Multiple physiological parameters other than CBF can be derived from ASL signal when the magnetically labeled blood passes through arterial trees and freely diffuses across the blood-brain barrier in capillaries, such as dynamic MR angiography, arterial cerebral blood volume (aCBV), vascular compliance (VC), and water permeability. This lecture will cover these recently developed advanced ASL techniques.
Non-contrast enhanced MR angiography
Detailed characterization of dynamic flow patterns plays an important role in the diagnosis and treatment of various cerebrovascular disorders, e.g. arteriovenous malformation, steno-occlusion, and aneurysm. Currently, diagnosis mainly relies on digital subtraction angiography and/or CT angiography, both of which are invasive with ionizing radiation. Different from ASL perfusion imaging, MR angiography can be obtained with a short post-labeling delay when the labeled blood is mainly within vessels. Various labeling strategies have been successfully applied in MRA, including pCASL3, 4, PASL5-9, vessel-encoded ASL10-12, and velocity-selective ASL. Furthermore, 4-dimensional dynamic MRA with high spatiotemporal resolution can be achieved by combing PASL with segmented cine readout6, 9. Accelerated acquisitions, as well as advanced image reconstructions including k-space weighted image contrast (KWIC)13, 14 and magnitude-subtraction compressed sensing (MS-CS)15, have been further developed to facilitate its clinical utilities by significantly shortening the scan time while preserving image quality.Arterial cerebral blood volume and vascular compliance
Arterial cerebral blood volume (aCBV) is another important hemodynamic parameter directly related to vascular autoregulation. In principle, aCBV can be assessable with multi-delay ASL when the labeled blood spins as endogenous tracers pass through arteries16-18. aCBV can be derived from multi-delay ASL with two-compartment model during the CBF calculation19. A fast dynamic ASL technique by combing pulsed ASL with cine bSSFP readout was proposed for aCBV measurement20. Similar to DSC MRI, the labeled blood behaviors as intravascular contrast agent by taking advantage of the phenomenon that the longitudinal magnetization of flowing blood is not or only marginally disturbed by the bSSFP pulse train. Without multi-delay, aCBV can be determined using pCASL when the labeling duration and repetition time are carefully adjusted based on the vascular transit time in a way that the tissue signals are identical in control and label acquisitions while arterial blood signal reaches maximum in the label acquisition and zero in the control21. Other ASL modules such as non-spatial selective ASL22, 23 have been also introduced for aCBV mapping.
Vascular compliance is an important vascular risk factor or marker, which is difficult to be directly detected in brain. By synchronizing ASL with systolic and diastolic phases using dynamic ASL technique24, 25, aCBV can be acquired at systole and diastole, respectively. Intracranial vascular compliance can be subsequently calculated as the ratio of aCBV change to the blood pressure change over a cardiac cycle.
Water permeability or water exchange rate
The blood brain barrier (BBB) plays a critical role in maintaining homeostasis in the brain. The BBB impairment is linked to a number of cerebral nervous system diseases. Existing methods to assess BBB permeability include PET, CT, and DCE-MRI26, all of which require exogenous contrast agents. Recently, several ASL techniques27-29 have been developed to assess BBB function through measuring the water exchange across BBB. 3D ASL combined with a diffusion preparation module can measure water exchange by calculating ASL fractions in the intra- and extravascular compartments30. On the other hand, making use of the intrinsic diffusion weighting in 3D-gradient and spin-echo (GRASE) sequence, an ASL technique termed intrinsic diffusivity encoding of arterial labeled spins (IDEALS) has been introduced without additional diffusion preparation31. “Water exchange time” can be also used as a surrogate measure of BBB permeability, which is measured using multi-echo ASL32. All the techniques above provide 3D whole brain water permeability measurement. A global assessment by targeting venous ASL signal in superior sagittal sinus has also been proposed by measuring permeability-surface-area product with a phase-contrast velocity-encoded pCASL sequence (WEPCAST) MRI technique33.Conclusion
Based on the ASL principle, multiple physiological parameters beyond CBF have been successfully assessed using advanced ASL techniques. All of these measures would provide additional physiological information to tissue perfusion. Taking advantage of the unique non-invasive nature, these advanced ASL techniques could become potentially useful in various clinical applications, such as neurodegenerative disease, stroke, and cerebrovascular malformation. A systematical evaluation of clinical utilities will be needed in the future.1. Alsop DC, Detre JA, Golay X, et al. 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;73:102-116.
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