A multimodality investigation of cerebral hemodynamics and autoregulation in pharmacological MRI.
Pharmacological MRI (phMRI) methods have been widely applied to assess the central hemodynamic response to pharmacological intervention as a surrogate for changes in the underlying neuronal activity. However, many psychoactive drugs can also affect cardiovascular parameters, including arterial blood pressure (BP). Abrupt changes in BP or the anesthetic agents used in preclinical phMRI may impair cerebral blood flow (CBF) autoregulation mechanisms, potentially introducing confounds in the phMRI response. Moreover, relative cerebral blood volume (rCBV), often measured in small-animal phMRI studies, may be sensitive to BP changes even in the presence of intact autoregulation. We applied laser Doppler flowmetry and MRI to measure changes in CBF and microvascular CBV induced by increasing doses of intravenous norepinephrine (NE) challenge in the halothane-anesthetized rat. NE is a potent vasopressor that does not cross the blood-brain barrier and mimics the rapid BP changes typically observed with acute drug challenges. We found that CBF autoregulation was maintained over a BP range of 60-120 mmHg. Under these conditions, no significant central rCBV responses were observed, suggesting that microvascular rCBV changes in response to abrupt changes in perfusion pressure are negligible within the autoregulatory range. Larger BP responses were accompanied by significant changes in both CBV and CBF that might confound the interpretation of phMRI results.
Gozzi
Alessandro
A
Department of Neuroimaging, Centre of Excellence for Drug Discovery, Psychiatry, GlaxoSmithKline Medicines Research Centre, 37135 Verona, Italy. alessandro.2.gozzi@gsk.com
Ceolin
Laura
L
Schwarz
Adam
A
Reese
Torsten
T
Bertani
Simone
S
Crestan
Valerio
V
Bifone
Angelo
A
D000777:Anesthetics; D000818:Animals; D001158:Arteries / Q000473:pathology; D001794:Blood Pressure; D001921:Brain / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D002245:Carbon Dioxide / Q000737:chemistry; D002560:Cerebrovascular Circulation; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D015233:Models, Statistical; D019047:Phantoms, Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
D000777:Anesthetics; D002245:Carbon Dioxide