Molecular imaging and its applications: visualization beyond imagination
Article first published online: 30 OCT 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 127, Issue 5, pages 575–577, December 2013
How to Cite
Williams, S. R., Hausmann, L. and Schulz, J. B. (2013), Molecular imaging and its applications: visualization beyond imagination. Journal of Neurochemistry, 127: 575–577. doi: 10.1111/jnc.12445
- Issue published online: 13 NOV 2013
- Article first published online: 30 OCT 2013
- Manuscript Received: 5 SEP 2013
- Manuscript Accepted: 5 SEP 2013
positron emission spectrometry
The Journal of Neurochemistry has a tradition of publishing new applications of imaging methods and was the journal chosen by Louis Sokoloff to publish his ground-breaking work in 1977 on deoxyglucose (Sokoloff et al., 1977, now cited nearly 5000 times) which established, in a series of classical manuscripts, the principle of glucose positron emission spectrometry. Within a few years of the first reports of NMR spectroscopy in vivo in animals, articles using the technique were being published in Journal of Neurochemistry (Behar et al. 1985a; Hope et al. 1987; Kopp et al. 1984; Nakada et al. 1986). It is no surprise that neuroscience journals now publish a lot of imaging studies, for it is applications to the brain that often provide the best examples of how science can be advanced by imaging. Much of the initial enthusiasm for magnetic resonance imaging (MRI) stemmed from its ability to identify pathology and pathogenesis in multiple sclerosis and stroke; early applications of positron emission spectrometry (PET) were concerned with imaging fluoro-deoxyglucose uptake in the brain; functional imaging with MRI, fluoro-deoxyglucose-PET and water-PET have transformed cognitive neurosciences. Recognizing that this journal is now routinely considered by imaging scientists as a good place to publish their study on the development and application of new imaging methods, the Editor decided it would be useful to bring together this virtual issue on Molecular Imaging, highlighting papers on this topic published in the last few years and asked me to draw up a shortlist (see http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1471-4159/homepage/virtual_issues.htm#molecularimaging).
The first consideration is to ask what constitutes molecular imaging and a good starting place is the World Molecular Imaging Society (WMIS) that defines this on their website http://www.wmis.org/about-us/:
The World Molecular Imaging Society is an international scientific educational organization dedicated to the understanding of biology and medicine through multimodal in vivo imaging of cellular and molecular events involved in normal and pathologic processes and utilization of quantitative molecular imaging in patient care.
This definition is very broad, but if applied strictly would rule out a number of interesting articles which have appeared in Journal of Neurochemistry, because of the insistence on ‘in vivo’ imaging. It is obviously possible to image molecules in tissue slices, cellular preparations and subcellular preparations which are able to provide insights which could not be achieved in vivo. Therefore, we have extended the World Molecular Imaging Society (WMIS) definition to include imaging of tissue and cellular preparations ex vivo. Biophysical imaging of molecular structures is very important for neuroscientists as well as for the understanding of the pathogenesis in neurodegenerative diseases. MRI, for example, images the distribution of the water molecule; hence, the technique underlying even anatomical or structural imaging is molecular. Nevertheless, to simplify selection of manuscripts we have excluded purely anatomical imaging from consideration and restricted ourselves to techniques which fit the WMIS definition of imaging molecular and cellular events. Here, we have chosen from recent articles published since 2010 to represent the latest research involving molecular imaging methods.
The articles cover six imaging methods with detection frequencies ranging from radio magnetic resonance, through optical (fluorescence) to X-ray (Dučić et al. 2013), investigating the distribution of metal ions in dopaminergic neurons) and gamma (PET), with the commonest method being MR (eight papers) followed by mass spectrometry (five papers). The magnetic resonance studies cited not only mainly focus on cerebral glucose, GABA and glutamate metabolism (Bagga et al. 2013; Dodd et al. 2010; Duarte and Gruetter 2012, 2013) but also extend to acetylcholine synthesis (Hall et al. 2013) or other changes in the neurochemical profile (Nilsen et al. 2012; Robertson et al. 2013; Wang et al. 2012). The technique has undeniable relevance for measurements of cerebral blood flow in ischemia and stroke (reviewed in Arsava 2012). A recent work published in Journal of Neurochemistry describes non-invasive imaging markers to detect early changes in spinocerebellar ataxia (Emir et al. 2013), this publication also being put into the context of literature in an Editorial (Mlynarik and McKenna 2013).
