Abstract
Contrast media are pharmaceuticals commonly used to improve the visualization of radiological images. Contrast-enhanced imaging provides, noninvasively, anatomical, functional, and metabolic information on tissues and organs in vivo, offering a powerful tool to investigate both physiological and pathological processes. Particularly for neurology, the development of new contrast media has drastically improved our knowledge of the central nervous system (CNS) and has facilitated the diagnosis of many common brain diseases. In this chapter, we will focus on contrast agents (CAs) for magnetic resonance (MR) and nuclear imaging and their applications in neurology and basic neuroscience.
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Abbreviations
- ASL:
-
Arterial spin labeling
- CEST:
-
Chemical exchange
- CNS:
-
Central nervous system
- CT:
-
Computed tomography
- DCE:
-
Dynamic contrast enhancement
- DOTATOC:
-
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-tyrosine-3-octreotide
- DTI:
-
Diffusion tensor imaging
- DTPA:
-
Diethylene-triamine-pentacetate
- DWI:
-
Diffusion-weighted imaging
- FDG:
-
2-fluoro-2-deoxy-D-glucose
- FET:
-
Fluoroethyl-tyrosine
- fMRI:
-
Functional MRI
- MRI:
-
Magnetic resonance imaging
- NMR:
-
Nuclear magnetic resonance imaging
- PET:
-
Positron emission tomography
- SPECT:
-
Single-photon emission computed tomography
- T1w:
-
T1 weighted
- T2*:
-
T2 star
- T2w:
-
T2 weighted
- FAZA:
-
Fluoroazomycin-arabinoside
References
Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333
Bauer WM, Fenzl G, Vogl T, Fink U, Lissner J (1988) Indications for the use of Gd-Dtpa in Mri of the central nervous system – experiences in patients with cerebral and spinal-diseases. Invest Radiol 23:S286–S288
Aime S, Botta M, Fasano M, Terreno E (1998) Lanthanide(III) chelates for NMR biomedical applications. Chem Soc Rev 27:19–29
Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 99:2293–2352
Idee JM, Port M, Robic C, Medina C, Sabatou M, Corot C (2009) Role of thermodynamic and kinetic parameters in gadolinium chelate stability. J Magn Reson Imaging 30:1249–1258
Giesel FL, Mehndiratta A, Essig M (2010) High-relaxivity contrast-enhanced magnetic resonance neuroimaging: a review. Eur Radiol 20:2461–2474
Bendszus M, Ladewig G, Jestaedt L, Misselwitz B, Solymosi L, Toyka K, Stoll G (2008) Gadofluorine M enhancement allows more sensitive detection of inflammatory CNS lesions than T2-w imaging: a quantitative MRI study. Brain 131:2341–2352
Le Duc G, Roux S, Paruta-Tuarez A, Dufort S, Brauer E, Marais A, Truillet C, Sancey L, Perriat P, Lux F, Tillement O (2014) Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment. Cancer Nanotechnol 5:4
Essig M, Nikolaou K, Meaney JF (2007) Magnetic resonance angiography of the head and neck vessels. Eur Radiol 17(Suppl 2):B30–B37
Chen JW, Breckwoldt MO, Aikawa E, Chiang G, Weissleder R (2008) Myeloperoxidase-targeted imaging of active inflammatory lesions in murine experimental autoimmune encephalomyelitis. Brain 131:1123–1133
Breckwoldt MO, Chen JW, Stangenberg L, Aikawa E, Rodriguez E, Qiu S, Moskowitz MA, Weissleder R (2008) Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci U S A 105:18584–18589
Forghani R, Wojtkiewicz GR, Zhang YN et al (2012) Demyelinating diseases: myeloperoxidase as an imaging biomarker and therapeutic target. Radiology 263:451–460
Weinstein JS, Varallyay CG, Dosa E, Gahramanov S, Hamilton B, Rooney WD, Muldoon LL, Neuwelt EA (2010) Superparamagnetic iron oxide nanoparticles: diagnostic magnetic resonance imaging and potential therapeutic applications in neurooncology and central nervous system inflammatory pathologies, a review. J Cereb Blood Flow Metab 30:15–35
