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Awake Mouse Imaging: From Two-Photon Microscopy to Blood Oxygen Level-Dependent Functional Magnetic Resonance Imaging.

ABSTRACT: BACKGROUND:Functional magnetic resonance imaging (fMRI) in awake behaving mice is well positioned to bridge the detailed cellular-level view of brain activity, which has become available owing to recent advances in microscopic optical imaging and genetics, to the macroscopic scale of human noninvasive observables. However, though microscopic (e.g., two-photon imaging) studies in behaving mice have become a reality in many laboratories, awake mouse fMRI remains a challenge. Owing to variability in behavior among animals, performing all types of measurements within the same subject is highly desirable and can lead to higher scientific rigor. METHODS:We demonstrated blood oxygenation level-dependent fMRI in awake mice implanted with long-term cranial windows that allowed optical access for microscopic imaging modalities and optogenetic stimulation. We started with two-photon imaging of single-vessel diameter changes (n = 1). Next, we implemented intrinsic optical imaging of blood oxygenation and flow combined with laser speckle imaging of blood flow obtaining a mesoscopic picture of the hemodynamic response (n = 16). Then we obtained corresponding blood oxygenation level-dependent fMRI data (n = 5). All measurements could be performed in the same mice in response to identical sensory and optogenetic stimuli. RESULTS:The cranial window did not deteriorate the quality of fMRI and allowed alternation between imaging modalities in each subject. CONCLUSIONS:This report provides a proof of feasibility for multiscale imaging approaches in awake mice. In the future, this protocol could be extended to include complex cognitive behaviors translatable to humans, such as sensory discrimination or attention.

SUBMITTER: Desjardins M

PROVIDER: S-EPMC6556427 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Awake Mouse Imaging: From Two-Photon Microscopy to Blood Oxygen Level-Dependent Functional Magnetic Resonance Imaging.

Desjardins Michèle M Kılıç Kıvılcım K Thunemann Martin M Mateo Celine C Holland Dominic D Ferri Christopher G L CGL Cremonesi Jonathan A JA Li Baoqiang B Cheng Qun Q Weldy Kimberly L KL Saisan Payam A PA Kleinfeld David D Komiyama Takaki T Liu Thomas T TT Bussell Robert R Wong Eric C EC Scadeng Miriam M Dunn Andrew K AK Boas David A DA Sakadžić Sava S Mandeville Joseph B JB Buxton Richard B RB Dale Anders M AM Devor Anna A

Biological psychiatry. Cognitive neuroscience and neuroimaging 20181212 6

<h4>Background</h4>Functional magnetic resonance imaging (fMRI) in awake behaving mice is well positioned to bridge the detailed cellular-level view of brain activity, which has become available owing to recent advances in microscopic optical imaging and genetics, to the macroscopic scale of human noninvasive observables. However, though microscopic (e.g., two-photon imaging) studies in behaving mice have become a reality in many laboratories, awake mouse fMRI remains a challenge. Owing to varia ...[more]

PMID: 30691968

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Project description:IntroductionKidney blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) has shown great promise in evaluating relative oxygen availability. This method is quite efficacious in evaluating acute responses to physiological and pharmacologic maneuvers. Its outcome parameter, R2∗ is defined as the apparent spin-spin relaxation rate measured in the presence of magnetic susceptibility differences and it is measured using gradient echo MRI. Although associations between R2∗ and renal function decline have been described, it remains uncertain to what extent R2∗ is a true reflection of tissue oxygenation. This is primarily because of not taking into account the confounding factors, especially fractional blood volume (fBV) in tissue.MethodsThis case-control study included 7 healthy controls and 6 patients with diabetes and chronic kidney disease (CKD). Using data before and after administration of ferumoxytol, a blood pool MRI contrast media, the fBVs in kidney cortex and medulla were measured.ResultsThis pilot study independently measured fBV in kidney cortex (0.23 ± 0.03 vs. 0.17 ± 0.03) and medulla (0.36 ± 0.08 vs. 0.25 ± 0.03) in a small number of healthy controls (n = 7) versus CKD (n = 6). These were then combined with BOLD MRI measurements to estimate oxygen saturation of hemoglobin (StO2) (0.87 ± 0.03 vs. 0.72 ± 0.10 in cortex; 0.82 ± 0.05 vs. 0.72 ± 0.06 in medulla) and partial pressure of oxygen in blood (bloodPO2) (55.4 ± 6.5 vs. 38.4 ± 7.6 mm Hg in cortex; 48.4 ± 6.2 vs. 38.1 ± 4.5 mm Hg in medulla) in control versus CKD. The results for the first time demonstrate that cortex is normoxemic in controls and moderately hypoxemic in CKD. In the medulla, it is mildly hypoxemic in controls and moderately hypoxemic in CKD. Whereas fBV, StO2, and bloodPO2 were strongly associated with estimated glomerular filtration rate (eGFR), R2∗ was not.ConclusionOur results support the feasibility of quantitatively assessing oxygen availability using noninvasive quantitative BOLD MRI that could be translated to the clinic.

Dataset Information

Awake Mouse Imaging: From Two-Photon Microscopy to Blood Oxygen Level-Dependent Functional Magnetic Resonance Imaging.

Publications

Awake Mouse Imaging: From Two-Photon Microscopy to Blood Oxygen Level-Dependent Functional Magnetic Resonance Imaging.

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