Labelled microspheres can be used to quantify tissue perfusion and blood flow distribution (Prinzen & Bassingthwaighte, 2000). Larger microspheres that are trapped in the precapillary arterioles measure total blood flow in the tissue, and smaller microspheres which are only trapped in the capillaries measure the nutritive blood flow. Microsphere method is not commonly used in humans, because it may cause ischemic organ damage. Microspheres can be used to validate the PET perfusion tracers, usually in animal studies (Kairento et al., 1983). Microspheres can be labelled with radionuclides, or alternatively with fluorescent dyes (Glenny et al., 1993). Albumin macroaggregates (MAA) have the advantage of being metabolized (Zolle et al., 1970). For instance, 131I- and 99mTc-labelled albumin macroaggregates have been commercially available and used for studying myocardial function and pulmonary perfusion and perfusion distribution in dogs (Poe, 1971; Schelbert et al., 1971; Richmond et al., 1973) and humans (Rhodes et al., 1973; Grames et al., 1974; Baker et al., 1984; Del Torso et al., 1985), and concluded to be safe.
For PET imaging, MAA has been labelled with 68Ga and 64Cu for perfusion imaging in dogs (Hnatowich, 1976; Wisenberg et al., 1981), rabbits (Kairento et al., 1983), rats (Richter et al., 2010; Boś et al., 2012; Amor-Coarasa et al., 2014) baboons (Steinling et al., 1985), and humans (Schuster et al., 1995). MAA has been covalently labelled with [11C]CH3-groups (Turton et al., 1984), and used to measure perfusion in humans (Wilson et al., 1984; Brooks et al., 1986; Selwyn et al., 1986). 68Ga-MAA could be used in human studies as surrogate for 99mTc-MAA microspheres (Matthies et al., 2008; Maus et al., 2011).
The microspheres are injected into the left atrium or left ventricle of the heart to avoid initial trapping in the lungs but allowing dispersion via the circulation into organs according to the distribution of the cardiac output (CO). Blood sample is collected from an artery (usually femoral artery) using a flow-rate controlled pump during the time that it takes for the microspheres to be completely distributed into tissues (usually 2-3 minutes). The organ is then removed, weighed, and its radioactivity is measured. Alternatively, radioactivity concentration can be measured with PET, if microspheres are labelled with positron-emitting isotope.
Organ perfusion (blood flow, f) can then be calculated in units mL/min per organ from the equation
, where Fs is the pump flow rate (mL/min), Atis is the radioactivity of the dissected organ, and Ab is the activity of the blood sample.
Alternatively, if radioactivity concentration in tissue (sample) was measured, either by weighing the tissue sample or by PET, the perfusion can be calculated in units mL/(min*g) or mL/(min*mL) from similar equation:
, where Ctis is the radioactivity concentration in the tissue sample (radioactivity per gram or mL).
Also cardiac output can be calculated in units mL/min from equation
, where Atot is the total radioactivity of the injected microspheres.
Kairento AL, Brownell GL, Schluederberg J, Elmaleh DR. Regional blood-flow measurement in rabbit soft-tissue tumor with positron imaging using the C15O2 steady-state and labeled microspheres. J Nucl Med. 1983; 24(12): 1135-1142. PMID: 6417285.
Prinzen FW, Bassingthwaighte JB. Blood flow distributions by microsphere deposition methods. Cardiovasc Res. 2000; 45(1): 13-21. doi: 10.1016/s0008-6363(99)00252-7.
Updated at: 2023-06-09
Created at: 2015-12-23
Written by: Vesa Oikonen