Saleh A, Schroeter M, Ringelstein A, Hartung HP, Siebler M, Modder U, Jander S (2007) Iron oxide particle-enhanced MRI suggests variability of brain inflammation at early stages after ischemic stroke. Stroke 38:2733–2737
Vellinga MM, Engberink RDO, Seewann A, Pouwels PJW, Wattjes MP, van der Pol SMA, Pering C, Polman CH, de Vries HE, Geurts JJG, Barkhof F (2008) Pluriformity of inflammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement. Brain 131:800–807
Farrell BT, Hamilton BE, Dosa E, Rimely E, Nasseri M, Gahramanov S, Lacy CA, Frenkel EP, Doolittle ND, Jacobs PM, Neuwelt EA (2013) Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL. Neurology 81:256–263
Dousset V, Brochet B, Deloire MSA, Lagoarde L, Barroso B, Caille JM, Petry KG (2006) MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium. Am J Neuroradiol 27:1000–1005
Michalska M, Machtoub L, Manthey HD, Bauer E, Herold V, Krohne G, Lykowsky G, Hildenbrand M, Kampf T, Jakob P, Zernecke A, Bauer WR (2012) Visualization of vascular inflammation in the atherosclerotic mouse by ultrasmall superparamagnetic iron oxide vascular cell adhesion molecule-1-specific nanoparticles. Arterioscler Thromb Vasc Biol 32:2350–2357
Frechou M, Beray-Berthat V, Raynaud JS, Meriaux S, Gombert F, Lancelot E, Plotkine M, Marchand-Leroux C, Ballet S, Robert P, Louin G, Margaill I (2013) Detection of vascular cell adhesion molecule-1 expression with USPIO-enhanced molecular MRI in a mouse model of cerebral ischemia. Contrast Media Mol Imaging 8:157–164
Montagne A, Gauberti M, Macrez R, Jullienne A, Briens A, Raynaud JS, Louin G, Buisson A, Haelewyn B, Docagne F, Defer G, Vivien D, Maubert E (2012) Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders. Neuroimage 63:760–770
Guivel-Scharen V, Sinnwell T, Wolff SD, Balaban RS (1998) Detection of proton chemical exchange between metabolites and water in biological tissues. J Magn Reson 133:36–45
Sun PZ, Benner T, Copen WA, Sorensen AG (2010) Early experience of translating pH-weighted MRI to image human subjects at 3 Tesla. Stroke 41:S147–S151
McVicar N, Li AX, Goncalves DF, Bellyou M, Meakin SO, Prado MA, Bartha R (2014) Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI. J Cereb Blood Flow Metab 34:690–698
Dula AN, Asche EM, Landman BA, Welch EB, Pawate S, Sriram S, Gore JC, Smith SA (2011) Development of chemical exchange saturation transfer at 7 T. Magn Reson Med 66:831–838
Ross BD, Bhattacharya P, Wagner S, Tran T, Sailasuta N (2010) Hyperpolarized MR imaging: neurologic applications of hyperpolarized metabolism. Am J Neuroradiol 31:24–33
Marjanska M, Iltis I, Shestov AA, Deelchand DK, Nelson C, Ugurbil K, Henry PG (2010) In vivo 13C spectroscopy in the rat brain using hyperpolarized [1-(13)C]pyruvate and [2-(13)C]pyruvate. J Magn Reson 206:210–218
Park JM, Recht LD, Josan S, Merchant M, Jang T, Yen YF, Hurd RE, Spielman DM, Mayer D (2013) Metabolic response of glioma to dichloroacetate measured in vivo by hyperpolarized (13)C magnetic resonance spectroscopic imaging. Neuro Oncol 15:433–441
Karlsson M, Jensen PR, in ’t Zandt R, Gisselsson A, Hansson G, Duus JO, Meier S, Lerche MH (2010) Imaging of branched chain amino acid metabolism in tumors with hyperpolarized 13C ketoisocaproate. Int J Cancer 127:729–736
Nelson SJ, Kurhanewicz J, Vigneron DB et al (2013) Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(13)C]pyruvate. Sci Transl Med 5:198ra108
Sabri O, Seibyl J, Rowe C, Barthel H (2015) Beta-amyloid imaging with florbetaben. Clin Transl Imaging 3:13–26
Dierckx RA, Otte A, de Vries EFJ, van Waarde A, Leenders KL (2014) PET and SPECT in neurology. Springer, Berlin
Wadsworth H, Jones PA, Chau WF et al (2012) [18F]-GE-180: a novel fluorine-18 labelled PET tracer for imaging translocator protein 18 kDa (TSPO). Bioorg Med Chem Lett 22:1308–1313
