Functional magnetic resonance imaging in awake animals

Abstract

Awake animal imaging is becoming an important tool in behavioral neuroscience and preclinical drug discovery. Non-invasive ultra-high-field, functional magnetic resonance imaging (fMRI) provides a window to the mind, making it possible to image changes in brain activity across distributed, integrated neural circuits with high temporal and spatial resolution. In theory, changes in brain function, anatomy, and chemistry can be recorded in the same animal from early life into old age under stable or changing environmental conditions. This prospective capability of animal imaging to follow changes in brain neurobiology after genetic or environmental insult has great value to the fields of psychiatry and neurology and probably stands as the key advantage of MRI over other methods in the neuroscience toolbox. In addition, awake animal imaging offers the ability to record signal changes across the entire brain in seconds. When combined with the use of 3D segmented, annotated, brain atlases, and computational analysis, it is possible to reconstruct distributed, integrated neural circuits or 'fingerprints' of brain activity. These fingerprints can be used to characterize the activity and function of new psychotherapeutics in preclinical development and to study the neurobiology of integrated neural circuits controlling cognition and emotion. In this review, we describe the methods used to image awake animals and the recent advances in the radiofrequency electronics, pulse sequences, and the development of 3D segmented atlases and software for image analysis. Results from pharmacological MRI studies and from studies using provocation paradigms to elicit emotional responses are provided as a small sample of the number of different applications possible with awake animal imaging.

Dissociable Effects of Antipsychotics on Ketamine-Induced Changes in Regional Oxygenation and Inter-Regional Coherence of Low Frequency Oxygen Fluctuations in the Rat

“…Such studies have explored the notion of functional connectivity between brain regions using low-frequency BOLD fluctuation correlations, and abnormalities have been identified in resting-state connectivity in numerous diseases, including schizophrenia (for review, see Fox and Greicius, 2010). Assessment of functional connectivity via functional MRI (fMRI) in rodents is possible but is presently limited to anesthetized or heavily restrained animals (see review by Ferris et al, 2011), greatly limiting the scope of behavioral studies.…”

Analgesic Efficacy and Safety of DALDA Peptide Analog Delivery to the Brain Using Oil-in-Water Nanoemulsion Formulation

“…The rats were lightly anesthetized and placed into a head coil and restrainer developed by the Animal Imaging Research (Holden, MA) [22, 23]. When fully conscious, the animals were placed in a dark mock scanner tube with a recording of a standard MRI pulse sequence playing in the background.…”

Recent Developments in Fast Kurtosis Imaging

“…However, the low data requirement of the 1-3-9/1-9-9 protocols enables higher spatial resolution or higher SNR in the same (or less) scan time as conventional DKI acquisitions, which is certainly a significant benefit for all areas of DKI related research. Furthermore, fast DKI may become increasingly valuable in preclinical studies as imaging of awake animals becomes more widely used to avoid physiological perturbations caused by either inhaled or injected anesthesia [88,89]. Here, methods with modest data demand are preferable to reduce animal stress and to afford data acquisition with gating or even reacquisition if data is affected by movement.…”