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Arterial Spin Labeling Imaging

Introduction

Quantification of cerebral blood perfusion is a crucial medical parameter to understand the ramifications of both chronic and acute cerebral pathologies. While the human brain amounts to only around 2% of body mass it utilizes around 20% of total energy consumption at rest.1 Thus, blood flow to the brain is essential for delivery of oxygen and energy substrates, as well as for the clearance of metabolic waste products. Deviations in the rate of blood flow can provide diagnostic information regarding various pathologies. Cerebral blood flow (CBF) is especially important in understanding ischemic injury to the brain where prolonged loss of perfusion can quickly lead to cell death and neurological impairment. CBF is also important in the diagnosis and understanding of various neurodegenerative pathologies where tissue structure may be relatively undifferentiated from healthy tissue. Tissue blood flow maps can be created from flow imaging to understand the role of perfusion for pathologies where tissue structure is relatively “normal”, for instance in early stage dementia, Alzheimer’s disease, and psychological disorders. Historically, quantification of CBF was accomplished using a variety of methods including 15O-H2O and 18F-FDG positron emission tomography (PET), 99mTc single-photon emission computed tomography, and xenon contrast enhanced x-ray CT.2 The majority of these methods either place a radiological burden on patients and/or require them to undergo invasive procedures. There are also two common MRI based techniques to measure CBF: 1). Dynamic susceptibility contrast (DSC): which involves administration of an exogenous intravascular contrast agent. However, DSC is still invasive as it uses contrast agent. 2). Arterial spin-labeling (ASL): which non-invasively and magnetically labels the endogenous water in blood.

Arterial Spin Labeling (ASL) is a novel noninvasive imaging technique utilized to quantify CBF through magnetic labeling of arterial blood. As ASL measures CBF through magnetization of blood, both of the significant drawbacks of radiological imaging can be avoided. ASL functions through tagging arterial blood to the brain with a magnetic label and measuring this signal in a region of interest in the brain. ASL differs from blood oxygenation level dependent contrast imaging (BOLD) fMRI in that ASL directly measures blood diffusion throughout tissue versus measuring magnetic inhomogeneities caused by differences in oxygenation state.3 Theory and Methods

The proton spins of blood water are inverted by a 180 degree radiofrequency (RF) pulse below a region of interest, resulting in magnetic labeling. The labeled blood water would then flow to a slice of interest over a period of time, later to exchange with water protons of tissue at a slice of interest. This would alter the magnetization of the tissue, with which the signal would be read when taking the image of the slice of interest, with this process of labeling and reading being the tagged image. The control would be obtaining the image without labeling the cerebral blood, with the difference between the tag and control image being proportional to the cerebral blood flow.

Steps 1. Arterial blood is magnetically labeled using RF excitation 2. MRI slice taken in region of interest in brain after some time for diffusion of labeled blood 3. Experiment is repeated to acquire control slice of same region of interest 4. Difference in magnetization between control and initial slice is proportional to cerebral blood perfusion 5. Multiple acquisitions are taken and averaged for desired SNR

Many types of ASL imaging have been developed since its inception in the early 1990’s targeted towards addressing various advantages and disadvantages of the imaging method.4 These parameters include SNR, patient energy absorption, scan time, and temporal accuracy among other factors. In our report, we specifically studied the applications of pulsed arterial spin labeling (PASL) and pseudocontinuous arterial spin labeling (PCASL). We were provided data sets for six healthy subjects that included 3D ASL perfusion maps, T1 weighted and Proton density weighted images. In our report, we estimate the cerebral blood flow in regions of interest and compare to expected values.

There are three main proton labeling techniques of ASL: 1. Continuous ASL (CASL) 2. Pulsed ASL (PASL) 3. Pseudo-continuous ASL (pCASL)

1. Continuous Arterial Spin Labeling (CASL)

CASL is the earliest labeling technique of all. The labeling in CASL is continuous through a thin slice at the neck level. The inversion of the magnetization is obtained by the joint application of continuous pulsed RF for (2 - 4 s) and a magnetic field gradient in the direction of the flow. CASL provides higher perfusion contrast than other types of labeling. However,CASL's has disadvantages as it produces considerable magnetization effects (MT) effects, and high level of energy is deposited in the tissue (SAR) from CASL. As a result of the disadvantages the technique has been abandoned.

