Reversal of startle gating deficits in transgenic mice overexpressing corticotropin-releasing factor by antipsychotic drugs.

Chronically elevated levels of corticotropin-releasing factor (CRF) in transgenic mice overexpressing CRF in the brain (CRF-OE) appear to be associated with alterations commonly associated with major depressive disorder, as well as with sensorimotor gating deficits commonly associated with schizophrenia. In the present study, we tested the hypothesis that antipsychotics may be effective in normalizing prepulse inhibition (PPI) of acoustic startle in CRF-OE mice, which display impaired sensorimotor gating compared to wild-type (WT) mice. The typical antipsychotic haloperidol and atypical antipsychotic risperidone improved PPI in the CRF-OE mice, but were ineffective in WT mice. The atypical antipsychotic clozapine did not influence PPI in CRF-OE mice, but reduced gating in WT mice. This effect of clozapine in the CRF-OE mice may thus be regarded as a relative improvement, consistent with the observed effect of haloperidol and risperidone. As expected, the anxiolytic, nonantipsychotic chlordiazepoxide was devoid of any effect. All four compounds dose-dependently reduced the acoustic startle response irrespective of genotype. These results indicate that antipsychotic drugs are effective in improving startle gating deficits in the CRF-OE mice. Hence, the CRF-OE mouse model may represent an animal model for certain aspects of psychotic depression, and could be a valuable tool for research addressing the impact of chronically elevated levels of CRF on information processing.     

Vascular Centerline Extraction in 3D MR Angiograms for Phase Contrast MRI Blood Flow Measurement

The accuracy of 2D phase contrast (PC) magnetic resonance angiography (MRA) depends on the alignment between the vessels and the imaging plane. PC MRA imaging of blood flow is challenging when the flow in several vessels is to be evaluated with one acquisition. For this purpose, semi-automatic determination of the plane most perpendicular to several vessels is proposed based on centerlines extracted from 3D MRA. Arterial centerlines are extracted from 3D MRA based on iterative estimation-prediction, multi-scale analysis of image moments, and a second-order shape model. The optimal plane is determined by minimizing misalignment between its normal vector and the centerlines’ tangent vectors. The method was evaluated on a phantom and on 35 patients, by seeking the optimal plane for cerebral blood flow quantification simultaneously in internal carotids and vertebral arteries. In the phantom, difference of orientation and of height between known and calculated planes was 1.2° and 2.5 mm, respectively. In the patients, all but one centerline were correctly extracted and the misalignment of the plane was within 12° per artery. Semi-automatic centerline extraction simplifies and automates determination of the plane orthogonal to one vessel, thereby permitting automatic simultaneous minimization of the misalignment with several vessels in PC MRA.