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| Reference | Method and application (models) | Imaging parameters | Contrast agent or molecular probe | Safety considerations for clinical translation | Applications |
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| Bosomtwi et al. [14] | MRI to observe poststroke vascular changes (rats) | FOV: 32 mm | Feridex | Noninvasive | Tissues can be monitored long term through stages of angiogenesis enabling evaluation of vascular remodelling |
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| Bosomtwi et al. [15] | MRI in combination with LSCM to visualise postischaemic changes in vasculature (rats) | FOV: 32 mm | MIONs | Noninvasive; high doses of intravascular agent are required | LSCM can be used to validate MRI data; poststroke vascular remodelling can be three-dimensionally quantified |
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| Brunner et al. [16] | fUS to measure postischaemic cerebral blood volume (rats) | Resolution: 100 μm, FOV: 12.8 × 9 mm2, duration: approx. 3 min | None | No contrast agent injections are required | Stroke longitudinally studied across all stages; can image whilst in motion, as the probe is implanted on the head |
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| Cai et al. [17] | PET to observe VEGFR expression in poststroke angiogenesis (rats) | — | 64Cu-DOTA-VEGF121 | — | Some cellular VEGFRs may be visualised, resulting in the potential to observe poststroke reorganisation and plasticity |
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| Deddens et al. [18] | MRI to detect vascular remodelling after cerebral ischaemia (mice) | FOV: 1 × 1.2 × 2 cm3 | PECAM-1-targetted FeOx microparticles | — | PECAM-1 can be used to assess poststroke vascular remodelling |
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| Ding et al. [19] | MRI to visualise poststroke cerebral angiogenesis (rats) | FOV: 32 × 32 × 16 mm3 | Gd-DTPA | Noninvasive | Detect angiogenesis and determine the temporal profile of angiogenic processes |
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| Errico et al. [20] | Ultrafast US localisation microscopy to visualise neurovasculature and quantify haemodynamic characteristics (rats) | Resolution: 12.5 × 2.5 × 1 μm3 | Inert perfluorocarbon-filled microbubbles | Microbubbles are clinically approved contrast agents | Even slight haemodynamic changes in neurovasculature can be monitored; the resolution can be enhanced by localising microbubbles directly from radiofrequency data; motion correction algorithms needed |
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| Figueiredo et al. [21] | CTA | To observe cerebral vascular anatomy and blood flow (mice) | Resolution: 163 μm3, duration: 20–40 s | Iomeprol | Injection of contrast agent is required | Can detect changes in the diameter of vasculature |
| MRA | Resolution: 31 × 31 × 93 μm3, FOV: 12 × 16 mm2, duration: 58 min | None | No ionising radiation | — |
| Digital subtraction angiography | Resolution: 14 × 14 μm2, duration: 3 s | Iomeprol | Low injection volume and dose of radiation, although much more invasive than CTA and MRA | Can detect changes in intracerebral blood flow |
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| Gramer et al. [22] | PET, LSI, and RGB reflectometry to measure CBF, blood oxygenation, and glucose metabolism (rats) | Resolution (PET): 1.3 mm (FWHM), FOV: 12 × 7 mm2 | [18F]FDG | Thin-skull preparation is required | Can be used to quantify metabolic activity of neurovasculature in real time making it suitable for studying pathological conditions. Partial volume is an issue |
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| Horton et al. [23] | Triphoton fluorescence microscopy to visualise hippocampal vasculature (mice) | Resolution: 4.4 μm (axial, FWHM) | Dextran-coupled Texas Red dye | — | Overcomes the limitations of two-photon microscopy, such as signal-to-background ratio of excitation in scattering tissues and lack of fluorescent labels that can be used |
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| Howles et al. [24] | Contrast-enhanced MRA to visualise neurovasculature (mice) | Resolution: 52 × 52 × 100 μm3, FOV: 20 × 20 × 8 mm3, duration: approx. 12 min | SC-Gd liposomal nanoparticles | — | SC-Gd allows for high contrast-to-noise ratio; useful to visualise very small vascular structures |
