Small animal PET: a review of what we have done and where we are going

Miyaoka, Robert S.; Lehnert, Adrienne L.

doi:10.1088/1361-6560/ab8f71

Cited by 58 publications

(55 citation statements)

References 232 publications

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“…Small animal positron emission tomography (PET) scanners are widely used in biomedical research. [1][2][3][4] In the past over two decades, many small animal PET scanners with spatial resolutions of 1-2 mm have been developed. [5][6][7][8][9][10][11][12][13][14] If one wants to obtain the relative spatial resolution for imaging a mouse at the same level of imaging of a human with a clinical wholebody PET (3-5 mm), a small animal PET scanners need to have a spatial resolution of 0.3-0.5 mm.…”

Section: Introductionmentioning

confidence: 99%

Ultra‐high‐resolution depth‐encoding small animal PET detectors: Using GAGG and LYSO crystal arrays

et al. 2022

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Purpose Small animal positron emission tomography (PET) scanners are widely used in current biomedical research. The study aimed to develop high‐efficiency and ultra‐high‐resolution detectors that could be used to develop a small animal PET scanner with high sensitivity and spatial resolution approaching to its physical limit. Methods Four crystal arrays were fabricated and measured in this study. Crystal arrays 1 and 2 consisted of 38 × 38 gadolinium aluminum gallium garnet (GAGG) and lutetium–yttrium oxyorthosilicate (LYSO) crystals of 0.4 × 0.4 × 20 mm3 size. Crystal array 3 consisted of 16 × 16 GAGG crystals of 0.3 × 0.3 × 20 mm3 size, and crystal array 4 consisted of 24 × 24 LYSO crystals 0.3 × 0.3 × 20 mm3 in size. The crystal arrays were dual‐ended readouts using 8 × 8 silicon photomultiplier (SiPM) arrays of 2 × 2 mm2 pixel area. The SiPM array was readout using a signal multiplexing circuit to convert the 64 output signals into four position‐encoding signals. The performances of the four detectors in terms of flood histogram, energy resolution, depth of interaction (DOI) resolution, and timing resolution were measured. Results The GAGG detectors provided better flood histograms, ∼30% higher photopeak amplitude, ∼20% higher energy resolution, ∼12% worse DOI resolution, and ∼15% worse timing resolution compared with LYSO detectors of the same crystal size. These four detectors provided DOI resolutions of <2 mm, energy resolutions of <22%, and timing resolutions of <1.6 ns. All crystals of 0.4 × 0.4 × 20 mm3 and 0.3 × 0.3 × 20 mm3 could be clearly resolved if the crystal array was 1 mm smaller in the four sides than that in the SiPM array. Conclusions High DOI resolution PET detectors were developed using both GAGG and LYSO arrays with crystal sizes of 0.3 and 0.4 mm, respectively, and a length of 20 mm. The detectors can be used in the future to develop small animal PET scanners, especially dedicated mouse imaging PET scanners, which can simultaneously achieve high sensitivity and ultra‐high spatial resolution.

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Section: Introductionmentioning

confidence: 99%

Ultra‐high‐resolution depth‐encoding small animal PET detectors: Using GAGG and LYSO crystal arrays

et al. 2022

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“…For clinical application in humans, 7 and 10.5T MRIs have been reported ( Ehman et al, 2017 ; Ladd et al, 2018 ). For small animal imaging, 7, 9.4, 11.7, 16, and up to 21.1 T high-field MRI has been utilized in the laboratory ( Schepkin et al, 2010 ; Miyaoka and Lehnert, 2020 ; Ni, 2021 ), providing insights into the function and pathophysiology of the brain. Higher magnetic fields substantially increase the sensitivity and signal-to-noise ratio for MRI, although the tissue heating and non-uniformity of the radio-frequency field might affect the image quality.…”

Section: Discussionmentioning

confidence: 99%

Magnetic Resonance Imaging in Tauopathy Animal Models

2022

Front. Aging Neurosci.

