MRI cerebral perfusion imaging is a widely disseminated technique on nearly all MRI scanners used for clinical diagnosis of brain disease and for neuroscience research. Over the last five years there has been considerably increased use of arterial spin labeling (ASL) for clinical diagnosis, while still i.v. injections of a gadoliium based contrast bolus are widely used clinically. Both brain perfusion methods, ASL and DSC techniques, involve making images very fast to identify the passage of blood through the capillary compartment. The image signal-to-noise ratio (SNR) is limited by the small (e.g., 3%) fraction of blood in tissue volumes. This is proportionately small but a second limitation is the time window of imaging, which is constrained to about 500-700 milliseconds for the capillary phase of blood passage. Therefore, rapid imaging of blood inflow is essential. For this reason DSC contrast based methods and ASL with multi-slice 2D EPI have not been able to satisfactorily image perfusion in the entire brain except with thick slices hence reduced spatial resolution. 3D imaging has therefore been developed as an alternative to 2D EPI. However, 2D images have certain desirable characteristics compared with 3D if there are patient motion artifacts. To overcome these limitations we propose to develop novel technology to acquire images simultaneously instead of separately. This approach called simultaneous multi-slice imaging ASL (SMS ASL) and SMS DSC increases by several fold the number of images that are acquired during the limited time window of capillary perfusion phase so the whole brain can be imaged. Another benefit of SMS-ASL is that the time to scan the brain can be greatly reduced by avoiding repeated scans of different brain areas, thus, reducing motion artifacts. A second major innovation in this project is the Hadamard encoded ASL, which is highly useful in clinical studies where the blood arterial transit time (ATT) is not known as in normal aging of people. The Hadamard-ASL acquires images at several different inflow times (TI) to be sure to capture the capillary perfusion phase of blood in at least one set of images. By acquiring the different TI values in a well-defined sub-bolus partitioning of the labeling period, their combination gives separated images at the distinct TI with essentially 2x the SNR and half the net scan time as required by current methodology which acquires each TI data set independently and sequentially. Both the Hadamard and the SMS can be combined for further improvements in SNR, speed and spatial resolution. This will highly impact the accessibility to patients and the robustness of the perfusion technology in clinical use. The availability of the new simultaneous perfusion imaging technology will give clinicians and researchers the capability of performing significantly improved MRI perfusion measurements in patients and these improvements will impact the diagnosis of many different brain diseases, including stroke, leukoencephalopathies and degenerative diseases;i.e., Alzheimer's disease and Parkinson's disease. Perfusion measurements of quantitative cerebral blood flow (CBF) and ATT are important quantitative biomarkers useful as physiological imaging in evaluating new drug therapies for brain diseases. This family of new perfusion imaging techniques utilizes more efficient pulse sequences that provide major advantages in resolution, slice coverage, SNR and speed. The new simultaneous imaging will have high utility and be highly desirable for use on clinical scanners worldwide. The improved quantitative MRI perfusion imaging offers overall increased efficiency that is highly commercializable given they provide improved diagnostic approaches to evaluate brain disease and further improve specificity and sensitivity in MRI neuroradiological exams. The new sequences will be designed, implemented and evaluated on MRI scanners operating at 1.5 Tesla at AMRIT, at 3T at University of California Berkeley and at 3T and 7T at University of California, San Francisco Medical Center and at Martinos Center for Biomedical Imaging, Massachusetts General Hospital, and Harvard Medical School. Once the new perfusion sequences are optimized they will be further evaluated and optimized in collaborative clinical test sites of UCSF Medical Center, UCLA and University of Pennsylvania. In addition to establishing their value in neuroradiology exams, they will be made into useful tools for basic and clinical neuroscience research.

Public Health Relevance

MRI is a proven non-invasive technique to measure blood perfusion in the brain, by both arterial spin labeling (ASL) which traces the passage of blood into the brain and by dynamic susceptibility contrast (DSC) perfusion measurements which rely on the i.v. injection of a small amount of tracer material without involving radiation. The widespread use of these promising techniques of MRI perfusion imaging have been prevented by the inefficiencies in the image formation process which is limited to sub-segments of the whole brain, or sacrifice detail when imaging the whole brain. We are proposing to develop a highly efficient imaging technique which will give researchers and clinicians the capability to perform 2D and 3D perfusion images of the whole brain by recording images simultaneously rather than separately as is currently performed in all scanners. The resulting quantitative measures of cerebral blood flow will very valuable for medical diagnosis and in research on neurovascular diseases including stroke, and wide spectrum of neurological diseases including brain tumors, as well as for medical research on neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and for leukoencephalopathies including multiple sclerosis.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1-SBIB-T (10))
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Babcock, Debra J
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Advanced MRI Technology, LLC
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Chen, Liyong; Beckett, Alexander; Verma, Ajay et al. (2015) Dynamics of respiratory and cardiac CSF motion revealed with real-time simultaneous multi-slice EPI velocity phase contrast imaging. Neuroimage 122:281-7
Feinberg, David A; Beckett, Alexander; Chen, Liyong (2013) Arterial spin labeling with simultaneous multi-slice echo planar imaging. Magn Reson Med 70:1500-6