Document Detail

Magnetic resonance imaging approaches for studying alcoholism using mouse models.
Jump to Full Text
MedLine Citation:
PMID:  23584868     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Mice are one of the most commonly used animal models of alcoholism, and extensive genetic and behavioral data related to alcohol consumption and its consequences in different strains are available. However, only recently have researchers begun to combine magnetic resonance imaging (MRI) technology with other experimental strategies to study the effects of alcohol in mice. This powerful combination enables structural and functional data of alcohol's effects on the brain of living animals to be obtained. This article reviews the challenges associated with the use of these technologies in mice and discusses the application of these advanced technologies to mouse models of alcoholism.
Authors:
Eilis A Boudreau; Gang Chen; Xin Li; Christopher D Kroenke
Related Documents :
3797668 - Venous clots: evaluation with mr imaging.
23584868 - Magnetic resonance imaging approaches for studying alcoholism using mouse models.
20934088 - Multidimensional gis modeling of magnetic mineralogy as a proxy for fire use and spatia...
19161188 - Spleen r2 and r2* in iron-overloaded patients with sickle cell disease and thalassemia ...
17450388 - Ct pitfalls in emergency radiology: a chronically ruptured intra-cranial dermoid tumor ...
9932258 - Virtual endoscopy (ve) of the basal cisterns: its value in planning the neurosurgical a...
Publication Detail:
Type:  Editorial    
Journal Detail:
Title:  Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism     Volume:  31     ISSN:  1535-7414     ISO Abbreviation:  Alcohol Res Health     Publication Date:  2008  
Date Detail:
Created Date:  2013-04-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100900708     Medline TA:  Alcohol Res Health     Country:  United States    
Other Details:
Languages:  eng     Pagination:  247-8     Citation Subset:  IM    
Affiliation:
Department of Neurology, Oregon Health & Science University, Portland, Oregon.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Alcohol Res Health
Journal ID (iso-abbrev): Alcohol Res Health
Journal ID (publisher-id): ARH
ISSN: 1535-7414
ISSN: 1930-0573
Publisher: National Institute on Alcohol Abuse and Alcoholism
Article Information
Download PDF
Copyright: 2008
public-domain:
Print publication date: Year: 2008
Volume: 31 Issue: 3
First Page: 247 Last Page: 248
PubMed Id: 23584868
ID: 3860481
Publisher Id: arh-31-3-247

Magnetic Resonance Imaging Approaches for Studying Alcoholism Using Mouse Models
Eilis A. Boudreau, M.D., Ph.D.
Gang Chen, Ph.D.
Xin Li, Ph.D.
Christopher D. Kroenke, Ph.D.
EILIS A. BOUDREAU, M.D., PH.D., is an assistant professor in the Department of Neurology, Oregon Health & Science University, Portland, Oregon.
GANG CHEN, PH.D., is a postdoctoral fellow in the Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon.
XIN LI, PH.D., is a staff scientist in the Advanced Imaging Research Center, Oregon Health & Science University, Portland, Oregon.
CHRISTOPHER D. KROENKE, PH.D., is an assistant professor in the Department of Behavioral Neuroscience and an assistant scientist in the Advanced Imaging Research Center and Oregon National Primate Research Center, Oregon Health & Science University, Portland, Oregon.

Mice are one of the most commonly used animal models of alcoholism, and extensive genetic and behavioral data related to alcohol consumption and its consequences in different strains are available. However, only recently have researchers begun to combine magnetic resonance imaging (MRI) technology with other experimental strategies to study the effects of alcohol in mice. This powerful combination enables structural and functional data of alcohol’s effects on the brain of living animals to be obtained. This article reviews the challenges associated with the use of these technologies in mice and discusses the application of these advanced technologies to mouse models of alcoholism.


Technological Advances Allowing MRI Studies in Mice

Application of MRI approaches to mouse model studies of human diseases, including alcoholism, has been limited by the small size of the mouse brain, which results in insufficient spatial resolution. However, these technological difficulties can be overcome with the use of modern high-field (7 to 12 Tesla [T]1) MRI systems suitable for scanning small animals. To obtain the requisite image resolution to study the mouse brain, the size of each volume element (i.e., voxel) analyzed must be reduced by a factor of approximately 100 compared with a typical MRI examination of the human brain. This reduction in voxel size is greatly facilitated by using small magnetic field gradient coils that are capable of rapidly generating extremely steep magnetic field gradients (Mayer et al. 2007). With these small-animal gradient systems, voxel sizes of less than 1 cubic millimeter (mm3) can be achieved using a variety of standard MRI techniques, whereas only a subset of imaging methods (such as T1-weighted imaging) can be used to generate submillimeter voxels in a clinical MRI system.

A second technical issue affecting MRI analyses in small animals, such as mice, relates to sensitivity (or signal-to-noise ratio [SNR]). If the same MRI instrumentation were used for small-animal imaging experiments as for clinical MRI analyses, the SNR would be expected to be reduced by about 100-fold, corresponding to the 100-fold reduction in voxel volume. This potential reduction in sensitivity can be avoided by using receiver elements matched in size to the volume under study (Doty et al. 2007). Other technical modifications (i.e., increased spin polarization at high magnetic field strength) have led to further gains in sensitivity relative to clinical MRIs (de Graf et al. 2006). These factors, combined with the feasibility of performing long MRI examinations with animals, typically result in relative increases in SNR when compared with similar human experiments. As a result, small-animal MRI has seen rapid growth in neuroscience research over recent years (for reviews, see Benveniste and Blackband 2002; Van der Linden et al. 2007).

