Interindividual variations of cerebral blood flow, oxygen delivery, and metabolism in relation to hemoglobin concentration measured by positron emission tomography in humans

Abstract

Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with (15)O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary determinant of arterial oxygen content (C(a)O(2)), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO(2)) in relation to Hb concentration in healthy human volunteers (n=17) and in patients with unilateral steno-occlusive disease (n=44). For the patients, data obtained only from the contralateral hemisphere (normal side) were analyzed. The CBF and OEF were inversely correlated with Hb concentration, but CMRO(2) was independent of Hb concentration. Oxygen delivery defined as a product of C(a)O(2) and CBF (C(a)O(2) CBF) increased with a rise of Hb concentration. The analysis with a simple oxygen model showed that oxygen diffusion parameter (L) was constant over the range of Hb concentration, indicating that a homeostatic mechanism controlling CBF is necessary to maintain CMRO(2). The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the (15)O PET data in clinical practice.

Figure 1

Relationship between PET parameters and Hb concentration: (A) CBF, (B) OEF, (C) CMRO₂, and (D) CBV. Filled circles indicate the subjects (n=7) illustrated in Figure 5. Solid lines in CBF and OEF represent the optimized models: CBF [mL/100 mL/min]=73.3−0.191 Age [years]—1.65 Hb [g/dL] (age was fixed to the average value, 64.3 years) and OEF [%]=80.5−1.75 Hb [g/dL]—0.317 CBF [mL/100 mL/min] (CBF was fixed to the average value, 39.8 mL/100 mL/min).

Figure 2

Relationship between PET parameters and age: (A) CBF, (B) OEF, (C) CMRO₂, and (D) CBV. Solid lines in CBF and CMRO₂ represent the optimized models: CBF [mL/100 mL/min]=73.3−0.191 Age [years]—1.65 Hb [g/dL] (Hb concentration was fixed to the average value, 12.9 g/dL) and CMRO₂ [mL/100 mL/min]=3.89−0.0131 Age [years].

Figure 3

Relationship between L derived from the simple oxygen model and Hb concentration. Multiple regression analysis provided no valid linear model, indicating that the oxygen diffusion parameter L is independent of Hb concentration.

Figure 4

Relationship between DO₂ defined as C_aO₂ × CBF (triangle) and CMRO₂ (circle) and Hb concentration. Upper solid line represents DO₂ as a function of Hb concentration, calculated from the regression line of CBF (equation (4)) and equation (2). CMRO₂ (=DO₂ × OEF) as a function of Hb concentration was also calculated from the DO₂ and the regression line of OEF (equation (5)), in which CBF was varied as a function of Hb concentration according to equation (4). In these calculations, age, S_aO₂, and P_aO₂ were fixed to their average values of 64.3 years, 96.1%, and 84.1 mm Hg, respectively.

Figure 5

Representative PET parametric maps of seven subjects with various degrees of Hb concentrations. Selections were based in accordance with the regression lines of CBF and OEF. These subjects are indicated by the filled circles in Figure 1.