There have been a number of recent advances in body ASL. ASL has been applied in the heart, liver, kidney and placenta with studies using ASL in diseases such as diabetes, compensated liver cirrhosis and chronic kidney disease. There are however a number of considerations that are required for use of ASL in the body including which labelling and readout schemes to use and how to deal with respiratory and cardiac motion. Efforts are now needed to harmonise techniques and assess variation in sensitivity, specificity and reproducibility in order to make ASL a clinically useable tool for body applications.
PURPOSE:
Arterial spin labelling (ASL) is an MRI technique that provides a non-contrast enhanced method to assess tissue perfusion using the intrinsic signal from water in the body. ASL is now becoming a well-established technique in the brain, however applications of ASL in the body are currently limited. To date, in the body ASL has been applied in the heart (1, 2), liver (3), kidney (4, 5), pancreas (6) and placenta (7).
Given the importance of tissue hypoxia and ischaemia to many disease processes, measurement of tissue perfusion using a non-invasive, repeatable method is of clinical relevance. Current techniques to assess perfusion include the use of gadolinium based contrast agents, which are contraindicated in kidney disease due to the risk of nephrogenic systemic fibrosis, and limited for dynamic studies. The development of non-invasive ASL to study abdominal organs is thus important.
METHODS AND RESULTS:
There are a number of considerations when applying ASL in the body. First, is the choice of how to label the magnetisation of the inflowing blood, with an option of either pulsed ASL (PASL) or pseudo continuous ASL (pCASL) each having associated pros and cons. There is also the question of which image readout scheme to use (8), with the choice dictating the achievable spatial resolution and number of slices acquired. Finally, there is the decision of how to deal with respiratory motion, with the added complication of cardiac motion for cardiac ASL.
The intrinsically low SNR of ASL leads to large number of signal averages and so a number of repeats required, and motion between these must be minimised. There are many techniques to overcome respiratory motion which include respiratory triggering, breath-holding or use of a navigator echo. Alternatively, motion correction and data sorting techniques can be applied in post-processing to eliminate any motion artefacts. To eliminate cardiac motion, cardiac triggering can be applied using a vectorcardiogram (VCG) or peripheral pulse unit (PPU). Background suppression methods can also be applied to supress any static tissue (9), although this can also decrease the measured perfusion signal.
There have been a number studies that use ASL in clinical studies of kidney and liver disease. Some of these studies combine assessment of organ perfusion with other measures such as T1 relaxation time mapping, diffusion measures and T2* mapping to assess multiparametric changes in disease. Studies have shown a decrease in renal perfusion with diseases such as Acute Kidney Injury (10), diabetes (11) and Chronic Kidney Disease (12). In liver disease, a decrease in liver perfusion as measured with ASL has been demonstrated in patients with compensated cirrhosis (13). There has also been studies looking at the application of ASL of the placenta, including a recent study that applied ASL in the placenta in pregnancies complicated by fetal heart disease (14). Recent work has also looked at cardiac ASL, with applications in dialysis patients (15).
Studies have also applied ASL at 7T to study kidney perfusion (16). 7T provides the advantage of increased SNR and a longer blood and tissue T1, this leads to a reduction in acquisition time as less ASL pairs are required to be averaged, which could minimise motion related artefacts. However, there are significant additional challenges associated with ASL at 7T. The increase of magnetic field strength increases the susceptibility induced inhomogeneity of the B0 field leading to image distortion and signal loss. In addition, the local power deposition, as measured by the specific absorption rate (SAR), is increased at higher field strength.
One major challenge in making body ASL a clinically useable tool is the current lack of large studies to validate or compare the variants in terms of sensitivity, specificity, reproducibility and change with disease. Although MRI vendors are now providing ASL sequences for use in the brain, sequences available for body ASL are limited.
CONCLUSION:
There have been a number of recent advances in body ASL, with studies using ASL in clinical applications. However, to make ASL a clinically useable tool for body applications there now needs to be efforts to harmonise techniques and assess variation in sensitivity, specificity and reproducibility.1. Zun Z, Wong EC, Nayak KS. Assessment of myocardial blood flow (MBF) in humans using arterial spin labeling (ASL): feasibility and noise analysis. Magn Reson Med 2009;62:975–983. doi: 10.1002/mrm.22088.
