Regional cerebral blood volume (CBV) and its dynamic change induced by neural activity are critical indices for evaluating tissue viability and function. Routine magnetic resonance imaging (MRI) of CBV in humans currently requires injection of gadolinium-based blood contrast agents, hampering repeated measurements and potentially causing nephrogenic systemic fibrosis. Therefore, alternative non-invasive techniques are required for CBV mapping in humans. Importantly, compartment-specific CBV measurements will be crucial to obtain insight into blood flow regulation during physiological responses, because arterial vessels dilate and constrict to actively control cerebral blood flow (CBF), while venous vessels respond passively. In this application, we propose in humans at 3 Tesla to evaluate and implement non-invasive, arterial CBV measurement techniques without contrast agents, to perform quantitative mapping of baseline arterial CBV, and to determine its relative change during stimulation. The hypotheses to be tested are to determine whether quantitative arterial CBV can be reliably mapped in humans by non-invasive MRI techniques and to determine whether the arterial CBV change is significant during neural activity in humans. Baseline arterial CBV can be measured by our recent arterial spin-labeling techniques, which have been successfully applied to quantitatively map arterial CBV and CBF in animals. Translation to 3-T awake human studies necessitates consideration of differences in species, physiological conditions, and magnetic field strengths. Therefore we will carefully evaluate and optimize human techniques for arterial CBV measurement, and examine the consistency of arterial CBV quantification. During stimulation, it is often assumed that the arterial CBV change is minimal and therefore can be ignored in functional MRI (fMRI) studies. However, this notion has recently been challenged by our animal studies showing that the arterial CBV increase is the dominant contribution to the total CBV response. Thus, we propose to apply this arterial CBV-based fMRI technique to humans to determine dynamic changes and spatial specificity of arterial CBV and 'true'BOLD signals during neural stimulation. The goal of these investigations is to implement non-invasive blood volume mapping techniques for routine human imaging without the injection of contrast agents, which will enable future diagnosis and study of vascular disease.

Public Health Relevance

Develop noval non-invasive MR blood volume imaging techniques and to measure baseline cerebral blood volume and its changes during stimulation in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB012140-01
Application #
7961928
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (90))
Program Officer
Liu, Guoying
Project Start
2010-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$219,216
Indirect Cost
Name
University of Pittsburgh
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Kim, Tae; Shin, Wanyong; Kim, Seong-Gi (2014) Fast magnetization transfer and apparent T1 imaging using a short saturation pulse with and without inversion preparation. Magn Reson Med 71:1264-71
Kim, Tae; Kim, Seong-Gi (2011) Quantitative MRI of cerebral arterial blood volume. Open Neuroimag J 5:136-45