Summary:The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO 2 ) during physiologic and pathophysiologic conditions remains the subject of debate. In the present study, we have developed a theoretical model for oxygen delivery and metabolism, which describes the diffusion of oxygen at the capillary-tissue interface and the nonlinear nature of hemoglobin (Hb) affinity to oxygen, allowing a variation in simple-capillary oxygen diffusibility, termed "effective oxygen diffusibility (EOD)." The model was used to simulate the relationship between CBF and CMRO 2 , as well as oxygen extraction fraction (OEF), when various pathophysiologic conditions were assumed involving functional activation, ischemia, hypoxia, anemia, or hypo-and hyper-capnic CBF variations.The simulations revealed that, to maintain CMRO 2 constant, a variation in CBF and Hb required active change in EOD. In contrast, unless the EOD change took place, the brain allowed small but significant nonlinear change in CMRO 2 directly dependent upon oxygen delivery. Application of the present model to quantitative neuroimaging of CBF and CMRO 2 enables us to evaluate the biologic response at capillary level other than Hb-and flow-dependent properties of oxygen transport and may give us another insight regarding the physiologic control of oxygen delivery in the human brain.

RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF.

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This study evaluated the feasibility of imaging rat brains using a human whole-body 3-T magnetic resonance imaging (MRI) scanner with specially developed transmit-and-receive radiofrequency coils. The T(1)- and T(2)-weighted images obtained showed reasonable contrast. Acquired contrast-free time-of-flight magnetic resonance angiography images clearly showed the cortical middle cerebral artery (MCA) branches, and interhemispheric differences could be observed. Dynamic susceptibility contrast MRI at 1.17 mm(3) voxel resolution, performed three times following administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, 0.1 mmol/kg), demonstrated that the arterial input function (AIF) can be obtained from the MCA region, yielding cerebral blood flow (CBF), cerebral blood volume, and mean transit time (MTT) maps. The hypothalamus (HT) to parietal cortex (Pt) CBF ratio was 45.11 +/- 2.85%, and the MTT was 1.29 +/- 0.40 s in the Pt region and 2.32 +/- 0.17 s in the HT region. A single dose of Gd-DTPA enabled the assessment of AIF within MCA territory and of quantitative CBF in rats.