Arterial spin labeling (ASL) has many advantages for the measurement of cerebral blood flow (CBF) and regional brain perfusion. Such measurements are significant for research and diagnosis and treatment of stroke, ischemia, brain tumors, and dementia. ASL is non-invasive, inexpensive, and produces high-resolution images that are easily compared with other anatomical and functional magnetic resonance imaging (MRI) scans acquired as part of the same session. The ASL method involves labeling inflowing arterial spins by inverting them at a plane proximal to the imaging volume. A major factor in the calculation of CBF is the transit time for the labeled protons to pass from the imaging plane and into the labeling plane. Most standard ASL sequences suffer from the limitation that they cannot measure transit times directly. Instead, they rely on a method of factoring out the effect of travel times that is introduces multiple sources of confound and limits signal-to-noise ratio, especially in white matter. Furthermore, standard ASL measurements are unable to determine whether the changes detected are truly reflections of changes in flow or the result of the alterations in transit times known to be involved in neural activation and stroke. In this proposal, we describe a novel method of arterial spin labeling that is able to directly measure transit times. Our method offers the advantages of standard ASL while removing some of its limitations. This is made possible by labeling the arterial spins according to a pseudo random sequence. The mathematical properties of the sequence used for pseudo random amplitude modulation, or PRAM, allow recovery of all the transit times present in the imaged tissue as part of a single integrated acquisition. Implementation of this method should provide novel insights into the details of cerebral blood flow at both the macroscopic and microscopic levels. Detailed specific aims are:
Specific Aim 1 a: Implement the pseudo random arterial modulation (PRAM) scheme on a Siemens 3T Trio scanner.
Specific Aim 2 : Validate the PRAM sequence developed in SA 1 using standard spin tagging and ASL techniques in phantoms.
Specific Aim 3 : Extend the validation studies to human volunteers undergoing visual stimulation by comparing the PRAM results to those acquired by standard PASL sequences.

Public Health Relevance

This project will improve our ability to non-invasively measure local blood flow in the brain, important for both clinical examinations and research studies. We will develop new imaging protocols for standard Siemens MR scanners that will transiently label inflowing arterial blood so we can directly measure how long it takes for the blood to flow from the neck into specific regions in the brain. Since these times change from person to person and during disease this method will provide novel information without the need for injecting radioactive tracers or other contrast material.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (NOIT)
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Liu, Guoying
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Medical University of South Carolina
Schools of Medicine
United States
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Zou, Xiaowei; Brown, Truman R (2014) Relaxation by amplitude modulation: A rapid T1 measurement method. Magn Reson Med 71:2155-65