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| Hu et al. [25] | Optical-resolution PAM to study micro-haemodynamic activities (rodents) | Resolution: 5 × 15 μm2 | — | Noninvasive | Can help quantify changes in metabolic parameters |
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| Huang et al. [26] | MRI to assess vascular reactivity and functionality during postischaemic proangiogenic vascular remodelling (rats) | FOV: 2.56 × 2.56 cm2 | — | — | Anaesthesia protocols must be optimised to minimise physiological disturbance |
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| Jimenez-Xarrie et al. [27] | MRI to assess postischaemic cerebrovascular damage | FOV: 32 × 32 mm, duration: 9 min 17 s | None | Isoflurane anaesthesia can affect stroke outcomes and evaluation of vascular changes | Long-term vascular consequences of ischaemia with coincident hypertension can be studied |
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| Kolodziej et al. [28] | SPECT to study CBF (mice) | Resolution: 0.7 mm (FWHM), FOV: 20.9 mm (axial), duration: approx. 2 h | 99mTc-HMPAO | 99mTc-HMPAO is lipophilic and is quickly cleared from the plasma | Uses pinhole imaging for higher resolution |
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| Lake et al. [29] | MRI to assess poststroke brain morphology and vascular function (rats) | Resolution: 0.1 × 0.1 mm2, duration: <12 min | — | Propofol anaesthesia induces 20–60% regional vasoconstriction, which may influence vascular studies | Functional MRI can be used to measure resting blood flow and cerebrovascular reactivity; structural MRI may have limited sensitivity to detect subtle changes in tissue morphology |
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| Lecoq et al. [30] | Two-photon phosphorescence lifetime microscopy to measure the partial pressure of oxygen and blood flow (mice) | Resolution: <1 μm (lateral) | Phosphorescent nanoprobe PtP-C343 | Minimally invasive; the probe is neither toxic nor phototoxic | Oxygen gradients in microvascular networks can be distinguished; this is particularly useful for postischaemia imaging |
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| Letourneur et al. [31] | Two-photon laser scanning microscopy to longitudinally image vascular development (mice) | Duration: 50–150 s | Fluorescein-conjugated dextran and Texas Red-dextran | Requires thinning of the skull; head must be immobilised | Can longitudinally image the same areas over many days; can measure flow dynamics over time in relation to changes in vessel diameter |
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| Li et al. [32] | LSI to study neurovasculature (rats) | Resolution: 6.7 × 6.7 μm2 | None | Requires thinning of the skull | Different circulatory dynamics can be observed at different spatial locations |
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| Liao et al. [33] | Functional PAM to study functional changes in total haemoglobin concentration, cerebral blood volume, and haemoglobin O2 saturation in cerebral blood vessels (rats) | Resolution: 36 × 65 μm2 | None | — | Can be complemented with other imaging modalities for label-free visualisation of neurovasculature |
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| Lin et al. [34] | 3D ΔR2-based microscopy of MRA to visualise poststroke changes in neurovasculature (rats) | Resolution: 54 × 54 × 72 μm3, FOV: 2.8 × 2.8 × 1.4 cm3, duration: 76 min | MIONs | Greater magnetic fields may be needed to visualise smaller vessels | Can simultaneously visualise microvascular morphology and reveal physiological properties of microvascular cerebral blood volume |
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| Luckl et al. [35] | LSI and imaging of intrinsic signals to study CBF dynamics during ischaemia (rats) | Resolution: 140 μm every 2 s, FOV: 5 × 5 mm2 | Erythrosin B dye | Requires thinning of the skull for better observation | Vascular changes in metabolism can be quantified |
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| Miao et al. [36] | LSI to study angiogenesis (rats) | FOV: 4.7 × 4.7 mm2 | None | Requires thinning of the skull | CBF under various pathological states can be analysed, and smaller vessels can be enhanced; results can be affected by motion artefacts |