Another problem associated with performing MRI scans in rodents is that the animals typically need to be sedated, potentially causing interactions between alcohol and the anesthetic used. To address the complications of scanning anesthetized animals, King and colleagues (2005) developed procedures for scanning conscious animals without the use of anesthetic. Their original procedure involved securing the animal in a restraining device that utilized a plastic headpiece to prevent movement. However, this treatment resulted in significant stress to the animals, as indicated by increased respiratory and heart rates and increased stress hormone (i.e., corticosterone) levels. The researchers therefore developed a protocol to gradually acclimate the animal to conscious scanning conditions by repeatedly placing them in a mock-MRI setup over a period of several days. Repeated measurements confirmed that as the animals acclimated to the procedure, their respiratory and heart rates and corticosterone levels declined.


Application of Recent Advances in Functional MRI to Mouse Models of Alcoholism

Functional MRI (fMRI) utilizes changes in the MRI signal between oxygen-rich (i.e., oxygenated) and oxygen-deprived (i.e., deoxygenated) blood to indirectly quantify alterations in blood flow associated with neuronal activity2 (Buxton et al. 2002). (This blood oxygen level–dependent mechanism of generating MRI contrast is termed the BOLD effect.) In a typical fMRI experiment, the MRI signal during a baseline state is compared with the MRI signal obtained following a stimulus. In an extension of this strategy, termed pharmacological MRI (phMRI), the baseline state may be compared to conditions following administration of a pharmacological agent (e.g., alcohol). With recent advances in small-animal MRI, it now is possible to study the effects of pharmacological agents, such as alcohol and other drugs (i.e., to perform phMRIs [Chen et al. 1997]), in very small animals such as mice with sufficient resolution and without the confounding factor of drug–anesthetic interactions.

Based on the acclimation strategy developed by King and colleagues (2005) for MRIs in rats, researchers have begun to modify the procedure further and develop a protocol for studying the acute response to alcohol administration in two strains of mice, called C57BL/6J and DBA/2J. These two strains were chosen because their genetic background (i.e., genotype) and behavior (i.e., phenotype) with regard to their response to alcohol have been studied extensively. For this approach, the animals also are acclimated to the scanning procedure by placing them in a mock-MRI set-up before the phMRI scanning was initiated. Initial experiments have indicated that high-quality anatomic scans of the mouse brain can be achieved at higher-field strengths (see figure 6) and that it is possible to obtain functional scans of good quality in awake, unsedated mice. Thus, this approach has great potential for future studies of alcohol’s effects on the brain using animal models.


Conclusions

Animal models, particularly studies in mice and rats, have greatly advanced researchers’ understanding of the effects that alcohol has on the body, including the brain. Because of the animals’ small size and the associated technical challenges, however, brain imaging studies in live animals only recently have become feasible, thanks to improvements in the required instrumentation and adaptations of the experimental designs. The full potential of these technological advances is only beginning to be realized.


Notes

FINANCIAL DISCLOSURE

The authors declare that they have no competing financial interests.

1The Tesla (T) is the unit of measurement for magnetic fields. For example, the strength of the Earth’s magnetic field at the equator is 31 microtesla (μT). Normal MRI systems have a magnetic field strength of 1.5 to 3 T.

2Neurons, like other cells, require oxygen for their activity. This oxygen is delivered to the cells by the blood. The more active a brain cell or brain region is, the more oxygen it requires. Thus, brain regions of high activity are characterized by increased blood flow. Moreover, in these regions oxygen is released from the oxygenated blood into the cells, leaving the blood deoxygenated. This oxygen release can be measured because oxygenated and deoxygenated blood generates different MRI signals.

References
Benveniste H,Blackband S. MR microscopy and high resolution small animal MRI: Applications in neuroscience researchProgress in Neurobiology675393420Year: 200212234501
Buxton RB. Introduction to Functional Magnetic Resonance Imaging: Principles & TechniquesCambridgeCambridge University PressYear: 2002
Chen YC,Galpern WR,Brownell AL,et al. Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: Correlation with PET, micro-dialysis, and behavioral dataMagnetic Resonance in Medicine383389398Year: 19979339439
De Graaf RA,Brown PB,McIntyre S,et al. High magnetic field water and metabolite proton T1 and T2 relaxation in rat brain in vivoMagnetic Resonance in Medicine562386394Year: 200616767752
Doty FD,Entzminger G,Kulkarni J,et al. Radio frequency coil technology for small-animal MRINMR in Biomedicine203304325Year: 200717451180
King JA,Garelick TS,Brevard ME,et al. Procedure for minimizing stress for fMRI studies in conscious ratsJournal of Neuroscience Methods1482154160Year: 200515964078
Mayer D,Zahr NM,Adalsteinsson E,et al. In vivo fiber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coilNeuroimage35310771085Year: 200717331742
Van der Linden A,Van Camp N,Ramos-Cabrer P,Hoehn M. Current status of functional MRI on small animals: Application to physiology, pathophysiology, and cognitionNMR in Biomedicine205522545Year: 200717315146

Article Categories:
  • Technologies from the Field

Keywords: Alcoholism, alcohol and other drug effects and consequences, animal studies, laboratory mice, mouse brain, brain function, brain structure, neuroimaging, magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), pharmacological magnetic resonance imaging (phMRI).

Previous Document:  The use of magnetic resonance spectroscopy and magnetic resonance imaging in alcohol research.
Next Document:  Laser-assisted microdissection.