# Measurement of VB with [15O]CO PET

Vascular volume fraction of blood ("blood volume", VB) 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), and in other tissues and organs, including skeletal muscle (Raitakari et al., 1995 and 1997).

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 haemoglobin in the red blood cells. After the "labelled" 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 VB in tissue, the tissue radioactivity concentration (CPET) is divided by concentration in blood (CB).

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 (HCTSV/HCTLV) in the brain is usually assumed to be 0.85.

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

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

## [15O]CO PET study

Labelled 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).

Regional VB values are easy to calculate even in a spreadsheet program.

## Calculation of VB image

A tool for calculating VB image will be implemented in Carimas.

VB images can also be calculated with command-line tool imgcalc:

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 (Windows) or cat in Linux/macOS, followed by the file name
2. Multiply the blood average by 0.85
3. Divide 100 by this product value; i.e. 100/(blood*0.85)
4. If VB is required 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:

imgcalc PETimage x Value VBimage


## Estimation of beta value for heart studies

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 VB, except that small-to-large vessel hematocrit ratio must not be corrected.

Gated PET with labelled CO can be used to measure absolute end-diastolic and end-systolic volumes and LV ejection fraction (Boyd et al., 1996; Hofman et al., 2005).

## Literature

Eichling JO, Raichle ME, Grubb RL Jr, Larson KB, Ter-Pogossian MM. In vivo determination of cerebral blood volume with radioactive oxygen-15 in the monkey. Circ Res. 1975; 37: 707-714. doi: 10.1161/01.res.37.6.707.

Grubb RL Jr, Raichle ME, Higgins CS, Eichling JO. Measurement of regional cerebral blood volume by emission tomography. Ann Neurol. 1978; 4: 322-328. doi: 10.1002/ana.410040407.

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. doi: 10.1038/jcbfm.1987.85.

Mintun MA, Raichle ME, Martin WRW, Herscovitch P. Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. J Nucl Med. 1984; 25; 177-187. PMID: 6610032.

Raitakari M, Knuuti JM, Ruotsalainen U, Laine H, Mäkelä P, Teräs M, Sipilä H, Niskanen T, Raitakari OT, Iida H, Härkönen R, Wegelius U, Yki-Järbinen H, Nuutila P. Insulin increases blood volume in human skeletal muscle: studies using [15]CO and positron emission tomography. Am J Physiol Endocrinol Metab. 1995; 269: E1000-E1005. doi: 10.1152/ajpendo.1995.269.6.e1000.

Raitakari M, Nuutila P, Knuuti J, Raitakari OT, Laine H, Ruotsalainen U, Kirvelä P, Takala TO, Iida H, Yki-Järvinen H. Effects of insulin on blood flow and volume in skeletal muscle of patients with IDDM: studies using [15O]H2O, [15]CO, and positron emission tomography. Diabetes 1997; 46(12): 2017-1021. doi: 10.2337/diab.46.12.2017.

Updated at: 2018-12-10
Created at: 2005-01-31
Written by: Vesa Oikonen