Sequential PET estimation of cerebral oxygen metabolism with spontaneous respiration of <sup>15</sup>O-gas in mice with bilateral common carotid artery stenosis

Temma, Takashi; Yamazaki, Makoto; Miyanohara, Jun; Shirakawa, Hisashi; Kondo, Naoya; Koshino, Kazuhiro; Kaneko, Shuji; Iida, Hidehiro

doi:10.1177/0271678x17692815

Cited by 17 publications

(12 citation statements)

References 22 publications

(60 reference statements)

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“…This is comparable to the results of a recent study using positron emission tomography (PET), in which the CBF in mice under 1.5% isoflurane anesthesia was found to be 0.62 ± 0.05 ml/g/min. 32 However, the CBF values in anesthetized mice in both studies were slightly higher than that reported for awake mice using the autoradiographic method, which was 0.5 ml/g/min. 33 It is likely that the anesthetic (isoflurane) contributed to the slightly higher CBF reported in our study.…”

Section: Discussioncontrasting

confidence: 57%

Reduced cerebral blood flow in an α-synuclein transgenic mouse model of Parkinson’s disease

Biju

Shen

Hernandez

et al. 2019

J Cereb Blood Flow Metab

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There is increasing evidence that widespread cortical cerebral blood flow deficits occur early in the course of Parkinson’s disease. Although cerebral blood flow measurement has been suggested as a potential biomarker for early diagnosis of Parkinson’s disease, as well as a means for tracking response to treatment, the relationship of cerebral blood flow to α-synucleinopathy, a major pathological hallmark of Parkinson’s disease, remains unclear. Therefore, we performed arterial spin-labeling magnetic resonance imaging and diffusion tensor imaging on transgenic mice overexpressing human wild-type α-synuclein and age-matched controls to measure cerebral blood flow and degenerative changes. As reported for early-stage Parkinson’s disease, α-synuclein mice exhibited a significant reduction in cortical cerebral blood flow, which was accompanied by motor coordination deficits and olfactory dysfunction. Although no overt degenerative changes were apparent in diffusion tensor imaging images, magnetic resonance imaging volumetric analysis revealed a significant reduction in olfactory bulb volume, similar to that seen in Parkinson’s disease patients. Our data, representing the first report of cerebral blood flow deficit in an animal model of Parkinson’s disease, suggest a causative role for α-synucleinopathy in cerebral blood flow deficits in Parkinson’s disease. Thus, α-synuclein transgenic mice comprise a promising model to study Parkinson’s disease-related mechanisms of cerebral blood flow deficits and to investigate further its utility as a potential biomarker for Parkinson’s disease.

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Section: Discussioncontrasting

confidence: 57%

Reduced cerebral blood flow in an α-synuclein transgenic mouse model of Parkinson’s disease

Biju

Shen

Hernandez

et al. 2019

J Cereb Blood Flow Metab

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“…Positron emission tomography (PET) with 15 O is considered the gold standard for the whole-brain oxygenation measurement in clinical setting [ 8 ]. While the method has been applied to mice [ 9 ], the method suffers from low spatial resolution which limits its usefulness for studying small species Moreover, the short half-life of [ 15 O] requires an on-site cyclotron, which restricts the widespread use of this approach. Alternatively, MRI-based techniques such as blood oxygenation level-dependent (BOLD), quantitative BOLD, susceptometry, T 2 -relaxation-under-spin-tagging and 17 O MR spectroscopy among others have been proposed for mapping oxygenation [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Cortical hypoperfusion and reduced cerebral metabolic rate of oxygen in the arcAβ mouse model of Alzheimer’s disease

