Measurement of tissue blood volume with [¹⁵O]CO PET

Blood volume (V_B) in the brain has been measured with PET using carbon monoxide as a tracer labeled with either C-11 or O-15 (Grubb et al., 1978; Martin et al., 1987). The model is very simple and applicable to other tissues than brain as well: inhaled tracer dose of labelled carbon monoxide is assumed to bind and stay bound to hemoglobin in the blood. After the "labeled" red blood cells are distributed evenly in the vasculature of the whole body, the concentrations of radioactivity in tissue (using PET) and in blood (manual venous sampling) are measured. To get an estimate of the volume fraction of blood in tissue, the tissue radioactivity concentration (C_tissue) is divided by concentration in blood (C_blood).

For precise quantitation, the difference between hematocrit values in tissue vasculature (small vessel hematocrit) and in large veins where blood sampling is done, must also be accounted for. The ratio of small-vessel and large-vessel hematocrits (HCT_SV/HCT_LV) in the brain is usually assumed to be 0.85.

The blood volume as percentage of tissue volume can be calculated from equation

If V_B is needed per mass of tissue (mL blood/100 g tissue) the tissue concentration (Bq/mL) must be divided by density of the tissue (ρ_tissue). Density of the brain tissue is 1.05 g/mL.

[¹⁵O]CO PET study

Labeled carbon monoxide is inhaled for about 2 min (Martin et al., 1987). After the inhalation, two minutes are waited before the beginning of a single 4-min scan. During the PET scanning, three whole blood samples are taken; samples can be either arterial or venous (Martin et al, 1987).

Calculation of V_B image

Regional VB values are easy to calculate even in spreadsheet program, and a tool for calculating V_B image will be implemented in Carimas. ECAT format V_B images can also be calculated withcommand-line tool ecatcalc:

1. Use a pocket calculator, or preferably a spreadsheet program, to calculate a coefficient with which the PET image will be multiplied with.
   1. Calculate an average of the measured three values of blood radioactivity. The blood datafile is in ASCII format and can be viewed with any word processor or listed on-screen with command 'type' followed by the filename in Windows command prompt window
   2. Multiply the blood average by 0.85
   3. Divide 100 by this product value; i.e. 100/(blood*0.85)
   4. If V_B is needed in unit ml blood/100 g tissue (i.e. per mass, not per volume), the value must be further divided by density of the tissue, e.g. 1.05
2. Multiply the PET image with this value using program ecatcalc:
   ecatcalc PETimage x Value VBimage

Estimation of beta value

Myocardial perfusion measurement using [¹⁵O]H₂O PET requires that beta value is measured (either individual or population average, based on the same scanner, same reconstruction parameters and similar LV cavity ROI size). Beta value can be measured like V_B, except that small-to-large vessel hematocrit ratio is not corrected.

References

Grubb RL Jr, Raichle ME, Higgins CS, Eichling JO. Measurement of regional cerebral blood volume by emission tomography. Ann Neurol. 1978; 4: 322-328.

Martin WRW, Powers WJ, Raichle ME. Cerebral blood volume measured with inhaled C¹⁵O and positron emission tomography. J Cereb Blood Flow Metab. 1987; 7: 421-426.