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The microtubule-associated protein tau plays an important role in tauopathic diseases such as Alzheimer’s disease and primary tauopathies such as progressive supranuclear palsy and corticobasal degeneration. Tauopathy animal models, such as transgenic, knock-in mouse and rat models, recapitulating tauopathy have facilitated the understanding of disease mechanisms. Aberrant accumulation of hyperphosphorylated tau contributes to synaptic deficits, neuroinflammation, and neurodegeneration, leading to cognitive impairment in animal models. Recent advances in molecular imaging using positron emission tomography (PET) and magnetic resonance imaging (MRI) have provided valuable insights into the time course of disease pathophysiology in tauopathy animal models. High-field MRI has been applied for in vivo imaging in animal models of tauopathy, including diffusion tensor imaging for white matter integrity, arterial spin labeling for cerebral blood flow, resting-state functional MRI for functional connectivity, volumetric MRI for neurodegeneration, and MR spectroscopy. In addition, MR contrast agents for non-invasive imaging of tau have been developed recently. Many preclinical MRI indicators offer excellent translational value and provide a blueprint for clinical MRI in the brains of patients with tauopathies. In this review, we summarized the recent advances in using MRI to visualize the pathophysiology of tauopathy in small animals. We discussed the outstanding challenges in brain imaging using MRI in small animals and propose a future outlook for visualizing tau-related alterations in the brains of animal models.

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“…Positron emission tomography/SPECT provides quantitative in vivo detection of picomolar concentrations of the target within a large field-of-view ( 26 – 28 ). The resolution of commercially available microPET is approximately 0.5–2 mm ( 29 – 32 ), which is sufficient for rat brain imaging but suboptimal for mouse brain imaging considering the spillover and size of the mouse brain (10 mm × 10 mm × 15 mm) ( 33 ).…”

Section: Hybrid Imagingmentioning

confidence: 99%

Recent Technical Advances in Accelerating the Clinical Translation of Small Animal Brain Imaging: Hybrid Imaging, Deep Learning, and Transcriptomics

Ren

Guan

et al. 2022

Front. Med.

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Small animal models play a fundamental role in brain research by deepening the understanding of the physiological functions and mechanisms underlying brain disorders and are thus essential in the development of therapeutic and diagnostic imaging tracers targeting the central nervous system. Advances in structural, functional, and molecular imaging using MRI, PET, fluorescence imaging, and optoacoustic imaging have enabled the interrogation of the rodent brain across a large temporal and spatial resolution scale in a non-invasively manner. However, there are still several major gaps in translating from preclinical brain imaging to the clinical setting. The hindering factors include the following: (1) intrinsic differences between biological species regarding brain size, cell type, protein expression level, and metabolism level and (2) imaging technical barriers regarding the interpretation of image contrast and limited spatiotemporal resolution. To mitigate these factors, single-cell transcriptomics and measures to identify the cellular source of PET tracers have been developed. Meanwhile, hybrid imaging techniques that provide highly complementary anatomical and molecular information are emerging. Furthermore, deep learning-based image analysis has been developed to enhance the quantification and optimization of the imaging protocol. In this mini-review, we summarize the recent developments in small animal neuroimaging toward improved translational power, with a focus on technical improvement including hybrid imaging, data processing, transcriptomics, awake animal imaging, and on-chip pharmacokinetics. We also discuss outstanding challenges in standardization and considerations toward increasing translational power and propose future outlooks.

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Small animal PET: a review of what we have done and where we are going

Cited by 58 publications

References 232 publications

Ultra‐high‐resolution depth‐encoding small animal PET detectors: Using GAGG and LYSO crystal arrays

Ultra‐high‐resolution depth‐encoding small animal PET detectors: Using GAGG and LYSO crystal arrays

Magnetic Resonance Imaging in Tauopathy Animal Models

Recent Technical Advances in Accelerating the Clinical Translation of Small Animal Brain Imaging: Hybrid Imaging, Deep Learning, and Transcriptomics

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