The recommended procedure of ASL registration for voxel-wise analysis is to register the perfusion map to a gray matter segmentation of each individual in a non-rigid procedure. Gray matter often requires more oxygenation and is the source of more brain activity compared to white matter. Therefore, gray matter CBF is often higher than white matter CBF. The single value of gray matter CBF is often isolated in order to give a broad overview of CBF differences. Gray matter and white matter CBF can be localized using atlases or Freesurfer.

ASL functional connectivity can be designed with parameters conducive to a long scan time. Studies have suggested that ASL complement resting state fMRI findings well but can differentiate between resting brain networks (such as the default mode network) less.[17]

## Comparison with fMRI

Functional MRI (fMRI) has been the modality of choice to visualize brain activity, and takes advantages of a range of techniques that can be used to interpret it. However, the signal that fMRI is acquiring is BOLD signal, which does not directly correlate with blood flow. Cerebral blood flow on the other hand does, allowing for cardiovascular disease (CVD) and inflammatory risk factor analysis, and disorders (such as schizophrenia and bipolar disorder) that have comorbid effects with CVD.[18] ASL imaging can be a useful tool to complement fMRI and vice versa.

## Clinical use

In cerebral infarction, the penumbra has decreased perfusion.[19] Besides acute and chronic neurovascular diseases, the value of ASL has been demonstrated in brain tumors, epilepsy and neurodegenerative disease, such as Alzheimer's disease, frontotemporal dementia and Parkinson disease.[20] Additionally, DP-pCASL has promising potential for assessing blood-brain barrier integrity in patients with ischemic stroke.[21]

Although the primary form of fMRI uses the blood-oxygen-level dependent (BOLD) contrast,[22] ASL is another method of obtaining contrast.[23]

There have been research to apply ASL to renal imaging,[24] pancreas imaging,[25] and placenta imaging. A challenge to this sort of non-cerebral perfusion is motion due to breathing. Additionally, there is a lot less development on the segmentation of theses specific organs, so the studies are relatively small scale.

## Safety

ASL is in general a safe technique, although injuries may occur as a result of failed safety procedures or human error like other MRI techniques.[26]

ASL, like other MRI modalities generate a fair amount of acoustic noise during the scan, so earplugs are advised.

