High-Resolution Optical Microscopy Imaging of Cortical Oxygen Delivery and Consumption

Sakadžić, Sava; Mandeville, Emiri T.; Gagnon, Louise; Musacchia, Joseph J.; Yaseen, Mohammad A.; Yücel, Meryem A.; Lefebvre, Joël; Dale, Anders M.; Eikermann-Haerter, Katharina; Ayata, Cenk; Srinivasan, Vivek J.; Lo, Eng H.; Devor, Anna; Boas, David A.

doi:10.1364/cleo_at.2014.af2b.3

Cited by 3 publications

(4 citation statements)

References 15 publications

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“…Although large decrease in partial pressure of oxygen in arterioles (P a O 2 [mmHg]) was observed with depth in anaesthetised animals, indicating a directly contribute to tissue oxygenation from arterioles [33,34], small to no variation in P a O 2 was detected along penetrating arterioles in awake mice [35,36]. Morphologically speaking, there are arterioles that exclusively vascularise the white matter [29].…”

Section: Model Formulationmentioning

confidence: 99%

Parameter quantification for oxygen transport in the human brain

Bing,

Józsa,

Payne

2024

Preprint

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Oxygen is carried to the brain by blood flow through generations of vessels across a wide range of length scales. This multi-scale nature of blood flow and oxygen transport poses challenges on investigating the mechanisms underlying both healthy and pathological states through imaging techniques alone. Recently, multi-scale models describing whole brain perfusion and oxygen transport have been developed. Such models rely on effective parameters that represent the microscopic properties. While parameters of the perfusion models have been characterised, those for oxygen transport are still lacking. In this study, we set to quantify the parameters associated with oxygen transport and their uncertainties. We first present a multi-scale, multi-compartment oxygen transport model based on a porous continuum approach. We then determine the effective values of the model parameters. By using statistically accurate capillary networks, geometric parameters (vessel volume fraction and surface area to volume ratio) that capture the microvascular topologies are found to be 1.42% and 627 [mm2/mm3], respectively. These values compare well with those obtained from human and monkey vascular samples. In addition, maximum consumption rates of oxygen are optimised to uniquely define the oxygen distribution over depth. Simulation results from a one-dimensional tissue column show qualitative agreement with experimental measurements of tissue oxygen partial pressure in rats. We highlight the importance of anatomical accuracy through simulation performed within a patient-specific brain mesh. Finally, one-at-a-time sensitivity analysis reveals that the oxygen model is not sensitive to most of its parameters; however, perturbations in oxygen solubilities and plasma to whole blood oxygen concentration ratio have a considerable impact on the tissue oxygenation. These findings demonstrate the validity of using a porous continuum approach to model organ-scale oxygen transport and draw attention to the significance of anatomy and certain parameter values.

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Section: Model Formulationmentioning

confidence: 99%

Parameter quantification for oxygen transport in the human brain

Bing,

Józsa,

Payne

2024

Preprint

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“…Morphological and functional changes in the microcirculation are linked to the onset and progression of many pathologies. [1,2] Disease biomarkers can efficiently be derived by imaging-based assessment of microvascular features, such as vessel size and density, perfusion, or blood flow velocity. [3] Of particular importance is the microcirculation in the brain, which has been extensively studied in preclinical rodent models thus contributing to a better understanding of how oxygen and nutrients are transported into cells and how normal function is altered in brain tumor, [4,5] stroke, [6] or Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

Depth‐Resolved Localization Microangiography in the NIR‐II Window

et al. 2022

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Detailed characterization of microvascular alterations requires high-resolution 3D imaging methods capable of providing both morphological and functional information. Existing optical microscopy tools are routinely used for microangiography, yet offer suboptimal trade-offs between the achievable field of view and spatial resolution with the intense light scattering in biological tissues further limiting the achievable penetration depth. Herein, a new approach for volumetric deep-tissue microangiography based on stereovision combined with super-resolution localization imaging is introduced that overcomes the spatial resolution limits imposed by light diffusion and optical diffraction in wide-field imaging configurations. The method capitalizes on localization and tracking of flowing fluorescent particles in the second near-infrared window (NIR-II, ≈1000-1700 nm), with the third (depth) dimension added by triangulation and stereo-matching of images acquired with two short-wave infrared cameras operating in a dual-view mode. The 3D imaging capability enabled with the proposed method facilitates a detailed visualization of microvascular networks and an accurate blood flow quantification. Experiments performed in tissue-mimicking phantoms demonstrate that high resolution is preserved up to a depth of 4 mm in a turbid medium. Transcranial microangiography of the entire murine cortex and penetrating vessels is further demonstrated at capillary level resolution.

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“…Combined with laser-scanned microscopes, the phosphorescence lifetime imaging microscopy (PLIM) can further map the microscopic distribution of oxygen in vivo. [14][15][16][17][18][19][20][21][22][23] For increased measurement depth, least photodamage, and high spatial resolution, near-infrared (NIR) excited two-photon (TP) and three-photon phosphorescence probes were developed for in vivo oxygen sensing. [9,18,19,[24][25][26] Strongly emissive complexes of Pt II , [14,[27][28][29] Ru II , [30] Eu III , [31][32][33] and heterometallic Ir-Eu [34] dyads commonly show rather poor (≈100 GM) two-photon absorption (TPA) cross-sections (𝜎2).…”

Section: Introductionmentioning

confidence: 99%

“…With high two-photon phosphorescence yields, properly long phosphorescence lifetime, high Stern-Volmer quenching constant for oxygen, good biocompatibility, and high vessel permeability, we believe the holistically advanced Re I -diimine luminescent probes have great advantages to be applied in the in vivo studies of cell metabolism, [16,20,21] stem cell niche, [19] tumor hypoxic niche in poorly-perfused tissues, [22] blood perfusion, [17,18] or oxygen transportation. [23]…”

Section: Introductionmentioning

confidence: 99%

Functionalizing Collagen with Vessel‐Penetrating Two‐Photon Phosphorescence Probes: A New In Vivo Strategy to Map Oxygen Concentration in Tumor Microenvironment and Tissue Ischemia

Kisel

Thangavel

et al. 2021

Advanced Science

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The encapsulation and/or surface modification can stabilize and protect the phosphorescence bio-probes but impede their intravenous delivery across biological barriers. Here, a new class of biocompatible rhenium (Re I ) diimine carbonyl complexes is developed, which can efficaciously permeate normal vessel walls and then functionalize the extravascular collagen matrixes as in situ oxygen sensor. Without protective agents, Re I -diimine complex already exhibits excellent emission yield (34%, 𝝀 em = 583 nm) and large two-photon absorption cross-sections (𝝈 2 = 300 GM @ 800 nm) in water (pH 7.4). After extravasation, remarkably, the collagen-bound probes further enhanced their excitation efficiency by increasing the deoxygenated lifetime from 4.0 to 7.5 μs, paving a way to visualize tumor hypoxia and tissue ischemia in vivo. The post-extravasation functionalization of extracellular matrixes demonstrates a new methodology for biomaterial-empowered phosphorescence sensing and imaging.

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High-Resolution Optical Microscopy Imaging of Cortical Oxygen Delivery and Consumption

Cited by 3 publications

References 15 publications

Parameter quantification for oxygen transport in the human brain

Parameter quantification for oxygen transport in the human brain

Depth‐Resolved Localization Microangiography in the NIR‐II Window

Functionalizing Collagen with Vessel‐Penetrating Two‐Photon Phosphorescence Probes: A New In Vivo Strategy to Map Oxygen Concentration in Tumor Microenvironment and Tissue Ischemia

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