This Program Project Grant proposal requests continued support for our investigations to assess and understand magnetic susceptibility effects in NMR, and to use these effects to detect and quantify physiological function. The dynamic effects of high magnetic susceptibility contrast agents are used to measure perfusion. Alterations in endogenous iron compounds are used to measure oxygen consumption. Targeted superparamagnetic iron oxides are used for anatomic and functional imaging. Microscopic variations in susceptibility generate a variety of macroscopic consequences. A coordinated investigation of these effects is proposed, in order to enhance NMR imaging in a variety of organ systems and in disease states, such as cancer and ischemia. Research has been conducted across a wide range of inquiry, including physical, biochemical and physiological mechanisms. This proposal is divided into five research Projects which interact constructively through the use of shared methodology and personnel and through the utilization of common Core resources: NMR brain studies of normal,ischemic and neoplastic tissues based on transient effects of paramagnetic contrast agents and on intrinsic effects of motion in tissue; NMR studies of myocardial perfusion using transient magnetic susceptibility effects, and infarct detection using iron oxide particles attached to antimyosin; NMR image-based assessment of oxygen consumption by measurement of signal changes resulting from intravascular deoxyhemoglobin; Analysis of the macroscopic contrast consequences of microscopic susceptibility variation; Receptor imaging by NMR using a novel contrast agent derived from the binding of monocrystalline iron oxide particles to a variety of biomolecules. The five projects are supported by an Administrative Core and three Core laboratories: the NMR facilities Core; the Computing and Technologies Core; and the High Speed Imaging Core.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA048729-04
Application #
3094306
Study Section
Special Emphasis Panel (SRC (D2))
Project Start
1989-01-05
Project End
1997-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Dijkhuizen, Rick M; Singhal, Aneesh B; Mandeville, Joseph B et al. (2003) Correlation between brain reorganization, ischemic damage, and neurologic status after transient focal cerebral ischemia in rats: a functional magnetic resonance imaging study. J Neurosci 23:510-7
Dijkhuizen, Rick M; Asahi, Minoru; Wu, Ona et al. (2002) Rapid breakdown of microvascular barriers and subsequent hemorrhagic transformation after delayed recombinant tissue plasminogen activator treatment in a rat embolic stroke model. Stroke 33:2100-4
Atalay, M K; Poncelet, B P; Kantor, H L et al. (2001) Cardiac susceptibility artifacts arising from the heart-lung interface. Magn Reson Med 45:341-5
Dijkhuizen, R M; Ren, J; Mandeville, J B et al. (2001) Functional magnetic resonance imaging of reorganization in rat brain after stroke. Proc Natl Acad Sci U S A 98:12766-71
Dijkhuizen, R M; Asahi, M; Wu, O et al. (2001) Delayed rt-PA treatment in a rat embolic stroke model: diagnosis and prognosis of ischemic injury and hemorrhagic transformation with magnetic resonance imaging. J Cereb Blood Flow Metab 21:964-71
Schellingerhout, D; Rainov, N G; Breakefield, X O et al. (2000) Quantitation of HSV mass distribution in a rodent brain tumor model. Gene Ther 7:1648-55
Marota, J J; Ayata, C; Moskowitz, M A et al. (1999) Investigation of the early response to rat forepaw stimulation. Magn Reson Med 41:247-52
Mandeville, J B; Marota, J J; Ayata, C et al. (1999) Evidence of a cerebrovascular postarteriole windkessel with delayed compliance. J Cereb Blood Flow Metab 19:679-89
Sanchez del Rio, M; Bakker, D; Wu, O et al. (1999) Perfusion weighted imaging during migraine: spontaneous visual aura and headache. Cephalalgia 19:701-7
Poncelet, B P; Koelling, T M; Schmidt, C J et al. (1999) Measurement of human myocardial perfusion by double-gated flow alternating inversion recovery EPI. Magn Reson Med 41:510-9

Showing the most recent 10 out of 43 publications