## References

1. ↑ Fortin, Francis; Gaillard, Frank. "Arterial spin labelling (ASL) MR perfusion". https://radiopaedia.org/articles/arterial-spin-labelling-asl-mr-perfusion-1.
2. ↑ "Arterial spin labeling". http://fmri.research.umich.edu/research/main_topics/asl.php.
3. ↑ Williams, D. S.; Detre, J. A.; Leigh, J. S.; Koretsky, A. P. (1992-01-01). "Magnetic resonance imaging of perfusion using spin inversion of arterial water." (in en). Proceedings of the National Academy of Sciences 89 (1): 212–216. doi:10.1073/pnas.89.1.212. ISSN 0027-8424. PMID 1729691. Bibcode: 1992PNAS...89..212W.
4. ↑ Detre, John A.; Leigh, John S.; Williams, Donald S.; Koretsky, Alan P. (January 1992). "Perfusion imaging". Magnetic Resonance in Medicine 23 (1): 37–45. doi:10.1002/mrm.1910230106. ISSN 0740-3194. PMID 1734182.
5. ↑ Leigh, J.S., Detre, J.A., Williams, D.S., Koretsky, A.P. "Methods for measuring perfusion using magnetic resonance imaging" US Patent No. 5,402,785 (1995).
6. ↑ "Early development of arterial spin labeling to measure regional brain blood flow by MRI". NeuroImage 62 (2): 602–7. August 2012. doi:10.1016/j.neuroimage.2012.01.005. PMID 22245338.
7. ↑ Nederveen, Aart J.; Smits, Marion; Majoie, Charles B. L. M.; Osch, Matthias J. P. van; Kuijer, Joost P. A.; Heijtel, Dennis F. R.; Steketee, Rebecca M. E.; Mutsaerts, Henri J. M. M. (2014-08-04). "Inter-Vendor Reproducibility of Pseudo-Continuous Arterial Spin Labeling at 3 Tesla". PLOS ONE 9 (8). doi:10.1371/journal.pone.0104108. ISSN 1932-6203. PMID 25090654. Bibcode: 2014PLoSO...9j4108M.
8. ↑ Alsop, David C.; Detre, John A.; Golay, Xavier; Günther, Matthias; Hendrikse, Jeroen; Hernandez-Garcia, Luis; Lu, Hanzhang; MacIntosh, Bradley J. et al. (January 2015). "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". Magnetic Resonance in Medicine 73 (1): 102–116. doi:10.1002/mrm.25197. ISSN 1522-2594. PMID 24715426.
9. ↑ Schmid, Sophie; Heijtel, Dennis F. R.; Mutsaerts, Henri J. M. M.; Boellaard, Ronald; Lammertsma, Adriaan A.; Nederveen, Aart J.; van Osch, Matthias J. P. (August 2015). "Comparison of velocity- and acceleration-selective arterial spin labeling with [15OH2O positron emission tomography"]. Journal of Cerebral Blood Flow & Metabolism 35 (8): 1296–1303. doi:10.1038/jcbfm.2015.42. ISSN 1559-7016. PMID 25785831.
10. ↑ Shao, Xingfeng; Jann, Kay; Ma, Samantha J.; Yan, Lirong; Montagne, Axel; Ringman, John M.; Zlokovic, Berislav V.; Wang, Danny J. J. (30 November 2020). "Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort". Frontiers in Neuroscience 14. doi:10.3389/fnins.2020.571480. PMID 33328848.
11. ↑ Shao, Xingfeng; Ma, Samantha J.; Casey, Marlene; D'Orazio, Lina; Ringman, John M.; Wang, Danny J.J. (May 2019). "Mapping water exchange across the blood–brain barrier using 3D diffusion-prepared arterial spin labeled perfusion MRI". Magnetic Resonance in Medicine 81 (5): 3065–3079. doi:10.1002/mrm.27632. PMID 30561821.
12. ↑ Mouchtouris, Nikolaos; Ailes, Isaiah; Gooch, Reid; Raimondo, Christian; Oghli, Yazan Shamli; Tjoumakaris, Stavropoula; Jabbour, Pascal; Rosenwasser, Robert et al. (June 2024). "Quantifying blood-brain barrier permeability in patients with ischemic stroke using non-contrast MRI". Magnetic Resonance Imaging 109: 165–172. doi:10.1016/j.mri.2024.03.027. PMID 38513785.
13. ↑ Ling, Chen; Zhang, Jinyuan; Shao, Xingfeng; Bai, Li; Li, Zhixin; Sun, Yunchuang; Li, Fan; Wang, Zhaoxia et al. (26 April 2023). "Diffusion prepared pseudo-continuous arterial spin labeling reveals blood–brain barrier dysfunction in patients with CADASIL". European Radiology 33 (10): 6959–6969. doi:10.1007/s00330-023-09652-7. PMID 37099178.
