Perfusion (blood flow)

Perfusion is the volume of blood flowing through certain mass (or volume) of tissue per unit time. Blood flow is usually given in units mL/(100 g * min) or mL/(mL * min).

Tissue perfusion can be measured noninvasively with positron emission tomography using the following general techniques:

The methods to measure perfusion with diffusible and inert tracers are based on the principle of exchange of inert gas between blood and tissues (Kety and Schmidt, 1945; Kety, 1985), and on the Fick's principle. External detection of radioactive 85Kr and 133Xe has been used to measure regional perfusion in the brain (Lassen & Ingvar, 1961; Ingvar & Lassen, 1962; Glass & Harper, 1963). 133Xe clearance method has been widely used, but it will only give an estimate of the total blood flow (both nutritive and non-nutritive), and is dependent on the tissue-blood -partition coefficient, which is dependent on the relative water and fat contents. The clearance methods were used also with [15O]H2O and [15O]O2 (Ter-Pogossian et al., 1969). Usage of short-lived isotopes allows perfusion measurement with equilibrium analysis during constant infusion (Huang et al., 1979). Kety model is not applicable to extracellular contrast media that are used in CT and MR imaging, but the model of Morales and Smith (1948) can be used instead (Brix et al., 1999).

Radiotracers that remain in vascular space cannot be used to measure blood flow (Lassen, 1984). Without an accurate deconvolution method with known local unit impulse residue function, at its best, such tracer can provide an estimate of plasma or blood volume in the tissue, which may vary in the same direction as the plasma flow, and thus appear to correlate with blood flow (Lassen, 1984). For instance, contrast agent based CT perfusion measurements provide variable results depending on the deconvolution method (Ibaraki et al., 2015).

Nutritive vs nonnutritive perfusion

The term blood flow commonly refers to the volume of blood passing through arteries and veins per unit time. Arterial bulk flow can end up in tissue capillaries (nutritive capillary blood flow), or flow into veins through shunts or arterio-venous anastomoses (nonnutritive blood flow). Depending on the blood flow measurement technique, and site of measurement, nutritive and nonnutritive flow may contribute to bulk blood flow with varied shares. For instance, indicator-dilution methods (Meier & Zierler, 1954) estimate the total blood flow. Blood perfusion refers to nutritive capillary blood flow.

When perfusion is measured using diffusible PET radiotracers, such as [15O]H2O, the nonnutritive (noneffective) fraction of blood flow (blood flowing through shunts is not included in the perfusion estimate. The fraction of nonnutritive flow is especially high the in the skin. By definition, in shunts arterial and venous blood concentrations are equal, Ca - Cv = 0, and thus it has no effect on the concentration in tissue, based on the Fick's principle.

However, nonnutritive blood flow will increase the estimate of arterial blood volume, because both the arterial and venous fraction of the shunt volume will have the same kinetics.

Microspheres of different diameters can be used in animal studies to measure nutritive and nonnutritive blood flow.

Effect on radiotracer uptake

Tissue perfusion has two conflicting effects on the uptake of the radiopharmaceutical: delivery of the tracer molecules is directly proportional to the perfusion, but, once delivered, chances of tissue extraction of the tracer molecule decreases with increasing perfusion. Depending on the relative rates of blood flow and transport, the effect of perfusion can range between two extremes: the uptake rate can be determined entirely by perfusion (perfusion-limited), or it can be essentially independent of perfusion and determined only by transport (Holden, 1985). Tracers that meet the first condition are perfect for measurement of perfusion, but useless for anything else. Most PET radiopharmaceuticals are in the middle-ground. Capillary walls and endothelial cells can be very different in different organs. Blood-brain barrier limits the transport of most radiopharmaceuticals, making the uptake less perfusion-dependent, but in another tissue the uptake may be perfusion-limited, and therefore useless for measuring any step beyond perfusion step. Uptake can be transport- or diffusion-limited at high blood flow, but perfusion-limited at low blood flow (Peters & Jamar, 1998).

Several capillary-tissue transport models have been presented and can be used for simulations (Sawada et al., 1991; Logan et al., 1994).


See also:


References:

Alpert NM, Eriksson L, Chang JY, Bergstrom M, Litton JE, Correia JA, Bohm C, Ackerman RH, Taveras JM. Strategy for the measurement of regional cerebral blood flow using short-lived tracers and emission tomography. J Cereb Blood Flow Metab. 1984; 4(1): 28-34. doi: 10.1038/jcbfm.1984.4.

Holden JE. Effects of blood flow on the positron-emission tomographic determination of substrate transport rates. Circulation 1985; 72(5 Pt 2): IV72-IV76. PMID: 3876895.

Huang S-C, Carson RE, Phelps ME. Measurement of local blood flow and distribution volume with short-lived isotopes: a general input technique. J Cereb Blood Flow Metab. 1982; 2: 99-108. doi: 10.1038/jcbfm.1982.11.

Jones SC, Greenberg JH, Dann R, Robinson GD Jr, Kushner M, Alavi A, Reivich M. Cerebral blood flow with the continuous infusion of oxygen-15-labeled water. J Cereb Blood Flow Metab. 1985; 5: 566-575. doi: 10.1038/jcbfm.1985.85.

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. doi: 10.1152/ajplegacy.1945.143.1.53.

Kety SS. Regional cerebral blood flow: estimation by means of nonmetabolized diffusible tracers - and overview. Semin Nucl Med. 1985; 15(4): 324-328. doi: 10.1016/S0001-2998(85)80010-6.

Koeppe RA, Holden JE, Ip WR. Performance comparison of parameter estimation techniques for the quantification of local cerebral blood flow by dynamic positron emission tomography. J Cereb Blood Flow Metab. 1985; 5: 224-234. doi: 10.1038/jcbfm.1985.29.

Lassen NA. Cerebral transit of an intravascular tracer may allow measurement of regional blood volume but not regional blood flow. J Cereb Blood Flow Metab. 1984; 4: 633-634. doi: 10.1038/jcbfm.1984.90.

Lassen N.A., Henriksen O. (1983) Tracer Studies of Peripheral Circulation. In: Lambrecht R.M., Rescigno A. (eds.) Tracer Kinetics and Physiologic Modeling. Lecture Notes in Biomathematics, vol 48. Springer, Berlin, Heidelberg. doi: 10.1007/978-3-642-50036-7_5.

LeBlanc AD, Riley RC, Robinson RG. Simultaneous measurement of total and nutritional coronary blood flow in dogs. Circulation 1974; 49(2): 338-347.

Meier P, Zierler KL. On the theory of the indicator-dilution method for measurement of blood flow and volume. J Appl Physiol. 1954; 6(12): 731-744. doi: 10.1152/jappl.1954.6.12.731.

Sharp PF. The measurement of blood flow in humans using radioactive tracers. Physiol Meas. 1994; 15: 339-379.

Traystman RJ. The paper that completely altered our thinking about cerebral blood flow measurement. J Appl Physiol. 2004; 97: 1601-1602. doi: 10.1152/classicessays.00023.2004.

Zierler KL. Equations for measuring blood flow by external monitoring of radioisotopes. Circ Res. 1965; 16: 309-321. doi: 10.1161/01.res.16.4.309.



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Updated at: 2019-01-16
Created at: 2014-04-07
Written by: Vesa Oikonen