An innovative new method is optical stimulated emission depletion that allows super-resolution imaging of subcellular structures, reviewed in (Eggeling et al. 2013). The variety of innovative methods includes visualization of ion channel activity using calcium sensor proteins as was done by (Mironov and Skorova 2011), and we are sure that Journal of Neurochemistry will continue to be a leading source in introducing new technologies.
Mass spectrometry applications range from membrane-level imaging of specific fatty acids (Amaya et al. 2011), phospholipids, gangliosides (Sparvero et al. 2010; Valdes-Gonzalez et al. 2011) or fusion-pore expansion in real-time (reviewed by (Anantharam et al. 2012), radio-labeling of cannabinoid receptors (Mu et al. 2013) to whole-tissue level, for example, imaging of postmortem spinal tissue with relevance to amyotrophic lateral sclerosis (Hanrieder et al. 2013). The use of mass spectrometry in imaging is a relatively new development and it is restricted to being used ex vivo, yet its superb specificity and unrivalled sensitivity are finding increasing use in understanding molecular and cellular events at a neurochemical level. Reflecting our departure from the WMIS definition of in vivo imaging, just under half the articles describe experiments ex vivo.
Selective radioligands used in PET can bind for example, to β-amyloid plaques and allow visualization of plaque deposition in the brain (Juréus et al., 2010), a leap forward in understanding and eventual treatment of Alzheimer's disease. Similarly, PET can be used to image receptor activity such as metabotropic glutamate receptor type 1 (Fujinaga et al. 2012), serotonergic receptors (Nahimi et al. 2012) and other activities. It is perhaps surprising that there are not many PET articles, but the journal has only published six articles with ‘PET’ in the abstract since 2010: evidently the community unfortunately and against the history of the journal finds other outlets for publishing such type of neurochemical investigation. The MR community has 16 ‘hits’ in the same period.
We hope that imagers and non-imagers alike will find material of interest in this virtual issue and stress that the articles we have chosen are personal choices designed to showcase the breadth of imaging research published in the journal recently. We ask for your understanding if your favourite article (or your own article) has been overlooked in this selection!
Conflict of interest
The authors have no conflict of interest to declare.
- 2011) Small molecule analysis and imaging of fatty acids in the zebra finch song system using time-of-flight-secondary ion mass spectrometry. J. Neurochem. 118, 499–511. , and (
- 2012) Real-time imaging of plasma membrane deformations reveals pre-fusion membrane curvature changes and a role for dynamin in the regulation of fusion pore expansion. J. Neurochem. 122, 661–671. , and (
- 2012) The role of MRI as a prognostic tool in ischemic stroke. J. Neurochem. 123, 22–28. (
- 2013) In vivo NMR studies of regional cerebral energetics in MPTP model of Parkinson's disease: recovery of cerebral metabolism with acute levodopa treatment. J. Neurochem. doi: 10.1111/jnc.12407. , , and (
- 1985a) Effect of hypoglycaemic encephalopathy upon amino acids, high energy phosphates and pHi in the rat brain in vivo: detection by sequential 1H and 31P NMR spectroscopy. J. Neurochem. 44, 1045–1055. , , , , and (
- 2010) Functional magnetic resonance imaging and c-Fos mapping in rats following a glucoprivic dose of 2-deoxy-d-glucose. J. Neurochem. 113, 1123–1132. , and (
- 2012) Characterization of cerebral glucose dynamics in vivo with a four-state conformational model of transport at the blood–brain barrier. J. Neurochem. 121, 396–406. and (
