PET imaging of spinal cord
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 gray 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.
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, causing partial volume effects. 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.
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, 2014).
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, 2014).
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 model (Radu et al., 2007; Buck et al., 2012). Buck et al. (2012) used also [18F]FLT to study proliferative activity, and [18F]FET, representing amino acid transport and protein synthesis rate.
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.
Spinal cord blood volume (SCBV) in humans has been measured using MRI and Gd-DTPA (Lu et al., 2007), 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).
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, gray 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 gray 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 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).
Abourbeh G, Thézé B, Maroy R, Dubois A, Brulon V, Fontyn Y, Dollé F, Tavitian B, Boisgard R. Imaging microglial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by positron emission tomography using the mitochondrial 18 kDa translocator protein radioligand [18F]DPA-714. J Neurosci. 2012; 32(17): 5728-5736.
Bingham WG, Goldman H, Friedman SJ, Murphy S, Yashon D, Hunt WE. Blood flow in normal and injured monkey spinal cord. J Neurosurg. 1975; 43: 162-171.
Bisdas S, Rumboldt Z, Surlan K, Koh TS, Deveikis J, Spampinato MV. Perfusion CT measurements in healthy cervical spinal cord: feasibility and repeatability of the study as well as interchangeability of the perfusion estimates using two commercially available software packages. Eur Radiol. 2008; 18(10): 2321-2328.
Buck D, Förschler A, Lapa C, Schuster T, Vollmar P, Korn T, Nessler S, Stadelmann C, Drzezga A, Buck AK, Wester HJ, Zimmer C, Krause BJ, Hemmer B. 18F-FDG PET detects inflammatory infiltrates in spinal cord experimental autoimmune encephalomyelitis lesions. J Nucl Med. 2012; 53(8): 1269-1276.
Chong A, Song HC, Byun BH, Hong SP, Min JJ, Bom HS, Ha JM, Lee JK. Changes in 18F-fluorodeoxyglucose uptake in the spinal cord in a healthy population on serial positron emission tomography/computed tomography. Chonnam Med J. 2013; 49(1): 38-42.
Figley CR, Stroman PW. Investigation of human cervical and upper thoracic spinal cord motion: implications for imaging spinal cord structure and function. Magn Reson Med. 2007; 58: 185-189.
Flanagan EP, Hunt CH, Lowe V, Madrekar J, Pittock SJ, O’Neill BP, Keegan BM. [18F]-Fluorodeoxyglucose-positron emission tomography in patients with active myelopathy. Mayo Clinic Proc. 2013; 88(11): 1204-1212.
Floeth FW, Stoffels G, Herdmann J, Eicker S, Galldiks N, Rhee S, Steiger HJ, Langen KJ. Prognostic value of 18F-FDG PET in monosegmental stenosis and myelopathy of the cervical spinal cord. J Nucl Med. 2011; 52(9): 1385-1391.
Floeth FW, Galldiks N, Eicker S, Stoffels G, Herdmann J, Steiger HJ, Antoch G, Rhee S, Langen KJ. Hypermetabolism in 18F-FDG PET predicts favorable outcome following decompressive surgery in patients with degenerative cervical myelopathy. J Nucl Med. 2013;54(9): 1577-1583.
Gage HD, Gage JC, Tobin JR, Chiari A, Tong C, Xu Z, Mach RH, Efange SM, Ehrenkaufer RL, Eisenach JC. Morphine-induced spinal cholinergic activation: in vivo imaging with positron emission tomography. Pain 2001; 91(1-2): 139-145.
Goto N, Otsuka N. Development and anatomy of the spinal cord. Neuropathology 1997; 17: 25-31.
Harakawa I, Yano T, Sakurai T, Nishikimi N, Nimura Y. Measurement of spinal cord blood flow by an inhalation method and intraarterial injection of hydrogen gas. J Vasc Surg. 1997; 26: 623-628.
Høy K, Hansen ES, He SZ, Soballe K, Henriksen TB, Kjolseth D, Hjortdal V, Bunger C. Regional blood flow, plasma volume, and vascular permeability in the spinal cord, the dural sac, and lumbar nerve roots. Spine 1994; 19(24): 2804-2811.
Imamoto N, Momosaki S, Fujita M, Omachi S, Yamato H, Kimura M, Kanegawa N, Shinohara S, Abe K. [11C]PK11195 PET imaging of spinal glial activation after nerve injury in rats. Neuroimage 2013; 79: 121-128.
Kamoto Y, Sadato N, Yonekura Y, Tsuchida T, Uematsu H, Waki A, Uchida K, Baba H, Imura S, Konishi J. Visualization of the cervical spinal cord with FDG and high-resolution PET. J Comput Assist Tomogr. 1998; 22(3): 487-91.
Kaur J, Khararjian A, Coleman RA, Constantinescu CC, Pan M-L, Mukherjee J. Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using 18F/11C-fallypride. Nucl Med Biol. 2014; 41: 841-847.
Khararjian A, Constantinescu C, Coleman R, Pan M-L, Mukherjee J. Comparative PET imaging of D2/D3 receptors in the rodent spinal cord with [18F]fallypride and [11C]fallypride. J Nucl Med. 2011; 52(Suppl 1): 1193.
Li X-Q, Wang J, Fang B, Tan W-F, Ma H. Intrathecal antagonism of microglial TLR4 reduces inflammatory damage to blood-spinal cord barrier following ischemia/reperfusion injury in rats. Molecular Brain 2014; 7: 28.
Lu H, Law M, Ge Y, Hesseltine SM, Rapalino O, Jensen JH, Helpern JA. Quantitative measurement of spinal cord blood volume in humans using vascular-space-occupancy MRI. NMR Biomed. 2008; 21: 226-232.
