PET imaging of the spleen
The spleen in humans is an oval-shaped organ with size of about 12-15 × 4-8 × 3-4 cm, weighting usually 100-200 grams (ex vivo; in vivo weight is probably higher). Size of the spleen is very variable between individuals, and accessory spleens are very common. Spleen is soft, and pushed against diaphragm by the stomach, left kidney, tail of pancreas, and left flexure of colon. Spleen is surrounded by a capsule of dense connective tissue, with fibroblasts and collagen covered (reticular fiber) trabeculae extending inwards, dividing the cortex of the spleen into lymphatic nodules (follicles). In lymphatic nodules the branches of the splenic artery are surrounded by white pulp (about 5-20% of spleen volume), lymphatic tissue composed of T- and B-lymphocytes and macrophages. Venous sinuses contain large volumes of blood, and are surrounded by splenic cords, together called red pulp. Splenic cords are composed of reticular fibres and erythrocytes, macrophages, lymphocytes, plasma cells, and granulocytes. The size of spleen, mainly red pulp, decreases with ageing.
Blood flow through the spleen is very high, about 5-10% of the cardiac output and 150 mL/min (ranging from 100 to 1200 mL/min) in the resting state. Part of the blood that enters the spleen flows intra-vascularly into the venous sinuses, while another part flows slowly through the lymphatic tissue and extracellular matrix of the red pulp before reaching the venous sinuses. Sinusoids (about 1/3 of the volume of the red pulp) form maze-like structures. Rats and humans have sinusoidal circulation, while mice do not. Endothelium consists of longitudinally arranged cells with adjustable slits, enabling cells to squeeze through into the venous sinuses. Erythrocytes that have lost their deformation capacity cannot pass through the slits and are destroyed by sinusoidal phagocytes. Blood flow through the red pulp is variable, which may lead to apparent heterogeneity in the early phases (<1 min) of imaging. Blood from the splenic vein is drained into the portal vein and into the liver. The spleen does not have afferent lymphatic vessels that lymph nodes have, therefore it collects the white blood cells only from the blood. Lymphatic capillaries and efferent vessels lead to lymph nodes outside of the spleen.
In cats and dogs and other carnivores the capsule of the spleen contains significant smooth muscle mass. Rhythmic contractions pump blood plasma to lymphatics, further concentrating the blood cells in the spleen. In humans the capsule contains only few smooth muscle cells.
The spleen is a reticuloendothelial lymphoid organ specialized in filtering blood and producing components of complement and specific antibodies. About 25% of white blood cells and 30% of platelets in the body are located or stored in the spleen. Blood inside the spleen contains considerably higher numbers (2×) of red blood cells than arterial blood at rest, but during strenuous exercise the extra erythrocytes leave the spleen, contributing to the increased blood haematocrit observed after and during exercise.
Phagocytes in the liver (Kupffer cells) can remove the opsonized particles from blood. The spleen is also able to remove particles such as bacteria, or labelled nanoparticles that are not yet opsonized well or at all, because in the red pulp the phagocytes and antigens are in close contact for relatively long time. The spleen works as a reservoir and nursery for bone marrow derived cells. Monocytes that relocate to the site of tumour or injury such as infarction originate from the spleen.
Splenosis is a benign condition that often develops after splenic rupture. Numerous splenic nodules can be formed in the body, usually in the liver and gut. These nodules may be few centimetres in size, but they usually possess only the functions of the red pulp.
Exercise, arousal, food ingestion, hypoxia (for example breath holding), and injection of catecholamines decreases the size of the spleen. Spleen volume can change rapidly; breath holding for 30 s reduces the volume by 10%, returning to normal after 2 min. Splenic contraction of about 30-40% is observed after maximal breath holding in humans (Espersen et al., 2002). Hematocrit increases subsequently (Laub et al., 1993). Pharmacological or exercise stress during myocardial perfusion imaging (MPI) reduces blood flow to spleen; failure of this response is an indicator of insufficient stress, which is a common cause of false-negative MPI (Bami et al., 2018).
Possible spleen contraction which must be taken into account when imaging splenic function. High and variable haematocrit in the spleen prevents quantification of vascular volume using labelled carbon monoxide.
Perfusion and metabolism
Perfusion of the spleen has been measured using [15O]H2O and [15O]CO2 (Oguro et al., 1993; Taniguchi et al., 1995; Taniguchi et al., 1999; Taniguchi et al., 2001; Kötz et al, 2009). Kötz et al. (2009) reported range 0.84-0.96 for partition coefficient of water, and 1.03-1.96 mL/(min mL) for blood flow in the spleen.
Glucose metabolism in the spleen can be studied with [18F]FDG (Sugawara et al., 1999; Liu, 2009; Pak et al., 2013; Emami et al., 2015; Kalkanis et al., 2016). Activation and reduction in cell proliferation in the spleen can be studied with [18F]FLT (Leimgruber et al., 2014).
Very high uptake of somatostatin receptor tracers is often seen in the spleen, which may hamper imaging of neuroendocrine tumours, and lead to false positives, especially in case of accessory spleen inside or close to other organs. Uptake is highest in the red pulp (Sarikaya et al., 2018), which mainly contains SSTR2 (Boy et al., 2011).
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Created at: 2016-02-08
Updated at: 2018-10-10
Written by: Vesa Oikonen