Endogenous tracer methods in perfusion MRI use a model that assumes that the tracer diffuses freely from the intravascular compartment into the tissue com partment. This model is similar to the one used in PET measuring the regional accumulation of the tracer, which is influenced by regional blood flow and its halflife .
Arterial spin labelling (ASL), also called arterial spin tagging, is an endogenous tracer perfusion method based on the measurement of the signal loss produced by magnetically labelled water protons flowing into the imaging plane and exchanging with tissue protons. Water protons within inflowing arterial blood are magnetically labelled (or „tagged") by application of a special radiofrequency pulse designed to invert spins in a thick slab proximal to the slice of interest [1,72 - 75]. By comparing tagged and untagged baseline images, qualitative or quantitative images can be obtained (Fig. 9.9).
The modelling of ASL is similar to that used in the analysis of PET perfusion imaging, since in ASL methods arterial blood water is labelled as an endogenous diffusible tracer that can detect functional deficiencies in a way similar to PET .
ASL has many advantages over PET as it is entirely non-invasive and does not entail exposure to ionizing radiation, intravenous contrast agents or radioactive isotopes.
It can be performed with most MR scanners in 10-15 min and can be rapidly repeated since labelled water is cleared after a few seconds because of T1 relaxation .
Compared with DSC methods, use of water as the label in ASL entails advantages over intravascular tracers, including the potential to be quantitative, repeat-able, and independent of BBB status [7, 9].
Difficulties associated with CBF quantitation are related to the relatively short half-life of the tracer due to T1 of blood, low SNR (especially in slow flow areas) and uncertainties regarding the precise timing of the arrival of labelled water at different voxels [7, 74]. In normal subjects ASL has been favourably compared with H215O PET .
All current ASL methods are based on the collection of image pairs, which are subsequently subtracted, in which arterial magnetization entering the imaging slice during the repetition time (TR) interval varies. For maximum contrast, inflowing spins should have control image and be inverted during the label image. In practice, the signal difference between label and control images is a tiny fraction (0.5-2%) of the source images, requiring collection of multiple image pairs and averaging of their small signal to provide adequate sensitivity .
Labelling can be achieved using either a short radio-frequency pulse to invert the spins, followed by a delay time to allow inflow (pulsed ASL - PASL) [77,78], or by continuous adiabatic inversion of spins crossing a predefined plane, defined by off-resonance low-level continuous wave radiofrequency radiation in the presence of a magnetic field gradient (continuous ASL - CASL) .
In theory, CASL permits an approximately threefold increase in SNR, although this advantage is partially mitigated by imperfect adiabatic labelling and by a longer distance between the labelling plane and the imaged slices .
Because the magnetic label decays with blood T1 (1.2-1.4 s at 1.5 T),both methods suffer from CBF underestimation in regions with prolonged arterial arrival times, defined as the average time needed for labelled blood to reach the capillaries, which has been measured to be between 4,000 and 1,500 ms in the normal brain . This problem can be minimized by inserting a post-labelling delay before imaging in CASL or by saturation pulses in PASL [74, 81].
However, in the diseased brain arterial arrival times maybe markedly increased (by up to 5 s) if flow is provided by collateral networks; in this case, by the time the label arrives, its has relaxed back to equilibrium and an erroneously low CBF will be measured. Unless diffusion gradients are used to suppress the signal from large arteries, regions with a delayed arrival time often show several serpiginous bright spots with decreased flow signal distal to the supplying vessels. Recently, two different methods have been proposed to measure CBF more accurately in the presence of unknown regional changes in arterial arrival times.
Considering the water inflow at multiple post-label delay times, the movement of labelled blood from the arteries to the parenchyma can be detected, but this is generally not time-efficient.
However, if the full wash-in curve is measured, arrival time and CBF can be measured independently [82, 83].
In a different approach, called velocity-selective ASL (VS ASL), a 90°-gradient-180°-gradient-90° labelling pulse can be used to create a label independent of position and sensitive only to spin velocity [84, 85].
Moreover, with VS ASL not only arterial arrival time effects but also the slow-flow CSF artefacts in regions surrounding the ventricles maybe reduced [86, 87].
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