- 2013) Glutamatergic and GABAergic energy metabolism measured in the rat brain by 13C NMR spectroscopy at 14.1 T. J. Neurochem. 126, 579–590. and (
- 2013) X-ray fluorescence analysis of iron and manganese distribution in primary dopaminergic neurons. J. Neurochem. 124, 250–261. , , , , and (
- 2013) STED microscopy of living cells - new frontiers in membrane and neurobiology. J. Neurochem. 126, 203–212. , and (
- 2013) Noninvasive detection of neurochemical changes prior to overt pathology in a mouse model of spinocerebellar ataxia type 1. J Neurochem. doi: 10.1111/jnc.12435. , , , and (
- 2012) Characterization of 1-(2-[18F] fluoro-3-pyridyl)-4-(2-isopropyl-1-oxo- isoindoline-5-yl)-5-methyl-1H-1,2,3-triazole, a PET ligand for imaging the metabotropic glutamate receptor type 1 in rat and monkey brains. J. Neurochem. 121, 115–124. , , et al. (
- 2013) Development of NMR spectroscopic methods for dynamic detection of acetylcholine synthesis by choline acetyltransferase in hippocampal tissue. J. Neurochem. 124, 336–346. , , and (
- 2013) MALDI imaging of post-mortem human spinal cord in amyotrophic lateral sclerosis. J. Neurochem. 124, 695–707. , , and (
- 1987) Brain metabolism and intracellular pH during ischaemia and hypoxia: an in vivo 31P and 1H nuclear magnetic. J. Neurochem. 49, 75–82. , , , , and (
- 2010) Characterization of AZD4694, a novel fluorinated Aβ plaque neuroimaging PET radioligand. J. Neurochem. 114, 784–794. , , et al. (
- 1984) P-31 nuclear magnetic resonance analysis of brain: II. effects of oxygen deprivation on isolated perfused and nonperfused rat brain. J. Neurochem. 43, 1716–1731. , , , , and (
- 2011) Stimulation of bursting in pre-Bötzinger neurons by Epac through calcium release and modulation of TRPM4 and K-ATP channels. J. Neurochem. 117, 295–308. and (
- 2013) Early impairment in brain metabolism detected by magnetic resonance (MR) spectroscopy antedates structural changes in mouse models of spinocerebellar ataxias. J Neurochem, doi: 10.1111/jnc.12448. and (
- 2013) Radiolabeling and in vitro/in vivo evaluation of N-(1-adamantyl)-8-methoxy-4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxamide as a PET probe for imaging cannabinoid type 2 receptor. J. Neurochem. 126, 616–624. , , , , , , , , and (
- 2012) Serotonergic modulation of receptor occupancy in rats treated with l-DOPA after unilateral 6-OHDA lesioning. J. Neurochem. 120, 806–817. , , et al. (
- 1986) Noninvasive in vivo demonstration of 2-fluoro-2-deoxy-d-glucose metabolism beyond the hexokinase reaction in rat brain by 19F nuclear magnetic resonance spectroscopy. J. Neurochem. 46, 198–201. , and (
- 2012) Altered neurochemical profile in the McGill-R-Thy1-APP rat model of Alzheimer's disease: a longitudinal in vivo1H MRS study. J. Neurochem. 123, 532–541. , , , and (
- 2013) Methyl-isobutyl amiloride reduces brain Lac/NAA, cell death and microglial activation in a perinatal asphyxia model. J. Neurochem. 124, 645–657. , , et al. (
- 1977) Deoxyglucose-c-14 method for measurement of local cerebral glucose-utilization - theory, procedure, and normal values in conscious and anesthetized albino-rat. J. Neurochem. 28, 897–916. , , et al. (
- 2010) Mass-spectrometry based oxidative lipidomics and lipid imaging: applications in traumatic brain injury. J. Neurochem. 115, 1322–1336. , , , , and (
- 2011) New approach for glyco- and lipidomics – Molecular scanning of human brain gangliosides by TLC-Blot and MALDI-QIT-TOF MS. J. Neurochem. 116, 678–683. , , , , , and (
- 2012) Effects of acute and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo1H MR spectroscopy at 9.4 T. J. Neurochem. 121, 407–417. , , , and (