Regional metabolic rate of oxygen in the brain using [15O]O2-PET

Single inhalation [15O]O2 bolus model

Steps of MRO2 calculation:

After processing the blood curves on SUN, the following steps can be done in Solaris terminal window or MS Windows command prompt window on SUN or PC platform.

1. Pre-processing of arterial blood curve

Arterial blood data from the on-line sampler needs to be processed before it can be used as input function in the calculation.

If you are working in TPC, use the script water_input to process the on-line detector (blood pump) data prior to the analysis. It requires the countrate curve (*.cr) or similar data for the time delay correction. Notice that in [15O]O2 PET studies the countrate curve has often been unusable, probably because of high random counts from dose collection system and/or exhaling of 15O gases; then we would advice to create "head curves" from dynamic PET images using ecathead for all studies and use these instead of countrate curves.

The corrected blood TAC should always be controlled visually. Water_input script creates a post-script (.ps) format plot of corrected input curve and countrate curve. Corrected blood curve often contains close-to-zero values in the end, which should be removed with a text editor, or left out when determining the fit time. Check also that sample times are in seconds, not minutes.

Convert the time units (sec) in blood curve to minutes with dftunit with option -ctimeunit=min. Note that although for calculation of parametric images the sample times of blood curve must not be converted to minutes, that is necessary for regional analysis. Alternatively, if time unit in both blood and regional tissue curves are in seconds, the results must be multiplied by 60 to achieve metabolic rate per minute.

2. Compute regional K1 values

2a. Constrained vascular volume fraction (recommended)

To reduce variance, a measured or population average based VB correction can be applied instead of fitting VB as one model parameter. Subtract the contribution of radioactivity from vascular blood in the volumes-of-interest with dftcbv.

After correction of vascular volume fraction, K1 is estimated using lhsol with command-line option -k2 and with the following command-line arguments:

  1. corrected arterial blood datafile that was made in step one (times in minutes)
  2. VB-corrected regional dynamic TACs (*.dft file)
  3. fit time in minutes (max 5.0 in this model)
  4. filename for the K1 result values
  5. filename for the fitted regional TACs (optional)

2b. Unconstrained vascular volume fraction

If the regional TACs are of very good quality (low noise), VB can be estimated as one model parameter when using program lhsol with command-line option -vk2 and with the following command-line arguments:

  1. corrected arterial blood datafile that was made in step one (times in minutes)
  2. regional dynamic TACs (*.dft file)
  3. fit time in minutes (max 5.0 in this model)
  4. filename for the K1 result values
  5. filename for the fitted regional TACs (optional)

The units of K1 are (ml blood)/(min * ml tissue).

3. Conversion of K1 values to MRO2

The metabolic rate of oxygen is calculated by multiplying the K1 (=f*OEF) by the concentration of O2 in arterial blood:
MRO2 = K1*[O2]a.
There is currently no software for this purpose, but result file can be read into a spreadsheet program and processed further there

Turku PET Centre recieves the arterial oxygen concentrations from the hospital laboratory in units ml O2/l blood, which have to be converted to ml O2/100 ml. The concentrations are normally about 20 ml O2/100 ml blood. If MRO2 is required in molar units, then [O2]a must be divided by the molar volume of an ideal gas, 22.4 ml/mmol; thereafter [O2]a values are about 0.9 mmol O2/100 ml blood.

After the multiplication, the unit of the MRO2 is either ml O2 / (min * 100 ml tissue) or mmol O2 / (min * 100 ml tissue), depending on the unit of [O2]a. If MRO2 is required per tissue mass instead of volume, the values can be divided by tissue density, 1.04 g/ml (Reference Man).

Cerebral MRO2 in normal subjects are in the range of 2.2 to 3.5 ml O2 / (min * 100 g tissue) in gray matter (Perlmutter et al. 1987; Leenders et al. 1990).


See also:



References:

Herscovitch P. (1995): Cerebral blood flow, volume, and oxygen metabolism. In: Principles of Nuclear Medicine. (Eds. Wagner HN Jr, Szabo Z, Buchanan JW) 2nd ed., W.B. Saunders Co, Philadelphia, 505-514.

ICRP Publication 23, Reference Man: Anatomical, Physiological, and Metabolic Characteristics, International Commission on Radiological Protection, Pergamon Press, New York (1975).

Ito H, Kanno I, iida H, Hatazawa J, Shimosegawa E, Tamura H, Okudera T. Arterial fraction of cerebral blood volume in humans measured by positron emission tomography. Ann Nucl Med 2001; 15: 111-116.

Leenders KL, Perani D, Lammertsma AA, Heather JD, Buckingham P, Healy MJR, Gibbs JM, Wise RJS, Hatazawa J, Herold S, Beaney RP, Brooks DJ, Spinks T, Rhodes C, Frackowiak RSJ, Jones T. Cerebral blood flow, blood volume and oxygen utilization: normal values and effect of age. Brain 1990; 113: 27-47.

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

Ohta S, Meyer E, Thompson CJ, Gjedde A. Oxygen consumption of the living human brain measured after a single inhalation of positron emitting oxygen. J Cereb Blood Flow Metab 1992; 12: 179-192.

Perlmutter JS, Powers WJ, Herscovitch P, Fox PT, Raichle ME. Regional asymmetries of cerebral blood flow, blood volume, oxygen utilization and extraction in normal subjects. J Cereb Blood Flow Metab 1987; 7: 64-67.



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