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| Nagaraja et al. [37] | MRI to visualise poststroke changes in the BBB (rats) | FOV: 32 mm | Gd-DTPA and Gd-DTPA linked to bovine serum albumin and Evans blue dye | Noninvasive | Different measurements are obtained with different contrast agents; quantifying BBB permeability can help in understanding the progression of ischaemic injury |
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| Sakadžić et al. [38] | Two-photon phosphorescence lifetime microscopy to measure partial pressure of oxygen in cortical microvasculature under hypoxic conditions (rats, mice) | — | Phosphorescent nanoprobe PtP-C343 | Minimally invasive with low doses of the probe required; no detected leakage of the probe into interstitial spaces | The partial pressure of oxygen can be simultaneously assessed at various positions and depths, making it more feasible to functionally study transient changes in oxygen levels |
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| Schambach et al. [39] | Volume-CTA to visualise cerebral vessels (mice) | Duration: 40 s | Iodinated contrast agent | Large dose of contrast agent is required | Changes in vessel diameter can be monitored |
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| Schroeter et al. [40] | PET | To observe postischaemic vascular changes (rats) | Duration: up to 60 min | [18F]FDG and [11C]PK11195 | Noninvasive | Characterise neuroinflammation and metabolic disruptions repeatedly over time. |
| | MRI | | FOV: 3.0 cm | — | Noninvasive | Can help localise areas of infarction |
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| Seo et al. [41] | Contrast-enhanced μCT to visualise poststroke changes in cerebral vasculature (rats) | Duration: approx. 2 min | Iopromide | High doses of iodinated contrast agent are needed | Images are subject to blurring due to physiological motion |
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| Stein et al. [42] | PAM to study blood oxygenation dynamics of hypoxic cerebral vasculature (mice) | Resolution: 70 × 54 μm2 | None; monitors “endogenous” haemodynamics | Noninvasive | Single blood vessels can be noninvasively assessed in real time |
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| Struys et al. [43] | PET | To characterise acute and long-term vascular and metabolic effects of unilateral common carotid artery occlusion (mice) | Resolution: 1.35 mm (transaxial, FWHM), duration: 10 min | [15O]H2O and [18F]FDG | — | Can be used to monitor short-term/long-term perfusion and vascular remodelling in ischaemic stroke models |
| MRI | | Resolution: 98 × 98 μm2, FOV: 2.5 × 2.5 cm2 | — |
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| Tsukada et al. [44] | PET to study postischaemic changes (monkeys) | Duration: 91 min | [18F]flurpiridaz and [18F]BCPP-EF | Surgical procedures are invasive and require anaesthesia | Study metabolic properties and distinguish inflammatory processes |
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| Yanev et al. [45] | Steady-state contrast-enhanced MRI to assess the changes in cerebral blood volume and microvascular density after transient stroke (rats) | FOV: 30 × 30 mm2, duration: approx. 135 min | Ultrasmall iron oxide particles | — | Changes in cerebral blood volume and microvascular density can be observed at least 3 months after stroke; only perfused (and therefore functional) vessels can be detected |
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| Yoon et al. [46] | Multiphoton luminescence to visualise morphological changes in cortical vasculature over time (mice) | — | PEG-GNPs | PEG-GNPs are highly biocompatible | Long circulation time of PEG-GNPs enables vascular imaging for several hours, making them suitable to observe remodelling |
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| Yu et al. [47] | Spectral Doppler OCT to quantitatively assess dynamic blood flow before and after stroke (mice) | Duration: approx. 20 min | Rose bengal | — | Mimics ischaemic conditions by reducing CBF in microvasculature; the pulsatility of CBF is quantified; changes in heart rate due to anaesthesia wearing off and being readministered must be considered |
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| Zhang et al. [48] | SR-PCI to visualise neural microvasculature (rats) | Resolution: <10 μm, FOV: approx. 3 mm | None | High doses of ionising radiation | Vascular architecture and volume can be visualised and quantified; FOV is limited |
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