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Perfusion image using [15O]H2O and dynamic PET

[15O]H2O bolus model

The methods to measure perfusion with [15O]H2O are based on the principle of exchange of inert gas between blood and tissues (Kety 1945).
Kety-Schmidt equation
A two compartment (i.e. one tissue compartment) model is used to describe the kinetics of [15O]H2O (diffusible tracer) concentration in the tissue, Ct(t), depending on the concentration in arterial blood, Ca(t), perfusion or blood flow (f), and the partition coefficient of water, p.
Kety-Schmidt equation for radiowater
When radioactivity in the volume of interest is measured with PET (CPET(t)), the radioactivity of vascular blood inside the measured volume should also be taken into account; Va is the arterial volume fraction in tissue:
Equation for radiowater and PET

Kinetic model vs. autoradiography (ARG) method

ARG method produces persion images that are of better quality (less noise) than images produced by kinetic (dynamic) model, although kinetic technique can also generate reproducible perfusion measurements (de Langen et al., 2008).

ARG method can be applied to static PET images, which reduces the image reconstruction time and file size. However, ARG method requires that the partion coefficient of water is known, and that it is uniform in all regions of interest. Dynamic method also avoids the tendency to underestimate the flow in the presence of flow heterogeneity within a ROI or pixel (Wells et al 2003). Therefore, if precise quantitation is required or partition coefficient is of interest, then dynamic PET imaging and kinetic modeling is recommended.

Calculation of perfusion image:

The following steps can be done in MS Windows command prompt window or Solaris terminal 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 perfusion 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; please note that in certain organs you should not use countrate curve, but a TAC from region-of-interest instead.

In some occations you can create arterial blood curve from the dynamic PET image. In this case no corrections need to be done.

2. Compute perfusion (blood flow, K1) image

Before calculation

Calculation of perfusion image

To compute the K1  image, the following command-line arguments need to be given to the program imgflow:

  1. corrected arterial blood datafile that was made in step one (times in seconds)
  2. dynamic [15O]H2O image file
  3. fit time in seconds
  4. filename for the perfusion image

The units in the resulting perfusion image are (ml blood)/(min * ml tissue) by default, but it can be changed to per 100 ml tissue with option -dl.

3. Conversion of perfusion image units

If perfusion is required in units (ml blood)/(min * 100 g tissue), the perfusion image need to be calculated withimgflow with options -dl and -density=1.04 (1.04 g/mL is the density of the brain tissue).

The perfusion image can then be used in SPM analysis, and/or ROIs can be drawn and regional perfusion values calculated as described elsewhere.

equation

Perfusion image of femoral region in an exercise study.

Validation

The results from parametric images should always be validated against results from regional average curves (Lodge et al., 2000). Noise in dynamic image may lead into biased results with distorted variance. Filtering of dynamic images may be needed to achieve the same quantitative results as in the regional analysis. To prevent artefacts and excessive loss of image resolution, the strength of filtering must not exceed the level that is required to achieve comparable results.



References:

Blomqvist G. On the construction of functional maps in positron emission tomography. J Cereb Blood Flow Metab 1984; 4: 629-632.

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).

Iida H, Kanno I, Miura S, Murakami M, Takahashi K, Uemura K. Error analysis of a quantitative cerebral blood flow measurement using H215O autoradiography and positron emission tomography, with respect to the dispersion of the input function. J. Cereb. Blood Flow Metab. 1986; 6: 536-545.

Kety SS, Schmidt CF. The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations. Am. J. Physiol. 1945; 143: 53-66.

de Langen Aj, Lubberink M, Boellaard R, Spreeuwenberg MD, Smit EF, Hoekstra OS, Lammertsma AA. Reproducibility of tumor perfusion measurements using 15O-labeled water and PET. J Nucl Med 2008; 49(11): 1763-1768.

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.

Lodge MA, Carson RE, Carrasquillo JA, Whatley M, Libutti SK, Bacharach SL. Parametric images of blood flow in oncology PET studies using [15O]water. J Nucl Med 2000; 41:1784–1792.

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.

Wells P, Jones T, Price P. Assessment of inter- and intrapatient variability in C15O2 positron emission tomography measurements of blood flow in patients with intra-abdominal cancers. Clin Cancer Res. 2003; 9: 6350-6356.



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