2. Pulsed Arterial Spin Labeling (PASL)

The first step is to acquire an unlabeled image of the region of interest to get the control image. This is done by applying an RF pulse which has a net zero effect on the blood water magnetization. Next, the water of arterial blood is labeled with a short adiabatic inversion pulse of around 10 ms which covers the entire labeling slab, located below the brain. This is a very efficient tagging method because the entire region is labeled instantaneously. After the labeling, there is a post label delay period, also known as the inflow time, where we allow the blood to travel into the brain to the tissue of interest. During this period, however, it is important to acknowledge the longitudinal T1 relaxation, which causes the gradual loss of the label. The tagged portions of blood vary in the distance they travel and the time it takes to arrive at the region of interest. Consequently, there will be a variation of T1 decay which will lead to a lower SNR than the SNR received through a Pseudocontinuous ASL. Fast acquisition time of the image is crucial in order to capture the blood before the magnetization reaches equilibrium relaxation.9

EPISTAR pulse sequence alternates between acquiring a tagged image and a control image. The tagging pulse sequence starts with a 900 slice-selective saturation pulse applied at the location where the perfusion measurement is sought. This pulse saturates the spins in the slice location of interest providing some immunity to any perturbation that can be caused by the subsequent tagging pulse. Following the saturation pulse, a spoiler gradient is typically used to dephase the magnetization. Note that the spoiling gradient lobe is bridged with the slice-selection gradient lobe. After the saturation pulse and its associated spoiler, a spatially selective inversion pulse (i.e., a tagging pulse) inverts spins within a thick slab proximal to the imaging slice. A hyperbolic secant adiabatic inversion pulse is most frequently used (although other adiabatic inversion pulses or non- adiabatic inversion pulses can also be employed.)

PICORE - Proximal inversion with a control for off-resonance effects, is a variation of EPISTAR. The tagging sequence is the same as that in EPISTAR, but an off-resonance inversion pulse in the control sequence is played without an accompanying slab-selection gradient. The carrier frequency of the inversion pulse is the same between the control and the tagging pulse sequences, so the MT effect can be subtracted out. The magnetization of the imaging slice is virtually unperturbed due to the large resonance offset (e.g., 5 kHz). Another advantage is that asymmetry in MT effects is compensated in PICORE, but not in EPISTAR. A disadvantage of PICORE is, however, that it is less robust against eddy-current effects than EPISTAR because the control sequence uses a different gradient waveform from the tagging sequence.

FAIR - Flow-sensitive alternating inversion recovery, employs a frequency-selective inversion pulse with and without an accompanying slice-selection gradient to produce the tagged and the control images. Similar to EPISTAR, the inversion pulse is typically adiabatic with a bandwidth of approximately 1-5 kHz. Unlike EPISTAR, however, the inversion pulses for the control and tagged images have the same carrier frequency.

3. Pseudo-continuous Arterial Spin Labeling (pCASL)

Unlike the Pulsed ASL, Pseudocontinuous ASL involves a long labeling period of about 1-2 seconds total. This period is made up of very short (~1ms) flow-induced adiabatic inversion pulses which continuously invert inflowing blood as it crosses the labeling plane. Instead of labeling an entire slab of blood at once, there is instead a labeling plane where blood is tagged as it flows. Additionally, the phase of every other pulse is shifted by 180°. By doing this phase shift, the flowing blood water is not inverted for those pulses, which allows for the acquisition of the control image.With PCASL, the same amount of T1 decay occurs for all of the blood. This allows the images to achieve a high SNR, which is ideal for clinical imaging.9

Clinical and Research Significance As a noninvasive quantification of cerebral blood flow (CBF/rCBF) to measure brain activity. It has a profound clinical and research significance in all Cerebral Pathologies including brain tumors(Gliomas), ischemia, vascular pathologies, traumatic brain injuries, cerebrovascular diseases, CNS neoplasm, epilepsy etc. ASL is particularly effective for pathologies with relatively normal tissue structure Dementia, Alzheimer’s disease, addiction pathologies. Research Uses - Functional neuro-imaging for cognitive neuroscience, social neuroscience, cognitive psychology, neuropsychology

Limitations

With ASL, we can reliably and quantitatively measure CBF - however, there are drawbacks with: 1. Subject motion - ASL relies on the perfect cancellation of static tissue when subtracting the tagged image from the control image 2. Partial Volume Effects- Fast acquisition is needed - the labeled blood must be captured before it relaxes to equilibrium state. Fast imaging means lower spatial resolution and bigger voxel size. A voxel contains mixture of GM, WM, and CSF. The flow values are different for each tissue, which can lead to error in CBF reading 3. SAR exposure due to RF energy deposition

References

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