Weichert JP, Clark PA, Kandela IK et al (2014) Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy. Sci Transl Med 6:240ra275
Barret O, Thomae D, Tavares A, Alagille D, Papin C, Waterhouse R, McCarthy T, Jennings D, Marek K, Russell D, Seibyl J, Tamagnan G (2014) In vivo assessment and dosimetry of 2 novel PDE10A PET radiotracers in humans: [18F]-MNI-659 and [18F]-MNI-654. J Nucl Med 55:1297–1304
Blasi F, Oliveira BL, Rietz TA, Rotile NJ, Day H, Looby RJ, Ay I, Caravan P (2014) Effect of chelate type and radioisotope on the imaging efficacy of 4 fibrin-specific PET probes. J Nucl Med 55:1157–1163
Wey HY, Wang C, Schroeder FA, Logan J, Price JC, Hooker JM (2015) Kinetic analysis and quantification of [11C]-Martinostat for in vivo HDAC imaging of the brain. ACS Chem Neurosci 6:708–715
Prinz M, Priller J (2014) Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci 15:300–312
Chauveau F, Boutin H, Van Camp N, Dolle F, Tavitian B (2008) Nuclear imaging of neuroinflammation: a comprehensive review of [11C]-PK11195 challengers. Eur J Nucl Med Mol Imaging 35:2304–2319
Dickens AM, Vainio S, Marjamaki P, Johansson J, Lehtiniemi P, Rokka J, Rinne J, Solin O, Haaparanta-Solin M, Jones PA, Trigg W, Anthony DC, Airas L (2014) Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers [11C]-(R)-PK11195 and [18F]-GE-180. J Nucl Med 55:466–472
Boutin H, Murray K, Pradillo J, Maroy R, Smigova A, Gerhard A, Jones PA, Trigg W (2015) [18F]-GE-180: a novel TSPO radiotracer compared to [11C]-R-PK11195 in a preclinical model of stroke. Eur J Nucl Med Mol Imaging 42:503–511
Wickstrom T, Clarke A, Gausemel I, Horn E, Jorgensen K, Khan I, Mantzilas D, Rajanayagam T, in ’t Veld DJ, Trigg W (2014) The development of an automated and GMP compliant FASTlab Synthesis of [18F]GE-180; a radiotracer for imaging translocator protein (TSPO). J Labelled Comp Radiopharm 57:42–48
Morris ZS, Weichert JP, Saker J, Armstrong EA, Besemer A, Bednarz B, Kimple RJ, Harari PM (2015) Therapeutic combination of radiolabeled CLR1404 with external beam radiation in head and neck cancer model systems. Radiother Oncol 116:504–509
Grudzinski JJ, Titz B, Kozak K, Clarke W, Allen E, Trembath L, Stabin M, Marshall J, Cho SY, Wong TZ, Mortimer J, Weichert JP (2014) A phase 1 study of [131I]-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety. PLoS One 9:e111652
Reiner A, Albin RL, Anderson KD, D’Amato CJ, Penney JB, Young AB (1988) Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci U S A 85:5733–5737
Russell DS, Barret O, Jennings DL, Friedman JH, Tamagnan GD, Thomae D, Alagille D, Morley TJ, Papin C, Papapetropoulos S, Waterhouse RN, Seibyl JP, Marek KL (2014) The phosphodiesterase 10 positron emission tomography tracer, [18F]-MNI-659, as a novel biomarker for early Huntington disease. JAMA Neurol 71:1520–1528
Ay I, Blasi F, Rietz TA, Rotile NJ, Kura S, Brownell AL, Day H, Oliveira BL, Looby RJ, Caravan P (2014) In vivo molecular imaging of thrombosis and thrombolysis using a fibrin-binding positron emission tomographic probe. Circ Cardiovasc Imaging 7:697–705
Blasi F, Oliveira BL, Rietz TA, Rotile NJ, Naha PC, Cormode DP, Izquierdo-Garcia D, Catana C, Caravan P (2015) Multisite thrombus imaging and fibrin content estimation with a single whole-body PET scan in rats. Arterioscler Thromb Vasc Biol 35:2114–2121
Blasi F, Oliveira BL, Rietz TA, Rotile NJ, Day H, Naha PC, Cormode DP, Izquierdo-Garcia D, Catana C, Caravan P (2015) Radiation dosimetry of the fibrin-binding probe 64Cu-FBP8 and its feasibility for PET imaging of deep vein thrombosis and pulmonary embolism in rats. J Nucl Med 56:1088–1093
Wang C, Schroeder FA, Wey HY, Borra R, Wagner FF, Reis S, Kim SW, Holson EB, Haggarty SJ, Hooker JM (2014) In vivo imaging of histone deacetylases (HDACs) in the central nervous system and major peripheral organs. J Med Chem 57:7999–8009