Marini C, Cistaro A, Campi C, Calvo A, Caponnetto C, Nobili FM, Fania P, Beltrametti MC, Moglia C, Novi G, Buschiazzo A, Perasso A, Canosa A, Scialò C, Pomposelli E, Massone AM, Bagnara MC, Cammarosano S, Bruzzi P, Morbelli S, Sambuceti G, Mancardi G, Piana M, Chiò A. A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis. Eur J Nucl Med Mol Imaging 2016; 43(11): 2061-2071.
Martirosyan NL, Feuerstein JS, Theodore N, Cavalcanti DD, Spetzler RF, Preul MC. Blood supply and vascular reactivity of the spinal cord under normal and pathological conditions. J Neurosurg Spine 2011; 15: 238-251.
Mautes AEM, Schröck H, Nacimiento AC, Paschen W. Regional spinal cord blood flow and energy metabolism in rats after laminectomy and acute compression injury. Eur J Trauma 2000; 26: 122-130.
Naidich TP, Castillo M, Cha S, Raybaud C, Smirniotopoulos J, Kollias S, Kleinman GM. Imaging of the Spine. 2011, Elsevier, ISBN-13: 9781437715514.
de Paula Faria D, de Vries EF, Sijbesma JW, Dierckx RA, Buchpiguel CA, Copray S. PET imaging of demyelination and remyelination in the cuprizone mouse model for multiple sclerosis: a comparison between [11C]CIC and [11C]MeDAS. Neuroimage 2014; 87: 395-402.
de Paula Faria D, Copray S, Sijbesma JW, Willemsen AT, Buchpiguel CA, Dierckx RA, de Vries EF. PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C]MeDAS, [11C]CIC and [11C]PIB. Eur J Nucl Med Mol Imaging 2014; 41(5): 995-1003.
de Paula Faria D, de Vries EF, Sijbesma JW, Buchpiguel CA, Dierckx RA, Copray SC. PET imaging of glucose metabolism, neuroinflammation and demyelination in the lysolecithin rat model for multiple sclerosis. Mult Scler. 2014; 20(11): 1443-1452.
de Paula Faria D, Vlaming ML, Copray SC, Tielen F, Anthonijsz HJ, Sijbesma JW, Buchpiguel CA, Dierckx RA, van der Hoorn JW, de Vries EF. PET imaging of disease progression and treatment effects in the experimental autoimmune encephalomyelitis rat model. J Nucl Med. 2014; 55: 1330-1335.
Radu CG, Shu CJ, Shelly SM, Phelps ME, Witte ON. Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 2007; 104(6): 1937-1942.
Stroman PW, Wheeler-Kingshott C, Bacon M, Schwab JM, Bosma R, Brooks J, Cadotte D, Carlstedt T, Ciccarelli O, Cohen-Adad J, Curt A, Evangelou N, Fehlings MG, Filippi M, Kelley BJ, Kollias S, Mackay A, Porro CA, Smith S, Strittmatter SM, Summers P, Tracey I. The current state-of-the-art of spinal cord imaging: methods. Neuroimage 2014; 84: 1070-1081.
Uchida K, Kobayashi S, Yayama T, Kokubo Y, Nakajima H, Kakuyama M, Sadato N, Tsuchida T, Yonekura Y, Baba H. Metabolic neuroimaging of the cervical spinal cord in patients with compressive myelopathy: a high-resolution positron emission tomography study. J Neurosurg Spine 2004; 1(1): 72-79.
Uchida K, Nakajima H, Okazawa H, Kimura H, Kudo T, Watanabe S, Yoshida A, Baba H. Clinical significance of MRI/18F-FDG PET fusion imaging of the spinal cord in patients with cervical compressive myelopathy. Eur J Nucl Med Mol Imaging 2012; 39(10): 1528-1537.
Wang X, Duffy P, McGee AW, Hasan O, Gould G, Tu N, Harel NY, Huang Y, Carson RE, Weinzimmer D, Ropchan J, Benowitz LI, Cafferty WB, Strittmatter SM. Recovery from chronic spinal cord contusion after Nogo receptor intervention. Ann Neurol. 2011; 70: 805-821.
Watson C, Paxinos G, Kayalioglu G (eds): The Spinal Cord. Academic Press, 2008.
Wilmshurst JM, Barrington SF, Protchard D, Cox T, Bullock P, Maisey M, Robinson RO. Positron emission tomography in imaging spinal cord tumors. J Child Neurol. 2000; 15: 465-472.
Wheeler-Kingshott CA, Stroman PW, Schwab JM, Bacon M, Bosma R, Brooks J, Cadotte DW, Carlstedt T, Ciccarelli O, Cohen-Adad J, Curt A, Evangelou N, Fehlings MG, Filippi M, Kelley BJ, Kollias S, Mackay A, Porro CA, Smith S, Strittmatter SM, Summers P, Thompson AJ, Tracey I. The current state-of-the-art of spinal cord imaging: applications. Neuroimage 2014; 84: 1082-1093.
Wu C, Zhu J, Baeslack J, Zaremba A, Hecker J, Kraso J, Matthews PM, Miller RH, Wang Y. Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord. Ann Neurol. 2013; 74: 688-698.
Xie L, Yamasaki T, Ichimaru N, Yui J, Kawamura K, Kumata K, Hatori A, Nonomura N, Zhang MR, Li XK, Takahara S. [11C]DAC-PET for noninvasively monitoring neuroinflammation and immunosuppressive therapy efficacy in rat experimental autoimmune encephalomyelitis model. J Neuroimmune Pharmacol. 2012; 7(1): 231-242.
Created at: 2014-06-09
Updated at: 2017-11-18
Written by: Vesa Oikonen