Rudin

Klohs

2018

Photoacoustics

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The effect of cerebral amyloidosis on cerebral hemodynamics was investigated with photoacoustic tomography (PAT) and magnetic resonance imaging (MRI). First, the sensitivity and robustness of PAT for deriving metrics of vascular and tissue oxygenation in the murine brain was assessed in wild-type mice with a hyperoxia-normoxia challenge. Secondly, cerebral oxygenation was assessed in young and aged arcAβ mice and wild-type controls with PAT, while cerebral blood flow (CBF) was determined by perfusion MRI. The investigations revealed that PAT can sensitively and robustly detect physiological changes in vascular and tissue oxygenation. An advanced stage of cerebral amyloidosis in arcAβ mice is accompanied by a decreases in cortical CBF and the cerebral metabolic rate of oxygen (CMRO2), as oxygen extraction fraction (OEF) has been found unaffected. Thus, PAT constitutes a robust non-invasive tool for deriving metrics of tissue oxygenation, extraction and metabolism in the mouse brain under physiological and disease states.

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“…Accordingly, few [ 15 O]H 2 O PET studies have been conducted to evaluate cerebral blood flow and other haemodynamics in small animals primarily due to the short half-life of 15 O and its potentially high-energy emitted positron, which render the PET images noisier and of lower resolution. Nevertheless, the development of [ 15 O]H 2 O-based imaging in small animals is an increasing focus of recent research, and the aforementioned challenges may be technically addressed in the near future (more information is available on the website of the project Small Animal Fast MRI Insert at https://safir.ethz.ch) [43, 79–82].…”

Section: Discussionmentioning

confidence: 99%

Preclinical Imaging Biomarkers for Postischaemic Neurovascular Remodelling

Gandhi

Tsoumpas

2019

Contrast Media & Molecular Imaging

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In the pursuit of understanding the pathological alterations that underlie ischaemic injuries, such as vascular remodelling and reorganisation, there is a need for recognising the capabilities and limitations of in vivo imaging techniques. Thus, this review presents contemporary published research of imaging modalities that have been implemented to study postischaemic neurovascular changes in small animals. A comparison of the technical aspects of the various imaging tools is included to set the framework for identifying the most appropriate methods to observe postischaemic neurovascular remodelling. A systematic search of the PubMed® and Elsevier’s Scopus databases identified studies that were conducted between 2008 and 2018 to explore postischaemic neurovascular remodelling in small animal models. Thirty-five relevant in vivo imaging studies are included, of which most made use of magnetic resonance imaging or positron emission tomography, whilst various optical modalities were also utilised. Notably, there is an increasing trend of using multimodal imaging to exploit the most beneficial properties of each imaging technique to elucidate different aspects of neurovascular remodelling. Nevertheless, there is still scope for further utilising noninvasive imaging tools such as contrast agents or radiotracers, which will have the ability to monitor neurovascular changes particularly during restorative therapy. This will facilitate more successful utility of the clinical imaging techniques in the interpretation of neurovascular reorganisation over time.

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Sequential PET estimation of cerebral oxygen metabolism with spontaneous respiration of ¹⁵O-gas in mice with bilateral common carotid artery stenosis

Cited by 17 publications

References 22 publications

Reduced cerebral blood flow in an α-synuclein transgenic mouse model of Parkinson’s disease

Reduced cerebral blood flow in an α-synuclein transgenic mouse model of Parkinson’s disease

Cortical hypoperfusion and reduced cerebral metabolic rate of oxygen in the arcAβ mouse model of Alzheimer’s disease

Preclinical Imaging Biomarkers for Postischaemic Neurovascular Remodelling

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Sequential PET estimation of cerebral oxygen metabolism with spontaneous respiration of 15O-gas in mice with bilateral common carotid artery stenosis

Cited by 17 publications

References 22 publications

Reduced cerebral blood flow in an α-synuclein transgenic mouse model of Parkinson’s disease

Reduced cerebral blood flow in an α-synuclein transgenic mouse model of Parkinson’s disease

Cortical hypoperfusion and reduced cerebral metabolic rate of oxygen in the arcAβ mouse model of Alzheimer’s disease

Preclinical Imaging Biomarkers for Postischaemic Neurovascular Remodelling

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Product

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Sequential PET estimation of cerebral oxygen metabolism with spontaneous respiration of ¹⁵O-gas in mice with bilateral common carotid artery stenosis