2. Wang DJJ, Bi X, Avants BB, Meng T, Zuehlsdorff S, Detre JA. Estimation of perfusion and arterial transit time in myocardium using free-breathing myocardial arterial spin labeling with navigator-echo. Magn. Reson. Med. 2010;64:1289–1295. doi: 10.1002/mrm.22630.
3. C. Hoad , C. Costigan , L. Marciani , P. Kaye , R. Spiller , P. Gowland , G. Aithal , and S. Francis. Quantifying Blood Flow and Perfusion in Liver Tissue using Phase Contrast Angiography and Arterial Spin Labelling. 3.Proc. Intl. Soc. Mag. Reson. Med. 19 (2011)
4. Cox EF, Buchanan CE,Bradley CR, Prestwich B, Mahmoud H, Taal M, Selby NM, Francis ST Multiparametric Renal Magnetic Resonance Imaging: Validation, Interventions, and Alterations in Chronic Kidney Disease. Front Physiol. 2017;8:696.
5. Rossi C, Artunc F et al. Histogram analysis of renal arterial spin labeling perfusion data reveals differences between volunteers and patients with mild chronic kidney disease. Invest Radiol, 2012; 47(8); 490-6.
6. Schawkat K, Ith M, Christie A, Kuhn W, Chittazhathu Y, Bains L, Runge VM, Heverhagen JT. Dynamic non-invasive ASL perfusion imaging of a normal pancreas with secretin augmented MR imaging. Eur Radoil, 2018:10.1007
7. Zun Z, Zaharchuk G, Andescavage NN, Donofrio MT, Limperopoulos C. Non-Invasive Placental Perfusion Imaging in Pregnancies Complicated by Fetal Heart Disease Using Velocity-Selective Arterial Spin Labeled MRI. Sci Rep, 2017 23;7(1):16126..
8. Charlotte E Buchanan, Eleanor F Cox, and Susan T Francis. Evaluation of Readout Schemes for Arterial Spin Labelling in the Human Kidney. Proc. Intl. Soc. Mag. Reson. Med. 23 (2015).
9. Gardener AG1, Francis ST. Multislice perfusion of the kidneys using parallel imaging: image acquisition and analysis strategies. Magn Reson Med. 2010 Jun;63(6):1627-36
10. Hueper K, Gutberlet M, Rong S, et al. Acute Kidney Injury: Arterial Spin Labeling to Monitor Renal Perfusion Impairment in Mice—Comparison with Histopathologic Results and Renal Function. Radiology, 2013;270:117-124
11. Mora-Gutierrez, Garcia-Fernandex N, Sion Robler MF, Maramo JA, Escalada FJ, Wang DJ, Benito A, Fernandez Seara MA. Arterial Spin labelling MRI is able to detect early hemodynamic changes in diabetic nephropathy. J Magn Reson Imaging. 2017 10.1002.
12. Charlotte Buchanan, Huda Mahmoud, Eleanor Cox, Benjamin Prestwich, Nicholas Selby, Maarten Taal, Susan Francis. Reproducibilty of Multiparametric Assessment of Chronic Kidney Disease. Proc. Intl. Soc. Mag. Reson. Med. 25 (2017).
13. N, Cox E, Bradley C, Scott R, Austin A, O'Neill R, Ramjas G, Travis S, White H, Singh R, Thurley P, Guha IN, Francis S, Aithal GP. J Non-invasive assessment of portal hypertension using quantitative magnetic resonance imagingPalaniyappan Hepatol. 2016 Dec;65(6):1131-1139. doi: 10.1016/j.jhep.2016.07.021. Epub 2016 Jul 27.
14. Zun Z, Zaharchuk G, Andescavage NN, Donofrio MT, Limperopoulos C.on-Invasive Placental Perfusion Imaging in Pregnancies Complicated by Fetal Heart Disease Using Velocity-Selective Arterial Spin Labeled MRI.. Sci Rep. 2017 Nov 23;7(1):16126.
15. Buchanan C, Mohammed A, Cox E, Köhler K, Canaud B, Taal MW, Selby NM, Francis S, McIntyre CW. Intradialytic Cardiac Magnetic Resonance Imaging to Assess Cardiovascular Responses in a Short-Term Trial of Hemodiafiltration and Hemodialysis. J Am Soc Nephrol. 2017 Apr;28(4):1269-1277.
16. Li X, Auerbach EJ, Van de Moortele PF, Ugurbil K, Metzger GJ Quantitative single breath-hold renal arterial spin labeling imaging at 7T. Magn Reson Med, 2018; 79(2): 815-825.