14. ↑ Li, Yingying; Ying, Yunqing; Yao, Tingyan; Jia, Xuejia; Liang, Huilou; Tang, Weijun; Jia, Xiuqin; Song, Haiqing et al. (3 July 2023). "Decreased water exchange rate across blood–brain barrier in hereditary cerebral small vessel disease". Brain 146 (7): 3079–3087. doi:10.1093/brain/awac500. PMID 36625892.
15. ↑ Tiwari, YV; Lu, J; Shen, Q; Cerqueira, B; Duong, TQ (August 2017). "Magnetic resonance imaging of blood-brain barrier permeability in ischemic stroke using diffusion-weighted arterial spin labeling in rats.". Journal of Cerebral Blood Flow and Metabolism 37 (8): 2706–2715. doi:10.1177/0271678X16673385. PMID 27742887.
16. ↑ Wang, Ze; Aguirre, Geoffrey K.; Rao, Hengyi; Wang, Jiongjiong; Fernández-Seara, María A.; Childress, Anna R.; Detre, John A. (February 2008). "Empirical optimization of ASL data analysis using an ASL data processing toolbox: ASLtbx". Magnetic Resonance Imaging 26 (2): 261–269. doi:10.1016/j.mri.2007.07.003. ISSN 0730-725X. PMID 17826940.
17. ↑ Chen, J. Jean; Jann, Kay; Wang, Danny J.J. (2015-11-01). "Characterizing Resting-State Brain Function Using Arterial Spin Labeling". Brain Connectivity 5 (9): 527–542. doi:10.1089/brain.2015.0344. ISSN 2158-0014. PMID 26106930.
18. ↑ Jann, Kay; Orosz, Ariane; Dierks, Thomas; Wang, Danny J. J.; Wiest, Roland; Federspiel, Andrea (2013-10-01). "Quantification of Network Perfusion in ASL Cerebral Blood Flow Data with Seed Based and ICA Approaches". Brain Topography 26 (4): 569–580. doi:10.1007/s10548-013-0280-3. ISSN 1573-6792. PMID 23508714. https://boris.unibe.ch/14355/1/10548_2013_Article_280.pdf.
19. ↑ "Magnetic resonance diffusion-perfusion mismatch in acute ischemic stroke: An update". World Journal of Radiology 4 (3): 63–74. March 2012. doi:10.4329/wjr.v4.i3.63. PMID 22468186.
20. ↑ "A neuroradiologist's guide to arterial spin labeling MRI in clinical practice". Neuroradiology 57 (12): 1181–202. December 2015. doi:10.1007/s00234-015-1571-z. PMID 26351201.
21. ↑ Mouchtouris, N; Ailes, I; Gooch, R; Raimondo, C; Oghli, YS; Tjoumakaris, S; Jabbour, P; Rosenwasser, R et al. (19 March 2024). "Quantifying blood-brain barrier permeability in patients with ischemic stroke using non-contrast MRI.". Magnetic Resonance Imaging 109: 165–172. doi:10.1016/j.mri.2024.03.027. PMID 38513785.
22. ↑ Functional Magnetic Resonance Imaging (2nd ed.). Sunderland, Massachusetts: Sinauer Associates. 2009. p. 26. ISBN 978-0-87893-286-3.
23. ↑ "Applications of arterial spin labeled MRI in the brain". Journal of Magnetic Resonance Imaging 35 (5): 1026–37. May 2012. doi:10.1002/jmri.23581. PMID 22246782.
24. ↑ Roberts, D A; Detre, J A; Bolinger, L; Insko, E K; Lenkinski, R E; Pentecost, M J; Leigh, J S (1995-07-01). "Renal perfusion in humans: MR imaging with spin tagging of arterial water.". Radiology 196 (1): 281–286. doi:10.1148/radiology.196.1.7784582. ISSN 0033-8419. PMID 7784582.
25. ↑ Taso, Manuel; Guidon, Arnaud; Zhao, Li; Mortele, Koenraad J.; Alsop, David C. (2019). "Pancreatic perfusion and arterial-transit-time quantification using pseudocontinuous arterial spin labeling at 3T". Magnetic Resonance in Medicine 81 (1): 542–550. doi:10.1002/mrm.27435. ISSN 1522-2594. PMID 30229559. http://nrs.harvard.edu/urn-3:HUL.InstRepos:38035040.
26. ↑ Watson, Robert E. (2015-10-01). "Lessons Learned from MRI Safety Events". Current Radiology Reports 3 (10): 37. doi:10.1007/s40134-015-0122-z. ISSN 2167-4825.

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