Wang C, Schroeder FA, Hooker JM (2014) Visualizing epigenetics: current advances and advantages in HDAC PET imaging techniques. Neuroscience 264:186–197
Catana C, Drzezga A, Heiss WD, Rosen BR (2012) PET/MRI for neurologic applications. J Nucl Med 53:1916–1925
Drzezga A, Barthel H, Minoshima S, Sabri O (2014) Potential clinical applications of PET/MR imaging in neurodegenerative diseases. J Nucl Med 55:47S–55S
Catana C, Guimaraes AR, Rosen BR (2013) PET and MR imaging: the odd couple or a match made in heaven? J Nucl Med 54:815–824
Werner P, Barthel H, Drzezga A, Sabri O (2015) Current status and future role of brain PET/MRI in clinical and research settings. Eur J Nucl Med Mol Imaging 42:512–526
Besson FL, La Joie R, Doeuvre L, Gaubert M, Mezenge F, Egret S, Landeau B, Barre L, Abbas A, Ibazizene M, de La Sayette V, Desgranges B, Eustache F, Chetelat G (2015) Cognitive and brain profiles associated with current neuroimaging biomarkers of preclinical Alzheimer’s disease. J Neurosci 35:10402–10411
Wey HY, Catana C, Hooker JM, Dougherty DD, Knudsen GM, Wang DJ, Chonde DB, Rosen BR, Gollub RL, Kong J (2014) Simultaneous fMRI-PET of the opioidergic pain system in human brain. Neuroimage 102(Pt 2):275–282
Yau WY, Tudorascu DL, McDade EM et al (2015) Longitudinal assessment of neuroimaging and clinical markers in autosomal dominant Alzheimer’s disease: a prospective cohort study. Lancet Neurol 14:804–813
Filss CP, Galldiks N, Stoffels G, Sabel M, Wittsack HJ, Turowski B, Antoch G, Zhang K, Fink GR, Coenen HH, Shah NJ, Herzog H, Langen KJ (2014) Comparison of [18F]-FET PET and perfusion-weighted MR imaging: a PET/MR imaging hybrid study in patients with brain tumors. J Nucl Med 55:540–545
Henriksen OM, Larsen VA, Muhic A, Hansen AE, Larsson HB, Poulsen HS, Law I (2015) Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [18F]-fluoroethyltyrosine (FET) PET/MRI: feasibility, agreement and initial experience. Eur J Nucl Med Mol Imaging 43(1):103–112
Larsen VA, Simonsen HJ, Law I, Larsson HB, Hansen AE (2013) Evaluation of dynamic contrast-enhanced T1-weighted perfusion MRI in the differentiation of tumor recurrence from radiation necrosis. Neuroradiology 55:361–369
Walter HL, Walberer M, Rueger MA, Backes H, Wiedermann D, Hoehn M, Neumaier B, Graf R, Fink GR, Schroeter M (2015) In vivo analysis of neuroinflammation in the late chronic phase after experimental stroke. Neuroscience 292:71–80
Belloli S, Brioschi A, Politi LS, Ronchetti F, Calderoni S, Raccagni I, Pagani A, Monterisi C, Zenga F, Zara G, Fazio F, Mauro A, Moresco RM (2013) Characterization of biological features of a rat F98 GBM model: a PET-MRI study with [18F]-FAZA and [18F]-FDG. Nucl Med Biol 40:831–840
Uppal R, Catana C, Ay I, Benner T, Sorensen AG, Caravan P (2011) Bimodal thrombus imaging: simultaneous PET/MR imaging with a fibrin-targeted dual PET/MR probe–feasibility study in rat model. Radiology 258:812–820
Lewis CM, Graves SA, Hernandez R, Valdovinos HF, Barnhart TE, Cai W, Meyerand ME, Nickles RJ, Suzuki M (2015) 52Mn production for PET/MRI tracking of human stem cells expressing divalent metal transporter 1 (DMT1). Theranostics 5:227–239
Terreno E, Castelli DD, Viale A, Aime S (2010) Challenges for molecular magnetic resonance imaging. Chem Rev 110:3019–3042
Acknowledgments
Dr. Aime acknowledges MIUR (PRIN 2012SK7ASN) and AIRC (Investigator Grant IG 14565) for research support.
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Arena, F., Aime, S., Blasi, F. (2016). Contrast Media. In: Ciarmiello, A., Mansi, L. (eds) PET-CT and PET-MRI in Neurology. Springer, Cham. https://doi.org/10.1007/978-3-319-31614-7_5
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