PET imaging of spinal cord

Anatomy

The length of spinal cord in adults is 40-45 cm, 2/3 of the length of the vertebral canal (Goto and Otsuka, 1997). It can be divided into three or five parts: either cervical, thoracic, and lumbar cords; or cervical (23.3%), thoracic (56.4%), lumbar (13.1%), sacral (7.3%), and coccygeal cords. The spinal cord consists of 31 spinal segments: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal.

In the spinal cord the grey matter (nerve cell bodies, glial cells, and interneurons) is inside a butterfly-shape cross-sectional area at the centre of the cord, surrounded by white matter (Stroman et al., 2014). The front "horns" contain motor nerve cells, which transmit information from the brain to muscles. The back horns contain sensory nerve cells, which transmit sensory information from other parts of the body to the brain. Transverse area of the spinal cord is about 40-50 mm2 in cervical cord, 25-30 mm2 in thoracic cord, and 30-40 mm2 in lumbar cord. Fractions of white and grey matter are about 30-50% and 6-10% in cervical, 20-30% and 2.5-6% in thoracic, and 15-25% and 8-14% in lumbar cords (Goto and Otsuka, 1997).

The cerebrospinal fluid (CSF) flows back and forth with each heart beat, with a peak flow speak of roughly 3 cm/s. Net flow is down one side and up the other side of the spinal cord (Stroman et al., 2014). The pulsation of CSF flow causes the spinal cord to move within the spinal canal. Movement is higher towards the head, but still only around 0.5 mm (Figley and Stroman, 2007). Blood supply of spinal cord has been reviewed by Martirosyan et al (2011).

Imaging

Spinal cord is part of the central nervous system (CNS), and is protected by blood-spinal cord barrier (BSCB), like the brain by blood-brain barrier (BBB), leading to low uptake of many of the radioactive metabolites of PET tracers, which often are a problem in analysis of organs other than the brain.

PET imaging of the spinal cord is technically challenging because of the small cross-sectional size (diameter ∼1 cm), causing partial volume effects, including spill-in from vertebral bone marrow (Gupta, 2013). Another problem is the respiratory and cardiac motion during the scan. Due to these, subregions of spinal cord can not be separated in the PET data. Despite of these hindrances, [18F]FDG PET/MRI is considered sufficiently reliable for detecting and quantifying abnormalities in spinal cord for clinical use (Gupta, 2013; Cizkova et al., 2020).

Preclinical studies

Myelin content of spinal cord has been measured in rat and mouse model using amyloid tracer [11C]MeDAS (Wu et al., 2013; de Paula Faria et al., 2014a and 2014b).

Microglial activation has been studied in rat model using TSPO ligands [18F]DPA-714 (Abourbeh et al., 2012), [11C]DAC (Xie et al., 2012), and [11C]PK11195 (Imamoto et al., 2013; de Paula Faria et al., 2014c).

Vesicular acetylcholine transporters in spinal cord were studied in rhesus monkeys using [18F]FBT by Gage et al (2001), using cerebellum as the reference region.

Serotonin transporters in spinal cord have been studied with [11C]AFM in rat model of spinal cord damage and recovery, with blocking study to subtract nonspecific uptake (Wang et al., 2011).

Dopamine D2/D3 receptor binding has been measured in rats using [11C]- and [18F]fallypride (Khararjian et al., 2011; Kaur et al., 2014).

[18F]FDG has been used to study glucose utilization in rat models (Radu et al., 2007; Buck et al., 2012; Ling et al., 2015). Buck et al (2012) used also [18F]FLT to study proliferative activity, and [18F]FET, representing amino acid transport and protein synthesis rate.

Clinical PET

Several studies on FDG uptake in patients with stenosis or myelopathy have been published, for example by Kamoto et al (1998), Floeth et al (2011 and 2013), Uchida et al (2004 and 2012), and Flanagan et al (2013). Marini et al (2016) studied ALS patients with PET/CT, using CT to identify image voxels of the spinal cord and spinal canal; SUV values were normalized using the SUV of liver. Normalization of the uptake to liver is recommended for multicentre studies (Aiello et al., 2020).

Normal variation of FDG uptake between different sections of spinal cord has been reported by Chong et al., 2013. PET studies have shown inconsistent results about the impact of gender, age, BMI, and blood glucose level on SUVmax of the spinal cord (Aiello et al., 2020).

Tumours in spinal cord have been studied with FDG and [11C]methionine (Wilmshurst et al., 2000).

Blood volume

Spinal cord blood volume (SCBV) in humans has been measured using MRI and Gd-DTPA (Lu et al., 2008), giving an estimate of 4.3±0.7 mL blood/100 mL tissue in the central portion of the spinal cord, mostly representing the grey matter. Høy et al (1994) measured the plasma volume of spinal cord in dogs using radiolabelled plasma proteins, and found it to be 0.85 mL plasma/100 g tissue; this would suggest that blood volume would be markedly lower than the estimate of Lu et al., but it may be explained by higher white matter portion, and also blood flow measured with microspheres was low, 10 mL×(100 g)-1×min-1 (Høy et al., 1994).

Perfusion

Spinal cord blood flow (SCBF) has been measured in pigs using microspheres, and it was found found to be around 60 mL×(100 g wet tissue)-1×min-1 (Kreyer et al., 2010).

Harakawa et al (1997) used hydrogen clearance technique to measure blood flow in the subregions of spinal cord in dogs. Blood flow was: gray matter 46±7 ; white matter 25 ± 7 ; intrathecal space 43 ± 0 ; and epidural space 11 ± 2 mL×(100 g)-1×min-1.

Bingham et al (1975) measured the SCBF in monkeys using antipyrine-14C method. SCBF in cervical cord was 48 and 20 mL×(100 g)-1×min-1 in grey and white matter, respectively, and in total spinal cord about 26 mL×(100 g)-1×min-1. In thoracic cord SCBF was lower, about 40 (gray matter), 16 (white matter), and 20 (total) mL×(100 g)-1×min-1. In lumbar cord the SCBF was about 44, 22, and 27 mL×(100 g)-1×min-1, respectively. Thus, grey matter perfusion is roughly 2 - 2.5 times that of the white matter. In thoracic cord the white:gray tissue ratio is about 5. Vasculature in grey matter was about six times greater than that of the white matter (Bingham et al., 1975). These perfusion values may be underestimated because of the permeability limitation of [14]antipyrine (Eckman et al., 1975). Autoradiographic perfusion images of spinal cord in rats are provided in the study by Mautes et al (2000).

Bisdas et al (2008) measured SCBF in human cervical spinal cord (total) using perfusion CT; median over subjects was low, about 6 mL×(100 g)-1×min-1. Similar results were reported by the same group later, with mean SCBF 8.7±7.6 mL×(100 g)-1×min-1 and SCBV 1.2±1 mL×(100 g)-1 (Spampinato et al., 2010). Quantitativity of the applied perfusion CT method has not been validated.

Spinal cord water volume was about 77% in rats (Li et al., 2014).

Inflammation

Spinal neuroimmune activation has a role in the pathogenesis of chronic pain. Increased uptake of inflammation marker [11C]PBR28 has been observed in relevant regions of spinal cord and neurofamina (containing dorsal root ganglion and nerve roots) in chronic radicular pain patients (Albrecht et al., 2018).


See also:



References:

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Updated at: 2021-04-19
Created at: 2014-06-09
Written by: Vesa Oikonen